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Outcomes of Elderly Patients with Organophosphate Intoxication

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Outcomes of Elderly Patients with Organophosphate Intoxication www.nature.com/scientificreports OPEN Outcomes of elderly patients with organophosphate intoxication 1 2 3 4 1 1 Jia‑Ruei Yu , Yi‑Chou Hou , Jen‑Fen Fu , I‑Kuan Wang , Ming‐Jen Chan , Chao‑Yu Chen , Cheng‑Hao Weng1, Wen‑Hung Huang1, Huang‑Yu Yang1, Ching‑Wei Hsu1 & Tzung‑Hai Yen1* This study analysed the clinical patterns and outcomes of elderly patients with organophosphate intoxication. A total of 71 elderly patients with organophosphate poisoning were seen between 2008 and 2017. Patients were stratifed into two subgroups: survivors (n = 57) or nonsurvivors (n = 14). Chlorpyrifos accounted for 33.8% of the cases, followed by methamidophos (12.7%) and mevinphos (11.3%). Mood, adjustment and psychotic disorder were noted in 39.4%, 33.8% and 2.8% of patients, respectively. All patients were treated with atropine and pralidoxime therapies. Acute cholinergic crisis developed in all cases (100.0%). The complications included respiratory failure (52.1%), aspiration pneumonia (50.7%), acute kidney injury (43.7%), severe consciousness disturbance (25.4%), shock (14.1%) and seizures (4.2%). Some patients also developed intermediate syndrome (15.5%) and delayed neuropathy (4.2%). The nonsurvivors sufered higher rates of hypotension (P < 0.001), shock (P < 0.001) and kidney injury (P = 0.001) than survivors did. Kaplan–Meier analysis indicated that patients with shock sufered lower cumulative survival than did patients without shock (log‑rank test, P < 0.001). In a multivariate‑Cox‑regression model, shock was a signifcant predictor of mortality after intoxication (odds ratio 18.182, 95% confdence interval 2.045–166.667, P = 0.009). The mortality rate was 19.7%. Acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 15.5%, and 4.2% of patients, respectively. Organophosphate intoxication is common in Asian populations because of easy access. In theory, the outcomes of organophosphate intoxication are split into three clear-cut clinical spectra, acute cholinergic crisis, intermediate syndrome and delayed neuropathy1. Acute cholinergic crisis arises rapidly following organophosphate exposure due to the acetylcholinesterase inhibition and the manifestations encompass muscarinic and nicotinic symptoms and signs2. Neuromuscular blockage and cerebral depression may develop and proceed to respiratory failure, consciousness disruption and mortality. Intermediate syndrome normally arises in 1–4 days, delayed neuropathy arises in 7–21 days, and both are characterized by neurologic impairment 3–6. Intermediate syndrome is diagnosed clinically by onset of muscular paralysis involving proximal limb muscles and muscles innervated by cranial nerves, occurring in conscious patients afer atropine treatment of cholinergic crisis 5. Delayed neuropathy is a sensory-motor peripheral neuropathy and is diagnosed clinically by distal motor weakness with sparing of neck, cranial nerves, and proximal muscles, or distal sensory symptoms, such as paresthesia or numbess6. Te intermediate syndrome presents with proximal muscle weakness and cranial nerve aberrations, while delayed polyneuropathy is exemplifed by stocking and glove distribution neuropathy and sensory defcit. Although the toxicity of organophosphate pesticides in the general population is well documented, there is still a paucity of studies that assess the outcomes of elderly patients with organophosphate intoxication. Table 1 summarizes published studies of organophosphate intoxication in elderly patients 7–14. Te mortality rates ranged between 12.9% and 22.9%. Te mean age of these studies was approximately 60 years. In a retrospective study of 42 patients with Class I organophosphate intoxication, Lee et al.7 reported four (9.5%) patients died of pneu- monia and acute respiratory distress syndrome. In another study of 26 patients with fenitrothion intoxication 8, two (7.7%) patients died of acute lung injury. In another retrospective study 9, 22 of 96 (22.9%) patients died. In another study of 131 patients10, 29 (22.1%) patients died. According to Cha et al. analysis11, 18 of 99 (18.2%) patients died afer admission. Furthermore, a 14.6% mortality rate was observed in Moon et al. investigation12. 1Department of Nephrology, Clinical Poison Center, Kidney Research Center, Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou, and Chang Gung University, 199 Tung Hwa North Road, Taipei, Taoyuan 105, Taiwan. 