Article, Forensic Medicine

Cyanide poisoning is a possible cause of cardiac arrest among fire victims, and empiric antidote treatment may improve outcomes

a b s t r a c t

Background: Carbon monoxide and Cyanide poisoning are important causes of death due to fire. Carbon monox- ide is more regularly assessed than cyanide at the site of burn or smoke inhalation treatment due to its ease in assessment and simplicity to treat. Although several forensic studies have demonstrated the significance of cya- nide poisoning in fire victims using Blood cyanide levels, the association between the cause of cardiac arrest and the concentration of cyanide among fire victims has not been sufficiently investigated. This study aimed to inves- tigate the frequency of cyanide-induced cardiac arrest in fire victims and to assess the necessity of early Empiric treatment for cyanide poisoning.

Methods: This study was a retrospective analysis of fire victims with cardiac arrest at the scene who were transported to a trauma and critical care center, Kyorin University Hospital, from January 2014 to June 2017. Pa- tients whose concentration of cyanide was measured were included.

Results: Five patients were included in the study; all died despite cardiopulmonary resuscitation. Three of these victims were later found to have lethal cyanide levels (N3 ug/ml). Two of the patients had non-lethal Carboxyhemoglobin levels under 50% and might have been saved if hydroxocobalamin had been administered during resuscitation.

Conclusion: According to our results, cyanide-induced cardiac arrest may be more frequently present among fire victims than previously believed, and early empiric treatment with hydroxocobalamin may improve outcomes for these victims in cases where cardiac arrest is of short duration.

(C) 2018

Introduction

Among fire victims, exposure to toxic fumes has been well established as a cause of death [1]; carbon monoxide (CO) and cyanide are regarded as the primary toxic constituents of these fumes [2]. CO has been more regularly assessed than cyanide in clinical settings because the concentration of carboxyhemoglobin (COHb) can be measured quickly and easily using blood gas analysis. In contrast, the concentra- tion of cyanide has not been estimated because the result cannot be im- mediately obtained in most hospitals.

Cyanide is formed during the incomplete combustion of nitrogen- containing materials, such as wool, silk, polyurethane foam, and mela- mine [3]. These materials are increasingly being used in homes [4]. As

? Source(s) of support in the form of (including grant numbers): None.

?? The name of organization and date of assembly if the article has been presented: None.

* Corresponding author at: Department of Trauma and Critical Care Medicine, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka, Tokyo 181-8611, Japan.

E-mail address: [email protected] (Y. Kaita).

a result, there is an increasing possibility that fire victims are exposed to cyanide. Forensic studies suggest that cyanide contributes to the cause of death among fire victims [5-8]. However, forensic reports may underestimate the clinical importance of cyanide toxicity as cya- nide is quickly eliminated in the blood following death [2]. A few clinical reports have demonstrated the importance of cyanide toxicity in smoke inhalation [9]. However, overall, the association between cyanide- induced cardiac arrest and the concentration of cyanide among fire vic- tims has not been sufficiently investigated.

In this study, we investigated the frequency of cyanide-induced car-

diac arrest among fire victims and assessed the possibility of early em- piric treatment for cyanide poisoning.

Methods

We retrospectively investigated nine out-of-hospital cardiac arrest patients due to fire who were transported to a trauma and critical care center, Kyorin University Hospital, from January 2014 to June 2017. Pa- tients whose cyanide concentrations were measured were included in the study. Four patients who had full body burns and were thought to

https://doi.org/10.1016/j.ajem.2018.01.054

0735-6757/(C) 2018

852 Y. Kaita et al. / American Journal of Emergency Medicine 36 (2018) 851853

be unable to resuscitate were excluded. Characteristics of patients, cya- nide concentrations, and the data from blood gas analysis were collect- ed from medical records and analyzed. For the measurement of cyanide concentrations, blood samples were collected in tubes with ethylene tetraAcetic acid (EDTA)-2 K and stored at 4 ?C. Blood cyanide levels were determined by Gas Chromatogrphy (GC-2010 Plus, Shimadzu, Kyoto, Japan). For cases 1 to 3, since the patients were transported to our hospital during the daytime, the blood cyanide levels were mea- sured within several hours. Cases 4 and 5 were transported in the night- time, and storage time before measurements was 8 to10 hours. COHb levels were measured by blood gas analysis (ABL800 FLEX, Radiometer, Copenhagen, Denmark).

Results

Five patients were included in the study. Clinical characteristics are displayed in Table 1. There were 3 men and 2 women included in this study, with ages ranging from 56 to 79 years old. Fires in 3 cases oc- curred in houses and fires in the other cases occurred in apartments. The time interval from the initial call for help to arrival at the hospital ranged from 35 to 64 min. All cases exhibited cardiac arrest on arrival, and all initial cardiac rhythms were asystolic. Of these cases, the return of spontaneous circulation (ROSC) was achieved in one case. Despite cardiopulmonary resuscitation, all cases died in the emergency room. No patients received a cyanide antidote. Blood specimens were collect- ed after arrival, and examination results are displayed in Table 1. Among all patients, 4 (80%) had cyanide levels above 0.5 ug/ml, which indicated significant cyanide exposure, and concentrations above 3 ug/ml (sug- gesting a lethal dose) were found in 3 cases. In the analysis of COHb, the median concentration of COHb was 59.1%. Concentrations above 50% (suggesting a lethal dose) were found in only 3 cases. Two of the 3 patients who had an above lethal dose of cyanide had COHb levels under 50%.

