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Background Extracorporeal membrane oxygenation (ECMO) is a life-saving modality but has the potential to alter the pharmacokinetics (PK) of antimicrobials. Imipenem/cilastatin/relebactam is an antibiotic with utility in treating certain multi-drug resistant Gram-negative infections. Herein, we describe the population pharmacokinetics of imipenem and relebactam in critically ill patients supported on ECMO. Methods Patients with infection supported on ECMO received 4–6 doses of imipenem/cilastatin/relebactam per current prescribing information based on estimated creatinine clearance. Blood samples were collected following the final dose of the antibiotic. Concentrations were determined via LC–MS/MS. Population PK models were fit with and without covariates using Pmetrics. Monte Carlo simulations of 1000 patients assessed joint PTA of f AUC0–24/MIC ≥ 8 for relebactam, and ≥40% f T > MIC for imipenem for each approved dosing regimen. Results Seven patients supported on ECMO were included in PK analyses. A two-compartment model with creatinine clearance as a covariate on clearance for both imipenem and relebactam fitted the data best. The mean ± standard deviation parameters were: CL0, 15.21 ± 6.52 L/h; Vc, 10.13 ± 2.26 L; K12, 2.45 ± 1.16 h−1 and K21, 1.76 ± 0.49 h−1 for imipenem, and 6.95 ± 1.34 L/h, 9.81 ± 2.69 L, 2.43 ± 1.13 h−1 and 1.52 ± 0.67 h−1 for relebactam. Simulating each approved dose of imipenem/cilastatin/relebactam according to creatinine clearance yielded PTAs of ≥90% up to an MIC of 2 mg/L. Conclusions Imipenem/cilastatin/relebactam dosed according to package insert in patients supported on ECMO is predicted to achieve exposures sufficient to treat susceptible Gram-negative isolates, including Pseudomonas aeruginosa. [ABSTRACT FROM AUTHOR]

Background: We analyzed the use of Extracorporeal Membranous Oxygenation (ECMO) in acute care surgery patients at our Level-1 trauma center. We hypothesized that this patient population has improved ECMO outcomes. Methods: This was a retrospective analysis of emergency general surgery and trauma patients placed on ECMO between the periods of October 2013 and February 2020. There were 10 surgical and 12 trauma patients studied, who eventually required ECMO support. ECMO support and ECMO type/modality were analyzed with injury and survival prognostic scores examined. Main results: Overall, 16 of the 22 patients survived to hospital discharge, for a survival rate of 73%. Mean age was 34.18 years. Mean hospital length of stay was 23.4 days with mean days on ECMO equal to 7.5. The net negative fluid balance was 5.36 L. Conclusions: The survival of our ECMO cohort is notably higher than previously cited studies. Our group demonstrated decreased length of time on ECMO, decreased length of stay in the hospital, and similar rates of complications compared to prior reports. ECMO is a useful modality in acute care surgical patients and should be considered in these patient populations. Our focus on net negative fluid balance for ECMO patients demonstrates improved survival. ECMO should be considered early in surgical patients and early in advanced trauma life support. [ABSTRACT FROM AUTHOR]

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Objective: To examine if older age (>70 years) should be a relative contraindication for heart transplantation, we evaluated the characteristics and outcomes of patients with age ≥70 years listed for heart transplantation; and whether post‐transplantation survival was inferior to younger counterparts. Design Retrospective cohort analysis. Setting: The scientific registry of transplant recipients (SRTR). Participants: Adults (≥18 years) listed for heart transplantation in the SRTR between 2000 and 2018. Interventions: Heart transplantation. Measurements Characteristics and outcomes were compared for adults ≥70 years and <70 years. We evaluated waitlist mortality and post‐transplant 1‐year and 5‐year survivals. Results: The study included 57,285 patients (age range 18–79 years) listed for heart transplantation; 1203 (2.1%) age ≥70 years. Of these, 37,135 patients underwent heart transplantation; 806 (2.2%) were age ≥70 years. Yearly listing of those age ≥70 years has consistently increased from 2.5% (n = 30) in 2000 to 11% (n = 132) in 2017 (p < 0.01). As compared with the age <70 years group, those ≥70 years had a similar risk of death while waiting (sub‐hazard ratio [SHR] 0.86, 95% confidence interval [HR] 0.68–1.08; p = 0.19) but were more likely to be transplanted (SHR 1.36, 95% CI 1.26–1.48; p < 0.01). Among the older patients, the overall post‐transplant 1‐ and 5‐year mortality rate was 10.4% and 19.2%, respectively. Older recipients had lower unadjusted survival compared with younger recipients (log‐rank p = 0.03). However, after adjustment for relevant covariates, there was no significant difference in 5‐year mortality between both groups (HR 1.06, 95% CI 0.91–1.254; p = 0.43). Conclusions: Post‐transplant survival up to 5 years among patients of age ≥70 years was similar to that of younger recipients. Older patients who received heart transplantation appear to have lower risk features but receive hearts from higher risk donors. Chronologic age alone should not constitute a contraindication for heart transplantation, although careful patient selection criteria should be applied. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 pandemic disrupted health care delivery in every respect, including critical care resources and the transport of patients requiring extracorporeal membrane oxygenation. Innovative solutions allowing for safe helicopter air transport of these critical patients is needed because extracorporeal membrane oxygenation resources are only available in specialty centers. We present a case demonstrating the interfacility collaboration of care for a patient with coronavirus disease 2019 infection and the lessons learned from the air transport. Careful planning, coordination, communication, and teamwork contributed to the safe transport of this patient and several others subsequently. [ABSTRACT FROM AUTHOR]

