case in point: critical care medicine handouts/sat1.2… · identify post-traumatic brain injury...

CASE IN POINT: CRITICAL CARE MEDICINE

SATURDAY/9:45-10:45AM

ACPE UAN: 0107-9999-20-031-L01-P 0.1 CEU/1.0 hr

Activity Type: Knowledge-Based

Learning Objectives for Pharmacists:

Upon completion of this CPE course participants should be able to:

1. Describe the role of enteral nutrition in stress ulcer prophylaxis in mechanically ventilated patients.

2. Examine the dosing of enoxaparin in obese patients for venous thromboembolism prophylaxis and the utility

of anti-Xa monitoring.

3. Identify post-traumatic brain injury (TBI) patients that require seizure prophylaxis and select an appropriate

initial regimen.

4. Employ pharmacologic approaches for managing elevated intracranial pressure following TBI.

5. Select an appropriate empiric antibiotic regimen for ventilator-associated pneumonia.

Speaker: Stacey Dull, PharmD, BCPS

Stacey Dull received her Pharm.D. degree from Creighton University School of Pharmacy and

Health Professions in 2009. After completion of a PGY1 pharmacy residency at the University of

Missouri Health Care in 2010, Stacey started working as a staff pharmacist at CHI Health

Creighton University Medical Center-Bergan Mercy. In 2011, she returned to her roots and

joined the faculty at Creighton University School of Pharmacy and Health Professions as an

assistant professor of pharmacy practice. She has been practicing in the intensive care unit at CHI

Health Creighton University Medical Center-Bergan Mercy since starting her faculty appointment

and currently serves as the clinical pharmacy specialist for the trauma ICU. In the trauma ICU, she works

closely with medical students, surgery residents, trauma surgeons, nurse practitioners, nurses, dieticians,

respiratory therapists, pharmacy students, and pharmacy residents to provide optimal care for those in

need.

Speaker Disclosure: Stacey Dull reports no actual or potential conflicts of interest in relation to this CPE

activity. Off-label use of medications will be discussed during this presentation.

#RxExpo20

Case in Point: Critical Care Medicine

Stacey Dull, Pharm.D., BCPS

Assistant Professor of Pharmacy Practice, Creighton University

Trauma Critical Care Pharmacist, CHI Health CUMC-Bergan Mercy

February 8th, 2020

#RxExpo20

Disclosure

Stacey Dull reports no actual or potential conflicts of interest associated with this presentation

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Learning Objectives• Upon successful completion of this course, participants should be able to:

• Employ pharmacologic approaches for managing elevated intracranial pressure (ICP) following traumatic brain injury (TBI)

• Identify post-TBI patients that require seizure prophylaxis and select an appropriate initial regimen

• Describe the role of enteral nutrition in stress ulcer prophylaxis (SUP) in mechanically ventilated patients

• Examine the dosing of enoxaparin in obese patients for venous thromboembolism (VTE) prophylaxis and the utility of anti-Xa monitoring

• Select an appropriate empiric antibiotic regimen for ventilator-associated pneumonia (VAP)

#RxExpo20

Patient Case• LD is a 42-year-old male that presents to the trauma bay after

his car left the road and drove into a tree at approximately 60 mph. He was unconscious at the scene and the windshield was starred. There is an obvious hematoma on his forehead. His Glasgow Coma Scale (GCS) score is 3, and he was intubated for airway protection. The urine drug screen was positive for methamphetamines and marijuana, and his alcohol level was 268 mg/dL. Radiological exams are notable for bilateral tibia-fibula fractures, left femur fracture, multiple bilateral rib fractures, sternal fracture, left clavicular fracture, and large subdural hematoma.

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TBI

• Alteration in brain function caused by an external force that damages brain tissue

• May be due to falls, assault, motor vehicle collisions (MVCs), objects that penetrate brain tissue, or blast injuries

• Subsequent cascade of injury mechanisms that can lead to neuronal cell death, cerebral edema, and increased ICP

• Complications include changes in mobility, behavior, language, sensation, and emotion

• Leading cause of disability in the United States

DeNett T, Feltner C. JAANP 2019;1-11.

