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CLINICAL DECISION MAKING TOOLKIT
Instant guidance for diagnosis, risk managementand treatment
2018 edition
The Clinical Decision Making Toolkit is produced by the Acute Cardiovascular Care Association (ACCA), developed and distributed through an educational grant from AstraZeneca. AstraZeneca was not involved in the development of this publication and in no way influenced its content.
ISBN: 978-2-9537898-7-4
The Acute Cardiovascular Care Association Clinical Decision-MakingTOOLKIT
Héctor Bueno, M.D., PhD., FESC Editor in Chief
Pascal Vranckx, M.D., PhD Associate Editor
The ACCA Toolkit is available through different platforms:
• Printed booklet, available at congresses where ESC-ACCA is represented
• Web-based pdf file downloadable at: www.escardio.org/ACCA
• Mobile application for smartphones/tablets available in both Apple & Googleplay stores
Héctor Bueno M.D., PhD., FESC Editor in Chief
The best care of patients with acute cardiovascular syndromes relies not only on specialists but also on systems of care that involve many non-cardiologists. Several of these syndromes require immediate diagnosis and decisions on treatment, some of them life-saving. Critical decisions must often be made quickly by professionals with different backgrounds and levels of expertise with limited resources. This poses a significant clinical challenge.
Against this background, the ACCA Clinical Decision-Making Toolkit was created as a comprehensive resource encompassing all aspects of acute cardiovascular care but structured as an easy-to-use instrument in environments where initial acute cardiovascular care is typically initiated. Comprehensive tables, clear diagrams and algorithms, based on the ESC clinical practice guidelines as well as in clinical experience should provide diagnostic and therapeutic guidance at a glance.
This 2018 Edition of the Clinical Decision Making Toolkit has been updated with the 2016 and 2017 ESC Guidelines, a chapter on secondary prevention was added and the chapter on acute heart failure benefited a major update. However, it does not replace textbooks and other sources of information that need to be consulted to reach an optimal management of these patients.
II
Preface
7 DAYS F R O M C A R D I A C E V E N TU N T I L P A T I E N T S T A B I L I S A T I O N
ICCUINTENSIVECARDIACCARE UNIT
CCUCORONARY CARE UNITPRE-HOSPITAL CARE
GENERALHOSPITAL
EMERGENCY ROOM
CARDIAC ARREST, STEMI, ACS, AHF, CARDIOGENIC SHOCK, ARRHYTHMIAS,VASCULAR SYNDROMES
List of Authors �������������������������������������������������������������������������������������������������������������������������� VI
CHAPTER 1: KEY SYMPTOMSChest Pain - M. Lettino, F. Schiele �������������������������������������������������������������������������������������������������� P. 2Dyspnea - C. Müller ��������������������������������������������������������������������������������������������������������������������� P. 9Syncope - R. Sutton ������������������������������������������������������������������������������������������������������������������� P. 16
CHAPTER 2: ACUTE CORONARY SYNDROMESGeneral concepts - H. Bueno ������������������������������������������������������������������������������������������������������ P. 24Non ST-segment elevation ACS - H. Bueno ���������������������������������������������������������������������������������� P. 29STEMI - P. Vranckx, B. Ibañez ������������������������������������������������������������������������������������������������������ P. 34
CHAPTER 3: SECONDARY PREVENTION AFTER ACSGeneral secondary prevention strategies and lipid lowering - H. Bueno, S. Halvorsen ����������������������� P. 38Antithrombotic treatment - F. Costa, S. Halvorsen ������������������������������������������������������������������������ P. 41
CHAPTER 4: ACUTE HEART FAILUREWet-and-warm heart failure patient - V.P. Harjola, O. Miró ������������������������������������������������������������� P. 52Cardiogenic shock (wet-and-cold) - P. Vranckx, U. Zeymer ������������������������������������������������������������� P. 61
IV
Contents
CHAPTER 5: CARDIAC ARREST AND CPR - N. Nikolaou, L. Bossaert ������������������������������������ P. 71
CHAPTER 6: RHYTHM DISTURBANCESSupraventricular tachycardias and atrial fibrillation - J. Brugada �������������������������������������������������� P. 80Ventricular tachycardias - M. Santini, C. Lavalle, S. Lanzara ���������������������������������������������������������� P. 84Bradyarrhythmias - B. Gorenek �������������������������������������������������������������������������������������������������� P. 87
CHAPTER 7: ACUTE VASCULAR SYNDROMESAcute aortic syndromes - A. Evangelista �������������������������������������������������������������������������������������� P. 92Acute pulmonary embolism - A. Torbicki ������������������������������������������������������������������������������������� P. 102
CHAPTER 8: ACUTE MYOCARDIAL/PERICARDIAL SYNDROMES Acute myocarditis - A. Keren, A. Caforio �������������������������������������������������������������������������������������� P. 112Acute pericarditis and cardiac tamponade - C. Vrints, S. Price ������������������������������������������������������� P. 117
CHAPTER 9: DRUGS IN ACUTE CARDIOVASCULAR CARE - A. de Lorenzo ���������������������� P. 121
Abbreviations ���������������������������������������������������������������������������������������������������������������������� P. 191References and copyright acknowledgments ������������������������������������������������������������������ P. 199
V
Contents (Cont.)
Leo Bossaert Department of Medicine, University and University Hospital Antwerp, Antwerp, Belgium
Josep Brugada Department of Cardiology, Hospital Clinic Universitat de Barcelona, Barcelona, SpainHéctor Bueno Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC),
and Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, SpainAlida Caforio Department of Cardiology, Padua University Medical School, Padua, ItalyFrancesco Costa Cardiovascular institute, Hospital Clínic, University of Barcelona, Barcelona, Spain
Department of Clinical and Experimental Medicine, University of Messina, Messina, ItalyArtur Evangelista Department of Cardiology, Hospital Universitario Vall d’Hebrón, Barcelona, SpainBulent Gorenek Department of Cardiology, Eskisehir Osmangazy University, Eskisehir, TurkeySigrun Halvorsen Department of Cardiology, Oslo University Hospital Ulleval and University of Oslo, Oslo, NorwayVeli-Pekka Harjola Division of Emergency Medicine, Department of Emergency Care and Services, Helsinki
University Hospital, FinlandBorja Ibañez Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC),
and Department of Cardiology, University Hospital Fundación Jiménez Díaz, Madrid, Spain Andre Keren Heart Failure and Heart Muscle Disease Centre, Hadassah University Hospital,
Jerusalem, Israel
VI
List of Authors
Stefania Lanzara Department of Emergency, Ospedale Madre Giuseppina Vannini, Rome, ItalyCarlo Lavalle Department of Cardiology, Ospedale San Filippo Neri, Rome ItalyMaddalena Lettino Clinical Cardiology Unit, IRCCS Istituto Clinico Humanitas, Milano, ItalyAna de Lorenzo Pharmacy Department, Hospital General Universitario Gregorio Marañón, Madrid, SpainÒscar Miró Emergency Department, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, SpainChristian Müller Department of Cardiology, University Hospital Basel, Basel,SwitzerlandNikolaos Nikolaou Departement of Cardiology, Konstantopouleio General Hospital, Athens, GreeceSusanna Price Consultant Cardiologist & Intensivist, Royal Brompton Hospital, London, United KingdomMassimo Santini Department of Cardiology, Ospedale San Filippo Neri, Rome, ItalyFrançois Schiele Department of Cardiology, University Hospital Jean-Minjoz, Besancon, FranceRichard Sutton Department of Cardiology, National Heart and Lung Institute Imperial College,
London, United Kingdom Adam Torbicki Department of Pulmonary Circulation and Thromboembolic Diseases, Centre of
Postgraduate Medical Education, ECZ Otwock, PolandPascal Vranckx Department of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, Hasselt, BelgiumChristiaan Vrints Department of Cardiology, Antwerp University Hospital, Edegem, BelgiumUwe Zeymer Department of Cardiology, Herzzentrum Klinikum Ludwigshafen, Ludwigshafen, Germany
VII
List of Authors (Cont.)
CHAPTER 1
KEY SYMPTOMS
1.1 CHEST PAIN ����������������������������������������������������������������� p.2 M. Lettino, F. Schiele
1.2 DYSPNEA �������������������������������������������������������������������� p.9 C. Müller
1.3 SYNCOPE ������������������������������������������������������������������� p.16 R. Sutton
P.1
1
1. Presentation
2. ECG
3. Troponin
4. Diagnosis
Reference: Roffi et al. Eur Heart J 2015; eurheartj.ehv320.
Low likelihood of Acute Coronary Syndrome
High likelihood of Acute Coronary Syndrome
NoncardiacOther
CardiacUA STEMINSTEMI
P.2
1.1Initial assessment of patients with CHEST PAIN
First call for chest pain Higher death risk / probability for ACS Lower death risk / probability for ACS
Arguments for vital risk
• Cardiorespiratory arrest, syncope/ loss of consciousness, neurological defect
• Dyspnea (see chapter 1.2 page 9)• Arrhythmias – tachycardia
• Normal consciousness• Normal breathing • Normal heart rhythm
Context, CV risk Age >40 years, previous CV disease(MI, stroke, PE), modifiable CV risk factors (smoker, HTN, hypercholesterolemia, diabetes), chronic CV treatment
• Age <40 years, • No previous CV disease• No CV risk factors• No chronic treatment
Chest Pain Medial/lateral thoracic pain, intense, with dyspnea
• Depends on position/palpation/ movements
• Variable intensity, short duration (<1 min)• Hyperthermia
Cardiac Ischemic Pain
Retro-sternal, constriction, jaw/cervical/arm/back irradiation, spontaneous, prolonged >20 min + dyspnea, sweating, lightheadedness, nausea
• Lateral, abdominal irradiation • No neuro-vegetative symptoms
P.3
1.1Factors to be considered in the evaluation
after the first call for CHEST PAIN
NoYes
Likelihood of ACS
High probability for ACS Low probability for ACS
Emergency transportwith trained medical team
ECG, decision for reperfusion,antithrombotics, immediate
transport to ED/CPU/ICCU/Cathlab(see chapter 2)
Emergency transportEmergency transportwith trained medical team
Hospital admissionto the ED/CPU
Emergency care: Resuscitation, hemodynamic or
rhythm restoration (see chapter 5)
Cardiology ward
Non-cardiology ward
Discharge afterprolonged observation
APPROACH AFTER FIRST CALL FOR OUT-OF-HOSPITAL CHEST PAIN
VITAL RISK? (see chapter 1.1 page 3)
P.4
1.1Approach after first call for out-of-hospital CHEST PAIN
NoYes
Likelihood of ACS
High probability for ACS Low probability for ACS
Emergency transportwith trained medical team
ECG, decision for reperfusion,antithrombotics, immediate
transport to ED/CPU/ICCU/Cathlab(see chapter 2)
Emergency transportEmergency transportwith trained medical team
Hospital admissionto the ED/CPU
Emergency care: Resuscitation, hemodynamic or
rhythm restoration (see chapter 5)
Cardiology ward
Non-cardiology ward
Discharge afterprolonged observation
APPROACH AFTER FIRST CALL FOR OUT-OF-HOSPITAL CHEST PAIN
VITAL RISK? (see chapter 1.1 page 3)
P.5
1.1
First medical contact Higher death risk / probability for ACS Lower death risk / probability for ACS
Hemodynamic, respiratory, neurological distress
• Cardiopulmonary arrest, hypotension, tachycardia, shock
• Dyspnea, hypoxemia, lung rales (Killip class >2)• ECG: ST-segment deviation
• Normal consciousness, no motion defects• Normal HR and BP• Normal breathing and SpO2,
no loss of pulse
Probability for ACS • Context, typical symptoms consistent with myocardial ischemia
• ECG changes• Hs cTn
• No CV risk, atypical symptoms, normal ECG
• Negative hs cTn only if onset of pain >3 hours (see chapter 2.1 page 24)
STEMI NSTE-ACS Uncertain diagnosis
(see chapter 2.1 page 24)
ECG criteria for STEMI ST depression or normal ECG
Normal ECG (repeat 12-lead ECG recording if symptoms persist/recur)
Other ST-segment abnormalities
Type of reperfusion
Time assessment
• Primary PCI or thrombolysis? Primary PCI if delay <120 min (preferably <90 min) or <60 min if onset of pain <120 min Consider age, anterior wall location
• Relevant times: Symptom onset, first medical contact (FMC). FMC → ECG/diagnosis; FMC → PCI; FMC → thrombolysis
• Primary PCI between 12-48 hours in patients with ongoing ischemia, symptoms or clinical/haemodynamic or electrical instability
• No reperfusion if delay >12 hours and stable, asymptomatic, without ST-segment elevation
P.6
1.1Factors to be considered in the evaluation
during the first medical contact for CHEST PAIN
Yes
Resuscitation, hemodynamic or respiratory support(see chapters 4 & 5)
Type of reperfusion (primary PCI or fibrinolysis)Record times (symptom onset, FMC)
High probability Low probability
No
FIRST MEDICAL CONTACT IN PATIENTS WITH CHEST PAIN (HOME-AMBULANCE)
Hemodynamic, respiratory or neurological distress?
ST-segment elevation
ECG <10 min → ACS ?
No ST-segment elevation butother ECG changes or persistent pain
Suspect ACS Uncertain diagnosis
No antithrombotic treatmentTransfer to a proximity centre
(with or without cath-lab)Start recommended medical therapy(including antithrombotic drugs)
Transfer to a centre with cath-lab
Non cardiovascular disease? • Sepsis• Acute respiratory distress• GI disease, bleeding, others
Acute cardiovascular disease other than ACS?• Acute aortic syndrome (see chapter 7)• Pulmonary embolism (see chapter 7)• Acute pericarditis (see chapter 8)• Acute heart failure (see chapter 4)
P.7
1.1First medical contact in patients with CHEST PAIN (home-ambulance)
• Diagnosis of NSTE-ACS (see chapter 2)• Acute aortic syndrome (see chapter 7)• Acute pulmonary embolism (see chapter 7)• Acute pericarditis (see chapter 8)• Acute heart failure (see chapter 4)• Aortic stenosis, hyperthrophic cardiomyopathy• Acute gastro-oesophageal disease• Acute pleuro-pulmonary disease• Acute psychogenic disorders
Repeat clinical and ECG examinationLaboratory: cTn, renal function, Hb,D-dimers Imaging: TTE, CT scanDiagnostic coronary angiography
Yes No
Yes No
MANAGEMENT OF PATIENTS WITH CHEST PAIN (EMERGENCY ROOM)
STEMI,NSTE-ACS with persistent pain,
Hemodynamic distress
No direct transfer to cath-lab → ED, Chest Pain Unit,
cardiology ward, other wards
Other CVD or No ACS
Resuscitation, hemodynamic or respiratory support(see chapters 4 & 5)
Direct transfer to cath-lab
Complicated NSTEMISTEMI (see chapter 2)
Hemodynamic, respiratory or neurological distress? P.8
1.1Management of patients with CHEST PAIN (emergency room)
DYSPNEA: DIFERENTIAL DIAGNOSIS
50% have ≥2 diagnoses, which may result in acute respiratory failure*!
• ECG • Chest X-ray • Blood count • cTn • BNP • Venous BG • D-dimers if suspicion of PE
Basic measures
• BP, HR, respiratory rate, SpO2 & temperature • Start oxygen to target SpO2 94-98% • Start i.v. line & monitor patient
Criteria for transfer to ICU (despite treatment for 30 minutes)
• Respiratory rate >35/min• SpO2 <85%
• SBP <90 mmHg • HR >120 bpm
Investigations:
Acute heartfailure
Acute coronary syndrome
Exacerbated COPDor other chronic
lung disease
Other causes, including• Asthma
• Severe sepsis • Tumor • Pneumothorax • Pleural effusion/ascites • Anxiety disorder • Anemia • Bronchitis • Metabolic acidosis • Neurologic disease
Pneumonia Pulmonaryembolism
* Defined as ≥1 criterion: • Respiratory rate ≥25/min • PaO2 ≤75 mmHg • SpO2 ≤92% in ambient air • PaCO2 ≥45 mmHg with arterial pH ≤7.35
Reference: Ray P et al. Acute respiratory failure in the elderly: etiology, emergency diagnosis and prognosis. Critical Care (2006); 10 (3):R82.
P.9
1.2DYSPNEA: Diferential diagnosis
BASIC WORK-UP
• Positioning Keep head of bed elevated above level of legs• Oxygen Up to 12 l/min via rebreather mask, titrate oxygen saturation to 94%• Nitroglycerin 1-2 SL tablets or 2-3 patches 10 mg (1st choice). In pulmonary edema with severe shortness of breath: NTG drip 0.05% (100 mg in 200 ml) - Start with 25 µg/min = 3 ml/h, check BP after 5 and 10 min - Increase dose by 25 µg/min at a time as long as SBP >90 mmHg - Additional BP check 5 and 10 min after each increase in dosing - Check BP every 20 min once a steady drip rate is reached• Furosemide 40-120 mg i.v. (adjust based on kidney function and clinical findings; monitor creatinine)• Morphine 2 mg i.v. (preceeded by 10 mg i.v. metoclopramide PRN) if patient is in severe dyspnoea• Consider digoxin 0.5 (-1.0) mg i.v. in patients with atrial fibrillation• Anticoagulation Therapeutic dosing in ACS and atrial fibrillation: Enoxaparin 1 mg/kg body weight as 1st dose
Unstable after 30 minutes
CCU/ICU transfer Ward transfer
Stable after 30 minutes
• Chest X-ray (lung ultrasound)• Echocardiogram During admission (earlier if decompensated aortic stenosis or endocarditis are suspected)• Coronary angiography Emergent in patients with ACS; delayed in patients with suspected coronary artery disease
• Immediate 12-lead ECG, cardiac monitor, BP, respiratory rate, pulse oximetry• Clinical findings Most commonly: lower extremity edema, jugular venous distension, rales, work up for underlying cardiac disease and triggers• Laboratory findings Complete blood count, chemistries, cardiac enzymes, BNP, TSH, ABG as needed
P.10
1.2DYSPNEA: Acute heart failure (see chapter 4.1)
Reference: Ware L B and Matthay M A. Acute Pulmonary Edema. New Engl J Med (2005); 353:2788-2796.
BASIC WORK-UP
• Positioning Keep head of bed elevated above level of legs• Oxygen Up to 12 l/min via rebreather mask, titrate oxygen saturation to 94%• Nitroglycerin 1-2 SL tablets or 2-3 patches 10 mg (1st choice). In pulmonary edema with severe shortness of breath: NTG drip 0.05% (100 mg in 200 ml) - Start with 25 µg/min = 3 ml/h, check BP after 5 and 10 min - Increase dose by 25 µg/min at a time as long as SBP >90 mmHg - Additional BP check 5 and 10 min after each increase in dosing - Check BP every 20 min once a steady drip rate is reached• Furosemide 40-120 mg i.v. (adjust based on kidney function and clinical findings; monitor creatinine)• Morphine 2 mg i.v. (preceeded by 10 mg i.v. metoclopramide PRN) if patient is in severe dyspnoea• Consider digoxin 0.5 (-1.0) mg i.v. in patients with atrial fibrillation• Anticoagulation Therapeutic dosing in ACS and atrial fibrillation: Enoxaparin 1 mg/kg body weight as 1st dose
Unstable after 30 minutes
CCU/ICU transfer Ward transfer
Stable after 30 minutes
• Chest X-ray (lung ultrasound)• Echocardiogram During admission (earlier if decompensated aortic stenosis or endocarditis are suspected)• Coronary angiography Emergent in patients with ACS; delayed in patients with suspected coronary artery disease
• Immediate 12-lead ECG, cardiac monitor, BP, respiratory rate, pulse oximetry• Clinical findings Most commonly: lower extremity edema, jugular venous distension, rales, work up for underlying cardiac disease and triggers• Laboratory findings Complete blood count, chemistries, cardiac enzymes, BNP, TSH, ABG as needed
P.11
1.2
Priorities: 1. Vital signs 2. Diagnostic screening dependent upon clinical stratification
Hemodynamically unstable Hemodynamically stable
Intermediateprobability
Total score 2-6
Highprobability
Total score >6
Lowprobability
Total score <2
Outpatient management possible?→ Risk stratification
Initiate transfer to ICU
Immediate TTE (if available)
PE confirmed: Treatment(see chapter 7.2)
Resultinconclusive→ CT-angio
Rightventriculardysfunction
Wells criteria for PE: Score• Clinical signs and symptoms of deep vein thrombosis (DVT) + 3.0• No alternative diagnosis (or alternative diagnosis less likely than PE) + 3.0• Heart rate >100/min + 1.5• Immobilization or operation within the last 4 weeks + 1.5• Previous DVT or PE + 1.5• Hemoptysis + 1.0• Malignant tumor with treatment within the last 6 months or palliative care + 1.0
ABG, ECG, chest X-ray plus clinical assessment of PE probability (risk factors) plus monitoring
(see chapter 7.2)
P.12
1.2DYSPNEA: Acute pulmonary embolism (see chapter 7.2)
Copyright: Stein PD, Woodard PK, Weg JG, et al. Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators. Am J Med (2006); 119:1048–55. - Goldhaber SZ. Pulmonary embolism. Lancet (2004); 363 (9417) 1295-1305. - Agnelli G and Becattini C. Acute Pulmonary Embolism. New Engl J Med (2010); 363:266-274.
Priorities: 1. Vital signs 2. Diagnostic screening dependent upon clinical stratification
Hemodynamically unstable Hemodynamically stable
Intermediateprobability
Total score 2-6
Highprobability
Total score >6
Lowprobability
Total score <2
Outpatient management possible?→ Risk stratification
Initiate transfer to ICU
Immediate TTE (if available)
PE confirmed: Treatment(see chapter 7.2)
Resultinconclusive→ CT-angio
Rightventriculardysfunction
Wells criteria for PE: Score• Clinical signs and symptoms of deep vein thrombosis (DVT) + 3.0• No alternative diagnosis (or alternative diagnosis less likely than PE) + 3.0• Heart rate >100/min + 1.5• Immobilization or operation within the last 4 weeks + 1.5• Previous DVT or PE + 1.5• Hemoptysis + 1.0• Malignant tumor with treatment within the last 6 months or palliative care + 1.0
ABG, ECG, chest X-ray plus clinical assessment of PE probability (risk factors) plus monitoring
(see chapter 7.2)
P.13
1.2
DYSPNEA: COPD EXACERBATION
• Verify diagnosis (DD: PE, acute heart failure, pneumothorax) • Oxygen administration → SpO2 target 88-92% (Beware of carbonarcosis: ABC after 1 h)
Definition: Known COPD and/or • Progressive dyspnea and/or • Change in quantitiy and color of sputum and/or • Heavy coughing
• COPD classification (GOLD)
• Etiology
• Hospitalisation indicated?
• Follow-up
• Evaluate ICU criteria• NIV indicated?
• Laboratory findings: Blood count, coagulation, ProCT, perhaps BNP, D-Dimers• Chest X-ray; ECG (exclusion of differential diagnoses)• Sputum cultures (always in case of hospitalisation or previousoutpatient antibiotic treatment)
• Oxygen therapy 2-(4) l; target saturation 90% • Salbutamol/ipratropium inhalations ≥4-6 x/d, if needed long-term inhalation• Systemic steroids prednisone 0.5 mg/kg of body weight for 5 days• Antibiotic treatment should be considered; always indicated in stage Gold IV• Physiotherapy
• History, clinical examination (blood pressure, pulse, oxygen saturation, vigilance)
Copyright: Leuppi JD et al. JAMA. 2013 Jun 5; 309(21):2223-31.
P.14
1.2DYSPNEA: COPD exacerbation
DYSPNEA: COMMUNITY-ACQUIRED PNEUMONIA
Objective: diagnostics, risk stratification & empirical immediate treatment <2(-4) hours
Definition
Complications
• Chest X-ray if dyspnea & cough • Laboratory workup clinical chemistry; BGA; procalcitonin• Sputum if patient admitted• Blood cultures (2x2) if patient admitted• Legionella antigen (urine) if Legionellosis suspected • Pneumococcus antigen (urine) if no other pathogen isolated
Risk stratification → manageable on an outpatient basis?- Pneumonia Severity Index- CURB-65
• Treatment; procalcitonin guided treatment• Consider outpatient treatment where PSI I-III or CURB65 0 or 1• Minimum 5-day course of treatment and afebrile for 48-72h, 7-10 days, 14 days where intracellular organisms (e.g. Legionella) are present
Copyrights: Mandell LA et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. (2007); 44 Suppl 2:S27-72. - Halm EA and Teirstein AS. Management of Community-Acquired Pneumonia New Engl J Med (2002); 347:2039-2045. - Woodhead M et al. Guidelines for the management of adult lower respiratory tract infections ERJ December 1, (2005); 26 (6) 1138-1180.
P.15
1.2DYSPNEA: Community-acquired pneumonia
Syncope is a transient loss of consciousness due to global cerebral hypoperfusion (usually, itself due to period of low blood pressure) characterised by rapid onset, short duration, spontaneous and complete recovery.
The differentiation between syncope and non-syncopal conditions with real or apparent LOC can be achieved in most cases with a detailed clinical history but sometimes can be extremely difficult. The following questions should be answered: • Was LOC complete? • Was LOC transient with rapid onset and short duration? • Did the patient recover spontaneously, completely and without sequelae? • Did the patient lose postural tone?
If the answers to these questions are positive, the episode has a high likelihood of being syncope. If the answer to one or more of these questions is negative, exclude other forms of LOC before proceeding with syncope evaluation.
Loss of Consciousness?
TLOCTrauma Not Trauma
• Accidental • Fall• Other abnormal mental state
No
No
Yes
Yes
• Coma• Intoxication
• Metabolic disturbance• Aborted sudden death
Transient, rapid onset,short time, self-terminating
Syncope Epilepsy Psychogenic
Reference: Sutton R. Clinical classification of syncope. - Prog Cardiovasc Dis. (2013); 55(4):339-44.
P.16
1.3SYNCOPE: Assessment of patients
with transient loss of conscioussness (TLOC)
Vasovagal syncope is diagnosed if syncope is precipitated by emotional distress or orthostatic stress and is associated with typical prodrome.
Situational syncope is diagnosed if syncope occurs during or immediately after specific triggers.
Orthostatic syncope is diagnosed when it occurs after standing up and there is documentation of orthostatic hypotension.
Arrhythmia related syncope is diagnosed by ECG when there is:
• Persistent sinus bradycardia <40 bpm in awake or repetitive sinoatrial block or sinus pauses >3 s • Mobitz II 2nd or 3rd degree AV block • Alternating left and right BBB • VT or rapid paroxysmal SVT • Non-sustained episodes of polymorphic VT and long or short QT interval • Pacemaker or ICD malfunction with cardiac pauses
Cardiac ischemia related syncope is diagnosed when syncope presents with ECG evidence of acute ischemia with or without myocardial infarction.
