Associations of Adverse Clinical Course and Ingested Substances among Patients with Deliberate Drug Poisoning: A Cohort Study from an Intensive Care Unit in Japan

RESEARCH ARTICLE Associations of Adverse Clinical Course and Ingested Substances among Patients with Deliberate Drug Poisoning: A Cohort Study from an Intensive Care Unit in Japan Kanako Ichikura1,2, Yasuyuki Okumura2*, Takashi Takeuchi3 a11111 1 Section of Liaison Psychiatry and Palliative Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan, 2 Research Department, Institute for Health Economics and Policy, Association for Health Economics Research and Social Insurance and Welfare, Tokyo, Japan, 3 Section of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan * OPEN ACCESS Citation: Ichikura K, Okumura Y, Takeuchi T (2016) Associations of Adverse Clinical Course and Ingested Substances among Patients with Deliberate Drug Poisoning: A Cohort Study from an Intensive Care Unit in Japan. PLoS ONE 11(8): e0161996. doi:10.1371/journal.pone.0161996 Editor: Chiara Lazzeri, Azienda Ospedaliero Universitaria Careggi, ITALY Received: April 11, 2016 Accepted: August 16, 2016 Published: August 25, 2016 Copyright: © 2016 Ichikura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: The ethical restrictions prohibit the authors from making the minimal dataset publicly available. Data sharing will be considered for researchers upon request and upon institutional review board approval from the research sites. Requests should be submitted to . Funding: Funding for this study was provided by a Grant-in-Aid for Young Scientists (B) (No. 26870914) by the Japan Society for the Promotion of Science. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Abstract Objectives Some patients with deliberate drug poisoning subsequently have an adverse clinical course. The present study aimed to examine whether the type of drugs ingested and psychiatric diagnoses were related to an adverse clinical course. Methods We conducted a cohort study of patients with deliberate drug poisoning admitted to the intensive care unit of a university hospital located in Tokyo, Japan, between September 2006 and June 2013. Intensive care unit (ICU) stay of 4 days was used as a primary outcome measure, while the incidence of aspiration pneumonitis was used as a secondary outcome measure. Ingested substances and psychiatric diagnoses were used as explanatory variables. Results Of the 676 patients with deliberate drug poisoning, 88% had a history of psychiatric treatment and 82% had ingested psychotropic drugs. Chlorpromazine-promethazine-phenobarbital combination drug (Vegetamin1) ranked fifth among the most frequently ingested substances in cases of deliberate drug poisoning and had the highest incidence of prolonged ICU stay (20%) and aspiration pneumonitis (29%). The top three major classes consisted of benzodiazepines (79%), new-generation antidepressants (25%), and barbiturates/non-barbiturates (23%). Barbiturate overdose was independently associated with increased odds of both prolonged ICU stay (8% vs. 17%; odds ratio [OR], 2.97; 95% confidence interval [CI], 1.60– 5.55) and aspiration pneumonitis (8% vs. 24%; OR, 3.83; 95% CI, 2.18–6.79) relative to those associated with overdose of only other sedative-hypnotics (i.e., benzodiazepines). PLOS ONE | DOI:10.1371/journal.pone.0161996 August 25, 2016 1 / 12 Adverse Clinical Course in Deliberate Drug Poisoning Competing Interests: KI are employed by Tokyo Medical and Dental University with contributions from several drug companies: Pfizer Inc., Astellas Pharma Inc., MSD Inc., Shionogi & Co., LTD., and Eisai Inc. YO has received research grants from the Japan Agency for Medical Research and Development; Ministry of Health, Labour and Welfare; Japan Society for the Promotion of Science; Institute for Health Economics and Policy; and Mental Health and Morita Therapy and served as a member of an advisory board for Janssen Pharmaceuticals, Inc. TT has received personal fees from Otsuka, GlaxoSmithKline, MSD, Dainippon-Sumitomo, Janssen, Eisai, Eli Lilly, Daiichi-Sankyo, Shionogi, and Tanabe-Mitsubishi. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Conclusion These results suggest that judicious prescribing of barbiturates by psychiatrists could reduce the risk of an adverse clinical course when a patient attempts an overdose. Introduction Drug poisoning is a worldwide public health concern and places a serious burden on emergency medical service. In Western countries, the annual incidence of drug poisoning has been estimated at 142–232 per 100,000 inhabitants [1–3] and drug poisoning accounts for 0.3%– 0.6% of all patients admitted to emergency departments [4, 5]. Deliberate drug poisoning is responsible for 60%–78% of all drug poisoning and is a more common cause of admission than accidental drug poisoning [6, 7]. A non-negligible subgroup of patients with deliberate drug poisoning may show an adverse clinical course such as aspiration pneumonia [8, 9], respiratory failure [10], hypothermia [9], and cardiovascular events [11], although almost all (99%) patients survive their hospital stay [12–14]. Aspiration pneumonia is the most common adverse event among patients with deliberate drug poisoning [8] and doubles the length of intensive care unit (ICU) stay owing to physical recovery from the overdose-related complications [10]. Indeed, 27%–28% of patients develop aspiration pneumonia [10, 15]. In addition, 35% of patients are hospitalized for more than 3 days in acute care hospitals [16], although these patients are generally discharged from the ICU within only 16–32 hours of admission [4, 10]. Several factors contribute to an adverse clinical course among patients with drug poisoning. For example, demographic characteristics (i.e., sex [17, 18] and age [18]), clinical characteristics (i.e., blood pressure [10, 19, 20], renal function [10], and level of consciousness [15, 19, 21]), and characteristics of the drugs ingested (dosage [20] and type [15]) are important contributing factors in adverse clinical courses among patients with drug poisoning. The dose and type of ingested drugs are particularly preventable factors associated with a severe adverse clinical course among patients with deliberate drug poisoning [22]. Although few studies have explored the associations between adverse clinical courses and ingested drugs in patients with deliberate drug overdose [15, 23–26], some specific drugs might increase the risk of an adverse clinical course. Tricyclic antidepressant poisoning leads to arrhythmia and an increased rate of mortality [23]. Barbiturate poisoning leads to respiratory depression a (...truncated)