Cumulative epinephrine dose during cardiac arrest and neurologic outcome after extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Epinephrine is recommended without an apparent ceiling dosage during cardiac arrest. However, excessive alpha- and beta-adrenergic stimulation may contribute to unnecessarily high aortic afterload, promote post-arrest myocardial dysfunction, and result in cerebral microvascular insufficiency in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: This was a retrospective cohort study of adults (≥ 18 years) who received ECPR at large academic ECMO center from 2018 to 2022. Patients were grouped based on the amount of epinephrine given during cardiac arrest into low (≤ 3 mg) and high (> 3 mg) groups. The primary endpoint was neurologic outcome at hospital discharge, defined by cerebral performance category (CPC). Multivariable logistic regression was used to assess the relationship between cumulative epinephrine dosage during arrest and neurologic outcome. RESULTS: Among 51 included ECPR cases, the median age of patients was 60 years, and 55% were male. The mean cumulative epinephrine dose administered during arrest was 6.2 mg but ranged from 0 to 24 mg. There were 18 patients in the low-dose (≤ 3 mg) and 25 patients in the high-dose (> 3 mg) epinephrine groups. Favorable neurologic outcome at discharge was significantly greater in the low-dose (55%) compared to the high-dose (24%) group (p = 0.025). After adjusting for age, those who received higher doses of epinephrine during the arrest were more likely to have unfavorable neurologic outcomes at hospital discharge (odds ratio 4.6, 95% CI 1.3, 18.0, p = 0.017). CONCLUSION: After adjusting for age, cumulative epinephrine doses above 3 mg during cardiac arrest may be associated with unfavorable neurologic outcomes after ECPR and require further investigation.

Unresponsiveness of Activated Partial Thromboplastin Time to Bivalirudin in Adults Receiving Extracorporeal Membrane Oxygenation.

Activated partial thromboplastin time (aPTT) is the standard for monitoring bivalirudin but demonstrates a nonlinear response at higher drug concentrations. The objective of this study was to assess the relationship between bivalirudin dose and aPTT in patients receiving extracorporeal membrane oxygenation (ECMO) to determine a threshold where aPTT unresponsiveness occurs. Two hundred fourteen adults receiving bivalirudin during ECMO between 2018 and 2022 were included. Piecewise regression in a linear mixed effects model was used to determine a bivalirudin dose threshold of 0.21 mg/kg/hr for aPTT unresponsiveness. For doses of less than 0.21 mg/kg/hr (n = 135), every 0.1 mg/kg/hr dose increase led to an aPTT increase of 11.53 (95% confidence interval [CI] = 9.85-13.20) seconds compared to only a 3.81 (95% CI = 1.55-6.06) seconds increase when dose was greater than or equal to 0.21 mg/kg/hr (n = 79) ( pinteraction < 0.001). In multivariable logistic regression, venovenous configuration (odds ratio [OR] = 2.83, 95% CI = 1.38-5.77) and higher fibrinogen concentration (OR = 1.22, 95% CI = 1.05-1.42) were associated with greater odds of unresponsiveness, whereas older age (OR = 0.79, 95% CI = 0.63-0.98), kidney dysfunction (OR = 0.48, 95% CI = 0.25-0.92), and a higher baseline aPTT (OR = 0.89, 95% CI = 0.82-0.97) were associated with lower odds. Alternative methods are necessary to ascertain bivalirudin's hemostatic impact when doses exceed 0.21 mg/kg/hr during ECMO.

Acute kidney injury in patients before and after extracorporeal membrane oxygenation (ECMO) - Retrospective longitudinal analysis of the hospital outcomes.

