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.

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.

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.

Postdischarge Survival After Sepsis: A Cohort Study.

BACKGROUND: After hospital discharge, patients who had sepsis have increased mortality. We sought to estimate factors associated with postdischarge mortality and how they vary with time after discharge. METHODS: This was a retrospective study of hospital survivors of sepsis using time-varying Cox proportional hazard models, which produce a baseline hazard ratio (HR) and a second number (δHR) that reflects the amount by which the baseline HR changes with time. RESULTS: Of the 32,244 patients who survived sepsis at hospital discharge, 13,565 patients (42%) died (mean ± standard deviation: 1.41 ± 1.87 years) after discharge from the index hospitalization, while 18,679 patients were still alive at follow-up (4.98 ± 2.86 years). The mortality rate decreased with time after discharge: approximately 8.7% of patients died during the first month after discharge, 1.1% of patients died during the 12th month after discharge, and 0.3%% died during the 60th month; after Kaplan-Meier analysis, survival was 91% (95% confidence interval [CI], 91%-92%) at 1 month, 76% (95% CI, 76%-77%) at 1 year, 57% (95% CI, 56%-58%) at 5 years, and 48% (95% CI, 47%-48%) at 10 years after discharge. Organ dysfunction at discharge was associated with worse survival. In particular, elevated urea nitrogen at discharge (HR, 1.10 per 10 mg/dL, 95% CI, 1.08-1.12, P < .001) was associated with increased mortality, but the HR decreased with time from discharge (δHR, 0.98 per 10 mg/dL per year, 95% CI, 0.98-0.99, P < .001). Higher hemoglobin levels were associated with lower mortality (HR, 0.92 per g/dL, 95% CI, 0.91-0.93, P < .001), but this association increased with increasing time after discharge (δHR, 1.02 per g/dL per year, 95% CI, 1.01-1.02, P < .001). Older age was associated with an increased risk of mortality (HR, 1.29 per decade of age, 95% CI, 1.27-1.31, P < .001) that grew with increasing time after discharge (δHR, 1.01 per year of follow-up per decade of age, 95% CI, 1.00-1.02, P < .001). Compared to private insurances Medicaid as primary insurance was associated with an increased risk of mortality (HR, 1.17, 95% CI, 1.10-1.25, P < .001) that did not change with time after discharge. In contrast, Medicare status was initially associated with a similar risk of mortality as private insurance at discharge (HR, 1), but was associated with greater risk as time after discharge increased (δHR, 1.04 per year of follow-up, 95% CI, 1.03-1.05, P < .001). CONCLUSIONS: Acute physiologic derangements and organ dysfunction were associated with postdischarge mortality with the associations decreasing over time.

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.

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.

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.

Predicting the Response of Hydroxocobalamin in Postoperative Vasoplegia in Recipients of Cardiopulmonary Bypass.

OBJECTIVE: The primary aim of this study was to identify predictors of response to hydroxocobalamin. DESIGN: A retrospective cohort study. SETTING: A single large academic medical center within the cardiovascular surgery intensive care unit. PARTICIPANTS: Postoperative cardiovascular surgery patients within 96 hours of cardiopulmonary bypass separation between May 7, 2018, and August 1, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 66 administrations, 43 administrations yielded hemodynamic improvements (65.2%). Comparing responders to nonresponders, nonresponders had a greater median cardiopulmonary bypass duration (223 v 131 minutes; p < 0.001) and a prolonged median cross-clamp time (153 v 77 minutes; p = 0.014). Multivariate modeling demonstrated a reduction in the odds of being a responder by 57% for every 60 minutes of cardiopulmonary bypass duration (odds ratio, 0.43; 95% confidence interval, 0.28-0.68; p < 0.001), but there was no significant difference based on time from intensive care unit admission to hydroxocobalamin administration (odds ratio, 0.95; 95% confidence interval, 0.88-1.03; p = 0.20). CONCLUSION: Shorter total bypass duration and more rapid utilization after bypass of hydroxocobalamin were associated with a higher likelihood of response to refractory vasoplegic shock.

