Resuscitation 85 (2014) 1313–1314
Contents lists available at ScienceDirect
Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Editorial
The drugs don’t work, they just make you worse
Drug induced cardiac arrest represent a significant proportion of cardiac arrests of non-cardiac cause. The proportion will vary from place to place and time to time as a result of what is currently being used as intoxicants within a community. This presents particular difficulties for the emergency physician as some of these arrests potentially need different treatment from other causes of arrest. For instance in those with sympathomimetic induced arrest (e.g. Cocaine, phenethylamine, or derivatives) the use of further sympathomimetics may be detrimental to outcome. Additionally, use of specific antidotes in the arrest situation may be indicated and therefore practitioners will deviate from ALS guidelines (for example, using naloxone in opiate induced arrest). Furthermore, there are many novel psychoactive substances coming onto the market every year (81 novel psychoactive substances were reported in 2013),1 with very little in the way of data on their effects and how to treat them. It is therefore important that as much information as possible is published on the characteristics of drug induced cardiac arrest, so that we can make reasonable decisions during managing an arrest. It is unlikely that such arrests will be amenable to use of strict protocols or guidelines as there is little that is standard about any drug ingestion. Sample purchases of illicit substances have shown that they may well not be what they are described as,2 they may be taken with other pharmacologically active substances, they may be contaminated with other pharmacologically active or biological substances, and the background pharmacology of the individuals will be variable (i.e. what they have been taking, for how long, and how they have been taking it). Koller et al.3 have looked at the characteristics of drug induced arrest over 4 years and over 4 separate Emergency Medical Services (EMS) agencies. These cases were identified by the use of naloxone in the arrest, or history given to the EMS or hospital consistent with a drug induced cause. Resuscitation parameters of compression fraction, rate and depth of compression, number of DC shocks, and administration of drugs. The authors have shown that in this cohort of patients, the mean age of the patients was significantly lower, that the use of adrenaline, bicarbonate, and atropine was higher in the drug induced group, and that the survival to hospital discharge rate was higher in the drug induced group. The paper did not include non-drug toxicological arrests (i.e. pesticide poisoning), and did not have enough patients with different toxins to determine whether practise changes depending on the drug taken (it would not be unreasonable to expect that those with tricyclic induced arrest would be more likely to be given bicarbonate than others, for example). This cohort also did not have any cases
http://dx.doi.org/10.1016/j.resuscitation.2014.07.001 0300-9572/© 2014 Elsevier Ireland Ltd. All rights reserved.
that received intralipid rescue therapy, hyperinsulinaemic euglycaemic therapy (HIET), or extracorporeal resuscitation which have all been investigated for those with cardiovascular collapse from drug ingestion. The use of intralipid in local anaesthetic toxicity is well established.4 The mechanism of action is unclear, but may be due to the lipophilic properties absorbing the circulating drug or it may be that by counteracting the inhibition of myocardial fatty acid metabolism, ATP is preserved in the myocardium, it is also thought to increase intracellular calcium in the myocardium. In 2009 a systematic review of 14 animal studies, 1 human study and 4 case reports demonstrated that data for intralipid as an antidote in lipophilic drug overdose, such as calcium channel blockers, was limited outside of local anaesthetic toxicity but in lethal cardiotoxicity or cardiac arrest due to suspected toxins it may be helpful.5 These case reports show promise, however we cannot confidently say that intralipid administration was the causative recovery agent, and caution must be used when interpreting data obtained from animal studies. The lipid rescue website is collecting case reports to improve the evidence base.6 HIET can be used for calcium-channel blocker (CCB) and betablocker overdose. CCBs act by blocking the L-type calcium channels in the myocardium and smooth muscle, this effectively results in decreased inotropy, chronotropy and hypotension. Hyperglycaemia is common in calcium channel blocker use because of impaired insulin release and impaired glucose uptake at a tissue level. During a period of severe myocardial stress, energy is gained via carbohydrate metabolism rather than the usual fatty acids, the relative hypo-insulinaemia and insulin resistance seen with CCB overdose will therefore have a further detrimental effect on myocardial function as glucose is not taken up into the myocardial cells.7 HIET is thought to overcome the hypo-insulinaemia and insulin resistance thereby improving myocardial metabolism. Currently HIET is recommended for CCB overdose, but the evidence for it is wider use is still limited. Advances in technology mean that we can now deliver ECLS peripherally without the need for sternotomy, widening its use to the resuscitation room and even pre-hospital. The aim of ECLS is to relieve the myocardium of undue pressure while perfusing vital end organs. Retrospective, observational data8 has shown a survival to hospital discharge of 76% without sequelae. However, this was only 17 patients and not controlled. It is implementation is also complicated, as it would need to be done on a regional scale so that those put onto ECLS could go on to ECMO centres if necessary.