PURPOSE: Acute Kidney Injury (AKI) occurs in up to 85% of patients managed by ECMO support. Limited data are available comparing the outcomes among patients who develop AKI before and after ECMO initiation. METHODS: A retrospective longitudinal observational study was performed on all adult patients placed on ECMO from January 2000 to December 2015 at our institution. Longitudinal multivariate logistic regressional analysis was performed to identify the variables that are associated with the outcome measures (post-ECMO AKI and in-hospital mortality). RESULTS: A total of 329 patients were included in our analysis in which AKI occurred in 176 (53%) and 137 (42%) patients before and after ECMO, respectively. In the multivariate analysis, increasing age, pre-existing chronic kidney disease (CKD), increasing bilirubin, decreasing fibrinogen, and use of LVAD had significant association with post-ECMO AKI. In-hospital mortality was seen in 128 out of 176 (73%) patients in the pre-ECMO AKI group and 32 out of 137 (42%) in the post-ECMO AKI group. In the multivariate analysis, age, interstitial lung disease, pre-ECMO AKI, and post-ECMO RRT requirement were independently associated with mortality. CONCLUSION: AKI before ECMO initiation and the need for RRT post-ECMO are independently associated with poor patient survival.

Tranexamic Acid for Bleeding Management in Adult Patients on Extracorporeal Membrane Oxygenation.

This study described the outcomes of patients receiving topical, nebulized, endobronchial, or systemic tranexamic acid (TXA) for bleeding events while on extracorporeal membrane oxygenation (ECMO). We performed a single-center case series including adult patients >18 years old supported on either venovenous (VV) or venoarterial (VA) ECMO from January 1, 2014, to April 21, 2021. The primary outcome was hemostatic control defined as a composite of initial cessation of therapeutic interventions to mitigate bleeding or resumption of anticoagulation if previously held. Secondary outcomes included changes in transfusion requirements and lysis at 30-minute (LY30) values, venous thromboembolism (VTE) events, and seizures. In total, 47 patients were included for full analysis. There were 19 patients with surgical bleeds, 18 patients with medical bleeds, and 10 patients with multiple bleeds. Overall, initial hemostatic control was achieved in 79%, 67%, and 90% of patients, respectively. Pre- and post-TXA transfusion requirements were not significantly different ( p = 0.2), although the intraindividual change in median LY30 was -5.1% compared with baseline (95% confidence interval [CI], -12.4% to -1.5%, p = 0.005). The occurrence of VTE and seizures was relatively low and similar among patient bleeding groups. Tranexamic acid provided initial hemostatic control in roughly three quarters of patients with bleeding events on ECMO and side effects were infrequent.

Intraoperative Versus Postoperative Hydroxocobalamin for Vasoplegic Shock in Cardiothoracic Surgery.

OBJECTIVES: Hydroxocobalamin inhibits nitric oxide pathways contributing to vasoplegic shock in patients undergoing cardiopulmonary bypass (CPB). The objective of this study was to evaluate the effect of intraoperative versus postoperative application of hydroxocobalamin for vasoplegic shock in patients undergoing CPB. DESIGN: This was a historic cohort study. SETTING: The study was conducted at a quaternary academic cardiovascular surgery program. PARTICIPANTS: Adults undergoing cardiac surgery using CPB were participants in the study. INTERVENTIONS: Hydroxocobalamin (5 g) intravenously over 15 minutes. MEASUREMENTS AND MAIN RESULTS: The treatment groups were assigned based on the receipt location of hydroxocobalamin (ie, intensive care unit [ICU] versus operating room [OR]). The primary outcome was vasopressor-free days in the first 14 days after CPB. Of the 112 patients included, 37 patients received hydroxocobalamin in the OR and 75 in the ICU. Patients in the OR group were younger than those in the ICU group (57.5 v 63.9 years, p = 0.007), with statistically similar American Society of Anesthesiologists scores. The mean CPB duration was 3.4 hours in the OR group and 2.9 hours in the ICU group (p = 0.09). In both groups, the norepinephrine-equivalent dose of vasopressors at hydroxocobalamin was 0.27 µg/kg/min. Days alive and free of vasopressors were not different between the OR and ICU groups (estimated difference 0.48 [95% CI -1.76-2.72], p = 0.67). The odds of postoperative renal failure, mesenteric ischemia, ICU, hospital length of stay, and in-hospital mortality were also similar between groups. CONCLUSIONS: A difference in vasopressor-free days after CPB was not found between patients who received hydroxocobalamin intraoperatively versus postoperatively for vasoplegic shock.

Bivalirudin or heparin for systemic anticoagulation during pediatric extracorporeal membrane oxygenation: Multicenter retrospective study.

