Table 3.
Factors associated with serious opioid-induced respiratory depression in a commercially insured population vs the VHA population, rank-ordered by odds ratio A) in each population and B) in CIP*
| A) CIP population |
VHA population† |
||||
|---|---|---|---|---|---|
| Covariate | OR | 95% CI | Covariate | OR | 95% CI |
| Substance use disorder | 10.20 | 9.06–11.40 | MED ≥100 mg/d | 4.13 | 2.61–6.54 |
| Depression | 3.12 | 2.84–3.42 | Opioid dependence | 3.86 | 2.57–5.78 |
| Fentanyl | 2.83 | 2.32–3.45 | ≥1 ED visit | 2.88 | 2.34–3.54 |
| Complications of chronic | 2.77 | 1.74–4.45 | ≥1 d hospitalization | 2.86 | 2.27–3.58 |
| liver disease | Complications of chronic | 2.67 | 1.07–6.65 | ||
| Morphine | 2.44 | 2.07–2.88 | liver disease | ||
| Myocardial infarction | 2.39 | 1.93–2.97 | Skin ulcers | 2.39 | 1.52–3.77 |
| Cerebrovascular disease | 2.35 | 2.01–2.75 | Hydromorphone | 2.39 | 1.21–4.72 |
| Methadone | 2.35 | 1.86–2.98 | Metastatic solid tumor | 2.25 | 1.25–4.04 |
| MED ≥100 mg/d | 2.31 | 1.90–2.81 | MED 50–<100 mg/d | 2.21 | 1.52–3.20 |
| Bipolar disorder | 2.18 | 1.83–2.60 | Nonmalignant | 2.19 | 1.07–4.46 |
| Schizophrenia | 2.06 | 1.17–3.69 | pancreatic disease | ||
| Nonmalignant | 1.97 | 1.46–2.66 | Widowed | 2.04 | 1.40–2.97 |
| pancreatic disease | Age 55–64 y | 1.93 | 1.14–3.25 | ||
| Renal disease with renal impairment | 1.93 | 1.61–2.31 | ER/LA | 1.88 | 1.12–3.18 |
| Heart failure | 1.92 | 1.60–2.29 | Age 65+ y | 1.84 | 1.07–3.17 |
| Benzodiazepines | 1.77 | 1.63–1.92 | Non-Hispanic white | 1.76 | 1.29–2.40 |
| Hydromorphone | 1.73 | 1.43–2.10 | West | 1.76 | 1.25–2.48 |
| Tobacco use disorder | 1.69 | 1.52–1.87 | Renal disease with renal impairment | 1.74 | 1.26–2.40 |
| Anxiety disorder | 1.64 | 1.50–1.80 | Bipolar disorder | 1.68 | 1.17–2.43 |
| Oxymorphone | 1.62 | 1.15–2.29 | Antidepressants | 1.63 | 1.31–2.02 |
| Serious autoimmune rheumatologic disease | 1.52 | 1.25–1.85 | Active traumatic injury | 1.62 | 1.28–2.04 |
| Other race/ethnicity | 1.57 | 1.10–2.23 | |||
| Skin ulcers | 1.49 | 1.16–1.91 | Chronic pulmonary disease | 1.50 | 1.21–1.87 |
| Recurrent headache | 1.48 | 1.34–1.64 | MED 20–<50 mg/d | 1.45 | 1.09–1.92 |
| West | 1.48 | 1.29–1.69 | Warfarin treatment | 1.43 | 1.02–2.00 |
| ER/LA | 1.48 | 1.27–1.72 | Oxycodone | 1.41 | 1.06–1.87 |
| Chronic pulmonary disease | 1.47 | 1.33–1.63 | Benzodiazepines | 1.38 | 1.11–1.71 |
| Other opioids‡ | 1.45 | 1.13–1.85 | Substance abuse and non- opioid substance dependence | 1.36 | 1.03–1.79 |
| Low back disorders | 1.42 | 1.30–1.55 | Never married | 1.35 | 1.01–1.82 |
| Peptic ulcer disease | 1.41 | 1.04–1.91 | Sleep apnea | 1.34 | 1.01–1.76 |
| Muscle relaxants | 1.40 | 1.28–1.53 | Antipsychotics | 1.29 | 1.01–1.66 |
