Abstract
This cohort study examines mortality following nonfatal opioid overdoses of intentional, unintentional, and undetermined intent.
Rising rates of unintentional and intentional opioid overdose deaths1 have sharpened interest in probing their association with each other.2 A unified perspective encompasses unintentional and intentional overdoses within self-injury3 and emphasizes shared biological (eg, impulsivity) or social (eg, economic insecurity) risk factors.4 By contrast, a psychological perspective distinguishes the motivation of overdoses as unintentional, intentional, or undetermined intent.5 To evaluate these competing perspectives, we examined mortality following nonfatal opioid overdoses of intentional, unintentional, and undetermined intent. We hypothesized that patients with nonfatal intentional overdoses would be more likely to die by suicide than patients with unintentional overdose while patients with nonfatal unintentional overdoses would be more likely to die of unintentional overdose than suicide.
Methods
Statewide California emergency department (ED) visit discharge data from 2009 to 2011 were linked to California death records and analyzed using Stata version 14.0 (StataCorp). Among ED patients with nonfatal opioid drug overdose codes (International Classification of Diseases, Ninth Revision, Clinical Modification codes 965.00 to 965.02 and 965.09), 3 hierarchical cohorts were constructed of patients with nonfatal intentional overdose (codes E950.0 to E952.9), unintentional overdose (codes E850.0 to E869.9), or overdose of undetermined intent (codes E980.0 to E982.9) codes. The Institutional Review Board of University of California, Merced, approved this study with a waiver of informed consent. We calculated 12-month crude mortality rates per 100 000 person-years and 95% CIs during the first 12 months following ED discharge. Deaths were subclassified as unintentional overdose, suicide, all external causes, and natural causes. Annualized standardized mortality rate ratios (SMRs) with 95% CIs were calculated based on 2009 to 2012 California cause-specific mortality rates standardized by sex, age, and race/ethnicity.6 Hazard ratios (HRs) for suicide and unintentional overdose death were estimated using Cox proportional hazard regression adjusting for age, sex, race/ethnicity, and payer.
Results
The sample included 6936 patients with nonfatal intentional opioid overdoses (306 deaths), 16 277 patients with nonfatal unintentional opioid overdoses (1770 deaths), and 5388 patients with nonfatal opioid overdoses of undetermined intent (430 deaths). Patients with nonfatal intentional overdoses included the highest percentage of females and lowest percentage of persons 65 years or older (Table 1). Each nonfatal overdose group had significantly elevated SMRs for natural-cause mortality, suicide, and unintentional overdose death. Suicide SMRs were 76.0 (95% CI, 59.0-93.0) for patients with nonfatal intentional overdoses, 14.5 (95% CI, 9.9-19.0) for patients with unintentional overdoses, and 29.3 (95% CI, 18.0-40.5) for patients with overdoses of undetermined intent. Unintentional overdose SMRs were 66.3 (95% CI, 51.0-81.7) for patients with nonfatal intentional overdoses, 103.3 (95% CI, 91.0-111.5) for patients with unintentional overdoses, and 126.0 (95% CI, 103.0-148.8) for patients with overdoses of undetermined intent (Table 2). In relation to patients with nonfatal unintentional overdoses, adjusted hazards of suicide were significantly greater for patients with nonfatal intentional overdoses (HR, 4.96; 95% CI, 3.34-7.36) and patients with nonfatal overdoses of undetermined intent (HR, 2.18; 95% CI, 1.32-3.60). Compared with patients with nonfatal unintentional overdoses, adjusted hazards of unintentional overdose death were significantly lower for patients with nonfatal intentional overdose (HR, 0.63; 95% CI, 0.48-0.82) but not for patients with nonfatal overdoses of undetermined intent (HR, 1.23; 95% CI, 0.99-1.52).
Table 1. Characteristics of 28 601 Patients Receiving Emergency Department Care for an Index Nonfatal Opioid Overdose According to Intent of the Overdose Event in California From 2009 to 2011a.
