A Retrospective Cohort Analysis of Analgosedation Requirements in COVID-19 Compared to Non-COVID-19 Extracorporeal Membrane Oxygenation Patients.

BACKGROUND: Reports have described increased sedation requirements in patients with acute respiratory distress syndrome (ARDS) while on extracorporeal membrane oxygenation (ECMO) and for intubated COVID-19 patients. Thus, the objective of this study was to assess the analgosedation requirements of COVID-19 patients receiving ECMO compared to non-COVID-19 ECMO patients. METHODS: This retrospective, observational cohort study included adult patients with ARDS requiring venovenous or venopulmonary arterial ECMO admitted to a single intensive care unit from January 2017 to December 2021. Patients were categorized as COVID-19 ECMO or non-COVID-19 ECMO. The primary outcome was median daily dosing of parenteral analgosedative medications. Pertinent secondary outcomes included incidence of extubation or tracheostomy and change in sedation following tracheostomy or addition of oral agents. RESULTS: A total of 109 patients were evaluated; 63 COVID-19 ECMO patients and 46 non-COVID ECMO patients. The primary outcome was statistically higher in the COVID-19 compared to non-COVID-19 patients for propofol (4131.0 mg vs 2704.8 mg, P < .001), dexmedetomidine (1581.4 mcg vs 1081.3 mcg, P = .016), and parenteral morphine equivalents ([PME], 209.3 mg vs 154.1 mg, P = .027), but only propofol remained significant after adjustment for weight (31.1 mcg/kg/day vs 37.7 mcg/kg/day, P = .014). COVID-19 was significantly associated with increased propofol and PME requirements after adjustment for confounders on linear regression analysis. COVID-19 patients had more days with non-zero dose for propofol (8 days vs 7 days), dexmedetomidine (13 days vs 8.5 days), and PME (17 days vs 8.5 days). The only interventions that were associated with reductions in propofol dose were tracheostomy and antipsychotics. CONCLUSIONS: COVID-19 patients on ECMO had significantly longer durations and higher doses of propofol, dexmedetomidine, and parenteral opioids over the first 28 days of cannulation. The only interventions that were associated with statistical reductions in propofol were antipsychotics and tracheostomy.

Comparison of Outcomes in Patients Requiring Mechanical Circulatory Support Who Received Cangrelor in Addition to Anticoagulation Versus Anticoagulation Alone.

OBJECTIVES: To evaluate the safety of cangrelor administered concurrently with heparin or bivalirudin in patients on mechanical circulatory support. DESIGN: A single-center, retrospective cohort study of adult patients consecutively admitted between January 2016 and October 2020. SETTING: A tertiary medical center. PARTICIPANTS: Adult patients admitted to the cardiovascular intensive care unit put on mechanical circulatory support for acute myocardial infarction (AMI) or non-AMI indications. Patients who received cangrelor underwent percutaneous coronary intervention with stenting during the index event or within the last year. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of major bleeding, defined by the Extracorporeal Life Support Organization criteria, in patients with mechanical circulatory support receiving cangrelor plus anticoagulation with heparin or bivalirudin with or without aspirin versus patients who did not receive cangrelor. Sixty-eight patients were included in the study. Twenty-nine patients received cangrelor, and 39 did not. Cangrelor was not associated with an increase in major bleeding; however, the CI was wide (adjusted hazard ratio 1.93, 95% CI 0.61-6.11; p = 0.262). CONCLUSIONS: Patients receiving cangrelor did not appear to be at higher risk of major bleeding compared to patients not receiving cangrelor. Larger trials should be conducted to better evaluate the safety of cangrelor in patients with mechanical circulatory support.

Heparin Monitoring with an Anti-Xa Protocol Compared to Activated Clotting Time in Patients on Temporary Mechanical Circulatory Support.

