briefly discuss a rational ed approach to poisoning patients assess level of evidence of...
TRANSCRIPT
UPDATES IN TOXICOLOGY: Critical Appraisal and updates of Interventions in the ED
Cherie Grace G. Quingking,MD
Objectives
Briefly discuss a rational ED approach to poisoning patients
Assess level of evidence of toxicologic interventions to provide rational ED management
Updates on management of specific xenobiotics requiring critical care at ED
Alteration of function of a cellular receptor, ion channel, organelle, or chemical pathway to the extent that critical organ systems can no longer support life.
Poisoning has been likened to trauma on the cellular level, destroying the natural workings of a victim’s physiology
Vanden Hoek et al (2010) Circulation: http://circ.ahajournals.org
GENERAL ED Management
Emergency Department Intervention of acute poisoning: 90% of cases in a nutshell Gastrointestinal
decontamination techniques
Investigations Antidotes Increasing Elimination Disposition10% Immediate care: BLS and Acute cardiac life support
Level of evidence (CEBM) & Clinical Toxicology
The evidence for recommendations :
I: Definitely recommended.Definitive, excellent evidence provides support. II: Acceptable and useful. Good evidence provides support. III: May be acceptable,possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research.
Clinical Pathway: Basic Toxicologic Interventions
Determine the need for lavage or charcoal Serious overdose
presenting to the ED within one hour?
Potentially serious overdose presenting to ED after one hour?
Determine whether toxin is adsorbed to charcoal
Routine administration in nontoxic ingestion is not indicated
Determine the need for whole bowel irrigation:• Large ingestion of iron, heavy
metals, lithium and other drugs poorly adsorbed by activated charcoal
• Drug packets (body packers)
• Gather lavage if life-threatening overdose within one hour of ED arrival (carries risk of aspiration , esophageal perforation) Class Interderminate
• Activated Charcoal 1 g/kg or 10:1 ratio of charcoal to toxin (Class II)
• MDAC: Antimalarials, Aminophylline, Barbiturates, Beta Blockers (Class II-III)• Polyethelene glycol (1-2L in adults, 25 cc/kg in children orally by NG Tube (Class III)
Determine suicide risk (Class I-II)Restrain as needed (Class II)Drug levelsSuicide attempt
• Cardiotoxin ingestion (known or potential
• Chest pain or shortness of breath
• Abnormal heart rate or hypotension
• Any unstable patient (Class II)
ECG?Yes, if
Xray ?
Chest x-ray (Class I-II)• Dyspnea , tachynea, coma, or
obtundation• Cyanosis• Symptomatic patients who
ingest: opiods, phenobarbital, phenothiazines and salicylates
KUB – suspected metals or drug packets (Class II)Enteric coated preparationsCocaine /opiate packetsArsenic other heavy metals
Yes, if
Toxicology ScreenQualitative/Quantitative: plasma drug concentrations of :
o Paracetamolo Salicylateso Irono Lithium o Ethylene glycol
o MEDICOLEGAL PURPOSES
Diagnostics/Labs• Abnormal vital signs• Altered mental status• Symptomatic patients and
unknown toxin• Ingestion of substance that
can produce metabolic acidosis
• Toxic alcohol?• Cyanosis or respiratory
distress• Suspected rhabdomyolysis• Female of childbearing age
CBGElectrolytesSerum osmolality, anion gapABGCPKPregnancy test, urinalysis
TOXICOLOGY SCREEN?
Need for antidote?
Dialysis?
Yes, if
Yes, if
Specific Agents
:Symptomatic patient with ingestion of (Class II)IsopropanolSalicylatesTheophyllineUremiaMethanolBarbiturates, beta blockersLithium Ethylene Glycol
Yes, if
Yes, if
Antidotes
AGENT ANTIDOTES AGENT ANTIDOTESparacetamol N-Acetylcysteine iron DeferoxamineAnticholinergics Physostigmine Isoniazid Pyridoxinebenzodiazepines Flumazenil metals BAL, EDTA, DMSABeta blockers Glucagon Nitrates/nitrites Methylene bluecarbamates Atropint opiates Naloxone,
nalmefernedigoxin Fab Fragments organophosphates Atropine,
pralidoximeEthylene glycol Ethanol, fomefizole snales Antivenin,crofab
Approach to critically ill patients
Caveats: Patients may not be able to provide
acute history of exposure to a toxic substance
In cases of suicide attempts, multiple substance exposure
Comprehensive toxicology laboratory testing is never available on time
Worst case scenario: cardiac arrest associated with toxic ingestion
Basic life support and ACLS current standards should be followed, except for toxin-specific interventions recommended once with ROSC Hypotension Arrhythmia seizures
toxidromes
A clinical syndrome – a constellation of signs , symptoms, and laboratory findings – suggestive of the effects of a specific toxin.