Cardiovascular syncope is diagnosed when syncope presents in patients with prolapsing atrial myxoma, severe aortic stenosis, pulmonary hypertension, pulmonary embolus or acute aortic dissection.
Reference: Moya A et al. Eur Heart J(2009) 30, 2631–2671 (1).
P.17
1.3SYNCOPE: Diagnostic criteria (1)
Diagnostic criteria with initial evaluation
Patients with suspected syncope presenting to ED or clinic
“Uncertain” or unexplained syncope Certain diagnosis of syncope
Risk stratification
High risk Intermediate risk Low risk
Observation UnitHome if stable,
Admit to hospitalif evidence of high risk
HomeOutpatient SMU
referral
Outpatient SMU for diagnosis, treatment and follow-up as appropriate
Hospital admissionInpatient SMU
Initiate therapyInpatient SMU, outpatient SMU orpersonal physician as appropriate
Copyright: Sutton R, Brignole M, Benditt DG. Key challenges in the current management of syncope. Nat Rev Cardiol. (2012 ); (10):590-8.
Once syncope is considered to be the likely diagnosis, risk stratification is required to determine further management. P.18
1.3SYNCOPE: Evaluation and risk stratification of patients
with suspected syncope
Carotid sinus massage Orthostatic Hypotension
Indications• CSM is indicated in patients >40 years with syncope
of unknown aetiology after initial evaluation;• CSM should be avoided in patients with previous MI,
TIA or stroke within the past 3 months and in patients with carotid bruits (except if carotid Doppler studies excluded significant stenosis)
Recommendations: Active standing Indications• Manual intermittent determination with
sphygmomanometer of BP supine and, when OH is suspected, during active standing for 3 min is indicated as initial evaluation;
• Continuous beat-to-beat non-invasive pressure measurement may be helpful in cases of doubt
Diagnostic criteria• CSM is diagnostic if syncope is reproduced in presence
of asystole longer than 3 s and/or a fall in systolic BP >50 mmHg
Diagnostic criteria• The test is diagnostic when there is a symptomatic
fall in systolic BP from baseline value ≥20 mmHg or diastolic BP ≥10 mmHg or a decrease in systolic BP to <90 mmHg;
• The test should be considered diagnostic when there is an asymptomatic fall in systolic BP from baseline value ≥20 mmHg or diastolic BP >10 mmHg or a decrease in systolic BP to <90 mmHg
Reference: Moya A et al. Eur Heart J(2009) 30; 2631–2671 (2).
P.19
1.3SYNCOPE: Diagnostic criteria (2)
Diagnostic criteria with provocation maneuvers
Treatment of reflex syncope Treatment of orthostatic hypotension
• Explanation of the diagnosis, provision of reassurance and explanation of risk of recurrence are in all patients
• Isometric PCM are indicated in patients with prodrome• Cardiac pacing should be considered in patients with dominant
cardioinhibitory CSS• Cardiac pacing should be considered in patients with frequent recurrent reflex
syncope, age >40 years and documented spontaneous cardioinhibitory response during monitoring
• Midodrine may be indicated in patients with VVS refractory to lifestyle measures• Tilt training may be useful for education of patients but long-term benefit depends
on compliance• Cardiac pacing may be indicated in patients with tilt-induced cardioinhibitory
response with recurrent frequent unpredictable syncope and age >40 after alternative therapy has failed
• Triggers or situations inducing syncope must be avoided as much as possible• Hypotensive drugs must be modified or discontinued• Cardiac pacing is not indicated in the absence of a documented cardioinhibitory
reflex• Beta-adrenergic blocking drugs are not indicated• Fluid consumption and salt in the diet should be increased
• Adequate hydration and salt intake must be maintained
• Midodrine should be administered as adjunctive therapy if needed
• Fludrocortisone should be administered as adjunctive therapy if needed
• PCM may be indicated • Abdominal binders and/or support
stockings to reduce venous pooling may be indicated
• Head-up tilt sleeping (>10°) to increase fluid volume may be indicated
• Triggers or situations inducing syncope must be avoided as much as possible
• Hypotensive drugs administered for concomitant conditions must be discontinued or reduced
Copyright: Moya A et al. Eur Heart J(2009) 30; 2631–2671 (3).
P.20
1.3Treatment according to type of SYNCOPE (1)
Treatment of arrhythmic syncope
Cardiac Pacing• Pacing is indicated in patients with sinus node disease in
whom syncope is demonstrated to be due to sinus arrest (symptom-ECG correlation) without a correctable cause
• Pacing is indicated in sinus node disease patients with syncope and abnormal CSNRT
• Pacing is indicated in sinus node disease patients with syncope and asymptomatic pauses >3 sec. (with possible exceptions of young trained persons, during sleep and in medicated patients)
• Pacing is indicated in patients with syncope and 2nd degree Mobitz II, advanced or complete AV block
• Pacing is indicated in patients with syncope, BBB and positive EPS
• Pacing should be considered in patients with unexplained syncope and BBB
• Pacing may be indicated in patients with unexplained syncope and sinus node disease with persistent sinus bradycardia itself asymptomatic
• Pacing is not indicated in patients with unexplained syncope without evidence of any conduction disturbance
Catheter ablation• Catheter ablation is indicated in patients with symptom/
arrhythmia ECG correlation in both SVT and VT in the absence of structural heart disease (with exception of atrial fibrillation)
• Catheter ablation may be indicated in patients with syncope due to the onset of rapid atrial fibrillation
Antiarrhythmic drug therapy• Antiarrhythmic drug therapy, including rate control drugs,
is indicated in patients with syncope due to onset of rapid atrial fibrillation
• Drug therapy should be considered in patients with symptom/ arrhythmia ECG correlation in both SVT and VT when catheter ablation cannot be undertaken or has failed
Implantable Cardioverter Defibrillator (ICD) • ICD is indicated in patients with documented VT
and structural heart disease• ICD is indicated when sustained monomorphic VT is induced
at EPS in patients with previous myocardial infarction• ICD should be considered in patients with documented VT
and inherited cardiomyopathies or channelopathies
Copyright: Moya A et al. Eur Heart J(2009) 30; 2631–2671 (4).
P.21
1.3Treatment according to type of SYNCOPE (2)
CHAPTER 2
ACUTE CORONARY SYNDROMES
2.1 GENERAL CONCEPTS ������������������������������������������������������ p.24 H. Bueno
2.2 NON ST-SEGMENT ELEVATION ACS ��������������������������������������� p.29 H. Bueno
2.3 ST-SEGMENT ELEVATION MI (STEMI) �������������������������������������� p.35 P. Vranckx, B. Ibañez
2
hs-cTn<ULNhs-cTn>ULN
ACUTE CORONARY SYNDROMES: DIAGNOSIS
CHEST PAIN or symptoms sugestive of myocardial ischemia
ECG
ST elevation(persistent)
Repolarization not interpretable(i.e. LBBB, pacemaker...)
ST/T abnormalities Normal ECG
STEMI
Pain resolves with nitroglycerin 1st hsTn
NSTEMI Unstable Angina Work-up
differential diagnoses
Pain onset >6 h Pain onset <6 h
Re-test hs-cTn (3h later)See next page for 1 h rule-in & rule-out algorithm
hs-cTnno change
∆ hs-cTn(1 value >ULN)
hs-cTn >x5 ULNor
clinicaldiagnosis
clear
Potential noncardiac
causes for abnormal Tn
ConsiderSTEMI
Yes
No
References: Roffi M. Eur Heart J 2016; 37:267-315. Ibañez B. Eur Heart J 2018; 39:119-177.
P.24
2.1ACUTE CORONARY SYNDROMES: Diagnosis (1)
Suspected NSTEMI
Other0h≥D ng/l
or≥
ObserveRule-out Rule-in
hs-cTnT (Elecsys)*
hs-cTnl (Architect)*
hs-cTnl (Dimension Vista)*
0-1h E ng/l0h<A ng/l
0h<B ng/l and
0-1h<Cng/l
A
5
2
0,5
B
12
5
5
C
3
2
2
D
52
52
107
E
5
6
19
oror
• NSTEMI can be ruled-out at presentation, if hs-cTn concentration is very low• NSTEMI can be ruled out by the combination of low baseline levels and the lack of a relevant increase within 1 h• NSTEMI is highly likely if initial hs-cTn concentration is at least moderately elevated or hs-cTn concentrations
show a clear rise within the first hour
Reference: Roffi M. Eur Heart J 2016; 37:267-315.
*Cut-off levels are assay-specific.
P.25
2.1ACUTE CORONARY SYNDROMES: Diagnosis (2)
0-1 H Rule-in & rule out test for NSTEMI
Causes of chest pain Not related to ACS
Causes of troponin elevationNot related to ACS
Primary cardiovascular• Acute pericarditis, pericardial effusion• Acute myocarditis• Severe hypertensive crisis• Stress cardiomyopathy (Tako-Tsubo syndrome)• Hypertrophic cardiomyopathy, aortic stenosis • Severe acute heart failure • Acute aortic syndrome (dissection, hematoma)• Pulmonary embolism, pulmonary infarction• Cardiac contusion
Primary cardiovascular• Acute myo(peri)carditis• Severe hypertensive crisis• Pulmonary edema or severe congestive heart failure• Stress cardiomyopathy (Tako-Tsubo syndrome)• Post- tachy- or bradyarrhythmias• Cardiac contusion or cardiac procedures
(ablation, cardioversion, or endomyocardial biopsy)• Aortic dissection, aortic valve disease or hypertrophic cardiomyopathy• Pulmonary embolism, severe pulmonary hypertension
Primary non-cardiovascular• Oesophageal spasm, oesophagitis, Gastro
Esophageal Reflux (GER)• Peptic ulcer disease, cholecystitis, pancreatitis• Pneumonia, bronchitis, asthma attack• Pleuritis, pleural effusion, pneumothorax• Pulmonary embolism, severe pulmonary
hypertension• Thoracic trauma• Costochondritis, rib fracture • Cervical / thoracic vertebral or discal damage• Herpes Zoster
Primary non-cardiovascular• Renal dysfunction (acute or chronic)• Critical illness (sepsis, repiratory failure…)• Acute neurological damage (i.e. stroke, subarachnoid hemorrhage)• Severe burns (affecting >30% of body surface area)• Rhabdomyolysis• Drug toxicity (chemotherapy with adriamycin, 5-fluorouracil,
herceptin, snake venoms…)• Inflammatory or degenerative muscle diseases• Hypothyroidism• Infiltrative diseases (amyloidosis, hemochromatosis, sarcoidosis)• Scleroderma
P.26
2.1ACUTE CORONARY SYNDROMES: Differential diagnosis (1)
ST-segment elevation Negative T waves
Fixed• LV aneurysm• LBBB, WPW, hypertrophic cardiomyopathy, LVH• Pacemaker stimulation• Early repolarisation (elevated J-point)Dynamic• Acute (myo)pericarditis• Pulmonary embolism• Electrolyte disturbances (hyperkalemia)• Acute brain damage (stroke, subarachnoid haemorrhage)• Tako Tsubo syndrome
• Normal variants, i.e. women (right precordial leads), children, teenagers
• Evolutive changes post myocardial infarction
• Chronic ischemic heart disease• Acute (myo)pericarditis,
cardiomyopathies• BBB, LVH, WPW• Post-tachycardia or
pacemaker stimulation• Metabolic or ionic disturbances
ST-segment depression Prominent T waves
Fixed• Abnormal QRS (LBBB, WPW, pacemaker stimulation…)• LVH, hypertrophic cardiomyopathy• Chronic ischemic heart disease
• Normal variants, i.e. early repolarisation
• Metabolic or ionic disturbances (i.e. hyperkalemia)
• Acute neurological damage (stroke, subarachnoid haemorrhage)
Dynamic • Acute (myo)pericarditis• Acute pulmonary hypertension• Electrolyte disturbances (hyperkalemia)• Intermitent LBBB, WPW, pacing• Post-tachycardia / cardioversion
• Severe hypertensive crisis• Drug effects (digoxin)• Shock, pancreatitis• Hyperventilation• Tako Tsubo syndrome
P.27
2.1ACUTE CORONARY SYNDROMES: Differential diagnosis (2)
Causes of repolarisation abnormalities in the ECG not related to ACS
2ECG
(<10 min)
3Diagnosis /
Risk assessment
4Medical
Treatment
5InvasiveStrategy
STEMI (see chapter 2.3)
Thrombolysisfor STEMI if
primary PCI nottimely available
PrimaryPCI
1Clinical
Evaluation
NSTE ACS(see chapter 2.2)
ACS unclear(Rule out ACS) (see chapter 1.1)
No ACS
Chest Pain Unit
• Clinical presentation (BP, HR)
• ECG presentation
• Past history
• Ischemic risk (i.e. GRACE, TIMI scores)
• Bleeding risk (i.e. CRUSADE score)
• Additional information (labs, imaging...) optional
Anti-ischemictherapy
Antiplatelettherapy
Anticoagulation
Emergent<2 hours
Urgent2-24 hours
Early24-72 hours
No /Elective
Quality ofchest pain
Clinicalcontext
Probabilityof CAD
Physicalexamination
GENERAL APPROACH TO THE PATIENT WITH CHEST PAIN / SUSPECTED ACS
ECG
Rule out noncardiac causes
P.28
2.1GENERAL APPROACH
to the patient with chest pain/suspected ACS
Ischemic risk
GRACE risk score TIMI risk score
Predictive Factors• Age• HR*
• SBP*
• Creatinine (mg/dl)*• Killip class*• Cardiac arrest*• ST-segment deviation• Elevated cardiac markers
OutcomesIn-hospital, 6-month, 1-year and 3-year mortality1-year death/MI
Predictive Factors• Age 65 years • At least 3 risk factors for CAD • Significant (>50%) coronary stenosis• ST deviation • Severe anginal symptoms (>2 events in last 24h)• Use of aspirin in last 7 days • Elevated serum cardiac markers
OutcomeAll-cause mortality/new or recurrent MI/severe recurrent ischemia requiring urgent revascularisation at 14 days
* At admission.
50
40
30
20
10
0 70 90 110 130 150 170 190 210
GRACE Risk Score
Probability of all-cause mortality from hopital discharge to 6 months (%)
50
40
30
20
10
00-1 2 3 4 5 >=6
TIMI Risk Score
Risk of 14 days events (%)
Risk calculation http://www.gracescore.org/WebSite/WebVersion.aspx
Risk calculation http://www.timi.org/index.php?page=calculators
P.29
2.2NON ST-SEGMENT ELEVATION ACS: Risk stratification (1)
Bleeding risk
CRUSADE risk score
Predictive Factors• Sex• HR*
• SBP*
• Creatinine (mg/dl)*• Baseline hematocrit*• GFR: Cockcroft-Gault*• Diabetes• Prior vascular disease• Signs of congestive heart failure*
OutcomeIn-hospital major bleeding
Copyrights: Eagle KA et al. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month post-discharge death in an international registry. JAMA. (2004); 291(22):2727-33. - Antman EM, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA. (2000); 284(7):835-42. - Subherwal S, et al Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) Bleeding Score. Circulation (2009); 119(14):1873-82.
* At admission.
50
40
30
20
10
00 20 40 60 80 100
CRUSADE Bleeding Score
Probability of in-hospital major bleeding(%)
Risk calculationwww.crusadebleedingscore.org
P.30
2.2NON ST-SEGMENT ELEVATION ACS: Risk stratification (2)
Initial treatment*• Nitrates• Morphine• Oxygen (if SpO2 <90%)
One of the following: • Fondaparinux • Enoxaparin • UFH • Bivalirudin
Aspirin + one of: • Ticagrelor • Prasugrel • Clopidogrel
Optionally: • GP IIb/IIIa inhibitors • Cangrelor
• Nitrates• Beta-blockers• Calcium antagonists
• Statins• ACE inh. (or ARB)• Aldosterone inhibitors
Pharmacologicaltreatment*
Anti ischemictreatment
Antithrombotictherapy
Anticoagulation Antiplatelets
PCICABG
Other preventivetherapies
Myocardialrevascularisation
*For more information on individual drug doses and indications,
SEE CHAPTER 3 SECONDARY PREVENTION AFTER ACS & CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
P.31
2.2NON ST-SEGMENT ELEVATION ACS: Treatment (1)
General overview
Very-high-risk criteria
• Haemodynamic instability or cardiogenic shock• Recurrent or ongoing chest pain refractory to medical treatment• Life-threatening arrhythmias or cardiac arrest• Mechanical complications of MI• Acute heart failure• Recurrent dynamic ST-T wave changes, particularly with intermittent ST-elevation
High-risk criteria • Rise or fall in cardiac troponin compatible with MI• Dynamic ST- or T-wave changes (symptomatic or silent)• GRACE score >140
Intermediate-risk criteria
• Diabetes mellitus• Renal insufficienty (eGFR <60 ml/min/1.73 m2)• LVEF <40% or congestive heart failure• Early post-infarction angina• Prior PCI• Prior CABG• GRACE risk score >109 and <140
Low-risk criteria • Any characteristics not mentioned above
Reference: Roffi M. Eur Heart J 2016; 37:267-315.
P.32
2.2NON ST-SEGMENT ELEVATION ACS: Treatment (2)
Risk criteria mandating invasive strategy in NSTE-ACS
Symptoms Onset
PCI centre
Very high
ImmediateInvasive (<2 hr)
Early invasive(<24 hr)
Invasive(<72 hr)
High
Intermediate
Immediate transfer to PCI centre
Same-day transfer
Transfer
Transfer optional Ris
k st
rati
fica
tion
The
rape
utic
stra
tegy
Low
EMS or Non–PCI centre
First medical contact NSTE-ACS diagnosis
Very high
High
Intermediate
Low
Non-invasivetesting if appropriate
Reference: Roffi M. Eur Heart J 2016; 37:267-315.
P.33
2.2NON ST-SEGMENT ELEVATION ACS: Treatment (3)
Timing and strategy for invasive management
0
24 hours
10 min
90 min
2 hours
Str
ateg
y cl
ock
ECG STEMI diagnosis
Time to PCI?
≤120min
Primary PCIstrategy
Fibrinolysisstrategya
Bolus offibrinolyticb
Transferto PCI centre
Meet reperfusioncriteria?
No Yes
Routine PCI strategy
RescuePCI
>120min
Alert & transferto PCI centre
Wire crossing(reperfusion)
≥120
min
60-9
0m
in
Reference: Ibañez B. Eur Heart J 2018; 39:119-177.
STEMI Treatment (1):Reperfusion strategy
a If fibrinolysis is contra-indicated, direct for primary PCI strategy regardless of time to PCI.b 10 min is the maximum target delay time from STEMI diagnosis to fibrinolytic bolus administration, however, it should be given as soon as possible after STEMI diagnosis (after ruling out contra-indications).
P.34
2.3
AspirinLoading
Prasugrel or ticagrelor loading(clopidogrel as alternative)
Aspirinmaintenance
Prasugrel or ticagrelor maintenance(clopidogrel as alternative)
Oxygen when SpO2 <90%
High dose statin(e.g. atorvastatin 80 mg or rosuvastatin 40 mg)
Oral β-blocker
ACE inhibitor
Mineralocorticoid receptor antagonist(if LVEF <40% and heart failure)
i.v. Beta-blocker
i.v. Opioids/tranquilizer
DURING PCI: radial access, UFH (enoxaparin/bivalirudin as alternatives)
STEMIdiagnosis
Wire crossing(reperfusion)
HospitalAdmission
HospitalDischarge
Reference: Ibañez B. Eur Heart J 2018; 39:119-177.
P.35
2.3STEMI Treatment (2):Medical management of patients treated with primary PCI
Aspirinloading
Clopidogrelloading
Fibrinolysis bolus Enoxaparin
Aspirinmaintenance
Clopidogrelmaintenance
Oxygen when SpO2 <90%
i.v. Opioids/tranquilizer
High dose statin(e.g. atorvastatin 80 mg or rosuvastatin 40 mg)
Oral β-blocker
ACE inhibitor
Mineralocorticoid receptor antagonist(if LVEF <40% and heart failure)
STEMIdiagnosis
HospitalAdmission
HospitalDischarge
10min
Coronary angiography ± PCI(2-24h)
Reference: Ibañez B. Eur Heart J 2018; 39:119-177.
P.36
2.3STEMI Treatment (3):Medical management of patients treated with fibrinolysis
CHAPTER 3
SECONDARY PREVENTION AFTER ACS
3.1 GENERAL SECONDARY PREVENTION STRATEGIES AND LIPID LOWERING ����������������������������������������������������� p.38 H. Bueno, S. Halvorsen
3.2 ANTITHROMBOTIC TREATMENT ������������������������������������������� p.41 F. Costa, S. Halvorsen
P.37
3
Acute Coronary Syndrome
Re-evaluate lifestyle, control of risk factors, psychosocial factors and adherance to therapy
Adjustment of secondary prevention therapies. Consider polypill, if needed
Antithrombotictherapy
Aspirin + P2Y12
inhibitor(12 months)
Consider addingEzetimibe*
PCSK9 inhibitor*
Considerdose adjustmentConsider ARNI*
Consider SGLT2 inhibitor*GLP-1 agonists*
Lipidlowering
High intensitystatin therapy
BP/LVD/HF control
ACEI / ARB*,Beta-blockers*,
MRA*
Glucosecontrol
MetforminInsulin*
Hospitalization
• Risk factor control (e.g.weight control, smoking cessation,blood pressure and lipid control)• Diet/nutritional counseling• Physical activity counseling/excercise training• Psychosocial management,sex advice• Vocational advice
Plan and scheduleCardiac Rehabilitation
Educationand counselling
Cardioprotective drugsin secondary prevention
Reinforce educationPsychosocial support
1- Acute care • Drug therapy • Coronary revascularisation2- Cardiovascular risk assessment (e.g. concealed and uncontrolled risk factors)3- Initiate secondary prevention and set treatment goals
After Discharge
CardiacRehabilitation
programme
After 12 monthsconsider*:Ticagrelor60 mg bid
Anticoagulation?**
P.38
3.1SECONDARY PREVENTION STRATEGIES after ACS
Acute Coronary Syndrome
Re-evaluate lifestyle, control of risk factors, psychosocial factors and adherance to therapy
Adjustment of secondary prevention therapies. Consider polypill, if needed
Antithrombotictherapy
Aspirin + P2Y12
inhibitor(12 months)
Consider addingEzetimibe*
PCSK9 inhibitor*
Considerdose adjustmentConsider ARNI*
Consider SGLT2 inhibitor*GLP-1 agonists*
Lipidlowering
High intensitystatin therapy
BP/LVD/HF control
ACEI / ARB*,Beta-blockers*,
MRA*
Glucosecontrol
MetforminInsulin*
Hospitalization
• Risk factor control (e.g.weight control, smoking cessation,blood pressure and lipid control)• Diet/nutritional counseling• Physical activity counseling/excercise training• Psychosocial management,sex advice• Vocational advice
Plan and scheduleCardiac Rehabilitation
Educationand counselling
Cardioprotective drugsin secondary prevention
Reinforce educationPsychosocial support
1- Acute care • Drug therapy • Coronary revascularisation2- Cardiovascular risk assessment (e.g. concealed and uncontrolled risk factors)3- Initiate secondary prevention and set treatment goals
After Discharge
CardiacRehabilitation
programme
After 12 monthsconsider*:Ticagrelor60 mg bid
Anticoagulation?**
Reference modified from Cortés-Beringola A. Eur J Prev Cardiol 2017; 24(3 suppl): 22-28.
* When individually indicated and without specific contraindications. - ** Rivaroxaban 2.5 mg bid pending approval for indication in chronic CAD.
P.39
3.1
Potential strategies to optimize secondary prevention therapy after ACS
• Participation in a comprehensive, multi-disciplinary cardiac rehabilitation programme after hospital discharge
• Coordination with primary care provider (and other specilaists) in therapeutic plan and objectives
• Re-check and reinforce advise on all lifestyle changes (diet, physical activity, smoking cessation…) during follow-up visits
• Check and optimise doses of all indicated secondary prevention drugs
• Use of specialist support, nicotine replacement therapies, varenicline, and/or bupropion individually or in combination for patients who do not quit or restart smoking
• Use of ezetimibe and/or a PCSK9 inhibitor in patients who remain at high risk with LDL-cholesterol >70 mg/dl despite apropriate diet and maximally tolerated doses of statins
• Use of a polypill or combination therapy in patients with suboptimal adherence to drug therapy
P.40
3.1After ACS: POTENTIAL STRATEGIES
TO OPTIMIZE SECONDARY PREVENTION THERAPY
PCI
Stable CAD
DES/BMS or DCB BRS DES/BMS or DCB
High Bleeding Risk
6mo DAPTClass I A1
1mo DAPT Class IIb C
3mo DAPT Class IIa B
≥12mo DAPTClass IIa C
12mo DAPTClass I A
6mo DAPTClass IIa B
>12mo DAPTClass IIb B
DAPT >6moClass IIb A
High Bleeding Risk
ACS
No
1mo
3mo
6mo
12mo
30mo
Yes No
or
Yes
A C
A C
A C
A C 2
A P A Tor
A C 3
A CA P A T
or A C 4
A PA T
A T
Treatmentindication
Device used
Time
A = Aspirin C = Clopidogrel P = Prasugrel T = Tricagrelor Reference: Valgimigli M, et al. Eur Heart J. 2018; 39:213-260.
P.41
3.2ANTITHROMBOTIC TREATMENT:
Dual antiplatelet therapy duration in patients with ACS (1)
Medical Treatment Alone
Stable CAD ACS
No indicationfor DAPT unlessconcomitant orprior indication
overrides
Stable CAD
No indicationfor DAPT unlessconcomitant orprior indication
overrides
12mo DAPTClass I C
6mo DAPTClass IIa C
>12mo DAPTClass IIb C
High Bleeding Risk
CABG
No
1mo
3mo
6mo
12mo
30mo
Yes
ACS
High Bleeding Risk
No YesTime
or
A C 3
A CA P A T
or
A CA PA T
A T
12mo DAPTClass I C
>1mo DAPTClass IIa C
>12mo DAPTClass IIb C
orA C
3A CA T
or A CA T
Treatmentindication
Device used
A = Aspirin C = Clopidogrel P = Prasugrel T = Tricagrelor Reference: Valgimigli M, et al. Eur Heart J. 2018; 39:213-260.
