Perioperative Risk Factors of Acute Kidney Injury After Heart Transplantation and One-Year Clinical Outcomes: A Retrospective Cohort Study.

OBJECTIVES: This study aimed to identify perioperative risk factors of acute kidney injury after heart transplantation and to evaluate 1-year clinical outcomes. DESIGN: A retrospective single-center cohort study. SETTING: At a university hospital. PARTICIPANTS: All patients who underwent heart transplantation from January 2015 to December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors recorded acute kidney injury after heart transplantation. One-year mortality and renal function also were recorded. Risk factors of acute kidney injury were evaluated using a multivariate logistic regression model. Long-term survival was compared between patients developing acute kidney injury and those who did not, using a log-rank test. Among 209 patients included in this study, 134 patients (64% [95% CI (58; 71)]) developed posttransplantation acute kidney injury. Factors independently associated with acute kidney injury were high body mass index (odds ratio [OR]: 1.18 [1.02-1.38] per kg/m2; p = 0.030), prolonged duration of cold ischemic period (OR: 1.11 [1.01-1.24] per 10 minutes; p = 0.039), and high dose of intraoperative dobutamine support (OR: 1.24 [1.06-1.46] per µg/kg/min; p = 0.008). At 1 year, patients who developed postoperative acute kidney injury had higher mortality rates (20% v 8%, p = 0.015). Among 172 survivors at 1 year, 82 survivors (48%) had worsened their renal function compared with preheart transplantation. CONCLUSIONS: This study highlighted the high incidence of acute kidney injury after heart transplantation and its impact on patient outcomes. Risk factors such as body mass index, prolonged cold ischemic period duration, and level of inotropic support with dobutamine were identified, providing insights for preventive strategies.

Heterogeneity in defining multiple trauma: a systematic review of randomized controlled trials.

INTRODUCTION: While numerous randomized controlled trials (RCTs) have been conducted in the field of trauma, a substantial portion of them are yielding negative results. One potential contributing factor to this trend could be the lack of agreement regarding the chosen definitions across different trials. The primary objective was to identify the terminology and definitions utilized for the characterization of multiple trauma patients within randomized controlled trials (RCTs). METHODS: A systematic review of the literature was performed in MEDLINE, EMBASE and clinicaltrials.gov between January 1, 2002, and July 31, 2022. RCTs or RTCs protocols were eligible if they included multiple trauma patients. The terms employed to characterize patient populations were identified, and the corresponding definitions for these terms were extracted. The subsequent impact on the population recruited was then documented to expose clinical heterogeneity. RESULTS: Fifty RCTs were included, and 12 different terms identified. Among these terms, the most frequently used were "multiple trauma" (n = 21, 42%), "severe trauma" (n = 8, 16%), "major trauma" (n = 4, 8%), and trauma with hemorrhagic shock" (n = 4, 8%). Only 62% of RCTs (n = 31) provided a definition for the terms used, resulting a total of 21 different definitions. These definitions primarily relied on the injury severity score (ISS) (n = 15, 30%), displaying an important underlying heterogeneity. The choice of the terms had an impact on the study population, affecting both the ISS and in-hospital mortality. Eleven protocols were included, featuring five different terms, with "severe trauma" being the most frequent, occurring six times (55%). CONCLUSION: This systematic review uncovers an important heterogeneity both in the terms and in the definitions employed to recruit trauma patients within RCTs. These findings underscore the imperative of promoting the use of a unique and consistent definition.

Levosimendan in patients undergoing extracorporeal membrane oxygenation after cardiac surgery: an emulated target trial using observational data.