Toxidrome Approach:
•Amphetamines* anticholinergic drugs*antihistamines*cocaine*theophylline/caffeine
Tachycardia/hypertention
•Beta blockers/calcium channel blockers; clonidine, digoxin, and related glycosides, organophosphates and carbamates
Bradycardia/hypotention
•Cocaine/ tricyclic antidepressants, local anethetics, antiarrythmics (quinidine, flecanide)
Cardiac conduction
delays (wide QRS)
THINK! Toxidrome Approach:
Toxidromes: cardiovascular and Central Nervous System
•Cyclic antidepressants;isoniazid; selective and nonselective norepinephrine reuptake inhibitors; withdrawal states
seizures
•Antidepressants, benzodiazepines, carbon monoxide, ethanol, methanol, opiods, oral hypoglycemics
CNS or respiratory depression
•Cyanide, ethylene glycol, metformin, methanol and salicylates
Metabolic acidosis
hypotension
Intravenous fluids NOREPINEPHRINE
Peripheral vasodilation
Epinephrine for myocardial depressants
OpioidsBeta blockersdigoxin
NaloxoneGlucagonDigoxin specific antibodies
Greene et al (2005) Postgrad Med J; 81:204-216
Arrythmias
Anti arrythmics : not first line agents Proarrythmics
Electrical Cardioversion May produce asystole in a
poisoned myocardium
Watch out for : conduction delays (widened
QRS) Torsade de pointes
Correction of:AcidosisHypokalemiaHypomagnesemiaHypoxia
Immediate antidotal therapy
Greene et al (2005) Postgrad Med J; 81:204-216
Seizures and agitations
Benzodiazepines as first line agents
Agitation: avoid phenothiazines or butyrophenones
Resistant seizures: General anesthetics: IV
barbiturates Supportive care
(intubation and mechanical ventilation)
Caveats:NO PHENYTOIN for: TCAs and cocaine
•has sodium channel blocking properties
Benzodiazepines
Benzodiazepines (BZD) exert their action by potentiating the activity of Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS
Flumazenil as an antidote Evidence: administration of flumazenil to
patients with undifferentiated coma confers risk and is not recommended (Class III, LOE B) : seizures, hypotension and arrhythmia with TCAs
Indication: reversal of excessive sedation during procedural sedation
Lheureux P, Vranckx M, Leduc D, Askenasi R. Flumazenil in mixed benzodiazepine/tricyclic antidepressant overdose: a placebo-controlled study in the dog. Am J Emerg Med. 1992;10:184 –188.Pitetti RD, Singh S, Pierce MC. Safe and efficacious use of procedural sedation and analgesia by nonanesthesiologists in a pediatric emergencydepartment. Arch Pediatr Adolesc Med. 2003;157:1090 –109
Antihypertensives :β-Blockers β-Blockers: myocardial membrane-
stabilizing activity >>> QRS widening and decreased myocardial contractility
Cardiovascular complications of B-blocker toxicity: include hypotension, bradycardia, AV blocks of different degrees, and CHF with or without pulmonary edema.
Most common: propranolol seizure is highest with propranolol,
particularly when the QRS complex is > 100 ms
Beta Blockers
Glucagon
-blocker
• Secreted by pancreas secondary to hypoglycemia• Glucagon Receptors found in heart muscle• Acts by stimulating adenylate cyclase.
independent of -receptorglucagon+
Glucagonreceptor
Drug of choice for -blocker (& CCB) O.D.
Beta Blockers: Glucagon
The final outcome:
positive chronotropic and inotropic effects despite -adrenergic blockade.
Onset within minutes, peak levels in 5-7 minutes, duration of action of 10-15 minutes.
Beta Blockers
Glucagon - precautions
2. Side effects from glucagon include:i. dose-dependent nausea and vomiting
aspirationii. hyperglycemia, hypokalemia (not
clinically important)iii. Some Reports of treatment failure
1. Diluent contains 2 mg/ml phenol as preservativei. Max 10-h dose of phenol = 50 mg = 5mg glucagonii. Use sterile water instead of diluent
Insulin??Shown to have positive inotropic effects on animal and human myocardium
Beta Blockers: Insulin
24 dogs, anesthetized and infused with propanol.Hemodynamics before & after treatment with: i. Normal Saline (n=6)ii. Insulin (4IU/min) + glucose PRN (n=6)iii. Glucagon (50 ug/kg) + infusion (n=6)iv. Epinephrine (1ug/kg/min) + titrated (n=6)
Kerns, et al. Ann Em Medicine. 1997. 29:748-757
Results:
6/6 Controls died within 150 min5/6 Epinephrine animals died after 240 min2/6 Glucagon animals died “ “ “0/6 Insulin animals died “ “ “
Kaplan-Meier Survival CurveInsulin vs. Glucagon (p<0.05)Insulin vs. Epinephrine (p<0.02)
Beta Blockers
1. May enhance catecholamine release2. May enhance myocardial substrate use In normal myocardium, FFA are preferred substrate. In poisoned myocardium, glucose becomes 1o
substrate3. May increase cytosolic calcium
Pathophysiology ?:
Beta Blockers
Insulin in Acute Beta Blocker OD.