| Viral hepatitis | 1.39 | 1.02–1.89 | Tramadol | 0.73 | 0.53–0.99 |
| Active traumatic injury | 1.38 | 1.27–1.50 | Skin infections/abscesses | 0.51 | 0.31–0.85 |
| Hydrocodone | 1.35 | 1.22–1.49 | ADHD | 0.33 | 0.11–0.99 |
| MED 50–<100 mg/d | 1.35 | 1.13–1.62 | Serious autoimmune rheumatologic disease | 0.32 | 0.11–0.88 |
| Other sedatives | 1.34 | 1.22–1.48 | |||
| Antidepressants | 1.33 | 1.22–1.45 | |||
| Oxycodone | 1.32 | 1.19–1.45 | |||
| Neuropathic disorders | 1.28 | 1.15–1.43 | |||
| Obesity | 1.26 | 1.09–1.44 | |||
| ≥1 ED visit | 1.25 | 1.15–1.36 | |||
| Midwest | 1.22 | 1.09–1.36 | |||
| Diabetes without chronic complications | 1.22 | 1.08–1.37 | |||
| Age 65+ y | 1.21 | 1.04–1.42 | |||
| Hypertension | 1.20 | 1.10–1.31 | |||
| Antipsychotics | 1.19 | 1.04–1.36 | |||
| Other back/neck disorders | 1.15 | 1.05–1.26 | |||
| Male | 1.10 | 1.01–1.20 | |||
| ≥1 d hospitalization | 0.841 | 0.76–0.93 | |||
| Age 35–44 y | 0.766 | 0.68–0.87 | |||
| Propoxyphene | 0.665 | 0.54–0.81 | |||
| Nonopioid analgesics | 0.614 | 0.53–0.71 | |||
| Endocarditis | 0.392 | 0.20–0.79 | |||
| Buprenorphine | 0.388 | 0.29–0.56 | |||
| B) CIP population |
VHA population† |
||||
|---|---|---|---|---|---|
| Covariate | OR | 95% CI | Covariate | OR | 95% CI |
| Opioid dependence | 3.86 | 2.57–5.78 | |||
| Substance use disorder | 10.20 | 9.06–11.40 | Substance abuse and nonopioid substance dependence | 1.36 | 1.03–1.79 |
| Depression | 3.12 | 2.84–3.42 | |||
| Fentanyl | 2.83 | 2.32–3.45 | |||
| Complications of chronic liver disease | 2.77 | 1.74–4.45 | Complications of chronic liver disease | 2.67 | 1.07–6.65 |
| Morphine | 2.44 | 2.07–2.88 | |||
| Myocardial infarction | 2.39 | 1.93–2.97 | |||
| Cerebrovascular disease | 2.35 | 2.01–2.75 | |||
| Methadone | 2.35 | 1.86–2.98 | |||
| MED ≥100 mg/d | 2.31 | 1.90–2.81 | MED ≥100 mg/d | 4.13 | 2.61–6.54 |
| Bipolar disorder | 2.18 | 1.83–2.60 | Bipolar disorder | 1.68 | 1.17–2.43 |
| Schizophrenia | 2.06 | 1.17–3.69 | |||
| Nonmalignant pancreatic disease | 1.97 | 1.46–2.66 | Nonmalignant pancreatic disease | 2.19 | 1.07–4.46 |
| Renal disease with renal impairment | 1.93 | 1.61–2.31 | Renal disease with renal impairment | 1.74 | 1.26–2.40 |
| Heart failure | 1.92 | 1.60–2.29 | |||
| Benzodiazepines | 1.77 | 1.63–1.92 | Benzodiazepines | 1.38 | 1.11–1.71 |
| Hydromorphone | 1.73 | 1.43–2.10 | Hydromorphone | 2.39 | 1.21–4.72 |
| Tobacco use disorder | 1.69 | 1.52–1.87 | |||
| Anxiety disorder | 1.64 | 1.50–1.80 | |||
| Oxymorphone | 1.62 | 1.15–2.29 | |||
| Serious autoimmune rheumatologic Disease | 1.52 | 1.25–1.85 | Serious autoimmune rheumatologic disease | 0.32 | 0.11–0.88 |
| Skin ulcers | 1.49 | 1.16–1.91 | Skin ulcers | 2.39 | 1.52–3.77 |
| Recurrent headache | 1.48 | 1.34–1.64 | |||
| West | 1.48 | 1.29–1.69 | West | 1.76 | 1.25–2.48 |
