Left ventricular unloading via percutaneous assist device during extracorporeal membrane oxygenation in acute myocardial infarction and cardiac arrest.

INTRODUCTION: A feared complication of an acute myocardial infarction (AMI) is cardiac arrest (CA). Even if return of spontaneous circulation is achieved, cardiogenic shock (CS) is common. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) supports patients with CS and is often used in conjunction with an Impella device (2.5 and CP) to off-load the left ventricle, although limited evidence supports this approach. METHODS: The goal of this study was to determine whether a mortality difference was observed in VA-ECMO alone versus VA-ECMO with Impella (ECPELLA) in patients with CS from AMI and CA. A retrospective chart review of 50 patients with AMI-CS and CA and were supported with VA-ECMO (n = 34) or ECPELLA (n = 16) was performed. The primary outcome was all-cause mortality at 6-months from VA-ECMO or Impella implantation. Secondary outcomes included in-hospital mortality and complication rates between both cohorts and intensive care unit data. RESULTS: Baseline characteristics were similar, except patients with ST-elevation myocardial infarction were more likely to be in the VA-ECMO group (p = 0.044). The ECPELLA cohort had significantly worse survival after VA-ECMO (SAVE) score (p = 0.032). Six-month all-cause mortality was not significantly different between the cohorts, even when adjusting for SAVE score. Secondary outcomes were notable for an increased rate of minor complications without an increased rate of major complications in the ECPELLA group. CONCLUSIONS: Randomized trials are needed to determine if a mortality difference exists between VA-ECMO and ECPELLA platforms in patients with AMI complicated by CA and CS.

Multicenter evaluation of left ventricular assist device implantation with or without ECMO bridge in cardiogenic shock.

BACKGROUND: The efficacy of extracorporeal membrane oxygenation (ECMO) as a bridge to left ventricular assist device (LVAD) remains unclear, and recipients of the more contemporary HeartMate 3 (HM3) LVAD are not well represented in previous studies. We therefore undertook a multicenter, retrospective study of this population. METHODS AND RESULTS: INTERMACS 1 LVAD recipients from five U.S. centers were included. In-hospital and one-year outcomes were recorded. The primary outcome was the overall mortality hazard comparing ECMO versus non-ECMO patients by propensity-weighted survival analysis. Secondary outcomes included survival by LVAD type, as well as postoperative and one-year outcomes. One hundred and twenty-seven patients were included; 24 received ECMO as a bridge to LVAD. Mortality was higher in patients bridged with ECMO in the primary analysis (HR 3.22 [95%CI 1.06-9.77], p = 0.039). Right ventricular assist device was more common in the ECMO group (ECMO: 54.2% vs non-ECMO: 11.7%, p < 0.001). Ischemic stroke was higher at one year in the ECMO group (ECMO: 25.0% vs non-ECMO: 4.9%, p = 0.006). Among the study cohort, one-year mortality was lower in HM3 than in HeartMate II (HMII) or HeartWare HVAD (10.5% vs 46.9% vs 31.6%, respectively; p < 0.001) recipients. Pump thrombosis at one year was lower in HM3 than in HMII or HVAD (1.8% vs 16.1% vs 16.2%, respectively; p = 0.026) recipients. CONCLUSIONS: Higher mortality was observed with ECMO as a bridge to LVAD, likely due to higher acuity illness, yet acceptable one-year survival was seen compared with historical rates. The receipt of the HM3 was associated with improved survival compared with older generation devices.

Effect of Anesthesia Induction on Cardiac Hemodynamics in Patients Undergoing Durable Left Ventricular Assist Device Implantation: The EACH-LVAD Study.

