The Safety of Continuous Infusion Propofol in Mechanically Ventilated Adults With Coronavirus Disease 2019.

BACKGROUND: Propofol is commonly used to achieve ventilator synchrony in critically ill patients with coronavirus disease 2019 (COVID-19), yet its safety in this patient population is unknown. OBJECTIVE: To evaluate the safety, in particular the incidence of hypertriglyceridemia, of continuous infusion propofol in patients with COVID-19. METHODS: This was a retrospective study at 1 academic medical center and 1 affiliated teaching hospital in New York City. Adult, critically ill patients with COVID-19 who received continuous infusion propofol were included. Patients who received propofol for <12 hours, were transferred from an outside hospital while on mechanical ventilation, or did not have a triglyceride concentration obtained during the infusion were excluded. RESULTS: A total of 252 patients were included. Hypertriglyceridemia (serum triglyceride concentration ≥ 400 mg/dL) occurred in 38.9% of patients after a median cumulative dose of 4307 mg (interquartile range [IQR], 2448-9431 mg). The median time to triglyceride elevation was 3.8 days (IQR, 1.9-9.1 days). In the multivariable regression analysis, obese patients had a significantly greater odds of hypertriglyceridemia (odds ratio = 1.87; 95% CI = 1.10, 3.21). There was no occurrence of acute pancreatitis. The incidence of possible propofol-related infusion syndrome was 3.2%. CONCLUSION AND RELEVANCE: Hypertriglyceridemia occurred frequently in patients with COVID-19 who received propofol but did not lead to acute pancreatitis. Elevated triglyceride concentrations occurred more often and at lower cumulative doses than previously reported in patients without COVID-19. Application of these data may aid in optimal monitoring for serious adverse effects of propofol in patients with COVID-19.

Corticosteroid use in ARDS and its application to evolving therapeutics for coronavirus disease 2019 (COVID-19): A systematic review.

Data regarding the use of corticosteroids for treatment of acute respiratory distress syndrome (ARDS) are conflicting. As the coronavirus disease 2019 (COVID-19) pandemic progresses, more literature supporting the use of corticosteroids for COVID-19 and non-COVID-19 ARDS have emerged. Glucocorticoids are proposed to attenuate the inflammatory response and prevent progression to the fibroproliferative phase of ARDS through their multiple mechanisms and anti-inflammatory properties. The purpose of this systematic review was to comprehensively evaluate the literature surrounding corticosteroid use in ARDS (non-COVID-19 and COVID-19) in addition to a narrative review of clinical considerations of corticosteroid use in these patient populations. OVID Medline and EMBASE were searched. Randomized controlled trials evaluating the use of corticosteroids for COVID-19 and non-COVID-19 ARDS in adult patients on mortality outcomes were included. Risk of bias was assessed with the Risk of Bias 2.0 tool. There were 388 studies identified, 15 of which met the inclusion criteria that included a total of 8877 patients. The studies included in our review reported a mortality benefit in 6/15 (40%) studies with benefit being seen at varying time points of mortality follow-up (ICU survival, hospital, and 28 and 60 days) in the COVID-19 and non-COVID-19 ARDS studies. The two non-COVID19 trials assessing lung injury score improvements found that corticosteroids led to significant improvements with corticosteroid use. The number of mechanical ventilation-free days significantly were found to be increased with the use of corticosteroids in all four studies that assessed this outcome. Corticosteroids are associated with improvements in mortality and ventilator-free days in critically ill patients with both COVID-19 and non-COVID-19 ARDS, and evidence suggests their use should be encouraged in these settings. However, due to substantial differences in the corticosteroid regimens utilized in these trials, questions still remain regarding the optimal corticosteroid agent, dose, and duration in patients with ARDS.

Impact of heart failure drug therapy on rates of gastrointestinal bleeding in LVAD recipients: An INTERMACS analysis.

INTRODUCTION: Gastrointestinal bleeding (GIB) remains a common and vexing complication of left ventricular assist device (LVAD) support. Recent single-center analyses suggest that ACE inhibitors (ACEi)/angiotensin receptor blockers (ARB) and digoxin may prevent GIB in LVAD patients. Here we evaluate the effect of guideline-directed medical therapies (GDMT) for heart failure (HF) on rates of GIB through analysis of the INTERMACS registry database. METHODS: Thirteen thousand seven hundred thirty-two patients who received a continuous-flow LVAD and were on antiplatelet therapy and anticoagulation with warfarin after 3 months of pump support were included in the analysis. GIB events following implant were assessed based on receipt of ACEi/ARB, beta-blockers (BB), mineralocorticoid receptor antagonist (MRA), amiodarone, digoxin, loop diuretics, and phosphiesterase-5 inhibitors (PDE5). Backwards stepwise cox regression was used to control for confounding of each drug class on each other, as well as for clinical variables like age, gender, renal function, HF etiology, and device strategy. RESULTS: After 3 months of pump support medications used in LVAD patients were BB (65.0%), ACEi/ARB (51.7%), Amio (43.7%), MRA (37.9%), and loop diuretics (70.1%). In patients with available data, PDE and digoxin use were 18.2% and 16.9%, respectively. The overall incidence of GIB was 19.5% at 2 years of support. After adjustment for other clinical variables, loop diuretics (HR 1.274, p < 0.001) and PDE5 (HR 1.241, p < 0.001) use were associated with increased risk of GIB, while use of BB (HR 0.871, p = 0.006) was associated with lower risk of GIB. ACEi/ARB (HR 1.002, p = 0.971), Amio (HR 1.083, p = 0.106), AA (HR 0.967, p = 0.522) or digoxin (HR 1.087, p = 0.169) did not affect GIB rates on LVAD support (Figure). CONCLUSION: Despite recent reports, ACEi/ARB, MRA, Amio, and digoxin use does not appear to be associated with GIB during LVAD support. The heightened risk seen in those on loop diuretics may reflect venous congestion in these patients, while antiplatelet effects of PDE5 could drive the higher risk of GIB.

