The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID‐19) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID‐19. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS‐CoV‐2. Critically ill patients with COVID‐19 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID‐19, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.

Approximately 16-31% of patients in the intensive care unit (ICU) have an alcohol use disorder and are at risk for developing alcohol withdrawal syndrome (AWS). Patients admitted to the ICU with AWS have an increased hospital and ICU length of stay, longer duration of mechanical ventilation, higher costs, and increased mortality compared with those admitted without an alcohol-related disorder. Despite the high prevalence of AWS among ICU patients, no guidelines for the recognition or management of AWS or delirium tremens in the critically ill currently exist, leading to tremendous variability in clinical practice. Goals of care should include immediate management of dehydration, nutritional deficits, and electrolyte derangements; relief of withdrawal symptoms; prevention of progression of symptoms; and treatment of comorbid illnesses. Symptom-triggered treatment of AWS with γ-aminobutyric acid receptor agonists is the cornerstone of therapy. Benzodiazepines (BZDs) are most studied and are often the preferred first-line agents due to their efficacy and safety profile. However, controversy still exists as to who should receive treatment, how to administer BZDs, and which BZD to use. Although most patients with AWS respond to usual doses of BZDs, ICU clinicians are challenged with managing BZD-resistant patients. Recent literature has shown that using an early multimodal approach to managing BZD-resistant patients appears beneficial in rapidly improving symptoms. This review highlights the results of recent promising studies published between 2011 and 2015 evaluating adjunctive therapies for BZD-resistant alcohol withdrawal such as antiepileptics, baclofen, dexmedetomidine, ethanol, ketamine, phenobarbital, propofol, and ketamine. We provide guidance on the places in therapy for select agents for management of critically ill patients in the presence of AWS.

Background and Objectives: Currently, no dosing information exists for ceftaroline fosamil in patients undergoing continuous renal replacement therapy (CRRT). The objectives of this study are to characterize the pharmacokinetics of ceftaroline in critically ill patients undergoing CRRT modalities and to derive individualized dosing recommendations. Methods: This pharmacokinetic study aimed to enroll critically ill patients receiving ceftaroline fosamil and any CRRT modality from adult intensive care units. Selection of the specific CRRT modality and dosing regimen was based on clinical discretion. Pre-filter, post-filter, and ultrafiltrate samples were obtained before the administration of the fourth dose, after the completion of the infusion, and up to five additional time points post-infusion. Plasma concentrations were measured using a validated ultra-high performance liquid chromatography assay. Individual pharmacokinetic parameters were calculated using non-compartmental analysis. Results: Four patients were enrolled to investigate the need for dosing adjustments. The average sieving coefficient for ceftaroline was 0.81 ± 0.1, indicating high filter efficiency. The average volume of distribution was 41.8 L (0.48 L/kg) and is within the previously reported range in patients with normal renal function. Non-renal clearance accounted for more than 50% of the total clearance observed in patients. The observed pharmacokinetic profiles suggest that the pharmacodynamic target for 2log 10 CFU reduction from baseline (%fT >1 mg/L of 50%) was met for each patient. Due to the impact of CRRT and non-renal clearance, dosing recommendations were derived for different ranges of effluent flow rates and adjusted body weights. For a patient with an adjusted body weight of 70 kg and receiving CRRT at an effluent flow rate of 3 L/h, a ceftaroline fosamil dosing regimen of 400 mg every 12 h is proposed. Conclusion: Ceftaroline is cleared extensively in critically ill patients receiving CRRT and may impact pharmacodynamic target achievement. Dose adjustments should be based on the intensity of the CRRT regimen, patient weight, and the clinical status of the patient.

Purpose: Opioids are one of the high-risk medication classes that are administered to critically ill patients during their intensive care unit (ICU) stay. However, little attention has been given to inpatient opioid prescribing practices, especially in critically ill patients. The purpose of our study was to characterize opioid prescribing practices across 2 transitions of care during an inpatient hospital stay: medical ICU (MICU)/intermediate care unit (IMC) to floor and floor to hospital discharge and identify potential patient-specific factors that impact opioid continuation. Methods: This is a retrospective cohort study evaluating opioid-naive adult patients with new opioid therapy initiated in MICU/IMC at a tertiary care academic medical center from December 1, 2016, to November 30, 2017. Opioid continuation rate was assessed twice: transition 1 (MICU/IMC to floor) and transition 2 (floor to hospital discharge). Results: In total, 112 opioid-naive patients with initial opioid administration in the MICU/IMC were included. Opioid therapy was continued in 56.1% (37/66) at transition 1 and 56.8% of patients (21/37) at transition 2. Patients with opioids continued at transition 1 had a longer hospital length of stay compared to those not continued on opioids, 22 (interquartile range [IQR] 11-36) vs 8 (IQR 6-14; P = .0004). Among the patients continued on opioids at hospital discharge, intubation during hospital stay and cumulative opioid dosage were greater than those not continued on opioids (17 [80.9%] vs 7 [43.8%], P = .019; and 3482 mcg [IQR 1690-9530] vs 732.5 mcg [IQR 187.5-1360.9], P = .0018, respectively). Conclusions: Opioid-naive patients receiving opioid therapy in the MICU/IMC had a continuation rate of >56% during transitions of care, including hospital discharge. Factors that contributed to the continuation of opioids at transitions of care included longer hospital length of stay, intubation, and cumulative hospital opioid dosage. These findings may help to provide health systems with guidance on targeted opioid stewardship programs.

Glycemic control is an important quality indicator in the management of intensive care unit patients. Tight glycemic control and/or insulin infusion protocols may reduce complications and improve outcomes in certain intensive care unit patients. Unfortunately, a consistent method of describing glycemic control has not been used for this population. A standardized metric is needed to adequately evaluate quality performance as well as interpret and apply the literature. The current glycemic control metrics such as mean, median, mean morning, hyperglycemic index, and time-weighted averages will be analyzed. The complexities associated with reporting glycemic control data for national quality performance will also be reviewed. The goal is to facilitate and propose the selection of a glycemic control metric for critically ill patients that can be universally applied in clinical trials and quality performance standards.