Comparison of Sedation and Analgesia Requirements in Patients With SARS-CoV-2 Versus Non-SARS-CoV-2 Acute Respiratory Distress Syndrome on Veno-Venous ECMO.

BACKGROUND: Increased analgosedation requirements have been described in patients with acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO) support due to unique pharmacokinetic challenges. There is a paucity of data comparing sedation requirements in patients on ECMO for ARDS secondary to SARS-CoV-2 versus other etiologies of respiratory failure. OBJECTIVE: To compare sedation and analgesia requirements in adult patients with SARS-CoV-2 versus non-SARS-CoV-2 ARDS requiring veno-venous (VV) ECMO support. METHODS: We performed a retrospective cohort study of adult patients receiving sedation and analgesia on VV-ECMO support. Patients were excluded if cannulated at an outside hospital for greater than 24 hours, expired within 48 hours of ECMO cannulation, or received neuromuscular blocking agents for greater than 7 consecutive days following ECMO cannulation. RESULTS: We evaluated 108 patients on VV-ECMO support, including 44 with non-SARS-CoV-2 ARDS and 64 with SARS-CoV-2 ARDS. The median daily dexmedetomidine requirements were significantly higher in the SARS-CoV-2 cohort (16.7 vs 13.4 mcg/kg/day, P = 0.03), while the median propofol daily requirements were significantly higher in the non-SARS-CoV-2 cohort (40.3 vs 53.5 mg/kg/day, P < 0.01). There was no difference in daily requirements of opioids, benzodiazepines, and ketamine between groups. Use of adjunct agents to facilitate weaning was significantly higher in the SARS-CoV-2 cohort (78.1% vs 43.2%, P < 0.01). CONCLUSION AND RELEVANCE: Patients with ARDS on VV-ECMO support require multiple analgosedative agents with concomitant use of nonparenteral adjunct agents. Further studies are needed to evaluate optimal analgosedation strategies in patients on ECMO support.

Approach to Sedation and Analgesia in COVID-19 Patients on Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVE: To describe clinically pertinent challenges of managing sedation in COVID-19 patients on venovenous extracorporeal membrane oxygenation (VV-ECMO) and describe considerations for enhanced safety and efficacy of pharmacological agents used. DATA SOURCES: A PubMed search was performed using the following search terms: ECMO, ARDS, sedation, COVID-19, coronavirus, opioids, analgesia, fentanyl, hydromorphone, morphine, oxycodone, methadone, ketamine, propofol, dexmedetomidine, clonidine, benzodiazepines, midazolam, lorazepam, and diazepam. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical and pharmacokinetic studies were considered. All studies included were published between January 1988 and March 2021. DATA SYNTHESIS: Patients with acute respiratory distress syndrome secondary to COVID-19 may progress to requiring VV-ECMO support. Agents frequently used for sedation and analgesia in these patients have been shown to have significant adsorption to ECMO circuitry, leading to possible diminished clinical efficacy. Use of hydromorphone-based analgesia has been associated with improved clinical outcomes in patients on VV-ECMO. However, safety and efficacy regarding use of other agents in this patient population remains an area of further research. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review addresses clinical challenges associated with sedation management in COVID-19 patients requiring VV-ECMO support and provides potential strategies to overcome these challenges. CONCLUSIONS: Historically, sedation and analgesia management in patients requiring ECMO support have posed a challenge for bedside clinicians given the unique physiological and pharmacokinetic changes in this patient population. A multimodal strategy to managing analgesia and sedation should be used, and the use of enteral agents may play a role in reducing parenteral agent requirements.

Evaluation of characteristics and dosing regimens in patients with new or recurrent thrombosis on apixaban and rivaroxaban.

Direct factor Xa inhibitors, such as apixaban and rivaroxaban, are widely used for treatment and prevention of venous thromboembolism; however, recent cases of therapeutic failure have been reported. Potential risk factors associated with therapeutic failure such as dose deviations outside of package labeling recommendations, and the use of direct factor Xa-specific inhibitor levels to guide clinical decision making continue to be areas of further investigation. Our study aimed to describe characteristics and dosing regimens in patients on apixaban or rivaroxaban who experienced a new or recurrent thrombosis. We performed a retrospective chart review on 190 patients on either apixaban or rivaroxaban presenting to our institution with new or breakthrough thromboembolism. Evaluation of prescribed anticoagulation regimens compared to package labeling recommendations, direct factor Xa inhibitor-specific anti-Xa levels, anticoagulation interruptions, use of parenteral bridge anticoagulation, final anticoagulation regimen disposition, and thrombosis-associated mortality were recorded. In patients presenting with breakthrough thromboembolism, 78% were on a regimen that matched package labeling recommendations. Anti-Xa levels were documented in 66 patients, the majority of which fell within institutional expected ranges at time of thrombosis. Therapy interruptions immediately prior to thrombosis were observed in 22% of patients and 21% of those patients received parenteral anticoagulation during interruption. Upon discharge, 46% of patients continued the same anticoagulation regimen with no changes. The mortality rate was 6%. In patients who present with new thromboembolism on apixaban or rivaroxaban, a thorough review of risks and benefits should be conducted to mitigate future risk of recurrent thrombosis.