| ER/LA | 1.48 | 1.27–1.72 | ER/LA | 1.88 | 1.12–3.18 |
| Chronic pulmonary disease | 1.47 | 1.33–1.63 | Chronic pulmonary disease | 1.50 | 1.21–1.87 |
| Other opioids‡ | 1.45 | 1.13–1.85 | |||
| Low back disorders | 1.42 | 1.30–1.55 | |||
| Peptic ulcer disease | 1.41 | 1.04–1.91 | |||
| Muscle relaxants | 1.40 | 1.28–1.53 | |||
| Viral hepatitis | 1.39 | 1.02–1.89 | |||
| Active traumatic injury | 1.38 | 1.27–1.50 | Active traumatic injury | 1.62 | 1.28–2.04 |
| Hydrocodone | 1.35 | 1.22–1.49 | |||
| MED 50–<100 mg/d | 1.35 | 1.13–1.62 | MED 50–<100 mg/d | 2.21 | 1.52–3.20 |
| Other sedatives | 1.34 | 1.22–1.48 | |||
| Antidepressants | 1.33 | 1.22–1.45 | Antidepressants | 1.63 | 1.31–2.02 |
| Oxycodone | 1.32 | 1.19–1.45 | Oxycodone | 1.41 | 1.06–1.87 |
| Neuropathic disorders | 1.28 | 1.15–1.43 | |||
| Obesity | 1.26 | 1.09–1.44 | |||
| ≥1 ED visit | 1.25 | 1.15–1.36 | ≥1 ED visit | 2.88 | 2.34–3.54 |
| Midwest | 1.22 | 1.09–1.36 | |||
| Diabetes without chronic complications | 1.22 | 1.08–1.37 | |||
| Age 65+ y | 1.21 | 1.04–1.42 | Age 65+ y | 1.84 | 1.07–3.17 |
| Hypertension | 1.20 | 1.10–1.31 | |||
| Antipsychotics | 1.19 | 1.04–1.36 | Antipsychotics | 1.29 | 1.01–1.66 |
| Other back/neck disorders | 1.15 | 1.05–1.26 | |||
| Male | 1.10 | 1.01–1.20 | |||
| ≥1 d hospitalization | 0.84 | 0.76–0.93 | ≥1 d hospitalization | 2.86 | 2.27–3.58 |
| Age 35–44 y | 0.77 | 0.68–0.87 | |||
| Propoxyphene | 0.67 | 0.54–0.81 | |||
| Nonopioid analgesics | 0.61 | 0.53–0.71 | |||
| Endocarditis | 0.39 | 0.20–0.79 | |||
| Buprenorphine | 0.39 | 0.29–0.56 | |||
| Metastatic solid tumor | 2.25 | 1.25–4.04 | |||
| Widowed | 2.04 | 1.40–2.97 | |||
| Age 55–64 y | 1.93 | 1.14–3.25 | |||
| Non-Hispanic white | 1.76 | 1.29–2.40 | |||
| Other race/ethnicity | 1.57 | 1.10–2.23 | |||
| MED 20–<50 mg/d | 1.45 | 1.09–1.92 | |||
| Warfarin treatment | 1.43 | 1.02–2.00 | |||
| Never married | 1.35 | 1.01–1.82 | |||
| Sleep apnea | 1.34 | 1.01–1.76 | |||
| Tramadol | 0.73 | 0.53–0.99 | |||
| Skin infections/abscesses | 0.51 | 0.31–0.85 | |||
| ADHD | 0.33 | 0.11–0.99 | |||
ADHD = attention deficit hyperactivity disorder; CI = confidence interval; ED = emergency department; ER/LA = extended-release/long-acting; MED = morphine equivalent dose; OCD = obsessive compulsive disorder; OR = odds ratio; PTSD = post-traumatic stress disorder.
*
Factors are presented based on their strength of association with serious opioid-induced respiratory depression. OR: >2.00 are bolded, >1.0 to 2.0 are regular font, and <1.0 are italicized.
†
From “Appendix II. Logistic regression results: Serious opioid-related toxicity or overdose” [26].
‡
Other prescription opioids included meperidine, pentazocine, dihydrocodeine, nalbuphine, and butorphanol.