Association Between Buprenorphine Dose and the Urine "Norbuprenorphine" to "Creatinine" Ratio: Revised.

Background: Utilizing a 1-year chart review as the data, Furo et al. conducted a research study on an association between buprenorphine dose and the urine "norbuprenorphine" to "creatinine" ratio and found significant differences in the ratio among 8-, 12-, and 16-mg/day groups with an analysis of variance (ANOVA) test. This study expands the data for a 2-year chart review and is intended to delineate an association between buprenorphine dose and the urine "norbuprenorphine" to "creatinine" ratio with a higher statistical power. Methods: This study performed a 2-year chart review of data for the patients living in a halfway house setting, where their drug administration was closely monitored. The patients were on buprenorphine prescribed at an outpatient clinic for opioid use disorder (OUD), and their buprenorphine prescription and dispensing information were confirmed by the New York Prescription Drug Monitoring Program (PDMP). Urine test results in the electronic health record (EHR) were reviewed, focusing on the "buprenorphine," "norbuprenorphine," and "creatinine" levels. The Kruskal-Wallis H and Mann-Whitney U tests were performed to examine an association between buprenorphine dose and the "norbuprenorphine" to "creatinine" ratio. Results: This study included 371 urine samples from 61 consecutive patients and analyzed the data in a manner similar to that described in the study by Furo et al. This study had similar findings with the following exceptions: (1) a mean buprenorphine dose of 11.0 ± 3.8 mg/day with a range of 2 to 20 mg/day; (2) exclusion of 6 urine samples with "creatinine" level <20 mg/dL; (3) minimum "norbuprenorphine" to "creatinine" ratios in the 8-, 12-, and 16-mg/day groups of 0.44 × 10-4 (n = 68), 0.1 × 10-4 (n = 133), and 1.37 × 10-4 (n = 82), respectively; however, after removing the 2 lowest outliers, the minimum "norbuprenorphine" to "creatinine" ratio in the 12-mg/day group was 1.6 × 10-4, similar to the findings in the previous study; and (4) a significant association between buprenorphine dose and the urine "norbuprenorphine" to "creatinine" ratios from the Kruskal-Wallis test (P < .01). In addition, the median "norbuprenorphine" to "creatinine" ratio had a strong association with buprenorphine dose, and this association could be formulated as: [y = 2.266 ln(x) + 0.8211]. In other words, the median ratios in 8-, 12-, and 16-mg/day groups were 5.53 × 10-4, 6.45 × 10-4, and 7.10 × 10-4, respectively. Therefore, any of the following features should alert providers to further investigate patient treatment compliance: (1) inappropriate substance(s) in urine sample; (2) "creatinine" level <20 mg/dL; (3) "buprenorphine" to "norbuprenorphine" ratio >50:1; (4) buprenorphine dose >24 mg/day; or (5) "norbuprenorphine" to "creatinine" ratios <0.5 × 10-4 in patients who are on 8 mg/day or <1.5 × 10-4 in patients who are on 12 mg/day or more. Conclusion: The results of the present study confirmed those of the previous study regarding an association between buprenorphine dose and the "norbuprenorphine" to "creatinine" ratio, using an expanded data set. Additionally, this study delineated a clearer relationship, focusing on the median "norbuprenorphine" to "creatinine" ratios in different buprenorphine dose groups. These results could help providers interpret urine test results more accurately and apply them to outpatient opioid treatment programs for optimal treatment outcomes.

Buprenorphine Dosage and Urine Quantitative Buprenorphine, Norbuprenorphine, and Creatinine Levels in an Office-Based Opioid Treatment Program.

