American Journal of Emergency Medicine 32 (2014) 1378–1381
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Original Contribution
Therapeutic hypothermia after cardiac arrest caused by self-inflicted intoxication: a multicenter retrospective cohort study Han Joon Kim, MD a, Gi Woon Kim, MD b,⁎, Sang Hoon Oh, MD a, Sang Hyun Park, MD c, Jae Hyung Choi, MD d, Kyung Hwan Kim, MD e, Woo Chan Jeon, MD e, Hui Jai Lee, MD f, Kyu Nam Park, MD a, for the Korean Hypothermia Network Investigators a
Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Department of Emergency Medicine, College of Medicine, Ajou University, Suwon, Republic of Korea c Department of Emergency Medicine, Seoul Medical Center, Seoul, Republic of Korea d Department of Emergency Medicine, College of Medicine, Soonchunhyang University, Bucheon, Republic of Korea e Department of Emergency Medicine, College of Medicine, Inje University, Ilsan, Republic of Korea f Department of Emergency Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea b
a r t i c l e
i n f o
Article history: Received 11 June 2014 Received in revised form 20 August 2014 Accepted 20 August 2014
a b s t r a c t Introduction: The aim of this study was to describe the epidemiology and outcomes of patients with therapeutic hypothermia after out-of-hospital cardiac arrest (OHCA) caused by self-inflicted intoxication. Methods: We performed a multicenter retrospective registry-based study of adult OHCA patients presenting to 24 hospitals over 6 years across South Korea. Data included demographics, resuscitation variables, postresuscitation variables, and self-inflicted intoxicants. Neurologic outcomes were categorized according to the Glasgow-Pittsburgh Cerebral Performance Categories (CPC) scale and were dichotomized as either good discharge outcomes (CPC 1 and 2) or poor discharge outcomes (CPC 3-5). Results: A total of 930 OHCA cases were identified, 24 (2.6%) of which were classified as cardiac arrest caused by acute intoxication. The mean age of cases was 57.2 ± 12.9 years. The mean time from collapse to return of spontaneous circulation was 35.4 ± 18.7 minutes. The presenting rhythm was pulseless electrical activity in 6 patients (25%) and asystole in 18 patients (75%). Eleven patients (46%) survived to hospital discharge, and of these, good discharge outcomes (CPC 1 and 2) were achieved in 21% (5/24). For pesticide intoxication, the survival-to-discharge rate was 62% (8/13), and the rate of good neurologic outcome was 23% (3/13). Conclusion: Patients with OHCA caused by self-inflicted intoxication represented 2.6% of all OHCA patients. They showed a high rate of unwitnessed cardiac arrest and a very low rate of bystander cardiopulmonary resuscitation. Pesticides were the main cause of cardiac arrest, and these cases had a very high discharge to survival rate. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Suicide is a major public health concern. Approximately 800 000 to 1 million people die of suicide each year, making suicide the 10th leading cause of death worldwide [1,2]. In 2011, the Statistics Korea reported a suicide rate of 31.7 per 100 000 people, which is 2.6 times higher than the Organization for Economic Cooperation and Development average and represents a 2-fold increase in suicides over the last decade [3]. The most commonly used method of suicide varies by country and is partially related to availability. In Asian countries (eg, the Republic of Conflicts of interest: The authors do not have any financial or other relationships that might pose any conflicts of interest. ⁎ Corresponding author. Department of Emergency Medicine, College of Medicine, Ajou University, Suwon, Republic of Korea. Tel.: +82 31 219 7750 (secretary); fax: +82 31 219 7760. E-mail address: fl[email protected] (G.W. Kim). http://dx.doi.org/10.1016/j.ajem.2014.08.045 0735-6757/© 2014 Elsevier Inc. All rights reserved.
Korea and Thailand) and Portugal, poisoning with pesticides has been a major problem [4]. In the Republic of Korea, the percentage of out-of-hospital cardiac arrest (OHCA) cases caused by self-inflicted intoxication represented 4.4% among of all OHCA patients [5]. In addition to other OHCA treatments, the medical treatments for cardiac arrest caused by intoxication are targeted antidotal therapy and various methods of enhanced elimination. Currently, therapeutic hypothermia (TH) is highly recommended by the American Heart Association for comatose adults resuscitated from OHCA caused by ventricular fibrillation or pulseless ventricular tachycardia. Furthermore, TH also may be considered for comatose adult patients with return of spontaneous circulation (ROSC) after inhospital cardiac arrest of any initial rhythm or after OHCA with an initial rhythm of pulseless electrical activity (PEA) or asystole [6]. Except for a few case reports, the role of TH in OHCA due to intoxication has not been widely studied [7,8]. The objective of this study is to describe the epidemiology
H.J. Kim et al. / American Journal of Emergency Medicine 32 (2014) 1378–1381
and outcomes of patients who received TH after OHCA caused by acute intoxication. 2. Methods This was a multicenter retrospective, observational, registry-based study. The data for this investigation were obtained from the Korean Hypothermia Network registry. Data were collected from January 1, 2007, to December 31, 2012, at 24 teaching hospitals throughout South Korea. Episodes were excluded for traumatic cardiac arrest patients younger than 18 years. Three clinical research associates examined the input data, corrected suspected errors, provided feedback to the researchers at each organization to double-check entries, and then finalized the case inputs after verification. The data manager then reaffirmed the final input data, reassessed the data for errors, and completed the case inputs with feedback from the clinical research associate and researchers of each organization. In this study, patients who received TH after OHCA caused by selfinflicted intoxication were enrolled. The data included demographics (age and underlying disease), resuscitation variables (witnessed arrest, bystander cardiopulmonary resuscitation, first monitored rhythm, time from collapse to ROSC, and Glasgow Coma Scale after ROSC), postresuscitation variables (TH characteristics, adverse events, and neurologic outcomes at discharge), and self-inflicted intoxicants. Return of spontaneous circulation is defined as a state in which circulation lasted more than 20 minutes. Adverse events were recorded as cooling related (eg, overcooling, bradycardia, tachycardia, hypokalemia, hyperglycemia, bleeding, and hypotension) and rewarming related (eg, hyperthermia, hyperkalemia, hypoglycemia, bleeding, and hypotension). In addition, pneumonia and sepsis were examined. Hypotension was defined as systolic blood pressure less than 90 mm Hg or mean arterial blood pressure is less than 60 mm Hg or that medications or mechanical support was required to maintain systolic blood pressure or mean arterial blood pressure. Pneumonia was defined as the presence of a new lesion on chest x-ray examination, fever, leukocytosis, or emission of purulent sputum.