Discussion

This study provided two important clinical suggestions. Cyanide- induced cardiac arrest might be more frequently present than expected, and early empiric treatment with antidotes such as hydroxocobalamin may improve the outcomes of these victims.

In this report, four of the five patients had toxic cyanide levels, and three had a lethal concentration. Furthermore, two patients had levels of COHb under 50; thus, their cause of cardiac arrest might have been cyanide poisoning rather than CO. Several studies have reported on the importance of cyanide toxicity, primarily in forensic medicine. Stamyr et al. reported that 257 (31%) of 824 fire victims had toxic cya- nide levels, and 33 (4%) of these victims had lethal levels [5]. Yeoh and Braitberg reported that 48 (35%) of 173 victims were found to have cyanide poisoning, and 11 (8%) of these victims had lethal cyanide levels [6]. Stoll et al. demonstrated that 23 (51%) of 45 victims in enclosed-space fires had toxic cyanide levels [7]. In this report, 6

(13%) of these victims had lethal concentrations of cyanide, and three of these victims had COHb levels under 50%. In Japan, Moriya and Hasimoto demonstrated that 19 (53%) of 36 forensic samples were found to have cyanide poisoning [8]. These forensic reports on the fre- quency of cyanide toxicity have discrepancies and may be underestimated as the blood samples were obtained from fire victims several hours after the fire, and cyanide is known to disappear rapidly from blood. In a clinical study, Borron et al. reported that 67% of smoke inhalation injury victims without major burns had toxic cyanide levels [9]. Furthermore, in this report, blood cyanide concentrations were higher among cardiac arrest patients than patients without cardiac arrest, while there was no difference in CO concentrations. Therefore, cyanide-induced cardiac arrest might be more frequently present in smoke inhalation injuries without major burns.

Early empiric treatment with hydroxocobalamin may improve car- diac arrest outcomes in fire victims. In this report, no patients received any antidotes for cyanide, although 3 patients possibly died due to cya- nide poisoning afterwards. The time delay to the administration of a cy- anide antidote is thought to have a significant impact on outcomes [10]. Bebarta et al. demonstrated that hydroxocobalamin and epinephrine were equally effective in improving survival in swine models of cyanide-induced cardiac arrest [11]. In this study, hydroxocobalamin was also found to improve blood pressure and pH and to decrease blood lactate and cyanide levels compared with epinephrine [11]. Dinh and Rosini suggested that empiric treatment may be useful for cy- anide toxicity in enclosed-space fire survivors [12]. Fortin et al. reported that 31 of 61 cardiac arrest fire victims had spontaneous Cardiac activity after the administration of hydroxocobalamin and that five of these vic- tims survived without any sequelae [13]. Moreover, Thompson and Marrs suggested that hydroxocobalamin was free from serious adverse effects even if the fire victims did not have cyanide poisoning [14]. In the present report, the two victims who were regarded as having cyanide poisoning might have survived better outcomes if hydroxocobalamin had been administered. Generally speaking, in cases where cardiac ar- rest is of short duration, ROSC and potential survivability would likely be enhanced by administration of cyanide antidotes, such as hydroxocobalamin.

In Japan, there are few reports on the use of hydroxocobalamin for burn or smoke inhalation treatment, and hydroxocobalamin is not pro- vided for emergency services. Moreover, concentrations of cyanide are not usually measured in clinical situations. If cyanide-induced cardiac arrest is more frequently present, hydroxocobalamin is worth consider- ing for fire victims. In France, physician-led ambulance teams can ad- ministrate cyanide antidotes to patients at the scene of fires. Given that the antidote should be administered as soon as possible if deemed necessary, this treatment at the scene should also be considered for Japan in the future.

The primary limitation of this study is the small sample size. Further reports should be collected to investigate whether cyanide-induced car- diac arrest is more frequently present and whether antidote use may improve outcomes of cyanide-induced cardiac arrest.

Table 1

Clinical characteristics and blood cyanide and Carboxyhemoglobin levels

Patient

Age (years)

Sex

Scene

Time to arrival (min)

Initial ECG

ROSCa

Outcome

Cyanide (ug/ml)

COHbb (%)

1

57

F

House

59

Asystole

n

Died

13.08

59.1

2

56

M

Apartment

35

Asystole

n

Died

6.62

42.7

3

79

M

House

35

Asystole

n

Died

3.86

30.2

4

60

F

Apartment

56

Asystole

y

Died

1.28

72.8

5

61

M

House

64

Asystole

n

Died

0.28

66.7

Median (IQRc)

60

(57-61)

56

(35-59)

3.86

(1.28-6.62)

59.1

(42.7-66.7)

a Return of spontaneous circulation.

b Carboxyhemoglobin.

c Interquartile range.

Y. Kaita et al. / American Journal of Emergency Medicine 36 (2018) 851853 853

In conclusion, cyanide-induced cardiac arrest is potentially more fre- quently present among fire victims than previously believed, and early empiric treatment with hydroxocobalamin may improve outcomes in cases where cardiac arrest is of short duration.

Ethics approval and consent to participate

The prospective observational case-series study was approved by the Local Ethical Committee of Kyorin university hospital in Tokyo.

Competing interests

The authors declare that they have no competing interests.

Funding

This research did not receive any specific grant from funding agen- cies in the public, commercial, or not-for-profit sectors.

Acknowledgements

We thank Mr. Hiroyuki Miyagi, clinical lab technician in Kyorin Uni- versity Hospital, for his excellent technical assistance in measuring cya- nide concentrations.

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