Table 2.
Multivariable logistic regression: factors associated with serious opioid-induced respiratory depression in a commercially insured population
| Covariate | Odds ratio | 95% confidence interval |
|---|---|---|
| Demographic | ||
| Age group, y | ||
| 18–34 (reference) | ||
| 35–44 | 0.77 | 0.68–0.87 |
| 45–54 | 0.95 | 0.84–1.07 |
| 55–64 | 0.94 | 0.87–1.07 |
| 65+ | 1.21 | 1.04–1.42 |
| Male | 1.10 | 1.01–1.20 |
| US census region | ||
| Northeast (reference) | ||
| Midwest | 1.22 | 1.09–1.36 |
| South | 1.10 | 0.99–1.23 |
| West | 1.48 | 1.29–1.69 |
| Clinical | ||
| Individual CCI comorbidities | ||
| Myocardial infarction | 2.39 | 1.93–2.97 |
| Heart failure | 1.92 | 1.60–2.29 |
| Peripheral vascular disease | 0.95 | 0.74–1.20 |
| Cerebrovascular disease | 2.35 | 2.01–2.75 |
| Dementia | 0.95 | 0.51–1.75 |
| Chronic pulmonary disease | 1.47 | 1.33–1.63 |
| Serious autoimmune rheumatologic disease | 1.52 | 1.25–1.85 |
| Peptic ulcer disease | 1.41 | 1.04–1.91 |
| Chronic hepatitis/cirrhosis | 0.75 | 0.48–1.17 |
| Diabetes without chronic complications | 1.22 | 1.08–1.37 |
| Hypertension | 1.20 | 1.10–1.31 |
| Depression | 3.12 | 2.84–3.42 |
| Warfarin treatment | 0.85 | 0.70–1.03 |
| Hemiplegia or paraplegia | 1.22 | 0.78–1.89 |
| Renal disease with renal impairment | 1.93 | 1.61–2.31 |
| Any malignancy, including leukemia and lymphoma | 1.10 | 0.93–1.31 |
| Diabetes with chronic complications | 1.19 | 0.95–1.48 |
| Skin ulcers | 1.49 | 1.16–1.91 |
| Complications of chronic liver disease | 2.77 | 1.74–4.45 |
| Metastatic solid tumor | 1.11 | 0.84–1.45 |
| HIV/AIDS | 1.12 | 0.55–2.22 |
| Other selected comorbidities | ||
| Non-pain-related | ||
| Substance use disorder | 10.20 | 9.06–11.40 |
| Tobacco use disorder | 1.69 | 1.52–1.87 |
| Bipolar disorder | 2.18 | 1.83–2.60 |
| Schizophrenia | 2.06 | 1.17–3.69 |
| Anxiety disorder | 1.64 | 1.50–1.80 |
| PTSD | 1.03 | 0.78–1.38 |
| OCD | 0.78 | 0.49–1.26 |
| ADHD | 0.93 | 0.72–1.19 |
| Sleep apnea | 1.11 | 0.97–1.28 |
| Cardiovascular disease | 0.84 | 0.68–1.03 |
| Endocarditis | 0.39 | 0.20–0.79 |
| Viral hepatitis | 1.39 | 1.02–1.89 |
| Alcoholic hepatitis | 1.87 | 0.79–4.84 |
| Nonmalignant pancreatic disease | 1.97 | 1.46–2.66 |
| Sexually transmitted disease | 0.92 | 0.76–1.10 |
| Herpes simplex | 0.80 | 0.51–1.21 |
| Skin infections/ abscesses | 1.13 | 0.99–1.30 |
| Obesity | 1.26 | 1.09–1.44 |
| Pain-related | ||
| Low back disorders | 1.42 | 1.30–1.55 |
| Other back/neck disorders | 1.15 | 1.05–1.26 |
| Neuropathic disorders | 1.28 | 1.15–1.43 |
| Fibromyalgia | 1.12 | 0.99–1.26 |
| Recurrent headache | 1.48 | 1.34–1.64 |
| Burns | 0.77 | 0.48–1.23 |
| Active traumatic injury | 1.38 | 1.27–1.50 |
| Prescription drugs | ||
| Opioids | ||
| By active ingredient | ||
| Hydrocodone | 1.35 | 1.22–1.49 |
| Oxycodone | 1.32 | 1.19–1.45 |
| Morphine | 2.44 | 2.07–2.88 |
| Fentanyl | 2.83 | 2.32–3.45 |
| Hydromorphone | 1.73 | 1.43–2.10 |
| Oxymorphone | 1.62 | 1.15–2.29 |
| Methadone | 2.35 | 1.86–2.98 |
| Buprenorphine | 0.39 | 0.29–0.51 |
| Codeine | 1.10 | 0.95–1.29 |
| Tramadol | 1.03 | 0.93–1.13 |
| Propoxyphene | 0.67 | 0.54–0.81 |
| Other* | 1.45 | 1.13–1.85 |
| By formulation | ||
| Not ER/LA (reference) | ||
| ER/LA | 1.48 | 1.27–1.72 |
| By route | ||
| Nonoral (reference) | ||
| Oral | 1.15 | 0.89–1.48 |
| Maximum prescribed daily morphine equivalent dose group, MED, mg/d | ||
| 1–<20 (reference) | ||
| 20–<50 | 0.96 | 0.81–1.15 |
| 50–<100 | 1.35 | 1.13–1.62 |
| ≥100 | 2.31 | 1.90–2.81 |
| Missing | 1.04 | 0.76–1.41 |
| Selected nonopioid drugs | ||
| Nonopioid analgesics | 0.62 | 0.53–0.71 |
| Benzodiazepines | 1.77 | 1.63–1.92 |
| Antidepressants | 1.33 | 1.22–1.45 |
| Muscle relaxants | 1.40 | 1.28–1.53 |
| Other sedatives | 1.34 | 1.22–1.48 |
| Antipsychotics | 1.19 | 1.04–1.36 |
| Stimulants | 1.04 | 0.87–1.23 |
| All-cause health care utililzation | ||
| ≥1 ED visit | 1.25 | 1.15–1.36 |
| ≥1 d hospitalization | 0.84 | 0.76–0.93 |
Model performance: C-statistic = 0.93.
ADHD = attention deficit hyperactivity disorder; CCI = Charlson Comorbidity Index; ED = emergency department; ER/LA = extended-release/long-acting; MED = morphine equivalent dose; OCD = obsessive compulsive disorder; PTSD = post-traumatic stress disorder.
Other prescription opioids included meperidine, pentazocine, dihydrocodeine, nalbuphine, and butorphanol. Missing opioid formulation (ER/LA) and route information were analyzed in the reference group in regression modeling. Sensitivity analyses were conducted to examine the impact of this and found no appreciable difference between such models relative to those in which the missing data were excluded.