ORIGINAL ARTICLE Nephrology http://dx.doi.org/10.3346/jkms.2013.28.8.1194 • J Korean Med Sci 2013; 28: 1194-1199 Incidence, Etiology, and Outcomes of Rhabdomyolysis in a Single Tertiary Referral Center Jae-Seok Park, Min-Sook Seo, We have encountered numerous cases of rhabdomyolysis associated with acute pesticide Hyo-Wook Gil, Jong-Oh Yang, intoxication; however, the cause, incidence, and treatment outcomes of rhabdomyolysis Eun-Young Lee, and Sae-Yong Hong have not been studied. The current study involved 2,125 patients hospitalized with acute chemical poisoning. Based on clinical and laboratory parameters and treatment outcomes, Department of Internal Medicine, Soonchunhyang we found that overall incidence of rhabdomyolysis in our hospital was 0.06% (93 of University, College of Medicine, Cheonan, Korea 143,830 patients admitted), but the incidence associated with acute pesticide intoxication Received: 25 March 2013 was 1.8% (33 of 1,793 cases). The incidence of rhabdomyolysis after pesticide intoxication Accepted: 14 May 2013 was significantly higher in men than in women (P = 0.010). The amount of pesticide ingested was significantly higher in rhabdomyolysis patients than that in those who did Address for Correspondence: Sae-Yong Hong, MD not develop rhabdomyolysis (mean ± SD, 114.1 ± 79.5 mL vs 74.1 ± 94.2 mL, P = 0.010). Department of Internal Medicine, Soonchunhyang University Our results show that pesticide intoxication is a frequent cause of rhabdomyolysis and is Cheonan Hospital, Soonchunhyang-6-gil, Dongnam-gu, Cheonan 330–721, Korea more common among men than women. The volume of pesticide ingested, and not the Tel: +82.41-570-3682, Fax: +82.41-574-5762 degree of human toxicity, is the main factor influencing the incidence of rhabdomyolysis. E–mail: [email protected] The work was carried out by the support of the “Cooperative Key Words: Acute Kidney Injury; Intoxication; Pesticides; Rhabdomyolysis; Surfactant Research Program for Agriculture Science & Technology Development (Project No. PJ008246)”, under the auspices of the Rural Development Administration, Republic of Korea. INTRODUCTION MATERIALS AND METHODS Various causes of rhabdomyolysis have been described, such as Study design and data collection exertion, crush injuries, ischemia, metabolic disorders, abnor- This cross-sectional study was performed by reviewing the mal body temperatures, infection, autoimmune muscle dam- medical records of rhabdomyolysis patients admitted to the age, and drugs and/or toxins (1). Among the drugs known to Department of Nephrotoxicology, Soonchunhyang Cheonan induce rhabdomyolysis, the most common examples are Hospital, Korea, between July 2006 and June 2011 (Fig. 1). The statins (2) and fibrates (3). Antipsychotic medications (4) and parent population included all patients admitted during the in- neuromuscular blocking agents (5) are also known to cause vestigation period. We screened patients with rhabdomyolysis rhabdomyolysis. In addition, substance abuse (6, 7) including on the basis of the current consensus definition of rhabdomy- alcohol, amphetamine, cocaine, heroin, and ketamine may in- olysis (creatine kinase [CK] level higher than 1,000 U/L), using duce the condition. Poisons linked to rhabdomyolysis include an order communication system and electronic medical re- heavy metals (8) and venoms from insects or snakes (9, 10). cords. We documented patient age, sex, hospitalization period, Acute pesticide intoxication, a method commonly used by the amount of pesticide ingested, the active toxic compounds, people commiting suicide, is unique in that a specific toxic sub- the time lag to hospital admission, and laboratory findings. We stance may be associated with the development of rhabdomy- also scored acute renal failure (ARF) and mortality to assess the olysis (11-14). We have encountered many patients with rhab- complications and outcomes of rhabdomyolysis. domyolysis associated with acute pesticide intoxication at our hospital, accounting for approximately 500 cases per year (15, Definition of ARF 16). The current study was designed to assess the etiology, inci- ARF was diagnosed according to the Risk, Injury, Failure, Loss, dence, and treatment outcomes of rhabdomyolysis at our hos- and End-Stage Renal Disease criteria for ARF (17). In brief, ARF pital over a 5-yr period. was diagnosed when the serum creatinine level increased 3 © 2013 The Korean Academy of Medical Sciences. pISSN 1011-8934 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. eISSN 1598-6357 Park J-S, et al. • Incidence and Etiology of Rhabdomyolysis Study population Total admission (143,830) Rhabdomyolysis (93) Group Chemical-induced group (54) Non-chemical group (39) Class Pesticide (33) Medicine (6) Other chemicals (15) Physical (29) Non-physical (10) Herb (1) Fungicide (2) Antihistamine (3) Immobilization (16) Infection (3) Surfactant (2) Herbicide (16) CNS-acting (3) Over-activity (9) Metabolic (7) Subclass Alcohol (11) Insecticide (15) Traume (4) Unknown (1) Fig. 1. Causes of rhabdomyolysis in the current study. The numbers of cases are shown in parentheses. CNS, central nervous system. times that of the lowest level during the observation period ret- used the Kruskal-Wallis test. Statistical analyses were per- rospectively, when the glomerular filtration rate decreased formed using SPSS software, version 14.0 (SPSS, Chicago, IL, > 75% of the lowest level during the admission, when the se- USA). P values less than 0.05 were considered statistically sig- rum creatinine level increased over 4 mg/dL without a history nificant. Because of the limited sample size, laboratory mea- of renal disease, when there was an acute rise of serum creati- surements of muscle enzyme levels were compared among the nine ≥ 0.5 mg/dL, and when the urine output decreased to pesticide, chemical (other than pesticide), and physical classes. < 0.3 mL/[kg.h], or if anuria persisted for > 12 hr. Ethics statement Causes of rhabdomyolysis The study protocol and design were reviewed and approved by Patients were divided into 2 groups based on the cause of rhab- the institutional review board (IRB) of Soonchunhyang Univer- domyolysis (the chemical-induced group and the non-chemi- sity Cheonan Hospital (IRB approval number: 2013-38). In- cal group). The chemical-induced group was further divided formed consent was not obtained because of retrospective de- into 3 classes based on the type of chemical agent (pesticide, sign of the study. medicine, and other chemicals) (Fig. 1). The pesticide class was further divided into 3 subclasses (fungicides, herbicides, and RESULTS insecticides). The medicine class, which included cases of acute overdose rather than actual intoxication, was categorized into 5 The overall incidence of rhabdomyolysis in our hospital was subclasses according to the World Health Organization Ana- 0.06% (93 cases of 143,830 total admissions) (Fig. 1), whereas tomical Therapeutic Chemical Classification System, as follows: the incidence of rhabdomyolysis in patients with acute pesti- analgesics (N02 and M01), antihistamines (D04), central ner- cide intoxication was much higher (1.8% [33 of 1,793 cases]) vous system (CNS)–acting agents (N03, N05, and N06), mixed (Table 1). The frequency of rhabdomyolysis caused by different medications, and others. For all pesticides, the amount ingest- active ingredients varied (Tables 2 and 3). Not all pesticides that ed was estimated based on the number of swallows (1 mouth- may cause severe human toxicity triggered rhabdomyolysis. For ful was equivalent to 20 mL). The non-chemical group was cat- example, among the 1,420 patients with acute paraquat intoxi- egorized into physical and non-physical subclasses (Fig. 1). cation, none had rhabdomyolysis. In contrast, the frequency of rhabdomyolysis was high in patients poisoned with certain Statistical analysis pesticides, as shown in Table 3. Continuous variables are shown as the mean ± SD, with or The incidence of rhabdomyolysis associated with pesticides without the median value and range, and categorical variables was significantly higher among men than that among women are shown as the frequency (the number of cases and percent- (Table 4). However, this sex difference was not observed for the age). The differences between groups were analyzed using Stu- other classes of chemicals. The amount of pesticide ingested dent’s t-test or the Mann-Whitney U test for continuous vari- was significantly higher among rhabdomyolysis patients than ables and the chi-square test or Fisher’s exact test for categori- among non-rhabdomyolysis patients (mean ± SD, 114.1 ± 79.5 cal variables. To analyze the differences among > 3 groups, we mL vs 74.1 ± 94.2 mL, P = 0.010); however, among the rhabdo- http://dx.doi.org/10.3346/jkms.2013.28.8.1194 http://jkms.org 1195 Park J-S, et al. • Incidence and Etiology of Rhabdomyolysis Table 1. Demographic characteristics of patients in the chemical-induced group Table 3. Frequency of rhabdomyolysis and WHO toxicity of pesticides Class of Cases Cases Mean Sex Frequency Active toxic compound Cases (No)* WHO toxicity† Subclass chemicals (No.)* (No.)* age (yr) (M/F) High Tebuconazole 1/1 III Pesticide 33/1,793 Paraquat 0/1,420 51.0 852/568 Mixture of carpropamid and edifenphos 1/1 U and Ib Fungicide 2/16 45.5