P.42
3.2ANTITHROMBOTIC TREATMENT:
Dual antiplatelet therapy duration in patients with ACS (2)
CLOPIDOGREL
Ticagrelor LD (180 mg)24h after last prasugrel dose
Prasugrel LD (60 mg)24h after last ticagrelor dose
Prasu
grel
LD (60 m
g)
irres
pecti
ce of
prior
clop
idogr
el
timing
and d
osing
Clopido
grel
LD (600 m
g)
24h afte
r last
pras
ugrel
dose
Ticagrelor LD (180 mg)
irrespectice of prior clopidogrel
timing and dosing
Clopidogrel LD (600 mg)
24h after last ticagrelor dose
Ticagrelor LD (90 mg b.i.d.)24h after last prasugrel dose
Prasugrel LD (60 mg)24h after last ticagrelor dose
Prasu
grel
MD (10 m
g q.d.
)
24h afte
r last
clopid
ogrel
dose
Clopido
grel
MD (75 m
g q.d.
)
24h afte
r last
pras
ugrel
dose
Tricagrelor MD (90 mg b.i.d.)
24h after last clopidogrel dose
Clopidogrel LD (600 mg)
24h after last ticagrelor dose
ACCUTE SETTINGALWAYS RELOAD
CLOPIDOGREL
CHRONICSETTING
PRASUGREL TICAGRELOR
PRASUGREL TICAGRELOR
Reference: Valgimigli M, et al. Eur Heart J. 2018;39:213-260.
P.43
3.2ANTITHROMBOTIC TREATMENT:
Switching between P2Y12 inhibitors for DAPT after ACS (1)
CLOPIDOGREL
Ticagrelor LD (180 mg)24h after last prasugrel dose
Prasugrel LD (60 mg)24h after last ticagrelor dose
Prasu
grel
LD (60 m
g)
irres
pecti
ce of
prior
clop
idogr
el
timing
and d
osing
Clopido
grel
LD (600 m
g)
24h afte
r last
pras
ugrel
dose
Ticagrelor LD (180 mg)
irrespectice of prior clopidogrel
timing and dosing
Clopidogrel LD (600 mg)
24h after last ticagrelor dose
Ticagrelor LD (90 mg b.i.d.)24h after last prasugrel dose
Prasugrel LD (60 mg)24h after last ticagrelor dose
Prasu
grel
MD (10 m
g q.d.
)
24h afte
r last
clopid
ogrel
dose
Clopido
grel
MD (75 m
g q.d.
)
24h afte
r last
pras
ugrel
dose
Tricagrelor MD (90 mg b.i.d.)
24h after last clopidogrel dose
Clopidogrel LD (600 mg)
24h after last ticagrelor dose
ACCUTE SETTINGALWAYS RELOAD
CLOPIDOGREL
CHRONICSETTING
PRASUGREL TICAGRELOR
PRASUGREL TICAGRELOR
Reference: Valgimigli M, et al. Eur Heart J. 2018;39:213-260.
P.44
3.2ANTITHROMBOTIC TREATMENT:
Switching between P2Y12 inhibitors for DAPT after ACS (2)
P.45
3.2ANTITHROMBOTIC TREATMENT:
Risk scores validated for DAPT duration decision-making
PRECISE-DAPT score DAPT score
Time of use At the time of coronary stenting After 12 months of uneventful DAPT
DAPT duration strategies assessed
Short DAPT (3-6 months)vs. Standard/long DAPT (12-24 monts)
Standard DAPT (12 months) vs. Long DAPT (30 months)
Score calculation HB Age ≥75 65 to <75 <65
Cigarette smokingDiabetes mellitusMI at presentationPrior PCI or prior MIPaclitaxel-eluting stentStent diameter <3 mmCHF or LVEF <30%Vein graft stent
— 2 pt— 1 pt0 pt
+ 1 pt+ 1 pt+ 1 pt+ 1 pt+ 1 pt+ 1 pt
+ 2 pt+ 2 pt
WBC
Age
CrCl
Prior Bleeding
ScorePoints
Score range 0 to 100 points — 2 to 10 points
Decision making cut-off
Score ≥25 → Short DAPTScore <25 → Standard/long DAPT
Score ≥2 → Long DAPTScore <2 → Standard DAPT
Electronic calculator www.precisedaptscore.com www.daptstudy.org
DUAL THERAPY strategy:
TRIPLE THERAPY strategy:
STEP
2:
Trea
tmen
t ty
peST
EP 3
:Tr
eatm
ent
dura
tion
STEP
1:Pa
tient
risk
asse
ssm
ent
BR>IR
DUAL (12 mo.) OAC alone
OAC alone
OAC alone
TRIPLE (for 1 mo.)
TRIPLE (up to 6 mo.)DUAL(up to 12 mo.)
DUAL (up to 12 mo.)
BR<IR
• NOAC* (preferable) - Apixaban 5 mg b.i.d. (reduce to 2.5 mg b.i.d. (1) - Dabigatran 110 mg b.i.d. (preferable while on DAPT) or 150 mg b.i.d. - Edoxaban 60 mg q.d. (reduce to 30 mg q.d. (2)
- Rivaroxaban 20 mg q.d. (reduce to 15 mg q.d. (3) or 15 mg (may be considered DAPT/SAPT)or• VKA dose ajusted: consider maintaining INR in the lower part of the recommended target range (e.g. 2.0-2.5 for AF and MV in aortic position, 2.5-3.0 for MV in mitral position)
OAC:• Clopidogrel 75 mg q.d. (preferable)*or
• Aspirin 75-100 mg q.d.
SAPT:
• Clopidogrel 75 mg q.d.and
• Aspirin 75-100 mg q.d.
DAPT:
• HIGH RISK OF BLEEDING?High HAS-BLED: Hypertension, abnormal liver/renal function, prior stroke, bleeding diathesis, labile INR if on VKA, age >65, drugs(e.g. NSAIDs or antiplatelets), alcohol abuse, ABC score: Age, Biomarkers (GDF-15, hs cTnT, Hb) and Clinical history of prior bleeding• HIGH RISK OF RECURRENT CORONARY ISCHEMIC EVENTS?ACS at presentation, prior ST, stenting of last remaining vessel, CrCL <60 ml/min, ≥3 stents implanted or lesions treated,bifurcation with 2 stents, overall stentlengh >60 mm, treatment of CTO
TRIPLETHERAPY
(If High BR Low IR)
(If High BR High IR)or
(If Low BR High IR)
DUALTHERAPY
Reference adapted from Valgimigli M et al. Eur Heart J. 2018;39:213-260.
* In case of selecting dual therapy immediately after stent implantation clopidogrel should be selected as single antiplatelet agent. Aspirin should however be administered at the time of the intervention.
(1) Age ≥80 years, body weight ≤60 kg or serum creatinine level ≥1.5 mg/dL. (2) CrCl of 30–50 ml/min, body weight ≤60 kg, concomitant use of verapamil, quinidine or dronedarone. (3) CrCl 30-49 ml/min.
P.46
3.2ANTITHROMBOTIC TREATMENT in patients with concomitant
indication for DAPT and chronic oral anticoagulation (1)
SURGERY
Minimal delay for P2Y12 interruption Days after surgery
CLOPIDOGREL
PRASUGREL
TICAGRELOR
CLOPIDOGREL
PRASUGREL(2)
TICAGRELOR(2)
ASPIRIN(1)
//••••••9••••••8••••••7••••••6••••••5••••••4••••••3••••••2••••••1•••••• 0••••••••••••••••••1-4
STOP
STOP
STOP
= Expected average platelet function recovery(1) Decision to stop aspirin throughout surgery should be made on a single case basis taking into account the surgical bleeding risk
(2) In patients not requiring OAC
Reference: Valgimigli et al. Eur Heart J.2018; 39:213-260.
P.47
3.2ANTITHROMBOTIC TREATMENT:
Management of DAPT after ACS in patients with indication for surgery
LIFE-THREATENING BLEEDINGe.g. massive overt genitourinary,respiratory or upper/lowergastrointestinal bleeding,active intracranial, spinalor intraocular haemorrhage,or any bleeding
STOP ALL ANTITHROMBOTIC MEDICATIONSand reverse OAC. Once bleeding has ceased, re-evaluate the needfor DAPT or SAPT, preferably with the P2Y12 inhibitorespecially in case of upper GI bleeding
CONTINUE DAPT a , CONTINUE OAC c
CONTINUE DAPT, CONTINUE OAC Consider skipping one single next pill
CONSIDER STOPPING DAPTand continue with SAPT, preferably with the P2Y12 inhibitorespecially in case of upper GI bleeding. Once bleeding has ceased,re-evaluate the need for DAPT or SAPTa
CONSIDER STOPPING OACor even reversal until bleeding is controlled, unless prohibitive thrombotic risk(i.e. mechanical heart valve in mitral position, cardiac assist device )b-c-d
Reinitiate treatment within one week if clinically indicated.If Bleeding persist despite treatment, or treatment is not possibleCONSIDER STOPPING ALL ANTITHROMBOTIC MEDICATIONS
CONSIDER STOPPING DAPTand continue with SAPT, preferably with the P2Y12 inhibitorespecially in caseof upper GI bleeding Reinitiate DAPT as soon as deemed safea
CONSIDER STOPPING OACor even reversal until bleeding is controlled, unless very high thrombotic risk(i.e. mechanical heart valves, cardiac assist device, CHA2DS2-VASc ≥4 ).b-c-d
Reinitiate treatment within one week if clinically indicated.
SEVERE BLEEDINGe.g. severe genitourinary,respiratory or upper/lowergastrointestinal bleeding
MODERATE BLEEDINGe.g. genitourinary, respiratoryor upper/lower gastrointestinalbleeding with significant bloodloss or requiring transfusion
MILD BLEEDINGe.g. not self resolving epistaxis,moderate conjunctival bleeding,genitourinary or upper/lowergastrointestinal bleedingwithout significant blood loss,mild haemoptysis
TRIVIAL BLEEDING e.g. skin bruising or ecchimosis,self-resolving epistaxis, minimal conjunctival bleeding
ANTITHROMBOTIC TREATMENTMANAGEMENT DURING BLEEDING
Active bleeding and unstable hemodynamicputting patient’s life immediately at risk?
Hospitalization required? Hb loss >5 g/dl
Hb loss <5 g/dl
Significant blood loss (>3 g/dl) ?
Requires medical interventionor further evaluation?
Yes
Yes
Yes
Yes
No
No
No
No
Reference: Valgimigli et al. Eur Heart J.2018; 39:213-260.
a Consider shortening DAPT duration or switching to less potent P2Y12 inhibitor (i.e. from ticagrelor/prasugrel to clopidogrel), especially if recurrent bleeding occurs b Reinitiate treatment within one week if clinically indicated. For Vitamin-K antagonist consider a target INR of 2.0-2.5 unless overriding indication (i.e. mechanical heart valves or cardiac assist device) for NOAC consider the lowest effective dose. - c In case of triple therapy consider downgrading to dual therapy, preferably with clopidogrel and OAC. - d If patients on dual therapy, consider stopping antiplatelet therapy if deemed safe.
P.48
3.2ANTITHROMBOTIC TREATMENT:
Management of acute bleeding after ACS
Acute upper GI haemorrhage in patient using antiplatelet agent(s) (APT)
Upper GI endoscopy demonstrates a nonvariceal source of bleeding (e.g. peptic ucler bleed)
High risk endoscopic stigmata identified(Forrest classification* Ia, Ib, IIa, IIb)
APT used for secondary prophylaxis(known cardiovascular disease)
Patients on low dose ASA alone• Resume low-lose ASA by day 3 following in dex endoscopy• Second-look endoscopy at the discretionof the endoscopist may be considered
Paptients on dual antiplatelet therapy (DAPT)• Continue low dose ASA without interruption• Early cardiology consultation for recommendationof second resumption/ continuation of second APT• Second-look endoscopy at the discretion of the endoscopoist may be considered
APT used for secondary prophylaxis(known cardiovascular disease)
Patients on low dose ASA alone• Continue low-dose ASA without interruption
Paptients on dual antiplatelet therapy (DAPT)• Continue DAPT without interruption
Low risk endoscopic stigmata identified(Forrest classification* IIc, III)
*The Forrest classification in defined as follows: Ia spuring hemorrhage, Ib oozing hemorrhage, IIa nonbleeding visible vessel, IIb an adherent clot, IIc flat pigmented spot, and III clean base ucler.
Reference: Halvorsen et al. Eur Heart J 2017; 38: 1455-62.
P.49
3.2ANTITHROMBOTIC TREATMENT:
Management of antiplatelet therapy after acute GI bleeding
CHAPTER 4
ACUTE HEART FAILURE
4.1 WET-AND-WARM HEART FAILURE PATIENT ������������������������������ p.52 V.P. Harjola, O. Miró
4.2 CARDIOGENIC SHOCK (WET-AND-COLD) ����������������������������������� p.61 P. Vranckx, U. Zeymer
4
Reference: Ponikowski P et al. Eur J Heart Fail. 2016; 18(8):891-975. DOI: 10.1002/ejhf.592.
WARM-DRY WARM-WET
COLD-DRY COLD-WET
HYPOPERFUSION (+)Cold sweaty extremities, Oliguria,
Mental confusion, Dizziness,Narrow pulse pressure
HYPOPERFUSION (-)
CONGESTION (-) CONGESTION (+)Pulmonary congestion, orthopnoea/paroxismal,
nocturnal dyspnoea, peripheral (bilateral) oedema, jugular venous dilatation, congested hepatomegaly,
gut congestion, ascites, hepatojugular reflux
Clinical profiles of patients with acute heart failure based on the presence/absence of congestion and/or hypoperfusion
Hypoperfusion is not synonymous with hypotension, but often hypoperfusion is accompanied by hypotension.
P.52
4.1Clinical profiles of patients with acute heart failure
Reference: McMurray JJ et al. Eur Heart J (2012); 33:1787-847.Ponikowski P et al. Eur J Heart Fail. 2016; 18:891-975.
1 Symptoms: Dyspnea (on effort or at rest)/breathlessness, fatigue, orthopnea, cough, weight gain/ankle swelling.
2 Signs: Tachypnea, tachycardia, low or normal blood pressure, raised jugular venous pressure, 3rd/4th heart sound, rales, oedema, intolerance of the supine position.
3 Cardiovascular risk profile: Older age, HTN, diabetes, smoking, dyslipidemia, family history, history of CVD.
4 Precipitants/causes that need urgent management (CHAMP): Acute coronary syndrome. Hypertensive emergency. Rapid arrhythmias or severe bradyarrhythmia/conduction disturbance. Mechanical causes. Pulmonary embolism.
5 Differential diagnosis: Exacerbated pulmonary disease, pneumonia, pulmonary embolism, pneumothorax, acute respiratory distress syndrome, (severe) anaemia, hyperventilation (metabolic acidosis), sepsis/septic shock, redistributive/hypovolemic shock.
FACTORS TRIGGERING ACUTE HEART FAILURE
• Acute coronary syndrome• Tachyarrhythmia (e.g. atrial fibrillation, ventricular tachycardia)• Excessive rise in blood pressure• Infection (e.g. pneumonia, infective endocarditis, sepsis).• Non-adherence with salt/fluid intake or medications• Toxic substances (alcohol, recreational drugs)• Drugs (e.g. NSAIDs, corticosteroids, negative inotropic
substances, cardiotoxic chemotherapeutics)• Exacerbation of chronic obstructive pulmonary disease• Pulmonary embolism• Surgery and perioperative complications• Increased sympathetic drive, stress-related cardiomyopathy• Metabolic/hormonal derangements (e.g. thyroid dysfunction,
diabetic ketosis, adrenal dysfunction, pregnancy and peripartum related abnormalities)
• Cerebrovascular insult• Acute mechanical cause : myocardial rupture complicating
ACS (free wall rupture, ventricular septal defect, acute mitral regurgitation), chest trauma or cardiac intervention, acute native or prosthetic valve incompetence secondary to endocarditis, aortic dissection or thrombosis
P.53
4.1ACUTE HEART FAILURE: Diagnosis and causes (2)
Reference: Ponikowski P et al. Eur J Heart Fail. 2016; 18(8): 891-975. DOI: 10.1002/ejhf.592.
Patient with suspected AHF
1. Cardiogenic shock ?Urgent phase after
first medical contact
Immediate stabilizationand transfer to ICU/CCU
Immediate initiationof specific treatement
Indentification of acute aeticology :C = Acute Coronary syndromeH = Hypertension emergencyA = ArrhythmiaM = Acute Mechanical causeP = Pulmonary embolism
Diagnostic work-up to confirm AHFClinical evaluation to select optimal management
Immediate phase(initial 60-120 minutes)
Circulatory support• pharmacological• mechanical
Ventilatory support• oxygen• non-invasive positivepressure ventilation (CPAP, BiPAP)• mechanical ventilation
2. Respiratory failure ?
YesNo
No
No
Yes
Yes
P.54
4.1Initial management of a patient with ACUTE HEART FAILURE
After 60-90 min
In hospital
Pre-hospital or emergency room
Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17:544-58.
Conventional oxygen therapy
Conventionaloxygen therapy
Intolerance
Weaning
CPAP
CPAP
FAILURE
PS-PEEP
SUCCESS
SIGNIFICANT HYPERCAPNIAAND ACIDOSIS
NORMAL pHAND pCO
2
Intubation
Intubation
RESPIRATORY DISTRESS?SpO2 <90%, RR>25,
Work of breathing, orthopnea
"PERSISTENT" RESPIRATORY DISTRESS?
Upright position
No Yes
Yes
Venous/Arterial blood gases
No
Room air
P.55
4.1ACUTE HEART FAILURE: Airway (A) and breathing (B)
Oxygen therapy and ventilatory support in acute heart failure
INSTRUMENTATION & INVESTIGATIONS: Intravenous line (peripheral/central) and BP monitoring (arterial line in shock and severe ventilatory/gas-exchange disturbances)Laboratory measures • Cardiac markers (troponin, BNP/NT-proBNP/MR-proANP) • Complete blood count, electrolytes, creatinine, urea, glucose,
inflammation, TSH • Consider arterial or venous blood gases, lactate, D-dimer
(suspicion of acute pulmonary embolism) Standard 12-lead ECG • Rhythm, rate, conduction times? • Signs of ischemia/myocardial infarction? Hypertrophy? Echocardiography a) Immediately in haemodynamically unstable patients b) Within 48 hours when cardiac structure and function are either not known or
may have changed since previous studies
Ventricular function (systolic and diastolic)? Estimated left-and right-side filling pressures? Lung ultrasound? Presence of valve dysfunction (severe stenosis/insufficiency)? Pericardial tamponade?
ACTIONS:
Rule in/out acute heart failure
as cause of symptoms and signs
Determine clinical profile
Start as soon as possible treatment of both heart failure and the factors identified
as triggers
Establish cause
C - CIRCULATION*
HR (bradycardia [<60/min], normal [60-100/min], tachycardia [>100/min]), rhythm (regular, irregular), SBP (very low [<90 mmHg], low, normal [110-140 mmHg], high [>140 mmHg]), and elevated jugular pressure should be checked.
P.56
4.1ACUTE HEART FAILURE: Initial diagnosis (CDE)
References: Mebazaa A et al. Intensive Care Med. (2016); 42(2):147-63; Mueller C et al. Eur Heart J Acute Cardiovasc Care. (2017); 6(1):81-6.
D – DISABILITY DUE TO NEUROLOGICAL DETERIORATION • Normal consiousness/altered mental status?
Measurement of mental state with AVPU (alert, visual, pain or unresponsive) or Glasgow • Coma Scale: EMV score <8 Consider endotracheal intubation and mechanical ventilation • Anxiety, severe dyspnea? Consider cautious administration of morphine 2 mg i.v. bolus,
preceded by antiemetic as needed
E – EXPOSURE & EXAMINATION • Temperature/fever: central and peripheral • Weight • Skin/extremities: circulation (e.g. capilary refill), color • Urinary output (<0.5 ml/kg/hr) Consider inserting indwelling catheter;
the benefits should outweigh the risks of infection and long-term complications
P.57
4.1
Patient with AHF
Bedside assessment to identify haemodynamic profiles
"DRY" patient
"WET" and "COLD" patient
Systolic blood pressure <90 mmHg
"WET" patient
No(5% of all AHF patients)
Yes(95% of all AHF patients)
Yes No
Yes No
Yes
No
PRESENCE OF CONGESTIONa?
ADEQUATE PERIPHERAL PERFUSION?
"DRY" and "COLD"Hypoperfused, hypovolemic
"DRY" and "WARM"Adequately perfused
≈ Compensated
• Inotropic agent• Consider vasopressor in refractory cases• Diuretic (when perfusion corrected)• Consider machanical circulatory support if no response to drugs
• Vasodilators• Diuretics• Consider inotropic agent In refractory cases• Vasodilator
• Diuretic• Diuretic• Vasodilator• Ultrafiltration (consider if diuretic resistance)
Consider fluid challengeConsider inotropic agent if still hypoperfusedAdjust oral therapy
"WET" and "WARM"patient (typically elevatedor normal systolic blood
pressure)
Vascular type-fluid redistribution
Hypertension predominates
Cardiac type-fluid accumulation
Congestion predominates
P.58
4.1ACUTE HEART FAILURE: Management of patients with acute heart
failure based on clinical profile during an early phase
Patient with AHF
Bedside assessment to identify haemodynamic profiles
"DRY" patient
"WET" and "COLD" patient
Systolic blood pressure <90 mmHg
"WET" patient
No(5% of all AHF patients)
Yes(95% of all AHF patients)
Yes No
Yes No
Yes
No
PRESENCE OF CONGESTIONa?
ADEQUATE PERIPHERAL PERFUSION?
"DRY" and "COLD"Hypoperfused, hypovolemic
"DRY" and "WARM"Adequately perfused
≈ Compensated
• Inotropic agent• Consider vasopressor in refractory cases• Diuretic (when perfusion corrected)• Consider machanical circulatory support if no response to drugs
• Vasodilators• Diuretics• Consider inotropic agent In refractory cases• Vasodilator
• Diuretic• Diuretic• Vasodilator• Ultrafiltration (consider if diuretic resistance)
Consider fluid challengeConsider inotropic agent if still hypoperfusedAdjust oral therapy
"WET" and "WARM"patient (typically elevatedor normal systolic blood
pressure)
Vascular type-fluid redistribution
Hypertension predominates
Cardiac type-fluid accumulation
Congestion predominates
a Symptoms/signs of congestion: orthopnoea, paroxysmal nocturnal dyspnoea, breathlessness, bi-basilar rales, abnormal blood pressure response to the Valsalva maneuver (left-sided); symptoms of gut congestion, jugular venous distension, hepatojugular reflux, hepatomegaly, ascites, and peripheral oedema (right-sided).
For more information on individual drug doses and indications,
SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
Reference: Ponikowski P et al. Eur J Heart Fail. 2016; 18(8):891-975. DOI: 10.1002/ejhf.592.
P.59
4.1
No acute heart failure
MONITORINGDyspnea (VAS, RR), BP, SpO2, HR and
rhythm, urine output, peripheral perfusion
REASSESSMENTClinical, biological and psychosocial parameters by trained nurses
Observation unit (<24h)
Discharge home
Ward (cardiology, internal medicine, geriatrics)
Rehabilitation program
Visit to cardiologist <1-2 weeks
Palliative care hospitals
ICU/CCU
Confirmed acute heart failure
DIAGNOSTIC TESTS
OBS
ERVA
TIO
N U
P TO
120
min
ADM
ISSI
ON
/DIS
CHA
RGE
Risk stratification: ensure patientis at low risk before direct dischargeRisk stratification: ensure patient
is at low risk before direct discharge
TREATMENT OBJECTIVES to prevent organ dysfunction:Improve symptoms, maintain SBP >90 mmHg and peripheral
perfusion, mantain SpO2 >90% (see table in pages 63-64)
Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17: 544-58 and Miró Ò et al. Ann Intern Med (2017); 167:698-705.
P.60
4.1ACUTE HEART FAILURE: Management of acute heart failure
Normotension/Hypertension
Hypotension Low heart rate Potassium Renal impairment
<100 >90 mmHg
<90 mmHg
<60≥50 bpm
<50 bpm ≤3.5 mmol/L
>5.5 mmol/L
Cr <2.5,eGFR >30
Cr >2.5,eGFR <30
ACE-I/ARB Review/increase
Reduce/ stop
Stop No change
No change
Review/increase
Stop Review Stop
Beta-blocker No change Reduce/ stop
Stop Reduce Stop No change
No change
No change
No change
MRA No change No change
Stop No change
No change
Review/increase
Stop Reduce Stop
Diuretics Increase Reduce Stop No change
No change
Review/ No change
Review/ increase
No change
Review
Sacubitril/Valsartan
Review/increase
Stop Stop No change
No change
Review/increase
Stop Review Stop
Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17(6):544-58.
Management of oral therapy in AHF in the first 48 hours P.61
ACUTE HEART FAILURE: Treatment (C) and preventive measures 4.04.1
Normotension/Hypertension
Hypotension Low heart rate Potassium Renal impairment
<100 >90 mmHg
<90 mmHg
<60≥50 bpm
<50 bpm ≤3.5 mmol/L
>5.5 mmol/L
Cr <2.5,eGFR >30
Cr >2.5,eGFR <30
Other vasodilators (nitrates)
Increase Reduce/stop
Stop No change
No change
No change
No change
No change
No change
Other heart rate slowing drugs (amiodarone, non-dihydropyridine CCB, ivabradine)
Review Reduce/stop
Stop Reduce/stop
Stop Review/stop(*)
No change
No change
No change
Thrombosis prophylaxis should be started in patients not anticoagulated.(*) Amiodarone.
Management of oral therapy in AHF in the first 48 hours
Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17(6):544-58.
P.62
ACUTE HEART FAILURE: Treatment (C) and preventive measures (Cont.) 4.1
Hemodynamic criteria to define cardiogenic shock
• Systolic blood pressure <80 to 90 mmHg or mean arterial pressure 30 mmHg lower than baseline
• Severe reduction in cardiac index: <1.8 l/min/m2 without support or <2.0 to 2.2 l/min/m2 with support
• Adequate or elevated filling pressure: Left ventricular end-diastolic pressure >18 mmHg or Right atrial pressure >10 to 15 mmHg
Clinical condition defined as the inability of the heart to deliver an adequate amount of blood to the tissues to meet resting metabolic demands as a result of impairment of its pumping function.
Cardiogenic shock is equal to wet-cold phenotype. The clinical signs of hypoperfusion are listed in page 65. In addition, blood lactate is typically elevated above 2 mmol/L.
P.63
4.2CARDIOGENIC SHOCK: Definition
LV pump failure is the primary insult in most forms of CS, but other parts of the circulatory system contribute to shock with inadequate compensation or additional defects P.64
4.2CARDIOGENIC SHOCK: Causes
This protocol should be initiated as soon as cardiogenic shock/end organ hypoperfusion is recognised and should not be delayed pending intensive care admission.