Right ventricular (RV) dysfunction is common after left ventricular assist device (LVAD) implantation leading to clinical right heart failure (RHF) associated with worsened survival and quality of life. It is likely that intraoperative events such as anesthesia induction play a role in the development or unmasking of RV dysfunction in addition to known effects from hemodynamic changes that occur after LVAD implantation. The EACH-LVAD Study is a prospective, single-center, single-arm, observational cohort study of adult patients with advanced heart failure undergoing durable LVAD implantation with standard anesthesia induction. Intraoperative RV hemodynamics via central venous pressure, mean pulmonary artery pressure, pulmonary artery pulsatility index, and vasoactive-inotropic score (a simple weighted summation of standardized drug doses) and echocardiographic parameters (RV fractional area change, RV area in diastole, RV basal diameter, septum position, RV function, tricuspid regurgitation) were measured and compared at prespecified timepoints, including postinduction. Postoperative clinical RHF was determined based on published definitions. Forty-two patients receiving a first-time LVAD were included between September 2017 and March 2019. Propofol-based induction was used in 31 patients and etomidate-based induction in eight patients. A significant increase in central venous pressure (CVP; p < 0.001), mean pulmonary artery pressure (mPAP; p < 0.001), and vasoactive inotropic score (VIS; p < 0.001) with associated decrease in pulmonary artery pulsatility index (PAPi; p < 0.001) was observed. Right ventricular function worsened throughout. Right heart failure occurred in 70% of patients. Propofol-based induction was not associated with a higher risk of RHF (relative risk [RR], 1.01 [95% confidence interval {CI}, 0.64-1.61]). The EACH-LVAD study demonstrates an effect of anesthesia induction on worsened RV hemodynamics and echocardiographic changes which may have an effect on the development of RHF.

QT interval measurement in ventricular pacing: Implications for assessment of drug effects and pro-arrhythmia risk.

QT interval prolongation is a known risk factor for development of malignant ventricular arrhythmias. Measurement of the QT interval is difficult in the setting of ventricular pacing (VP), which can prolong depolarization and increase the QT interval, overestimating repolarization time. VP and cardiac resynchronization therapies have become commonplace in modern cardiac care and may contribute to repolarization heterogeneity and subsequent increased risk for ventricular arrhythmias including Torsades de Pointes. It is imperative for the clinician caring for acutely ill cardiac patients to understand the relationship between QT interval prolongation, both drug-induced and pacing-induced, and repolarization changes with subsequent ventricular arrhythmia risk. In this review, we discuss the components of QT interval assessment for arrhythmogenic risk including arrhythmogenic QT prolongation, methods for adjusting the QT interval to identify repolarization changes, methods to adjust for heart rate, and propose a framework for medication management to assess for drug-induced long QT syndrome in patients with VP.

SAVE score with lactate modification predicts in-hospital mortality in patients with ongoing cardiac arrest during VA-ECMO cannulation.

The survival after veno-arterial extracorporeal membrane oxygenation score and its lactate modification predict in-hospital mortality in patients based on pre-extracorporeal membrane oxygenation variables. Cardiac arrest history is a significant variable in these scores; however, patients with ongoing cardiac arrest during cannulation were excluded from these models. The goal of this study is to validate the survival after veno-arterial extracorporeal membrane oxygenation score with a lactate modification among patients with ongoing cardiac arrest. In our study, the survival after veno-arterial extracorporeal membrane oxygenation score predicted mortality in all patients, but did so with higher discrimination among ongoing cardiac arrest patients with a lactate modification.

