[HARMRED] FYI: American Heart Association releases new CPR guidelines - see section on opiate overdose

Tue Oct 19 11:25:50 CDT 2010

Extracted here in part – section 12.7 on cardiac arrest due to poisoning – see sections on opiates and cocaine. Full guidelines at www.heart.org <http://www.heart.org/> .   

2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science

Part 12: Cardiac Arrest in Special Situations

2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care 

Terry L. Vanden Hoek, Chair; Laurie J. Morrison; Michael Shuster; Michael Donnino; Elizabeth Sinz; Eric J. Lavonas; Farida M. Jeejeebhoy; Andrea Gabrielli 

   Part 12.7: Cardiac Arrest Associated With Toxic Ingestions 

Poisoning has been likened to trauma on the cellular level, destroying the natural workings of a victim's physiology.218 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B218>  Severe poisoning alters the function of a cellular receptor, ion channel, organelle, or chemical pathway to the extent that critical organ systems can no longer support life. 

As with any patient in cardiac arrest, management of the patient with a toxic exposure begins with support of airway, breathing, and circulation. Cardiac arrest due to toxicity is managed in accordance with the current standards of BLS and ACLS. With few exceptions, there are no unique antidotes or toxin-specific interventions that are recommended during resuscitation from cardiac arrest. 

Once return of spontaneous circulation is achieved, urgent consultation with a medical toxicologist or certified regional poison center is recommended, as the postarrest management of the critically poisoned patient may benefit from a thorough understanding of the toxic agent. Consultation is also recommended early in the management of a patient with potentially life-threatening poisoning, when appropriate interventions might prevent deterioration to cardiac arrest. In the United States a certified poison center can be reached by calling 1-800-222-1222; in Canada, call 1-800-268-9017. 

It is extremely difficult to conduct clinical trials of acute life-threatening poisoning. Challenges include the infrequency with which most specific conditions occur, the heterogeneity of presentation, and ethical challenges related to withholding established care from patients who are unable to provide informed consent because the patient has an altered mental status, the patient is suicidal, or there is a lack of time to explain treatment alternatives.219 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B219>  

The majority of questions addressing cardiac arrest due to drug toxicity remain unanswered. Epidemiological studies are required to document the incidence rate of cardiac arrests secondary to drug toxicity and the safety and efficacy baseline rates for current therapeutic strategies. This section presents recommendations for the care of the patient with a toxicological problem causing cardiac arrest or severe cardiovascular instability (respiratory depression, hypotension, life-threatening alterations of cardiac conduction, etc). Some recommendations are evidence-based, but most research in this area consists of case reports, small case series, animal studies, and pharmacokinetic studies in healthy volunteers. Virtually no toxicology research involves human cardiac arrest. Thus, many of these recommendations are based on expert consensus, and further research is needed to validate them. 

Initial Approach to the Critically Poisoned Patient
Management of the critically poisoned patient begins with airway protection, support of respiration and circulation, and rapid assessment. Patients may or may not be able to provide an accurate history of exposure to a toxic substance. Whenever possible, history gathering should include questioning of persons who accompany the patient, evaluation of containers, review of pharmacy records, and examination of the patient's prior medical record.220 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B220>  Many patients who ingest medications in a suicide attempt take more than 1 substance, and the number of substances ingested is greater in fatal than in nonfatal suicide attempts.221 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B221>  Comprehensive toxicology laboratory testing is virtually never available in a time frame that supports early resuscitation decisions.222 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B222>  

Poisoned patients may deteriorate rapidly. Care for all adult patients who are critically ill or under evaluation for possible toxin exposure or ingestion, particularly when the history is uncertain, should begin in a monitored treatment area where the development of central nervous system depression, hemodynamic instability, or seizures can be rapidly recognized and addressed.223 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B223>  

Gastrointestinal decontamination, once a mainstay in the management of ingested toxins, has a less significant role in poisoning treatment today. With rare exceptions, gastric lavage, whole bowel irrigation, and administration of syrup of ipecac are no longer recommended.224 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B224> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B225> 226 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B226>  Administration of single-dose activated charcoal to adsorb ingested toxins is generally recommended for the ingestion of life-threatening poisons for which no adequate antidotal therapy is available and when the charcoal can be administered within 1 hour of poisoning.228 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B228>  Multiple-dose activated charcoal should be considered for patients who have ingested a life-threatening amount of specific toxins (eg, carbamazepine, dapsone, phenobarbital, quinine, or theophylline) for which a benefit of this strategy has been established.229 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B229>  Charcoal should not be administered for ingestions of caustic substances, metals, or hydrocarbons.228 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B228>  

Charcoal should only be administered to patients with an intact or protected airway. In patients who are at risk for aspiration, endotracheal intubation and head-of-bed elevation should be performed before charcoal administration.229 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B229> ,230 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B230>  Because the decision to perform gastrointestinal decontamination is complex, multifactorial, and associated with risk, expert advice can be helpful. 