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Neurologic outcomes were assessed at discharge by using the Glasgow-Pittsburgh Cerebral Performance Categories (CPC) and were dichotomized as either good discharge outcomes (CPC 1 and 2) or poor discharge outcomes (CPC 3-5) [9]. Categorical variables were presented as counts and percentage; continuous variables were presented as mean ± SD. All statistical analyses were performed using SPSS software, version 16.0 (SPSS, Chicago, IL). The institutional review board of each institution approved the study protocols before data collection. Informed consent was waived because of the retrospective nature of the study. 3. Results A total 930 OHCA cases were identified, 366 (39.3%) of which were classified as cardiac arrests of noncardiac origin. Of these 366 patients, 27 patients were classified as cardiac arrest caused by self-inflicted intoxication and accounted for 2.9% of all patients and 7.3% of patients whose cardiac arrest was of noncardiac origin. Three patients had incomplete data because their medical records did not include information about TH and thus were excluded from the study; finally, 24 patients enrolled in the study (Figure). The baseline characteristics and resuscitation variables of the study patients are summarized in Table 1. The mean age was 57.2 ± 12.9 years, and 13 patients (54.2%) were male and 11 patients (45.8%) were female. Cardiac arrest was witnessed in 11 patients (45.8%). Two patients (8.3%) received basic life support by bystanders. The mean time from collapse to ROSC was 35.4 ± 18.7 minutes. The presenting rhythm was PEA in 6 patients (25%) and asystole in 18 patients (75%). The resuscitation variables, postresuscitation variables, and selfinflicted intoxicants are displayed for each patient in Table 2. The materials of self-inflicted intoxication were pesticides (n = 13, 54%); pharmaceuticals: psychotropic medications (n = 5, 21%), cardiovascular medications (n = 2, 8%), and antihistamines (n = 1, 4%); household products (n = 2, 8%); and natural toxins (n = 1, 4%). An endovascular catheter for 8 cases, cooling blanket or mattress for 10 cases, hydrogel pad for 4 cases, and cooling garment for 2 cases were used for TH.
Figure. Template for the inclusion of patients in the study.
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Table 1 Patient and cardiac arrest characteristics
Table 3 Therapeutic hypothermia characteristics n = 24
Age, y Male sex Comorbidity Coronary heart disease Congestive heart failure Stroke Hypertension Diabetes mellitus Lung disease Renal impairment Liver cirrhosis Malignancy Witness Bystander CPR First monitored rhythm Vf/pulseless VT PEA Asystole Unknown Time from collapse to ROSC, min GCS after ROSC
n = 24
57.2 ± 12.9 13 (54.2) 0 (0.0) 0 (0.0) 0 (0.0) 4 (16.7) 4 (16.7) 0 (0.0) 1 (4.2) 0 (0.0) 0 (0.0) 11 (45.8) 2 (8.3) 0 6 (25) 18 (75) 0 35.4 ± 18.7 3.17 ± 0.5
Data are presented as median with interquartile range or number (%). Abbreviations: Vf, ventricular fibrillation; VT, ventricular tachycardia; GCS, Glasgow Coma Scale.
