Low-dose overlap initiation with split tablets of buprenorphine in intubated intensive care unit patients with opioid use disorder.

BACKGROUND: As the opioid public health crisis evolves to include fentanyl and other potent synthetic opioids, more patients are admitted to the hospital with serious complications of drug use and frequently require higher levels of care, including intensive care unit (ICU) admission, for acute and chronic conditions related to opioid use disorder (OUD). This patient population poses a unique challenge when managing sedation and ensuring adequate ventilation while intubated given their high opioid requirements. Starting a patient on medications such as buprenorphine may be difficult for inpatient providers unfamiliar with its use, which may lead to undertreatment of patients with OUD, prolonged mechanical ventilation and length of stay. METHODS: We developed a 7-day buprenorphine low dose overlap initiation (LDOI) schedule for patients with OUD admitted to the ICU (Table 1). Buprenorphine tablets were split by pharmacists and placed into pre-made blister packs as a kit to be loaded into the automated medication dispensing machine for nursing to administer daily. An internal quality review validated the appropriate dosing of split-dose tablets. To simplify order entry and increase prescriber comfort with this new protocol, we generated an order set within our electronic health record software with prebuilt buprenorphine titration orders. This protocol was implemented alongside patient and healthcare team education and counseling on the LDOI process, with follow-up offered to all patients upon discharge. RESULTS: Here we report a series of 6 ICU patients started on buprenorphine using the LDOI schedule with split buprenorphine tablets. None of the 6 patients experienced precipitated withdrawal upon buprenorphine initiation using the LDOI schedule, and 5/6 patients were successfully extubated during the buprenorphine initiation. Four of six patients had a decrease in daily morphine milligram equivalents, with 3 patients transitioning to buprenorphine alone. CONCLUSION: Initiating buprenorphine via LDOI was found to be successful in the development of a protocol for critically ill patients with OUD. We examined LDOI of buprenorphine in intubated ICU patients and found no events of acute precipitated withdrawal. This protocol can be used as a guide for other institutions seeking to start critically ill patients on medication treatment for OUD during ICU admission.

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.

Microdose Induction of Buprenorphine in a Patient Using Tianeptine.

BACKGROUND: Opioids and opioid alternatives are a serious threat to public health in the United States and other countries. Patients are looking to the internet increasingly as a source of opioid alternatives to self-treat addiction or other psychiatric conditions. It is imperative that patients receive proper treatment to prevent morbidity and mortality related to opioid use disorder. CASE SUMMARY: We report a case of a middle-aged male with a 3-year history of tianeptine use who presented to an outpatient clinic looking for addiction treatment options after failed attempts at tapering his daily dosage of approximately 10 grams per day. The patient underwent a microdose induction of sublingual buprenorphine over a 7-day period (0.25-12 mg) while continuing tianeptine use, and self-monitored for withdrawal symptoms daily using the Clinical Opiate Withdrawal Scale. The patient was seen over the course of treatment by a board-certified toxicologist and addiction specialist on day 2, 5, 6, and 14 to ensure patient safety and treatment adherence. After 14 days of treatment, the patient was able to stop tianeptine use without any major symptoms of withdrawal, anxiety, or depression. DISCUSSION: This case report highlights the effectiveness of buprenorphine in the treatment of opioid use disorder in a patient using tianeptine and further exemplifies the utility of buprenorphine in an outpatient setting.

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.

Retrospective Assessment of Desmopressin Effectiveness and Safety in Patients With Antiplatelet-Associated Intracranial Hemorrhage.