BACKGROUND: Retrospective cohorts have suggested that levosimendan may facilitate the weaning of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). We therefore studied this clinical question by emulating a randomized trial with observational data. METHODS: All patients with refractory postcardiotomy cardiogenic shock and assisted with VA-ECMO, admitted to a surgical intensive care unit at La Pitié-Salpêtrière Hospital between 2016 and 2019, were eligible. To avoid immortal-time bias, we emulated a target trial sequentially comparing levosimendan administration versus no levosimendan administration in patients treated with VA-ECMO. The primary outcome was time to successful ECMO weaning. The secondary outcomes were 30-day and 1-year mortality. We performed a multivariable analysis to adjust for confounding at baseline. RESULTS: Two hundred and thirty-nine patients were included in the study allowing building a nested trials cohort of 1434 copies of patients. No association of levosimendan treatment and VA-ECMO weaning was found (HR = 0.91, [0.57; 1.45], p = 0.659 in multivariable analysis), or 30-day mortality (OR = 1.03, [0.52; 2.03], p = 0.940) and 1-year mortality (OR = 1.00, [0.53; 1.89], p = 0.999). CONCLUSIONS: Using the emulated target trial framework, this study did not find any association of levosimendan treatment and ECMO weaning success after postcardiotomy cardiogenic shock. However, the population of interest remains heterogeneous and subgroups might benefit from levosimendan.

Weaning-Related Shock in Patients With ECMO: Incidence, Mortality, and Predisposing Factors.

OBJECTIVE: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) commonly is used to manage refractory cardiogenic shock after cardiac surgery, with 31% to 76% of patients successfully weaned off their ECMO. However, it is associated with high mortality rates, and 20% to 65% of weaned patients do not survive to hospital discharge. This study aimed to assess the incidence of ECMO weaning-related shock, the risk factors, and prognosis in the intensive care unit (ICU). DESIGN: Retrospective observational cohort study. SETTING: Surgical ICU of Cardiology Institute of Pitié-Salpêtrière University Hospital (Paris-France). PARTICIPANTS: Patients who were assisted with a peripheral VA-ECMO from January 2015 to December 2017 were included. Patients with venovenous, central, or right ECMO were excluded. MEASUREMENTS: The authors collected data on patients' characteristics, during and after surgery. The indications for VA-ECMO implantation were ventricular dysfunction, primary graft dysfunction, and refractory cardiac arrest. Weaning-related shock was defined as the need to introduce or increase the dose of catecholamine at ECMO explantation or in the following week. RESULTS: After weaning off VA-ECMO, 56 of 146 patients (38.4%) presented weaning-related shock: 55% were septic shocks, 12.5 % were caused by right ventricle failure, and 7.1% by hemorrhage. ICU mortality was 42% versus 8% in patients who did not present shock. Multivariate analysis showed that patients with pulmonary hypertension and those with norepinephrine before weaning were more likely to develop shock. CONCLUSION: ECMO weaning-related shock is frequent in patients with refractory cardiogenic shock after cardiac surgery. This is most commonly caused by sepsis and causes higher mortality rates, calling for further evaluation.

Pulmonary embolism in COVID-19 patients: a French multicentre cohort study.

AIMS: While pulmonary embolism (PE) appears to be a major issue in COVID-19, data remain sparse. We aimed to describe the risk factors and baseline characteristics of patients with PE in a cohort of COVID-19 patients. METHODS AND RESULTS: In a retrospective multicentre observational study, we included consecutive patients hospitalized for COVID-19. Patients without computed tomography pulmonary angiography (CTPA)-proven PE diagnosis and those who were directly admitted to an intensive care unit (ICU) were excluded. Among 1240 patients (58.1% men, mean age 64 ± 17 years), 103 (8.3%) patients had PE confirmed by CTPA. The ICU transfer and mechanical ventilation were significantly higher in the PE group (for both P < 0.001). In an univariable analysis, traditional venous thrombo-embolic risk factors were not associated with PE (P > 0.05), while patients under therapeutic dose anticoagulation before hospitalization or prophylactic dose anticoagulation introduced during hospitalization had lower PE occurrence [odds ratio (OR) 0.40, 95% confidence interval (CI) 0.14-0.91, P = 0.04; and OR 0.11, 95% CI 0.06-0.18, P < 0.001, respectively]. In a multivariable analysis, the following variables, also statistically significant in univariable analysis, were associated with PE: male gender (OR 1.03, 95% CI 1.003-1.069, P = 0.04), anticoagulation with a prophylactic dose (OR 0.83, 95% CI 0.79-0.85, P < 0.001) or a therapeutic dose (OR 0.87, 95% CI 0.82-0.92, P < 0.001), C-reactive protein (OR 1.03, 95% CI 1.01-1.04, P = 0.001), and time from symptom onset to hospitalization (OR 1.02, 95% CI 1.006-1.038, P = 0.002). CONCLUSION: PE risk factors in the COVID-19 context do not include traditional thrombo-embolic risk factors but rather independent clinical and biological findings at admission, including a major contribution to inflammation.