Therapeutic hypothermia characteristics are shown in Table 3. The time from start of TH to achievement of target temperature was 205.0 ± 182.2 minutes. The adverse events are shown in Table 4. Hypokalemia was the most frequent adverse event in the cooling phase, followed by hypotension and hyperglycemia; hypotension was the most common adverse event in the rewarming phase. The other adverse events in the intensive care unit were sepsis in 3 cases and pneumonia in 11 cases. On the other hand, in the 564 patients who had cardiac arrest from cardiac causes, hyperglycemia was the most frequent adverse event in the cooling phase, and the most common adverse event in the rewarming phase was hypotension. Of the 24 patients who were treated with TH after OHCA caused by self-inflicted intoxication, 11 patients (46%) survived to discharge; of these cases, the causative agents were 8 of 13 for pesticides and 3 of 8 for pharmaceuticals. Five of the 24 patients had good neurologic outcomes; of
Time from ROSC to start of TH, min Time from start of TH to achieve target temperature, min Duration of maintenance, min Duration of rewarming, min
183.2 ± 153.0 205.0 ± 182.2 1482.6 ± 504.3 716.2 ± 363.6
these patients, acute intoxication was due to pesticides in 3 and pharmaceuticals (psychotropic medications) in 2 patients, respectively. 4. Discussion To our knowledge, this is the first study about TH after OHCA caused by self-inflicted intoxication. Therapeutic hypothermia has become the standard of care for comatose ventricular fibrillation or pulseless ventricular tachycardia arrest patients. In addition, TH is recommended for comatose adults who have been resuscitated from OHCA caused by nonshockable rhythms or inhospital cardiac arrest (class IIb) patients. In the latter patients, the role of TH is uncertain, especially if the cardiac arrest is due primarily to noncardiac causes, such as drug overdose. In previous studies of noncardiac OHCA etiology, poisoning accounted for approximately 10% of cases in developed countries [10-12]. According to Park et al [5], OHCA caused by self-inflicted intoxication was documented in 900 (4.4%) of 20 536 cases of OHCA of noncardiac etiology from 2006 to 2008 in Korea. In our study, 27 patients were classified as cardiac arrest caused by self-inflicted intoxication, which accounted for 7.3% of patients with cardiac arrest of noncardiac origin. Of patients with TH after OHCA caused by self-inflicted intoxication, pesticides (54%) were the most common cause of OHCA. These findings (54%) are consistent with Park et al (49.3%) [5]. Among our cases, there was no shockable rhythm in the first monitoring after ROSC, and time from collapse to ROSC was 35.4 ± 18.7 minutes. This result is similar to Oddo et al [13], who reported a collapse to ROSC interval of 34.6 ± 11.9 minutes in nonshockable cases. There is no definitive research on the relationship between collapse to ROSC interval and favorable neurologic outcome in cases of nonshockable cardiac arrest. Bernard et al [14] found that the probability of favorable neurologic outcomes drops by 14% for every 1.5 minutes of
Table 2 Characteristics of OHCA caused by self-inflicted intoxication for patients who underwent TH No.
Sex
Age
Agent
Witnessed
Bystander CPR
Initial rhythm
Anoxic time
TH methods
Discharge CPC
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
M M M F F F M M F M M F F M M F F M F F M F M M
66 38 57 45 70 44 58 52 48 45 47 45 82 71 53 49 75 51 76 40 62 71 54 74
Carbamate Carbamate Glyphosate Organophosphate Organophosphate Carbamate Sulfosate Poisonous plant Psychotropic Organophosphate Cardiovascular Antihistamine Psychotropic Organophosphate Carbamate Carbamate Psychotropic Organophosphate Household products Psychotropic Household products Psychotropic Carbamate Cardiovascular
No No Yes Yes Yes No No Yes No Yes Yes No No No Yes Yes No No No Yes No No Yes Yes
No No No No No No No No No No No Yes No No No No No No No Yes No No No No
Asystole Asystole PEA PEA Asystole Asystole Asystole Asystole Asystole Asystole Asystole Asystole PEA PEA Asystole Asystole Asystole Asystole Asystole Asystole Asystole PEA Asystole Asystole
49 63 23 50 20 70 14 15 68 15 31 41 11 70 20 40 50 25 45 27 48 4 30 54
Blanket Endovascular Blanket Endovascular Blanket Blanket Blanket Blanket Endovascular Blanket Garment Endovascular Endovascular Blanket Blanket Blanket Hydrogel pad Garment Endovascular Endovascular Hydrogel pad Hydrogel pad Endovascular Hydrogel pad
5 5 1 4 4 5 4 5 5 1 4 5 1 5 4 1 5 5 5 5 5 2 4 5
H.J. Kim et al. / American Journal of Emergency Medicine 32 (2014) 1378–1381 Table 4 Number and frequency of adverse events in OHCA caused by self-inflicted intoxication for patients who underwent TH n = 24 Cooling phase
Rewarming phase
Critical care phase
Overcooling Bradycardia Tachycardia Hypokalemia Hyperglycemia Bleeding Hypotension Hyperthermia Arrhythmia Hypokalemia Hypoglycemia Bleeding Hypotension Sepsis Pneumonia
1 (4.2) 3 (12.5) 1 (4.2) 13 (54.2) 8 (33.3) 1 (4.2) 11 (45.8) 2 (8.3) 0 (0.0) 1 (4.2) 1 (4.2) 1 (4.2) 6 (25.0) 3 (12.5) 11 (45.8)
the collapse to ROSC interval in cases of shockable cardiac arrest; the probability of a good neurologic outcome in patients with OHCA caused by self-inflicted intoxication is very low. In our study, patients with good neurologic outcomes represented 5 of the 24 patients. The collapse to ROSC interval of these patients was a median of 15 minutes (range, 4-40 minutes). The role of TH is uncertain when cardiac arrest is primarily due to a noncardiac cause, such as acute intoxication. However, TH is likely to be helpful for cerebral metabolic and edema changes and in patients with anoxic brain injury after nonshockable cardiac arrest. In animal studies, the beneficial effects of TH on neurologic recovery have been observed primarily after asphyxiation-induced PEA or asystolic cardiac arrest [15,16]. In this study, of 24 patients treated with TH after OHCA caused by acute intoxication, 11 patients (46%) survived to discharge, and 5 patients (21%) had good neurologic function at the time of hospital discharge. These results were superior to those of Dumas et al [17], where 15% (38/261) of the cases of nonshockable cardiac arrest were treated with post-ROSC cooling and resulted in favorable neurologic outcomes. In addition, compared with Park et al, our survival-to-discharge discharge