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ICP Monitoring• Not indicated for all patients• May be accomplished by:

• Intraventricular – “gold standard”• Intraparenchymal• Subarachnoid (e.g., bolt)• Epidural

• Goals:• ICP < 22 mmHg• Cerebral perfusion pressure (CPP) 60-70 mmHg• SBP > 100 mmHg (50-69 y/o) and > 110 mmHg (15-49 y/o and > 70 y/o)• Brain tissue oxygenation (pBtO2) > 15 mmHg

Carney N, Totten AM, O’Reilly C, et al. Neurosurgery 2017;80:6‐15.

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ICP Management

Hyperosmolar therapy

Analgesia and sedation

medicationsCSF drainage

Head of bed at 30°


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Hyperosmolar Therapy

Mechanism Draws water across the blood brain barrier decreases brain volume reduces ICP

Therapy Options

Hypertonic saline (HTS) 2%, 3%, 7.5%, and 23.4%

Must be given via central lineVolume overloadHyperchloremic metabolic acidosis

Mannitol 0.25‐1 gm/kg IV every 4‐6 hoursMust use 0.22 micron filterAvoid in patients with hypovolemic shock

Monitoring Serum electrolytes and osmolality, osmolar gap (mannitol), renal function, fluid balance

Goals of Therapy Titrate to a serum Na+ 145‐155 mEq/L and/or osmolality 300‐320 mOsm/L

Peters NA, Farrell LB, Smith JP. US Pharm 2018;43(1):8‐11.

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Mannitol versus HTS• Identify effects of HTS compared to mannitol on mortality,

functional outcome, and cerebral physiological variables• Randomized controlled trials – quasi-randomized, cross-over,

and unblinded in patients with severe TBI• Primary outcomes

• Mortality• Favorable outcome

• Secondary outcomes• ICP, CPP, and pBtO2• Duration of elevated ICP per day• Treatment failure

Schwimmbeck F, Voellger B, Chappell D, Eberhart L. J Neurosurg Anesthesiol 2019.

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Mannitol versus HTS• 12 studies included in meta-analysis• Primary outcomes:

• Nonsignificant tendency to lower mortality with HTS compared to mannitol (RR: 0.69, 95% CI: 0.45, 1.04; P = 0.08)

• No significant difference in patients with favorable outcome between HTS and mannitol (RR: 1.28, 95% CI: 0.86, 1.90; P = 0.23)

• Secondary outcomes:• HTS significantly lowered ICP at 90 and 120 minutes (MD: -2.33 mmHg, 95%

CI: -3.17, -1.50; P < 0.00001)• CPP was higher between 30 and 60 minutes after treatment with HTS (MD:

5.48 mmHg, 95% CI: 4.84, 6.12; P < 0.00001)• CPP was higher between 90 and 120 minutes after treatment with HTS (MD:

9.08 mmHg, 95% CI: 7.54, 10.62; P < 0.00001)

Schwimmbeck F, Voellger B, Chappell D, Eberhart L. J Neurosurg Anesthesiol 2019.

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Patient Case

Our patient had an intraparenchymal ICP monitor placed at admission. He was intubated in the trauma bay and head of bed was placed at 30°. Currently, he is on fentanyl 150 mcg/hr and propofol 50 mcg/kg/min. His BP is 115/60 mmHg. For the past 20 minutes, his ICP ranged between 25-30 mmHg despite increasing the fentanyl and propofol infusions. There are no signs of impending cerebral herniation. The Neurosurgeon would like to initiate hyperosmolar therapy. Which agent would you use to manage LD’s elevated ICP?

#RxExpo20

Refractory Elevated ICP

Decompressive craniectomy

Barbiturate coma

Hypothermia


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Impending Cerebral Herniation

• Significant pupillary asymmetry

• Unilateral or bilateral fixed and dilated pupils

• Decorticate or decerebrate posturing

• Respiratory depression• "Cushing triad" =

hypertension, bradycardia, and irregular respiration

• Management:• Endotracheal intubation• Head of bed to 30-45°• Brief hyperventilation• Mannitol 1-1.5 gm/kg IV infused

over 30 minutes OR 23.4% NaCl 30-60 mL IV over 10 minutes

• MAP 80-100 mmHg


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Post-Traumatic Seizures (PTS)

• May occur as a result of TBI

• Classification• Immediate: at time of injury• Early: < 7 days of injury• Late: > 7 days after injury

