Effectiveness of Substance Use Navigation for Emergency Department Patients With Substance Use Disorders: An Implementation Study.

STUDY OBJECTIVE: We implemented a whole person care-informed intervention delivered by substance use navigators (SUN) for emergency department (ED) patients with substance use disorders. METHODS: This was an implementation study of adult patients discharged from 3 public hospital EDs between September 1, 2021 through January 31, 2022 with cocaine, methamphetamine, alcohol, and opioid use-related diagnoses. The primary effectiveness outcome was treatment engagement within 30 days of ED discharge among patients with and without the SUN intervention. We used logistic regression and nearest neighbor propensity score matching without replacement to control for confounding effects. RESULTS: There were 1,328 patients in the cohort, and 119 (9.0%) received the SUN intervention; 50.4% of patients in the SUN intervention group and 15.9% of patients without the SUN intervention were engaged in outpatient treatment within 30 days of ED discharge (difference in proportions: 34.5%, 95% confidence interval [CI] 25.3% to 43.8%). In the unadjusted analysis, the SUN intervention was associated with higher rates of treatment engagement after ED discharge for patients with alcohol, opioid, and cocaine-related diagnoses; patients with methamphetamine-related diagnoses had low engagement rates with or without the SUN intervention. In addition, the SUN intervention was associated with higher odds of treatment engagement in the multivariable model (aOR 3.7, 95% CI 2.4 to 5.8) and in the propensity score-matched analysis (OR 2.1, 95% CI 1.2 to 3.5). CONCLUSION: A whole person care-informed intervention delivered by SUNs for ED patients with substance use disorders was strongly associated with higher engagement rates in addiction treatment after discharge.

Synergistic Effect of Ketamine and Buprenorphine Observed in the Treatment of Buprenorphine Precipitated Opioid Withdrawal in a Patient With Fentanyl Use.

BACKGROUND: Optimal treatment of buprenorphine precipitated opioid withdrawal (BPOW) is unclear. Full agonist treatment of BPOW is limited by buprenorphine's high-affinity blockade at mu-opioid receptors (µORs). Buprenorphine's partial agonism (low intrinsic efficacy) at µORs can limit the effectiveness of even massive doses once BPOW has begun. Adjunct medications, such as clonidine, are rarely effective in severe BPOW. Ketamine is an N -methyl-D-aspartate receptor antagonist with a potentially ideal pharmacologic profile for treatment of BPOW. Ketamine reduces opioid withdrawal symptoms independently of direct µOR binding, synergistically potentiates the effectiveness of buprenorphine µOR signaling, reverses (resensitizes) fentanyl induced µOR receptor desensitization, and inhibits descending pathways of hyperalgesia and central sensitization. Ketamine's rapid antidepressant effects potentially address depressive symptoms and subjective distress that often accompanies BPOW. Ketamine is inexpensive, safe, and available in emergency departments. To date, neither ketamine as treatment for BPOW nor to support uncomplicated buprenorphine induction has been described. CASE DESCRIPTION: We report a case of an illicit fentanyl-using OUD patient who experienced severe BPOW during an outpatient low-dose cross taper buprenorphine induction (ie, "microdose"). The BPOW was successfully treated in the emergency department with a combination of ketamine (0.6 mg/kg intravenous over 1 hour) combined with high-dose buprenorphine (16 mg sublingual single dose); 3 days later he was administered a month-long dose of extended-release subcutaneous buprenorphine which was repeated monthly (300 mg). At 90 days the patient remained in treatment and reported continuous abstinence from fentanyl use. CONCLUSIONS: This single case observation raises important questions about the potential therapeutic role of ketamine as a treatment for BPOW. BPOW is an important clinical problem for which there is currently only limited guidance and no universally accepted approach. Prospective study comparing the effectiveness of differing pharmacologic approaches to treat BPOW is urgently needed.

A Nonopioid, Nonbenzodiazepine Treatment Approach for Intractable Nausea and Vomiting in the Emergency Department.

GOAL: We sought to assess the feasibility and efficacy of a treatment protocol for nausea and vomiting using the combination of chlorpromazine, a dopamine antagonist antiemetic, and ketamine, a nonopioid analgesic. BACKGROUND: Increasing numbers of patients with cannabis use disorder are presenting to emergency departments with a poorly understood syndrome characterized by intractable nausea and vomiting. METHODS: This is a prospective, observational study involving a convenience sample of patients with unexplained nausea and vomiting. Subjects were given ketamine 15 mg slow intravenous push and chlorpromazine 12.5 mg intravenous over 15 minutes. Outcomes were number of episodes of emesis after study drug administration; change in nausea severity; change in pain severity; adverse events; and patient satisfaction. RESULTS: We enrolled 28 subjects on 30 emergency department visits. Twenty-three subjects (82%) reported at least weekly cannabis use with 19 reporting daily use. Initial symptoms were severe, with median pain and nausea scores both 10. After receiving study medication, the mean decrease in pain score over 120 minutes was 4.1 (95% confidence interval: 3.2, 5.0) and the mean decrease in nausea score was 4.9 (95% confidence interval: 4.0, 5.8). There were no adverse events. All 28 subjects who were asked reported they would want to receive these medications again. CONCLUSION: In this single-center study, the majority of patients presenting with intractable nausea and vomiting reported heavy cannabis use, and symptoms were severe. The combination of chlorpromazine plus ketamine resulted in rapid, definitive cessation of symptoms in most of these patients without the need for opioids or benzodiazepines.