rate was higher: 46% vs 3.6%, respectively [5]. In both Park et al and our study, OHCA resulted from similar causative agents in the same geographic region, and thus, it may be said that TH improves the survival-to-discharge rate. In a study by Soga et al [18], a rate of 32% in good neurologic function was reported among the nonshockable cardiac arrest cases with TH. We think that this good neurologic outcome was found because study was witnessed OHCA [18]. Comparing with patients who had cardiac arrest from cardiac causes in Korean Hypothermia Network registry, greatest differences in the resuscitation characteristics are the first monitored rhythm (shockable rhythm: n = 180, 31.9%) and witness (n = 428, 75.9%) and bystander cardiopulmonary resuscitation (CPR) (n = 195, 34.6%). Of 564 patients treated with TH after OHCA caused by cardiac cause, 394 patients (70%) survived to discharge, and 221 patients (39%) had good neurologic function at the time of hospital discharge. Pesticides showed very high survival-to-discharge rates. According to a report by Gordon et al [19], hypothermia increases the median lethal dose of ethanol, heavy metals, methyl-mercury, and pesticides despite decreasing drug clearance in animals. Hypothermia increases the median lethal dose, which may be one of the reasons for the high survival-to-discharge rates. Finally, the effects of TH after OHCA caused by self-inflicted intoxication still have not been demonstrated. However, TH will become more widely used in the management of anoxic neurologic injury regardless of the presenting cardiac rhythm and cause of OHCA [20,21]. Further
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high-quality randomized clinical trials would confirm the actual benefit of TH caused by acute intoxication. The limitations of this study are as follows. First, the study population was only composed of patients who received treatment for hypothermia and, therefore, did not verify the availability of TH. Second, data in this study did not include specific treatments for intoxication, such as antidote therapy or gastrointestinal decontamination. This incomplete information may bias the results. Third, although this study was a multicenter retrospective registry-based study, the number of patients was relatively small. 5. Conclusions Based on this study of OHCA patients with self-inflicted intoxication who received TH, 11 patients (46%) survived to discharge, and good neurologic outcomes occurred in 5 (21%) of the 24 patients. Pesticides showed very high survival-to-discharge rates. However, the results of this study are insufficient to explain the benefits of TH for OHCA patients with self-inflicted intoxication. Thus, future studies are needed for further clinical investigation of the potential efficacy of TH in such patients. References [1] Hawton K, van Heeringen K. Suicide. Lancet 2009;373:1372–81. [2] Värnik P. Suicide in the world. Int J Environ Res Public Health 2012;9:760–71. [3] Statistics Korea. Annual report on the cause of death statistics. http://kostat.go.kr/ portal/korea/index.action. [Accessed December 30, 2013]. [4] Ajdacic-Gross V, Weiss MG, Ring M, et al. Methods of suicide: international suicide patterns derived from the WHO mortality database. Bull World Health Organ 2008;86:726–32. [5] Park JH, Shin SD, Song KJ, Park CB, Ro YS, Kwak YH. Epidemiology and outcomes of poisoning-induced out-of-hospital cardiac arrest. Resuscitation 2012;83:51–7. [6] Peberdy MA, Callaway CW, Neumar RW, et al. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S768–86. [7] Mumma BE, Shellenbarger D, Callaway CW, Katz KD, Guyette FX, Rittenberger JC. Neurologic recovery following cardiac arrest due to benzodiazepine and opiate toxicity. Resuscitation 2009;80:1446–7. [8] Lee HY, Lee BK, Jeung KW, Lee GS, Jung YH, Jeong IS. A case of near-fatal fenpyroximate intoxication: the role of percutaneous cardiopulmonary support and therapeutic hypothermia. Clin Toxicol 2012;50:858–61. [9] Booth CM, Boone RH, Tomlinson G, Detsky AS. Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest. JAMA 2004;291:870–9. [10] Kuisma M, Määttä T. Out-of-hospital cardiac arrests in Helsinki: Utstein style reporting. Heart 1996;76:18–23. [11] Engdahl J, Bång A, Karlson BW, Lindqvist J, Herlitz J. Characteristics and outcome among patients suffering from out of hospital cardiac arrest of non-cardiac aetiology. Resuscitation 2003;57:33–41. [12] Hess EP, Campbell RL, White RD. Epidemiology, trends, and outcome of out-ofhospital cardiac arrest of non-cardiac origin. Resuscitation 2007;72:200–6. [13] Oddo M, Schaller MD, Feihl F, Ribordy V, Liaudet L. From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest. Crit Care Med 2006;34:1865–73. [14] Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-ofhospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–63. [15] Hicks SD, DeFranco DB, Callaway CW. Hypothermia during reperfusion after asphyxial cardiac arrest improves functional recovery and selectively alters stressinduced protein expression. J Cereb Blood Flow Metab 2000;20:520–30. [16] Logue ES, McMichael MJ, Callaway CW. Comparison of the effects of hypothermia at 33 degrees C or 35 degrees C after cardiac arrest in rats. Acad Emerg Med 2007;14:293–300. [17] Dumas F, Grimaldi D, Zuber B, et al. Is hypothermia after cardiac arrest effective in both shockable and nonshockable patients?: insights from a large registry. Circulation 2011;123:877–86. [18] Soga T, Nagao K, Sawano H, et al. Neurological benefit of therapeutic hypothermia following return of spontaneous circulation for out-of-hospital non-shockable cardiac arrest. Circ J 2012;76:2579–85. [19] Gordon CJ, Mohler FS, Watkinson WP, Rezvani AH. Temperature regulation in laboratory mammals following acute toxic insult. Toxicology 1988;53:161–78. [20] Kim YM, Yim HW, Jeong SH, Klem ML, Callaway CW. Does therapeutic hypothermia benefit adult cardiac arrest patients presenting with non-shockable initial rhythms?: a systematic review and meta-analysis of randomized and non-randomized studies. Resuscitation 2012;83:188–96. [21] Shin J, Lee H, Kim J, et al. Outcomes of hanging-induced cardiac arrest patients who underwent therapeutic hypothermia: a multicenter retrospective cohort study. Resuscitation 2014. http://dx.doi.org/10.1016/j.resuscitation.2014.04.012 [S03009572(14)00494-8. [Epub ahead of print]].