• In patients with severe TBI:• Clinical seizures may be as high as 12%• Subclinical seizures detected on EEG ~ 20-25%


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Risk Factors for Early PTS

• GCS < 10

• Immediate seizures

• Post-traumatic amnesia > 30 minutes

• Linear or depressed skull fracture

• Penetrating head injury

• Subdural, epidural, or intracerebral hematoma

• Cortical contusion

• Age < 65 years

• Chronic alcoholism


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Complications of Early PTS

• Can aggravate systemic injuries

• Recurrent seizures increase CBF and ICP

• Place metabolic demand on damaged brain tissue

• May exacerbate secondary brain injury

• Development of late PTS


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Current Guideline Recommendations

• Phenytoin is recommended to decrease the incidence of early PTS (within 7 days of injury), when the overall benefit is felt to outweigh the complications associated with such treatment. However, early PTS have not been associated with worse outcomes.


#RxExpo20

Current Practice Patterns

0 10 20 30 40 50 60 70

None

Levetiracetam

Phenytoin

Valproate

Which anti‐epileptic drug do you use as first choice for seizure prevention in moderate to severe TBI?

Mee H, Kolias AG, Chari A, et al. Acta Neurochirurgica 2019;161:457-64.

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Current Practice Patterns

0

5

10

15

20

25

30

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40

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50

Don't use 7 days 10 days 14 days Discharge ICU Discharge NS Other

How long do you continue seizure prophylaxis?

Mee H, Kolias AG, Chari A, et al. Acta Neurochirurgica 2019;161:457-64.

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Effectiveness of Antiepileptic Drugs (AEDs) for PTS Prophylaxis

• Pool available data for rates of early seizures after TBI for patients treated with phenytoin, levetiracetam, valproate, or carbamazepine compared with placebo or no prophylaxis

• Randomized and non-randomized clinical trials and comparative observational studies

Wat R, Mammi M, Paredes J, et al. World Neurosurg 2019;122:433-40.

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Effectiveness of AEDs for PTS Prophylaxis

• 9 studies included in meta-analysis

• Loading and maintenance doses of AEDs varied

• Randomized controlled trials• No significant difference in rate of early seizures for patients treated

with AEDs versus placebo (RR: 0.58, 95% CI: 0.20, 1.72)

• Observational studies• Lower rate of early seizures in patients who received AEDs versus no

treatment (RR: 0.42, 95% CI: 0.29, 0.62)

Wat R, Mammi M, Paredes J, et al. World Neurosurg 2019;122:433-40.

#RxExpo20

Patient Case

Our patient presented after sustaining a MVC. The patient’s family reports chronic alcohol abuse. His GCS was 3 in the trauma bay. Blood alcohol level was 268 mg/dL. CT scan of his head revealed a large subdural hematoma. The patient has no known past medical history. Would you place LD on PTS prophylaxis?

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Stress-Related Mucosal Disease (SRMD)

• Consequence of critical illness

• Pathogenesis: Proinflammatory states, splanchnic hypoperfusion, and impaired microcirculation can induce ischemia, reperfusion injury, and low gastric intramucosal pH

• Approximately 50 years ago, endoscopies demonstrated SRMD in 75-100% of critically ill, injured, or burned patients

• Rates of overt and clinically important GI bleeding (CIB) range from 0-5.5% in recent studies

Cook D, Guyatt G. N Engl J Med 2018;378:2506-16.

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Risk Factors for Stress Ulcer Development

• Respiratory failure (mechanical ventilation > 48 hours)

• Coagulopathy (INR > 1.5, platelet count < 50,000 mm3, PTT > 2 times control)

• Hypotension• Sepsis• Hepatic failure• Acute kidney injury• Renal replacement therapy• Severe head injury

• Thermal injury involving > 35% of total BSA

• Traumatic spinal cord injury• Major surgery > 4 hours• ICU stay > 7 days• Occult bleeding > 6 days• GI ulceration or bleeding within

1 year• High-dose corticosteroid therapy

(> 250 mg/day hydrocortisone or equivalent)

Cook D, Guyatt G. N Engl J Med 2018;378:2506-16.

