Wittwer, Erica D.

ABSTRACT Background The Extracorporeal Life Support Organization recommends daily antithrombin monitoring and supplementation to achieve > 50%–80% activity during extracorporeal membrane oxygenation (ECMO). Evidence supporting this practice is uncertain, and whether it confers clinical benefit or harm is unclear. Methods This was a systematic review with meta‐analysis to evaluate the safety and efficacy of antithrombin supplementation during ECMO. We systematically searched databases and registers for studies comparing patients on ECMO who received antithrombin supplementation to those who did not. Random effects meta‐analysis was performed. Risk of bias was independently assessed by two investigators. A priori subgroup and sensitivity analyses were performed to explore reasons for heterogeneity. Results A total of 11 studies were identified. In the pooled meta‐analysis, antithrombin supplementation resulted in no difference in bleeding events (OR 1.38, 95% CI, 0.88–2.17, p = 0.16), thrombotic events (OR 1.57, 95% CI, 0.84–2.90, p = 0.15), or mortality (OR 1.21, 95% CI, 0.81–1.81, p = 0.35) when compared to those who did not receive antithrombin. Subgroup analysis revealed no difference in bleeding events or mortality in pediatric or adult patients; however, pediatric patients that received antithrombin were more likely to experience a thrombotic event (OR 1.70, 95% CI, 1.51–1.91). Sensitivity analysis in only low risk of bias studies confirmed these findings. Conclusions Antithrombin supplementation was not associated with differences in mortality or hemostatic outcomes during ECMO support and may be associated with harm in pediatric patients on ECMO.

Refractory anaphylaxis is rare but carries high mortality, particularly when complicated by severe bronchospasm and respiratory failure. We present a 32-year-old individual with food-induced anaphylaxis and profound bronchospasm unresponsive to first- and second-line therapies, resulting in severe hypoxemic and hypercapnic respiratory failure despite mechanical ventilation. Peripheral venovenous extracorporeal membrane oxygenation (VV-ECMO) was emergently initiated, leading to rapid stabilization and full recovery. This case demonstrates the successful use of VV-ECMO as a life-saving bridge in anaphylaxis-induced respiratory failure. This is one of the few reported cases of successful use of VV-ECMO for refractory bronchospasm secondary to anaphylaxis.

Empirical evidence suggests direct thrombin inhibitors (DTIs) produce more favorable hemostatic outcomes than heparin in patients supported by extracorporeal membrane oxygenation (ECMO), yet the exact mechanisms responsible are unknown. We systematically searched databases and registers for studies comparing DTIs to heparin in humans receiving ECMO. A total of 28 studies were identified, most of which (n = 25) used bivalirudin, while the rest (n = 3) used argatroban. In random-effects meta-analysis, DTIs achieved the therapeutic anticoagulation range faster (mean difference = −6.96 hours, 95% confidence interval [CI] = −11.98 to −1.95, p = 0.006) and maintained the therapeutic range for a greater proportion of time (mean difference = 18.6%, 95% CI = 8.78–28.42, p < 0.001) than heparin. Subgroup analysis revealed these effects were similarly significant in adult patients and when bivalirudin was the DTI; however, they were not significant in pediatric patients or when argatroban was the DTI. Sensitivity analysis confirmed robustness of the primary findings in only low-risk of bias studies and in only studies published as full papers. In summary, DTIs—specifically bivalirudin—were associated with faster time to therapeutic anticoagulation and maintained the goal range for a greater percentage of time than heparin during ECMO support.

Abstract RATIONALE: Clinical practice guidelines recommend that mechanically ventilated patients (MVPs) receiving sedative therapy achieve a target goal of ‘awake and calm’ when medically possible. However, ICU sedation practices rely on clinicians’ administration of medications based on observations of patients’ arousal/motor activity that are not consistently based on symptom assessments nor consider patients’ preferences. We hypothesized that MVPs would safely self-manage sedative therapy (SMST) base on individual needs and perceived anxiety while experiencing less sedative exposure and delirium. METHODS: A two-group randomized clinical trial conducted in two Midwestern academic medical centers enrolled 161 MVPs willing and able to depress a medication delivery push-button device who remained on protocol for 7 days or until extubated, withdrew or died. Control group (CG) patients (n=81) received sedative medications administered by ICU nurses per unit protocols. Experimental SMST group patients (n=80) received a basal infusion of dexmedetomidine (0.2 mcg/kg/hr titrated per algorithm) + self-administered bolus doses (0.25 mcg/kg up to 3/hour). Primary outcomes were anxiety ratings using a 100-mm visual analog scale (VAS-A), sedation intensity score (aggregate summary of 9 intravenous sedative/opioid medications received range 0-36), and incidence of delirium using the CAM-ICU. Analyses were descriptive and parametric statistics and Generalized Estimating Equations. RESULTS: Patients were predominantly White (93%) females (55%), mean age 58.9+15.1 years receiving mechanical ventilation for respiratory failure (60%) with mean APACHE III of 84.5 + 32.5. Anxiety was highly variable over time wherein patients in both groups endorsed the full range from 0-100. VAS-A over time between groups was -0.06 (p=0.98) indicating that anxiety was 0.06 units lower for SMST patients versus CG. Median sedation intensity in SMST group 11.8 + 9.6, compared to CG 12.7 + 9.6 (p = 0.55) over 7 days. 10.2% of SMST patients had one or more incident delirium events compared to 8.5% of CG (p =.97). Hypotension was experienced equally between groups: 22 in SMST, 23 in CG (p = 1.0) as were device disruptions: 2 in SMST versus 3 in CG (p = 1.0). 82% of SMST were satisfied/very satisfied with ability to self-administer dexmedetomidine; 70% were satisfied/very satisfied with ability to control anxiety; 68% were satisfied/very satisfied with the level of relaxation experienced. CONCLUSIONS: Although there were no significant differences between groups on the primary outcomes, the experimental SMST intervention was safe with high patient-reported satisfaction. SMST may be a viable new paradigm for sedative therapy administration among select ICU patients.

