Major Publications in the Critical Care Pharmacotherapy Literature: 2022.

OBJECTIVES: A number of trials related to critical care pharmacotherapy were published in 2022. We aimed to summarize the most influential publications related to the pharmacotherapeutic care of critically ill patients in 2022. DATA SOURCES: PubMed/Medical Literature Analysis and Retrieval System Online and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. STUDY SELECTION: Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2022, and December 31, 2022, were included in this article. DATA EXTRACTION: Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included and stratified into clinical domains based upon consistent themes. Consensus was obtained on the most influential publication within each clinical domain utilizing an a priori defined three-round modified Delphi process with the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature. DATA SYNTHESIS: The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update yielded a total of 704 articles, of which 660 were excluded. The remaining 44 articles were stratified into the following clinical domains: emergency/neurology, cardiovascular, gastroenterology/fluids/nutrition, hematology, infectious diseases/immunomodulation, and endocrine/metabolic. The final article selected from each clinical domain was summarized following a three-round modified Delphi process and included three randomized controlled trials and three systematic review/meta-analyses. Article topics summarized included dexmedetomidine versus other sedatives during mechanical ventilation, beta-blocker treatment in the critically ill, restriction of IV fluids in septic shock, venous thromboembolism prophylaxis in critically ill adults, duration of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia, and low-dose methylprednisolone treatment in severe community-acquired pneumonia. CONCLUSIONS: This concise review provides a perspective on articles published in 2022 that are relevant to the pharmacotherapeutic care of critically ill patients and their potential impact on clinical practice.

Benefits and harms of treatments for chronic nonspecific low back pain without radiculopathy: systematic review and meta-analysis.

BACKGROUND CONTEXT: Currently, there are no published studies that compare nonpharmacological, pharmacological and invasive treatments for chronic low back pain in adults and provide summary statistics for benefits and harms. PURPOSE: The aim of this review was to compare the benefits and harms of treatments for the management of chronic low back pain without radiculopathy and to report the findings in a format that facilitates direct comparison (Benefit-Harm Scale: level 1 to 7). DESIGN: Systematic review and meta-analysis of randomized controlled trials, including trial registries, from electronic databases up to 23rd May 2022. PATIENT SAMPLE: Adults with chronic nonspecific low back pain, excluding radicular pain, in any clinical setting. OUTCOME MEASURES: Comparison of pain at immediate-term (≤2 weeks) and short-term (>2 weeks to ≤12 weeks) and serious adverse events using the Benefit-Harm Scale (level 1 to 7). METHODS: This was a registered systematic review and meta-analysis of randomized controlled trials. Interventions included nonpharmacological (acupuncture, spinal manipulation), pharmacological and invasive treatments compared to placebo. Best evidence criteria was used. Two independent reviewers conducted eligibility assessment, data extraction and quality appraisal. RESULTS: The search retrieved 17,362 records. Three studies provided data on the benefits of interventions, and 30 provided data on harms. Studies included interventions of acupuncture (n=8); manipulation (n=2); pharmacological therapies (n=9), including NSAIDs and opioid analgesics; surgery (n=8); and epidural corticosteroid injections (n=3). Acupuncture (standardized mean difference (SMD) -0.51, 95%CI -0.88 to -0.14, n=1 trial, moderate quality of evidence, benefit rating of 3) and manipulation (SMD -0.39, 95%CI -0.56 to -0.21, n=2 trials, moderate quality of evidence, benefit rating of 5) were effective in reducing pain intensity compared to sham. The benefit of the other interventions was scored as uncertain due to not being effective, statistical heterogeneity preventing pooling of effect sizes, or the absence of relevant trials. The harms level warnings were at the lowest (eg, indicating rarer risk of events) for acupuncture, spinal manipulation, NSAIDs, combination ingredient opioids, and steroid injections, while they were higher for single ingredient opioid analgesics (level 4) and surgery (level 6). CONCLUSIONS: There is uncertainty about the benefits and harms of all the interventions reviewed due to the lack of trials conducted in patients with chronic nonspecific low back pain without radiculopathy. From the limited trials conducted, nonpharmacological interventions of acupuncture and spinal manipulation provide safer benefits than pharmacological or invasive interventions. However, more research is needed. There were high harms ratings for opioids and surgery.

Thrombotic Events and Anticoagulation-Related Bleeding Complications in Critically Ill Patients with Coronavirus Disease 2019.