Use of meropenem to treat valproic acid overdose.

Overdose of valproic acid (VPA) or its derivatives can cause significant toxicities such as hyperammonemia or altered mental status. While levocarnitine has been used historically to manage VPA-associated hyperammonemia, no standard of therapy exists to manage VPA toxicity. We present a case of VPA overdose managed with meropenem in addition to levocarnitine. A 38-year old female presented to the emergency department after intentionally ingesting 20 tablets of extended release divalproex sodium. She received a 4-gram loading dose of levocarnitine. She developed altered mental status, and a repeat VPA level yielded a result of 278 µg/mL. She was given 1 g of meropenem and her subsequent VPA level was 193 µg/mL. Approximately 8 h after the initial dose, another 1 g of meropenem was administered. Additionally, she received 1 g of levocarnitine every 4 h for a total of six doses. A repeat VPA level returned at 62 µg/mL. The patient was transferred to the intensive care unit for further management. Carbapenem antibiotics inhibit acylpeptide hydrolase in the gastrointestinal tract. Inhibition of this enzyme prevents the reabsorption of metabolized VPA and therefore causes increased elimination. Our patient demonstrated a rapid lowering of VPA levels after administration of meropenem.

Bloodstream infections in prolonged use of axillary-placed, intra-aortic balloon-pump support: A single-center study.

Infections from prolonged use of axillary intra-aortic balloon pumps (IABPs) have not been well studied. Bloodstream infection (BSI) occurred in 13% of our patients; however, no difference in outcome was noted between those with BSI and those without. Further studies regarding protocol developments that minimize BSI risk are needed.

Evaluation of Anti-Xa Apixaban and Rivaroxaban Levels With Respect to Known Doses in Relation to Major Bleeding Events.

BACKGROUND: Although not routinely recommended, anti-Xa level monitoring for apixaban or rivaroxaban may be useful in certain clinical scenarios. There are currently no laboratory standards, therapeutic ranges, or proven correlation between anti-Xa levels and clinical outcomes. OBJECTIVE: This study describes the utilization, application, and association of anti-Xa levels with clinical outcomes in patients receiving apixaban or rivaroxaban. METHODS: This retrospective, descriptive study included adult inpatients within the Houston Methodist System on apixaban or rivaroxaban with at least one anti-Xa level ordered subsequent to administered doses. The primary endpoint was major bleeding according to International Society on Thrombosis and Haemostasis criteria. Secondary endpoints included reasons for anti-Xa level ordering, anti-Xa levels at different time intervals post-dose, and thrombotic events. Pre-specified subgroup analyses were performed to further evaluate the primary endpoint. RESULTS: The study population consisted of 169 patients and 234 anti-Xa levels. Twenty-nine levels were obtained in context of major bleeding. The majority of levels were not drawn as peak levels 2-4 hours post-dose, however remained quantifiable above typical observed levels within this timeframe and well beyond 24 hours post-dose. Patient characteristics with major bleeding included elderly age, acute renal impairment, and low body weight. At least 14 unique reasons for anti-Xa level ordering were identified. Twenty-nine levels were associated with thrombotic events. CONCLUSION: Anti-Xa levels may be useful for assessment of current drug concentrations, immediate safety of therapy, and guidance for possible clinical interventions. Dose titration and reversal therapies based on anti-Xa level results in major bleeding warrant further research.

Clinical Outcomes Following Tocilizumab Administration in Mechanically Ventilated Coronavirus Disease 2019 Patients.

Effective treatments for the critically ill patient with novel coronavirus disease 2019 are desperately needed. Given the role of cytokine release syndrome in the pathogenesis of coronavirus disease 2019-associated respiratory distress, therapies aimed at mitigating cytokine release, such as the interleukin-6 receptor-inhibiting monoclonal antibody tocilizumab, represent potential treatment strategies. Therefore, we examined the outcomes of critically ill coronavirus disease 2019 patients treated with tocilizumab and factors associated with clinical improvement. DESIGN: A retrospective cohort analysis of 21-day outcomes for consecutive mechanically ventilated patients treated with tocilizumab from March 24, 2020, to May 4, 2020. SETTING: Nine ICUs at six hospitals within a hospital system in Houston, Texas, United States. PATIENTS: The first 62 coronavirus disease 2019 patients on invasive mechanical ventilation who were treated with tocilizumab, which was considered for all patients with severe disease. INTERVENTIONS: Tocilizumab was administered either at a weight-based dose of 4-8 mg/kg or at a flat dose of 400 mg, with repeat administration in some patients at the physician's discretion. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were mortality and clinical improvement, defined as extubation. By day 21 post-tocilizumab, clinical improvement occurred in 36 patients (58%) and 13 patients (21%) died. In both univariable and multivariable analyses, age less than 60 years was associated with clinical improvement. Transient transaminitis was the most common adverse reaction, occurring in 25 patients (40%). CONCLUSIONS: Based on clinical outcomes and mortality rates seen in previous reports of mechanically ventilated patients, tocilizumab, as part of the management strategy for severe coronavirus disease 2019, represents a promising option. These findings support the need for evaluation of tocilizumab in a randomized controlled trial.