Background: Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are leading causes of transfusion-related morbidity and mortality. Soluble factors in erythrocyte supernatant may increase risk for these complications. The authors hypothesized that point-of-care allogeneic erythrocyte washing may be an effective intervention to mitigate elevations in soluble factors as well as physiologic responses associated with transfusion-associated respiratory complications in the setting of cardiac surgery. Methods: This is a two-center, nonblinded, randomized clinical trial evaluating point-of-care washed versus standard issue allogeneic erythrocyte transfusions administered during or on the day of cardiac surgery. The primary analysis was performed via modified intention to treat. The primary outcomes assessed were changes in intermediate markers of lung injury as well as cardiopulmonary physiologic responses to erythrocyte transfusion. Secondary outcomes included the duration of intensive care unit and hospital stay, durations of mechanical ventilation and oxygen supplementation, presence of TRALI or TACO, and mortality. Results: Among 154 analyzed patients (81 washed, 73 standard issue), the median age was 66 yr, and 77 (50.0%) were women. The median (interquartile range) number of allogeneic erythrocyte units transfused on the day of surgery was 3.0 (2.0 to 5.0) in the washed erythrocyte group and 3.0 (2.0 to 4.0) in the standard issue group (P = 0.13). No between-group differences were identified in any of the assessed recipient lung injury biomarkers (all P values > adjusted alpha). Durations of intensive care unit stay (median [interquartile range], 3.0 [2.0 to 5.0] vs. 3.0 [2.0 to 4.0] days; P = 0.117) and hospital length of stay (12.0 [9.0 to 17.0] vs. 12.0 [9.0 to 17.0] days; P = 0.801) were similar, as were the number of ventilator-free days at day 28 (27.0 [27.0 to 27.0] vs. 27.0 [26.0 to 27.0]; P = 0.699) and oxygen-free days at day 28 (24.0 [19.0 to 26.0] vs. 24.0 [22.0 to 26.0]; P = 0.400). No significant differences were noted in mortality rate or in incidence rates for TRALI, TACO, and acute kidney injury. Conclusions: Among patients undergoing cardiovascular surgery with high risk of erythrocyte transfusion, point-of-care washing of allogeneic erythrocyte transfusions did not mitigate changes in intermediate markers of lung injury or cardiopulmonary physiologic responses to erythrocyte transfusion and was not associated with improved clinical outcomes.

A 40 year old woman who underwent combined heart-lung transplant for familial severe pulmonary hypertension experienced episodes of nonsustained ventricular tachycardia followed by sudden ventricular fibrillation arrest 8 days after transplant. Postarrest investigations revealed left lower lobe herniation into the right lower hemithorax, prompting emergent reoperation, and hernia reduction. Arrhythmias resolved following reduction of the herniated lung and facilitated rapid weaning from vasopressor and ventilatory support. To our knowledge, this is the first reported case of cardiac arrest due to lung herniation after combined heart-lung transplantation. Herein, we describe this rare presentation and offer insights and management strategies for the cardiac intensivist.

Background: While criteria for the diagnosis of nosocomial pneumonias exist, objective definitions are a challenge and there is no gold standard for diagnosis. We analyzed the impact of the implementation of a logical, consensus-based diagnostic and treatment protocol for managing nosocomial pneumonias in the cardiovascular surgery intensive care unit (CVS-ICU). Methods: We conducted a quasi-experimental, interrupted time series analysis to evaluate the impact of a diagnostic and treatment protocol for nosocomial pneumonias in the CVS-ICU. Impacts were measured relative to patient outcomes, diagnostic processes, and antimicrobial stewardship improvement. Descriptive statistics were used to analyze results. Results: Overall, 35 pre-protocol and 39 post-protocol patients were included. Primary clinical variables suggesting pneumonia in pre- and post-protocol patients were new lung consolidation (50% vs. 71%), new leukocytosis (59% vs. 64%), and positive culture (32% vs. 55%). Appropriate diagnostic testing improved (23% vs. 54%, p = 0.008) after protocol implementation. The proportion of patients meeting the criteria for nosocomial pneumonia (77% vs. 87%) was not statistically significant, though more patients in the post-protocol group met probable diagnostic criteria (51% vs. 77%). Duration of therapy was not significantly different (6 days [IQR = 5.0, 10.0] vs. 7 days [IQR = 6.0, 9.0]). Conclusions: The implementation of a diagnostic and treatment protocol for management of nosocomial pneumonias in the CVS-ICU resulted in improved diagnostic accuracy, advanced antimicrobial and diagnostic stewardship efforts, and laboratory cost savings without an adverse impact on patient-centered outcomes.