OBJECTIVE: Current international guidelines offer a conditional recommendation to consider a single dose of IV desmopressin (DDAVP) for antiplatelet-associated intracranial hemorrhage based on low-quality evidence. We provide the first comparative assessment analyzing DDAVP effectiveness and safety in antiplatelet-associated intracranial hemorrhage. DESIGN: Retrospective chart review. SETTING: Single tertiary care academic medical center. PATIENTS: Adult patients taking at least one antiplatelet agent based on presenting history and documented evidence of intracranial hemorrhage on cerebral CT scan were included. Patients were excluded for the following reasons: repeat cerebral CT scan not performed within the first 24 hours, noncomparative repeat cerebral CT scan, chronic anticoagulation, administration of fibrinolytic medications, concurrent ischemic stroke, and neurosurgical intervention. In total, 124 patients were included, 55 received DDAVP and 69 did not. INTERVENTIONS: DDAVP treatment at recognition of antiplatelet-associated intracranial hemorrhage versus nontreatment. MEASUREMENTS AND MAIN RESULTS: Primary effectiveness outcome was intracranial hemorrhage expansion greater than or equal to 3 mL during the first 24 hospital hours. Primary safety outcomes were the largest absolute decrease from baseline serum sodium during the first 3 treatment days and new-onset thrombotic events during the first 7 days. DDAVP was associated with 88% decreased likelihood of intracranial hemorrhage expansion during the first 24 hours ([+] DDAVP, 10.9% vs [-] DDAVP, 36.2%; p = 0.002; odds ratio [95% CI], 0.22 [0.08-0.57]). Largest median absolute decrease from baseline serum sodium ([+] DDAVP, 0 mEq/L [0-5 mEq/L] vs [-] DDAVP, 0 mEq/L [0-2 mEq/L]; p = 0.089) and thrombotic events ([+] DDAVP, 7.3% vs [-] DDAVP, 1.4%; p = 0.170; odds ratio [95% CI], 5.33 [0.58-49.16]) were similar between groups. CONCLUSIONS: DDAVP was associated with a decreased likelihood of intracranial hemorrhage expansion during the first 24 hours. DDAVP administration did not significantly affect serum sodium and thrombotic events during the study period.

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.

Cyber threats to health information systems: A systematic review.

BACKGROUND: Recent legislation empowering providers to embrace the electronic exchange of health information leaves the healthcare industry increasingly vulnerable to cybercrime. The objective of this systematic review is to identify the biggest threats to healthcare via cybercrime. OBJECTIVE: The rationale behind this systematic review is to provide a framework for future research by identifying themes and trends of cybercrime in the healthcare industry. METHODS: The authors conducted a systematic search through the CINAHL, Academic Search Complete, PubMed, and ScienceDirect databases to gather literature relative to cyber threats in healthcare. All authors reviewed the articles collected and excluded literature that did not focus on the objective. RESULTS: Researchers selected and examined 19 articles for common themes. The most prevalent cyber-criminal activity in healthcare is identity theft through data breach. Other concepts identified are internal threats, external threats, cyber-squatting, and cyberterrorism. CONCLUSIONS: The industry has now come to rely heavily on digital technologies, which increase risks such as denial of service and data breaches. Current healthcare cyber-security systems do not rival the capabilities of cyber criminals. Security of information is a costly resource and therefore many HCOs may hesitate to invest what is required to protect sensitive information.

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.

The synthetic cannabinoid withdrawal syndrome.

BACKGROUND: Little is known about the effects of synthetic cannabinoids. There has been only one previous report of a withdrawal syndrome from synthetic cannabinoids. We report two cases of a withdrawal syndrome from prolonged habitual use of synthetic cannabinoids. DISCUSSION: Withdrawal from delta-9-THC has been described as a syndrome of anxiety, myalgias, chills, and anorexia. Synthetic cannabinoids are potent than delta-9-THC and thus the withdrawal syndrome is similar but more severe; however the symptoms do not seem to improve with delta-9-THC. The differences in presentation could be due to the fact that synthetic products may contain several heterogeneous compounds, including amphetamine-like substances. CONCLUSIONS: The acute withdrawal syndrome appears to be characterized mainly by anxiety and tachycardia in the absence of any neurological findings or electrolyte disturbances. We describe two patients with symptoms consistent with withdrawal presumably due to synthetic cannabinoid use. The most appropriate treatment for such patients remains unknown, however benzodiazepines are a reasonable first line approach and quetiapine may have some efficacy.

Baclofen overdose mimicking brain death.

