Role of hemolysis on pulmonary arterial compliance and right ventricular systolic function after cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with intravascular hemolysis which depletes endogenous nitric oxide (NO). The impact of hemolysis on pulmonary arterial compliance (PAC) and right ventricular systolic function has not been explored yet. We hypothesized that decreased NO availability is associated with worse PAC and right ventricular systolic function after CPB. METHODS: This is a secondary analysis of an observational cohort study in patients undergoing cardiac surgery with CPB at Massachusetts General Hospital, USA (2014-2015). We assessed PAC (stroke volume/pulmonary artery pulse pressure ratio), and right ventricular function index (RVFI) (systolic pulmonary arterial pressure/cardiac output), as well as NO consumption at 15 min, 4 h and 12 h after CPB. Patients were stratified by CPB duration. Further, we assessed the association between changes in NO consumption with PAC and RVFI between 15min and 4 h after CPB. RESULTS: PAC was lowest at 15min after CPB and improved over time (n = 50). RVFI was highest -worse right ventricular function- at CPB end and gradually decreased. Changes in hemolysis, PAC and RVFI differed over time by CPB duration. PAC inversely correlated with total pulmonary resistance (TPR). TPR and PAC positively and negatively correlated with RVFI, respectively. NO consumption between 15min and 4 h after CPB correlated with changes in PAC (-0.28 ml/mmHg, 95%CI -0.49 to -0.01, p = 0.012) and RVFI (0.14 mmHg*L-1*min, 95%CI 0.10 to 0.18, p < 0.001) after multivariable adjustments. CONCLUSION: PAC and RVFI are worse at CPB end and improve over time. Depletion of endogenous NO may contribute to explain changes in PAC and RVFI after CPB.

High-Dose Inhaled Nitric Oxide in Acute Hypoxemic Respiratory Failure Due to COVID-19: A Multicenter Phase II Trial.

Rationale: The effects of high-dose inhaled nitric oxide on hypoxemia in coronavirus disease (COVID-19) acute respiratory failure are unknown. Objectives: The primary outcome was the change in arterial oxygenation (PaO2/FiO2) at 48 hours. The secondary outcomes included: time to reach a PaO2/FiO2.300mmHg for at least 24 hours, the proportion of participants with a PaO2/FiO2.300mmHg at 28 days, and survival at 28 and at 90 days. Methods: Mechanically ventilated adults with COVID-19 pneumonia were enrolled in a phase II, multicenter, single-blind, randomized controlled parallel-arm trial. Participants in the intervention arm received inhaled nitric oxide at 80 ppm for 48 hours, compared with the control group receiving usual care (without placebo). Measurements and Main Results: A total of 193 participants were included in the modified intention-to-treat analysis. The mean change in PaO2/FiO2 ratio at 48 hours was 28.3mmHg in the intervention group and 21.4mmHg in the control group (mean difference, 39.1mmHg; 95% credible interval [CrI], 18.1 to 60.3). The mean time to reach a PaO2/FiO2.300mmHg in the interventional group was 8.7 days, compared with 8.4 days for the control group (mean difference, 0.44; 95% CrI, 23.63 to 4.53). At 28 days, the proportion of participants attaining a PaO2/FiO2.300mmHg was 27.7% in the inhaled nitric oxide group and 17.2% in the control subjects (risk ratio, 2.03; 95% CrI, 1.11 to 3.86). Duration of ventilation and mortality at 28 and 90 days did not differ. No serious adverse events were reported. Conclusions: The use of high-dose inhaled nitric oxide resulted in an improvement of PaO2/FiO2 at 48 hours compared with usual care in adults with acute hypoxemic respiratory failure due to COVID-19.

Obesity and Extracorporeal Membrane Oxygenation (ECMO): Analysis of Outcomes.

Traditionally, patients with obesity have been deemed ineligible for extracorporeal life support (ELS) therapies such as extracorporeal membrane oxygenation (ECMO), given the association of obesity with chronic health conditions that contribute to increased morbidity and mortality. Nevertheless, a growing body of literature suggests the feasibility, efficacy, and safety of ECMO in the obese population. This review provides an in-depth analysis of the current literature assessing the effects of obesity on outcomes among patients supported with ECMO (venovenous [VV] ECMO in noncoronavirus disease 2019 and coronavirus disease 2019 acute respiratory distress syndrome, venoarterial [VA] ECMO, and combined VV and VA ECMO), offer a possible explanation of the current findings on the basis of the obesity paradox phenomenon, provides a framework for future studies addressing the use of ELS therapies in the obese patient population, and provides guidance from the literature for many of the challenges related to initiating, maintaining, and weaning ELS therapy in patients with obesity.

Society of Critical Care Medicine Clinical Practice Guidelines for Rapid Sequence Intubation in the Critically Ill Adult Patient.