Survival and Outcomes After Cardiac Arrest With VA-ECMO Rescue Therapy.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) use in patients with cardiac arrest is increasing. Utilization remains variable between centers using ECMO as a rescue therapy or early protocolized extracorporeal cardiopulmonary resuscitation. METHODS: Single-center, retrospective evaluation of cardiac arrest with cardiopulmonary resuscitation and rescue ECMO support from 2011 through 2019. Study objectives included survival, non-neurologic, and neurologic outcomes; validation of the SAVE and modified SAVE (mSAVE) scores for survival and favorable neurologic outcome; and predictive factor identification in cardiac arrest with ECMO rescue therapy. RESULTS: Eighty-nine patients were included. In-hospital survival was 38.2% and median CPC score was 2. Survivors had lower BMI (27.9 ±â€Š4.2 kg/m2 vs. 32.3 ±â€Š7.5 kg/m2, P = 0.003), less obesity (BMI ≥ 30 kg/m2) (26.5% vs. 49.1%, P = 0.035), shorter CPR duration (35.5 ±â€Š31.7 m vs. 58.0 ±â€Š49.5 m, P = 0.019), more tracheostomy (38.2% vs. 7.3%, P < 0.001), and less renal replacement therapy (RRT) (17.6% vs. 38.2%, P = 0.031). Patients with a favorable neurologic outcome had lower body weight (86.2 ±â€Š17.9 kg vs. 98.1 ±â€Š19.4 kg, P = 0.010), lower BMI (28.1 ±â€Š4.5 kg/m2 vs. 33.9 ±â€Š7.9 kg/m2, P < 0.001), and less obesity (29.7% vs. 56.3%, P = 0.026). mSAVE score predicted in-hospital survival (OR 1.11; 95%CI 1.03-1.19; P = 0.004) and favorable neurologic outcome (OR 1.11; 1.03-1.20; P = 0.009). Multivariate analysis for in-hospital survival included mSAVE, BMI, CPR-time, tracheostomy, and RRT (c-statistic: 0.864). Favorable neurologic outcome included mSAVE and BMI (c-statistic: 0.805). CONCLUSIONS: mSAVE, BMI, RRT, and tracheostomy are predictors of in-hospital survival and mSAVE and BMI are predictors of favorable neurologic outcome in cardiac arrest with ECMO rescue therapy.

Fever Associated With Dexmedetomidine in Adult Acute Care Patients: A Systematic Review of the Literature.

Dexmedetomidine-associated fever has been reported in the literature and can lead to lengthy workups and unnecessary antibiotic exposure. We conducted a systematic review to evaluate and describe the evidence of fever or hyperthermia caused by dexmedetomidine in adult patients. Data sources included PubMed/MEDLINE, EMBASE, CINAHL, and Web of Sciences. English-language studies of any design published from inception through April 2020 including conference abstracts were included. The target population was hospitalized adult patients. Quality of evidence was determined based on GRADE recommendations and risk of bias assessed using the Evidence Project Risk of Bias tool. Naranjo scores were assessed to determine the likeliness of adverse event being caused by dexmedetomidine. All data were extracted independently and with the guidance of a medical librarian. Four hundred and eighty-eight total citations were found on formal search, with 329 left after removal of duplicates. Independent record screening was performed, leaving 17 citations including 4 retrospective cohort studies, 1 case series, and 12 case reports. Quality of evidence ranged from very low to low for identified analyses. Evidence with patient-level data (case reports and series) were combined to establish a cohort for descriptive results. The median Naranjo score was 4 (range, 3 to 8), and dexmedetomidine doses ranged from 0.1 to 2 µg·h/kg. Obesity and cardiac surgery appear to be significant risk factors. Dexmedetomidine-associated fever appears uncommon, but the true incidence is unknown. Clinicians should keep dexmedetomidine-associated fever in their differential, and stewardship programs should consider assessing for this adverse effect in their patient monitoring.

Long-term discontinuation of antithrombotic therapy in patients with HeartMate II continuous-flow left ventricular assist device support.

Recurrent bleeding events are a common complication of left ventricular assist devices leading to significant morbidity. Clinicians may be reluctant to discontinue all antithrombotic therapies in this setting because of the risk of thrombotic events. To evaluate the safety of this strategy, we conducted a retrospective review of patients within our institution's left ventricular assist device program from February 2010 to July 2018 who had all antithrombotic therapies discontinued in response to recurrent bleeding events requiring hospitalization. Thrombotic and bleeding outcomes after discontinuation of therapy were assessed and compared. Seven patients out of 87 (8%) were identified and included in this analysis. One patient experienced pump thrombosis in the setting of driveline infection with an overall rate of thrombotic events of 0.08 per-patient-year. Sixteen gastrointestinal bleeding events occurred after discontinuation of antithrombotic therapy (1.35 per-patient-year) compared with 37 prior to discontinuation (4.28 per-patient-year) resulting in a significant reduction (reduction rate = 0.32; 95% confidence interval = [0.17, 0.58]; p < .001). Thrombotic complications were rare among patients with HeartMate II left ventricular assist device support who suffered recurrent bleeding events and in whom antithrombotic therapy was, therefore, discontinued. Gastrointestinal bleeding was significantly reduced in this group; however, angioectasia-related gastrointestinal bleedings remained problematic.