Comparison of Bivalirudin Versus Heparin for Maintenance Systemic Anticoagulation During Adult and Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: To provide a comparative analysis of conventional heparin-versus bivalirudin-based systemic anticoagulation in adult and pediatric patients supported on extracorporeal membrane oxygenation. DESIGN: Retrospective chart review study of adult and pediatric patients receiving extracorporeal membrane oxygenation from January 1, 2014, to October 1, 2019. SETTING: A large, high-volume tertiary referral adult and pediatric extracorporeal membrane oxygenation center. PATIENTS: Four hundred twenty-four individuals requiring extracorporeal membrane oxygenation support and systemically anticoagulated with either unfractionated heparin (223 adult and 65 pediatric patients) or bivalirudin (110 adult and 24 pediatric patients) were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Digital data abstraction was used to retrospectively collect patient details. The majority of both groups were cannulated centrally (67%), and the extracorporeal membrane oxygenation type was predominantly venoarterial (84%). The adult bivalirudin group had a greater occurrence of heparin-induced thrombocytopenia (12% vs 1%; p < 0.01) and was more likely to require postcardiotomy extracorporeal membrane oxygenation (36% vs 55%; p < 0.01). There were no statistical differences between the groups in regards to age, sex, and extracorporeal membrane oxygenation initiation location. The main finding was a reduced mortality in the adult bivalirudin group (odds ratio, 0.39; p < 0.01), whereas no difference was noted in the pediatric group. A significant reduction in the composite transfusion requirement in the first 24 hours was noted in the pediatric bivaluridin group with an odds ratio of 0.28 (p = 0.02). Groups did not differ in regard to laboratories per day, anticoagulant dose adjustments, or ischemic complications. CONCLUSIONS: When compared with heparin-based systemic anticoagulation, bivalirudin demonstrated feasibility and safety as established by the absence of increases in identifiable adverse outcomes while manifesting substantial improvements in hospital mortality in adult patients. Further studies are necessary to corroborate these findings and further elucidate the role of bivalirudin during extracorporeal membrane oxygenation support.

Description of Pharmacogenomic Testing Among Patients Admitted to the Intensive Care Unit After Cardiovascular Surgery.

BACKGROUND: Pharmacogenomic (PGx) testing has the potential to provide information on specific drug-metabolizing enzymes that may lead to an absence, reduction, or increase in medication effect in patients. There is a paucity of prospective studies examining PGx testing in the intensive care unit (ICU) setting. RESEARCH AIMS: To (1) obtain a PGx panel in a sample of cardiovascular (CV) surgical patients with a planned ICU stay and identify phenotypes, and (2) identify PGx variants that may inform treatment regimens and may warrant prescribing adjustments. DESIGN AND METHODS: Descriptive, single cohort cross-sectional design. Adult (≥18 years) CV patients with an anticipated postoperative ICU stay were enrolled from a large Midwestern tertiary academic medical center. Eligible patients provided informed consent at the time of their CV clinic appointment; PGx testing was then ordered. Pharmacogenomic testing consisted of the Focused Pharmacogenomics panel which included 10 genes and 55 medications. RESULTS: Of the 272 patients screened, 100 (68% male) patients completed PGx testing (mean age 66.2 ± 9.6 years, mean Acute Physiology, Age and Chronic Health Evaluation III score 76.1 ± standard deviation). Pharmacogenomic results were available in the medical record within a median of 52.4 hours (interquartile range: 33.4-80.3). Pharmacogenomic testing results identified 5 CYP2C19 poor metabolizers, 26 CYP2C19 rapid metabolizers, 5 CYP2C19 ultrarapid metabolizers, 6 CYP2D6 poor metabolizers, 5 CYP2D6 poor to intermediate metabolizers, and 2 CYP2D6 rapid metabolizers identified. Overall, 98% of patients had actionable or potentially actionable PGx results, including 82% for warfarin, 65% for propafenone, 65% for tramadol, 46% for oxycodone, 45% for metoprolol, 33% for clopidogrel, 32% for proton pump inhibitors, 25% for statins, and 12% for haloperidol. CONCLUSIONS: A significant portion of patients had identified genetic variants that may warrant changes in medication management during and after CV-ICU stay. It remains to be seen if PGx testing leads to improvements in ICU patient outcomes.

Bivalirudin for Maintenance Anticoagulation During Venovenous Extracorporeal Membrane Oxygenation for COVID-19.