RATIONALE: Controversies and practice variations exist related to the pharmacologic and nonpharmacologic management of the airway during rapid sequence intubation (RSI). OBJECTIVES: To develop evidence-based recommendations on pharmacologic and nonpharmacologic topics related to RSI. DESIGN: A guideline panel of 20 Society of Critical Care Medicine members with experience with RSI and emergency airway management met virtually at least monthly from the panel's inception in 2018 through 2020 and face-to-face at the 2020 Critical Care Congress. The guideline panel included pharmacists, physicians, a nurse practitioner, and a respiratory therapist with experience in emergency medicine, critical care medicine, anesthesiology, and prehospital medicine; consultation with a methodologist and librarian was available. A formal conflict of interest policy was followed and enforced throughout the guidelines-development process. METHODS: Panelists created Population, Intervention, Comparison, and Outcome (PICO) questions and voted to select the most clinically relevant questions for inclusion in the guideline. Each question was assigned to a pair of panelists, who refined the PICO wording and reviewed the best available evidence using predetermined search terms. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used throughout and recommendations of "strong" or "conditional" were made for each PICO question based on quality of evidence and panel consensus. Recommendations were provided when evidence was actionable; suggestions, when evidence was equivocal; and best practice statements, when the benefits of the intervention outweighed the risks, but direct evidence to support the intervention did not exist. RESULTS: From the original 35 proposed PICO questions, 10 were selected. The RSI guideline panel issued one recommendation (strong, low-quality evidence), seven suggestions (all conditional recommendations with moderate-, low-, or very low-quality evidence), and two best practice statements. The panel made two suggestions for a single PICO question and did not make any suggestions for one PICO question due to lack of evidence. CONCLUSIONS: Using GRADE principles, the interdisciplinary panel found substantial agreement with respect to the evidence supporting recommendations for RSI. The panel also identified literature gaps that might be addressed by future research.

Molecular mechanisms of muscular and non-muscular actions of neuromuscular blocking agents in critical illness: a narrative review.

Despite frequent use of neuromuscular blocking agents in critical illness, changes in neuromuscular transmission with critical illness are not well appreciated. Recent studies have provided greater insights into the molecular mechanisms for beneficial muscular effects and non-muscular anti-inflammatory properties of neuromuscular blocking agents. This narrative review summarises the normal structure and function of the neuromuscular junction and its transformation to a 'denervation-like' state in critical illness, the underlying cause of aberrant neuromuscular blocking agent pharmacology. We also address the important favourable and adverse consequences and molecular bases for these consequences during neuromuscular blocking agent use in critical illness. This review, therefore, provides an enhanced understanding of clinical therapeutic effects and novel pathways for the salutary and aberrant effects of neuromuscular blocking agents when used during acquired pathologic states of critical illness.

Should Obesity Be an Exclusion Criterion for Extracorporeal Membrane Oxygenation Support? A Scoping Review.

Obesity is often considered a contraindication to extracorporeal membrane oxygenation (ECMO) candidacy due to technical challenges with vascular access, higher cardiac output requirements, and known associations between obesity and overall increased morbidity and mortality due to chronic health conditions. However, a growing body of literature suggests that ECMO may be as safe and efficacious in both obese and nonobese patients. This scoping review provides a synthesis of the available literature on the outcomes of obese patients supported with (1) venovenous (VV)-ECMO in acute respiratory distress syndrome (ARDS) not due to coronavirus disease 2019 (COVID-19), (2) VV-ECMO in ARDS due to COVID-19, (3) venoarterial (VA)-ECMO for all indications, and (4) studies combining data of patients supported with VA- and VV-ECMO. A librarian-assisted search was performed using 4 primary electronic medical databases (PubMed, Web of Science, Excerpta Medica database [Embase], and Cochrane Library) from January 2003 to March 2023. Articles that reported outcomes of obese patients requiring ECMO support were included. Two reviewers independently screened titles, abstracts, and full text of articles to determine eligibility. Data extraction was performed using customized fields established a priori within a systematic review software system. A total of 354 publications were imported for screening on titles and abstracts, and 30 studies were selected for full-text review. A total of 26 publications met the inclusion criteria: 7 on VV-ECMO support in non-COVID-19 ARDS patients, 6 on ECMO in COVID-19 ARDS patients, 8 in patients supported with VA-ECMO, and 5 combining both VA- and VV-ECMO data. Although the included studies are limited to retrospective analyses and display a heterogeneity in definitions of obesity and comparison groups, the currently available literature suggests that outcomes and complications of ECMO therapy are equivalent in obese patients as compared to nonobese patients. Hence, obesity as measured by body mass index alone should not be considered an exclusion criterion in the decision to initiate ECMO.

High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in Acute Respiratory Distress Syndrome with Class III Obesity. A Clinical Trial.

