Sedation, Analgesia, and Paralysis in COVID-19 Patients in the Setting of Drug Shortages.

The rapid spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a global pandemic. The 2019 coronavirus disease (COVID-19) presents with a spectrum of symptoms ranging from mild to critical illness requiring intensive care unit (ICU) admission. Acute respiratory distress syndrome is a major complication in patients with severe COVID-19 disease. Currently, there are no recognized pharmacological therapies for COVID-19. However, a large number of COVID-19 patients require respiratory support, with a high percentage requiring invasive ventilation. The rapid spread of the infection has led to a surge in the rate of hospitalizations and ICU admissions, which created a challenge to public health, research, and medical communities. The high demand for several therapies, including sedatives, analgesics, and paralytics, that are often utilized in the care of COVID-19 patients requiring mechanical ventilation, has created pressure on the supply chain resulting in shortages in these critical medications. This has led clinicians to develop conservation strategies and explore alternative therapies for sedation, analgesia, and paralysis in COVID-19 patients. Several of these alternative approaches have demonstrated acceptable levels of sedation, analgesia, and paralysis in different settings but they are not commonly used in the ICU. Additionally, they have unique pharmaceutical properties, limitations, and adverse effects. This narrative review summarizes the literature on alternative drug therapies for the management of sedation, analgesia, and paralysis in COVID-19 patients. Also, this document serves as a resource for clinicians in current and future respiratory illness pandemics in the setting of drug shortages.

Itraconazole vs. posaconazole for antifungal prophylaxis in patients with acute myeloid leukemia undergoing intensive chemotherapy: A retrospective study.

OBJECTIVE: The objective of this study was to compare itraconazole with posaconazole for antifungal prophylaxis in acute myeloid leukemia (AML) patients undergoing intensive chemotherapy. METHODS: Adult patients with AML received either itraconazole or posaconazole for antifungal prophylaxis while undergoing intensive chemotherapy. The primary endpoint was incidence of prophylaxis failure (change in antifungal agent due to suspected invasive fungal infection [IFI], drug intolerance, drug interaction, or adverse event). RESULTS: From February 2016 to January 2018, 90 patients were included in the itraconazole group and 45 patients in the posaconazole group. Prophylaxis failure occurred in 88% of itraconazole recipients compared with 33% of posaconazole recipients (P<0.001). The primary reason for prophylaxis failure with itraconazole was suspected IFI (58%) whereas for posaconazole, failure predominantly related to drug interaction (60%). An antifungal regimen was continued upon discharge in 47% of itraconazole recipients compared with 9% of posaconazole recipients (P<0.001). The use of breakthrough IFI diagnostic tests was not significantly different in the two groups. A larger proportion of drug concentrations were collected in the posaconazole group. CONCLUSIONS: In AML patients undergoing intensive chemotherapy, posaconazole was associated with significantly lower rates of prophylaxis failure and less need for continued antifungal therapy on discharge compared with itraconazole.

Predictors of response to fixed-dose vasopressin in adult patients with septic shock.

BACKGROUND: Vasopressin is often utilized for hemodynamic support in patients with septic shock. However, the most appropriate patient to initiate therapy in is unknown. This study was conducted to determine factors associated with hemodynamic response to fixed-dose vasopressin in patients with septic shock. METHODS: Single-center, retrospective cohort of patients receiving fixed-dose vasopressin for septic shock for at least 6 h with concomitant catecholamines in the medical, surgical, or neurosciences intensive care unit (ICU) at a tertiary care center. Patients were classified as responders or non-responders to fixed-dose vasopressin. Response was defined as a decrease in catecholamine dose requirements and achievement of mean arterial pressure ≥ 65 mmHg at 6 h after initiation of vasopressin. RESULTS: A total of 938 patients were included: 426 responders (45%), 512 non-responders (55%). Responders had lower rates of in-hospital (57 vs. 72%; P < 0.001) and ICU mortality (50 vs. 68%; P < 0.001), and increased ICU-free days at day 14 and hospital-free days at day 28 (2.3 ± 3.8 vs. 1.6 ± 3.3; P < 0.001 and 4.2 ± 7.2 vs. 2.8 ± 6.0; P < 0.001, respectively). On multivariable analysis, non-medical ICU location was associated with increased response odds (OR 1.70; P = 0.0049) and lactate at vasopressin initiation was associated with decreased response odds (OR 0.93; P = 0.0003). Factors not associated with response included APACHE III score, SOFA score, corticosteroid use, and catecholamine dose. CONCLUSION: In this evaluation, 45% responded to the addition of vasopressin with improved outcomes compared to non-responders. The only factors found to be associated with vasopressin response were ICU location and lactate concentration.

Initial Care for Patients with Severe Sepsis and Septic Shock: The Next ICU Quality Measure.

In 2001, the landmark trial of early goal-directed therapy versus standard care for the treatment of severe sepsis and septic shock was published. The marked decrease in mortality with early recognition of sepsis and quantitative resuscitation revolutionized the treatment of patients with these conditions. Specific pieces of the early goal-directed therapy protocol have not been routinely adopted into bedside care; however, early administration of antibiotics, resuscitation with intravenous fluids, and attainment of hemodynamic stability to achieve end-organ perfusion have become the standard of care. To help ensure all patients receive optimal therapy at the first signs of severe sepsis or septic shock, the Surviving Sepsis Campaign has developed a core set of initial process steps and treatment goals grouped into a care bundle. Recognizing the benefit of early quantitative resuscitation on patient care, the National Quality Forum adopted a severe sepsis and septic shock care bundle that is similar to the Surviving Sepsis Campaign bundle. This care bundle has been adopted by the US Centers for Medicare & Medicaid Services, with reimbursement to be influenced beginning in 2017. The purpose of this review is to summarize evidence supporting the sepsis quality measure and care bundle and simplify key components of the care bundle where pharmacists can be impactful in ensuring optimal patient care and bundle compliance.