Derivation and Validation of Age- and Body Mass Index-Adjusted Weight-Based Unfractionated Heparin Dosing.

Unfractionated heparin dosing is unpredictable and subject to numerous pharmacokinetic changes including distribution and metabolic changes associated with obesity and age. Weight-based dosing is commonly used to better predict the dose for a patient when targeting a therapeutic range. A dosing equation that adjusts weight-based doses for age and body mass index may improve therapeutic dose prediction. We conducted a 2-phase observational study with a derivation and validation period to develop an equation to adjust weight-based unfractionated heparin for age and body mass index to target a therapeutic activated partial thromboplastin time of 60 to 80 seconds. The first phase retrospectively identified patients who acheived therapeutic anticoagulation and utilized linear regression to determine a predictive equation for weight-based dosing that adjusts for age and body mass index. The second phase prospectively identified patients in an observational manner and compared the dose of unfractionated heparin on which they became therapeutic against both the weight-based dose and the predicted dose adjusted for age and body mass index. The correlation between predictive age and body mass index adjusted dose and actual therapeutic dose was 0.703 compared to the correlation between the empiric weight-based dose and actual therapeutic dose which was 0.532 ( P = .05). Age and body mass index adjusted weight-based dosing significantly improved therapeutic dose prediction for unfractionated heparin. Further study in a prospective, randomized trial is warranted for validation of this approach in a real world setting.

Time in the Therapeutic Range for Assessing Anticoagulation Quality in Patients Receiving Continuous Unfractionated Heparin.

Due to variable pharmacokinetic properties, therapeutic anticoagulation with continuous unfractionated heparin (UFH) requires ongoing laboratory monitoring, generally with activated partial thromboplastin time (aPTT). In the ambulatory setting, clinicians who manage warfarin therapy often use time in the therapeutic range (TTR) to estimate a percentage of time the international normalized ratio is therapeutic. We applied the TTR concept to aPTT monitoring for therapeutic UFH and used 2 methodologies for estimation: percentage of aPTT values in range (%aIR) and a modification of the Rosendaal method (mod-Rosendaal). This study included adult inpatients admitted between September 30, 2015, and September 30, 2016, at Brigham and Women's Hospital. For each patient, all available aPTT values were extracted to calculate 2 individual TTRs according to each methodology. Comparison between methods was performed using Student t test, and correlation was assessed with simple linear regression. A total of 255 patients were included in this study. The major outcome of TTR estimation was significantly higher using mod-Rosendaal (43.7% [26.5%]) versus %aIR (37.7% [25.7%], P = .012) by a mean difference of 6% points (95% confidence interval: 1.3-10.7). Time in the therapeutic range estimated by mod-Rosendaal significantly correlated with those estimated by %aIR (r = 0.84, P < .001). Further studies should evaluate the correlation between TTR and clinical outcomes and establish a benchmark for quality therapeutic anticoagulation with continuous UFH.

Evaluation of Compliance with a Weight-based Nurse-driven Heparin Nomogram in a Tertiary Academic Medical Center.