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Original Contribution
Therapeutic hypothermia after cardiac arrest caused by self-inflicted intoxication: a multicenter retrospective cohort study Han Joon Kim, MD a, Gi Woon Kim, MD b,⁎, Sang Hoon Oh, MD a, Sang Hyun Park, MD c, Jae Hyung Choi, MD d, Kyung Hwan Kim, MD e, Woo Chan Jeon, MD e, Hui Jai Lee, MD f, Kyu Nam Park, MD a, for the Korean Hypothermia Network Investigators a
Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Department of Emergency Medicine, College of Medicine, Ajou University, Suwon, Republic of Korea c Department of Emergency Medicine, Seoul Medical Center, Seoul, Republic of Korea d Department of Emergency Medicine, College of Medicine, Soonchunhyang University, Bucheon, Republic of Korea e Department of Emergency Medicine, College of Medicine, Inje University, Ilsan, Republic of Korea f Department of Emergency Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea b
a r t i c l e
i n f o
Article history: Received 11 June 2014 Received in revised form 20 August 2014 Accepted 20 August 2014
a b s t r a c t Introduction: The aim of this study was to describe the epidemiology and outcomes of patients with therapeutic hypothermia after out-of-hospital cardiac arrest (OHCA) caused by self-inflicted intoxication. Methods: We performed a multicenter retrospective registry-based study of adult OHCA patients presenting to 24 hospitals over 6 years across South Korea. Data included demographics, resuscitation variables, postresuscitation variables, and self-inflicted intoxicants. Neurologic outcomes were categorized according to the Glasgow-Pittsburgh Cerebral Performance Categories (CPC) scale and were dichotomized as either good discharge outcomes (CPC 1 and 2) or poor discharge outcomes (CPC 3-5). Results: A total of 930 OHCA cases were identified, 24 (2.6%) of which were classified as cardiac arrest caused by acute intoxication. The mean age of cases was 57.2 ± 12.9 years. The mean time from collapse to return of spontaneous circulation was 35.4 ± 18.7 minutes. The presenting rhythm was pulseless electrical activity in 6 patients (25%) and asystole in 18 patients (75%). Eleven patients (46%) survived to hospital discharge, and of these, good discharge outcomes (CPC 1 and 2) were achieved in 21% (5/24). For pesticide intoxication, the survival-to-discharge rate was 62% (8/13), and the rate of good neurologic outcome was 23% (3/13). Conclusion: Patients with OHCA caused by self-inflicted intoxication represented 2.6% of all OHCA patients. They showed a high rate of unwitnessed cardiac arrest and a very low rate of bystander cardiopulmonary resuscitation. Pesticides were the main cause of cardiac arrest, and these cases had a very high discharge to survival rate. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Suicide is a major public health concern. Approximately 800 000 to 1 million people die of suicide each year, making suicide the 10th leading cause of death worldwide [1,2]. In 2011, the Statistics Korea reported a suicide rate of 31.7 per 100 000 people, which is 2.6 times higher than the Organization for Economic Cooperation and Development average and represents a 2-fold increase in suicides over the last decade [3]. The most commonly used method of suicide varies by country and is partially related to availability. In Asian countries (eg, the Republic of Conflicts of interest: The authors do not have any financial or other relationships that might pose any conflicts of interest. ⁎ Corresponding author. Department of Emergency Medicine, College of Medicine, Ajou University, Suwon, Republic of Korea. Tel.: +82 31 219 7750 (secretary); fax: +82 31 219 7760. E-mail address: fl[email protected] (G.W. Kim). http://dx.doi.org/10.1016/j.ajem.2014.08.045 0735-6757/© 2014 Elsevier Inc. All rights reserved.