CONTEXT: Brain death guidelines should be used with caution in patients with drug intoxication. It is often suggested that physicians use five half-lives of a drug when observing a patient with an overdose. We report two cases of baclofen intoxication where brain death was entertained as an explanation for prolonged coma, with arousal seen days later, suggesting that routine use of a 5-half-life observation period is insufficient with baclofen intoxication. CASE PRESENTATION: A 40-year-old woman was found unresponsive by her family. Baclofen was found to be the responsible overdose. The patient had absent brain stem reflexes and was intubated and in the ICU for several days. Although EEG and Apnea test were inconclusive, the patient was thought to be brain dead and organ procurement was arranged. On hospital day 5, the patient started having purposeful movements. The patient had progressive arousal and was eventually transferred without neurologic sequelae to psychiatry. The second patient also had a massive baclofen overdose, had absence of almost all brain stem reflexes and was also intubated and in the ICU. Brain death was felt to be imminent, but the patient began to awake on hospital day 7. DISCUSSION: Our two cases suggest that baclofen intoxication may result in very prolonged and profound coma and may, in fact, mimic brain death. Conclusion. The determination of brain death in the comatose overdose patient must proceed with caution. An adequate period of time to allow drug clearance must be allowed.

Behavioral and neuroendocrine consequences of social subjugation across adolescence and adulthood.

BACKGROUND: Social subjugation is a very significant and natural stressor in the animal kingdom. Adult animals defeated and subjugated during establishment of dominance hierarchies or territorial encounters can be highly submissive in future agonistic interactions. While much is know about the biological and behavioral consequences of winning and losing fights in adulthood, little is known about adolescence; a developmental period noted for impulsivity and heightened agonistic behavior. The present studies were undertaken to determine if the behavioral and neuroendocrine consequences of social subjugation are comparable in adolescent versus adult Syrian golden hamsters (Mesocricetus auratus). Male siblings were studied from adolescence into adulthood following exposure to counterbalanced episodes of either a benign stressor, i.e., isolation in a novel cage, or the more severe stressor of social subjugation. RESULTS: As adults, hamsters with a history of social subjugation in adolescence show high levels of aggression toward intruders as compared to siblings subjugated in adulthood. Sibling controls subjugated in adulthood are highly submissive with little or no aggressive behavior. However, when subjugated in adulthood, hamsters with the earlier history of subjugation are no different than their sibling controls, i.e., adult subjugation promotes submissive behavior. Sexual motivation is high in adult hamsters with adolescent subjugation and testosterone levels remained stable over adulthood. In contrast, sibling controls subjugated in adulthood show lower levels of sexual motivation and reduced levels of testosterone. Release of cortisol during agonistic encounters is blunted in animals subjugated in adolescence but not adulthood. Measures of anxiety are reduced in hamsters with adolescent subjugation as compared to their sibling controls. CONCLUSION: These data demonstrate a pronounced difference in behavior and neuroendocrinology between adolescent and adult hamsters in their response to social subjugation and suggest adolescence is a resilient period in development.

Regional cerebral blood flow and BOLD responses in conscious and anesthetized rats under basal and hypercapnic conditions: implications for functional MRI studies.

Anesthetics, widely used in magnetic resonance imaging (MRI) studies to avoid movement artifacts, could have profound effects on cerebral blood flow (CBF) and cerebrovascular coupling relative to the awake condition. Quantitative CBF and tissue oxygenation (blood oxygen level-dependent [BOLD]) were measured, using the continuous arterial-spin-labeling technique with echo-planar-imaging acquisition, in awake and anesthetized (2% isoflurane) rats under basal and hypercapnic conditions. All basal blood gases were within physiologic ranges. Blood pressure, respiration, and heart rates were within physiologic ranges in the awake condition but were depressed under anesthesia (P < 0.05). Regional CBF was heterogeneous with whole-brain CBF values of 0.86 +/- 0.25 and 1.27 +/- 0.29 mL. g-1. min-1 under awake and anesthetized conditions, respectively. Surprisingly, CBF was markedly higher (20% to 70% across different brain conditions) under isoflurane-anesthetized condition compared with the awake state (P < 0.01). Hypercapnia decreased pH, and increased Pco(2) and Po(2). During 5% CO(2) challenge, under awake and anesthetized conditions, respectively, CBF increased 51 +/- 11% and 25 +/- 4%, and BOLD increased 7.3 +/- 0.7% and 5.4 +/- 0.4%. During 10% CO(2) challenge, CBF increased 158 +/- 28% and 47 +/- 11%, and BOLD increased 12.5 +/- 0.9% and 7.2 +/- 0.5%. Since CBF and BOLD responses were substantially higher under awake condition whereas blood gases were not statistically different, it was concluded that cerebrovascular reactivity was suppressed by anesthetics. This study also shows that perfusion and perfusion-based functional MRI can be performed in awake animals.