Risk Factors for Developing Severe Acute Kidney Injury in Adult Patients With Refractory Postcardiotomy Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: Postcardiotomy cardiogenic shock occurs in 2-6% of patients undergoing cardiac surgery, and 1% of cardiac surgery patients will require mechanical circulatory support using venoarterial extracorporeal membrane oxygenation. Acute kidney injury is a frequent complication in this population and negatively impacts the survival. We aimed to determine whether the timing of extracorporeal membrane oxygenation implantation influences the renal prognosis of these patients. DESIGN: Retrospective observational cohort study between January 2013 and December 2016. SETTING: An 18-bed surgical ICU in a university hospital. PATIENTS: A total of 4,796 consecutive adult patients who underwent cardiac surgery were included in the study, and 347 (7.2%) were assisted with venoarterial extracorporeal membrane oxygenation for refractory postcardiotomy cardiogenic shock. The patients who died during the first 48 hours after venoarterial extracorporeal membrane oxygenation implantation were excluded. The complete-case analysis included 257 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence, within 10 days following the venoarterial extracorporeal membrane oxygenation implantation, of a stage 3 acute kidney injury defined by the Kidney Disease: Improving Global Outcomes group. One hundred sixty-nine patients (65.7%) presented with a Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury; 14 patients (5.4%) died before the end of the follow-up period, without developing the primary outcome. Ninety-two percent of patients with Kidney Disease: Improving Global Outcomes 3 acute kidney injury received renal replacement therapy, for a median duration of 7 days (3-16 d). Late implantation of venoarterial extracorporeal membrane oxygenation was independently associated with an increased risk of Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury (odds ratio, 2.81 [95% CI, 1.31-6.07]; p = 0.008). The other factors associated with Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury were preoperative left ventricular ejection fraction (odds ratio, 1.03 [95% CI, 1.01-1.05]; p = 0.007), intraoperative plasma transfusion (odds ratio, 1.13 [95% CI, 1.02-1.26]; p = 0.022), increased bilirubinemia level (odds ratio, 1.013 [95% CI, 1.001-1.026]; p = 0.032), and increased creatinine levels (odds ratio, 1.012 [95% CI, 1.006-1.018]; p < 0.001) on the day of implantation. CONCLUSIONS: Significant kidney dysfunction is particularly frequent in patients with refractory postcardiotomy cardiogenic shock assisted with venoarterial extracorporeal membrane oxygenation. Early implantation of extracorporeal membrane oxygenation may help prevent acute kidney injury.

Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. METHODS: The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7. RESULTS: Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7. CONCLUSION: In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.

Neutropenic Enterocolitis in Critically Ill Patients: Spectrum of the Disease and Risk of Invasive Fungal Disease.