EARLY TRIAGE & MONITORINGStart high flow O2 Establish i.v. access
• Age: 65–74, ≥75• Heart rate >100 beats per minute• Systolic blood pressure <100 mmHg• Proportional pulse pressure ≤25 % (CI <2.2 l/min/m2)• Orthopnea (PCWP >22 mmHg)• Tachypnea (>20/min), >30/min (!)• Killip class IV • Clinical symptoms of tissue hypoperfusion/hypoxia:
- cool extremities - decreased urine output (urine output <40 ml/h) - decreased capillary refill or mottling - alteration in mental status
INITIAL RESUSCITATION• Arterial and a central venous
catheterization with a catheter capable of measuring central venous oxygen saturation
• Standard transthoracic echocardiogram to assess left (and right) ventricular function and for the detection of potential mechanical complications following MI
• Early coronary angiography in specialized myocardial intervention centre when signs and/or symptoms of ongoing myocardial ischemia (e.g. ST-segment elevation myocardial infarction).
• CORRECT: hypoglycemia & hypocalcemia,• TREAT: sustaned arrhythmias: brady- or tachycardia• Isotonic saline-fluid challenge - 200-300 ml
over 30 min period to achieve a central venous pressure of 8 to 12 mmHg or until perfusion improves (with a maximum of 500 ml)
• CONSIDER NIMV for comfort (fatigue, distress) or as needed: - To correct acidosis - To correct hypoxemia
• INOTROPIC SUPPORT (dobutamine, levosimendan and/or vasopressor support)
TREATMENT GOALS • a mean arterial pressure of 60 mmHg or above, • a mean pulmonary artery wedge pressure of 18 mmHg or below, • a central venous pressure of 8 to 12 mmHg, • a urinary output of 0,5 ml or more per hour per kilogram of body weight • an arterial pH of 7.3 to 7.5 • a central venous saturation (ScvO2) ≥70% (provided SpO2 ≥93%
and Hb level ≥9 g/dl)
In persistent drug-resistant cardiogenic shock,consider mechanical circulatory support
0 min
5 min
15 min
60 min
EMER
GEN
CY
DEP
AR
TMEN
T
CA
RD
IAC
INTE
NS
IVE
CA
RE
UN
ITP.65
4.2CARDIOGENIC SHOCK: Initial triage and management
Ventilator modeTidal Volume goalPlateau Pressure goalAnticipated PEEP levelsVentilator rate and pH goalInspiration: Expiration timeOxygenation goal: • PaO2
• SpO2
Pressure assist/controlReduce tidal volume to 6-8 ml/kg lean body weight≤30 cm H2O5-10 cm H2O12-20, adjusted to achieve a pH ≥7.30 if possible1:1 to 1:2
50-80 mmHg>90%
Predicted body weight calculation: • Male: 50 + 0.91 (height in cm - 152.4) • Female: 45.5 + 0.91 (height in cm - 152.4)
Some patients with CS will require increased PEEP to attain functional residual capacity and maintain oxygenation, and peak pressures above 30 cm H2O to attain effective tidal volumes of 6-8 ml/kg with adequate CO2 removal.
For more informations on individual drug doses and indications:
For more information on individual drug doses and indications,
SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
P.66
4.2CARDIOGENIC SHOCK: Treatment and ventilator procedures
CARDIOGENIC SHOCK: MANAGEMENT FOLLOWING STEMI
Assess volume statusTreat sustained arrhythmias: brady - or tachy -Consider mechanical ventilation for comfort (during PCI) and/or as needed: • to correct acidosis • to correct hypoxemiaInotropic support (dobutamine and/or vasopressor support)
Signs (ST-segment elevation or new LBBB)and/or clinical symptoms of ongoing
myocardial ischemia
Early coronary angiography± Pulmonary artery catheter± IABP in selected patientsin a specialised Myocardial
Intervention Centre
PCI ± stentingof the culprit lesion
CABG+ correct mechanical complications
Pump failureRV, LV, both
Sho
rt-t
erm
mec
hani
cal
circ
ulat
ory
supp
ort
AorticdissectionPericardialtamponade
• Acute severe mitral valve regurgitation • Ventricular septum rupture • Severe aortic/mitral valve stenosis
Operating theater ± coronary angiography
Emergency echocardiography± Tissue doppler imaging
± Color flow imagingNo
NSTEACS,Delayed CSYes
P.67
4.2CARDIOGENIC SHOCK: management following STEMI
72-hrs
2-weeks
1-month ...
Left ventricular support BiVentricular support
Partial support
IABP Impella 2.5 Tandem-heart
Impella 5.0 ImplantableECMOLevitronix
Full support
Level of support
Pulmonary support
P.68
4.2CARDIOGENIC SHOCK:
Mechanical circulatory support, basic characteristics
Different systems for mechanical circulatory support are available to the medical community. The available devices differ in terms of the insertion procedure, mechanical properties, and mode of action. A minimal flow rate of 70 ml/kg/min, representing a cardiac index of at least 2.5 L/m2, is generally required to provide adequate organ perfusion. This flow is the sum of the mechanical circulatory support output and the remaining function of the heart.
The SAVE-score may be a tool to predict survival for patients receiving ECMO for refractory cardiogenic shock
Type Support Access
Intra-aortic balloon pump
Balloon counterpulsation
Pulsatile flow <0.5 L Arterial: 7.5 French
Impella Recover LP 2.5 CP LP 5.0
Axial flow Continuous flow <2.5 L <4.0 L <5.0 L
Arterial: 12 FrenchArterial: 14 FrenchArterial: 21 French
Tandemheart
Centrifugal flow
<5.0 L
Continuous flow
<5.0 L
Venous: 21 FrenchArterial: 15-17 French
Venous: 15-29 FrenchArterial: 15-29 French
Cardiohelp
(www.save-score.com).
P.69
4.2
Monsieurs KG, et al. European Resuscitation Council Guidelines for Resuscitation 2015. Section 1 Executive Summary. Resuscitation 2015; 95C:1-80, DOI:10.1016/j.resuscitation.2015.07.038
CHAPTER 5 CARDIAC ARREST AND
CARDIOPULMONARY RESUSCITATIONN. Nikolaou, L. Bossaert
5
THE CHAIN OF SURVIVAL
P.71
OUT OF HOSPITAL CARDIAC ARREST: ASSESSMENT OF A COLLAPSED VICTIM AND INITIAL TREATMENT
VICTIM COLLAPSES
Victim respondsVictim unresponsive
Leave victim as foundFind out what is wrong
Reassess victim regularly Shout for helpOpen airway
Assess breathing
Not breathing normally
Call for an ambulanceStart CPR 30:2
Send or go for an AED
As soon as AED arrives
Start AED,listen to and follow voice prompts
AED Assesses rhythm
AED not available
30 chest compressions: 2 rescue breaths
Continue until victim starts to wake up: to move, open eyes, and breathe normally
No shock advised
Immediately resume CPR 30:2 for 2 min
Shock advised
1 shock
Immediately resumeCPR 30:2 for 2 min
Breathing normally
Put victim in recovery positionand call for an ambulance
Approach safelyCheck response
P.72
5OUT OF HOSPITAL CARDIAC ARREST:
Assessment of a collapsed victim and initial treatment
OUT OF HOSPITAL CARDIAC ARREST: ASSESSMENT OF A COLLAPSED VICTIM AND INITIAL TREATMENT
VICTIM COLLAPSES
Victim respondsVictim unresponsive
Leave victim as foundFind out what is wrong
Reassess victim regularly Shout for helpOpen airway
Assess breathing
Not breathing normally
Call for an ambulanceStart CPR 30:2
Send or go for an AED
As soon as AED arrives
Start AED,listen to and follow voice prompts
AED Assesses rhythm
AED not available
30 chest compressions: 2 rescue breaths
Continue until victim starts to wake up: to move, open eyes, and breathe normally
No shock advised
Immediately resume CPR 30:2 for 2 min
Shock advised
1 shock
Immediately resumeCPR 30:2 for 2 min
Breathing normally
Put victim in recovery positionand call for an ambulance
Approach safelyCheck response
P.73
5
IN-HOSPITAL CARDIAC ARREST: ASSESSMENT OF A COLLAPSED VICTIM AND INITIAL TREATMENT
Collapsed/sick patient
Shout for HELP & assess patient
YesNo
Assess ABCDERecognise & treat
oxygen; monitoring, i.v. access
Call resuscitationteam
CPR 30:2with oxygen and airway adjuncts
Call resuscitation teamif appropriate
Apply pads/monitorAttempt defibrillation
if appropriate
Handover to resuscitation teamAdvanced Life Supportwhen resuscitation team arrives
Signs of life?
P.74
5IN-HOSPITAL CARDIAC ARREST:
Assessment of a collapsed victim and initial treatment
IN-HOSPITAL CARDIAC ARREST: ASSESSMENT OF A COLLAPSED VICTIM AND INITIAL TREATMENT
Collapsed/sick patient
Shout for HELP & assess patient
YesNo
Assess ABCDERecognise & treat
oxygen; monitoring, i.v. access
Call resuscitationteam
CPR 30:2with oxygen and airway adjuncts
Call resuscitation teamif appropriate
Apply pads/monitorAttempt defibrillation
if appropriate
Handover to resuscitation teamAdvanced Life Supportwhen resuscitation team arrives
Signs of life?
P.75
5
IN-HOSPITAL CARDIAC ARREST: ADVANCED LIFE SUPPORT
Unresponsiveand not breathing
normally ?
Assessrhythm
CPR 30:2Attach defibrillator/monitor
Minimise interruptions
DURING CPR• Ensure high-quality chest compressions• Minimise interruptions to compressions• Give Oxygen• Use waveform capnography• Continuous chest compressions when advanced airway in place• Vascular access (intravenous, intraosseous) • Give adrenaline every 3-5 min• Give amiodarone after 3 shocks• Correct reversible causes
REVERSIBLE CAUSES • Hypoxia• Hypovolaemia• Hypo-/hyperkalaemia/metabolic• Hypothermia
• Thrombosis• Tamponade - cardiac• Toxins• Tension pneumothorax
Call resuscitationteam
Shockable(VF/Pulseless VT)
1 ShockReturn of
spontaneous circulation
IMMEDIATE POST CARDIACARREST TREATMENT
Immediately resume:CPR for 2 min
Minimise interruptions
Non-shockable(PEA/Asystole)
Immediately resume:CPR for 2 min
Minimise interruptions • Use ABCDE approach• Aim for SaO2 94-98%• Aim for normal PaCO2
• 12-lead ECG• Treat precipitating cause• Temperature control / Therapeutic hypothermia
CONSIDER• Ultrasound imaging• Mechanical chest compressions to facilitate transfer/treatment• Coronary angiography and PCI• Extracorporeal CPR
P.76
5IN-HOSPITAL CARDIAC ARREST: Advanced life support
IN-HOSPITAL CARDIAC ARREST: ADVANCED LIFE SUPPORT
Unresponsiveand not breathing
normally ?
Assessrhythm
CPR 30:2Attach defibrillator/monitor
Minimise interruptions
DURING CPR• Ensure high-quality chest compressions• Minimise interruptions to compressions• Give Oxygen• Use waveform capnography• Continuous chest compressions when advanced airway in place• Vascular access (intravenous, intraosseous) • Give adrenaline every 3-5 min• Give amiodarone after 3 shocks• Correct reversible causes
REVERSIBLE CAUSES • Hypoxia• Hypovolaemia• Hypo-/hyperkalaemia/metabolic• Hypothermia
• Thrombosis• Tamponade - cardiac• Toxins• Tension pneumothorax
Call resuscitationteam
Shockable(VF/Pulseless VT)
1 ShockReturn of
spontaneous circulation
IMMEDIATE POST CARDIACARREST TREATMENT
Immediately resume:CPR for 2 min
Minimise interruptions
Non-shockable(PEA/Asystole)
Immediately resume:CPR for 2 min
Minimise interruptions • Use ABCDE approach• Aim for SaO2 94-98%• Aim for normal PaCO2
• 12-lead ECG• Treat precipitating cause• Temperature control / Therapeutic hypothermia
CONSIDER• Ultrasound imaging• Mechanical chest compressions to facilitate transfer/treatment• Coronary angiography and PCI• Extracorporeal CPR
P.77
5
Give adrenaline and amiodaroneafter 3rd shock
Adrenaline: 1 mg i.v.(10 ml 1:10,000 or 1 ml 1:1000)
repeated every 3-5 min(alternate loops)
given without interrupting chest compressions
Amiodarone 300 mg bolus i.v.
Second bolus dose of 150 mg i.v.if VF/VT persists
followed by infusion of900 mg over 24 h
Adrenaline: 1mg i.v. (10 ml 1:10,000 or 1 ml 1:1000)given as soon as circulatory access is obtained
Repeat every 3-5 min (alternate loops)Give without interrupting chest compressions
IN-HOSPITAL CARDIAC ARREST: DRUG THERAPY DURING ADVANCED LIFE SUPPORT
Cardiac Arrest
Non-shockable rhythm
Shockable rhythm(VF, pulseless VT)
P.78
5IN-HOSPITAL CARDIAC ARREST:
Drug therapy during advanced life support
CHAPTER 6
RHYTHM DISTURBANCES
6.1 SUPRAVENTRICULAR TACHYCARDIAS AND ATRIAL FIBRILLATION ���� p.80 J. Brugada
6.2 VENTRICULAR TACHYCARDIAS ������������������������������������������ p.84 M. Santini, C. Lavalle, S. Lanzara
6.3 BRADYARRHYTHMIAS ���������������������������������������������������� p.87 B. Gorenek
6
QRS morphology similar to QRS morphologyin sinus rhythm?
QRS morphology similar to QRS morphologyin sinus rhythm?
YES
QRS complex <120 msec
Supraventr.Tachycardia
QRS complex >120 msec
Supraventr.Tachycardia
+ BBB
QRS complex <120 msec
QRS complex >120 msec
Fascicular Tachycardiaor SVT with
aberrant conduction
Ventricular Tachycardia or SVT with
aberrant conduction
QRS complex <120 msec
QRS complex >120 msec
AFconductingover AVN
AF + BBBor
AF + WPW
AF+
WPW
IrregularVentricular Tachycardia
Variable QRSmorphology
NO YES NO
TACHYARRHYTHMIAS: DIAGNOSTIC CRITERIA
Tachycardia >100 beats/min
IrregularRegular
P.80
6.1TACHYARRHYTHMIAS: Diagnostic criteria
• Concordant precordial pattern (all leads + or all leads –)• No RS pattern in precordial leads • RS pattern with beginning of R wave to nadir of S wave >100 msec
Consider SVT using
the AV node (AVNRT, AVNT)
Atrial flutteror atrial
tachycardiaVentricular
Tachycardia Ventricular
Tachycardia Ventricular
Tachycardia
Consider Sinus tachycardia
or non properadministrationof adenosine
(too slow, insufficient dose, etc)
Typicalmorphologyin V1 & V6
More As than Vs
More Vs than As
WideQRS complex
NarrowQRS complex
Regular tachycardia
Vagal maneuversor
i.v. adenosine
No changeTachycardia terminates
AV relation changes
P.81
6.1TACHYARRHYTHMIAS: Diagnostic maneuvers
Hemodynamicallynon-stable
Immediate electricalcardioversion
No termination
Hemodynamicallystable
Vagal maneuversand/or i.v. Adenosine
Less than 48 hourssince initiation
ANDhemodynamically stable
CardioversionElectrical or pharmacologicalusing oral or i.v. flecainide
(only in normal heart)or i.v. vernakalant
Anticoagulationis initiated using i.v. heparine
Hemodynamically non-stable
Immediate electricalCardioversion
If no cardioversionis considered: rate control
using betablockers orcalcium antagonists,together with proper
anticoagulation, if required
Narrow QRScomplex tachycardia
Reconsider diagnosis: sinus tachycardia,atrial tachycardia
If no evidence:Intravenous verapamil
Wide QRScomplex tachycardia
Reconsider the diagnosis of Ventricular Tachycardia even
if hemodynamically stable
Do not administerverapimil
More than 48 hours ORunknown time of initiation,
ANDPatient chronically anticoagulated
ORa TEE showing no thrombus
Electrical or pharmacological Cardioversion
Termination
TACHYARRHYTHMIAS: THERAPEUTIC ALGORITHMS (1)
Regular Supraventricular Tachycardias with or without bundle branch block
Irregular and narrow QRS complexTachycardia
Hemodynamicallynon-stable
Immediate electricalcardioversion
No termination
Hemodynamicallystable
Vagal maneuversand/or i.v. Adenosine
Less than 48 hourssince initiation
ANDhemodynamically stable
CardioversionElectrical or pharmacologicalusing oral or i.v. flecainide
(only in normal heart)or i.v. vernakalant
Anticoagulationis initiated using i.v. heparine
Hemodynamically non-stable
Immediate electricalCardioversion
If no cardioversionis considered: rate control
using betablockers orcalcium antagonists,together with proper
anticoagulation, if required
Narrow QRScomplex tachycardia
Reconsider diagnosis: sinus tachycardia,atrial tachycardia
If no evidence:Intravenous verapamil
Wide QRScomplex tachycardia
Reconsider the diagnosis of Ventricular Tachycardia even
if hemodynamically stable
Do not administerverapimil
More than 48 hours ORunknown time of initiation,
ANDPatient chronically anticoagulated
ORa TEE showing no thrombus
Electrical or pharmacological Cardioversion
Termination
TACHYARRHYTHMIAS: THERAPEUTIC ALGORITHMS (1)
Regular Supraventricular Tachycardias with or without bundle branch block
Irregular and narrow QRS complexTachycardia
P.82
6.1TACHYARRHYTHMIAS: Therapeutic algorithms (1)
Hemodynamically non-stable
Immediate electricalCardioversion
If no cardioversion is considered:rate control using betablockers orcalcium antagonists (only if VT and
AF+WPW is excluded), togetherwith proper anticoagulation
if required
Less than 48 hours since initiationAND
hemodynamically stable
Cardioversionelectrical or pharmacologicalusing oral or i.v. flecainide
(only in normal heart)or i.v. amiodarone
Anticoagulationis initiated using i.v. heparin
More than 48 hoursor unknown initiation,
ANDpatient chronically anticoagulated
or a TEE showing no thrombus
Electrical or pharmacologicalCardioversion
TACHYARRHYTHMIAS: THERAPEUTIC ALGORITHMS (2)
Irregular and wide QRS complex Tachycardia
P.83
6.1TACHYARRHYTHMIAS: Therapeutic algorithms (2)
VENTRICULAR TACHYCARDIAS: DIFERENTIAL DIAGNOSIS OF WIDE QRS TACHYCARDIA
EKG signs of atrio-ventricular dissociationRandom P waves unrelated to QRS complexesCapture beats / fusion beats / second degree V-A block
1st Step
2nd Step
3rd Step
Concordant pattern in precordial leadsNo RS morphology in any of the precordial leads
An interval >100 ms from the beginning of theQRS complex to the nadir of S in a precordial lead
Morphology in precordial leads
RBBB morphology LBBB morphology
Morphologyin aVR lead
Initial R wave
Initial R waveor q >40 msec
V1: qR, R, R’V6: rS,QS
V1: rsR’, RSR’V6: qRs
Aberrant conduction
V6: R V1: rS; R >30 ms,S nadir >60 ms,notching of the
S wave
V6: qR, QS
Yes
Yes
Yes
No
No
No
Yes
No
No
No
No
Yes
Yes
Yes
Notch in thedescendingQ wave limb
Vi/Vt ≤1
VT
VT
Aberrant conduction
VT
P.84
6.2VENTRICULAR TACHYSCARDIAS:
Diferential diagnosis of wide QRS tachyscardias
VENTRICULAR TACHYCARDIAS: DIFERENTIAL DIAGNOSIS OF WIDE QRS TACHYCARDIA
EKG signs of atrio-ventricular dissociationRandom P waves unrelated to QRS complexesCapture beats / fusion beats / second degree V-A block
1st Step
2nd Step
3rd Step
Concordant pattern in precordial leadsNo RS morphology in any of the precordial leads
An interval >100 ms from the beginning of theQRS complex to the nadir of S in a precordial lead
Morphology in precordial leads
RBBB morphology LBBB morphology
Morphologyin aVR lead
Initial R wave
Initial R waveor q >40 msec
V1: qR, R, R’V6: rS,QS
V1: rsR’, RSR’V6: qRs
Aberrant conduction
V6: R V1: rS; R >30 ms,S nadir >60 ms,notching of the
S wave
V6: qR, QS
Yes
Yes
Yes
No
No
No
Yes
No
No
No
No
Yes
Yes
Yes
Notch in thedescendingQ wave limb
Vi/Vt ≤1
VT
VT
Aberrant conduction
VT
P.85
6.2
MANAGEMENT OF WIDE QRS TACHYCARDIAS
Hemodynamic Tolerance
Stable
Regular rhythmIrregular rhythm
Vagal maneuverand/or
i.v. adenosine (push)
Differential Diagnosis
Interruption orslow down HR
Yes
YesNo
No
DifferentialDiagnosis
(see chapter 6.1page 81)
SVT
AF with aberrant ventricular conduction • β-blockers• i.v.• Verapamil or diltazem Pre excited AF • Class 1 AADs Polymorphic VT • Amiodarone
Amiodarone 150 mg i.v.(can be repeated up to
a maximum dose of 2.2 g in 24 h) Synchronised cardioversion
With pulsePulseless
Non-stable
• Sedationor analgesia
• Synchronised cardioversion 100 to 200 J (monophasic)or 50-100 J (biphasic)
ACLS Resuscitation algorithm
• Immediate high- energydefibrillation (200 J biphasicor 360 monophasic)• Resume CPR and continue according to the ACLS algorithm
Drugs used in the ACLS algorithm
• Epinephrine 1 mg i.v./i.o.(repeat every 3-5 min)• Vasopressin 40 i.v./i.o. • Amiodarone 300 mg i.v./i.o. once then consider an additional150 mg i.v./i.o. dose• Lidocaine 1-1.5 mg/kg first dosethen 0.5-0-75 mg/kg i.v./i.o.for max 3 doses or 3 mg/kg• Magnesium loading dose 1-2 gr i.v./i.o. for torsade des pointes
P.86
6.2Management of wide QRS TACHYSCARDIAS
Sinus node dysfunction Atrioventricular (AV) blocks
• Sinus bradycardia: It is a rhythm that originates from the sinus node and has a rate of under 60 beats per minute
• Sinoatrial exit block: The depolarisations that occur in the sinus node cannot leave the node towards the atria
• Sinus arrest: Sinus pause or arrest is defined as the transient absence of sinus P waves on the ECG
• First degree AV block: Atrioventricular impulse transmission is delayed, resulting in a PR interval longer than 200 msec
• Second degree AV block: Mobitz type I (Wenckebach block): Progressive PR interval prolongation, which precedes a nonconducted P wave
• Second degree AV block: Mobitz type II: PR interval remains unchanged prior to a P wave that suddenly fails to conduct to the ventricles
• Third degree (complete) AV block: No atrial impulses reach the ventricle
P.87
6.3BRADYARRHYTHMIAS: Definitions and diagnosis
• Rule out and treat any underlying causes of bradyarrhythmia• Treat symptomatic patients only
For more information on individual drug doses and indications,
SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
Temporary transvenous pacing
Be Careful! • Complications are common! • Shall not be used routinely • Use only as a last resource when chronotropic drugs are insufficient • Every effort should be made to implant a permanent pacemaker
as soon as possible, if the indications are established.
Indications limited to: • High-degree AV block without escape rhythm • Life threatening bradyarrhythmias, such as those that occur during interventional
procedures, in acute settings such as acute myocardial infarction, drug toxicity.
P.88
6.3BRADYARRHYTHMIAS: Treatment (1)
Permanent pacemaker is indicated in the following settings:
• Documented symptomatic bradycardia, including frequent sinus pauses that produce symptoms • Symptomatic chronotropic incompetence • Symptomatic sinus bradycardia that results from required drug therapy for medical conditions
Permanent pacemaker is not recommended in the following settings:
• Asymptomatic patients • Patients for whom the symptoms suggestive of bradycardia
have been clearly documented to occur in the absence of bradycardia • Symptomatic bradycardia due to nonessential drug therapy
P.89
6.3BRADYARRHYTHMIAS: Treatment (2)
Pacemaker therapies in sinus node dysfunction
Permanent pacemaker therapy is indicated in the following settings regardless of associated symptoms:
• Third-degree AV block • Advanced second-degree AV block • Symptomatic Mobitz I or Mobitz II second-degree AV block • Mobitz II second-degree AV block with a wide QRS or chronic bifascicular block • Exercise-induced second- or third-degree AV block • Neuromuscular diseases with third- or second-degree AV block • Third- or second-degree (Mobitz I or II) AV block after catheter ablation or valve surgery
when block is not expected to resolve
Permanent pacemaker is not recommended in the following settings:
• Asymptomatic patients • Patients for whom the symptoms suggestive of bradycardia have been clearly documented
to occur in the absence of bradycardia • Symptomatic bradycardia due to nonessential drug therapy
P.90
6.3BRADYARRHYTHMIAS: Treatment (3)
Pacemaker therapies in atrioventricular blocks
CHAPTER 7
ACUTE VASCULAR SYNDROMES
7.1 ACUTE AORTIC SYNDROMES ���������������������������������������������� p.92 A. Evangelista
7.2 ACUTE PULMONARY EMBOLISM ������������������������������������������ p.102 A. Torbicki
7
Classic aortic dissectionSeparation of the aorta media with presence
of extraluminal blood within the layers of the aortic wall.The intimal flap divides the aorta into two lumina, the true and the false
Penetrating aortic ulcer (PAU)Atherosclerotic lesion penetrates
the internal elastic lamina of the aorta wall
Aortic aneurysm rupture (contained or not contained)
Intramural hematoma (IMH)Aortic wall hematoma with no entry tear and no two-lumen flow
P.92
7.1ACUTE AORTIC SYNDROMES: Concept and classification (1)
Types of presentation
DeBakey’s Classification• Type I and Type II dissections both originate in the ascending aorta
In type I, the dissection extends distally to the descending aorta In type II, it is confined to the ascending aorta
• Type III dissections originate in the descending aorta
Stanford Classification• Type A includes all dissections involving the ascending
aorta regardless of entry site location• Type B dissections include all those distal to the
brachiocephalic trunk, sparing the ascending aorta
Time course• Acute: <14 days• Subacute: 15-90 days• Chronic: >90 days
Copyright: Nienaber CA, Eagle KA. Aortic dissection: new frontiers in diagnosis and management: Part II: therapeutic management and follow-up. Circulation (2003); 108(6),772-778.