Toxidromes
A "toxidrome" is a clinical syndrome—a constellation of signs, symptoms, and laboratory findings—suggestive of the effects of a specific toxin. By recognizing these presentations, the clinician can establish a working diagnosis that guides initial management. Some common toxidromes are presented in the Table <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#TU1> . Practically every sign and symptom observed in poisoning can be produced by natural disease, and many clinical presentations associated with natural disease can be mimicked by some poison.231 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B231>  It is important to maintain a broad differential diagnosis, particularly when the history of toxic chemical exposure is unclear. 

View this table:
[in this window] <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829/TU1> 
[in a new window] <http://circ.ahajournals.org/cgi/content-nw/full/122/18_suppl_3/S829/TU1> 

Table. Common Toxidromes*

Opioid Toxicity
There are no data to support the use of specific antidotes in the setting of cardiac arrest due to opioid overdose. Resuscitation from cardiac arrest should follow standard BLS and ACLS algorithms. 

Naloxone is a potent antagonist of the binding of opioid medications to their receptors in the brain and spinal cord. Administration of naloxone can reverse central nervous system and respiratory depression caused by opioid overdose. Naloxone has no role in the management of cardiac arrest. 

In the patient with known or suspected opioid overdose with respiratory depression who is not in cardiac arrest, ventilation should be assisted by a bag mask,232 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B232> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B233>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B234>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B235>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B236>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B237> 238 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B238>  followed by administration of naloxone and placement of an advanced airway if there is no response to naloxone (Class I, LOE A). 

Administration of naloxone can produce fulminate opioid withdrawal in opioid-dependent individuals, leading to agitation, hypertension, and violent behavior. For this reason, naloxone administration should begin with a low dose (0.04 to 0.4 mg), with repeat dosing or dose escalation to 2 mg if the initial response is inadequate.239 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B239>  Some patients may require much higher doses to reverse intoxication with atypical opioids, such as propoxyphene, or following massive overdose ingestions.240 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B240> ,241 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B241>  Naloxone can be given IV,235 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B235> ,236 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B236> ,242 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B242> ,243 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B243>  IM,232 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B232> ,235 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B235> ,236 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B236>  intranasally,232 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B232> ,242 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B242>  and into the trachea.244 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B244>  

The duration of action of naloxone is approximately 45 to 70 minutes, but respiratory depression caused by ingestion of a long-acting opioid (eg, methadone) may last longer. Thus, the clinical effects of naloxone may not last as long as those of the opioid, and repeat doses of naloxone may be needed. 

Patients with life-threatening central nervous system or respiratory depression reversed by naloxone administration should be observed for resedation. Although a brief period of observation may be appropriate for patients with morphine or heroin overdose,245 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B245>  a longer period of observation may be required to safely discharge a patient with life-threatening overdose of a long-acting or sustained-release opioid.239 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B239> ,246 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B246>  

Benzodiazepines
There are no data to support the use of specific antidotes in the setting of cardiac arrest due to benzodiazepine overdose. Resuscitation from cardiac arrest should follow standard BLS and ACLS algorithms. 

Flumazenil is a potent antagonist of the binding of benzodiazepines to their central nervous system receptors. Administration of flumazenil can reverse central nervous system and respiratory depression caused by benzodiazepine overdose. Flumazenil has no role in the management of cardiac arrest. 

The administration of flumazenil to patients with undifferentiated coma confers risk and is not recommended (Class III, LOE B). Flumazenil administration can precipitate seizures in benzodiazepine-dependent patients and has been associated with seizures, arrhythmia, and hypotension in patients with coingestion of certain medications, such as tricyclic antidepressants.247 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B247> ,248 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B248>  However, flumazenil may be used safely to reverse excessive sedation known to be due to the use of benzodiazepines in a patient without known contraindications (eg, procedural sedation).249 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B249>  

β-Blockers
There are no data to support the use of specific antidotes in the setting of cardiac arrest due to β-blocker overdose. Resuscitation from cardiac arrest should follow standard BLS and ACLS algorithms. 