BACKGROUND: Recently, our institution adopted a weight-based nurse-driven heparin titration protocol that relies on nurses ordering laboratories, adjusting doses, and initiating boluses. Numerous institutions have implemented similar protocols with reported success. METHODS: A single-center retrospective analysis was conducted at the Brigham and Women's Hospital in Boston, Massachusetts that included all patients who were initiated on the weight-based nurse-driven heparin nomogram during a 30-day period. Nomogram compliance was defined as the rate of correct titrations per nomogram encounter and further separated into laboratory, titration, or dosing compliance. Spearman's coefficient was utilized to determine the correlation between noncompliance and percentage of activated partial thromboplastin time (aPTT) values in range. RESULTS: Overall, 211 patients were evaluated for inclusion, of which 95 patients were determined to meet criteria for evaluation. The total nomogram compliance rate was 84.6% ± 10.5%. Laboratory, titration, and dosing compliances were 77.6% ± 19.2%, 87.2% ± 14.5%, and 91.8% ± 10.6%, respectively. The percent of aPTT values in therapeutic range was 39.6% ± 24.6%. A moderate negative correlation between the percentage of aPTT values in range and the nomogram error rate was observed (r = -0.452, P < 0.001). This relationship was found to be driven by the rate of dosing error, which showed the strongest correlation with percentage of aPTT values out of range (r = -0.465, P = 0.001). CONCLUSIONS: Implementation of a nurse-driven heparin titration nomogram relies on compliance with the prescribed protocol. Dosing compliance had the lowest error rate, whereas dosing noncompliance had the strongest impact on percentage of aPTT values in range.

Description and Evaluation of the Implementation of a Weight-Based, Nurse-Driven Heparin Nomogram in a Tertiary Academic Medical Center.

Weight-based, nurse-driven heparin nomograms are reported in the medical literature to improve the time it takes to reach a minimum threshold for anticoagulation without compromising patient safety in specific indications or patient populations. This is the first report in the literature of an institution-wide protocol implementation and evaluation of effectiveness with simultaneous transition to an electronic health record. The purpose of implementing this practice change at our institution was to standardize practice, improve time to reach therapeutic anticoagulation, and improve patient safety. We conducted a retrospective analysis utilizing a pre/postimplementation design to compare outcomes. The primary end point evaluated was the time to reach minimum threshold value for therapeutic anticoagulation. Additionally, we assessed the percentage of patients who reached minimum threshold therapeutic anticoagulation within 24 hours, the percentage of patients with a critically supratherapeutic activated partial thromboplastin time (aPTT) value (≥120 seconds) during therapy, and a description of heparin titration for the first 4 aPTT results with nomogram use. Overall time to therapeutic anticoagulation decreased from a mean 18.7 to 11.7 hours (hazard ratio [HR] 1.59; 95% confidence interval 1.22-2.08; P < .0005). Percentage of patients receiving therapeutic anticoagulation within 24 hours increased from 74.4 to 88.5 (odds ratio [OR 2.97, P = .002) and the percentage of patients with an aPTT ≥120 seconds remained constant at 49.9 versus 46.8 (OR 0.92, P = .73). This practice change reduced time to therapeutic anticoagulation without an increase in the proportion of patients with a critically supratherapeutic aPTT at our institution.

Neuroendocrine Derangements in Early Septic Shock: Pharmacotherapy for Relative Adrenal and Vasopressin Insufficiency.

Septic shock is a leading cause of mortality in intensive care units throughout the world. While this disease state represents a highly complex pathophysiology involving numerous organ systems, the early approach to care includes adequate hemodynamic support traditionally achieved via infusions of vasoactive medications after adequate fluid resuscitation. Relative adrenal and vasopressin deficiencies are a common feature of septic shock that contribute to impaired hemodynamics. Hydrocortisone and vasopressin are endocrine system hormone analogues that target the acute neuroendocrine imbalance associated with septic shock. This clinically focused annotated review describes the pathophysiological mechanisms behind their use and explores the potential clinical roles of early administration and synergy when combined.

Intravenous Immune Globulin Stewardship Program at a Tertiary Academic Medical Center.

