An ISHLT consensus statement on strategies to prevent and manage hemocompatibility related adverse events in patients with a durable, continuous-flow ventricular assist device.

Life expectancy of patients with a durable, continuous-flow left ventricular assist device (CF-LVAD) continues to increase. Despite significant improvements in the delivery of care for patients with these devices, hemocompatability-related adverse events (HRAEs) are still a concern and contribute to significant morbility and mortality when they occur. As such, dissemination of current best evidence and practices is of critical importance. This ISHLT Consensus Statement is a summative assessment of the current literature on prevention and management of HRAEs through optimal management of oral anticoagulant and antiplatelet medications, parenteral anticoagulant medications, management of patients at high risk for HRAEs and those experiencing thrombotic or bleeding events, and device management outside of antithrombotic medications. This document is intended to assist clinicians caring for patients with a CF-LVAD provide the best care possible with respect to prevention and management of these events.

Cardiogenic shock etiology and exit strategy impact survival in patients with Impella 5.5.

BACKGROUND: Despite historical differences in cardiogenic shock (CS) outcomes by etiology, outcomes by CS etiology have yet to be described in patients supported by temporary mechanical circulatory support (MCS) with Impella 5.5. OBJECTIVES: This study aims to identify differences in survival and post-support destination for these patients in acute myocardial infarction (AMI) and acute decompensated heart failure (ADHF) CS at a high-volume, tertiary, transplant center. METHODS: A retrospective review of patients who received Impella 5.5 at our center from November 2020 to June 2022 was conducted. RESULTS: Sixty-seven patients underwent Impella 5.5 implantation for CS; 23 (34%) for AMI and 44 (66%) for ADHF. AMI patients presented with higher SCAI stage, pre-implant lactate, and rate of prior MCS devices, and fewer days from admission to implantation. Survival was lower for AMI patients at 30 days, 90 days, and discharge. No difference in time to all-cause mortality was found when excluding patients receiving transplant. There was no significant difference in complication rates between groups. CONCLUSIONS: ADHF-CS patients with Impella 5.5 support have a significantly higher rate of survival than patients with AMI-CS. ADHF patients were successfully bridged to heart transplant more often than AMI patients, contributing to increased survival.

Nationwide variability in the use of induction immunosuppression for adult heart transplantation.

BACKGROUND: Institutional factors have been shown to impact outcomes following orthotopic heart transplantation (OHT). This study evaluated center variability in the utilization of induction therapy for OHT and its implications on clinical outcomes. METHODS: Adult OHT patients between 2010 and 2018 were identified from the United Network for Organ Sharing registry. Transplant centers were stratified based on their rates of induction therapy utilization. Mixed-effects logistic regression models were created with drug-treated rejection within 1 year as primary endpoint and individual centers as a random parameter. Risk-adjusted Cox regression was used to evaluate patient-level mortality outcomes. RESULTS: In 17,524 OHTs performed at 100 centers, induction therapy was utilized in 48.6% (n = 8411) with substantial variability between centers (interquartile range, 21.4%-79.1%). There were 36, 30, and 34 centers in the low (<29%), intermediate (29%-66%), and high (>67%) induction utilization terciles groups, respectively. Induction therapy did not account for the observed variability in the treated rejection rate at 1 year among centers after adjusting for donor and recipient factors (p = .20). No differences were observed in postoperative outcomes among induction utilization centers groups (all, p > .05). Furthermore, there was a weak correlation between the percentage of induction therapy utilization at the center-level and recipients found to have moderate (r = .03) or high (r = .04) baseline risks for acute rejection at 1 year. CONCLUSIONS: This analysis demonstrates that there is substantial variability in the use of induction therapy among OHT centers. In addition, there was a minimal correlation with baseline recipient risk or 1-year rejection rates, suggesting a need for better-standardized practices for induction therapy use in OHT.

Outcomes of Adult Heart Transplantation Using Hepatitis C-Positive Donors.