BACKGROUND: The objective of this study is to evaluate the outcomes of unfractionated heparin (UFH) compared to bivalirudin anticoagulation in pediatric ExtraCorporeal Membrane Oxygenation (ECMO). METHODS: A multicenter retrospective study, that included pediatric patients <18 years of age, who were supported on ECMO between June 2017 and May 2020. Patients treated with UFH were matched 2:1 by age and type of ECMO support to the bivalirudin group. RESULTS: The bivalirudin group (75 patients) were matched to 150 patients treated with UFH. Baseline characteristics and comorbidities of the two groups were similar. Veno-Arterial ECMO was the most common mode (141/225 [63 %]) followed by extracorporeal cardiopulmonary resuscitation (48/225 [21 %]). Bivalirudin treatment was associated with lower odds of bleeding events (aOR 0.23, 95%CI 0.12-0.45, p < 0.001) and lower odds of thrombotic events (aOR 0.48, 95%CI 0.23-0.98, p = 0.045). Patients who received bivalirudin had lesser odds for transfusion with fresh frozen plasma, and platelets (aOR 0.26, CI 0.12-0.57, p ≤0.001 and aOR 0.28, CI 0.15-0.53, p < 0.001, respectively). After adjusting for the type of ECMO support and adjusting for age, bivalirudin was associated with a decrease in hospital mortality by 50 % compared to the UFH group (aOR 0.50, 95%CI 0.27-0.93, p = 0.028). Similarly, for neurological disability at time of discharge, bivalirudin was associated with higher odds of intact neurological outcomes compared to UFH (OR 1.99 [95%CI 1.13-3.51], p = 0.017). CONCLUSIONS: This study demonstrated that effective anticoagulation can be achieved with bivalirudin, which was associated with lesser odds of bleeding events and utilization of blood products. Bivalirudin, in comparison with UFH, was associated with greater odds of hospital survival and intact neurological function at the time of discharge. A prospective randomized trial is required to validate the results of this study.

Hydroxocobalamin for Vasodilatory Hypotension in Shock: A Systematic Review With Meta-Analysis for Comparison to Methylene Blue.

Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating hypotension remain unclear. The authors systematically searched Ovid Medline, Embase, EBM Reviews, Scopus, and Web of Science Core Collection for clinical studies reporting on adult persons who received hydroxocobalamin for vasodilatory shock. A meta-analysis was performed with random-effects models comparing the hemodynamic effects of hydroxocobalamin to methylene blue. The Risk of Bias in Nonrandomized Studies of Interventions tool was used to assess the risk of bias. A total of 24 studies were identified and comprised mainly of case reports (n = 12), case series (n = 9), and 3 cohort studies. Hydroxocobalamin was applied mainly for cardiac surgery vasoplegia, but also was reported in the settings of liver transplantation, septic shock, drug-induced hypotension, and noncardiac postoperative vasoplegia. In the pooled analysis, hydroxocobalamin was associated with a higher mean arterial pressure (MAP) at 1 hour than methylene blue (mean difference 7.80, 95% CI 2.63-12.98). There were no significant differences in change in MAP (mean difference -4.57, 95% CI -16.05 to 6.91) or vasopressor dosage (mean difference -0.03, 95% CI -0.12 to 0.06) at 1 hour compared to baseline between hydroxocobalamin and methylene blue. Mortality was also similar (odds ratio 0.92, 95% CI 0.42-2.03). The evidence supporting the use of hydroxocobalamin for shock is limited to anecdotal reports and a few cohort studies. Hydroxocobalamin appears to positively affect hemodynamics in shock, albeit similar to methylene blue.

Analysis of Wholesale Drug Acquisition and Laboratory Assessment Costs Between Heparin Compared With Bivalirudin-Based Systemic Anticoagulation Strategies in Adult Extracorporeal Membrane Oxygenation.

