Emergency. 2018; 6 (1): e56 BR I E F RE P O RT Rhabdomyolysis and Acute Poisoning; a Brief Report Abdolkarim Pajoumand1,2, Farshid Fahim3,4∗, Meisam Akhlaghdoust5, Nasim Zamani1,2, Zeinab Amirfirooz6, Mahnaz Dehdehasti6 1. Toxicological Research Center, Department of Clinical Toxicology, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Excellence Center of Clinical Toxicology, Iranian Ministry of Health, Tehran, Iran. 3. Amir-al-Momenin Hospital, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran. 4. Department of Clinical Toxicology, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5. Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran. 6. Loghman-Hakim Hospital Poison Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Received: March 2018; Accepted: August 2018; Published online: 26 September 2018 Abstract: Introduction: Some studies have reported creatinine phosphokinase (CPK) as a new emerging way in predicting the outcomes of poisoned patients. This study aimed to evaluate the association of serum CPK level in the first 24 hours with outcomes of poisoned patients. Methods: This retrospective cross-sectional study was performed using the medical profiles of poisoned patients aged between 13 and 70 years old who were referred to the emergency department of a big referral medical toxicology center during 6 years and whose necessary data for this study was available. Results: 318 patients with the mean age of 34.9±14.5 years were studied (77.1% male). The mean serum CPK level of patients was 4693.1 ± 10303.8 (35–89480) IU/L. There was no significant correlation between serum CPK level and cause of poisoning (r= 0.16; p=0.51), age (r = -0.021; p = 0.651), sex (r = 0.131; p = 0.281), seizure (r = -0.022; p = 0.193), level of consciences (r = -0.138; p = 0.167), and duration of hospital stay (r= 0.242, p = 0.437). The mean serum CPK level was significantly higher in ICU admitted (p<0.0001), AKI (p<0.0001), hyperkalemia (p<0.0001), hypophosphatemia (p=0.045), and hypocalcaemia (p=0.008) cases. The best cut off point of serum CPK level in predicting acute kidney injury (AKI) was estimated to be 10000 IU/L (sensitivity = 83.8% and specificity = 68.8%). Conclusion: It seems that CPK could be considered as a candidate tool for screening the intoxicated patients in need for ICU admission and at risk for AKI. Keywords: Poisoning; creatine kinase; rhabdomyolysis; patient outcome assessment © Copyright (2018) Shahid Beheshti University of Medical Sciences Cite this article as: Pajoumand A, Fahim F, Akhlaghdoust M, Zamani N, Amirfirooz Z, Dehdehasti M. Rhabdomyolysis and Acute Poisoning; a Brief Report. 2018; 6(1): e56. 1. Introduction Acute poisoning is a major and common cause of mortal- ity worldwide, especially in developing and low income countries (1). Based on World Health Organization (WHO) reports, poisoning is responsible for 45000 deaths per year in people younger than twenty years old (available on: http://www.who.int/violence_injury_prevention/child/injur y/world_report/Poisoning_english.pdf ). Developing out- come prediction tools for screening and disposition of these ∗Corresponding Author: Farshid Fahim; Amir-al-Momenin Hospital, Nazi Abad, Tehran, Iran. Email: drfahim909@gmail.com Tel: 009821 5534 6262. patients is one of the interesting fields of research. Some studies have reported that serum creatine phosphokinase (CPK) level may become a newly emerging way in prediction of poisoning severity and outcome (1-4). It has been shown that CPK more than 10000 IU/L in poisoned patients could be associated with more complications (3, 5). CPK increase occurs in acute muscle necrosis and rhabdomyolysis. There are some possible mechanisms for increase of serum CPK in poisoning patients (6, 7). Toxic serum level of any drug, muscle necrosis following substance overdose, seizure and serotonergic and neuroleptic syndromes may be possible causes of increase in the CPK level in poisoned patients (8, 9). This study aimed to evaluate the association of serum CPK level in the first 24 hours with outcomes of poisoned patients. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com A. Pajoumand et al. 2 2. Methods 2.1. Study design and setting This retrospective cross-sectional study was performed on medical profiles of poisoning patients who were referred to emergency department (ED) of Loghman Hakim Educational Hospital, Tehran, Iran, between July 2011 and July 2017. Loghman Hakim Hospital is a big referral toxicology center in the Middle East. This study was approved by Research Ethics Committee of Shahid Beheshti University of Medical Sciences and Health Services. 