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Pharmacologic Options

• Proton pump inhibitors (PPIs)• Irreversibly bind to and inhibit H+/K+-ATPase pump • Ex. Pantoprazole 40 mg IV daily

• Histamine-2 receptor antagonists (H2RAs)• Antagonize H2 receptors on parietal cells • Ex. Famotidine 20 mg IV Q12H

• Concerns: Increased rates of Clostridioides difficile infection (CDI) and ventilator-associated pneumonia (VAP)

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What is the Role of Enteral Nutrition?

• Helps prevent bacterial translocation

• Regulates GI immune and resorptive functions

• Stimulates blood flow and gut motility

• Early initiation in the absence of contraindications

Cook D, Guyatt G. N Engl J Med 2018;378:2506-16.Jalil BA, El-Kersh K. Curr Opin Crit Care 2019;25:334-9.

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SUP in Patients Receiving Enteral Nutrition• Determine if there are differences between pharmacologic SUP and

placebo or no prophylaxis in enterally fed patients• Randomized controlled trials in adult ICU patients receiving enteral

nutrition• Primary outcome:

• Bleeding rate

• Secondary outcomes:• Incidence of hospital-acquired pneumonia (HAP)• Overall mortality• CDI• Length of ICU stay• Duration of mechanical ventilation

Huang HB, Jiang W, Wang CY, Qin HY, Du B. Crit Care 2018;22:20.

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SUP in Patients Receiving Enteral Nutrition

• 7 studies included in meta-analysis

• Primary outcome:• In enterally fed patients, SUP did not reduce the risk of GI bleeding

(RR: 0.80; 95% CI: 0.49, 1.31; I2 = 8%; P = 0.96)

• Secondary outcomes:• No statistically significant difference in mortality, CDI, length of ICU

stay, duration of mechanical ventilation, or VAP between the SUP and no SUP groups

• Incidence of HAP was higher in SUP group (RR: 1.53; 95% CI: 1.04, 2.27; I2 = 0%; P = 003)

Huang HB, Jiang W, Wang CY, Qin HY, Du B. Crit Care 2018;22:20.

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Patient Case

LD was intubated in the trauma bay and remains on the ventilator. Enteral nutrition was started 12 hours after admission and has been advanced to goal. He was started on famotidine 20 mg IV Q12H at admission for SUP. Would you recommend discontinuing LD’s famotidine?

#RxExpo20

VTE

• Risk especially high in trauma patients• Injury type and severity• Massive transfusion protocol• Surgical intervention• Immobility• Extended hospital stays• Acute inflammatory responses

• In absence of preventative therapies, DVT rate as high as 70%

Bethea A, Adams E, Lucente FC, Samanta D, Chumbe JT. Ann Surg 2018;84(6):1097-1104.

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VTE Prophylaxis• In the United States, 45-60% of trauma patients receive

pharmacologic VTE prophylaxis• Trauma Quality Improvement Program (TQIP) data state that

70% of patients receive LMWH• TQIP cites an average DVT and PE rate of 1.5% and 0.6%,

respectively• Recommended agents are LMWHs with enoxaparin 30 mg SBQ

BID used most often• Standard enoxaparin dosing may be insufficient to achieve

prophylactic anti-Xa levels in up to 70% of all trauma patients


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IMPACT-IT QI Project• Implementation of VTE prophylaxis algorithm

• Enoxaparin 30 mg SBQ Q12H (< 100 kg) and 40 mg SBQ Q12H (> 100 kg)

• Anti-Xa levels obtained ~ 4 hours after 3rd or 4th dose

• Rates of symptomatic VTE evaluated 12 months pre- and post-algorithm implementation

• 1542 (pre-implementation) and 1802 (post-implementation) patients were admitted to trauma services

• Overall rate of symptomatic VTE significantly decreased from pre- to post-implementation (2% vs 0.9%, P = 0.009)


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Patient Case

LD is a 42-year-old, 90-kg male with lower extremity injuries that preclude the use of mechanical compression devices. He has been in the hospital for 72 hours, and his repeat head CT is stable. The physician wants to initiate enoxaparin 30 mg SBQ Q12H for VTE prophylaxis and asks you if he should obtain an anti-Xa level. Would you recommend getting an anti-Xa level to manage LD’s enoxaparin therapy?