Background This study evaluated the impact of hepatitis C-positive (HCV+) donors on outcomes of heart transplantation in the United States. Methods and Results Adults undergoing isolated heart transplantation in the United States between January 1, 2016, and December 31, 2018, were included. The primary outcome was 1-year post-transplant survival. Multivariable Cox regression and 2:1 propensity matching were used to compare outcomes between transplants with HCV+ and hepatitis C-negative (HCV-) donors. A subanalysis was performed to evaluate the impact of nucleic acid amplification test positivity on outcomes. Of 7889 isolated heart transplants performed during the study period, 343 (4.4%) used HCV+ donors. Overall unadjusted 1-year posttransplant survival was not statistically different between HCV- versus HCV+ donors (91.1% versus 90.2%; P=0.86), a finding that persisted after risk adjustment (hazard ratio, 1.05; 95% CI, 0.70-1.58; P=0.80). Propensity matching resulted in 675 well-balanced patients (437 HCV- and 238 HCV+). Overall 1-year posttransplant survival was not statistically different in propensity-matched analysis (89.8% HCV- versus 89.2% HCV+; P=0.88). Rates of 1-year drug-treated rejection (21.1% versus 22.1%; P=0.84), postoperative dialysis (11.4% versus 14.7%; P=0.22), and stroke (4.6% versus 2.1%; P=0.10) were also not statistically different between HCV- and HCV+ groups, respectively. Outcomes were not statistically different between nucleic acid amplification test-negative and nucleic acid amplification test-positive HCV+ donors. Conclusions Adult heart transplants using HCV+ donors, including those that are nucleic acid amplification test positive, can be performed without an adverse impact on 1-year survival. Wider implementation of protocols for using HCV+ donors and an assessment of longer-term outcomes including seroconversion rates will be important in maximizing the effect of HCV+ donors on national donor shortages.

Separate and combined effects of low dose ketamine and nicotine on behavioural and neural correlates of sustained attention.

Given the cognitive-promoting properties of the nicotinic acetylcholinergic receptor (nAChR) agonist, nicotine, the increased prevalence of smoke-inhaled nicotine in schizophrenia has been interpreted as an attempt to self-correct cognitive deficits, which have been particularly pronounced in the attentional domain. As glutamatergic abnormalities have been implicated in these attentional deficiencies, this study attempted to shed light on the separate and interactive roles of the N-methyl-d-aspartate receptor (NMDAR) and nAChR systems in the modulation of attention by investigating, in healthy volunteers, the separate and combined effects of nicotine and the NMDAR antagonist ketamine on neural and behavioural responses in a sustained attention task. In a randomized, double-blind, placebo controlled study, performance and the P300 event-related brain potential (ERP) in a visual information processing (RVIP) task were examined in 20 smokers and 20 non-smokers (both male and female). Assessment involved intravenous injection of a low subperceptual bolus dose (.04mg/kg) of ketamine or placebo, which was accompanied by acute treatment with nicotine (4mg) or placebo gum. Nicotine-enhanced attentional processing was most evident in nonsmokers, with both performance accuracy and P300 amplitude measures. Ketamine's detrimental effects on these behavioural and electrophysiologic measures were negatively moderated by acute nicotine, the synergistic effects being expressed differently in smokers and nonsmokers. These findings support the view that acute alterations and individual differences in nAChR function can moderate even subtle glutamatergic-driven cognitive deficiencies in schizophrenia and can be important therapeutic targets for treating cognitive impairments in schizophrenia.

Public health and environmental response to the first case of naturally acquired inhalational anthrax in the United States in 30 years: infection of a new york city resident who worked with dried animal hides.

In Pennsylvania on February 16, 2006, a New York City resident collapsed with rigors and was hospitalized. On February 21, the Centers for Disease Control and Prevention and the New York City Department of Health and Mental Hygiene were notified that Bacillus anthracis had been identified in the patient's blood. Although the patient's history of working with dried animal hides to make African drums indicated the likelihood of a natural exposure to aerosolized anthrax spores, bioterrorism had to be ruled out first. Ultimately, this case proved to be the first case of naturally occurring inhalational anthrax in 30 years. This article describes the epidemiologic and environmental investigation to identify other cases and persons at risk and to determine the source of exposure and scope of contamination. Because stricter regulation of the importation of animal hides from areas where anthrax is enzootic is difficult, public healthcare officials should consider the possibility of future naturally occurring anthrax cases caused by contaminated hides. Federal protocols are needed to assist in the local response, which should be tempered by our growing understanding of the epidemiology of naturally acquired anthrax. These protocols should include recommended methods for reliable and efficient environmental sample collection and laboratory testing, and environmental risk assessments and remediation.

Erythropoietic agents for anemia of critical illness.