2Division of Nephrology, Department of Internal Medicine, Cardinal Tien Hospital, and School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan. 3Department of Medical Research, Chang Gung Memorial Hospital, Linkou, and Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan. 4Department of Nephrology, China Medical University Hospital, China Medical University, Taichung, Taiwan. *email: [email protected] Scientifc Reports | (2021) 11:11615 | https://doi.org/10.1038/s41598-021-91230-2 1 Vol.:(0123456789) www.nature.com/scientificreports/ Types of Hospitalization Year Study Hospital Area Sample size Time period organophosphates Age (year) length (day) Mortality rate (%) Chonnam National January 2005 to 2011 Lee et al. 7 Korea 42 Class I 60.5 (44.0–68.3) 18.0 (8.0–32.0) 9.5 University Hospital December 2010 Kawasaki Medical 2011 Matsuda et al. 8 Japan 26 Not mentioned Fenitrothion 62.4 ± 14.5 Not mentioned 7.7 School Hospital Samsung Chang- January 2007 to 2013 Lee et al. 9 Korea 96 Not mentioned 60.9 ± 17.1 Not mentioned 22.9 won Hospital February 2012 Samsung Chang- September 2006 to 2013 Kim et al. 10 Korea 131 Not mentioned 61.8 ± 16.3 Not mentioned 22.1 won Hospital December 2012 Class I (15.2%), II Wonju Severance March 2008 to 2014 Cha et al. 11 Korea 99 (39.4%), III (0.0%), 61.0 ± 17.0 10.0 (4.0–21.0) 18.2 Christian Hospital December 2013 U (45.5%) Chonnam National Class Ia (29.3%), Ib 2015 Moon et al. 12 University Medical Korea 198 2004 to 2014 (21.1%), II (30.8%), 61.0 ± 16.2 Not mentioned 14.6 School III (3.8%), U (3.8%) Class Ia (17.0%), Ib Chonnam National January 2011 to (31.0%), II (42.0%), 2018 Lee and Lee 13 Korea 100 61.0 (52.0–72.8) 14.0 (6.0–25.0) 19.0 University Hospital December 2015 III (0.0%), U (10.0%) Dimethyl subtype: dichlorvos (n = 10), phosphamidon (n = 14), methi- dathion (n = 4), Yonsei University March 2011 to fenthion (n = 2). 2018 Kwon et al. 14 Wonju College of Korea 62 60.0 ± 16.0 15.5 (8.0–29.5) 12.9 December 2016 Diethyl subtype: Medicine chlorpyrifos (n = 13), parathion (n = 1), diazinon (n = 2). Others: not mentioned Class Ia (16.9%), Ib Chang Gung 2021 Current study Taiwan 71 2008 to 2017 (19.7%), II (60.6%), 70.8 ± 7.7 20.4 ± 16.9 19.7 Memorial Hospital III (2.8%), U (0.0%) Table 1. Study of organophosphate intoxication in elderly patients (sample size more than 5). Age and hospitalization length are presented as the mean ± standard deviation or median with interquartile range. Pesticide toxicity was categorized as follows, according to World Health Organization recommendations: Ia extremely hazardous, Ib highly hazardous, II moderately hazardous, III slightly hazardous and U unlikely to present acute hazards42. In another study13, it was demonstrated that the in-hospital mortality rate was 19%, and nine patients died within 2 days of ingestion. Finally, in another study of 62 patients 14, pneumonia and multiple organ failure led to mortality in 8 (12.9%) patients. Some clinical studies15–18 reported that aging was a risk factor for mortality in organophosphate intoxication. For example, Liu et al.15 demonstrated that decreasing pH values (pH < 7.2) and increasing age (≥ 50 years) were associated with mortality in patients with organophosphate intoxication. Tis could be explained by poor health conditions in the elderly patients. In addition, some laboratory studies19,20 reported that aged animals were more sensitive to cholinergic (muscarinic) agonists. Tis may be associated with age-related changes in cholinergic neurochemical processes due to a reduction in muscarinic receptors with aging21. According to the National Development Council of Taiwan 22, Taiwan shall become a super-aged society in which at least 20% of the population is 65 or older by 2026. Acute pesticide intoxication is a common method of suicide globally 23. Elderly people are a sensitive group in terms of pesticide intoxication because many farm workers are elderly people rather than young people. Young people ofen tend to seek work in cities. Terefore, this study attempted to analyse the clinical patterns and outcomes of mortality in elderly patients with organo- phosphate intoxication. Results Table 2 outlines the baseline demographic data of 71 elderly patients with organophosphate poisoning, stratifed according to status at discharge as survivors (n = 57) or nonsurvivors (n = 14). Te patients were 70.8 ± 7.7 years old, and most patients were male (60.6%). Chlorpyrifos accounted for one-third of the cases (33.8%), followed by methamidophos (12.7%) and mevinphos (11.3%). Te majority of exposures occurred via the oral route (88.7%), but some occurred via the dermal route (11.3%). Hypertension, diabetes mellitus and chronic kidney disease were found in 45.1%, 12.7% and 7.0% of patients, respectively. Many of the patients did not have a job (42.3%) or worked as farmers (32.4%). Mood, adjustment and psychotic disorder were noted in 39.4%, 33.8% and 2.8% of patients, respectively. Notably, it was revealed that the nonsurvivors had a higher rate of chronic kidney disease than survivors
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