A reappraisal of the pharmacologic management of gastrointestinal bleeding in patients with continuous flow left ventricular assist devices.

Advancements in the design and functionality of continuous flow left ventricular assist devices (CF-LVADs), as well as a limited number of donor hearts, have resulted in an increased utilization of this therapy among advanced heart failure (HF) patients. Despite these advancements, gastrointestinal bleeding (GIB) remains a common complication after CF-LVAD implantation. The mechanism of GIB in these patients is complex and includes a combination of angiodysplasia, platelet dysfunction, acquired von Willebrand disease, and a variety of patient-specific factors including advanced age and history of GIB. Several pharmacotherapy options have been reported in the literature, though studies supporting the use of these agents are often small, retrospective reports. Within this review, we discuss the various pharmacologic agents, their proposed mechanisms of action, and the available literature pertaining to their effectiveness and tolerability. Additionally, we propose an evidence-based treatment algorithm, encompassing the updated literature, cost of therapy, medication side effects, and ease of administration.

Analgesia and Sedation Strategies in Mechanically Ventilated Adults with COVID-19.

Evidence-based management of analgesia and sedation in COVID-19-associated acute respiratory distress syndrome remains limited. Non-guideline recommended analgesic and sedative medication regimens and deeper sedation targets have been employed for patients with COVID-19 due to exaggerated analgesia and sedation requirements with extended durations of mechanical ventilation. This, coupled with a desire to minimize nurse entry into COVID-19 patient rooms, marked obesity, altered end-organ function, and evolving medication shortages, presents numerous short- and long-term challenges. Alternative analgesic and sedative agents and regimens may pose safety risks and require judicious bedside management for appropriate use. The purpose of this commentary is to provide considerations and solutions for designing safe and effective analgesia and sedation strategies for adult patients with considerable ventilator dyssynchrony and sedation requirements, such as COVID-19.

Engineering a Brighter Future: The Evolving Role of the Pharmacist in the Era of the HeartMate 3.

Continuous-flow left-ventricular assist devices (CF-LVADs) are an option for patients with end-stage heart failure requiring durable mechanical circulatory support. Two of the older-generation CF-LVADs have been associated with multiple device-related complications, including bleeding and thrombosis. The newest generation CF-LVAD, the HeartMate 3, was engineered specifically to prevent device-related thrombosis. As more data enhance our understanding of the burden of bleeding and thrombotic adverse events, patients with durable mechanical circulatory support may require less-aggressive antithrombotic therapy.

Correlation Between mMINDS and CIWA-Ar Scoring Tools in Patients With Alcohol Withdrawal Syndrome.

BACKGROUND: Many alcohol withdrawal scoring tools are used in hospitalized patients to assess the severity of alcohol withdrawal and guide treatment. The revised Clinical Institute Withdrawal Assessment (CIWA-Ar) and the modified Minnesota Detoxification Scale (mMINDS) are commonly used but have never been correlated. OBJECTIVE: To determine the strength of correlation between the CIWA-Ar and mMINDS scoring tools in patients with alcohol withdrawal syndrome. METHODS: A single-center, prospective correlation study conducted at a large academic medical center. Patients treated for alcohol withdrawal syndrome according to the Yale Alcohol Withdrawal Protocol were identified daily, and both the CIWA-Ar and mMINDS were administered at each time point required by the protocol. Clinical data were obtained from the electronic medical records. RESULTS: A total of 185 CIWA-Ar and mMINDS scores were collected in 30 patients. The Pearson correlation coefficient across all scores was 0.82, indicating a strong correlation. The Pearson correlation coefficient was 0.87 for CIWA-Ar scores of 10 or less and 0.52 for CIWA-Ar scores above 10. Strong correlations were also shown for tremor (0.98), agitation (0.84), and orientation (0.87). CONCLUSIONS: The correlation between the CIWA-Ar and mMINDS tools is strong and appears to be most robust in patients with CIWA-Ar scores of 10 or less.