BACKGROUND: Treatment progress is routinely monitored by urine testing in patients with opioid use disorder (OUD) undergoing buprenorphine medication-assisted treatment (MAT). However, interpretation of urine test results could be challenging. This retrospective study aims to examine the results of quantitative buprenorphine, norbuprenorphine, and creatinine levels in urine testing in relation to sublingual buprenorphine dosage to facilitate an accurate interpretation of urine testing results. METHODS: We reviewed the medical charts of 41 consecutive patients, who were residing in halfway houses where their medication intake was closely monitored and who had enrolled in an office-based MAT program at an urban clinic between July 2018 and June 2019. The patients' urine testing results were reviewed, and demographic variables were recorded. We focused on the patients treated with 8-, 12-, or 16-mg/day of buprenorphine, examining their urine buprenorphine, norbuprenorphine, and creatinine levels. Analysis of variance tested the statistical association between the dosage and urine testing results on the norbuprenorphine-to-creatinine ratio. RESULTS: A total of 240 urine samples from 41 patients were included for this study. The 41 patients received a mean buprenorphine dose of 10.5 ± 3.7 mg/day (range, 4-20 mg/day). Then, this study examined the distribution of the 240 urine samples and then focused on 184 urine samples that came from the 33 patients who were treated with 8-, 12-, and 16-mg/day of buprenorphine, the 3 most common dosages. All of the 184 urine samples had a creatinine level of >20 mg/dL and buprenorphine-to-norbuprenorphine ratio <50:1. The average norbuprenorphine-to-creatinine ratio in the 8 mg/day dosage group was 3.85 ± 2.24 × 10-4 (n = 66; range, 0.44-11.12). The respective ratios in the 12- and 16-mg dosage groups were 5.64 ± 3.40 × 10-4 (n = 83; range, 1.55-22.72) and 6.23 ± 4.92 × 10-4 (n = 35; range, 1.37-27.12). The 3 dosage groups differed significantly in the mean ratios (P < .01), except when the 12- and 16-mg dosage groups were compared (P = .58). The results of this study thus suggest that prescribers should pay attention to the following features: (1) unexpected substance(s) in urine testing, (2) creatinine level under 20 mg/dL, (3) buprenorphine-to-creatinine ratio over 50:1, (4) buprenorphine dosage over 24 mg/day, and (5) norbuprenorphine-to-creatinine ratio consistently under 0.5 × 10-4 in patients treated with 8 mg/day or 1.5 × 10-4 in patients treated with 12 mg/day or more. CONCLUSION: This study suggested parameters for interpreting quantitative urine test results in relation to buprenorphine intake dose in office-based opioid treatment programs.

Bridge clinic buprenorphine program decreases emergency department visits.

INTRODUCTION: Opioid withdrawal due to opioid use disorder (OUD) is an increasing health emergency and complaint in emergency departments (EDs) across the United States. As a response to the increased need for OUD treatment, a low threshold buprenorphine program, or Bridge Clinic, was established within our hospital system. Patients are primarily connected to the Bridge Clinic through the ED, and are able to complete their consultation appointment reliably within 1-3 days of referral. This program also serves to connect patients to community resources for continued treatment of OUD. METHODS: A retrospective chart review was performed to identify ED-based referrals to the Bridge Clinic in the period from January 1, 2017 - December 31, 2018. Outcomes of interest included: (1) ED utilization in the six months before and after consultation at the Bridge Clinic and (2) adherence to buprenorphine therapy at 2-year follow-up. RESULTS: A total of 269 patients were included in the study, with 167 males (62%) and a mean age of 37.8 years. There were 654 total visits to the ED six months before referral to the Bridge Clinic and 381 visits in the six-month period after the initial appointment. There was a high adherence to buprenorphine treatment at 2 year follow up (56%). CONCLUSIONS: These early results suggest that prompt referral to a buprenorphine treatment program significantly reduces ED utilization and connects patients to community resources for continued buprenorphine treatment for OUD.

Buprenorphine therapy in the setting of induced opioid withdrawal from oral naltrexone: a case report.

BACKGROUND: Patients with opioid use disorder (OUD) frequently present to the emergency department for acute treatment of overdose and withdrawal. CASE PRESENTATION: A 29-year-old male presented to the emergency room after intravenous heroin use followed by accidental ingestion of naltrexone. He was treated with buprenorphine with significant improvement in his Clinical Opioid Withdrawal Score, from moderately severe to mild withdrawal symptoms within a few hours. CONCLUSION: Buprenorphine and minimal supportive care can be used to treat acute withdrawal precipitated by oral naltrexone in patients with OUD.

A randomized usability assessment of simulated naloxone administration by community members.