Korea and Thailand) and Portugal, poisoning with pesticides has been a major problem [4]. In the Republic of Korea, the percentage of out-of-hospital cardiac arrest (OHCA) cases caused by self-inflicted intoxication represented 4.4% among of all OHCA patients [5]. In addition to other OHCA treatments, the medical treatments for cardiac arrest caused by intoxication are targeted antidotal therapy and various methods of enhanced elimination. Currently, therapeutic hypothermia (TH) is highly recommended by the American Heart Association for comatose adults resuscitated from OHCA caused by ventricular fibrillation or pulseless ventricular tachycardia. Furthermore, TH also may be considered for comatose adult patients with return of spontaneous circulation (ROSC) after inhospital cardiac arrest of any initial rhythm or after OHCA with an initial rhythm of pulseless electrical activity (PEA) or asystole [6]. Except for a few case reports, the role of TH in OHCA due to intoxication has not been widely studied [7,8]. The objective of this study is to describe the epidemiology
H.J. Kim et al. / American Journal of Emergency Medicine 32 (2014) 1378–1381
and outcomes of patients who received TH after OHCA caused by acute intoxication. 2. Methods This was a multicenter retrospective, observational, registry-based study. The data for this investigation were obtained from the Korean Hypothermia Network registry. Data were collected from January 1, 2007, to December 31, 2012, at 24 teaching hospitals throughout South Korea. Episodes were excluded for traumatic cardiac arrest patients younger than 18 years. Three clinical research associates examined the input data, corrected suspected errors, provided feedback to the researchers at each organization to double-check entries, and then finalized the case inputs after verification. The data manager then reaffirmed the final input data, reassessed the data for errors, and completed the case inputs with feedback from the clinical research associate and researchers of each organization. In this study, patients who received TH after OHCA caused by selfinflicted intoxication were enrolled. The data included demographics (age and underlying disease), resuscitation variables (witnessed arrest, bystander cardiopulmonary resuscitation, first monitored rhythm, time from collapse to ROSC, and Glasgow Coma Scale after ROSC), postresuscitation variables (TH characteristics, adverse events, and neurologic outcomes at discharge), and self-inflicted intoxicants. Return of spontaneous circulation is defined as a state in which circulation lasted more than 20 minutes. Adverse events were recorded as cooling related (eg, overcooling, bradycardia, tachycardia, hypokalemia, hyperglycemia, bleeding, and hypotension) and rewarming related (eg, hyperthermia, hyperkalemia, hypoglycemia, bleeding, and hypotension). In addition, pneumonia and sepsis were examined. Hypotension was defined as systolic blood pressure less than 90 mm Hg or mean arterial blood pressure is less than 60 mm Hg or that medications or mechanical support was required to maintain systolic blood pressure or mean arterial blood pressure. Pneumonia was defined as the presence of a new lesion on chest x-ray examination, fever, leukocytosis, or emission of purulent sputum.
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Neurologic outcomes were assessed at discharge by using the Glasgow-Pittsburgh Cerebral Performance Categories (CPC) and were dichotomized as either good discharge outcomes (CPC 1 and 2) or poor discharge outcomes (CPC 3-5) [9]. Categorical variables were presented as counts and percentage; continuous variables were presented as mean ± SD. All statistical analyses were performed using SPSS software, version 16.0 (SPSS, Chicago, IL). The institutional review board of each institution approved the study protocols before data collection. Informed consent was waived because of the retrospective nature of the study. 3. Results A total 930 OHCA cases were identified, 366 (39.3%) of which were classified as cardiac arrests of noncardiac origin. Of these 366 patients, 27 patients were classified as cardiac arrest caused by self-inflicted intoxication and accounted for 2.9% of all patients and 7.3% of patients whose cardiac arrest was of noncardiac origin. Three patients had incomplete data because their medical records did not include information about TH and thus were excluded from the study; finally, 24 patients enrolled in the study (Figure). The baseline characteristics and resuscitation variables of the study patients are summarized in Table 1. The mean age was 57.2 ± 12.9 years, and 13 patients (54.2%) were male and 11 patients (45.8%) were female. Cardiac arrest was witnessed in 11 patients (45.8%). Two patients (8.3%) received basic life support by bystanders. The mean time from collapse to ROSC was 35.4 ± 18.7 minutes. The presenting rhythm was PEA in 6 patients (25%) and asystole in 18 patients (75%). The resuscitation variables, postresuscitation variables, and selfinflicted intoxicants are displayed for each patient in Table 2. The materials of self-inflicted intoxication were pesticides (n = 13, 54%); pharmaceuticals: psychotropic medications (n = 5, 21%), cardiovascular medications (n = 2, 8%), and antihistamines (n = 1, 4%); household products (n = 2, 8%); and natural toxins (n = 1, 4%). An endovascular catheter for 8 cases, cooling blanket or mattress for 10 cases, hydrogel pad for 4 cases, and cooling garment for 2 cases were used for TH.
Figure. Template for the inclusion of patients in the study.
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H.J. Kim et al. / American Journal of Emergency Medicine 32 (2014) 1378–1381
Table 1 Patient and cardiac arrest characteristics
Table 3 Therapeutic hypothermia characteristics n = 24
Age, y Male sex Comorbidity Coronary heart disease Congestive heart failure Stroke Hypertension Diabetes mellitus Lung disease Renal impairment Liver cirrhosis Malignancy Witness Bystander CPR First monitored rhythm Vf/pulseless VT PEA Asystole Unknown Time from collapse to ROSC, min GCS after ROSC
n = 24
57.2 ± 12.9 13 (54.2) 0 (0.0) 0 (0.0) 0 (0.0) 4 (16.7) 4 (16.7) 0 (0.0) 1 (4.2) 0 (0.0) 0 (0.0) 11 (45.8) 2 (8.3) 0 6 (25) 18 (75) 0 35.4 ± 18.7 3.17 ± 0.5
Data are presented as median with interquartile range or number (%). Abbreviations: Vf, ventricular fibrillation; VT, ventricular tachycardia; GCS, Glasgow Coma Scale.