The clinical course and outcomes of immunocompromised patients, such as transplant recipients, with COVID‐19 remain unclear. It has been postulated that a substantial portion of the disease burden seems to be mediated by the host immune activation to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Herein, we present a simultaneous heart‐kidney transplant (SHKT) recipient who was hospitalized for the management of respiratory failure from volume overload complicated by failure to thrive, multiple opportunistic infections, and open non‐healing wounds in the setting of worsening renal dysfunction weeks prior to the first case of SARS‐CoV‐2 being detected in the state of Connecticut. After his third endotracheal intubation, routine nucleic acid testing (NAT) for SARS‐CoV‐2, in anticipation of a planned tracheostomy, was positive. His hemodynamics, respiratory status, and ventilator requirements remained stable without any worsening for 4 weeks until he had a negative NAT test. It is possible that the immunocompromised status of our patient may have prevented significant immune activation leading up to clinically significant cytokine storm that could have resulted in acute respiratory distress syndrome and multisystem organ failure. [ABSTRACT FROM AUTHOR]

Background: Historically, there is perceived pressure to achieve therapeutic levels of tacrolimus quickly after heart transplant (HT). We evaluated the association between time within therapeutic tacrolimus range and time to therapeutic trough and rejection in the 30 days following HT. Methods: This is a single‐center retrospective cohort study of consecutive adult HT patients receiving immunosuppression. Goal trough tacrolimus levels were 10–15 ng/ml. Surveillance endomyocardial biopsies were performed weekly for 4 weeks. Outcomes included the effect of time to and time‐in‐therapeutic tacrolimus range (Rosendaal method) on 30‐day clinical rejection, 1R/1B, and 2R or higher histologic occurrences. Results: We reviewed 67 HT patients (median age 58.8 yrs). For clinical rejection versus no‐rejection groups, the median (25th, 75th percentile) time to therapeutic tacrolimus levels was 9.5 (8, 12.3) days versus 9.0 (7, 13) days (p=0.623). The median time‐in‐therapeutic tacrolimus range was 34.1% (23.2, 42.2) versus 36.2% (19.9, 51.2), respectively (p=0.512). Similarly, we observed no significant differences in time to and time‐in‐therapeutic tacrolimus range in patients who developed grade 1R/1B (p=0.650 and p=0.725) or grade 2R or higher histology (p=0.632 and p=0.933). Conclusions: Our small single‐center analysis suggests that neither time to nor time in therapeutic tacrolimus range predicted acute rejection within 30 days of HT. [ABSTRACT FROM AUTHOR]

Background: Arginine vasopressin (AVP) is a naturally occurring peptide with diverse effects mediated through selective V1 and V2 receptors. About 10% of patients undergoing cardiopulmonary bypass develop postoperative vasodilatory shock requiring high-dose catecholamines. We sought to examine the role of AVP therapy in cardiac surgery.Methods: A search of Medline was conducted through September 2018 using key words and medical subject headings (MeSH) relating to AVP, copeptin, and cardiac surgery. A systematic review was performed on articles as they pertained to AVP for use as a vasopressor after cardiovascular surgery complicated by vasodilatory shock.Results: A relative or absolute deficiency of Arginine vasopressin is associated with vasodilatory shock after cardiopulmonary bypass. Physiologic replacement with exogenous Arginine vasopressin results in significant increases in systemic vascular resistance and mean arterial pressure with decreased requirements of catecholamines. At doses of <0.1 U/min Arginine vasopressin is safe with very few adverse effects.Conclusion: Post-cardiopulmonary bypass vasodilatory shock is largely due to a relative deficiency of Arginine vasopressin. Exogenous administration of low-dose Arginine vasopressin alone or in combination with traditional catecholamines is a safe and effective way to manage this type of vasodilatory shock. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) and diabetes mellitus (DM) often coexist and have bidirectional association. Advanced HF is associated with worsened glycaemic control. This meta‐analysis investigated the effects of left ventricular assist device (LVAD) implantation on markers of DM control. Methods and results: We performed a systematic search of MEDLINE and Cochrane through October 2017 to identify studies evaluating advanced HF patients who had received an LVAD and reported markers of glycaemic control. The primary outcome was glycosylated haemoglobin A1c (HbA1c), and the secondary outcomes included fasting glucose, daily insulin requirements, and body mass index (BMI). Outcomes were pooled using a Hartung–Knapp random‐effects model producing a mean difference (MD) and 95% confidence interval (CI). Thirteen studies, including 820 participants, were included. HbA1c was 1.23% lower following LVAD implantation (95% CI −1.49 to −0.98). Greater HbA1c reductions were seen with higher pre‐LVAD values. Similarly, fasting plasma glucose (−24.4 mg/dL, 95% CI −33.4 to −15.5), daily insulin requirements (−18.8 units, 95% CI −28.8 to −8.7), and serum creatinine levels (MD −0.20, 95% CI −0.35 to −0.06) were significantly lower than pre‐LVAD levels. We saw no difference in BMI (MD 0.09, 95% CI −1.24 to 1.42). Conclusions: LVAD implantation was associated with significant improvement in HbA1c, fasting plasma glucose, and daily insulin need in advanced HF patients. [ABSTRACT FROM AUTHOR]