BACKGROUND AND AIMS: Expanded access to naloxone has been identified as a key intervention for reducing opioid-related morbidity and mortality. It is not known which naloxone device will result in rapid, successful administration when administered by community members. The aims of this study were to estimate and compare (1) the rate of successful administration and (2) time to successful administration for single-step nasal spray, multi-step atomized nasal spray and intramuscular simulated naloxone by community members. DESIGN: A prospective, single-site, open-label, randomized usability assessment of simulated naloxone administration in a convenience sample of community members. Participants were randomized to single-step nasal spray (SP), multi-step atomized nasal spray (AT) or intramuscular simulated (IM) naloxone and asked to administer the simulated medication to a mannequin after completing a 2-minute training video. SETTING: New York, USA at a state fair that attracts between 60 000 and 120 000 individuals daily. PARTICIPANTS: A total of 138 participants completed the study over a 2-day period in September 2016. All participants were at least 18 years of age and had no prior naloxone training. MEASUREMENTS: The rate of successful administration and time to successful administration were recorded for each device. FINDINGS: The SP device (100%; P < 0.001) had a higher rate of success compared with the IM device (69.6%). Although success differed between the AT (89.1%) device and IM device, as well as the AT device and SP device, these differences were not significant. The SP device also had a shorter median time to successful administration (34.3 sec) compared with the IM (99.9 sec; P < 0.001) and AT (110.3; P < 0.001) devices. CONCLUSIONS: After video training, community members are able to (1) administer single-step nasal spray naloxone with a higher rate of success than intramuscular naloxone in a simulated overdose setting and (2) administer single-step nasal spray naloxone more rapidly than both intramuscular and multi-step atomized nasal spray naloxone.

Ventricular Tachycardia: A Rare Commotio Cordis Presentation.

Commotio cordis is a rare event caused by an unfortunately timed blunt anterior chest wall impact that most commonly presents in young male adolescents and is the second leading cause of death in young athletes. The most common initial presenting dysrhythmias are ventricular fibrillation and asystole, although other rare dysrhythmias have been reported-predominantly in animal models. To our knowledge, this is the first telemetry-confirmed case of commotio cordis with a presenting cardiac rhythm of ventricular tachycardia. While prompt recognition of commotio cordis and early cardiopulmonary resuscitation and defibrillation (if applicable) are still the treatment in these cases, our case offers potential insight into the underlying commotio cordis process.

Compounded ointment results in severe toxicity in a pediatric patient.

BACKGROUND: Dermal drug delivery is becoming more common, as evidenced by the increased numbers of compounding pharmacies preparing topical products for chronic pain management. Consumers may not appreciate the potency or dangers associated with some of the drugs in these preparations. Pediatric patients are especially at risk for significant toxicity with accidental exposures. We report a case of severe toxicity in an 18-month-old boy from exposure to his father's compounded pain ointment. CASE: An 18-month-old previously healthy child had an ointment applied topically to a diaper rash by his mother, consisting of a single pump of a prescription ointment that her husband received from a compounding pharmacy for neck pain. Approximately 20 minutes later, when the child had been put down for a nap, he had gasping respiration but was otherwise unresponsive. Emergency medical services was called, and the child was unresponsive. In the ED, vital signs were pulse of 57 beats/min, blood pressure 74/35 mm Hg, respiratory rate 21 breaths/min, and O2 saturation 98% on a nonrebreather. Fingerstick glucose was 105 mg/dL. In the ED, physical examination was significant for unresponsiveness, pinpoint pupils, and hyporeflexia. The patient's mental status continued to deteriorate with depressed respirations, and he was intubated. Laboratory results were noncontributory. Electrocardiogram revealed only sinus bradycardia. The patient was transported to a pediatric intensive care unit. He did well over the next several hours with supportive care and had return to normal vital signs over the following 12 hours. He was extubated the following morning without problems. Blood taken at the time of ED presentation had a serum clonidine level of 9.2 ng/mL (reference range, 0.5-4.5 ng/mL) and a norketamine level of 41 ng/mL (reporting limit, >20 ng/mL). CONCLUSIONS: Dermal absorption of drugs leading to significant toxicity in children is well known. Our patient had toxicity from a topical pain medication compounded with several potent drugs known to cause central nervous system depression. There has been an increase in the use of this drug delivery system for management of chronic painful conditions. The popularity and attractiveness of such preparations may be the perception that they are somehow safer and more natural than taking pills. This perception and the fact that these are not dispensed in child-proof containers and are often mailed to the patients without pharmacist counseling can lead to increased inadvertent exposures in the pediatric population.