PURPOSE: Evidence regarding the cost-effective use of and benefits associated with epoetin alfa in treating anemia of critically ill patients is assessed. SUMMARY: Anemia of critical illness is a leading cause of inadequate oxygen delivery that affects almost all patients in the intensive care unit setting after day 3. Red blood cell transfusions are commonly used to correct anemia of critical illness, but they are also associated with risks including hemolytic reactions and viral transmission. The latest evidence suggests that when a strict transfusion protocol is implemented, epoetin alfa does not decrease the transfusion requirements of critically ill patients. In the absence of a strict transfusion protocol, an average of 5.1 doses of epoetin, at a cost of $2154, is required to avoid one transfusion. Evidence is accumulating that epoetin may reduce mortality rates in trauma patients. However, important questions remain regarding the magnitude and mechanism of the potential benefit and if the benefit outweighs the risk of thromboembolism. Therefore, the reduction in transfusion-related adverse events is the only clinical outcome benefit that is well-supported by current evidence. However, the known risk of transfusion-related adverse events is low; approximately 29,000 patients would need to be treated to avoid a serious transfusion-related event. Treating these patients would cost over $25 million, and it would take over 100 years to prevent one serious event in a unit admitting 20 epoetin-eligible patients per month. CONCLUSION: Published data suggest a prohibitive cost associated with epoetin alfa use in critically ill patients given that the only well-supported clinical benefit of this treatment is the avoidance of transfusion-related adverse events. Continued research is necessary to clarify if there is a net clinical benefit of epoetin use (especially in trauma patients) and to develop optimal blood management strategies.

The critical care clinical pharmacist: evolution of an essential team member.

OBJECTIVE: To review the history, training requirements, contributions to patient care outcomes, and workforce issues of critical care pharmacists. DATA SOURCE AND SELECTION: Literature obtained through Medline search with manual cross-referencing. DATA EXTRACTION AND SYNTHESIS: Original and selected review articles and guideline documents were reviewed for references to critical care pharmacists and their role on the multiprofessional critical care team. CONCLUSIONS: Critical care pharmacists are recognized as essential members of the critical care team as a result of contributions to medication safety, improved patient outcomes, and reduced drug costs and as a source of drug information and provider of education. A growing number of pharmacists practice in critical care. Additional opportunities exist and can be met if an adequate supply of trained specialists can be developed.

Number needed to treat and cost of recombinant human erythropoietin to avoid one transfusion-related adverse event in critically ill patients.

OBJECTIVE: To calculate the absolute risk reduction of transfusion-related adverse events, the number of patients needed to treat, and cost to avoid one transfusion-related adverse event by using erythropoietin in critically ill patients DESIGN: Number needed to treat with sensitivity analysis. SETTING: Teaching hospital. PATIENTS: Hypothetical cohort of critically ill patients who were candidates to receive erythropoietin. INTERVENTIONS: Using vs. not using erythropoietin to reduce the need for packed red blood cell transfusions. MEASUREMENTS AND MAIN RESULTS: We used published estimates of known transfusion risks: transfusion-related acute lung injury, transfusion-related errors, hepatitis B and C, human immunodeficiency virus, human T-cell lymphotropic virus, and bacterial contamination, stratified by severity. Based on the estimated risk and frequency of transfusions with and without erythropoietin, we calculated the absolute risk reduction of transfusion-related adverse events, the number needed to treat, and cost to avoid one transfusion-related adverse event by using erythropoietin. The estimated incidence of transfusion-related adverse event was 318 permillion units transfused for all transfusion-related adverse events, 58 per million for serious transfusion-related adverse events, and 21 per million for likely fatal transfusion-related adverse events. The routine use of erythropoietin resulted in an absolute risk reduction of 191 per million for all transfusion-related adverse events, 35 per million for serious transfusion-related adverse events, and 12 per million for likely fatal transfusion-related adverse events. The number needed to treat was 5,246 to avoid one transfusion-related adverse event, 28,785 to avoid a serious transfusion-related adverse event, and 81,000 for a likely fatal transfusion-related adverse event. The total cost was $4,700,000 to avoid one transfusion-related adverse event, $25,600,000 to avoid one serious transfusion-related adverse event, and $71,800,000 to avoid a likely fatal transfusion-related adverse event. The magnitude of these results withstood extensive sensitivity analysis. CONCLUSIONS: From the perspective of avoidance of adverse events, erythropoietin does not appear to be an efficient use of limited resources for routine use in critically ill patients.

Pharmacology and pharmacokinetics of sedatives and analgesics.

The agents used for sedation and analgesia during endoscopy have complex pharmacokinetic and pharmacodynamic properties. Knowledge of these characteristics is necessary for determining the proper agent and dose for specific patient needs. Short-acting agents, such as fentanyl, midazolam, and propofol, provide rapid sedation with a short duration of action that allows patients to return to normal functioning rapidly. When designing a dosing regimen with these agents, age and organ (liver, kidney) function of patients and concomitant medications that may interfere with metabolic and elimination pathways must be considered.