The article discusses Survival After Veno-Arterial Extracorporeal membrane oxygenation (ECMO). Topics discussed include association between Veno-Arterial ECMO (SAVE) and Respiratory ECMO Survival Prediction (RESP) scores and survival; survival to discharge rates; and patients initiated on ECMO through a mobile program which have improved short-term survival compared with those initiated in-house.

Cardiac arrest in patients on mechanical support is a new phenomenon brought about by the increased use of this therapy in patients with end-stage heart failure. This American Heart Association scientific statement highlights the recognition and treatment of cardiovascular collapse or cardiopulmonary arrest in an adult or pediatric patient who has a ventricular assist device or total artificial heart. Specific, expert consensus recommendations are provided for the role of external chest compressions in such patients. [ABSTRACT FROM AUTHOR]

Background: Enlargement of the left atrium is a marker of mortality in the general population. Left atrial volume index (LAVI) has long been proposed as a measure of prognosis in patients with heart failure (HF). The aim of this meta-analysis was to assess the utility of using baseline LAVI as an independent predictor of all-cause mortality in patients with HF. Methods: A search of Medline and Embase bibliographic databases was performed to identify studies meeting the following inclusion criteria: 1) studies evaluating a cohort of patients with HF (both reduced and preserved ejection fraction); 2) studies conduct-ing multivariate analysis or patient matching to determine the relationship between baseline LAVI measured by echocardiography and all-cause mortality; and 3) studies reporting data on the relationship between baseline LAVI (per difference in mL/m²) and all-cause mortality. Adjusted hazard ratios depicting the association between baseline LAVI and all-cause mortality were pooled using traditional random-effects meta-analysis. Results: 1,188 publications were reviewed from which four studies were included in the present meta-analysis. We found each 10 mL/m² increase in baseline LAVI was associated with a 22% increased adjusted hazard of all-cause mortality (95% confidence interval, 13% to 31%, I² = 14%). Conclusion: Baseline LAVI is an important independent predictor of all-cause mortality in patients with heart failure and should be reported routinely in these patients undergoing echocardiography. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a novel, service-centric, medical emergency team (MET) model can impact cardiac arrest (CA) rates. Methods: A retrospective pre- vs. postintervention analysis was performed on patients ≥18 years who had a CA between 2007 and 2012. A service centric MET model was initially implemented on the inpatient cardiology service and expanded hospital wide during 2008-2009, maturing to 10 teams in 2010. Service centric is defined as a medical or surgical service-specific MET team based on the location of the patient. Results: The rate of CA (per 1,000 hospital days) in the year 2007 prior to the initiation of MET was compared to rates during program maturation (2008/2009) and after full maturation to 10 teams (2010-2012). A total of 1,140,233 hospital-care days were analyzed between 2007 and2012, with 745 CAs recorded (0.65 events per 1,000 hospital days). The overall CA rate was higher prior to MET initiation (0.84 in 2007) compared to postinitiation (0.59 in 2008/09) and maturation to 10 teams (0.64 in 2010-12) (P<0.003 for both pre- vs postcomparisons). No differences in CA rates were detected between either post-MET initiation time frames (P=0.342). Similar trends in CA rates were observed in the intensive care unit (ICU) (3.96 vs 2.14 vs 2.68 per 1,000 hospital daysin2007,2008/2009,and2010-2012respectively, with P<0.001 for both pre- vs postcomparisons). Conclusions: A service-centric MET program was associated with a reduction in the rate of CAs both hospital wide and in the ICU. These observations maybe explained by the earlier intervention in care of unstable patients by an expanded group of caregivers. [ABSTRACT FROM AUTHOR]