BACKGROUND: Temporary mechanical circulatory support (tMCS) devices are used for patients with severe cardiac or respiratory failure; however, these patients are at high risk for clotting and bleeding. The best method to monitor heparin in these patients has not been established. OBJECTIVE: To determine the risks for bleeding and clotting while monitoring heparin with either anti-Xa or activated clotting time (ACT) in tMCS patients. METHODS: A retrospective cohort study was conducted on tMCS patients who received heparin adjusted according to an anti-Xa or ACT protocol. The primary outcome was incidence of major bleeding. Pertinent secondary outcomes were individual components of the primary outcome, clotting events, and time to therapeutic range. RESULTS: There were 103 patients included in the study: 53 in the ACT group and 50 in the anti-Xa group. Overall, there were 30 (56.6%) patients with major bleeding in the ACT group, compared with 16 (32%) patients in the anti-Xa group (P = 0.017). An anti-Xa-based protocol was associated with a decreased hazard of major bleeding (hazard ratio = 0.388 [0.215-0.701]; P = 0.002) in the univariate analysis. In the multivariable analysis, an anti-Xa protocol remained associated with a significantly lower hazard of bleeding. Findings were similar when broken down into more discrete subgroups of the entire cohort, extracorporeal membrane oxygenation life support (ECMO), and non-ECMO groups. CONCLUSION AND RELEVANCE: Anti-Xa monitoring was associated with a lower hazard of bleeding during tMCS compared to an ACT-based protocol. Further studies should evaluate if anti-Xa monitoring should be preferentially used in tMCS.

Adequacy of hemostatic resuscitation improves therapeutic efficacy of recombinant activated factor VII and reduces reexploration rate for bleeding in postoperative cardiac surgery patients with refractory hemorrhage.

Background: Excessive bleeding and surgical reexploration are common complications that increase the risk of multi-organ failure and prolonged hospitalization after cardiac surgery. Off-label use of recombinant activated factor VII (rFVIIa) is a recommended treatment for refractory bleeding. Objective: The objective of the study is to determine if the adequacy of hemostatic resuscitation enhances the efficacy of rFVIIa. Methods: This retrospective, observational, cohort study included patients who received rFVIIa for refractory postoperative bleeding after cardiac surgery. Patients were divided into two groups based on the presence or absence of adequate coagulation resuscitation before rFVIIa administration, defined as international ratio (INR) ≤1.5, platelet count ≥100 K/mL, and fibrinogen ≥200 mg/dL. The failure of rFVIIa treatment was defined as surgical reexploration within 24 h, thoracostomy drainage >400 mL/h within 6 h or transfusion of additional blood products or another rFVIIa dose within 6 h after initial rFVIIa dose. Results: Of the 3833 patients, screened who underwent cardiothoracic surgery procedures, 58 patients received rFVIIa for refractory postoperative bleeding. Successful hemostasis with rFVIIa was more likely in patients who were adequately resuscitated compared with those who were not (20 [71.4%] vs. 10 [33.3%], respectively; P = 0.0046). Multiple logistic regression analysis indicated that patients who were adequately resuscitated before rFVIIa were less likely to fail treatment (odds ratio, 0.16; 95% confidence interval [0.04-0.62]; P = 0.007). Conclusions: The therapeutic efficacy of rFVIIa is dependent on the adequacy of hemostatic resuscitation; restoration of normal serum fibrinogen, INR, and platelet counts >100 K/mL may provide an adequate substrate for rFVIIa to be effective in managing refractory postoperative cardiac surgical bleeding.

New developments in the treatment of acute bacterial skin and skin structure infections: considerations for the effective use of dalbavancin.

Dalbavancin, an intravenous glycopeptide, was approved by the US Food and Drug Administration in May 2014 for use in adult patients with acute bacterial skin and skin structure infections. The recommended dosing regimen for effective use of dalbavancin is 1,000 mg followed by a 500 mg dose after 1 week. Two multinational, identically designed, non-inferiority trials, DISCOVER 1 and 2, demonstrated similar early clinical success with dalbavancin compared to vancomycin with an option to switch to oral linezolid. In a recently published non-inferiority trial, a single-dose regimen of dalbavancin was compared to the traditional two-dose administration and was found to have a non-inferior clinical response. In the aforementioned trials, dalbavancin was well tolerated, with patients experiencing transient adverse events of mild to moderate severity. The prolonged half-life, excellent skin and soft tissue penetration, bactericidal activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus, and convenient dosing make dalbavancin a reasonable option for the treatment of acute bacterial skin and skin structure infections in adult patients who have tried and failed other therapies.