buprenorphine and Asphyxia

Buprenorphine is an opioid agonist-antagonist with a 'ceiling effect' for respiratory depression. Compared with methadone, its unique pharmacology offers practical advantages and enhanced safety when prescribed as recommended and supervised by a physician. Buprenorphine has been approved in several countries as an efficient and safe maintenance therapy for heroin addiction. Its use resulted in a salutary effect with a reduction in heroin overdose-related deaths in countries that implemented office-based buprenorphine maintenance. In France, however, where high-dose buprenorphine has been marketed since 1996, several cases of asphyxic deaths were reported among addicts treated with buprenorphine. Death resulted from buprenorphine intravenous misuse or concomitant sedative drug ingestion, such as benzodiazepines. In these situations of abuse, misuse, or in association with elevated doses of psychotropic drugs, buprenorphine may cause severe respiratory depression. Unlike other opiates, the respiratory effects from buprenorphine are not responsive to naloxone. However, the exact mechanism of buprenorphine-induced effects on ventilation is still unknown. The role of norbuprenorphine, the main N-dealkylated buprenorphine metabolite with potent respiratory depressor activity, also remains unclear. Experimental studies investigating the respiratory effects of combinations of high doses of buprenorphine and benzodiazepines suggested that this drug-drug interaction may result from a pharmacodynamic interaction. A pharmacokinetic interaction between buprenorphine and flunitrazepam is also considered. As there are many questions regarding the possible dangers of death or respiratory depression associated with buprenorphine use, we aimed to present a comprehensive critical review of the published clinical and experimental studies on buprenorphine respiratory effects.

Topics: Analgesics, Opioid; Anti-Anxiety Agents; Asphyxia; Benzodiazepines; Buprenorphine; Drug Interactions; Heroin Dependence; Humans; Respiratory Insufficiency

The first case involving repetitive sexual abuse linked to the use of buprenorphine is reported. Under the tradename Subutex, buprenorphine is largely used for the substitution management of opiate-dependent individuals, but it can also be easily found on the black market. A 14-year-old boy was found dead at the home of a well-known sex offender of minors. At the autopsy, no particular morphological changes were noted, except for pulmonary and visceral congestion. There was no evidence of violence, and no needle marks were found by the pathologist. Toxicological analyses, as achieved by liquid chromatography-mass spectrometry, demonstrated both recent and repetitive buprenorphine exposure in combination with nordiazepam. Buprenorphine concentrations were 1.1 ng/mL and 23 pg/mg in blood and hair, respectively. The boy's death was attributed to accidental asphyxia in a facilitated repetitive sexual abuse situation due to the combination of buprenorphine and benzodiazepines, even at therapeutic concentrations. The use of buprenorphine as a sedative drug was not challenged by the perpetrator.

Topics: Accidents; Adolescent; Asphyxia; Buprenorphine; Child Abuse, Sexual; Fatal Outcome; Hair; Humans; Male; Nordazepam; Substance Abuse Detection