| Characteristic | No. (%) | ||
|---|---|---|---|
| Intentional overdose (n = 6936) | Unintentional overdose (n = 16 277) | Overdose of undetermined intent (n = 5388) | |
| Female | 4095 (59.0) | 8425 (51.8) | 2278 (42.3) |
| Age, y | |||
| 10-24 | 1336 (19.3) | 1763 (10.8) | 846 (15.7) |
| 25-44 | 2638 (38.0) | 4113 (25.3) | 1767 (32.8) |
| 45-64 | 2587 (37.3) | 7183 (44.1) | 2319 (43.0) |
| ≥65 | 375 (5.4) | 3218 (19.8) | 456 (8.5) |
| Race/ethnicity | |||
| Non-Hispanic white | 4729 (68.2) | 11 438 (70.3) | 3530 (65.5) |
| Non-Hispanic black | 526 (7.5) | 1496 (9.2) | 442 (8.2) |
| Hispanic | 1214 (17.5) | 2488 (15.3) | 1112 (20.6) |
| Asian/Pacific Islander | 137 (2.0) | 284 (1.7) | 62 (1.2) |
| Non-Hispanic other | 330 (4.8) | 571 (3.5) | 242 (4.5) |
| Insurance type | |||
| Private | 2423 (35.0) | 4124 (25.4) | 1254 (23.3) |
| Medicare | 1150 (16.6) | 5217 (32.1) | 988 (18.4) |
| Medicaid | 1874 (27.1) | 3904 (24.0) | 1440 (26.8) |
| Self-pay | 1295 (18.7) | 2636 (16.2) | 1546 (28.7) |
| Other | 187 (2.7) | 367 (2.7) | 155 (2.9) |
Data from the California Office of Statewide Health Planning and Development from 2009 to 2011. Among patients with opioid poisoning codes (International Classification of Diseases, Ninth Revision, Clinical Modification codes 965.00, 965.01, 965.02, or 965.09), the 3 hierarchical groups are defined as (1) intentional overdose (codes E950.0-E952.9), (2) unintentional overdose (codes E850.0-E869.9), and (3) overdose of undetermined intent (codes E980.0-E982.9).
Table 2. Unintentional Overdose, Suicide, and Other Mortality Within 1 Year Among California Emergency Department Patients Presenting From 2009 to 2011 With an Index Opioid Overdose According to Intent of the Overdose.
| Manner of death | Intentional overdose (n = 6936) | Unintentional overdose (n = 16 277) | Overdose of undetermined intent (n = 5388) | |||
|---|---|---|---|---|---|---|
| Mortality rate (95% CI) | SMR (95% CI) | Mortality rate (95% CI) | SMR (95% CI) | Mortality rate (95% CI) | SMR (95% CI) | |
| Unintentional overdose | 1067.5 (847.4-1344.9) | 66.3 (51.0-81.7) | 1801.3 (1599.8-2028.1) | 103.3 (91.0-111.5) | 2285.5 (1906.7-2739.5) | 126.0 (103.0-148.8) |
| No. of deaths | 72 | NA | 273 | NA | 117 | NA |
| Suicide | 1141.7 (913.1-1427.4) | 76.0 (59.0-93.0) | 257.3 (188.0-352.2) | 14.5 (9.9-19.0) | 507.9 (354.8-745.9) | 29.3 (18.0-40.5) |
| No. of deaths | 77 | NA | 39 | NA | 26 | NA |
| All external-cause injuries | 2461.3 (2113.9-2865.7) | 42.0 (35.6-48.4) | 2414.9 (2179.7-2675.4) | 32.6 (29.3-36.0) | 3223.2 (2767.0-3754.5) | 46.3 (39.3-53.4) |
| No. of deaths | 166 | NA | 366 | NA | 165 | NA |
| Natural-cause mortality | 2075.8 (1758.9-2449.7) | 4.6 (3.8-5.4) | 9263.6 (8791.5-9761.0) | 8.2 (7.8-8.6) | 5176.6 (4589.4-5838.9) | 8.3 (7.3-9.3) |
| No. of deaths | 140 | NA | 1404 | NA | 265 | NA |
| All-cause mortality | 4537.0 (4056.1-5075.0) | 8.9 (7.9-9.9) | 11 678.4 (11 146.9-12 235.4) | 9.7 (9.2-10.1) | 8399.7 (7642.2-9232.4) | 12.1 (11.0-13.3) |
| No. of deaths | 306 | NA | 1770 | NA | 430 | NA |
Abbreviations: NA, not applicable; SMR, standardized mortality rate ratios.
Data from the California Office of Statewide Health Planning and Development from 2009 to 2011 and state vital records from 2009 to 2012. Mortality rates and 95% CIs expressed per 100 000 person-years. Deaths were subclassified as unintentional overdose (International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes X40-X44), suicide (codes X60-X84, Y87.0, U03), all external-cause injuries (codes X00-X99, U01-U03, Y00-Y14, Y35, Y85-87.1, V01-W99), and natural-cause mortality (all other codes).
Discussion
Following nonfatal opioid overdose, patients were at high risk of mortality from several causes. Suicide risks were greater for patients with nonfatal intentional overdoses compared with unintentional overdoses, while risks of unintentional overdose death were greater for patients with nonfatal unintentional overdoses than intentional overdoses. Shared increased risks for all external-cause mortality across groups support a unified self-injury conceptualization that emphasizes common underlying determinants, while differential mortality risks for suicide and unintentional overdose supports the clinical utility of distinguishing nonfatal overdoses by intent.
Study limitations include potential misclassification related to diagnostic errors in EDs, imprecision in manner of death determinations, and age of the data (from 2009 to 2012), although national fatal intentional opioid overdose rates were nearly constant between 2009 to 2012 and 2017.1 The high risk of unintentional overdose and suicide death following nonfatal opioid overdoses underscore the importance of initiating opioid agonist treatment in the ED for patients with opioid use disorder and performing mental health assessments to evaluate underlying suicide risk.
References
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