Hepatitis C viral clearance with coadministration of crushed sofosbuvir/velpatasvir and high-dose pantoprazole after liver transplantation.

PURPOSE: Direct-acting antivirals (DAAs) allow for successful transplantation of livers from hepatitis C nucleic acid test (NAT)-positive donors to negative recipients. However, limited data exist to support crushing DAAs in patients with multiple absorption concerns or significant drug interactions. SUMMARY: Crushed sofosbuvir/velpatasvir has been successfully used in nontransplant patients with dysphagia, but data in transplant patients with absorption concerns are limited. A 31-year-old hepatitis C-negative female underwent liver transplantation from a hepatitis C NAT-positive donor. Her postoperative course was complicated by a mucormycosis infection, gastrointestinal bleed, and necrotizing pancreatitis requiring treatment with liposomal amphotericin B and pantoprazole 80 mg twice daily. Surgical interventions included an above-the-knee amputation and ileostomy. Hepatitis C treatment was initially delayed because of concern for reduced absorption with crushed DAA administration through the nasogastric (NG) tube, high ileostomy output, gastrointestinal bleed, pancreatitis, and a known drug interaction with pantoprazole. One month after transplantation, the patient's bilirubin level remained elevated and hepatitis C treatment was initiated with sofosbuvir/velpatasvir. Crushed sofosbuvir/velpatasvir was mixed with 30 mL of water and administered through the NG tube daily. Hepatitis C viral loads were obtained weekly during treatment to monitor efficacy. Although the patient died before evaluation of sustained virological response at 12 weeks, hepatitis C viral clearance was observed within 4 weeks of initiating treatment. CONCLUSION: A liver transplant patient exhibited viral clearance of hepatitis C following administration of crushed sofosbuvir/velpatasvir in the setting of multiple absorption concerns.

Perioperative methadone prescribing and association with respiratory depression.

OBJECTIVE: Over 80 percent of surgery patients experience acute post-operative pain and less than half feel their pain is adequately controlled. Patients receiving chronic opioids, including methadone, are at the highest risk of inadequate pain control. Guidelines do not provide specific recommendations for analgesia management in this population. The purpose of this study was to evaluate the association between post-operative methadone use and respiratory depression. DESIGN: This study was a single center, retrospective, cohort study of adult patients. SETTING: Patients included were admitted to a single academic medical center from July 2016 to September 2018. PARTICIPANTS: Medical records of adult inpatients with an operative procedure who received perioperative methadone were reviewed. MAIN OUTCOME MEASURES: Preoperative methadone use was evaluated for all patients. Post-operative methadone dosing was compared to preoperative methadone dosing. Post-operative respiratory depression was evaluated. Logistic regression was performed to identify risk factors for respiratory depression. RESULTS: Two hundred ninety-eight patients were included in the study. Patients were divided into groups based on pre-operative methadone use. Over 90 percent of patients were on preoperative methadone. There were no significant differences in baseline characteristics between groups. In the initial seven post-operative days, 14.8 percent of patients had documented respiratory depression. Respiratory depression was more common among patients who were newly initiated on methadone post-operatively. Factors associated with respiratory depression included male sex, increased age, and new post-operative methadone initiation. CONCLUSIONS: Most patients who were administered post-operative methadone were on preoperative methadone. New post-operative methadone initiation was a risk factor for respiratory depression.