2.2. Participants Using census sampling, patients who were at least 13 years old and were referred to the mentioned ED and whose nec- essary data for this study was available (e.g.: serum CPK level of the first 24 hours of admission) were evaluated. Patients with recent trauma, myocardial infarction (MI), cerebrovas- cular accident (CVA), cardiopulmonary resuscitation (CPR) or surgery in the past 6 months, pregnancy or lactation, renal or hepatic diseases, and history of substance or fitness drug use were excluded. Creatinine ≥ 1.8 mg/dl was considered as acute kidney injury (AKI). 2.3. Data gathering Data gathering was performed using a checklist that con- sisted of demographic variables, consciousness level based on Glasgow coma scale (GCS), history of hematuria and seizure, urinary output, serum CPK level, blood urea nitrogen (BUN), creatinine level in the first 24 hours of admission, and outcomes (disposition, need for dialysis, acute kidney injury (AKI), mortality, need for intubation and need for ICU admis- sion). A trained toxicology resident was responsible for gath- ering data from the patients’ profiles. 2.4. Statistical analysis Data were analyzed using IBM SPSS statistical software (Chicago, USA) version 22 and t- test and chi square tests. P< 0.05 was considered significant. Findings were presented us- ing mean ± standard deviation or frequency and percentage. Chi square, Fisher’s exact, and student t tests were used for comparisons. Area under the receiver operating characteris- tic (ROC) curve was used for estimating the best cutoff point of serum CPK in predicting the occurrence of AKI. 3. Results: 3.1. Baseline characteristics 318 patients with the mean age of 34.9±14.5 (13-85) years were studied (77.1% male). Baseline characteristics of partic- Table 1: Baseline characteristics of studied patients Variable Values Sex Female 72 (22.9) Male 243 (77.1) Age group (year) < 18 19 (6.0) 18 - 35 163 (51.4) 35- 60 102 (32.2) ≥60 33 (10.4) Seizure Yes 51 (18.7) No 222 (81.3) Hematuria Yes 2 (0.8) No 260 (99.2) GCS Mild (14- 15) 56 (21.0) Moderate (9- 13) 102 (38.4 ) Severe (3- 8) 105 (39.6 ) Vital signs Systolic blood pressure (mmHg) 107.67 ± 21.50 Pulse rate (/minute) 97 ± 26 Respiration rate (/minute) 19 ± 4 Oxygen Saturation (%) 88.6 ± 12.3 Urinary Output (ml) 1s t day 1856.9 ± 1533.9 2n d day 2832.2 ± 2462.1 3r d day 2941.4 ± 1768.7 4t h day 3316.4 ± 2009.6 Creatine phosphokinase (IU/L) <1000 150 (50.5) 1000- 5000 74 (24.9) 5000- 10000 36 (12.1) 10000-15000 12(4.0) 15000-20000 6 (2.4) >20000 19 (6.4) Data are presented as mean ± standard devia- tion or number (%). There is missing data in some variables. Table 2: Causes of poisoning in the studied patients Cause Number (%) Neuropsychiatric drugs 135 (42.4) Acetaminophen 70 (22.1) Alcohol 63 (19.8) Opium 29 (9.1) Carbone monoxide 7 (2.2) Other 14 (4.4) ipants are shown in table 1. The most important cause of poi- soning were benzodiazepines (24.6%) and acetaminophen (22.1%), respectively (table 2). Mean serum blood urea nitro- gen (BUN) and creatinine levels of the studied patients were 52.89 ± 46.1 mg/dl and 1.7 ± 1.2 mg/dl, respectively. Patients This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com 3 Emergency. 2018; 6 (1): e56 Figure 1: Area under the receiver operating characteristic (ROC) curve of serum creatine phosphokinase (CPK) level of poisoned pa- tients on the first day in predicting acute Kidney injury (p< 0.0001). were hospitalized for 12.74 ± 12.05 (1-72) days on average. The mean serum CPK level of studied patients was 4693.1 ± 10303.8 (35–89480) IU/L. There was no significant corre- lation between serum CPK level and cause of poisoning (r= 0.16; p=0.51), age (r = -0.021; p = 0.651), sex (r = 0.131; p = 0.281), seizure (r = -0.022; p = 0.193), level of consciences (r = -0.138; p = 0.167), and duration of hospital stay (r= 0.242, p = 0.437). 3.2. Outcomes 37 (11.6%) cases were admitted to intensive care unit (ICU), 83 (26.1%) died, and 198 (62.3%) were discharged from hos- pital. AKI was developed in 79 (26.5%) cases out of which 14 (17.7%) needed dialysis. Table 3 compares the mean serum CPK level of patients based on the studied outcomes. The mean serum CPK level was significantly higher in ICU ad- mitted (p<0.0001), AKI (p<0.0001), hyperkalemia (p<0.0001), hypophosphatemia (p=0.045), and hypocalcaemia (p=0.008) cases. Figure 1 shows the area under the ROC curve of first day serum CPK level in predicting AKI (AUC= 0.752, 95%CI: 0.688-0.815; p< 0.0001). The best cut off point of serum CPK level in this regard was estimated to be 10000 IU/L based on the ROC curve analysis (sensitivity = 83.8% and specificity = 68.8%). 