In its severe manifestation, coronavirus disease 2019 (COVID-19) compromises oxygenation in a manner that is refractory to maximal conventional support and requires escalation to extracorporeal membrane oxygenation (ECMO). Maintaining ECMO support for extended durations requires a delicately balanced anticoagulation strategy to maintain circuit viability by preventing thrombus deposition while avoiding excessive anticoagulation yielding hemorrhage-a task that is complicated in COVID-19 secondary to an inherent hypercoagulable state. Bivalirudin, a member of the direct thrombin inhibitor drug class, offers potential advantages during ECMO, including to its ability to exert its effect by directly attaching to and inhibiting freely circulating and fibrin-bound thrombin. Herein, the successful use of an anticoagulation strategy using the off-label use of a continuous infusion of bivalirudin in a case of severe hypoxemic and hypercarbic respiratory failure caused by COVID-19 requiring venovenous ECMO is reported. Importantly, therapeutic anticoagulation intensity was achieved rapidly with stable pharmacokinetics, and there was no need for any circuit interventions throughout the patient's 27-day ECMO course. In COVID-19, bivalirudin offers a potential option for maintaining systemic anticoagulation during ECMO in a manner that may mitigate the prothrombotic nature of the underlying pathophysiologic state.

Outcomes of adult patients supported by extracorporeal membrane oxygenation (ECMO) following cardiopulmonary arrest. The Mayo Clinic experience.

INTRODUCTION: To describe our experience in use of extracorporeal life support (ECLS) as a rescue strategy in patients following cardiopulmonary resuscitation. METHODS: A retrospective analysis was performed for patients (n = 101) who received ECLS after cardiorespiratory arrest between May 2001 and December 2014. The primary outcome was survival to hospital discharge. RESULTS: In this cohort median (IQR) age was 56 (37-67) years, 53 (53%) were male, and 90 (89%) were Caucasian. Ventricular tachycardia or ventricular fibrillations were the initial cardiac rhythm in 49 (48.5%) and asystole/pulseless electrical activity in 37 (36.8%). Median (IQR) time to initiation of extracorporeal support from arrest time was 72 (43-170) min. The median (IQR) duration of support was 100 (47-157) hours. Renal failure (66%) and bleeding (66%) were the two most commonly observed complications during ECLS support. The survival to hospital discharge was seen in 47 (47%) patients, and good neurologic outcome (mRs 0-3) was seen in 29%. Acidosis, lactate and continuous renal replacement therapy were independent predictors of mortality. The median (IQR) intensive care unit stay was 14 (4-28) days and hospital stay was 17 (4-35) days. CONCLUSION: Our institutional experience with ECLS as a rescue measure following cardiac arrest is associated with improvement in mortality, and favorable neurologic status at hospital discharge.

A Comparison of Sepsis-2 (Systemic Inflammatory Response Syndrome Based) to Sepsis-3 (Sequential Organ Failure Assessment Based) Definitions-A Multicenter Retrospective Study.

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.

Anesthetic management for medialization laryngoplasty using concurrent infusions of dexmedetomidine, remifentanil, and propofol versus controls.

PURPOSE: Medialization laryngoplasty (ML) ±â€¯arytenoid adduction (AA) surgery poses a unique anesthetic challenge that requires periods of deep sedation and patient cooperation with phonation to assess voice function. The purpose of this study was to assess if the protocolized administration of dexmedetomidine, remifentanil, and propofol (DRP) is associated with reduced procedural duration and administration of other sedating medications. MATERIALS AND METHODS: This was a retrospective 2:1 case matched study design; matched on age, sex, body mass index, AA, and surgical revision status. Data was obtained from the electronic medical record of a tertiary referral center. Cases underwent ML ±â€¯AA using DRP. Control subjects underwent surgery ML ±â€¯AA without DRP. RESULTS: 58 DRP cases (43.1% AA) were matched with 116 control patients (44.8% AA). DRP was associated with decreases in fentanyl dose (50 [25, 100] vs. 100 [50, 150] mcg; p < 0.01), incidence and dose of midazolam (4 [6.9%] vs. 70 [60.3%]; p < 0.01; 1 [1, 1] vs. 2 [2, 2]; p < 0.02), operative duration (131 ±â€¯33 vs. 160 ±â€¯50 min; p < 0.01), and anesthetic duration (182 ±â€¯35 vs. 219 ±â€¯60.3 min; p < 0.01). When adjusted for timeline, it was observed that case duration was declining prior to DRP introduction; this trend persisted after DRP introduction. Hypopnea was more common with DRP (14 [24.1%] vs. 7 [6.0%]; p < 0.01). CONCLUSIONS: DRP was associated with a substantial decrease in opioid and benzodiazepine administration. A reduction in procedural duration over time was also observed.