β-Blocker medication overdose may cause such severe inhibition of β-adrenergic receptors that high-dose vasopressors cannot effectively restore blood pressure, cardiac output, or perfusion. Therapeutic options in the treatment of refractory hemodynamic instability due to β-blocker overdose include administration of glucagon, high-dose insulin, or IV calcium salts. 

Glucagon
Administration of glucagon may be helpful for severe cardiovascular instability associated with β-blocker toxicity that is refractory to standard measures, including vasopressors. The recommended dose of glucagon is a bolus of 3 to 10 mg, administered slowly over 3 to 5 minutes, followed by an infusion of 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).250 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B250> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B251>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B252>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B253>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B254>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B255>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B256>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B257>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B258>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B259>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B260>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B261> 262 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B262>  The infusion rate is titrated to achieve an adequate hemodynamic response (appropriate mean arterial pressure and evidence of good perfusion). Because the amount of glucagon required to sustain this therapy may exceed 100 mg in a 24-hour period, plans should be made early to ensure that an adequate supply of glucagon is available. Glucagon commonly causes vomiting. In patients with central nervous system depression, the airway must be protected before glucagon administration. Animal studies have suggested that the concomitant use of dopamine alone or in combination with isoproterenol and milrinone may decrease the effectiveness of glucagon.263 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B263> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B264> 265 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B265>  

Insulin
Animal studies suggest that high-dose IV insulin, accompanied by IV dextrose supplementation and electrolyte monitoring, may improve hemodynamic stability and survival in β-blocker overdose by improving myocardial energy utilization.266 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B266> ,267 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B267>  A single human case report268 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B268>  showed improved hemodynamic stability and survival to discharge following administration of high-dose insulin in refractory shock due to a massive overdose of metoprolol. Administration of high-dose insulin in patients with shock refractory to other measures may be considered (Class IIb, LOE C). 

Although the ideal human dose has not been determined, a commonly used protocol calls for IV administration of 1 U/kg regular insulin as a bolus, accompanied by 0.5 g/kg dextrose, followed by continuous infusions of 0.5 to 1 U/kg per hour of insulin and 0.5 g/kg per hour of dextrose.269 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B269>  The insulin infusion is titrated as needed to achieve adequate hemodynamic response, whereas the dextrose infusion is titrated to maintain serum glucose concentrations of 100 to 250 mg/dL (5.5 to 14 mmol/L). Very frequent serum glucose monitoring (up to every 15 minutes) may be needed during the initial phase of dextrose titration. Sustained infusions of concentrated dextrose solutions (<10%) require central venous access. Insulin causes potassium to shift into the cells. Moderate hypokalemia is common during high-dose insulin-euglycemia therapy, and animals treated with aggressive potassium repletion developed asystole.266 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B266>  To avoid overly aggressive potassium repletion, 1 human protocol targets potassium levels of 2.5 to 2.8 mEq/L.269 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B269>  

Calcium
One human case report270 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B270>  and a large-animal study271 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B271>  suggest that calcium may be helpful in β-blocker overdose. Administration of calcium in patients with shock refractory to other measures may be considered (Class IIb, LOE C). 

One approach is to administer 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.269 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B269>  The infusion rate is titrated to adequate hemodynamic response. Serum ionized calcium levels should be monitored, and severe hypercalcemia (ionized calcium levels greater than twice the upper limits of normal) should be avoided. Sustained infusions of IV calcium require central venous access. 

Other Therapies
Case reports have suggested that in patients who remain critically hypotensive despite maximal vasopressor therapy, specific interventions using intra-aortic balloon counterpulsation, ventricular assist devices, and extracorporeal membrane oxygenation or other extra corporeal life support (ECLS) devices may be lifesaving.272 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B272> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B273> 274 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B274>  While evidence remains weak, at least two human case reports indicate a possible benefit from lipid emulsion infusion for overdose by β-blockers.275 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B275> ,276 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B276>  Animal studies are mixed.277 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B277> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B278>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B279> 280 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B280>  Because this area of therapy is rapidly evolving,281 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B281> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B282> 283 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B283>  prompt consultation with a medical toxicologist or other specialists with up-to-date knowledge is recommended when managing treatment-refractory hypotension from β-blocker overdosage. 

Calcium Channel Blockers
There are no data to support the use of specific antidotes in the setting of cardiac arrest due to calcium channel blocker overdose. Resuscitation from cardiac arrest should follow standard BLS and ACLS algorithms. 