4. Discussion Based on the results of the present study, there was a signif- icant correlation between serum CPK level of poisoned pa- tients and need for ICU admission and AKI development. The best CPK cut off point in predicting AKI was 10000 IU/L. There was no significant correlation between serum CPK level and age, sex, level of conciseness, seizure, need for intu- bation, duration of hospital stay, and mortality. Some of the patients that survive poisoning face mortality due to other side effects. Rhabdomyolysis and its side effects including AKI should be counted as common complications in these patients. If the definition of rhabdomyolysis is considered CPK level over 1000 IU/L, the prevalence of rhabdomyolysis in the patients studied in the present research will be about 50% and this emphasizes the necessity of paying attention to this matter. Mild and moderate rhabdomyolysis by itself is a curable and self-limiting problem but there is controversy regarding the level of CPK that is associated with nephrotox- icity and kidney failure. This level was estimated at 15000 IU/L and higher in patients with traumatic rhabdomyolysis following Bam earthquake (10-12). It seems that the cause of rhabdomyolysis affects the toxic level of this enzyme. What can be concluded from the findings of the present study is that poisoned patients with serum level of 10000 IU/L and higher are at a significant risk of nephrotoxicity and AKI due to it. Eizadi et al. (2012) study showed that higher levels of serum CPK level correlated with a higher risk of develop- ing complications, increased need for dialysis and mortality (13). Our findings were similar regarding the increasing risk of complication development such as AKI but we had differ- ent findings regarding the correlation of serum CPK levels and need for dialysis and mortality. Dadpour et al. (2017) showed that, about 80% of patients with serum CPK level > 10000 IU/L, were in need of dialysis (14). In the present study, there was no significant correlation between CPK level and need for dialysis. Only 22.2% of cases in need of dialysis had CPK > 10000 IU/L in this study. Nevertheless, it should be noted that rhabdomyolysis is not the sole cause of AKI in poi- soning patients and unlike traumatic rhabdomyolysis cases in which CPK nephrotoxicity could be considered the cause of AKI with higher confidence, here more caution should be taken while interpreting the findings. It seems that when fac- ing this type of patients, screening cases with a higher level of muscular enzymes, as well as considering other conditions, is a wise thing to do for referring them to more advanced cen- ters with better treatment equipment. 5. Limitations The limitation of this study was performing it in a retrospec- tive manner and having missing data. 6. Conclusion Based on the results of the present study, there was a signif- icant correlation between serum CPK level of poisoned pa- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com A. Pajoumand et al. 4 Table 3: Outcomes of studied patients and its relation with serum creatine phosphokinase (CPK) levels in the first 24 hours Outcome Number (%) CPK level P value Treated and discharged Yes 196 (61.6) 4296.8±9240.5 0.323 No 122 (38.4) 5636.4±10288.3 Intubation Yes 98 (30.8) 5385.8±9719.9 0.216 No 193 (66.2) 3975.7±8369.8 ICU admission Yes 37 (11.6) 21519.9±17582.8 <0.0001 No 281 (88.4) 2246.9±3798.9 Acute kidney injury Yes 76 (25.9) 11731.6±15406.2 <0.0001 No 217 (74.1) 2222.9±4274.5 Dialysis Yes 29 (9.1) 7968.1±12763.4 0.062 No 289 (90.9) 4338.2±9202.8 Mortality Yes 83 (26.1) 4524.9±9168.0 0.873 No 235 (73.9) 4732.5±9798.8 Hyperkalemia Yes 76 (23.9) 8930.3±14716.6 <0.0001 No 242 (76.1) 1796.7±5782.9 Hyperphosphatemia Yes 31 (27.4) 8663.2±13855.8 0.045 No 82 (72.6) 4036.7±9243.1 Hypocalcemia Yes 69 (56.6) 8170.3±12647.8 0.008 No 53 (43.4) 2797.1±7855.1 tients and need for ICU admission and AKI development. The best CPK cut off point in predicting the AKI was 10000 IU/L. There was no significant correlation between serum CPK level and age, sex, level of conciseness, seizure, need for intubation, duration of hospital stay, and mortality. 7. Appendix 7.1. Acknowledgements The authors would like to thank all those who have helped in this research. 7.2. Author contribution None. Abdolkarim Pajoumand: 0000-0002-5741-455X Farshid Fahim: 0000-0002-5064-1303 Meisam Akhlaghdoust: 0000-0003-0484-9098 Nasim Zamani: 0000-0002-2091-0197 Zeinab Amirfirooz: 0000-0002-7810-9415 Mahnaz Dehdehasti: 0000-0002-4770-3075 7.3. Conflict of interest The authors declare that there is no conflict of interest. 7.4. Funding None. References 1. Asadi R, Afshari R. Ten-year disease burden of acute poi- sonings in northeast Iran and estimations for national rates. Human & experimental toxicology. 2016;35(7):747- 59. 2. Stewart IJ, Faulk TI, Sosnov JA, Clemens MS, Elterman J, Ross JD, et al. 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Downloaded from: www.jemerg.com Introduction Methods Results: Discussion Limitations Conclusion Appendix References