Background: In the era of highly potent illicit opioids, such as fentanyl and carfentanil, injectable opioid agonist treatment (iOAT) is an effective treatment for those with severe and treatment-refractory opioid use disorder. Untreated opioid use disorder in pregnancy can lead to maternal and neonatal morbidity and mortality. There are currently limited reports on the use of iOAT in pregnant women. The in-patient setting may provide an opportunity to pregnant women for stabilization with iOAT where first line therapies have been ineffective. Case Summary: We report a case of a pregnant individual who engaged in daily intravenous fentanyl who was admitted to the hospital at 29 weeks gestation for stabilization with iOAT, methadone, and slow-release oral morphine. Before admission, she endured 6 opioid overdoses in her pregnancy and continued to use illicit intravenous opioids in the community despite high dose methadone combined with slow-release oral morphine. Her withdrawal symptoms and cravings were ameliorated with hydromorphone 90 mg IM/IV BID, methadone 135 mg daily, and morphine sulfate sustained release 600 mg daily. With this regimen, she was able to reduce her intravenous fentanyl use to a single episode during her hospitalization. She completed her pregnancy in hospital, delivering a full-term live infant after receiving comprehensive prenatal care. Discussion: This case report highlights iOAT as an option during pregnancy and describes the in-patient setting as appropriate to retain high-risk patients in care. This approach may benefit those who are refractory to standard opioid agonist treatment, the numbers of whom may be rising as tolerance to the illicit supply increases.

Background: Methadone is a first-line option for medication-assisted treatment (MAT) of opioid use disorder in pregnancy. However, titration requires low dose initiation and slow titration to avoid respiratory suppression. This presents a problem in pregnancy when subtherapeutic doses may lead to preterm labor and stillbirth. Slow-release oral morphine (SROM) has a superior safety profile in terms of respiratory risks and Qt prolongation but there are fewer studies to support the use and therefore is typically reserved as the third line after methadone and buprenorphine have failed. Together methadone and SROM titrated concurrent may offer an opportunity to optimize the dose of MAT while reducing the time needed to reach a therapeutic dose. Case Summary: We report the case of a pregnant fentanyl user in the second trimester, presenting with threatened preterm labor, stabilizing on a therapeutic dose of methadone and SROM while in a hospitalized setting. Discussion: Over a 7-day period, while admitted to a hospitalized setting, this patient stabilized on a total morphine dose of 1000 mg (divided as 80 mg of methadone and 360 mg of SROM). There were no episodes of oversedation or respiratory suppression during her hospitalization. This case report describes a rapid method to concurrently titrate methadone and SROM to reach therapeutic doses of MAT that can reduce illicit opioid use in pregnancy. Historique: La méthadone est une option de premier choix pour le traitement médicalement assistés (MAT) des troubles liés à l’utilisation d’opioïdes pendant la grossesse. Cependant, la titration nécessite une initiation à faible dose et une titration lente afin d’éviter une suppression respiratoire. Cela pose un problème pendant la grossesse lorsque des doses subthérapeutiques peuvent entraîner un travail prématuré et une mortinatalité. La morphine orale à libération prolongée (MOLP) a un profil de sécurité supérieur en termes de risques respiratoires et d’allongement de l’intervalle Qté, mais il y a moins d’études pour soutenir son utilisation et donc, elle est généralement réservée en troisième ligne après l’échec de la méthadone et de la buprénorphine. L’association de la méthadone et de la MOLP titrée simultanément peut offrir l’occasion d’optimiser la dose de MAT tout en réduisant le temps nécessaire pour atteindre une dose thérapeutique. Résumé du cas: Nous rapportons le cas d’une utilisatrice de fentanyl enceinte au deuxième trimestre, présentant un danger de travail prématuré, se stabilisant sur une dose thérapeutique de méthadone et de MOLP pendant son hospitalisation. Discussion: Sur une période de 7 jours, alors qu’elle était admise en milieu hospitalier, cette patiente s’est stabilisée sur une dose totale de morphine de 1000 mg (divisée en 80 mg de méthadone et 360 mg de MOLP). Il n’y a eu aucun épisode de sédation excessive ou de suppression respiratoire pendant son hospitalisation. Ce rapport de cas décrit une méthode rapide pour titrer simultanément la méthadone et la MOLP afin d’atteindre des doses thérapeutiques de MAT qui peuvent réduire l’utilisation illicite d’opioïdes pendant la grossesse.

poison-induced shock, we administered a 2 mg/kg bolus of amlodipine followed by an infusion of 0.3 mg/kg/hr. The dose was adjusted in the subsequent pigs if a predefined point of toxicity was reached too quickly or not at all during the fivehour study period. Throughout the study period, hemodynamic and laboratory parameters were monitored.Results: Amlodipine preparation: From a total of 2500 mg of amlodipine tablets, our procedure produced 300 mL of amlodipine dissolved in DMSO with a concentration confirmed by UV/vis spectroscopy of 6.9 mg/mL, an 83% yield. Pilot study: The first pig developed hypotension and death within fifteen minutes of the bolus infusion. We thus eliminated the bolus and initiated a more conservative drug infusion rate of 0.25 mg/kg/hour, increasing the infusion every 20 minutes up to 1 mg/kg/hour. This pig lived until the end of the five-hour protocol, but only displayed mild evidence of amlodipine toxicity. The DMSO solvent was found to depolymerize the polyethylene and polyvinylchloride intravenous tubing and much of the drug leaked. For the third pig, the drug was infused through a more durable polytetrafluoroethylene line. The same initial infusion rate was used, increasing the dose until desired effect. This animal had hemodynamic patterns consistent with our expectation of amlodipine toxicity using infusion rates of 2 to 5.5 mg/kg/hour. Conclusion:We piloted a porcine model of amlodipine toxicity for the purpose of studying a novel antidote. Amlodipine can be reliably extracted from tablets in a DMSO solution using a vacuum filtration procedure and concentrations can be confirmed using UV/vis spectroscopy. IV line and catheter material must be considered when using DMSO as a solvent, as many plastics are not compatible with DMSO infusion. An infusion rate of 2 to 5.5 mg/kg/hour in a porcine model, without an initial bolus, will likely produce expected amlodipine toxicity.