Pharmacotherapy optimization for rapid sequence intubation in the emergency department.

PURPOSE: Rapid-sequence intubation (RSI) is the process of administering a sedative and neuromuscular blocking agent (NMBA) in rapid succession to facilitate endotracheal intubation. It is the most common and preferred method for intubation of patients presenting to the emergency department (ED). The selection and use of medications to facilitate RSI is critical for success. The purpose of this review is to describe pharmacotherapies used during the RSI process, discuss current clinical controversies in RSI medication selection, and review pharmacotherapy considerations for alternative intubation methods. SUMMARY: There are several steps to the intubation process requiring medication considerations, including pretreatment, induction, paralysis, and post-intubation sedation and analgesia. Pretreatment medications include atropine, lidocaine, and fentanyl; but use of these agents in clinical practice has fallen out of favor as there is limited evidence for their use outside of select clinical scenarios. There are several options for induction agents, though etomidate and ketamine are the most used due to their more favorable hemodynamic profiles. Currently there is retrospective evidence that etomidate may produce less hypotension than ketamine in patients presenting with shock or sepsis. Succinylcholine and rocuronium are the preferred neuromuscular blocking agents, and the literature suggests minimal differences between succinylcholine and high dose rocuronium in first-pass success rates. Selection between the two is based on patient specific factors, half-life and adverse effect profiles. Finally, medication-assisted preoxygenation and awake intubation are less common methods for intubation in the ED but require different considerations for medication use. AREAS FOR FUTURE RESEARCH: The optimal selection, dosing, and administration of RSI medications is complicated, and further research is needed in several areas. Additional prospective studies are needed to determine optimal induction agent selection and dosing in patients presenting with shock or sepsis. Controversy exists over optimal medication administration order (paralytic first vs induction first) and medication dosing in obese patients, but there is insufficient evidence to significantly alter current practices regarding medication dosing and administration. Further research examining awareness with paralysis during RSI is needed before definitive and widespread practice changes to medication use during RSI can be made.

Real-world utilization of andexanet alfa.

OBJECTIVE: In 2018, the FDA approved andexanet alfa for the reversal of life-threatening hemorrhages in patients anticoagulated with apixaban or rivaroxaban. Yet, cost-effective factor Xa inhibitor reversal remains controversial. The objective of this study was to describe real world utilization of andexanet alfa. METHODS: This was a retrospective case series of patients receiving andexanet alfa between July 28, 2018 and April 29, 2019 at a large academic health system. Baseline demographics, anticoagulant type and reversal, as well as brain imaging were collected. Primary endpoints were stability of hematoma for intracranial hemorrhage (ICH), and hemostatic effectiveness for patients undergoing surgical procedures. Secondary endpoints were thromboembolism and 30 day mortality. RESULTS: Of the 25 patients evaluated, 13 received andexanet alfa for ICH. Eleven of the 13 had follow-up imaging available and stability was observed in 90.9%. Three patients received andexanet alfa for reversal prior to surgical procedures, and 100% hemostatic effectiveness was achieved. Nine patients received andexanet alfa for reversal of extracranial bleeding, including gastrointestinal bleed (n=4). There were no thrombotic events in our cohort, and 30 day mortality was 24%. Sixty-four percent of patients would have met exclusion criteria for the ANNEXA-4 trial. CONCLUSION: This is the largest series to date describing real-world utilization of andexanet alfa. Our series showed hemostatic efficacy in 90.9% of patients with ICH, and 100% in patients undergoing surgical procedures. There were no thrombotic complications. Yet, larger and comparative studies are needed to clarify the optimal agent and patient selection for reversal of factor Xa inhibitors.

Accuracy of Point-of-Care Blood Glucose Level Measurements in Critically Ill Patients with Sepsis Receiving High-Dose Intravenous Vitamin C.

STUDY OBJECTIVE: High-dose intravenous vitamin C is a potential treatment option for patients with sepsis and may interfere with point-of-care (POC) blood glucose (BG) testing. This study aimed to determine if vitamin C dosing used for sepsis affected POC BG level results. DESIGN: Prospective observational pilot study. SETTING: Intensive care unit in a large academic tertiary care medical center. PATIENTS: Five consecutive critically ill adults hospitalized between April 1 and June 1, 2017, who received two or more doses of intravenous vitamin C 1500 mg for the treatment of sepsis and had at least two paired POC BG levels and laboratory venous BG levels measured within 1 hour of each other during vitamin C therapy. MEASUREMENTS AND MAIN RESULTS: The performance of POC BG level measurement was compared with the reference method of laboratory BG level measurement. The concordance to minimum accuracy criteria for BG meters set forth by the International Organization for Standardization (ISO) 15197:2013, the measurement of agreement between POC BG level and laboratory BG level using the Bland-Altman method, and the clinical accuracy through Parkes error grid analysis were assessed. A total of 16 paired POC and laboratory BG level measurements from the five patients were included. The accuracy of POC BG with laboratory BG level measurements during vitamin C administration according to ISO 15197:2013 criteria was 81.3%, which did not meet the minimum accuracy criteria of 95%. The Bland-Altman analysis showed a mean difference between POC and laboratory BG levels of 8.9 mg/dl, and the Parkes error grid analysis showed that the differences between POC and laboratory BG level measurements would not have resulted in a change in clinical action. CONCLUSION: The accuracy and agreement of POC and laboratory BG level measurements in critically ill patients receiving vitamin C were consistent with previously published reports in critically ill patients not receiving vitamin C and did not demonstrate clinically significant interference due to vitamin C dosing for sepsis.