Calcium channel blocker overdose also may cause life-threatening hypotension and bradycardia that are refractory to standard agents. Treatment with high-dose insulin has been described in a number of clinical case reports284 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B284> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B285>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B286>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B287>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B288>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B289>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B290>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B291>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B292>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B293>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B294> 295 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B295>  and animal studies.296 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B296> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B297>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B298> 299 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B299>  High-dose insulin, in the doses listed in the β-blocker section above, may be effective for restoring hemodynamic stability and improving survival in the setting of severe cardiovascular toxicity associated with toxicity from a calcium channel blocker overdose (Class IIb, LOE B). 

Limited evidence supports the use of calcium in the treatment of hemodynamically unstable calcium channel blocker overdose refractory to other treatments.285 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B285> ,286 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B286> ,289 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B289> ,290 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B290> ,292 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B292> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B293> 294 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B294> ,297 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B297> ,300 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B300> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B301>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B302> 303 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B303>  Administration of calcium in patients with shock refractory to other measures may be considered (Class IIb, LOE C). 

There is insufficient and conflicting evidence to recommend the use of glucagon289 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B289> ,290 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B290> ,294 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B294> ,296 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B296> ,297 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B297> ,300 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B300> ,303 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B303> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B304>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B305> 306 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B306>  in the treatment of hemodynamically unstable calcium channel blocker overdose. 

Cocaine
There are no data to support the use of cocaine-specific interventions in the setting of cardiac arrest due to cocaine overdose. Resuscitation from cardiac arrest should follow standard BLS and ACLS algorithms, with specific antidotes used in the postresuscitation phase if severe cardiotoxicity or neurotoxicity is encountered. A single case series demonstrated excellent overall and neurologically intact survival (55%) in patients with cardiac arrest associated with cocaine overdose who were treated with standard therapy.319 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B319>  

Cocaine-induced tachycardia and hypertension are predominantly caused by central nervous system stimulation. Treatment strategies are extrapolated from acute coronary syndrome studies, small case series, and experiments in cocaine-naïve human volunteers. It may be reasonable to try agents that have shown efficacy in the management of acute coronary syndrome in patients with severe cardiovascular toxicity.  -Blockers (phentolamine),320 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B320>  benzodiazepines (lorazepam, diazepam),321 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B321>  calcium channel blockers (verapamil),322 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B322>  morphine,323 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B323>  and sublingual nitroglycerin324 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B324> ,325 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B325>  may be used as needed to control hypertension, tachycardia, and agitation (Class IIb, LOE B). The available data do not support the use of 1 agent over another in the treatment of cardiovascular toxicity due to cocaine (Class IIb, LOE B). 

There is clear evidence that cocaine can precipitate acute coronary syndromes.326 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B326>  For cocaine-induced hypertension or chest discomfort, benzodiazepines, nitroglycerin, and/or morphine can be beneficial (Class IIa, LOE B).321 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B321> ,324 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B324> ,327 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B327>  Because the effects of cocaine and other stimulant medications are transient, drugs and doses should be chosen carefully to minimize the risk of producing hypotension after the offending agent has been metabolized. Catheterization laboratory studies demonstrate that cocaine administration leads to reduced coronary artery diameter. This effect is reversed by morphine,323 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B323>  nitroglycerin,325 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B325>  phentolamine,320 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B320>  and verapamil322 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B322> ; is not changed by labetalol328 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B328> ; and is exacerbated by propranolol.329 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B329>  Several studies suggest that administration of β-blockers may worsen cardiac perfusion and/or produce paradoxical hypertension when cocaine is present.329 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B329> ,330 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B330>  Although contradictory evidence exists,331 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B331> ,332 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B332>  current recommendations are that pure β-blocker medications in the setting of cocaine are not indicated (Class IIb, LOE C).333 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B333>  

In severe overdose, cocaine acts as a Vaughan-Williams class Ic antiarrhythmic, producing wide-complex tachycardia through several mechanisms, including blockade of cardiac sodium channels.107 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B107>  Although there is no human evidence in cocaine poisoning, extrapolation from evidence in the treatment of wide-complex tachycardia caused by other class Ic agents (flecainide) and tricyclic antidepressants suggests that administration of hypertonic sodium bicarbonate may be beneficial.334 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B334>  A typical treatment strategy used for these other sodium channel blockers involves administration of 1 mL/kg of sodium bicarbonate solution (8.4%, 1 mEq/mL) IV as a bolus, repeated as needed until hemodynamic stability is restored and QRS duration is  120 ms.335 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B335> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B336>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B337>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B338>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B339>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B340>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B341> 342 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B342>  Current evidence neither supports nor refutes a role for lidocaine in the management of wide-complex tachycardia caused by cocaine. 