1314
Editorial / Resuscitation 85 (2014) 1313–1314
There are some interesting therapies available for treatment of drug induced cardiac arrest, but they are difficult to get compelling evidence for. Some of them are also agent specific and so even harder to get into studies due to lack of numbers. The intralipid register is an excellent attempt at getting all possible available evidence for a treatment that is suitable for only a very small number of patients. Observational studies such as this one are a vital part of that effort, even when they do not include these novel therapies. Conflict of interest statement The authors have no conflicts of interest. References 1. European Monitoring Centre for drugs and drug addiction. European Drug Report: Trends and developments 2014 May; 2014, accessed on 30.05.14 http://www.emcdda.europa.eu/publications/edr/trends-developments/2014 2. Brandt SD, Sumnall HR, Measham F, et al. Analyses of second-generation ‘legal highs’ in the UK: initial findings. Drug Test Anal 2010;2: 377–82. 3. Koller AC, Salcido DD, Calloway CW, Menogazzi JJ. Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest. Resuscitation, http://dx.doi.org/10.1016/j.resuscitation.2014.05.036
4. Ozcan MS, Weinberg G. Intravenous lipid emulsion for the treatment of drug toxicity. J Intensive Care Med 2014;29:59–70. 5. Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: a systematic review. Acad Emerg Med 2009;16:815–24. 6. Weinberg G. www.lipidrescue.org 7. Lheureux P, Zahir S, Gris M, Derry A-S, Penaloza A. Bench-to-beside review: hyperinsulinaemia/euglycaemia therapy in the management of overdose of calcium-channel blockers. Crit Care 2006;10:212. 8. Daubin C, Lehoux P, Ivascau C, et al. Extracorporeal life support in severe drug intoxication: a retrospective cohort study of seventeen cases. Crit Care 2009;13:R138.
Stephen Haig ∗ Great Western Hospital, Marlborough Road, Swindon SN3 6BB, United Kingdom Joy Ferguson ACCS CT1, Great Western Hospital, Swindon SN3 6BB, United Kingdom ∗ Corresponding
author. E-mail addresses: [email protected], [email protected] (S. Haig). 30 June 2014
Contents lists available at ScienceDirect
Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Editorial
The drugs don’t work, they just make you worse
Drug induced cardiac arrest represent a significant proportion of cardiac arrests of non-cardiac cause. The proportion will vary from place to place and time to time as a result of what is currently being used as intoxicants within a community. This presents particular difficulties for the emergency physician as some of these arrests potentially need different treatment from other causes of arrest. For instance in those with sympathomimetic induced arrest (e.g. Cocaine, phenethylamine, or derivatives) the use of further sympathomimetics may be detrimental to outcome. Additionally, use of specific antidotes in the arrest situation may be indicated and therefore practitioners will deviate from ALS guidelines (for example, using naloxone in opiate induced arrest). Furthermore, there are many novel psychoactive substances coming onto the market every year (81 novel psychoactive substances were reported in 2013),1 with very little in the way of data on their effects and how to treat them. It is therefore important that as much information as possible is published on the characteristics of drug induced cardiac arrest, so that we can make reasonable decisions during managing an arrest. It is unlikely that such arrests will be amenable to use of strict protocols or guidelines as there is little that is standard about any drug ingestion. Sample purchases of illicit substances have shown that they may well not be what they are described as,2 they may be taken with other pharmacologically active substances, they may be contaminated with other pharmacologically active or biological substances, and the background pharmacology of the individuals will be variable (i.e. what they have been taking, for how long, and how they have been taking it). Koller et al.3 have looked at the characteristics of drug induced arrest over 4 years and over 4 separate Emergency Medical Services (EMS) agencies. These cases were identified by the use of naloxone in the arrest, or history given to the EMS or hospital consistent with a drug induced cause. Resuscitation parameters of compression fraction, rate and depth of compression, number of DC shocks, and administration of drugs. The authors have shown that in this cohort of patients, the mean age of the patients was significantly lower, that the use of adrenaline, bicarbonate, and atropine was higher in the drug induced group, and that the survival to hospital discharge rate was higher in the drug induced group. The paper did not include non-drug toxicological arrests (i.e. pesticide poisoning), and did not have enough patients with different toxins to determine whether practise changes depending on the drug taken (it would not be unreasonable to expect that those with tricyclic induced arrest would be more likely to be given bicarbonate than others, for example). This cohort also did not have any cases
http://dx.doi.org/10.1016/j.resuscitation.2014.07.001 0300-9572/© 2014 Elsevier Ireland Ltd. All rights reserved.