Therapeutic hypothermia characteristics are shown in Table 3. The time from start of TH to achievement of target temperature was 205.0 ± 182.2 minutes. The adverse events are shown in Table 4. Hypokalemia was the most frequent adverse event in the cooling phase, followed by hypotension and hyperglycemia; hypotension was the most common adverse event in the rewarming phase. The other adverse events in the intensive care unit were sepsis in 3 cases and pneumonia in 11 cases. On the other hand, in the 564 patients who had cardiac arrest from cardiac causes, hyperglycemia was the most frequent adverse event in the cooling phase, and the most common adverse event in the rewarming phase was hypotension. Of the 24 patients who were treated with TH after OHCA caused by self-inflicted intoxication, 11 patients (46%) survived to discharge; of these cases, the causative agents were 8 of 13 for pesticides and 3 of 8 for pharmaceuticals. Five of the 24 patients had good neurologic outcomes; of
Time from ROSC to start of TH, min Time from start of TH to achieve target temperature, min Duration of maintenance, min Duration of rewarming, min
183.2 ± 153.0 205.0 ± 182.2 1482.6 ± 504.3 716.2 ± 363.6
these patients, acute intoxication was due to pesticides in 3 and pharmaceuticals (psychotropic medications) in 2 patients, respectively. 4. Discussion To our knowledge, this is the first study about TH after OHCA caused by self-inflicted intoxication. Therapeutic hypothermia has become the standard of care for comatose ventricular fibrillation or pulseless ventricular tachycardia arrest patients. In addition, TH is recommended for comatose adults who have been resuscitated from OHCA caused by nonshockable rhythms or inhospital cardiac arrest (class IIb) patients. In the latter patients, the role of TH is uncertain, especially if the cardiac arrest is due primarily to noncardiac causes, such as drug overdose. In previous studies of noncardiac OHCA etiology, poisoning accounted for approximately 10% of cases in developed countries [10-12]. According to Park et al [5], OHCA caused by self-inflicted intoxication was documented in 900 (4.4%) of 20 536 cases of OHCA of noncardiac etiology from 2006 to 2008 in Korea. In our study, 27 patients were classified as cardiac arrest caused by self-inflicted intoxication, which accounted for 7.3% of patients with cardiac arrest of noncardiac origin. Of patients with TH after OHCA caused by self-inflicted intoxication, pesticides (54%) were the most common cause of OHCA. These findings (54%) are consistent with Park et al (49.3%) [5]. Among our cases, there was no shockable rhythm in the first monitoring after ROSC, and time from collapse to ROSC was 35.4 ± 18.7 minutes. This result is similar to Oddo et al [13], who reported a collapse to ROSC interval of 34.6 ± 11.9 minutes in nonshockable cases. There is no definitive research on the relationship between collapse to ROSC interval and favorable neurologic outcome in cases of nonshockable cardiac arrest. Bernard et al [14] found that the probability of favorable neurologic outcomes drops by 14% for every 1.5 minutes of
Table 2 Characteristics of OHCA caused by self-inflicted intoxication for patients who underwent TH No.
Sex
Age
Agent
Witnessed
Bystander CPR
Initial rhythm
Anoxic time
TH methods
Discharge CPC
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
M M M F F F M M F M M F F M M F F M F F M F M M
66 38 57 45 70 44 58 52 48 45 47 45 82 71 53 49 75 51 76 40 62 71 54 74
Carbamate Carbamate Glyphosate Organophosphate Organophosphate Carbamate Sulfosate Poisonous plant Psychotropic Organophosphate Cardiovascular Antihistamine Psychotropic Organophosphate Carbamate Carbamate Psychotropic Organophosphate Household products Psychotropic Household products Psychotropic Carbamate Cardiovascular
No No Yes Yes Yes No No Yes No Yes Yes No No No Yes Yes No No No Yes No No Yes Yes
No No No No No No No No No No No Yes No No No No No No No Yes No No No No
Asystole Asystole PEA PEA Asystole Asystole Asystole Asystole Asystole Asystole Asystole Asystole PEA PEA Asystole Asystole Asystole Asystole Asystole Asystole Asystole PEA Asystole Asystole
49 63 23 50 20 70 14 15 68 15 31 41 11 70 20 40 50 25 45 27 48 4 30 54
Blanket Endovascular Blanket Endovascular Blanket Blanket Blanket Blanket Endovascular Blanket Garment Endovascular Endovascular Blanket Blanket Blanket Hydrogel pad Garment Endovascular Endovascular Hydrogel pad Hydrogel pad Endovascular Hydrogel pad
5 5 1 4 4 5 4 5 5 1 4 5 1 5 4 1 5 5 5 5 5 2 4 5
H.J. Kim et al. / American Journal of Emergency Medicine 32 (2014) 1378–1381 Table 4 Number and frequency of adverse events in OHCA caused by self-inflicted intoxication for patients who underwent TH n = 24 Cooling phase
Rewarming phase
Critical care phase
Overcooling Bradycardia Tachycardia Hypokalemia Hyperglycemia Bleeding Hypotension Hyperthermia Arrhythmia Hypokalemia Hypoglycemia Bleeding Hypotension Sepsis Pneumonia
1 (4.2) 3 (12.5) 1 (4.2) 13 (54.2) 8 (33.3) 1 (4.2) 11 (45.8) 2 (8.3) 0 (0.0) 1 (4.2) 1 (4.2) 1 (4.2) 6 (25.0) 3 (12.5) 11 (45.8)