:β-Blockers: Management Supportive therapy : activated charcoal for
decontamination; combinations of fluid resuscitation, vasopressor agents, atropine, transvenous pacing
Specific antidotes: glucagon bolus of 3 to 10 mgadministered slowly over
3 to 5 minutes, followed by an infusionof 3 to 5 mg/h (0.05 to 0.15 mg/kg followed by an infusion of 0.05 to 0.10 mg/kg per hour) (Class IIb, LOE C)
high-dose IV insulin, accompanied by IV dextrose supplementation (Class IIb,LOE C)
Other: Calcium, 0.3 mEq/kg of calcium (0.6 mL/kg of 10% calcium gluconate solution or 0.2 mL/kg of 10% calcium chloride solution) IV over 5 to 10 minutes,followed by an infusion of 0.3 mEq/kg per hour.
Calcium Channel Blockers hypotension and bradycardia extended-release (ER) formulations can
result in delayed onset of arrhythmias, shock, sudden cardiac collapse, and bowel ischemia.
Treatment: IV insulin/Dextrose Calcium (Calcium chloride (1-4 g IV; preferably via
central line; (30 mL) of 10% calcium gluconate can be administered IV over 10-15 minutes in adults. Boluses may be repeated every 15-20 minutes for a total of 3 doses)
Haddad LM. Resuscitation after nifedipine overdose exclusively with intravenous calcium chloride. Am J Emerg Med. Oct 1996;14(6):602-3Hung YM, Olson KR. Acute amlodipine overdose treated by high dose intravenous calcium in a patient with severe renal insufficiency. Clin Toxicol (Phila). 2007;45(3):301-3
Cocaine and methamphetamine and derivaties
Arrhythmia, hypertension, acute coronary syndrome HX: Onset and duration of symptoms depend on
route of administration, dose, and patient tolerance Clinical Presentation
Central Nervous System: agitation, psychosis, AMS etc Cardiovascular: ACS (6% ), hypertension, hyperthermia Acute Pulmonary Syndrome: y dyspnea, diffuse infiltrates,
and hemoptysisCan act as a Vaughan-Williams class Ic antiarrhythmic, producing wide-complex tachycardia through several mechanisms, including blockade of cardiac sodium channels >>> Wide complex tachycardia
Treatment and Caveats
Methamphetamine – MDAC Ascorbic acid no longer recommended
Cocaine related ACS Diagnosis of cocaine related MI is difficult as 84% of
patients with cocaine related chest pain have abnormal ECGs Half of all cocaine users have increased creatinine
kinase concentrations in the absence of myocardial infarction
Troponin concentrations are more sensitive and specific Pathophysiology: sympathomimetic action of cocaine
produces an increase in myocardial oxygen demand and direct cocaine induced coronary artery vasospasm
Treatment and Caveats
Benzodiazepines (lorazepam, diazepam), calcium channel blockers (verapamil), morphine, and sublingual nitroglycerin
(Class IIb, LOE B) Aspirin for Cocaine ACS ; Lidocaine? Supportive: rapid cooling measures Caveats: phentolamine can be used but
not propranolol, labetalol ineffective ( Class IIb, LOE C)
Cocaine induced Arrhythmia
(+) Wide complex tachycardia
Sodium bicarbonate 1 mL/ kg (cocaine) IV as a
bolus, repeated as needed until hemodynamic stability is
restored and QRS duration is < 120 ms
Cyanide
cyanide can be found in jewelry cleaners,
electroplating solutions; fire smoke Joint DOH-DENR Advisory: Series of
2010-001 on reporting of cases to DOH-FDA
Clinical Manifestations: causes rapid cardiovascular collapse,
which manifests as hypotension, lactic acidosis, central apnea, and seizures
management
Enhancement of body’s natural mechanisms for dealing with cyanide:i. oxygen
ii. Sodium thiosulphate
Cyanide will also bind to methaemoglobin formed after administration of:i. Amyl nitrite;ii. Sodium nitrite, or;iii. 4-dimethylaminophenol
(4-DMAP)
Cobalt containing drugs:
i. Hydroxocobalamin, orii. Dicobalt edetate.
In summary
Approach using evidenced based toxicologic interventions and supportive care guided by expert referrals on intervention and disposition from poison control centers
Consider the toxidromes In critical care situations utilize
standard AHA/ECC guidelines for BLS and ACLS Consider exceptions among severely
poisoned individuals with exposure to specific toxic agents
Hotlines: Information Services
UP PGH NPMCC: 02-5218451 loc 2311
Department of Health:East Avenue Medical Center: (02)
4342511 Rizal Medical Center: (02) 5241078Batangas Regional Medical Center:
(043) 7233578