Rapid Sequence Intubation, is it Time to Find an Alternative Induction Agent? A Narrative Review.

OBJECTIVE: To review the efficacy, safety, and place in therapy of fentanyl as an induction agent for rapid sequence intubation (RSI) in critically ill patients. DATA SOURCES: A comprehensive search of PubMed, EMBASE, and clinical trial registries (1964-June 2021) was performed utilizing the keywords fentanyl, rapid sequence intubation, intubation, induction, anesthesia, hemodynamics, operating room (OR), and emergency. STUDY SELECTION AND DATA EXTRACTION: Only primary literature evaluating fentanyl in combination with a sedative or as the sole induction agent was included in the final analysis. Primary literature included peer-reviewed publications and results posted on ClinicalTrials.gov actively recruiting participants. DATA SYNTHESIS: Fentanyl has been used for decades as an adjunct, and sole induction agent in the OR. Questions surrounding the use of fentanyl as a sole induction agent include optimal dosing and safety in critically ill patients as evaluation in non-OR settings remain limited. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Commonly used induction agents (eg, etomidate and ketamine) are associated with adverse events that may increase risk of morbidity and mortality. Fentanyl, a high-potency opioid could serve as an alternative induction agent for RSI due to its neutral hemodynamic response and fast onset of action. This paper compiles and describes existing data on the use of fentanyl as an induction agent for RSI. CONCLUSION: Fentanyl in combination with sedatives provides optimal intubating conditions with minimal impact on hemodynamic parameters. Future studies should focus on safety and impact of awareness during paralysis before fentanyl can be considered as a sole induction agent.

Tacrolimus Drug-Drug Interaction with Nirmatrelvir/Ritonavir (Paxlovid™) Managed with Phenytoin.

INTRODUCTION: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) pandemic has had a significant impact on communities and health systems. The Federal Drug Administration (FDA) authorized Pfizer's nirmatrelvir/ritonavir (Paxlovid™) through an EUA for the treatment of mild to moderate cases of COVID-19 at high risk for progression to severe disease. Patients with a history of transplant who test positive for COVID-19 are considered high risk because of their immunosuppression and are therefore candidates for nirmatrelvir/ritonavir. CASE REPORT: This is a case of a 67-year-old female with a past medical history of orthotopic heart transplant who received tacrolimus as part of her immunosuppressive regimen. She originally presented with complaints of dyspnea and cough for several days in the setting of COVID-19. The patient was started on nirmatrelvir/ritonavir due to her high risk for progression to severe disease. Four days after starting nirmatrelvir/ritonavir, she presented to the ED for slowed speech, fatigue, weakness, and loss of appetite. Upon admission she was found to have a supratherapeutic tacrolimus level of 176.4 ng/mL and an acute kidney injury. In this case, phenytoin was used as a CYP3A4 inducer to quickly decrease the tacrolimus level to within therapeutic range. CONCLUSION: This case highlights the strong and important drug-drug interaction between tacrolimus and nirmatrelvir/ritonavir leading to toxic levels of tacrolimus. It also demonstrates the utility and effectiveness of phenytoin as a "rescue" medication for tacrolimus toxicity.

Comparison of two different intravenous serotonin antagonists used for chemotherapy-induced nausea and vomiting prophylaxis in patients treated with moderately emetogenic risk regimens: A retrospective analysis from a large academic medical center.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) can be a serious and debilitating adverse effect that is highly feared by cancer patients. For patients receiving moderately emetogenic chemotherapy regimens at our institution in the ambulatory infusion center, palonosetron was selected as the preferred serotonin (5-HT3) antagonist for CINV prophylaxis per the 2016 NCCN Guidelines, when a neurokinin1 antagonist was not included in the prophylactic regimen. The purpose of this study was to evaluate the efficacy of dexamethasone and palonosetron versus granisetron for the prevention of CINV in patients receiving moderately emetogenic chemotherapy regimens. METHODS: This study is an Institutional Review Board-approved, single-center retrospective review of electronic health records including patients who received moderately emetogenic chemotherapy regimens with CINV prophylaxis with dexamethasone and either palonosetron or granisetron. RESULTS: A total of 268 eligible patients were included in the study. Eighty-eight patients received palonosetron and 180 patients received granisetron as their 5-HT3 receptor antagonist between October 31, 2014 and October 31, 2016. There were no statistically significant differences between the two antiemetic groups for the primary outcome of presence of any change in day 1 intravenous prophylactic antiemetics. Nine (10.23%) palonosetron patients and 15 (8.33%) granisetron patients required a change in their day 1 intravenous prophylactic antiemetics (P = 0.610). CONCLUSIONS: Despite palonosetron's better efficacy, longer half-life, and higher binding affinity, the results of this retrospective review demonstrates that the choice of serotonin antagonist, palonosetron or granisetron, did not result in a change in day 1 intravenous prophylactic antiemetics or antiemetic outpatient medications for patients undergoing moderately emetogenic chemotherapy regimens.