the collapse to ROSC interval in cases of shockable cardiac arrest; the probability of a good neurologic outcome in patients with OHCA caused by self-inflicted intoxication is very low. In our study, patients with good neurologic outcomes represented 5 of the 24 patients. The collapse to ROSC interval of these patients was a median of 15 minutes (range, 4-40 minutes). The role of TH is uncertain when cardiac arrest is primarily due to a noncardiac cause, such as acute intoxication. However, TH is likely to be helpful for cerebral metabolic and edema changes and in patients with anoxic brain injury after nonshockable cardiac arrest. In animal studies, the beneficial effects of TH on neurologic recovery have been observed primarily after asphyxiation-induced PEA or asystolic cardiac arrest [15,16]. In this study, of 24 patients treated with TH after OHCA caused by acute intoxication, 11 patients (46%) survived to discharge, and 5 patients (21%) had good neurologic function at the time of hospital discharge. These results were superior to those of Dumas et al [17], where 15% (38/261) of the cases of nonshockable cardiac arrest were treated with post-ROSC cooling and resulted in favorable neurologic outcomes. In addition, compared with Park et al, our survival-to-discharge discharge rate was higher: 46% vs 3.6%, respectively [5]. In both Park et al and our study, OHCA resulted from similar causative agents in the same geographic region, and thus, it may be said that TH improves the survival-to-discharge rate. In a study by Soga et al [18], a rate of 32% in good neurologic function was reported among the nonshockable cardiac arrest cases with TH. We think that this good neurologic outcome was found because study was witnessed OHCA [18]. Comparing with patients who had cardiac arrest from cardiac causes in Korean Hypothermia Network registry, greatest differences in the resuscitation characteristics are the first monitored rhythm (shockable rhythm: n = 180, 31.9%) and witness (n = 428, 75.9%) and bystander cardiopulmonary resuscitation (CPR) (n = 195, 34.6%). Of 564 patients treated with TH after OHCA caused by cardiac cause, 394 patients (70%) survived to discharge, and 221 patients (39%) had good neurologic function at the time of hospital discharge. Pesticides showed very high survival-to-discharge rates. According to a report by Gordon et al [19], hypothermia increases the median lethal dose of ethanol, heavy metals, methyl-mercury, and pesticides despite decreasing drug clearance in animals. Hypothermia increases the median lethal dose, which may be one of the reasons for the high survival-to-discharge rates. Finally, the effects of TH after OHCA caused by self-inflicted intoxication still have not been demonstrated. However, TH will become more widely used in the management of anoxic neurologic injury regardless of the presenting cardiac rhythm and cause of OHCA [20,21]. Further
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high-quality randomized clinical trials would confirm the actual benefit of TH caused by acute intoxication. The limitations of this study are as follows. First, the study population was only composed of patients who received treatment for hypothermia and, therefore, did not verify the availability of TH. Second, data in this study did not include specific treatments for intoxication, such as antidote therapy or gastrointestinal decontamination. This incomplete information may bias the results. Third, although this study was a multicenter retrospective registry-based study, the number of patients was relatively small. 5. Conclusions Based on this study of OHCA patients with self-inflicted intoxication who received TH, 11 patients (46%) survived to discharge, and good neurologic outcomes occurred in 5 (21%) of the 24 patients. Pesticides showed very high survival-to-discharge rates. However, the results of this study are insufficient to explain the benefits of TH for OHCA patients with self-inflicted intoxication. Thus, future studies are needed for further clinical investigation of the potential efficacy of TH in such patients. References [1] Hawton K, van Heeringen K. Suicide. Lancet 2009;373:1372–81. [2] Värnik P. Suicide in the world. Int J Environ Res Public Health 2012;9:760–71. [3] Statistics Korea. Annual report on the cause of death statistics. http://kostat.go.kr/ portal/korea/index.action. [Accessed December 30, 2013]. [4] Ajdacic-Gross V, Weiss MG, Ring M, et al. Methods of suicide: international suicide patterns derived from the WHO mortality database. Bull World Health Organ 2008;86:726–32. [5] Park JH, Shin SD, Song KJ, Park CB, Ro YS, Kwak YH. Epidemiology and outcomes of poisoning-induced out-of-hospital cardiac arrest. Resuscitation 2012;83:51–7. [6] Peberdy MA, Callaway CW, Neumar RW, et al. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S768–86. [7] Mumma BE, Shellenbarger D, Callaway CW, Katz KD, Guyette FX, Rittenberger JC. Neurologic recovery following cardiac arrest due to benzodiazepine and opiate toxicity. Resuscitation 2009;80:1446–7. [8] Lee HY, Lee BK, Jeung KW, Lee GS, Jung YH, Jeong IS. A case of near-fatal fenpyroximate intoxication: the role of percutaneous cardiopulmonary support and therapeutic hypothermia. Clin Toxicol 2012;50:858–61. [9] Booth CM, Boone RH, Tomlinson G, Detsky AS. Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest. JAMA 2004;291:870–9. [10] Kuisma M, Määttä T. Out-of-hospital cardiac arrests in Helsinki: Utstein style reporting. Heart 1996;76:18–23. [11] Engdahl J, Bång A, Karlson BW, Lindqvist J, Herlitz J. 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[21] Shin J, Lee H, Kim J, et al. Outcomes of hanging-induced cardiac arrest patients who underwent therapeutic hypothermia: a multicenter retrospective cohort study. Resuscitation 2014. http://dx.doi.org/10.1016/j.resuscitation.2014.04.012 [S03009572(14)00494-8. [Epub ahead of print]].