OBJECTIVES: To assess the wholistic costs of systemic anticoagulation delivery in heparin versus bivalirudin-based maintenance of adult patients supported on extracorporeal membrane oxygenation (ECMO). DESIGN: Single-center retrospective cohort study. SETTING: Large academic ECMO center. PATIENTS: Adults on ECMO receiving heparin or bivalirudin for primary maintenance systemic anticoagulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Electronic data were abstracted from a database maintained by our ECMO center, which transitioned to a preferred bivalirudin-based anticoagulation management in 2017. The pretransition group consisted of 126 patients (123 heparin and three bivalirudin), whereas the posttransition group included 275 patients (82 heparin and 193 bivalirudin). Drug costs were estimated using the wholesale acquisition cost, and laboratory assays costs were estimated using reimbursement fee schedules. Cost data were normalized to the duration of the ECMO run and reported in U.S. Dollar per ECMO day. Following the practice change, bivalirudin patients were less likely to receive AT supplementation (31.0 vs 12.4%; p < 0.0001) and had fewer coagulation assays ordered (6.1 vs 5.4 per ECMO day; p = 0.0004). After the transition, there was a dramatic decrease in costs related to AT assay assessments ($11.78 [interquartile range {IQR}, $9.48-$13.09] vs $1.03 [IQR, $0-$5.75]; p < 0.0001) and AT supplementation ($0 [IQR, $0-$312.82] vs $0 [IQR, $0-$0]; p < 0.0001) per ECMO day. Unadjusted survival at 28 days was higher posttransition (64.3 vs 74.9%; p = 0.0286). CONCLUSIONS: Antithrombin assays and supplementation compromise a significant proportion of heparin-based anticoagulation costs in ECMO patients and is substantially reduced when a bivalirudin-based anticoagulation strategy is deployed. A favorable association exists between the aggregate cost of administration of bivalirudin compared with heparin-based systemic anticoagulation in adults supported on ECMO driven by reductions in antithrombin activity assessments and the cost of antithrombin replacement.

Extracorporeal Membrane Oxygenation in Acute Respiratory Failure.

Venovenous (VV) extracorporeal membrane oxygenation (ECMO) is a form of mechanical life support that provides full respiratory bypass in patients with severe respiratory failure as a bridge to recovery or lung transplantation. The use of ECMO for respiratory failure and capable centers offering ECMO has expanded over the years, increasing its availability. As VV-ECMO provides an artificial mechanism for oxygenation and decarboxylation of native blood, it allows for an environment in which safer mechanical ventilatory care may be provided, allowing for treatment and resolution of underlying respiratory pathologies. Landmark clinical trials have provided a framework for better understanding patient selection criteria, resource utilization, and outcomes associated with ECMO when applied in settings of refractory respiratory failure. Maintaining close vigilance and management of complications during ECMO as well as identifying strategies post-ECMO (e.g., recovery, transplantation, etc.), are critical to successful ECMO support. In this review, we examine considerations for candidate selection for VV-ECMO, review the evidence of utilizing VV-ECMO in respiratory failure, and provide practical considerations for managing respiratory ECMO patients, including complication identification and management, as well as assessing for the ability to separate from ECMO support and the procedures for decannulation.

Angiotensin II for Vasodilatory Hypotension in Patients Requiring Mechanical Circulatory Support.

Background: Patients supported on mechanical circulatory support devices experience vasodilatory hypotension due to high surface area exposure to nonbiological and non-endothelialized surfaces. Angiotensin II has been studied in general settings of vasodilatory shock, however concerns exist regarding the use of this vasopressor in patients with pre-existing cardiac failure. The objective of this study was to assess the systemic and central hemodynamic effects of angiotensin II in patients with primary cardiac or respiratory failure requiring treatment with mechanical circulatory support devices. Methods: Multicenter retrospective observational study of adults supported on a mechanical circulatory support device who received angiotensin II for vasodilatory shock. The primary outcome was the intraindividual change from baseline in mean arterial pressure (MAP) and vasopressor dosage after angiotensin II. Results: Fifty patients were included with mechanical circulatory devices that were primarily used for cardiac failure (n = 41) or respiratory failure (n = 9). At angiotensin II initiation, the norepinephrine equivalent vasopressor dosage was 0.44 (0.34, 0.64) and 0.47 (0.33, 0.73) mcg/kg/min in the cardiac and respiratory groups, respectively. In the cardiac group, MAP increased from 60 to 70 mmHg (intraindividual P < .001) in the 1 h after angiotensin II initiation and the vasopressor dosage declined by 0.04 mcg/kg/min (intraindividual P < .001). By 12 h, the vasopressor dosage declined by 0.16 mcg/kg/min (P = .001). There were no significant changes in cardiac index or mean pulmonary artery pressure throughout the 12 h following angiotensin II. In the respiratory group, similar but nonsignificant effects at 1 h on MAP (61-81 mmHg, P = .26) and vasopressor dosage (decline by 0.13 mcg/kg/min, P = .06) were observed. Conclusions: In patients requiring mechanical circulatory support for cardiac failure, angiotensin II produced beneficial systemic hemodynamic effects without negatively impacting cardiac function or pulmonary pressures. The systemic hemodynamic effects in those with respiratory failure were nonsignificant due to limited sample size.