Adapted with permission from Nienaber CA, Eagle KA, Circulation 2003;108(6):772-778. All rights reserved.
De Bakey
Stanford
Type I
Type A
Type II
Type A
Type III
Type B
P.93
7.1ACUTE AORTIC SYNDROMES: Concept and classification (2)
Anatomic classification and time course
SYMPTOMS AND SIGNS SUGGESTIVE OF AAS
• Abrupt and severe chest/back pain with maximum intensity at onset
• Pulse/pressure deficit - Peripheral or visceral ischemia - Neurological deficit
• Widened mediastinum on chest X -ray• Risk factors for dissection• Other
- Acute aortic regurgitation - Pericardial effusion - Hemomediastinum/hemothorax
DIFFERENTIAL DIAGNOSIS
• Acute coronary syndrome (with/without ST-segment elevation)
• Aortic regurgitation without dissection• Aortic aneurysms without dissection• Musculoskeletal pain• Pericarditis• Pleuritis• Mediastinal tumours• Pulmonary embolism• Cholecystitis• Atherosclerosis or cholesterol embolism
P.94
7.1ACUTE AORTIC SYNDROME:
Clinical suspicion and differential diagnosis
Copyright: Hiratzka et al. 2010 Guidelines on Thoracic Aortic Disease. Circulation. (2010) ; 121: page-310 (fig 25 step 2).
Consider acute aortic dissection in all patients presenting with:
• Chest, back or abdominal pain• Syncope• Symptoms consistent with perfusion deficit (central nervous system, visceral myocardial or limb ischemia)
Pre-test risk assessment for acute aortic dissection
• Marfan’s syndrome• Connective tissue disease• Family history of aortic disease• Aortic valve disease• Thoracic aortic aneurysm
• Perfusion deficit: - Pulse deficit - SBP differential - Focal neurological deficit• Aortic regurgitation murmur• Hypotension or shock
Chest, back or abdominal paindescribed as:
Abrupt at onset, severe in intensity, and ripping/sharp or stabbing quality
High-risk conditions High-risk pain features High-risk exam features
P.95
7.1General approach to the patient
with suspected ACUTE AORTIC SYNDROME
Laboratory tests To detect signs of:
Red blood cell count Blood loss, bleeding, anaemia
White blood cell count Infection, inflammation (SIRS)
C-reactive protein Inflammatory response
ProCalcitonin Differential diagnosis between SIRS and sepsis
Creatine kinase Reperfusion injury, rhabdomyolysis
TroponinIorT Myocardial ischaemia, myocardial infarction
D-dimer Aortic dissection, pulmonary embolism, thrombosis
Creatinine Renal failure (existing or developing)
Aspartate transaminase / alanine aminotransferase Liver ischaemia, liver disease
Lactate Bowel ischaemia, metabolic disorder
Glucose Diabetes mellitus
Blood gases Metabolic disorder, oxygenation
Reference: Eur Heart J 2014; eurheartj.ehu281.
P.96
7.1Laboratory tests required for patients
with ACUTE AORTIC dissection
a STEMI can be associated with AAS in rare cases.
b Pending local availability, patient characteristics, and physician experience.
c Proof of type-A AD by the presence of flap, aortic regurgitation, and/or pericardial effusion.
d Preferably point-of-care, otherwise classical.
e Also troponin to detect non–ST-segment elevation myocardial infarction.
Flowchart for decision-making based on pre-test sensitivity of acute aortic syndrome. Reference: Eur Heart J 2014; eurheartj.ehu281.
ACUTE CHEST PAIN
High probability (score 2-3)or typical chest pain
Medical history + clinical examination + ECG STEMIa: see ESC guidelines169
HAEMODYNAMIC STATEUNSTABLE
Low probability (score 0-1)TTE + TOE/CT°
STABLE
AASconfirmed
AASexcludedConsideralternatediagnosis
D-dimers d,e + TTE + Chest X-ray TTE
Consideralternatediagnosis
No argumentfor AD
Signsof AD
Widenedmedia- stinum
DefiniteType A -AD c
Inconclusive
Refer on emergencyto surgical team andpre-operative TOE
CT (or TOE)
AASconfirmed
Consideralternatediagnosisrepeat CT
if necessaryAAS
confirmedConsideralternatediagnosis
CT (MRI or TOE)b
P.97
7.1ACUTE CHEST PAIN
Aortic dissection • Visualization of intimal flap• Extent of the disease according to the aortic anatomic segmentation• Identification of the false and true lumens (if present)• Localization of entry and re-entry tears (if present)• Identification of antegrade and/or retrograde aortic dissection• Identification grading, and mechanism of aortic valve regurgitation• Involvement of side branches• Detection of malperfusion (low flow or no flow)• Detection of organ ischaemia (brain, myocardium, bowels, kidneys, etc.)• Detection of pericardial effusion and its severity• Detection and extent of pleural effusion• Detection of peri-aortic bleeding• Signs of mediastinal bleeding
Intramural haematoma
• Localization and extent of aortic wall thickening• Co-existence of atheromatous disease (calcium shift)• Presence of small intimal tears
Penetrating aortic ulcer
• Localization of the lesion (length and depth)• Co-existence of intramural haematoma• Involvement of the peri-aortic tissue and bleeding• Thickness of the residual wall
In all cases • Co-existence of other aortic lesions: aneurysms, plaques, signs of inflammatory disease, etc.
P.98
7.1Details required from imaging in ACUTE AORTIC dissection
ACUTE AORTIC SYNDROMES MANAGEMENT: GENERAL APPROACH
ACUTE AORTIC DISSECTION
Type A(Ascending aorta
involvement)
Type B(No ascending
aorta involvement)
Uncomplicated
Medical treatment
Open Surgery with/without Endovascular
Therapy
Endovascular Therapy or
Open Surgery(TEVAR)
Complicated(malperfusion,
rupture)
P.99
7.1ACUTE AORTIC SYNDROMES MANAGEMENT: General approach
1 • Detailed medical history and complete physical examination (when possible)
2 • Standard 12-lead ECG: Rule-out ACS, documentation of myocardial ischemia
3 • Intravenous line, blood sample (CK, cTn, myoglobin, white blood count, D-dimer, hematocrit, LDH)
4 • Monitoring: HR and BP
5 • Pain relief (morphine sulphate) (see chapter 4)
6 • Noninvasive imaging (see previous page)
7 • Transfer to ICU
For more information on individual drug doses and indications,
SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
P.100
7.1ACUTE AORTIC SYNDROMES: Initial management
URGENT SURGERY (<24h)
Emergency Surgery
Graft replacement of ascending aorta +/- arch with/without aortic valve or aortic root
replacement/repair (depending on aortic regurgitationand aortic root involvement)
ACUTE AORTIC SYNDROMES: SURGICAL MANAGEMENT
TYPE A ACUTE AORTIC DISSECTION TYPE B ACUTE AORTIC DISSECTION
• Haemodynamic instability (hypotension/shock) • Tamponade• Severe acute aortic regurgitation• Impending rupture• Flap in aortic root• Malperfusion syndrome
Elective/individualisedSurgery
• Non-complicated intramural hematoma• Comorbidities• Age >80 years
Definitive diagnosis
COMPLICATEDdefined as:
by clinical presentation and imaging
• Impending rupture • Malperfusion • Refractory HTN • SBP (<90 mmHg) • Shock
UNCOMPLICATEDdefined as:No features
of complicateddissection
MEDICALMANAGEMENT
and imagingsurveillance protocol• On admission• At 7 days• At discharge• Every 6 months thereafter
MEDICALMANAGEMENT
andTEVAR
MEDICALMANAGEMENT
and OPEN SURGERY
REPAIRif TEVAR
contraindicated
Yes No
P.101
7.1ACUTE AORTIC SYNDROMES: Surgical management
Diagnostic algorithm
as for suspected high-risk PE
Diagnostic algorithm as for suspected not high-risk PE
Assess clinical risk (PESI or SPESI)
RV function (echo or CT) a
Laboratory testing b
Intermediate risk
PE confirmed
Consider further risk stratificaiton
PESI Class III-IVor sPESI ≥ I
PESI Class I-IIor sPESI = 0
PE confirmed
Both positive One positiveor both negative
Clinical suspicion
Shock / hypotension?NoYes
P.102
7.2Risk-adjusted management strategies
in ACUTE PULMONARY EMBOLISM
Reference: Eur Heart J 2014; 35:3033-3073.
a If echocardiography has already been performed during diagnostic work-up for PE and detected RV dysfunction, or if the CT already performed for diagnostic work–up has shown RV enlargement (RV/LV (left ventricular) ratio ≥0.9, a cardiac troponin test should be performed except for cases in which primary reperfusion is not a therapeutic option (e.g. due to severe comorbidity or limited life expectancy of the patient).
b Markers of myocardial injury (e.g. elevated cardiac troponin I or T concentrations in plasma), or of heart failure as a result of (right) ventricular dysfunction (elevated natriuretic peptide concentrations in plasma). If a laboratory test for a cardiac biomarker has already been performed during initial diagnostic work-up (e.g. in the chest pain unit) and was positive, then an echocardiogram should be considered to assess RV function, or RV size should be (re)assessed on CT.
c Patients in the PESI Class I-II, or with sPESI of 0, and elevated cardiac biomarkers or signs of RV dysfunction on imaging tests, are also to be classified into the intermediate-low risk category. This might apply to situations in which imaging or biomarker results become available before calculation of the clinical severity index. These patients are probably no candidates for home treatment.
d Thrombolysis, if (and as soon as) clinical signs of haemodynamic decompensation appear; surgical pulmonary embolectomy or percutaneous catheter-directed treatment may be considered as alternative options to systemic thrombolysis, particularly if the bleeding risk is high.
e Monitoring should be considered for patients with confirmed PE and a positive troponin test, even if there is no evidence of RV dysfunction on echocardiography or CT.
f The simplified version of the PESI has not been validated in prospective home treatment trials; inclusion criteria other than the PESI were used in two single-armed (non-randomized) management studies.
Intermediate-high risk Intermediate-low risk
A/C; monitoringconsider rescue
reperfusiondHospitalization A/C e
Consider early discharge and home treatment if feasible f
Primary reperfusion
High-risk Low riskc
P.103
7.2
CARDIOVASCULARSymptoms/Signs
including but not limited to:
Shock? orSBP <90 mmHg?
orSBP fall by >40 mmHg?
persisting >15 min, otherwise unexplained
RESPIRATORYSymptoms/Signs
including but not limited to:
ACUTE PULMONARY EMBOLISM: DIAGNOSIS
YES NO
Dyspnea
• Chest pain (angina)• Syncope • Tachycardia• ECG changes• NT-proBNP ↑• Troponin ↑
• Chest pain (pleural)• Pleural effusion• Tachypnea• Hemoptysis• Hypoxemia• Atelectasis
Suspectacute
PE
Management algorithmfor UNSTABLE patients
Management algorithmfor initially STABLE patients
Reference: IACC Textbook (2015) chapter 66 Pulmonary embolism - page 638 - figure 66.1.
P.104
7.2ACUTE PULMONARY EMBOLISM: Diagnosis
MANAGEMENT ALGORITHM FOR UNSTABLE PATIENTS WITHSUSPECTED ACUTE PULMONARY EMBOLISM
CT angiography immediately availableand patient stabilised
Primary PA reperfusion
Primary PA reperfusion not justified
patient stabilised
No further diagnostictests feasible
Right heart,pulmonary artery or
venous thrombi?
Echocardiography(bedside)
CT*
Angio
RV pressure overload
CUS
No Yes
Yes
Yes positive
negative
No
TEE
Search for other causes
* Consider also pulmonary angiography if unstable patient in hemodynamic lab.
Reference: IACC Textbook (2015) chapter 66 Pulmonary embolism - page 639 - figure 66.2.
P.105
7.2Management algorithm for unstable patients
with suspected ACUTE PULMONARY EMBOLISM
Shock or hypotension YES
Contraindications for thrombolysis
No Relative Absolute
Primary PAreperfusion strategy
Thrombolysis
Low- dose transcatheterthrombolysis /
clot fragmetation
Surgical orPercutaneous catheter
embolectomy(availability/experience)
Supportive treatment i.v. UFH, STABILISE SYSTEMIC BLOOD PRESSURE, CORRECT HYPOXEMIA
P.106
7.2ACUTE PE: Management strategy for initially unstable patients
with confirmed high risk pulmonary embolism
MANAGEMENT ALGORITHM FOR INITIALLY STABLE PATIENTS WITHSUSPECTED ACUTE PULMONARY EMBOLISM
Low or intermediate“PE unlikely“
positive
negative D-dimer
CT angiography
negative positivenegative
Confirm by CUSV/Q scan or angiography
positive
CT angiography
CUS
CUSpositive
High or“PE likely“
Anticoagulationnot justified
Anticoagulationrequired
Anticoagulationnot justified
Anticoagulationrequired
Asses clinical (pre-test) probalility
Reference: IACC Textbook (2015) chapter 66 Pulmonary embolism - page 640 - figure 66.3.
P.107
7.2Management algorithm for initially stable patients
with suspected ACUTE PULMONARY EMBOLISM
Markers for myocardial injury Positive Positive Negative
Markers for RV overload Positive Positive Negative
Clinical risk assessment score (PESI)
Positive (class III-V) Positive (class III-V) Negative (class I-II)
Suggested initial anticoagulation
UFH i.v./LMWH s.c.LMWH/Fonda/apixaban/
rivaroxabanapixaban/rivaroxaban
STRATEGYMonitoring (ICU)*
rescue thrombolysisHospitalisation**
(telemonitoring)Early
discharge***
* When all markers are positive. - ** When at least one marker is positive. - *** When all markers are negative.
For more information on individual drug doses and indications,
SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
P.108
7.2Suggested management strategy for initially stable patients
with (non-high risk) confirmed PE
Key drugs for initial treatment of patients with confirmed PE
Uns
tabl
e
Alteplase (rtPA) (intravenous) 100 mp/2h or 0.6 mp/kg/15 min (max 50 mp)
Urokinase (intravenous) 3 million IU over 2h
Streptokinase (intravenous) 1.5 million IU over 2h
Unfractionated heparin (intravenous) 80 IU/kg bolus + 18 IU/kg/h
Sta
ble
Enoxaparine (subcutaneous) 1 mp/kg BID or 1.5 mp/kg QD
Tinzaparin (subcutaneous) 175 U/kg QD
Fondaparinux (subcutaneous) 7.5 mp (50-100 kg of body weight)5 mp for patients <50 kg, 10 mp for patients >100 kg
Rivaroxaban (oral) 15 mp BID (for 3 weeks, then 20 mp QD)
Apixaban (oral) 10 mg bid (for 7 days, than 5 mg bid)
For more information on individual drug doses and indications,
SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
P.109
7.2PULMONARY EMBOLISM: Pharmacological treatment
CHAPTER 8
ACUTE MYOCARDIAL/PERICARDIAL SYNDROMES
8.1 ACUTE MYOCARDITIS ����������������������������������������������������� p.112 A. Keren, A. Caforio
8.2 ACUTE PERICARDITIS AND CARDIAC TAMPONADE ���������������������� p.117 C. Vrints, S. Price
8
CAUSES OF MYOCARDITIS
MYOCARDITIS (WHO /ISFC): Inflammatory disease of the myocardium diagnosedby established histological, immunological and immunohistochemical criteria.
INFECTIOUS TOXICIMMUNE-MEDIATED
• Viral• Bacterial• Spirochaetal• Fungal • Protozoal• Parasitic• Rickettsial
• Drugs • Heavy Metals• Hormones, e.g. catecholamines (Pheochromocytoma)• Physical agents
• Allergens: Tetanus toxoid, vaccines, serum sickness, Drugs• Alloantigens: Heart transplant rejection• Autoantigens: Infection-negative lymphocytic, infection-negative giant cell, associated with autoimmune or immune oriented disorders
P.112
8.1ACUTE MYOCARDITIS: Definition and causes
Reference: Caforio ALP et al. Eur Heart J. (2013) Jul 3 (15).
Clinical presentationswith or without ancillary findings Diagnostic criteria
• Acute chest pain (pericarditic or pseudo-ischemic)• New-onset (days up to 3 months) or worsening
dyspnea or fatigue, with or without left/right heart failure signs
• Palpitation, unexplained arrhythmia symptoms, syncope, aborted sudden cardiac death
• Unexplained cardiogenic shock and/or pulmonary oedema
I. ECG/Holter/stress test features: Newly abnormal ECG and/or Holter and/or stress testing, any of the following: • I to III degree atrioventricular block, or bundle branch block,
ST/T wave changes (ST elevation or non ST elevation, T wave inversion), • Sinus arrest, ventricular tachycardia or fibrillation and asystole,
atrial fibrillation, frequent premature beats, supraventricular tachycardia• Reduced R wave height, intraventricular conduction delay
(widened QRS complex), abnormal Q waves, low voltage
II. Myocardiocytolysis markers: Elevated cTnT/cTnI
III. Functional/structural abnormalities on echocardiography• New, otherwise unexplained LV and/or RV structure and function
abnormality (including incidental finding in apparently asymptomatic subjects): regional wall motion or global systolic or diastolic function abnormality, with or without ventricular dilatation, with or without increased wall thickness, with or without pericardial effusion, with or without endocavitary thrombi
IV. Tissue characterisation by CMR: Edema and/or LGE of classical myocarditic pattern
Ancillary findings which support the clinical suspicion of myocarditis
• Fever ≥38.1°C within the preceding 30 days • A respiratory or gastrointestinal infection• Previous clinically suspected or biopsy proven
myocarditis• Peri-partum period• Personal and/or family history of allergic asthma• Other types of allergy• Extra-cardiac autoimmune disease • Toxic agents• Family history of dilated cardiomyopathy, myocarditis
P.113
8.1ACUTE MYOCARDITIS: Diagnostic criteria (1)
Diagnostic criteria for clinically suspected myocarditis
One or more of the clinical presentations shown in the Diagnostic Criteria* with or without Ancillary Features*
ANDOne or more Diagnostic Criteria from different categories (I to IV)*
OR
when the patient is asymptomatic, two or more diagnostic criteria from different categories (I to IV)*
in the absence of:
1) angiographically detectable coronary artery disease2) known pre-existing cardiovascular disease or extra-cardiac causes that could explain the syndrome
(e.g. valve disease, congenital heart disease, hyperthyroidism, etc.)
Suspicion is higher with higher number of fulfilled criteria*
Endomyocardial biopsy is necessary to:
1) confirm the diagnosis of clinically suspected myocarditis, 2) identify the type and aetiology of inflammation,
and 3) provide the basis for safe immunosuppression (in virus negative cases).
Reference: Caforio ALP et al. Eur Heart J. (2013) Jul 3 (16).
*SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
P.114
8.1ACUTE MYOCARDITIS: Diagnostic criteria (2)
Acute myocarditis should be clinically suspected in the presence of:
Hemodynamically stable Preserved LV function
No eosinophiliaNo significant rhythm or conduction disturbances
Not associated with systemic immune disease*
General supportive therapy
General supportive therapyImmunosuppression if
unresponsive and virus negative EMB
Hemodynamically unstable,decreased LV function, cardiogenic shock
Pharmacological and, if needed,mechanical circulatory support (ECMO, LVAD/Bi-VAD,
bridge to heart transplant or to recovery)
Lymphocytic Giant cell, eosinophilic,sarcoidosis (acute decompensation)
Immunosuppressionif infection-negative EMB
History, Physycal examination; ECG; Echocardiogram; Laboratory tests (Troponin, CRP, ESR, blood cell count, BNP); CMR; If available, serum cardiac autoantibodies
Clinically suspected myocarditis
Consider coronary angiography and EMB
No coronary artery disease
*If myocarditis is associated with systemic immune disease exacerbation, therapy overlaps with treatment of the background disease (usually immunosuppression).
P.115
8.1ACUTE MYOCARDITIS: Diagnostic and management protocol
• Patients with a life-threatening presentation should be sent to specialised units with capability for hemodynamic monitoring, cardiac catheterisation and expertise in endomyocardial biopsy.
• In patients with hemodynamic instability a mechanical cardio-pulmonary assist device may be needed as a bridge to recovery or to heart transplantation.
• Heart transplant should be deferred in the acute phase, because recovery may occur, but can be considered for hemodynamically unstable myocarditis patients, including those with giant cell myocarditis, if optimal pharmacological support and mechanical assistance cannot stabilise the patient
• ICD implantation for complex arrhythmias should be deferred until resolution of the acute episode, with possible use of a lifevest during the recovery period.
Reference: Caforio ALP et al. Eur Heart J. 2013 Jul 3 (18).
P.116
8.1Management of patients
with life-threatening ACUTE MYOCARDITIS
DIAGNOSIS (≥ 2 of the following):
• Chest pain (pleuritic) varying with position• Pericardial friction rub• Typical ECG changes (PR depression and/or diffuse concave ST-segment elevation)• Echocardiography: new pericardial effusion
Yes
Myopericarditis if:↑ TroponinEchocardiography: ↓ LV-function
Acutepericarditis
Equivocal or no
Consider cardiac
MRI
Delayedenhancementpericardium
Consider alternative diagnoses
P.117
8.2ACUTE PERICARDITIS: Diagnosis
ACUTE PERICARDITIS: MANAGEMENT
Acute pericarditis
High-risk features?
• Fever >38°C • Subacute onset • Anticoagulated • Trauma • Immunocompromised • Hypotension • Jugular venous distension • Large effusion
Other causes
• Post cardiac injury syndrome• Post cardiac surgery• Post MI: Dressler syndrome• Uremic• Neoplastic• Collagen vascular diseases (e.g. SLE)• Bacterial• Tuberculous
Yes
Hospital admissionStable
Ibuprofen + colchicineFurther testing for underlying etiology
Tamponade?
Pericardiocentesis
No
Most frequent cause:Viral pericarditis
Outpatient treatment
Aspirin 800 mgor Ibuprofen 600 mg BID - 2 weeks
If persisting or recurrent chest pain :Add colchicine 0.5 mg once (<70 kg)or 0.5 mg BID (≥70 kg) for 3 monthsAvoid corticosteroids!
P.118
8.2ACUTE PERICARDITIS: Management
CARDIAC TAMPONADE: DIAGNOSIS AND MANAGEMENT
Tamponade ?
Tamponade
Echocardiographywith respirometer
• Presence of a moderate to large pericardial effusion
• Diastolic collapses of right atrium and right ventricle
• Ventricular interdependence
• Increased tricuspid and pulmonary flow velocities (>50%) with decreased mitral and aortic flow velocities (>25%) during inspiration (predictive value >90%)
Physical examination• Distended neck veins• Shock• Pulsus paradoxus• Muffled heart sounds
ECG• Sinus tachycardia• Microvoltage QRS• Electrical alternans
Cardiac catheterization Early• Right atrial pressure ↑• Loss of X-descent
Late• Aortic pressure ↓• Pulsus paradoxus• Intracardiac diastolic pressure equilibration
Percutaneouspericardiocentesis & drainage
Consider surgical drainageAvoid PEEP ventilation
Not performed in routineP.119
8.2CARDIAC TAMPONADE: Diagnosis and management
CHAPTER 9
DRUGS IN ACUTE CARDIOVASCULAR
CAREAna de Lorenzo
P.121
9
Drug Indications Dose Dose adjustments Comments
Asp
irin Primary (not universally approved)
and secondary cardiovascular disease prevention
LD (if ACS): 150-300 mg oralMD: 75-100 mg oral QD
-
Major contraindications: GI bleeding-active peptic ulcer
Tica
grel
or
ACS (all patients at moderate-to-high risk of ischaemic events, e.g. elevated cardiac troponins)
LD: 180 mg oralMD: 90 mg oral BID -
Major contraindications: previous intracerebral hemorrhage, severe hepatic impairment, strong CYP3A4 inhibitors
Secondary prevention 1-3 years post-MI
MD: 60 mg oral BID-
Pra
sugr
el ACS with planned PCI LD: 60 mg oralMD: 10 mg oral QD
MD: 5 mg QD weight <60kg
Contraindication: previous stroke/TIA Prasugrel is generally not recommended in elderly, and if positive benefit/risk 5 mg is recommended
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.122
Oral antiplatelets 9
Drug Indications Dose Dose adjustments Comments
Clo
pido
grel
ACS + PCI or medical management (patients who cannot receive ticagrelor or prasugrel) and in ACS patients at high bleeding risk (e.g. patients who require oral anticoagulation)
LD: 300-600 mg oralMD: 75 mg oral QD
-
Prasugrel and ticagrelor have not been studied as adjuncts to fibrinolysis and oral anticoagulants
STEMI + fibrinolysis <75 years
LD: 300 mg oralMD: 75 mg oral QD
-
Prasugrel and ticagrelor have not been studied as adjuncts to fibrinolysis and oral anticoagulants
STEMI + fibrinolysis ≥75 years
LD: 75 mg oral MD: 75 mg oral QD
-
Secondary prevention >12 months post coronary stenting
MD: 75 mg oral QD-
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.123
Oral antiplatelets (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Abc
ixim
ab
Adjunct to PCI for bailout situations or thrombotic complications
LD: 0.25 mg/Kg i.v. MD: 0.125 μg/Kg/min i.v. (max: 10 μg/min) for 12h
-
Contraindications:
Active internal bleeding - History of CVA within 2 years - Bleeding diathesis - Preexisting thrombocytopenia - Recent (within 2 months) intracranial or intraspinal surgery or trauma - Recent (within 2 months) major surgery - Intracranial neoplasm, arteriovenous malformation, or aneurysm - Severe uncontrolled hypertension - Presumed or documented history of vasculitis - Severe hepatic failure or severe renal failure requiring haemodialysis - Hypertensive retinopathy
Ept
ifib
atid
e
ACS treated medically or with PCI
LD: 180 μg/Kg i.v. (at a 10 min interval)If STEMI and PCI: add a second 180 mcg/kg i.v. bolus at 10 minMD: 2 μg/Kg/min i.v. infusion
Reduce infusion dose to 1 μg/kg/min if CrCl 30-50 ml/min
Contraindications:
Bleeding diathesis or bleeding within the previous 30 days - Severe uncontrolled hypertension - Major surgery within the preceding 6 weeks - Stroke within 30 days or any history of hemorrhagic stroke - Coadministration of another parenteral GP II b/III a inhibitor - Severe renal impairment or dependency on renal dialysis - History of intracranial disease - Clinically significant hepatic impairment - Thrombocytopenia - Prothrombine time >1.2 times control or INR ≥2
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.124
Intravenous antiplatelets 9
Drug Indications Dose Dose adjustments Comments
Tiro
fiba
n
ACS treated medically or with PCI
LD: 25 μg/Kg i.v. over 5 minMD: 0.15 μg/Kg/min i.v. Infusion to 18 hours
CrCl <30 ml/min: decrease 50% bolus and infusion dose
Contraindications:
A history of thrombocytopenia following prior exposure
Active internal bleeding or a history of bleeding diathesis, major surgical procedure or severe physical trauma within the previous month
Can
grel
or
All patients undergoing PCI(elective + ACS)immediate onset + rapid offset (platelet recovery in 60min)
IV Bolus of 30 μg/Kg+ IV infusion of 4 μg/kg/min for at least 2 hours from start of PCI
-
Major contraindications:
Significant active bleeding or stroke
Transition to oral P2Y12 inhibitors variable according to type of agent
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.125
Intravenous antiplatelets (Cont.) 9
Drug Indications Dose Dose adjustments Comments
War
fari
n A
ceno
coum
arol Treatment and
prophylaxis of thrombosis
INR goal of 2-3 (INR: 2.5-3.5 for mechanical mitral valve prostheses or double valve replacement)
Assessing individual risks for thromboembolism and bleeding
-
Api
xaba
n
Prevention of stroke and systemic embolism in NVAF
5 mg oral BID 2.5 mg oral BID1) when at least 2 of the following characteristics: age ≥80, Cr >1.5 mg/dl or weight <60Kg2) when CrCl 15-29 ml/min
Contraindicated if CrCl <15 ml/min or severe hepatic impairmentTreatment of DVT and PE 10 mg oral BID for the first
7 days followed by 5 mg oral BID
-
Prevention of recurrent DVT and PE
2.5 mg oral BID
-
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.126
Oral anticoagulants and antagonists 9
Drug Indications Dose Dose adjustments Comments
Dab
igat
ran
Prevention of stroke and systemic embolism in NVAF
150 mg oral BID 110 mg BID (if age ≥80, increased bleeding risk or concomitant use of verapamil)
Contraindicated if CrCl <30 ml/min or severe hepatic impairment
Active clinically significant bleeding
Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole and dronedarone
Treatment of DVT and PE in patients who have been treated with a parenteral anticoagulant for 5-10 days and prevention of recurrent DVT and PE in patients who have been previously treated
Edox
aban
Prevention of stroke and systemic embolism in NVAF
60 mg oral QD 30 mg oral QD 1) when CrCl 15-50 ml/min2) weight <60Kg3) concomitant use of the following P-glycoprotein inhibitors: ciclosporin, dronedarone, erythromycin, or ketoconazole.