BACKGROUND: In October 2010, a pharmacist-driven stewardship program was implemented at the Brigham and Women's Hospital to ensure continued adherence to the prescribing guideline, focusing on indications for intravenous immune globulin (IVIG) use and dosing per ideal body weight. OBJECTIVE: The primary objective was to describe an IVIG stewardship program at a tertiary academic medical center. METHODS: This was a prospective, observational study from January 2013 through December 2014. All patients ordered to receive IVIG during the defined study period were included. The intervention assessed describes a pharmacist-driven IVIG stewardship program for medication approval. The primary end point was guideline compliance based on indication, dose, dosing weight, and frequency. Secondary end points included the number of patients receiving IVIG, indications, orders discontinued as a result of guideline nonadherence, and total amount dispensed. RESULTS: A total of 418 patients were identified during the study time frame. The top indications were: hypogammaglobulinemia in bone marrow transplantation and hematological malignancy (50.7%), acute solid organ rejection (11.8%), and immune thrombocytopenia with bleeding (10.1%). In all, 12 patients (2.9%) received IVIG for an indication nonadherent with the IVIG prescribing guideline; 9 patients (2.2%) and 2 patients (0.5%), respectively, received a different dose or frequency per the prescribed indication; and 12 orders (2.9%) for indications nonadherent to the guideline were discontinued. A total of 26 033 g of IVIG were dispensed during the study period. CONCLUSIONS: An IVIG stewardship program, including an institution-specific prescribing guideline and a pharmacist-driven stewardship program, may ensure guideline compliance for appropriateness of indication and dose at an academic medical center.

Incidence of Sepsis and Mortality With Prior Exposure of HMG-COA Reductase Inhibitors in a Surgical Intensive Care Population.

The anti-inflammatory properties of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may reduce the risk of developing sepsis in surgical intensive care patients and improve outcomes in those who do become septic. The objective of this study was to assess whether surgical intensive care unit (SICU) patients with prior exposure to HMG-CoA reductase inhibitors had a lower incidence of developing sepsis and improved outcomes. A retrospective cohort study was conducted. Patient demographic data, statin use, sequential organ failure assessment (SOFA) scores, vasopressor requirements, ventilator days, length of SICU stay, and mortality in septic patients were collected. Incidence of development of sepsis was determined using systemic inflammatory response syndrome criteria. Patients were grouped into cohorts based on whether they met the sepsis criteria and if they had previously received statins. Cohorts of patients who did and did not become septic with prior statin exposure were compared and an odds ratio was calculated to determine a protective effect. The setting was a SICU. The study comprised of 455 SICU patients and had no interventions. Among the 455 SICU patients, 427 patients were included for the final results. Patients receiving statins verses not receiving statins were similar in demographics. Previous statin exposure had a protective effect in the development of sepsis (9.77% on statins vs. 33.6% without statins; odds ratio 0.203, confidence interval 0.118-0.351). Of those patients who developed sepsis, there was a statistically significant decrease in 28-day mortality in patients with prior statin exposure (P = 0.0341). No statistical difference was noted in length of stay, vasopressor requirements, or days on mechanical ventilation. Prior exposure to statins may have a protective effect on the development of sepsis and decrease mortality in critically ill surgical patients.

Controversial therapeutics: the ß-adrenergic antagonist and cocaine-associated cardiovascular complications dilemma.

Cocaine abuse is associated with cardiovascular complications that include chest pain and myocardial infarction. Traditional therapy for these conditions includes a ß-adrenergic antagonist. However, guidelines released in 2008 recommended against this treatment option because of the prevailing theory that cocaine will potentiate vasospasm secondary to unopposed α-adrenergic effects. Subsequently, further evidence and updated guidelines have become available, debunking this claim. Current literature is limited but suggests that ß-adrenergic antagonists are harmful. Although case reports support a detrimental effect of ß-adrenergic antagonists, the anecdotal data are inconsistent, and the conclusions from case studies are overruled by larger studies. The pharmacology, pathophysiology, and literature on the use of ß-adrenergic antagonists in association with cocaine are reviewed. Future studies that focus on outcomes and different pharmacologic profiles of ß-adrenergic antagonists are needed.