Background: Thrombosis (T) is common in coronavirus disease 2019 (COVID-19) patients, and d-dimer concentrations correlate with outcomes. Controversy exists with regards to anticoagulation (AC) for patients. We implemented a full-heparinization AC protocol from the onset of the pandemic and hypothesized that a safety signal would be undetectable. Patients and Methods: Prospective evaluation of 111 patients with COVID-19 critical illness hospitalized from March to June 2020. All patients received therapeutic heparinoid-based AC from admission. Incidences of T, bleeding (B), or both (BT) were noted. The primary outcome was mortality. Kruskal-Wallis test and logistic regression were performed. Results are expressed as n (%), median (interquartile range) and odds ratios with 95% confidence intervals. Alpha was set at 0.05. Results: Thirty-two patients (28%) had T, 23 (20%) had B, and 14 (12%) had BT; 42 (40%) patients were unaffected. Two logistic regression models (outcome = mortality) evaluated BT as T, or BT as B. For BT as T, neither T, B, nor male gender predicted mortality; similarly, for BT as B, neither T, B, nor male gender predicted mortality. Factors associated with higher odds of death included higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00-1.13; p = 0.0045), higher d-dimer concentration (OR, 1.00; 95% CI, 1.00-1.01; p = 0.043), and higher activated partial thromboplastin time (aPTT; OR, 1.09; 95% CI, 1.02-1.16; p = 0.010). Conclusions: Neither T nor B predicted mortality in this prospective cohort of anticoagulated patients with COVID-19 critical illness. These data support continued full-dose heparinoid prophylaxis.

Effect of desmopressin acetate on acute spontaneous intracranial hemorrhage in patients on antiplatelet therapy.

PURPOSE: To evaluate the impact of desmopressin acetate (DDAVP) on poor outcomes, hematoma expansion, and adverse events in patients diagnosed with a non-traumatic, antiplatelet-associated intracranial hemorrhage (ICH). METHODS: This was a multicenter, retrospective, propensity-matched cohort study comparing DDAVP to control in patients diagnosed with a non-traumatic ICH previously on antiplatelet therapy. Notable exclusion criteria included admission to trauma service, subarachnoid hemorrhages, confounding coagulopathic factors, and hematoma evacuation. Poor outcome, defined as discharge to hospice or in-patient mortality, was the primary outcome. Secondary outcomes included intracranial hematoma expansion and occurrence of adverse events, which included hyponatremia and thromboembolic events. RESULTS: A total of 49 patients receiving DDAVP were compared to 107 controls in the unmatched cohort. Thirty-seven patients treated with DDAVP and 55 controls were included in the propensity-matched analysis, which was adjusted for age, ethnicity, history of diabetes, receipt of platelet transfusion, and thromboembolism prophylaxis. Poor outcome (16.2% DDAVP vs 29% control, p = 0.13), rates of hematoma expansion (11.8% DDAVP vs 11.1% control, p = 0.99), and adverse events (21.6% DDAVP vs 20% control, p = 0.99) were statistically similar between the matched groups. CONCLUSIONS: DDAVP administration in patients with spontaneous antiplatelet-associated ICH was not associated with a reduction in poor outcomes, hematoma expansion, or an increase in adverse events. Use of DDAVP in this patient population appears to be safe. Larger prospective studies are warranted to evaluate DDAVP utility in this patient population.

The Safety and Efficacy of Desmopressin in Patients With Intracranial Hemorrhage and a History of Alcohol Use.

BACKGROUND: Patients with a history of alcohol use disorder are at an increased risk of hematoma expansion following intracranial hemorrhage (ICH) due to the effects of alcohol on platelet aggregation. Desmopressin (DDAVP) improves platelet aggregation and may decrease hematoma expansion in patients with ICH. However, DDAVP may also increase the risk of hyponatremia and thrombotic events. Evidence is limited regarding the safety and efficacy of DDAVP in alcohol use (AU)-associated ICH. METHODS: This was a retrospective chart review of adult patients with radiographic evidence of ICH and a confirmed or suspected history of alcohol use upon admission. Patients were categorized into groups based on DDAVP administration. Safety outcomes included hyponatremia (serum sodium <135 mEq/L or decrease in serum sodium of ≥ 5 mEq/L for patients with baseline sodium <135 mEq/L) within 24 hours of ICH and thrombotic events within 7 days of ICH. The primary efficacy outcome was the incidence of hematoma expansion, defined as any expansion of the hemorrhage noted on repeat imaging within 32 hours. RESULTS: In total, 52 patients were included in the safety analysis (27 DDAVP and 25 non-DDAVP). Although hyponatremia was numerically higher in the DDAVP group, there was no significant difference between groups (19.2% vs 4.2%, P = 0.192). Thrombotic complications were similar between the DDAVP and non-DDAVP groups (11.1% vs. 8%, P = 1.0). Thirty-nine patients met criteria for hemostatic efficacy analysis. There was no difference in hematoma expansion between the DDAVP and non-DDAVP groups (23.1% vs 34.6%, P = 0.71) and these findings were consistent after adjusting for differences in baseline characteristics (OR 0.63, 95% CI 0.1-3.3). CONCLUSION: The administration of DDAVP was not associated with adverse safety events, but did not significantly reduce the incidence of hematoma expansion in patients with AU-associated ICH.