Edoxaban can be initiated in patients who may require cardioversion. Treatment should be started at least 2 hours before cardioversionTreatment of DVT and
PE and prevention of recurrent DVT and PE
60 mg oral QD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.127
Oral anticoagulants and antagonists (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Riv
arox
aban
Prevention of stroke and systemic embolism in NVAF
20 mg oral QD CrCl <50 ml/min: 15 mg QD Contraindicated if CrCl <15 ml/min or hepatic disease associated with coagulopathy and clinically relevant bleeding risk
Rivaroxaban can be initiated in patients who may require cardioversion
Treatment should be started at least 4 hours before cardioversion
Treatment of DVT and PE and prevention of recurrent DVT and PE
15 mg oral BID for the first 3 weeks followed by 20 mg QD
Reduce the maintenance dose to 15 mg QD if bleeding risk outweighs the risk for recurrent DVT and PE (not formally approved)
Prevention of atherothrombotic events
2.5 mg oral BID-
Anticoagulant antagonists
Idar
uciz
umab
Specific reversal agent for dabigatran
5g i.v. over 5 to 10 min
Another 5g dose if prolonged clotting times and:- recurrence of clinically
relevant bleeding- if potential re-bleeding
would be life-threatening- second emergency
surgery/urgent procedure
-
Dabigatran treatment can be re-initiated 24h after administration of idarucizumab, other antithrombotic therapy at any time
Relevant coagulation parameters are aPTT, dTT or ECT
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.128
Oral anticoagulants and antagonists (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Anticoagulant antagonists
Phy
tom
enad
ione
(V
itam
in K
)
Reversal for vitamin K antagonists
Patients with asymptomatic high INR with or without mild haemorrhage
Anticoagulant INR Oral Vitamin K i.v. Vitamin K
Warfarin
5-9 1-2.5 mg or 2-5 mg for a rapid reversal (additional dose of 1-2 mg if INR remains high after 24h)
0.5-1 mg
>9 2.5-5 mg (up to 10 mg) 1 mg
Acenocoumarol5-8 1-2 mg 1-2 mg
>8 3-5 mg 1-2 mg
Severe or life-threatening haemorrhage
Anticoagulant Situation i.v. Vitamin K Concomitant treatment
Warfarin
Severe haemorrhage
5-10 mg CCP or FFP
Life-threatening 10 mg CCP, FFP or rFVIIa
AcenocoumarolSevere haemorrhage
5 mg CCP, FFP or rFVIIa
P.129
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Oral anticoagulants and antagonists (Cont.) 9
Drug Indications Dose Dose adjustments Comments
UFH
NSTE-ACS LD: 4,000 IU i.v. MD: 1,000 IU/h i.v. Target aPTT: 50-70s or 1.5 to 2.0 times that of control to be monitored at 3, 6, 12 and 24h
Monitoring for heparin-induced thrombocytopenia (HIT)
Dose-independent reaction
STEMI Primary PCI: 70-100 IU/Kg i.v. when no GP-IIb/IIIa inhibitor is planned. 50-60 IU/Kg i.v. bolus with GP-IIb/IIIa inhibitors - Fibrinolysis/No reperfusion: 60 IU/kg i.v. bolus (max: 4,000 IU) followed by an i.v. infusion of 12 IU/kg (max: 1,000 IU/h) for 24-48h
Target aPTT: 50-70s or 1.5 to 2.0 times that of control to be monitored at 3, 6, 12 and 24h
Treatment of DVT and PE
80 IU/Kg i.v. bolus followed by 18 IU/Kg/h
According to aPTT, thromboembolic and bleeding risk
Fond
apar
inux
NSTE-ACS 2.5 mg QD s.c. up to 8 days or hospital discharge - Acute bacterial endocarditis
Severe hepatic impairment: caution advised
Contraindicated if CrCl <20 ml/min
Contraindicated for DVT/PE treatment if CrCl <30 ml/min
STEMI Fibrinolysis/No reperfusion: 2.5 mg i.v. bolus followed by 2.5 mg QD s.c. up to 8 days or hospital discharge
-
Treatment of DVT and PE
5 mg QD s.c. (<50kg); 7.5 mg QD s.c. (50-100kg); 10 mg QD s.c. (>100kg)
If >100Kg and CrCl 30-50 ml/min: 10 mg followed by 7.5 mg/24h s.c.
Prevention of VTE 2.5 mg QD s.c. CrCl 20-50 ml/min: 1.5 mg QD s.c.
P.130
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Parenteral anticoagulants 9
Drug Indications Dose Dose adjustments Comments
Biv
alir
udin
PCI for NSTE-ACS 0.75 mg/kg i.v. bolus followed immediatelly by 1.75 mg/kg/h infusion which may be continued for up to 4h post PCI as clinically warranted and further continued at a reduced infusion dose of 0.25 mg/kg/h for 4-12h as clinically necessary
Patients undergoing PCI with CrCl 30-50 ml/min should receive a lower infusion rate of 1.4 mg/kg/h
No change for the bolus dose
Contraindicated if CrCl <30 ml/min
Active bleeding or increased risk of bleeding, severe uncontrolled hypertension, subacute bacterial endocarditis
PCI for STEMI 0.75 mg/kg i.v. bolus followed immediatelly by 1.75 mg/kg/h infusion which should be continued for up to 4h after the procedureAfter cessation of the 1.75 mg/kg/h infusion, a reduced infusion dose of 0.25 mg/kg/h may be continued for 4-12h
PCI for elective cases
0.75 mg/kg i.v. bolus followed immediatelly by 1.75 mg/kg/h infusion which may be continued for up to 4h post PCI as clinically waranted
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.131
Parenteral anticoagulants (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Eno
xapa
rin
NSTE-ACS 30 mg i.v. + 1 mg/kg s.c. BID If >75 years: no LD and MD 0.75 mg/Kg BID s.c.CrCl <30 ml/min: no LD and MD 1 mg/Kg QD s.c.If >75 years and CrCl <30 ml/min: no LD and 0.75 mg/Kg QD s.c.
Monitoring for HIT
Anti Xa monitoring during treatment with LMWH might be helpful in pregnancy, extreme body weights and renal impairment
STE-ACS Primary PCI: 0.5 mg/Kg i.v. bolusFibrinolysis/No reperfusion:
a) Age <75 years: 30 mg i.v. bolus followed by 1 mg/Kg BID s.c. until hospital discharge for a max of 8 days The first two doses should not exceed 100 mg
b) Age >75 years: no bolus; 0.75 mg/Kg BID s.c. - The first two doses should not exceed 75 mg
In patients with CrCl <30 ml/min: regardless of age, the s.c. doses are given once daily
Treatment of DVT and PE
1 mg/Kg s.c. BID or 1.5 mg/Kg s.c. QD CrCl <30 ml/min: 1 mg/Kg/24h s.c.
Prevention of VTE 40 mg s.c. QD CrCl <30 ml/min: 20 mg s.c. QD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.132
Parenteral anticoagulants (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Tinz
apar
in Prevention of VTE 3,500 IU s.c. QD (moderate risk)4,500 IU s.c. QD (high risk)
-Monitoring for HIT
Anti Xa monitoring during treatment with LMWH might be helpful in pregnancy, extreme body weights and renal impairment
Dalteparin: In cancer patients, dose of 200 IU/kg (max: 18,000 IU)/24h for 1 month, followed by 150 IU/kg/24h for 5 months After this period, vitamin K antag or a LMWH should be continued indefinitely or until the cancer is considered cured
Treatment of DVT and PE
175 IU/Kg s.c. QD -
Dal
tepa
rin
Prevention of VTE 2,500 IU s.c. QD (moderate risk)5,000 IU s.c. QD (high risk)
-
Treatment of DVT and PE
200 IU/Kg QD or 100 IU/Kg BID s.c. Anti Xa monitoring if renal impairment
Arg
atro
ban Anticoagulant in
patients with HITInitial i.v. infusion dose: 2 μg/kg/min (not to exceed 10 μg/kg/min)Patients undergoing PCI: 350 μg/kg i.v. followed by 25 μg/kg/min i.v.
Renal and hepatic impairment: caution advised
Monitored using aPTT goal:
1.5 to 3.0 times the initial baseline value
PCI: ACT goal: 300-450s
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.133
Parenteral anticoagulants (Cont.) 9
Drug Indications DoseDose
adjustmentsComments
Str
epto
kina
se (S
K)
STEMI <12 hours 1.5 million units over 30-60 min i.v. -
Absolute contraindications to fibrinolytics:
Previous intracranial haemorrhage or stroke of unknown origin at any time
Ischaemic stroke in the preceding 6 months
Central nervous system damage or neoplasms or atrioventricular malformation
Recent major trauma/surgery/head injury (within the preceding 3 weeks)
Gastrointestinal bleeding within the past month
Known bleeding disorder (excluding menses)
Aortic dissection
Non-compressible punctures in the past 24h (e.g. liver biopsy, lumbar puncture)
Treatment of PE 250,000 IU as a LD over 30min, followed by 100,000 IU/h over 12-24h
-
Alt
epla
se (t
PA)
STEMI <12 hours 15 mg i.v. bolus:0.75 mg/kg over 30 min (up to 50 mg) then0.5 mg/kg over 60 min i.v. (up to 35 mg)
-
Treatment of PE Total dose of 100 mg: 10 mg i.v. bolus followed by 90 mg i.v. for 2h
If weight <65 Kg: max dose <1.5 mg/kg
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.134
Fibrinolytics 9
Drug Indications DoseDose
adjustmentsComments
Ret
epla
se
(rt-
PA)
STEMI <12 hours 10 units + 10 units i.v. bolus given 30 min apart
Renal and hepatic impairment: caution advised
Absolute contraindications to fibrinolytics:
Previous intracranial haemorrhage or stroke of unknown origin at any time
Ischaemic stroke in the preceding 6 months
Central nervous system damage or neoplasms or atrioventricular malformation
Recent major trauma/surgery/head injury (within the preceding 3 weeks)
Gastrointestinal bleeding within the past month
Known bleeding disorder (excluding menses)
Aortic dissection
Non-compressible punctures in the past 24h (e.g. liver biopsy, lumbar puncture)
Tene
ctep
lase
(T
NK-
tPA
)
STEMI <12 hours Single i.v. bolus over 10 seconds:
30 mg if <60kg35 mg if 60 to <70kg40 mg if 70 to <80kg45 mg if 80 to <90kg50 mg if ≥90kg -
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.135
Fibrinolytics (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Beta-blockers: Preferred over calcium channel blockers - Contraindicated if coronary spasm, severe bradycardia, AV block, severe bronchospasm
Ate
nolo
l
NSTE-ACS LD: 25-100 mg oral MD: 25-100 mg QD
Elderly: start at a lower doseCrCl 15-35 ml/min: max dose 50 mg/day; CrCl <15 ml/min: max dose 25 mg/day
Only if normal LVEF
STEMI 25-100 mg QD,titrate as tolerated up to 100 mg QD only if no LVSD or CHF
Car
vedi
lol NSTE-ACS LD: 3.125-25 mg oral
MD: 3.125-25 mg BID Caution in elderly and hepatic impairment
Preferred if LVSD/HF
STEMI 3.125-6.25 mg BID, titrated as tolerated up to 50 mg BID
Bis
opro
lol NSTE-ACS LD: 1.25-10 mg oral
MD: 1.25-10 mg QDCaution in renal or hepatic impairment Preferred if LVSD/HF
STEMI 1.25-5 mg QD, titrate as tolerated up to 10 mg QD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.136
Antiischemic drugs 9
Drug Indications Dose Dose adjustments Comments
Beta-blockers: Preferred over calcium channel blockers - Contraindicated if coronary spasm, severe bradycardia, AV block, severe bronchospasm
Met
opro
lol NSTE-ACS LD: 25-100 mg oral
MD: 25-100 mg BIDCaution in hepatic impairment Preferred if LVSD/HF
STEMI 5-25 mg BID, titrate as tolerated up to 200 mg QD
Calcium antagonists: Consider if beta-blockers are contraindicated. First option in vasospastic angina
Ver
apam
il ACS LD: 80-120 mg oralMD: 80-240 mg TID-QD
Caution in elderly, renal or hepatic impairment
Contraindicated if bradycardia, HF, LVSD
Dilt
iaze
m ACS LD: 60-120 mg oralMD: 60-300 mg TID-QD
Caution in elderly and hepatic impairment
Contraindicated if bradycardia, HF, LVSD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.137
Antiischemic drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Calcium antagonists: Consider if beta-blockers are contraindicated. First option in vasospastic angina
Am
lodi
pine ACS LD: 5-10 mg oral, MD: 5-10 mg QD Caution in hepatic impairment Contraindicated
if hypotension
Nitrates
Nit
rogl
ycer
in
i.v.
ACS If intolerant or unresponsive to nitroglycerin s.l. 5 μg/min - Increase by 5 mcg/min q 3-5 min up to 20 μg/min
If 20 mcg/min is inadequate, increase by 10 to 20 μg/min every 3 to 5 min
Max dose: 400 μg/min
-
Contraindicated if severe hypotension and co-administration with phosphodiesterase inhibitors
The most common adverse effects are headache and dizziness
i.v. nitroglycerin requires NON-PVC containers
spra
y Angina 1-2 puff s.l. every 5 min as needed, up to 3 puffs in 15 min -
subl
ingu
al
tabl
et
Angina 0.3 to 0.6 mg s.l. or in the buccal pouch every 5 min as needed, up to 3 doses in 15 min -
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.138
Antiischemic drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Isos
orbi
de m
onon
itra
te Angina 5-10 mg BID with the two doses given 7h apart (8am and 3pm) to decrease tolerance development - then titrate to 10 mg BID in first 2-3 days Extended release tablet: Initial: 30-60 mg given in the morning as a single dose Titrate upward as needed, giving at least 3 days between increases Max daily single dose: 240 mg
-
Contraindicated if severe hypotension and co-administration with phosphodiesterase inhibitors
The most common adverse effects are headache and dizziness
Isos
orbi
de
dini
trat
e Angina Initial dose: 5 to 20 mg orally 2 or 3 times/dayMD: 10 to 40 mg orally 2 or 3 times a dayExtended release: 40 to 160 mg/day orally
-
Nit
rogl
ycer
in
tran
sder
mal
p
atch
Angina 0.2 to 0.4 mg/h patch applied topically once a day for 12 to 14h per day; titrate as needed and tolerated up to 0.8 mg/h -
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.139
Antiischemic drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Other antiishemic drugs
Ivab
radi
ne Stable angina 5-7.5 mg oral BID Caution in elderly and CrCl <15 ml/min Contraindicated if severe hepatic impairment
Ran
olaz
ine
Stable angina Initial dose: 375 mg oral BIDAfter 2-4 weeks, the dose should be titrated to 500 mg BID and, according to the patient’s response, further titrated to a recommended max dose of 750 mg BID
Use with caution in renal and hepatic impairment, CHF, elderly, low weight
Contraindicated if CrCl <30 ml/min, concomitant administration of potent CYP3A4 inhibitors, moderate or severe hepatic impairment
Trim
etaz
idin
e
Stable angina Modified-release: 35 mg oral BID Caution in elderly and 30 <CrCl <60 ml/min
Contraindicated in parkinson disease, parkinsonian symptoms, tremors, restlessleg syndrome, movement disorders, severe renal impairment
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.140
Antiischemic drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Statins: Primary or secondary prevention of cardiovascular disease For secondary prevention, start with high doses initiated early after admission and downtitrate if side effects. Target LDL-C levels <70 mg/dl
AtorvastatinLDL-C reduction
<30% 30-40% 40-50% >50%
Simva 10 mg
Simva 20-40 mg
Simva/ezet 20/10 mg
Simva/ezet 40/10 mg
Lova 20 mg
Ator 10 mg
Ator 20-40 mg
Ator 40-80 mg
Prava 10-40 mg
Rosu 5 mg Rosu 10 mgRosu 20-40 mg
Pita 1 mg Pita 2 mg Pita 4 mg
Fluva 20-40 mg
Fluva 80 mg
-
Contraindicated in patients with active liver disease or with unexplained elevation of liver function enzyme levels
RosuvastatinCrCl <30 ml/min: start 5 mg QD, max: 10 mg QD
PitavastatinCrCl 30-59 ml/min: start 1 mg QD, max 2 mg/day; CrCl 10-29 ml/min: not defined
SimvastatinSevere renal impairment: start 5 mg QPM
FluvastatinCaution in severe renal impairment
PravastatinSignificant renal impairment: start 10 mg QD
LovastatinCrCl <30 ml/min: caution if dose >20 mg QD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.141
Lipid lowering drugs 9
Drug Indications Dose Dose adjustments Comments
Others
EzetimibeHypercholesterolaemia 10 mg oral QD Avoid use if moderate-severe
hepatic impairment-
FenofibrateHyperlipidemia 48-160 mg oral QD
May adjust dose q 4-8 weeks
CrCl 50-90 ml/min: start 48-54 mg QD
Contraindicated if CrCl <50 ml/min or hepatic impairment
Gemfibrozil
Hyperlipidemia 900-1,200 mg/day oral
-
Contraindicatedif severe renal impairment or hepatic dysfunctionStatins may increase muscle toxicity: avoid concomitant use
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.142
Lipid lowering drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
PCSK9 Inhibitors
Evolocumab
Hypercholesterolaemia and mixed dyslipidaemia Homozygous familial hypercholesterolaemia
140 mg s.c. every 2 weeks or 420 mg every month
Homozygous familial hypercholesterolaemia: 420 mg s.c every month Up-titrate to 420 mg every 2 weeks if a response is not achieved
-
Most common side effects:
Nasopharingitis, upper respiratory tract infection, headache and back pain
Alirocumab
Hypercholesterolaemia and mixed dyslipidaemia
Start dose: 75 mg s.c. every 2 weeks
If a larger LDL-C reduction (>60%) is required, the start dose could be 150 mg every 2 weeks, or 300 mg every 4 weeks
The dose can be individualised based on LDL-C level, goal of therapy, and response. Max dose: 150 mg once every 2 weeks
Most common side effects:
Upper respiratory tract signs and symptoms, pruritus and injection site reactions
P.143
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Lipid lowering drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
ACEI
Cap
topr
il
HF Start: 6.25 mg oral TID Target dose: 50 mg TID
CrCl >50 ml/min: 75-100% of the normal doseCrCl 10-50 ml/min: 25-50%CrCl <10 ml/min: 12.5%
Check renal function, electrolytes, drug interactions
Major contraindications:
History of angioedema, known bilateral renal artery stenosis, pregnancy (risk)
HTN Start: 12.5 mg oral BID Target dose: 25-50 mg TID Max 450 mg/day
Ena
lapr
il HF, HTN Start: 2.5 mg oral BID Target dose: 10-20 mg BID
CrCl 30-80 ml/min: start 5 mg/dayCrCl 10-30 ml/min: start 2.5 mg/day
Lisi
nopr
il
HF Start: 2.5-5.0 mg oral QD Target dose: 20-35 mg QD
CrCl 31-80 ml/min: start 5-10 mg/day CrCl 10-30 ml/min: start 2.5-5 mg/day CrCl <10 ml/min: start 2.5 mg/day
HTN 10-20 mg oral QD Max: 80 mg QD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.144
Heart failure & hypertension 9
Drug Indications Dose Dose adjustments Comments
Per
indo
pril HF Start: 2 mg oral QD
Target dose: 8 mg QDCrCl >60 ml/min: start 4 mg/dayCrCl 31-60 ml/min: start 2 mg/dayCrCl 15-30 ml/min: start 2 mg every other dayCrCl <15ml/min: 2 mg on the day of dialysis
Check renal function, electrolytes, drug interactions
Major contraindications:
History of angioedema, known bilateral renal artery stenosis, pregnancy (risk)
HTN Start: 4 mg QDMax dose: 8 mg QD
Ram
ipri
l HF, HTN Start: 2.5 mg oral QDTarget dose: 5 mg BID
CrCl <40 ml/min: start 1.25 mg QD, max 5 mg/dayCaution in elderly and hepatic impairment
Tran
dola
pril
HF Start: 0.5 mg oral QDTarget dose: 4 mg QD
CrCl <30 ml/min or severe hepatic impairment: start 0.5 mg
HTN 2-4 mg oral QD CrCl <30 ml/min or severe hepatic impairment: start 0.5 mg
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.145
Heart failure & hypertension (Cont.) 9
Drug Indications Dose Dose adjustments Comments
ARB
Can
desa
rtan
HF, HTN Start: 4-8 mg oral QDTarget dose: 32 mg QD
If renal or hepatic impairment: start 4 mg/day
If ACEI is not tolerated
Check renal function, electrolytes, drug interactions
Major contraindications:
History of angioedema, known bilateral renal artery stenosis, pregnancy (risk)
Losa
rtan
HF Start: 50 mg oral QDTarget dose: 150 mg QD
CrCl <20 ml/min: 25 mg QDCaution if hepatic impairment
HTN 50-100 mg oral QD CrCl <20 ml/min: 25 mg QDCaution if hepatic impairment
Vals
arta
n HF Start: 40 mg oral BIDTarget dose: 160 mg BID
If mild-moderate hepatic impairment: max dose 80 mg/day
HTN 80-160 mg QD If mild-moderate hepatic impairment: max dose 80 mg/day
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.146
Heart failure & hypertension (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Neprilysin inhibitor/ARB
Sac
ubit
ril/
Val
sart
an
Symptomatic chronic HF with reduced ejection fraction
Start: 49 mg/51 mg oral BID Target dose: 97 mg/103 mg BID
Do not initiate if K >5.4 mmol/l or SBP <100 mmHg Start dose of 24 mg/26 mg BID if SBP 100-110 mmHg or CrCl 30-60 ml/min
Do not co-administer with an ACEI or ARB. It must not be started for at least 36 hours after discontinuing an ACEI
Contraindicated if history of angioedema related to ACEI or ARB
Hereditary or idiopathic angioedema
Concomitant use with aliskiren if diabetes mellitus or renal impairment
Severe hepatic impairment, biliary cirrhosis and cholestasis
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.147
Heart failure & hypertension (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Beta-blockers: Check 12 - lead ECG
Car
dios
elec
tive
(1)
Ate
nolo
l HTN Start: 25 mg oral QD Usual dose: 50-100 mg QD
CrCl 10-50 ml/min: decrease dose 50% CrCl <10 ml/min: decrease dose 75%
Major contraindications: asthma, 2nd or 3rd degree AV block
Bis
opro
lol
HF Start: 1.25 mg oral QD Target dose: 10 mg QD
CrCl <20 ml/min: max dose 10 mg QD Hepatic impairment: avoid use
HTN Start: 2.5-5 mg oral QD Usual dose: 5-10 mg QD Max dose: 20 mg QD
Met
opro
lol
HF Start: 12.5-25 mg oral QD Target dose: 200 mg QD
Hepatic impairment: start with low doses and titrate gradually
HTN 100-400 mg QD Max dose: 400 mg QD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.148
Heart failure & hypertension (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Beta-blockers: Check 12- lead ECG
Car
dios
elec
tive
(2
)
Neb
ivol
ol
HF Start: 1.25 mg oral QD Target dose: 10 mg QD
Renal impairment or elderly: start dose 2.5 mg QD, titrate to 5 mg QD Hepatic impairment: contraindicated
Major contraindications: asthma, 2nd or 3rd degree AV block
HTN Start: 2.5 mg oral QD Usual dose: 5 mg QD
Non
-car
dios
elec
tive
Car
vedi
lol
HF Start: 3.125 mg oral BID Target dose: 25-50 mg BID
Caution in elderly Contraindicated if hepatic impairment
HTN Start: 12.5 mg oral QD Usual dose: 25 mg QD and max dose: 25 mg BID or 50 mg QD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.149
Heart failure & hypertension (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Other vasodilators
Am
lodi
pine
HTN Start: 5 mg oral QD, increase after 1-2 weeksMax: 10 mg/day
Elderly or secondary agent: start 2.5 mg QD Hepatic impairment: start 2.5 mg QD
Contraindicated if cardiogenic shock, 2nd or 3rd degree AV block, severe hypotension
Nife
dipi
ne
HTN Extended-release form: Start 20 mg oral BID or TID Max: 60 mg BID
Renal and hepatic impairment: caution advised
Ver
apam
il HTN Immediate-release form: Dose: 80-120 mg oral TID; Start: 80 mg TID; Max: 480 mg/day
Start 40 mg oral TID in elderly or small stature patients
Contraindicated if bradycardia, HF, LVSD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.150
Heart failure & hypertension (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Loop diuretics
Furo
sem
ide HF 20-40 mg i.v. bolus, continuous
100 mg/6h (adjust based on kidney function and clinical findings; monitor creatinine)
Anuria: contraindicated Cirrhosis/ascites: caution advised
-
HTN 10-40 mg oral BID
Tors
emid
e HF 10-20 mg oral or i.v. QD Hepatic impairment: initial dose should be reduced by 50% and dosage adjustments made cautiously -
HTN 5 mg oral or i.v. QD Max 10 mg QD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.151
Heart failure & hypertension (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Thiazides
Chl
orth
alid
one
HF 50-100 mg oral QD MD: 25-50 mg QD
Elderly: max dose 25 mg/day CrCl <25 ml/min: avoid use -
HTN Start 12.5-25 mg oral QD; Max: 50 mg/day
Elderly: max dose 25 mg/day CrCl <25 ml/min: avoid use -
Hyd
roch
loro
thia
zide HF 25-200 mg oral/day CrCl <25 ml/min: avoid use
Hepatic impairment: caution advised -
HTN Start 12.5-25 mg oral QD MD: may increase to 50 mg oral as a single or 2 divided doses
CrCl <25 ml/min: avoid use Hepatic impairment: caution advised
-
Inda
pam
ide HTN Start 1.25 mg PO QAM x4weeks,
then increase dose if no response Max: 5 mg/day
CrCl <25 ml/min: avoid use Hepatic impairment: caution advised
-
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.152
Heart failure & hypertension (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Aldosterone-antagonists
Spi
rono
lact
one HF Start 25 mg oral QD
Target dose: 25-50 mg QDCrCl <10 ml/min, anuria or acute renal impairment: contraindicated Severe hepatic impairment and elderly: caution advised
Check renal function, electrolytes, drug interactionsProduces gynecomastiaHTN 50-100 mg/day oral
Epl
eren
one HF Start 25 mg oral QD
Target dose: 50 mg QDElderly: caution advised CrCl <50 ml/min: contraindicated
Check renal function, electrolytes, drug interactionsMajor contraindications: strong CYP3A4 inhibitors
HTN 50 mg oral QD-BIDMax: 100 mg/day
Others
Ivab
radi
ne HF 5-7.5 mg oral BID Caution in elderly and CrCl <15ml/min
Contraindicated if severe hepatic impairment
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.153
Heart failure & hypertension (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Levo
sim
enda
n HF/cardiogenic shock
LD: 6 to 12 μg/kg i.v. over 10 min (given only if immediate effect is needed) followed by 0.05 to 0.2 μg/kg/min as a continuous infusion for 24h
Avoid use if CrCl <30 ml/min or severe hepatic impairment
Calcium sensitizer and ATP-dependent potassium channel opener
Milr
inon
e
HF/cardiogenic shock
50 μg/kg i.v. in 10-20 min, continuous 0.375-0.75 μg/kg/min
Renal: Same bolus. Adjust infusion: CrCl 50 ml/min: start 0.43 μg/kg/min CrCl 40 ml/min: start 0.38 μg/kg/min CrCl 30 ml/min: start 0.33 μg/kg/min CrCl 20 ml/min: start 0.28 μg/kg/minCrCl 10 ml/min: start 0.23 μg/kg/minCrCl 5 ml/min: start 0.20 μg/kg/min
Phosphodiesterase inhibitor
Caution if atrial flutter
Hypotensive drug
Isop
rena
line/
Is
opro
tere
nol Cardiogenic
shock0.5-5 μg/min (0.25-2.5ml of a 1:250,000 dilution) i.v. infusion
-
ß1, ß2 agonist
Contraindicated in patients with tachyarrhythmia, tachycardia or heart block caused by digitalis intoxication, ventricular arrhythmias which require inotropic therapy, angina pectoris, recent ACS, hyperthyroidism
Bradyarrhythmias Bolus: 20-40 μg i.v.Infusion: 0.5 μg/min of 2 mg/100 ml normal saline
ß ef
fect
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.154
Inotropics & vasopressors 9
Drug Indications Dose Dose adjustments Comments
Dob
utam
ine Cardiogenic
shock2-20 μg/kg/min i.v.