Heparin Versus Bivalirudin for Anticoagulation in Adult Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

Extracorporeal membrane oxygenation (ECMO) poses unique thrombotic and hemorrhagic risks, and the optimal anticoagulant choice is unknown. We systematically searched Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection for randomized-, crossover-, retrospective cohort-, or parallel-designed clinical studies of adult patients receiving ECMO that compared heparin recipients with bivalirudin recipients. Meta-analysis was performed with random-effects models. The ROBINS-I tool was used to assess the risk of bias. Six retrospective observational studies met the inclusion criteria for the qualitative summary. Five studies were suitable for meta-analysis. Those who received heparin were more likely to experience circuit-related thrombosis (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.25-3.37, p = 0.005, I2 = 0%) and die (OR 1.62, 95% CI 1.19-2.21, p = 0.002, I2 = 0%) compared with those who received bivalirudin. There were no differences in major bleeding events between heparin and bivalirudin recipients (OR 1.83, 95% CI 0.55-6.09, p = 0.33, I2 = 82.7%). In retrospective settings compared with heparin anticoagulation, bivalirudin was associated with less circuit-related thrombotic events and greater survival in adults supported on ECMO, without contributing to more bleeding complications. Prospective controlled studies comparing heparin and bivalirudin in adult ECMO patients are warranted to corroborate these findings.

Evaluation of Bivalirudin Dosing in Pediatric Extracorporeal Membrane Oxygenation with Renal Insufficiency or Renal Replacement Therapy.

Bivalirudin offers several important advantages of relevance to the management of extracorporeal membrane oxygenation (ECMO) patients. This multicenter retrospective analysis evaluated the bivalirudin dosing in pediatric ECMO and correlated these doses with the severity of renal dysfunction. A total of 75 patients were included in this analyses: estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73 m 2 (n = 29), eGFR 30-60 (n = 18), eGFR < 30 (n = 28), and of those 23 were on renal replacement therapy (RRT). The initial bivalirudin dose used to reach therapeutic anticoagulation in patients with eGFR > 60 was significantly higher than the dose required in those with renal impairment (0.25 mg/kg/hr in patients with eGFR > 60 and 0.19 mg/kg/hr in patients on RRT, 0.18 mg/kg/hr in patients with eGFR 30-60 and 0.13 mg/kg/hr in patients with eGFR < 30 with no RRT). Progressive dose escalations (two to threefold increase) were required to maintain therapeutic range over the initial 4 days of ECMO that coincided with improving renal creatinine clearance during that same time period. Establishing an initial starting dose of bivalirudin contingent upon eGFR is essential for the rapid achievement of target anticoagulation intensity. Further dose adjustments guided by laboratory monitoring is necessary given the dynamic changes in creatinine clearance following ECMO initiation.

The Year in Extracorporeal Membrane Oxygenation: Selected Highlights From 2021.

This review summarizes the extracorporeal membrane oxygenation (ECMO) or extracorporeal life support literature published in 2021. This Selected Highlights article is not intended to be an exhaustive review of the literature, but rather a summarizing of key themes that developed in the ECMO literature during 2021. The primary topics presented include the following: ECMO for coronavirus disease 2019, extracorporeal cardiopulmonary resuscitation, periprocedural cardiopulmonary support with ECMO, and anticoagulation for ECMO.

Cardiac tamponade in a patient supported by veno-arterial extracorporeal membrane oxygenation.

Cardiac tamponade occurring in a patient supported on central veno-arterial extracorporeal membrane oxygenation is depicted in a transesophageal echocardiography image and associated rendering. Prompt recognition of tamponade, which can be assisted with echocardiography, and emergent evacuation is critical to restoring cardiovascular stability.