Seelhammer, Troy G.

Objectives: Recently, the definition of sepsis has changed from a physiologic derangement (Sepsis-1 and -2) to organ dysfunction (Sepsis-3) based. We sought to determine the concordance between the different sepsis phenotypes and how that affected mortality. Design: Retrospective, multicenter study. Setting: Three academic medical centers. Patients: 29,459 patients who had suspected infection, defined as obtaining blood cultures and receiving antibiotics: 18,183 (62%) had either Sepsis-2 or Sepsis-3. Measurements and Main Results: Kappa was used to show agreement between phenotypes. Conditional logistic regression was used to create models of associations between factors and phenotypes and between factors and mortality. About 12,981 patients had Sepsis-2; 12,043 had Sepsis-3; and 6,841 patients had both Sepsis-2 and Sepsis-3. Fifty-three percent of Sepsis-2 patients also had Sepsis-3, whereas 57% of Sepsis-3 patients also had Sepsis-2. Agreement between the two phenotypes was poor: kappa = 0.213 ± 0.006. Mortality was 6% in patients with only Sepsis-2, 10% with only Sepsis-3, and 18% in patients who had both phenotypes. Combining the variables in Sepsis-2 and Sepsis-3 improved the discrimination (C-statistic = 0.742 ± 0.005, p < 0.001) of mortality. Conclusions: We found that Sepsis-2 and Sepsis-3-based sepsis diagnoses represent separate phenotypes with poor agreement. Patients who have both phenotypes are at increased risk of mortality compared with having either phenotype alone. Inclusion of both systemic inflammatory response syndrome and Sequential Organ Failure Assessment criteria in the same model improves the discrimination of mortality.

Drug pharmacokinetics may be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). Ensuring the optimized effective dosing of antimicrobials on ECMO remains a challenge. To date, limited data are available regarding the optimal use of amphotericin and triazoles during ECMO. We report a case of altered pharmacokinetics, insufficient liposomal amphotericin B and isavuconazole levels, and the need for escalated doses during ECMO in a patient with severe acute respiratory distress syndrome secondary to pulmonary blastomycosis. A 2‐fold increase in the standard total daily dose of both drugs was necessary to overcome low serum concentrations thought to be secondary to drug loss from ECMO circuit sequestration. These findings have important implications for optimizing antimicrobial therapy in patients receiving ECMO to maximize therapeutic efficacy. The use of therapeutic drug monitoring for patients receiving antimicrobial therapy with concurrent ECMO may facilitate appropriate drug dosing to achieve adequate serum concentrations and optimize favorable patient outcomes. Further studies exploring antimicrobial pharmacokinetics during ECMO are needed to inform dosing recommendations in critically ill patients.

We retrospectively reviewed all pertinent extracorporeal membrane oxygenation (ECMO) studies (January 1995 to September 2017) of adults with sepsis as a primary indication for intervention and its association with morbidity and mortality. Collected data included study type, ECMO configuration, outcomes, effect size, and other features. Advanced age was a risk factor for death. Compared with nonsurvivors, survivors had a lower median Sepsis-Related Organ Failure Assessment score on day 3 (15 vs. 18, p = 0.01). Biomarkers in survivors and nonsurvivors, respectively, were peak lactate (from two studies: 4.5 vs. 15.1 mmol/L, p = 0.03; 3.6 ± 3.7 vs. 3.3 ± 2.4 mmol/L, p = 0.850) and procalcitonin levels (41 vs. 164 ng/ml, p = 0.008). Bacteremia was associated with catheter colonization, and 90.5% of a group without bloodstream infections survived to discharge; ECMO weaning was possible for less than half the bloodstream infection group. Myocarditis portended favorable outcomes for patients with sepsis who received ECMO. Extracorporeal membrane oxygenation was used in immunosuppressed patients with refractory cardiopulmonary insufficiency from severe sepsis with successful weaning from ECMO for most patients. Overall survival varied substantially among studies (15.38–71.43%). Existing studies do not present well-defined patterns supporting use of ECMO in sepsis because of sample sizes and disparate study designs.

Extracorporeal membrane oxygenation (ECMO) is used to treat severe hypoxemic respiratory failure and as a rescue therapy for patients with cardiopulmonary arrest within a narrow window of time. A failure modes and effects analysis (FMEA) was conducted to analyze the clinical and operational processes leading to delays in initiating ECMO. FMEA determined these highest-risk failure modes that were contributing to process failure: (1) ECMO candidacy not determined in time, (2) no or incomplete evaluation for ECMO prior to consult or arrest, (3) ECMO team not immediately available, and (4) cannulation not completed in time. When implemented collectively, a total of 4 interventions addressed more than 95% of the system failures. These interventions were (1) ECMO response pager held by a team required for decision, (2) distribution of institutionally defined inclusion/exclusion criteria, (3) educational training for clinicians consulting the ECMO team, and (4) establishment of a mobile ECMO insertion cart.