-
ß1, a1/ß2 agonist
Increases contractility with little effect on heart rate and blood pressure. Reduces pulmonary and systemic VR, PCP
Dop
amin
e Cardiogenic shock
Dopaminergic effect: 2-5 μg/Kg/min i.v.ß effect : 5-15 μg/Kg/min i.v.a effect : 15-40 μg/Kg/min i.v.
-
ß, a, dopaminergic agonist
Increases BP, PAP, heart rate, cardiac output and pulmonary and systemic VR
More arrhythmogenic than dobutamine and noradrenaline
Nor
adre
nalin
e Cardiogenic shock
0.05-0.2 μg/kg/min i.v. titrate to effect
-
a 1, ß1 agonist
Increases BP and PAP
Little arrhythmogenic
ß ef
fect
a ef
fect
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.155
Inotropics & vasopressors (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Group I
Pro
cain
amid
e i.v
.
AF (termination); stable VT (with a pulse)
15-18 mg/kg i.v. over 60min, followed by infusion of 1-4 mg/min
Reduce LD to 12 mg/kg in severe renal impairmentReduce MD by one-third in moderate renal impairment and by two-thirds in severe renal impairmentCaution in elderly and asthma
Hypotension (negative inotropic agent)
Lupus-like syndrome
Contraindicated if myasthenia gravis, AV block, severe renal impairment
Lido
cain
e i.v
.
Pulseless VT/VF
1-1.5 mg/kg i.v./i.o. bolus (can give additional 0.5-0.75 mg/kg i.v./i.o. push every 5-10 min if persistent VT/VF, max cumulative dose = 3 mg/kg), followed by infusion of 1-4 mg/min
1-2 mg/min infusion if liver disease or HF
Contraindicated if advanced AV block, bradycardia,
hypersensitivity to local anesthetics
Caution in HF, renal impairment and elderly
May cause seizures, psychosis
Stop if QRS widens >50%
Stable VT (with a pulse)
1-1.5 mg/kg i.v. bolus (can give additional 0.5-0.75 mg/kg i.v. push every 5-10 min if persistent VT, max cumulative dose = 3 mg/kg), followed by infusion of 1-4 mg/min
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.156
Antiarrhythmics 9
Drug Indications Dose Dose adjustments Comments
Group I
Flec
aini
de
i.v.
SVT, ventricular arrhythmias
2 mg/kg (max 150 mg) i.v. over 30 minThis may be followed by an infusion at a rate of 1.5 mg/kg/h for 1 h, reduced to 0.1-0.25 mg/kg/h for up to 24h, max cumulative dose = 600 mg
Severe renal impairment: caution advised
Contraindicated if cardiogenic shock, recent MI, 2nd or 3rd degree AV block
Pro
pafe
none
i.v
.
PSVT, ventricular arrhythmias
LD: 0.5-2 mg/kg i.v. direct over aminimum of 3-5minMD: 0.5-2.5 mg/kg i.v. direct q8h (max 560 mg/day) or continuous infusion up to 23 mg/h
May need to reduce dose in renal or hepatic failure
Contraindicated if unstable HF, cardiogenic shock, AV block, bradycardia, myasthenia gravissevere hypotension,bronchospastic disorders, Brugada syndrome
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.157
Antiarrhythmics (Cont.) 9
Drug Indications DoseDose
adjustmentsComments
Group II
Ate
nolo
l i.v
.
Arrhythmias 2.5 mg i.v. over 2.5 min every 5 min(max 10 mg)
Caution in elderly and/or severe renal impairment
Contraindicated if cardiogenic shock, bradycardia and greater than first-degree block, unstable HF
Met
opro
lol
i.v.
Arrhythmias 2.5-5 mg i.v. over 5min, may repeat every 5 min (max 15 mg)
Caution if severe hepatic impairment
Contraindicated if cardiogenic shock, bradycardia and greater than first-degree block, unstable HF
Pro
pran
olol
i.v
.
Arrhythmias Initially given as slow i.v. boluses of 1 mg, repeated at 2 min intervals (max: 10 mg in conscious patients and 5 mg if under anesthesia) -
Contraindicated if cardiogenic shock, bradycardia and greater than first-degree block, asthma, unstable HF
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.158
Antiarrhythmics (Cont.) 9
Drug Indications DoseDose
adjustmentsComments
Group III
Am
ioda
rone
i.v
.
AF (termination) 5 mg/Kg i.v. over 30min, followed by infusion of 1 mg/min for 6h, then 0.5 mg/min
-Reduce infusion rate if bradycardia, AV block, hypotension
Bolus should be avoided if hypotension or severe LV dysfunction
Highly vesicant agent
Stable VT (with a pulse)
150 mg i.v. over 10 min followed by infusion of 1 mg/min for 6h, then 0.5 mg/min
-
Pulseless VT/VF 300 mg bolus i.v. (can give additional150 mg i.v. bolus if VF/VT persists) followed by infusion of 900 mg over 24h
-
Dro
neda
rone Paroxysmal
or persistent AF prevention
400 mg oral BID
-
Contraindicated if severe renal or liver dysfunction, LVSD, symptomatic HF, permanent AF, bradycardia… (multiple contraindications)
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.159
Antiarrhythmics (Cont.) 9
Drug Indications DoseDose
adjustmentsComments
Group IV
Dilt
iaze
m
i.v.
PSVT; AF (rate control) 0.25 mg/kg i.v. over 2 min (may repeat with 0.35 mg/kg i.v. over 2 min), followed by infusion of 5-15 mg/h
Hepatic impairment: caution advised -
Ver
apam
il i.v
.
PSVT; AF (rate control) 2.5-5 mg i.v. over 2 min (may repeat up to max cumulative dose of 20 mg); can follow with infusion of 2.5-10 mg/h -
Contraindicated if AF+WPW, tachycardias QRS (except RVOT-VT), fascicular VT, bronchospasm, age >70 years
Antidote: - LVD: Calcium gluconate, dobutamine
- Bradycardia/AV block: Atropine, Isoproterenol
Ade
nosi
ne
i.v.
Rapid conversion to a normal sinus rhythm of PSVT including those associated with accessory by-pass tracts (WPW syndrome)
Rapid i.v. boluses separated by 2 min: 6 mg → 6 mg → 12 mg
-
Contraindicated if sick sinus syndrome, second or third degree Atrio-Ventricular (AV) block (except in patients with a functioning artificial pacemaker), chronic obstructive lung disease with evidence of bronchospasm (e.g. asthma bronchiale), long QT syndrome, severe hypotension; decompensated states of heart failure - Adenosine can cause AF
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.160
Antiarrhythmics (Cont.) 9
Drug Indications DoseDose
adjustmentsComments
Others
Mag
nesi
um
sulfa
te
VT-Torsades de Pointes
Bolus: 1-2g i.v./i.o. over 5 minPerfusion: 5-20 mg/min i.v.
Caution if severe renal failure
Contraindicated if myasthenia gravis
Ver
naka
lant
Conversion of recent onset AF
3 mg/kg i.v. over 10 min
If AF persists, a second 10min-infusion of 2 mg/kg, 15 min later may be administered
-
Contraindicated if ACS within the last 30 days, severe aortic stenosis, SBP <100 mmHg, HF class NYHA III/IV, severe bradycardia, sinus node dysfunction or 2nd or 3rd degree heart block, prolonged QT at baseline, use of i.v. antiarrhythmics (class I and class III) within 4h prior to, as well as in the first 4h after, vernakalant administration
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.161
Antiarrhythmics (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Benzodiazepines: Use of benzodiazepines may lead to the development of physical and psychic dependence upon these products. The risk of dependence increases with dose and duration of treatment. Benzodiazepines may induce anterograde amnesia. Discontinuation: dosage should be reduced slowly
Short-acting benzodiazepines
Alp
razo
lam
Moderate or severe anxiety or anxiety associated with depression
250-500mcg oral TID as short as possible, increasing if required to a total of 3 mg daily
Elderly or debilitating disease: 250mcg BID or TID and gradually increased if needed and tolerated
Renal impairment or mild-moderate hepatic impairment: caution
Contraindicated if myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome, severe hepatic insufficiency
Lopr
azol
am
Insomnia 1 mg oral at bedtime. This may be increased to 1.5 mg or 2 mg if necessary
Frail, debilitated or elderly: start with half a tablet. Max dose: 1 mg
Chronic pulmonary, insufficiency, cerebrovascular disease and chronic renal or hepatic impairment: caution
Contraindicated if acute pulmonary insufficiency, severe respiratory insufficiency, myasthenia gravis, phobic or obsessional states and sleep apnoea syndrome, monotherapy in depression or anxiety associated with depression and chronic psychosis and alcohol intake
P.162
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs 9
Drug Indications Dose Dose adjustments Comments
Short-acting benzodiazepines
Lora
zepa
m o
ral
Severe anxiety
Premedication before surgery
Anxiety: 1-4 mg oral in divided doses
Insomnia: 1-2 mg oral before retiring
Premedication before surgery: 2-3 mg oral the night before operation 2-4 mg oral 1-2h before the procedure
Elderly: may respond to lower doses
Renal or hepatic impairment: lower doses may be sufficient
Contraindicated if acute pulmonary insufficiency, respiratory depression, sleep apnoea, obsessional states, severe hepatic insufficiency, myasthenia gravis
Lora
zepa
m in
ject
ion Pre-operative
medication, acute anxiety states, acute excitement or acute mania, status epilepticus
Premedication: 0.05 mg/Kg
By the i.v. route the injection should be given 30-45 min before surgery
By the i.m. route the injection should be given 1-1.5h before surgery
Acute anxiety: 0.025-0.03 mg/kg i.v./i.m. Repeat 6 hourly
Status epilepticus: 4 mg i.v.
P.163
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs 9
Drug Indications Dose Dose adjustments Comments
Short-acting benzodiazepines
Lorm
etaz
epam
ora
l Short-term treatment of insomnia
0.5-1.5 mg oral before retiring. The initial dosage may be increased to 2 mg in individual cases if this proves necessary
Elderly: may respond to lower doses
Chronic respiratory insufficiency: a lower dose is recommended
Severe renal impairment: caution
Contraindicated if myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome, acute intoxication with alcohol, hypnotics, analgesics or psychotropic drugs, severe liver insufficiency
Mid
azol
am o
ral
Insomnia DOSE / DOSE ADJUSTMENTS: 7.5-15 mg oral at bedtime
COMMENTS: Caution in adults >60years, chronically ill or debilitated patients, patients with chronic respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or with impaired cardiac function - Contraindicated if conscious sedation in patients with severe respiratory failure or acute respiratory depression - Severe cardiorespiratory adverse events have been reported (respiratory depression, apnoea, respiratory arrest and/or cardiac arrest). Such life-threatening incidents are more likely to occur when the injection is given too rapidly or when a high dosage is administered
P.164
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Short-acting benzodiazepines
Mid
azol
am in
ject
ion
(1)
Short-acting sleep-inducing drug
DOSE / DOSE ADJUSTMENTS:
Indications Adults <60 y Adults ≥60 y/debilitated or chronically ill
Conscious sedation i.v. Initial dose: 2-2.5 mg Titration doses: 1 mg Total dose: 3.5-7.5 mg
i.v Initial dose: 0.5-1 mg Titration doses: 0.5-1 mg Total dose: <3.5 mg
Anaesthesia premedication
i.v. 1-2 mg repeatedi.m. 0.07-0.1 mg/kg
i.v. Initial dose: 0.5 mg Slow uptitration as needed
i.m. 0.025-0.05 mg/kg
COMMENTS: Caution in adults >60years, chronically ill or debilitated patients, patients with chronic respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or with impaired cardiac function - Contraindicated if conscious sedation in patients with severe respiratory failure or acute respiratory depression - Severe cardiorespiratory adverse events have been reported (respiratory depression, apnoea, respiratory arrest and/or cardiac arrest). Such life-threatening incidents are more likely to occur when the injection is given too rapidly or when a high dosage is administered
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
P.165
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Mid
azol
am in
ject
ion
(2)
Short-acting sleep-inducing drug
DOSE / DOSE ADJUSTMENTS:
Indications Adults <60 y Adults ≥60 y/debilitated or chronically ill
Anaesthesia induction i.v. 0.15-0.2 mg/kg (0.3-0.35 without premedication)
i.v. 0.05-0.15 mg/kg (0.15-0.3 without premedication)
Sedative component in combined anaesthesia
i.v. Intermittent doses of 0.03-0.1 mg/kg or continuous infusion of 0.03-0.1 mg/kg/h
i.v. Lower doses than recommended for adults <60 years
Sedation in ICU i.v. LD: 0.03-0.3 mg/kg in increments of 1-2.5 mg MD: 0.03-0.2 mg/kg/h
COMMENTS: Caution in adults >60years, chronically ill or debilitated patients, patients with chronic respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or with impaired cardiac function - Contraindicated if conscious sedation in patients with severe respiratory failure or acute respiratory depression - Severe cardiorespiratory adverse events have been reported (respiratory depression, apnoea, respiratory arrest and/or cardiac arrest). Such life-threatening incidents are more likely to occur when the injection is given too rapidly or when a high dosage is administered
P.166
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications DoseDose
adjustmentsComments
Long-acting benzodiazepines
Bro
maz
epam
Insomnia, short-term treatment of anxiety or panic attacks
1.5-3 mg oral up to TID
If a severe condition: 6-12 mg oral BID or TID
Elderly or hepatic impairment: lower doses are recommended
Contraindicated if myasthenia gravis, severe hepatic impairment, severe respiratory insufficiency, sleep apnoea syndrome
Clo
baza
m
Anxiety, adjunctive therapy in epilepsy
Anxiety: 20-30 mg oral daily in divided doses or as a single dose given at night. Doses up to 60 mg daily have been used in severe anxiety
Epilepsy: starting dose of 20-30 mg oral per day, increasing up to a max of 60 mg daily
Elderly: lower doses may be used
Chronic or acute severe respiratory insufficiency, renal or hepatic impairment: lower doses are recommended
Contraindicated if history of drug or alcohol dependence, myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome, severe hepatic impairment
P.167
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications DoseDose
adjustmentsComments
Long-acting benzodiazepines
Clo
naze
pam
Epileptic disease and seizures
Oral: Initial dose not to exceed 1 mg/day; MD: 4-8 mg
i.v.: 1 mg by slow injection or slow infusion. Repeat dose if needed (1-4 mg are usually sufficient)
Elderly: initial dose should not exceed 0.5 mg/day
Chronic pulmonary insufficiency, renal or mild-moderate hepatic impairment: may require lower doses
Contraindicated if acute pulmonary insufficiency, severe respiratory insufficiency, sleep apnoea syndrome, myasthenia gravis, severe hepatic insufficiency, coma or in patients known to be abusing pharmaceuticals, drugs or alcohol
Clo
raze
pate
ora
l Anxiety, insomnia
5-30 mg oral at bedtime or in divided doses
Elderly, renal and hepatic impairment: lower doses may be required
Contraindicated if myasthenia gravis, severe decompensated respiratory insufficiency, sleep apnoea syndrome, severe hepatic impairment
Caution if alcohol deprivation, give thiamine before administering glucose containing i.v. fluids
P.168
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications DoseDose
adjustmentsComments
Long-acting benzodiazepines
Clo
raze
pate
in
ject
ion
Agitation, confusion, aggressiveness, premedication, tetanus, alcoholism
Agitation, confusion, aggressiveness: 20-200 mg/day, i.m./i.v. followed by oral therapy
Premedication: 20-50 mg/day i.m./i.v. Alcoholism: 50-100 mg every 3-4h
Benign tetanus (without tracheostomy) 120-500 mg/day i.v.
Malignant tetanus (with tracheostomy and assisted ventilation): 500-2,000 mg/day i.v.
Elderly, renal and hepatic impairment: lower doses may be required
Contraindicated if myasthenia gravis, severe decompensated respiratory insufficiency, sleep apnoea syndrome, severe hepatic impairment
Caution if alcohol deprivation, give thiamine before administering glucose containing i.v. fluids
Ch
lord
iaze
pox
ide Anxiety,
muscle spasm, symptomatic relief of acute alcohol withdrawal
Anxiety: starting dose 5 mg/day oral: usual dose up to 30 mg in divided doses increasing to a max of 100 mg/day, in divided doses, adjusted on an individual basis
Insomnia associated with anxiety: 10-30 mg oral at bedtime
Muscle spasm: 10-30 mg/day oral in divided doses
Alcohol withdrawal: 25-100 mg, repeated if necessary, in 2-4h
Elderly and/or debilitated patients, renal or hepatic impairment: dosage should not exceed half the adult dose
Contraindicated if acute pulmonary insufficiency, sleep apnoea, respiratory depression, phobic and obsessional states, chronic psychosis, severe hepatic impairment, myasthenia gravis
P.169
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications DoseDose
adjustmentsComments
Long-acting benzodiazepines
Dia
zepam
(1)
Anxiety 5-30 mg oral daily in divided doses or 10 mg i.v. or i.m. and repeated after an interval of not less than 4h
0.5 mg/kg rectal Dose can be repeated every 4-12h. Max 30 mg
Elderly and debilitated patients: half of the recommended dose
Hepatic impairment and severe renal impairment: a lower dose is recommended
Contraindicated if phobic or obsessional states; chronic psychosis, hyperkinesis, acute pulmonary insufficiency; respiratory depression, acute or chronic severe respiratory insufficiency, myasthenia gravis, sleep apnoea, severe hepatic impairment, acute porphyriaInsomnia associated
with anxiety5-15 mg oral before retiring
Cerebral palsy 5-60 mg oral daily in divided doses
Upper motor neuronic spasticity
5-60 mg oral daily in divided doses
P.170
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications DoseDose
adjustmentsComments
Long-acting benzodiazepines
Dia
zepam
(2
)
Muscle spasm 5-15 mg oral daily in divided doses or
10 mg i.v. or i.m. and repeated after after an interval of not less than 4h
0.5 mg/Kg rectal. Dose can be repeated every 4-12h. Max 30 mg
Elderly and debilitated patients: half of the recommended dose
Hepatic impairment and severe renal impairment: a lower dose is recommended
Contraindicated if phobic or obsessional states; chronic psychosis, hyperkinesis, acute pulmonary insufficiency; respiratory depression, acute or chronic severe respiratory insufficiency, myasthenia gravis, sleep apnoea, severe hepatic impairment, acute porphyria
Tetanus 0.1-0.3 mg/Kg i.v. and repeated every 1-4h; alternatively, a continuous infusion of 3-10 mg/kg/24h may be used.
0.5 mg/kg rectal. Dose can be repeated every 4-12h. Max 30 mg
P.171
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9Sedatives and neuropsychiatric drugs (Cont.)
Drug Indications DoseDose
adjustmentsComments
Long-acting benzodiazepines
Dia
zepam
(3
)
Epilepsy 2-60 mg oral daily in divided doses
or 10-20 mg i.v.or i.m. The dose can be repeated if necessary after 30-60min. If indicated, this may be followed by slow i.v. infusion (max total dose 3 mg/kg over 24h)
or 0.5 mg/kg rectal Dose can be repeated every 4-12h. Max 30 mg
Elderly and debilitated patients: half of the recommended dose
Hepatic impairment and severe renal impairment: a lower dose is recommended
Contraindicated if phobic or obsessional states; chronic psychosis, hyperkinesis, acute pulmonary insufficiency; respiratory depression, acute or chronic severe respiratory insufficiency, myasthenia gravis, sleep apnoea, severe hepatic impairment, acute porphyria
Alcohol withdrawal 5-20 mg oral, repeated if necessary in 2-4h
0.5 mg/kg rectal Dose can be repeated every 4-12h. Max 30 mg
Delirium tremens: 10-20 mg i.v. or i.m.
Premedication before surgery
5-20 mg oral
P.172
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Long-acting benzodiazepines
Flur
azep
am
Insomnia 15 mg oral at bedtime.