OBJECTIVES: Neutropenic enterocolitis occurs in about 5.3% of patients hospitalized for hematologic malignancies receiving chemotherapy. Data from critically ill patients with neutropenic enterocolitis are scarce. Our objectives were to describe the population of patients with neutropenic enterocolitis admitted to an ICU and to investigate the risk factors of invasive fungal disease. DESIGN: A multicentric retrospective cohort study between January 2010 and August 2017. SETTING: Six French ICUs members of the Groupe de Recherche Respiratoire en Onco-Hématologie research network. PATIENTS: Adult neutropenic patients hospitalized in the ICU with a diagnosis of enteritis and/or colitis. Patients with differential diagnosis (Clostridium difficile colitis, viral colitis, inflammatory enterocolitis, mesenteric ischemia, radiation-induced gastrointestinal toxicity, and Graft vs Host Disease) were excluded. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We included 134 patients (median Sequential Organ Failure Assessment 10 [8-12]), with 38.8% hospital mortality and 32.1% ICU mortality rates. The main underlying malignancies were acute leukemia (n = 65, 48.5%), lymphoma (n = 49, 36.6%), solid tumor (n = 14, 10.4%), and myeloma (n = 4, 3.0%). Patients were neutropenic during a median of 14 days (9-22 d). Infection was documented in 81 patients (60.4%), including an isolated bacterial infection in 64 patients (47.8%), an isolated fungal infection in nine patients (6.7%), and a coinfection with both pathogens in eight patients (5.0%). Radiologically assessed enteritis (odds ratio, 2.60; 95% CI, 1.32-7.56; p = 0.015) and HIV infection (odds ratio, 2.03; 95% CI, 1.21-3.31; p = 0.016) were independently associated with invasive fungal disease. CONCLUSIONS: The rate of invasive fungal disease reaches 20% in patients with neutropenic enterocolitis when enteritis is considered. To avoid treatment delay, antifungal therapy might be systematically discussed in ICU patients admitted for neutropenic enterocolitis with radiologically assessed enteritis.

Pupillary Reflex for Evaluation of Thoracic Paravertebral Block: A Prospective Observational Feasibility Study.

BACKGROUND: Although thoracic paravertebral block (TPVB) is recommended in major breast surgery, there is no gold standard to assess the success of TPVB. Pupillary dilation reflex (PDR) is the variation of the pupillary diameter after a noxious stimulus. The objective was to evaluate the feasibility of recording the PDR to assess analgesia in an anesthetized thoracic dermatome after TPVB. METHODS: This prospective, observational, single-center study included 32 patients requiring breast surgery under general anesthesia and TPVB. TPVB was performed before surgery under ultrasound guidance with 20 mL of 0.75% ropivacaine. At the end of the surgery, remifentanil was stopped and the PDR was recorded after a 5-second tetanic stimulation (60 mA, 100 Hz) applied to the anterior chest wall. The PDR was defined as the maximal increase in pupil diameter after a standardized noxious stimulus, expressed as a percentage of the initial pupil diameter. The PDR was recorded twice in the same eye for each patient after a stimulus on both the TPVB and the control sides. Postoperative pain scores were recorded in a postanesthesia care unit. The primary outcome was the difference between the PDR on the TPVB and the control sides. RESULTS: The median (interquartile range) PDR was 9% (4%-13%) on the TPVB side and 41% (27%-66%) on the control side. There was a significant difference in the PDR between the TPVB and the control sides with a Hodges-Lehmann estimate of absolute difference of 37% points (95% confidence interval, 25-52, P < .001). Median postoperative pain scores (interquartile range) in the postanesthesia care unit were 1 (0-3) at rest and 1 (0-3) during mobilization, respectively. There was a linear correlation between maximal postoperative pain scores and the PDR on the TPVB side with a Pearson's correlation coefficient r = 0.40 (95% confidence interval, 0.06-0.66, P = .02). No correlation was found between the number of blocked dermatomes and maximal postoperative pain scores (P = .06) or between the number of blocked dermatomes and the PDR on the TPVB side (P = .15). CONCLUSIONS: This proof-of-concept trial suggests that the effect of TPVB could be monitored by measuring the PDR after anterior chest wall stimulation in the dermatome of interest.