Cyclic Antidepressants
Many drugs can prolong the QRS interval in overdose. These include Vaughan-Williams class Ia and Ic antiarrhythmics (eg, procainamide, quinidine, flecainide), cyclic antidepressants (eg, amitriptyline), and cocaine. Type Ia and Ic antiarrhythmics were not reviewed in 2010. Similar to the type Ia antiarrhythmics, cyclic antidepressants block cardiac sodium channels, leading to hypotension and wide-complex arrhythmia in overdose. 

Cardiac arrest caused by cyclic antidepressant toxicity should be managed by current BLS and ACLS treatment guidelines. A small case series of cardiac arrest patients demonstrated improvement with sodium bicarbonate and epinephrine,343 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B343>  but the concomitant use of physostigmine in the prearrest period in this study reduces the ability to generalize this study. Administration of sodium bicarbonate for cardiac arrest due to cyclic antidepressant overdose may be considered (Class IIb, LOE C). 

Therapeutic strategies for treatment of severe cyclic antidepressant cardiotoxicity include increasing serum sodium, increasing serum pH, or doing both simultaneously. The relative contributions of hypernatremia and alkalemia are controversial, but in practice most experience involves administration of hypertonic sodium bicarbonate solution (8.4% solution, 1 mEq/mL). Sodium bicarbonate boluses of 1 mL/kg may be administered as needed to achieve hemodynamic stability (adequate mean arterial blood pressure and perfusion) and QRS narrowing (Class IIb, LOE C).335 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B335> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B336>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B337>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B338>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B339>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B340>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B341> 342 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B342>  Serum sodium levels and pH should be monitored, and severe hypernatremia (sodium >155 mEq/L) and alkalemia (pH >7.55) should be avoided. A number of vasopressors and inotropes have been associated with improvement in the treatment of tricyclic-induced hypotension, ie, epinephrine,239 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B239> ,344 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B344> ,345 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B345>  norepinephrine,345 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B345> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B346>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B347> 348 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B348>  dopamine,348 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B348> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B349> 350 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B350>  and dobutamine.349 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B349>  

Local Anesthetic Toxicity
Inadvertent intravascular administration of local anesthetics, such as bupivacaine, mepivacaine, or lidocaine, can produce refractory seizures and rapid cardiovascular collapse leading to cardiac arrest. Clinical case reports351 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B351> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B352>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B353>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B354> 355 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B355>  and controlled animal studies356 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B356> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B357>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B358>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B359> 360 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B360>  have suggested that rapid IV infusion of lipids may reverse this toxicity either by redistributing the local anesthetic away from its site of action or by augmenting metabolic pathways within the cardiac myocyte. 

Case reports have shown return of spontaneous circulation in patients with prolonged cardiac arrest unresponsive to standard ACLS measures,361 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B361> ,362 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B362>  suggesting a role for administration of IV lipids during cardiac arrest. Although ideal dosing has not been determined, because dosage varied across all studies, it may be reasonable to consider 1.5 mL/kg of 20% long-chain fatty acid emulsion as an initial bolus, repeated every 5 minutes until cardiovascular stability is restored (Class IIb, LOE C).363 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B363>  After the patient is stabilized, some papers suggest a maintenance infusion of 0.25 mL/kg per minute for at least 30 to 60 minutes. A maximum cumulative dose of 12 mL/kg has been proposed.363 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B363>  

Some animal data suggest that lipid infusion alone may be more effective than standard doses of epinephrine or vasopressin.357 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B357> ,360 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B360>  Although there is limited evidence to change routine care for severe cardiotoxicity, several professional societies advocate protocolized clinical use.364 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B364> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B365> 366 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B366>  Because this is a rapidly evolving clinical area,367 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B367> ,368 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B368>  prompt consultation with a medical toxicologist, anesthesiologist, or other specialist with up-to-date knowledge is strongly recommended. 

Carbon Monoxide
Apart from complications from deliberate drug abuse, carbon monoxide is the leading cause of unintentional poisoning death in the United States.369 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B369>  In addition to reducing the ability of hemoglobin to deliver oxygen, carbon monoxide causes direct cellular damage to the brain and myocardium.370 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B370>  Survivors of carbon monoxide poisoning are at risk for lasting neurological injury.370 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B370>  

Several studies have suggested that very few patients who develop cardiac arrest from carbon monoxide poisoning survive to hospital discharge, regardless of treatment administered following return of spontaneous circulation.371 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B371> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B372> 373 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B373>  Routine care of patients in cardiac arrest and severe cardiotoxicity from carbon monoxide poisoning should comply with standard BLS and ACLS recommendations. 