If severe insomnia: 30 mg oral but residual effects on awakening are more frequent at this dose
Elderly, chronic pulmonary insufficiency, renal or hepatic impairment: lower dose is recommended
Contraindicated if myasthenia gravis, severe pulmonary insufficiency, respiratory depression, phobic or obsessional states, chronic psychosis, sleep apnoea, severe hepatic insufficiency
Other sedatives
Clo
met
hia
zole
(1) Management of
restlessness and agitation in the elderly
192 mg (1 capsule) oral TID Elderly, renal impairment, gross liver damage, decreased liver function, sleep apnoea and chronic pulmonary insufficiency: caution
Contraindicated if acute pulmonary insufficiency
Alcohol combined with clomethiazole particularly in alcoholics with cirrhosis can lead to fatal respiratory depression even with short term use
Severe insomnia in the elderly
192-384 mg oral (1-2 capsules) at bedtime
P.173
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Other sedatives
Clo
met
hia
zole
(2
) INDICATIONS: Alcohol withdrawal INITIAL DOSE : 2-4 capsules oral, if necessary repeated after some hoursDay 1: first 24h: 9-12 capsules, divided into 3 or 4 doses
Day 2: 6-8 capsules, divided into 3 or 4 doses
Day 3: 4-6 capsules, divided into 3 or 4 doses
Days 4-6: A gradual reduction in dosage until the final dose
Administration for more than 9 days is not recommended
Elderly, renal impairment, gross liver damage, decreased liver function, sleep apnoea and chronic pulmonary insufficiency: caution
Contraindicated if acute pulmonary insufficiencyAlcohol combined with clomethiazole particularly in alcoholics with cirrhosis can lead to fatal respiratory depression even with short term use
Dex
med
etom
idin
e Sedation of adult ICU patients
Switch to dexmedetomidine: initial i.v. infusion rate of 0.7 mcg/kg/hTitrate upwards to achieve desired level of sedation, range 0.2-1.4 mcg/kg/hMax dose: 1.4 mcg/kg/hMax duration: 14 days
Caution if hepatic impairment, impaired peripheral autonomic activity, pre-existing bradycardiaFrail patients: a lower starting infusion rate should be considered
The drug provides analgesia and does not cause respiratory depression. Associated with a lower prevalence of ICU delirium compared to benzodiazepines. Primary adverse effects are dose-related bradycardia and hypotension.Dexmedetomidine should not be administered by loading or bolus dose
P.174
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Other sedatives
Dox
yla
min
e
Insomnia 12.5-25 mg oral at bedtime Max duration: 7 days
Renal and hepatic impairment: caution
Contraindicated if hypersensitive to other antihistaminesCaution if: asthma, narrow angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloric/duodenal obstruction, bladder neck obstruction, concurrent use with MAOIs
Mel
aton
in Insomnia in patients ≥55 years
2 mg oral at bedtimeMax duration: 13 weeks
Renal impairment: cautionHepatic impairment: not recommended
Do not use in patients with autoimmune diseasesDo not crush or chew tablets
Pro
pof
ol
Sedation during intensive care
Initiate at 5 mcg/Kg/min i.v. (0.3 mcg/Kg/h) and titrate to achieve sedation goals by 5 mcg/Kg/min every 5 minMaintenace rates of 5-50 mcg/Kg/min may be requiredAvoid prolonged infusions >50 mcg/Kg/min
Elderly: rate of infusion should be reduced. Rapid bolus administration is not indicated in this group of patients
Rapid onset (1-2 min) and short duration (3-5 min or longer if prolonged infusion)Avoid loading doses because of the risk of hypotensionMonitor blood lipid levels, blood pressurePropofol has no analgesic properties
P.175
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Other sedatives
Zol
pide
m Insomnia 10 mg oral at bedtime
Max duration: 4 weeks
Elderly, debilitated patients, hepatic impairment: initial dose 5 mg
Contraindicated if obstructive sleep apnoea, myasthenia gravis, severe hepatic insufficiency, acute and/or severe respiratory depression
Zop
iclo
ne Insomnia 7.5 mg oral at bedtime
Max duration: 4 weeks
Elderly, hepatic or renal impairment: initial dose 3.75 mg
Contraindicated if myasthenia gravis, severe sleep apnoea syndrome, severe respiratory or severe hepatic insufficiency
P.176
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications DoseDose
adjustmentsComments
Neuroleptics: Extrapyramidal symptoms and neuroleptic malignant syndrome may occur with all neuroleptics. Elderly people with dementia who are treated with antipsychotics are at a small increased risk of death compared with those who are not treated
Typical neuroleptics
Chlo
rpro
maz
ine
Schizophrenia and other psychoses
Oral: Initially 25 mg TID or 75 mg at bedtime increasing by daily amounts of 25 mg to an effective MD (75-300 mg daily, some patients may require up to 1g)
I.M.: 25-50 mg every 6-8h
Elderly (schizophrenia, nausea and vomiting): start with ⅓ - ½ usual adult dose
Contraindicated if liver or renal dysfunction, epilepsy, Parkinson, hypothyroidism, cardiac failure, phaeochromocytoma, agranulocytosis myasthenia gravis, prostate hypertrophy, history of narrow angle glaucoma
Caution in patients with risk factor for stroke, seizures, cardiovascular disease or a family history of QT prolongation
Intractable hiccup Oral: 25-50 mg TID or QD
I.M.: 25-50 mg and if this fails 25-50 mg by slow i.v. infusion
Nausea and vomiting in terminal illness
Oral: 10-25 mg every 4-6h
I.M.: 25 mg initially then 25-50 mg every 3-4h until vomiting stops, then change to orally
P.177
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications DoseDose
adjustmentsComments
Typical neuroleptics
Flu
phen
azin
e
Schizophrenia and other psychoses
Patients without previous exposure of fluphenazine: start 12.5 mg i.m Next dose depends on patient’s response (12.5-100 mg)
When administered as maintenance therapy, a single injection may be effective for up to 4weeks or longer
Elderly (over 60): a lower dose is recommended
Liver and renal disease: caution
Contraindicated if comatose states, marked cerebral atherosclerosis, liver failure, renal failure, phaeochromocytoma, severe cardiac insufficiency, severely depressed states, existing blood dyscrasias
Caution if arrythmias, Parkinson, narrow angle glaucoma, thyrotoxicosis, hypothyroidism, epilepsy, myasthenia gravis, prostatic hypertrophy, severe respiratory disease
P.178
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Typical neuroleptics
Hal
oper
idol
ora
l (1)
Schizophrenia, psychoses and mania
Acute phase: 2-20 mg/day oral as a single dose or in divided doses
Chronic phase: 1-3 mg oral TID, may be increased up to 20 mg/day in divided doses, depending on the response
Max daily dose: 20 mg
DOSE ADJUSTMENTS:
Elderly: start with half the dosage stated for adults and adjusted according to the results if necessary
COMMENTS: Contraindicated if comatose states, CNS depression, Parkinson, lesions of the basal ganglia, clinical significant cardiac disorders, QT interval prolongation, history of ventricular arrhythmia or Torsades de pointes, clinically significant bradycardia, 2nd or 3rd degree heart block, uncorrected hypokalaemia and use of other QT prolonging drugs
Caution if renal failure, liver disease, epilepsy, hyperthyroidism, phaeochromocytoma
Bioavailability from the oral route is about 60% of that from the i.m. route and readjustment of dose may be required i.v. haloperidol can be associated with QT prolongation and torsades de pointes
Psychomotor anti-agitation
Acute phase: Moderate symptomatology 1.5-3.0 mg oral BID or TID
Severe symptomatology/resistant patients 3-5 mg oral BID or TID
Chronic phase: 0.5-1 mg oral TID, may be increased to 2-3 mg TID, if required, MD: gradually reduced to the lowest effective MD
Max daily dose: 20 mg
P.179
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Typical neuroleptics
Hal
oper
idol
or
al (
2)
Gilles de la Tourette syndrome, severe tics, intractable hiccup
Starting dose 1.5 mg oral TID adjusted according to responseA daily MD of 10 mg may be required in Gilles de la Tourette syndromeMax daily dose: 20 mg
DOSE ADJUSTMENTS:Elderly: start with half the dosage stated for adults and adjusted according to the results if necessary
COMMENTS: Contraindicated if comatose states, CNS depression, Parkinson, lesions of the basal ganglia, clinical significant cardiac disorders, QT interval prolongation, history of ventricular arrhythmia or Torsades de pointes, clinically significant bradycardia, 2nd or 3rd degree heart block, uncorrected hypokalaemia and use of other QT prolonging drugs
Caution if renal failure, liver disease, epilepsy, hyperthyroidism, phaeochromocytoma
Bioavailability from the oral route is about 60% of that from the i.m. route and readjustment of dose may be required i.v. haloperidol can be associated with QT prolongation and torsades de pointes H
alop
erid
ol in
ject
ion
Rapid control of the symptoms of hostility, aggression, hyperactivity, disruptive and violent behaviour, confusion, emotional withdrawal, hallucinations and delusions associated with acute and chronic schizophrenia, mania, and hypomania, and organic brain syndrome Nausea and vomiting
Initial doses of 2-10 mg i.m.Depending on the response of the patients, subsequent doses may be given every 4-8h up to a max of 18 mg/day
P.180
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Typical neuroleptics
Lev
om
epro
mazin
e
Management of pain, restlessness or distress in terminally ill patient
12.5-25 mg i.m. or i.v. injection. In cases of severe agitation, up to 50 mg may be used, repeated every 6-8hor25-200 mg/day by continuos s.c. infusionor12.5-50 mg oral every 4-8h
Elderly: caution Caution if liver dysfunction or cardiac disease, bradycardia or 2nd or 3rd degree heart block, risk of QT interval prolongation
Psychiatric conditions
Bed patients: initially the total daily dose 100-200 mg oral, usually divided into 3 doses, gradually increased to 1g daily if necessary
Per
icya
zine
Anxiety, psichiatric conditions
Severe conditions: Initially 75 mg/day oral in divided doses. Titrate according to patient response at weekly intervals; MD: max dose 300 mg/dayMild or moderate conditions: Initially 15-30 mg/day oral divided in two doses, with a larger dose being given in the evening
ElderlySevere conditions: Initially 15-30 mg/day in divided doses Mild or moderate conditions: start 5-10 mg/day. Half or quarter the normal adult dose may be sufficient as MD
Caution if liver or renal dysfunction, epilepsy, Parkinson, hypothyroidism, cardiac failure, phaeochromocytoma, myasthenia gravis, prostrate hypertrophy, history of narrow angle glaucoma, agranulocytosis, risk of QT interval prolongationDiscontinue if unexplained fever
P.181
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Typical neuroleptics
Per
ph
enazin
e
Anxiety, psichiatric conditions, nausea and vomiting, intractable hiccup
DOSE: 4 mg oral TID. Titrate according to patient response. Max daily dose: 24 mg
DOSE ADJUSTMENTS: Elderly: one quarter or one half of the recommended adult dosage
COMMENTS: Contraindicated if leucopenia, or in association with drugs liable to cause bone marrow depression, or to patients in comatose states - Caution if liver disease, severe respiratory disease, renal failure, epilepsy, Parkinson, history of narrow angle glaucoma, hypothyroidism, myasthenia gravis, phaeochromocytoma, prostatic hypertrophy, risk of QT interval prolongation
Pim
ozid
e
Schizophrenia, other psychoses
DOSE: Chronic schizophrenia: 2-20 mg oral daily, with 2 mg as a starting dose
This may be increased according to response and tolerance
Other psychoses: an initial dose of 4 mg oral daily which may then be gradually increased, if necessary, according to response, max 16 mg daily
DOSE ADJUSTMENTS: Elderly: half the normal starting dose
Caution if hepatic, renal impairment or phaeochromocytoma
COMMENTS: Contraindicated if risk of QT interval prolongation, known uncorrected hypokalaemia, hypomagnesaemia, clinically significant cardiac disorders, clinically significant bradycardia, severe central nervous system depression, depression, Parkinson, concomitant use with CYP3A4 or CYP2D6 inhibiting drugs, serotonin uptake inhibitors
P.182
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Typical neuroleptics
Trif
luoper
azin
e Anxiety, depressive symptoms, agitation, nausea and vomiting
Low dosage: 2-4 mg/day oral, given in divided doses, according to the severity of the patient’s condition
High dosage: 5 mg oral BID, after a week this may be increased to 15 mg/day. If necessary, further increases of 5 mg may be made at three-day intervals
DOSE ADJUSTMENTS: Elderly: starting dose should be reduced by at least half
COMMENTS: Contraindicated if comatose patients, existing blood dyscrasias or known liver damage, uncontrolled cardiac decompensation
Caution if CV disease , Parkinson, risk of QT interval prolongation
Zu
clopen
thix
ol
Acute psychoses 50-150 mg i.m., repeated if necessary after 2-3 days
Some patients may need an additional injection between 1-2 days after the first injection
Max accumulated dosage: 400 mg
DOSE ADJUSTMENTS: Elderly, renal or hepatic impairment: caution, a lower dose may be necessary
COMMENTS: Contraindicated if circulatory collapse, depressed level of consciousness
Caution if Parkinson, epilepsy, risk of QT interval prolongation, cardiac disease, or arrhythmias, narrow angle glaucoma, myasthenia gravis, prostatic hypertrophy, hypothyroidism, hyperthyroidism, phaeochromocytoma
P.183
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Atypical neuroleptics: 3 differences with typical neuroleptics: the risk of extrapyramidal symptoms is lower, tardive dyskinesia is reduced and the ability to block serotonin-2 receptors is present. Atypical neuroleptics have been associated with new-onset diabetes and metabolic syndrome
Am
isulp
ride
Schizophrenia For acute psychotic episodes: 400-800 mg/day oral In individual cases, the daily dose may be increased up to 1,200 mg/day
Doses should be adjusted individually
Administered QD at oral doses up to 300 mg, higher doses BID
Elderly: caution
CrCl 30-60 ml/min: reduce to a half
CrCl 10-30 ml/min: reduce to a third
Contraindicated if concomitant prolactin-dependent tumours, phaeochromocytoma, combination with levodopa
Caution if epilepsy, risk of QT interval prolongation
Ase
nap
ine Severe manic
episodes associated with bipolar type I disorder
5 mg s.l. BID The dose can be increased to 10 mg BID based on individual clinical response and tolerability
Elderly, moderate hepatic impairment: caution
Caution if Parkinson, risk of QT interval prolongation, seizures
Do not use in severe hepatic impairment or CrCl <15ml/min
Do not chew or swallow tablets
P.184
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Atypical neuroleptics
Ari
pipr
azol
e
Schizophrenia, manic episodes in bipolar type I disorder
Oral: 10-15 mg QD with a MD of 10-30 mg QDi.m.: Recommended initial dose: 9.75 mg Dose range: 5.25-15 mgA second injection may be administered 2h after the first injection, on the basis of individual clinical status and no more than three injections should be given in any 24h periodMax daily dose: 30 mg/day
Caution if elderly, severe hepatic impairment
Orodispersible tablet should be placed in the mouth, it will rapidly disperse in salivaCaution if known CV disease, history of QT prolongation, epilepsy, concomitant administration of potent CYP3A4 or CYP2D6 inhibitors
Ola
nza
pine
Psichiatric conditions
Schizophrenia: recommended starting dose 10 mg/day orally
Manic episode: Starting dose 15 mg QD oral in monotherapy or 10 mg QD in combination therapy. Then, adjust dose according to response: 5-20 mg/day
Elderly, renal or hepatic impairment: consider a lower starting dose (5 mg/day)
Contraindicated if risk of narrow-angle glaucomaCaution if Parkinson, low leukocyte and/or neutrophil counts for any reason, risk of QT interval prolongationOrodispersible tablet should be placed in the mouth, it will rapidly disperse in saliva
P.185
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Atypical neuroleptics
Pal
iper
idon
e
Schizophrenia, schizoaffective disorder
6 mg oral QD, administered in the morning. Some patients may benefit from lower or higher doses within the recommended range of 3-12 mg QD (6-12 mg for schizoaffective disorder)
Caution if elderly patients with dementia with risk factors for stroke
Mild renal impairment: initial dose 3 mg QD (max 6 mg)
Moderate-severe renal impairment: initial dose 1.5 mg QD (max 3 mg)
CrCl <10 ml/min: not recommended
Caution if severe hepatic impairment, seizures, Parkinson, risk of QT interval prolongation, low leukocyte and/or neutrophil counts for any reason, known CV disease, cerebrovascular disease or conditions that predispose the patient to hypotension
Do not chew, divide, or crush
Take it the same way with regard to meals
P.186
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications DoseDose
adjustmentsComments
Atypical neuroleptics
Quet
iapi
ne
Schizophrenia IRF: Total daily dose for the first 4 days is: 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4), then 150-750 mg/day Administered in 2 divided doses PRF: Starting dose 300 mg oral on Day 1 and 600 mg on Day 2 MD: 400-800 mg/day
DOSE ADJUSTMENTS: Elderly, hepatic impairment: caution, a lower dose may be necessary
COMMENTS: Contraindicated if concomitant administration of cytochrome P450 3A4 inhibitors, such as HIV-protease inhibitors, azole-antifungal agents, erythromycin, clarithromycin and nefazodone
Caution if low leukocyte and/or neutrophil counts for any reason, history of seizures, cerebrovascular disease, cardiovascular disease, risk of QT interval prolongation
It could be used if Parkinson disease
PRF: tablets should not be split, chewed or crushed
Moderate-severe manic episodes in bipolar disorder
IRF: Total daily dose for the first 4 days is: 100 mg (Day 1), 200 mg (Day 2), 300 mg (Day 3) and 400 mg (Day 4) Further dosage adjustments up to 800 mg/day Administered in 2 divided doses PRF: Starting dose 300 mg oral on Day 1 and 600 mg on Day 2 MD: 400-800 mg/day
Depression in bipolar disorders
IRF: Total daily dose for the first 4days is: 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4) The recommended daily dose is 300 mg Administered at bedtimePRF: Total daily dose for the first 4 days is: 50 mg oral (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4) Recommended daily dose: 300 mg
Major depressive episodes
PRF: 50 mg on Day 1 and 2, and 150 mg on Day 3 and 4 at bedtimeMax dose 300 mg/day
P.187
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Atypical neuroleptics
Ris
peri
done
(1)
Schizophrenia Start 2 mg/day oral (QD or in 2 divided doses)
The dosage may be increased on the 2nd day to 4 mg
MD: 4-6 mg
Elderly: 0.5 mg BID
Caution if renal or hepatic impairment
Caution if known cardiovascular disease, low leukocyte and/or neutrophil counts for any reason, Parkinson, risk of QT interval prolongation
Orodispersable tablet: place the tablet on the tongue
Manic episodes in bipolar disorder
Start with 2 mg oral QD
Dosage adjustments, if needed, should occur at intervals of not less than 24h and in dosage increments of 1 mg/day. Max daily dose 6 mg
Elderly: start with 0.5 mg BID
This dosage can be individually adjusted with 0.5 mg BID increments to 1-2 mg BID
Caution if renal or hepatic impairment
Persistent aggression in patients with moderate to severe Alzheimer’s dementia
Start with 0.25 mg oral BID
This dosage can be individually adjusted by increments of 0.25 mg BID, not more frequently than every other day, if needed. Optimum dose is 0.5 mg BID for most patients
Caution if renal or hepatic impairment
P.188
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Atypical neuroleptics
Ris
peri
done
(2) Conduct disorder ≥50kg: starting dose 0.5 mg oral QD
This dosage can be individually adjusted by increments of 0.5 mg QD not more frequently than every other day, if needed. Optimum dose is 1 mg QD for most patients<50kg: starting dose 0.25 mg oral QD This dosage can be individually adjusted by increments of 0.25 mg QD not more frequently than every other day, if needed. Optimum dose is 0.5 mg QD
Caution if renal or hepatic impairment
Caution if known cardiovascular disease, low leukocyte and/or neutrophil counts for any reason, Parkinson, risk of QT interval prolongationOrodispersable tablet: place the tablet on the tongue
Sulp
irid
e
Acute and chronic schizophrenia
Starting dose: 400-800 mg oral daily, given as one or two tablets twice daily (morning and early evening)Predominantly positive symptons: starting dose of at least 400 mg oral BID, increasing if necessary up to a max of 1,200 mg BIDPredominantly negative symptoms respond to doses below 800 mg oral daily, a starting dose of 400 mg BID is recommendedPatients with mixed positive and negative symptoms: 400-600 mg oral BID
Renal impairment: caution
Contraindicated if phaeochromocytoma and acute porphyria, concomitant prolactin-dependent tumours, association with levodopa or antiparkinsonian drugsCaution if Parkinson, epilepsy, low leukocyte and/or neutrophil counts for any reason, risk of QT interval prolongation
P.189
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
Drug Indications Dose Dose adjustments Comments
Atypical neuroleptics
Tia
prid
e
Behavioral disorders in dementia patients
Starting dose 50 mg oral/i.m./i.v. BID, increasing if necessary to 100 mg TID
Max dose 400 mg/day
Elderly: caution
CrCl 30-60 ml/min: 75% of the normal dose
CrCl 10-30 ml/min: 50% of the normal dose
CrCl <10 ml/min: 25% of the normal dose
Contraindicated if phaeochromocytoma, concomitant prolactin-dependent tumours, association with levodopa or antiparkinsonian drugs
Caution if epilepsy, Parkinson, low leukocyte and/or neutrophil counts for any reason, risk of QT interval prolongation
Huntington’s disease 1,200 mg/day oral/i.m./i.v. divided in 3 doses
Progressive reduction to a MD
Zip
rasi
done
Schizophrenia
Bipolar type I disorder
Initial dose 40 mg oral BID with food Then, dose may be increased to 60-80 mg BID
Max dose 80 mg BID
Elderly, renal or hepatic impairment: caution, a lower dose may be necessary
Contraindicated if known history of QT prolongation, decompensated heart failure, recent MI
It could the parenteral drug of choice for patients with Parkinson disease
Acute treatment of agitation in schizophrenia
10-20 mg i.m. administered as required up to a max dose of 40 mg/day
Doses of 10 mg may be administered every 2h
P.190
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Sedatives and neuropsychiatric drugs (Cont.) 9
APTT = Activated partial thromboplastin timeAB = Airway and breathingABG = Arterial blood gasAADs = Antiarrhythmic drugsAAS = Acute aortic syndromeACEI = Angiotensin converting enzyme inhibitorACLS = Advanced cardiovascular life supportACS = Acute coronary syndromeACT = Activated clotting timeAD = Aortic DissectionAED = Automated external defibrillator AF = Atrial fibrillationAo = Aortic aPTT = Activated partial thromboplastin timeARB = Angiotensin receptor blockersAS = Aortic stenosisAV = Atrioventricular AVN = Atrioventricular nodeAVNRT = Atrioventricular nodal re-entrant
tachycardiaAVNT = Atrioventricular nodal tachycardiaBID = Twice a dayBBB = Bundle branch block
BLS = Basic life support BNP = Brain natriuretic peptideBP = Blood pressureCABG = Coronary artery bypass graftingCAD = Coronary artery diseaseCath Lab = Catheterisation laboratoryCCB = Calcium channel blockers CCU = Coronary care unitCHF = Congestive heart failureCMR = Cardiovascular magnetic resonanceCOPD = Chronic obstructive pulmonary diseaseCPAP = Continuous positive airway pressure CPR = Cardiopulmonary resuscitationCr = Creatinine blood level (mg/dL)CrCl = Creatinine clearanceCS = Cardiogenic shockCSM = Carotid sinus massage CSNRT = Corrected sinus node recovery timeCSS = Carotid sinus syndromeCT = Computed tomographyCT-angio = Computed tomography angiographycTn = Cardiac troponinCUS = Compression venous ultrasound
P.191
Abbreviations
CV = CardiovascularCVA = Cerebrovascular accident CXR = Chest X-rayDAPT = Dual antiplatelet therapyDD = Dyastolic dysfunctionDM = Diabetes mellitusdTT = Diluted thrombin time DVT = Deep vein thrombosis ECG = ElectrocardiogramECT = Ecarin clotting time ED = Emergency department EG = ElectrogramseGFR = Estimated glomerular filtration rate
(ml/min/1.73 m2) EMB = Endomyocardial biopsyEMS = Emergency medical servicesEPS = Electrophysiological study ERC = European Resuscitation CouncilESR = Erythrocyte sedimentation rate ETT = Exercice treadmill testing FFP = Fresh frozen plasmaFMC = First medical contact
GER = Gastroesophageal refluxGFR = Glomerular flow rateGI = GastrointestinalGP = GlycoproteinHb = haemoglobinHF = Heart failureHIT = Heparin-induced thrombocytopeniaHOCM = Hypertrophic obstructive cardiomyopathy HTN = Hypertension HR = Heart ratehsTn = High-sensitive troponinIABP = Intra-aortic balloon pump ICC = Intensive cardiac careICCU = Intensive cardiac care unitICD = Implantable cardioverter defibrillatorIHD = Ischemic heart diseaseIMH = Intramural hematomaIRF = Immediate-release formulationISFC = International Society and Federation
of Cardiologyi.o. = Intraosseous IV = Invasive ventilation
P.192
Abbreviations (Cont.)
i.v. = IntravenousKD = Kidney diseaseLBBB = Left bundle branch blockLD = Loading doseLGE = Late gadolinium enhancement LMWH = Low-molecular weight heparinLOC = Loss of consciousness LV = Left ventricularLVD = Left ventricular dysfunctionLVEF = Left ventricular ejection fraction LVH = Left ventricular hypertrophyLVSD = Left ventricular systolic dysfunctionMCS = Mechanical circulatory support MD = Maintenance doseMDCT = Computed tomography with >4 elementsMI = Myocardial infarctionMRA = Mineralocorticoid receptor antagonistMRI = Magnetic resonance imagingMvo = Microvascular obstructionNIV = Non-invasive ventilationNOAC = New oral anticoagulantsNSAID = Non-steroidal anti-inflammatory drugs
NSTE-ACS = Non ST-segment elevation acute coronary syndrome
NSTEMI = Non ST-segment elevation myocardial infarction NTG = NitroglycerinNT-proBNP = N-terminal pro brain natriuretic
peptideNVAF = Non-valvular atrial fibrillationNYHA = New York Heart AssociationOH = Orthostatic hypotensionPAP = Pulmonary arterial pressurePAU = Penetrating aortic ulcer PCI = Percutaneous coronary interventionPCM = Physical counter-measures PCP = Pulmonary capillary pressurePE = Pulmonary embolismPEA = Pulmonary endarterectomyPEEP = Positive end expiratory pressurePPC = Prothrombin complex concentratePR = Pulmonary regurgitationPRECISE-DAPT = PREdicting bleeding Complications
In patients undergoing Stent implantation and subsEquent Dual Anti Platelet Therapy
P.193
Abbreviations (Cont.)
PRF = Prolonged-release formulationProCT = ProcalcitoninPRN = Pro re nata PS-PEEP = Pressure support-positive end-
expiratory pressure PSVT = Paroxysmal supraventricular tachycardiaQD = Once a dayQPM = Every eveningrFVIIa = Recombinant factor VIIartPA = Recombinant tissue plasminogen activatorRV = Right ventricularRVOT-VT = Right ventricular outflow tract
ventricular tachycardiaSBP = Systemic blood pressures.c = SubcutaneousSIRS = systemic inflammatory response syndrome SLE = Systemic lupus erythematosusSMU = Syncope management unitsSTE-ACS = ST-segment elevation acute
coronary syndromeSTEMI = ST-segment elevation myocardial
infarction
SVT = Supraventricular tachycardiaSpo2 = Oxygen saturation TEE = Transesophageal echocardiographyTEVAR = Thoracic endovascular aortic repair TIA = Transient ischemic attack TID = Three times a dayTLOC = Transient loss of consciousnessTOE = Transoesopageal echocardiographyTSH = Thyroid-stimulating hormone TTE = Transthoracic echocardiographyUA = Unstable anginaUFH = Unfractionated heparinULN = Upper limit of normalVF = Ventricular fibrillationVR = Vascular resistanceVT = Ventricular tachycardia VTE = Venous thromboembolismVVS = Vasovagal syncopeWBC = white blood cell count WHO = World Health OrganizationWPW = Wolff-Parkinson-White
P.194
Abbreviations (Cont.)
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P.195
Notes
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Reproduced With permission of Oxford University Press (UK) © European Society of Cardiology
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References and copyright acknowledgments (Cont.)
This is a publication of the Acute Cardiovascular Care Association (ACCA), a branch of the European Society of Cardiology. Its content reflects the opinion of the authors based on the evidence available at the time it was written and does not necessarily imply an endorsement by ACCA or the ESC.
The guidance suggested in the Clinical Decision Making Toolkit does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Some content, illustrations/tables/figures were inspired and/or adapted from ESC Guidelines and other existing sources, with permission granted by the original publishers.
AcknowledgementsWe are indebted to all the authors for their commitment and for the strong effort to synthesise their wide scientific knowledge and clinical experience into simple algorithms and schemes using the aim to help clinicians in everyday clinical practice in the easiest possible manner as the main driver of their work.
The support of this initiative by the ACCA board members was essential to launch this initiative as was the hard work of the ESC staff to make this project move forward.
January 2018
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2018 edition