that received intralipid rescue therapy, hyperinsulinaemic euglycaemic therapy (HIET), or extracorporeal resuscitation which have all been investigated for those with cardiovascular collapse from drug ingestion. The use of intralipid in local anaesthetic toxicity is well established.4 The mechanism of action is unclear, but may be due to the lipophilic properties absorbing the circulating drug or it may be that by counteracting the inhibition of myocardial fatty acid metabolism, ATP is preserved in the myocardium, it is also thought to increase intracellular calcium in the myocardium. In 2009 a systematic review of 14 animal studies, 1 human study and 4 case reports demonstrated that data for intralipid as an antidote in lipophilic drug overdose, such as calcium channel blockers, was limited outside of local anaesthetic toxicity but in lethal cardiotoxicity or cardiac arrest due to suspected toxins it may be helpful.5 These case reports show promise, however we cannot confidently say that intralipid administration was the causative recovery agent, and caution must be used when interpreting data obtained from animal studies. The lipid rescue website is collecting case reports to improve the evidence base.6 HIET can be used for calcium-channel blocker (CCB) and betablocker overdose. CCBs act by blocking the L-type calcium channels in the myocardium and smooth muscle, this effectively results in decreased inotropy, chronotropy and hypotension. Hyperglycaemia is common in calcium channel blocker use because of impaired insulin release and impaired glucose uptake at a tissue level. During a period of severe myocardial stress, energy is gained via carbohydrate metabolism rather than the usual fatty acids, the relative hypo-insulinaemia and insulin resistance seen with CCB overdose will therefore have a further detrimental effect on myocardial function as glucose is not taken up into the myocardial cells.7 HIET is thought to overcome the hypo-insulinaemia and insulin resistance thereby improving myocardial metabolism. Currently HIET is recommended for CCB overdose, but the evidence for it is wider use is still limited. Advances in technology mean that we can now deliver ECLS peripherally without the need for sternotomy, widening its use to the resuscitation room and even pre-hospital. The aim of ECLS is to relieve the myocardium of undue pressure while perfusing vital end organs. Retrospective, observational data8 has shown a survival to hospital discharge of 76% without sequelae. However, this was only 17 patients and not controlled. It is implementation is also complicated, as it would need to be done on a regional scale so that those put onto ECLS could go on to ECMO centres if necessary.
1314
Editorial / Resuscitation 85 (2014) 1313–1314
There are some interesting therapies available for treatment of drug induced cardiac arrest, but they are difficult to get compelling evidence for. Some of them are also agent specific and so even harder to get into studies due to lack of numbers. The intralipid register is an excellent attempt at getting all possible available evidence for a treatment that is suitable for only a very small number of patients. Observational studies such as this one are a vital part of that effort, even when they do not include these novel therapies. Conflict of interest statement The authors have no conflicts of interest. References 1. European Monitoring Centre for drugs and drug addiction. European Drug Report: Trends and developments 2014 May; 2014, accessed on 30.05.14 http://www.emcdda.europa.eu/publications/edr/trends-developments/2014 2. Brandt SD, Sumnall HR, Measham F, et al. Analyses of second-generation ‘legal highs’ in the UK: initial findings. Drug Test Anal 2010;2: 377–82. 3. Koller AC, Salcido DD, Calloway CW, Menogazzi JJ. Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest. Resuscitation, http://dx.doi.org/10.1016/j.resuscitation.2014.05.036
4. Ozcan MS, Weinberg G. Intravenous lipid emulsion for the treatment of drug toxicity. J Intensive Care Med 2014;29:59–70. 5. Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: a systematic review. Acad Emerg Med 2009;16:815–24. 6. Weinberg G. www.lipidrescue.org 7. Lheureux P, Zahir S, Gris M, Derry A-S, Penaloza A. Bench-to-beside review: hyperinsulinaemia/euglycaemia therapy in the management of overdose of calcium-channel blockers. Crit Care 2006;10:212. 8. Daubin C, Lehoux P, Ivascau C, et al. Extracorporeal life support in severe drug intoxication: a retrospective cohort study of seventeen cases. Crit Care 2009;13:R138.
Stephen Haig ∗ Great Western Hospital, Marlborough Road, Swindon SN3 6BB, United Kingdom Joy Ferguson ACCS CT1, Great Western Hospital, Swindon SN3 6BB, United Kingdom ∗ Corresponding
author. E-mail addresses: [email protected], [email protected] (S. Haig). 30 June 2014