Hyperbaric Oxygen
Two studies suggest that neurological outcomes were improved in patients with carbon monoxide toxicity of all severity (excluding "moribund" patients)374 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B374>  and mild to moderate severity (excluding loss of consciousness and cardiac instability)375 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B375>  who received hyperbaric oxygen therapy for carbon monoxide poisoning. Other studies found no difference in neurologically intact survival.376 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B376> ,377 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B377>  A systematic review378 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B378> ,379 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B379>  and a recent evidence-based clinical policy review380 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B380>  concluded that, based on the available evidence, improvement in neurologically intact survival following treatment for carbon monoxide poisoning with hyperbaric oxygen is possible but unproven. 

Hyperbaric oxygen therapy is associated with a low incidence of severe side effects. Because hyperbaric oxygen therapy appears to confer little risk,380 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B380>  the available data suggest that hyperbaric oxygen therapy may be helpful in treatment of acute carbon monoxide poisoning in patients with severe toxicity (Class IIb, LOE C). 

Patients with carbon monoxide poisoning who develop a cardiac injury have an increased risk of cardiovascular and all-cause mortality for at least 7 years after the event, even if hyperbaric oxygen is administered.381 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B381> ,382 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B382>  Although data about effective interventions in this population are lacking, it is reasonable to advise enhanced follow-up for these patients. 

On the basis of this conflicting evidence, the routine transfer of patients to a hyperbaric treatment facility following resuscitation from severe cardiovascular toxicity should be carefully considered, weighing the risk of transport against the possible improvement in neurologically intact survival. 

Cyanide
Cyanide is a surprisingly common chemical. In addition to industrial sources, cyanide can be found in jewelry cleaners, electroplating solutions, and as a metabolic product of the putative antitumor drug amygdalin (laetrile). Cyanide is a major component of fire smoke, and cyanide poisoning must be considered in victims of smoke inhalation who have hypotension, central nervous system depression, metabolic acidosis, or soot in the nares or respiratory secretions.383 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B383>  Cyanide poisoning causes rapid cardiovascular collapse, which manifests as hypotension, lactic acidosis, central apnea, and seizures. 

Patients in cardiac arrest383 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B383> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B384> 385 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B385>  or those presenting with cardiovascular instability383 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B383> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B384>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B385>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B386>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B387>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B388> 389 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B389>  caused by known or suspected cyanide poisoning should receive cyanide-antidote therapy with a cyanide scavenger (either IV hydroxocobalamin or a nitrate such as IV sodium nitrite and/or inhaled amyl nitrite), followed as soon as possible by IV sodium thiosulfate.387 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B387> ,390 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B390> ,391 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B391>  

Both hydroxocobalamin383 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B383> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B384>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B385>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B386>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B387>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B388> 389 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B389>  and sodium nitrite387 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B387> ,390 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B390> ,391 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B391>  serve to rapidly and effectively bind cyanide in the serum and reverse the effects of cyanide toxicity. Because nitrites induce methemoglobin formation390 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B390>  and can cause hypotension,392 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B392>  hydroxocobalamin has a safety advantage, particularly in children and victims of smoke inhalation who might also have carbon monoxide poisoning. A detailed comparison of these measures has been recently published.393 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B393>  

Sodium thiosulfate serves as a metabolic cofactor, enhancing the detoxification of cyanide to thiocyanate. Thiosulfate administration enhances the effectiveness of cyanide scavengers in animal experimentation394 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B394> – <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B395>  <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B396> 397 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B397>  and has been used successfully in humans with both hydroxocobalamin383 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B383> ,389 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B389>  and sodium nitrite.387 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B387> ,390 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B390> ,391 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B391>  Sodium thiosulfate is associated with vomiting but has no other significant toxicity.398 <http://circ.ahajournals.org/cgi/content/full/122/18_suppl_3/S829#B398>  Therefore, based on the best evidence available, a treatment regimen of 100% oxygen and hydroxocobalamin, with or without sodium thiosulfate, is recommended (Class I, LOE B).

Rachel McLean, MPH

Adult Viral Hepatitis Prevention Coordinator

STD Control Branch

California Department of Public Health

Phone: (510) 620-3403

Email: Rachel.McLean at cdph.ca.gov

Website: www.cdph.ca.gov/programs/pages/ovhp.aspx 

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