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.

Skin Failure Among Critically Ill Patients Afflicted with Coronavirus Disease 2019 (COVID-19).

Objective: To characterize skin integrity among coronavirus disease 2019 (COVID-19) patients treated in the intensive care unit (ICU), and identify risk factors for skin failure (SF) in these patients. Design: The characteristic, profound pro-inflammatory, hypercoagulable state of COVID-19 is manifested by the high severity of illness and extensive organ dysfunction observed in these patients. SF in critically ill patients, although described previously, exhibits a uniquely complex pathogenesis in this population. Patients: Retrospective review of all COVID-19 patients (confirmed positive for severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) admitted to a single surgical ICU for at least 48 hours between March-June 2020. Interventions: Data were extracted from a COVID-19 institutional data repository that harvested data from electronic health records and other clinical data sources. Demographics; coagulation/inflammation biomarkers; number, location, and stage of SF lesions; resource utilization; and outcomes were captured. Measurements and Main Results: 64 patients met inclusion criteria; 51 (80%) developed SF (SF+ ). Forty-three (85%) developed stage 3 or higher SF (χ2 = 22.66, P < .0001). Thirty-nine of 51 (76%) SF+ patients developed more than one SF lesion (χ2 = 13.26, P = .0003). SF+ patients manifested a profound pro-inflammatory, hypercoagulable phenotype (lower serum albumin and higher ferritin, interleukin [IL]-6 and D-dimer concentrations [all, P < .001]). Durations of mechanical ventilation, vasopressor therapy, and ICU length of stay were significantly longer (all, P < .05) in the SF + patients. Conclusions: The unique characteristics of COVID-19 dermatopathology and the strong correlation between markers of inflammation and development of SF reflect COVID-19-related organ dysfunction and its deleterious effects on the microcirculation. Considering that skin is invaded directly by SARS-CoV-2 and affected by COVID-19-related immune complex deposition and microthrombosis, SF may reflect disease as opposed to pressure injuries related to processes of care. In the context of COVID-19 critical illness, SF should not be considered a "never event."

Rethinking the Drug Distribution and Medication Management Model: How a New York City Hospital Pharmacy Department Responded to COVID-19.

Beginning in March 2020, New York City began the fight against coronavirus disease 2019. Health care workers were faced with a disease that led to significant morbidity and mortality with no proven therapies. As hospitals became inundated with patients and underwent rapid expansion of capacity, resources such as drugs, protective and medical equipment, and hospital staff became limited. Pharmacists played a critical role in the management of clinical care and drug delivery during the pandemic. As members of the department of pharmacy within NewYork-Presbyterian Hospital, we describe our experiences and processes to overcome challenges faced during the pandemic. Strict inventory management through the use of daily usage reports, frequent communication, and minimization of waste was critical for the management of drug shortages. The creation of guidelines, protocols, and restrictions were not only used to mitigate drug shortages, but also helped educate health care providers and guided medication use. Managing technology through setting up new automatic dispensing cabinets to address hospital expansions and modifying the electronic order entry system to include new protocols and drug shortage information were also vital. Additional key pharmacist functions included provision of investigational drug service support and training of pharmacists, prescribers, nurses, and respiratory therapists to educate and standardize medication use. Through implementation of operational and clinical processes, pharmacists managed critical drug inventory and guided patient treatment. As the pandemic continues, pharmacists will remain vital members of the multidisciplinary team dedicated to the fight against the virus.

Serotonin syndrome caused by fentanyl and methadone in a burn injury.

Serotonin syndrome is a syndrome identified by a triad of altered mental status, neuromuscular overactivity, and autonomic instability caused by the overstimulation of serotonin in the central nervous system and periphery. Serotonin syndrome may be provoked with the addition or increase in serotonergic agents such as selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors as well as other agents with serotonergic properties. Some narcotics, including fentanyl and methadone, have these properties and may be associated with the development of serotonin syndrome when used in conjunction with other agents. Currently, there are no identified case reports of narcotics as the sole agent causing serotonin syndrome. This report provides a brief overview of serotonin syndrome, particularly with cases involving administration of narcotics such as fentanyl and methadone. The case described is the first report associated with fentanyl and methadone without the coadministration of other serotonergic agents, and a possible drug interaction with voriconazole is discussed. This raises awareness of using multiple serotonergic narcotics and the potential precipitation of serotonin syndrome.

Considerations for the appropriate use of skeletal muscle relaxants for the management of acute low back pain.

For patients with low back pain, skeletal muscle relaxants are often initiated after failure of first-line analgesics. However, these medications (reviewed in this article) are controversial alternatives that carry risks of adverse effects and increased cost.