#RxExpo20

VAP• Type of HAP that develops > 48 hours after endotracheal intubation

• Risk factors:• Older age• Depressed consciousness• Multiple trauma• Intracranial pressure monitor• Agents that increase gastric pH• Total opioid exposure• Paralysis• Reintubation or prolonged intubation• Number of surgeries

Kalil AC, Metersky ML, Klompas M. CID 2016;63(5):e61-111.Meduri GU. Clin Chest Med 1995;16(1):61-93.

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Clinical Features of VAP

Symptoms Dyspnea

SignsFever, tachypnea, increased or purulent secretions, hemoptysis, rhonchi, crackles, reduced breath sounds, bronchospasm

Ventilator mechanics Reduced tidal volume, increased inspiratory pressures

Laboratory findings Leukocytosis, worsening hypoxemia

Imaging New or progressive infiltrate on CXR or CT

Kalil AC, Metersky ML, Klompas M. CID 2016;63(5):e61-111.Meduri GU. Clin Chest Med 1995;16(1):61-93.

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Treatment of VAP

Risk factors for MDR pathogen

IV antibiotic use within the previous 90 daysSeptic shock at the time of VAP diagnosisAcute respiratory distress syndrome (ARDS) preceding VAP≥5 days of hospitalization prior to the occurrence of VAPAcute renal replacement therapy (RRT) prior to VAP onset

Risk factors for MDR Pseudomonas and other gram‐negative bacilli (GNB)

Treatment in an ICU in which > 10% of GNB are resistant to an agent being considered for monotherapyTreatment in an ICU in which local antimicrobial susceptibility rates among GNB are unknownColonization with OR prior isolation of MDR Pseudomonas or other GNB

Risk factors for MRSA

Treatment in a unit in which > 10 to 20% of S. aureus isolates are methicillin resistantTreatment in a unit in which the prevalence of MRSA is unknownColonization with OR prior isolation of MRSA

Kalil AC, Metersky ML, Klompas M. CID 2016;63(5):e61-111.

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Treatment of VAP

Gram‐Positive Antibiotics with MRSA Activity

VancomycinLinezolid

Gram‐Negative Antibiotics with Anti‐Pseudomonal Activity (β‐lactam‐based)

Piperacillin‐tazobactamCefepime or ceftazidimeImipenem or meropenemAztreonam

Gram‐Negative Antibiotics with Anti‐Pseudomonal Activity (Non‐β‐lactam‐based)

Ciprofloxacin or levofloxacinAmikacin, gentamicin, or tobramycinColistin or polymyxin B

Kalil AC, Metersky ML, Klompas M. CID 2016;63(5):e61-111.

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Gram-Positive Antibiogram

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Gram-Negative Antibiogram

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Patient Case

On day #3 of hospitalization, LD develops new left lower and middle lobe infiltrates on CXR. His maximum temperature was 39.6°C and WBC count is 18.9 k/µL. The respiratory therapist reports increased purulent secretions and oxygen requirements. The physician diagnoses the patient with VAP based on these findings and asks you to provide an appropriate antibiotic recommendation. After review of his record, you note he has not received IV antibiotics within the past 90 days, doesn’t have septic shock or ARDS, and has not required RRT. What antimicrobial regimen would you recommend for LD?

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Take Home Points• Pharmacologic approaches for managing elevated ICP following TBI

include analgesia and sedation medications and hyperosmolar therapy

• A number of factors contribute to the development of PTS, and current literature is unclear on the efficacy of AEDs for PTS prophylaxis

• Several studies and meta-analyses demonstrate that pharmacologic SUP in addition to enteral nutrition does not reduce the rate of GI bleeding

• Controversy exists regarding dosing and monitoring for enoxaparin in trauma patients; however, some studies demonstrate a reduction in VTE rates when anti-Xa-guided dosing is employed

• VAP is a frequent complication in TBI patients – it is important to use your antibiogram and patient risk factors to guide therapy

#RxExpo20

Case in Point: Critical Care Medicine

Stacey Dull, Pharm.D., BCPS

Assistant Professor of Pharmacy Practice, Creighton University

Trauma Critical Care Pharmacist, CHI Health CUMC-Bergan Mercy

February 8th, 2020

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case in point: critical care medicine handouts/sat1.2… · identify post-traumatic brain injury...

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