Intravenous Lidocaine Provides Similar Analgesia to Intravenous Morphine for Undifferentiated Severe Pain in the Emergency Department: A Pilot, Unblinded Randomized Controlled Trial.

OBJECTIVES: We compared the analgesic effects of intravenous (IV) lidocaine and IV morphine for the treatment of severe pain in the emergency department (ED). METHODS: This was a pilot, unblinded randomized controlled study comparing the efficacy of IV lidocaine vs IV morphine for patients aged ≥18 years with severe pain (numerical rating scale [NRS] ≥ 7). Participants were randomized to receive IV lidocaine (75 mg if <50 kg, 100 mg if 50-100 kg, and 150 mg if >100 kg) over 10 minutes, followed by a 50-minute IV lidocaine infusion of the same dose or provider-chosen dose of morphine. Participants were eligible for rescue morphine. The primary outcome was the difference in patients' mean reported pain at 60 minutes. Secondary outcomes included total morphine consumption, patient satisfaction, and side effects. RESULTS: Thirty-two patients were enrolled. The lidocaine arm's mean pain NRS at 60 minutes was 5.1 (95% confidence interval [CI] = 3.3 to 6.8) compared with 4.2 (95% CI = 3.0 to 5.4) in the morphine arm, and the absolute difference was 0.9 (95% CI = -1.2 to 2.9). Among participants in the lidocaine and morphine arms, 13% and 38%, respectively, had side effects. Patient satisfaction was similar in both arms (87% and 88%). Lidocaine arm patients averaged 4.5 mg of IV morphine (95% CI = 3.0 to 6.0) compared with 8.4 mg (95% CI = 6.9 to 9.8) in the morphine arm, an absolute difference of 3.9 mg (95% CI = 1.8 to 5.9). CONCLUSIONS: We found similar pain relief and satisfaction in both study arms. Lidocaine arm participants had fewer side effects and required less morphine. Lidocaine is a potential opioid-sparing analgesic that deserves further study for severe pain in ED patients.

Slow Infusion of Low-dose Ketamine Reduces Bothersome Side Effects Compared to Intravenous Push: A Double-blind, Double-dummy, Randomized Controlled Trial.

OBJECTIVE: We compared the analgesic efficacy and incidence of side effects when low-dose (0.3 mg/kg) ketamine (LDK) is administered as a slow infusion (SI) over 15 minutes versus an intravenous push (IVP) over 1 minute. METHODS: This was a prospective, randomized, double-blind, double-dummy, placebo-controlled trial of adult ED patients presenting with moderate to severe pain (numerical rating scale [NRS] score ≥ 5). Patients received 0.3 mg/kg ketamine administered either as a SI or a IVP. Our primary outcome was the proportion of patients experiencing any psychoperceptual side effect over 60 minutes. A secondary outcome was incidence of moderate or greater psychoperceptual side effects. Additional outcomes included reduction in pain NRS scores at 60 minutes and percent maximum summed pain intensity difference (%SPID). RESULTS: Fifty-nine participants completed the study. A total of 86.2% of the IVP arm and 70.0% of the SI arm experienced any side effect (difference = 16.2%, 95% confidence interval [CI] = -5.4 to 37.8). We found a large reduction in moderate or greater psychoperceptual side effects with SI administration-75.9% reported moderate or greater side effects versus 43.4% in the SI arm (difference = 32.5%, 95% CI = 7.9 to 57.1). Additionally, the IVP arm experienced more hallucinations (n = 8, 27.6%) than the SI arm (SI n = 2, 6.7%, difference = 20.9%, 95% CI = 1.8 to 43.4). We found no significant differences in analgesic efficacy. At 60 minutes, the mean %SPID values in the IVP and SI arms were 39.9 and 33.5%, respectively, with a difference of 6.5% (95% CI = -5.8 to 18.7). CONCLUSION: Most patients who are administered LDK experience a psychoperceptual side effect regardless of administration via SI or IVP. However, patients receiving LDK as a SI reported significantly fewer moderate or greater psychoperceptual side effects and hallucinations with equivalent analgesia.