Rationale: Obesity is characterized by elevated pleural pressure (Ppl) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS).Objectives: To determine the effects of a lung recruitment maneuver (LRM) in the presence of elevated Ppl on hemodynamics, left and right ventricular pressure, and pulmonary vascular resistance. We hypothesized that elevated Ppl protects the cardiovascular system against high airway pressure and prevents lung overdistension.Methods: First, an interventional crossover trial in adult subjects with ARDS and a body mass index ≥ 35 kg/m2 (n = 21) was performed to explore the hemodynamic consequences of the LRM. Second, cardiovascular function was studied during low and high positive end-expiratory pressure (PEEP) in a model of swine with ARDS and high Ppl (n = 9) versus healthy swine with normal Ppl (n = 6).Measurements and Main Results: Subjects with ARDS and obesity (body mass index = 57 ± 12 kg/m2) after LRM required an increase in PEEP of 8 (95% confidence interval [95% CI], 7-10) cm H2O above traditional ARDS Network settings to improve lung function, oxygenation and [Formula: see text]/[Formula: see text] matching, without impairment of hemodynamics or right heart function. ARDS swine with high Ppl demonstrated unchanged transmural left ventricular pressure and systemic blood pressure after the LRM protocol. Pulmonary arterial hypertension decreased (8 [95% CI, 13-4] mm Hg), as did vascular resistance (1.5 [95% CI, 2.2-0.9] Wood units) and transmural right ventricular pressure (10 [95% CI, 15-6] mm Hg) during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized the [Formula: see text]/[Formula: see text] ratio.Conclusions: High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. In addition, patients with ARDS and class III obesity hemodynamically tolerate LRM with high airway pressure.Clinical trial registered with www.clinicaltrials.gov (NCT02503241).

Right Ventricular Strain Is Common in Intubated COVID-19 Patients and Does Not Reflect Severity of Respiratory Illness.

BACKGROUND: Right ventricular (RV) dysfunction is common and associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19). In non-COVID-19 acute respiratory distress syndrome, RV dysfunction develops due to pulmonary hypoxic vasoconstriction, inflammation, and alveolar overdistension or atelectasis. Although similar pathogenic mechanisms may induce RV dysfunction in COVID-19, other COVID-19-specific pathology, such as pulmonary endothelialitis, thrombosis, or myocarditis, may also affect RV function. We quantified RV dysfunction by echocardiographic strain analysis and investigated its correlation with disease severity, ventilatory parameters, biomarkers, and imaging findings in critically ill COVID-19 patients. METHODS: We determined RV free wall longitudinal strain (FWLS) in 32 patients receiving mechanical ventilation for COVID-19-associated respiratory failure. Demographics, comorbid conditions, ventilatory parameters, medications, and laboratory findings were extracted from the medical record. Chest imaging was assessed to determine the severity of lung disease and the presence of pulmonary embolism. RESULTS: Abnormal FWLS was present in 66% of mechanically ventilated COVID-19 patients and was associated with higher lung compliance (39.6 vs 29.4 mL/cmH2O, P = 0.016), lower airway plateau pressures (21 vs 24 cmH2O, P = 0.043), lower tidal volume ventilation (5.74 vs 6.17 cc/kg, P = 0.031), and reduced left ventricular function. FWLS correlated negatively with age (r = -0.414, P = 0.018) and with serum troponin (r = 0.402, P = 0.034). Patients with abnormal RV strain did not exhibit decreased oxygenation or increased disease severity based on inflammatory markers, vasopressor requirements, or chest imaging findings. CONCLUSIONS: RV dysfunction is common among critically ill COVID-19 patients and is not related to abnormal lung mechanics or ventilatory pressures. Instead, patients with abnormal FWLS had more favorable lung compliance. RV dysfunction may be secondary to diffuse intravascular micro- and macro-thrombosis or direct myocardial damage. TRIAL REGISTRATION: National Institutes of Health #NCT04306393. Registered 10 March 2020, https://clinicaltrials.gov/ct2/show/NCT04306393.

Free Hemoglobin Ratio as a Novel Biomarker of Acute Kidney Injury After On-Pump Cardiac Surgery: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with a high risk of postoperative acute kidney injury (AKI). Due to limitations of current diagnostic strategies, we sought to determine whether free hemoglobin (fHb) ratio (ie, levels of fHb at the end of CPB divided by baseline fHb) could predict AKI after on-pump cardiac surgery. METHODS: This is a secondary analysis of a randomized controlled trial comparing the effect of nitric oxide (intervention) versus nitrogen (control) on AKI after cardiac surgery (NCT01802619). A total of 110 adult patients in the control arm were included. First, we determined whether fHb ratio was associated with AKI via multivariable analysis. Second, we verified whether fHb ratio could predict AKI and incorporation of fHb ratio could improve predictive performance at an early stage, compared with prediction using urinary biomarkers alone. We conducted restricted cubic spline in logistic regression for model development. We determined the predictive performance, including area under the receiver-operating-characteristics curve (AUC) and calibration (calibration plot and accuracy, ie, number of correct predictions divided by total number of predictions). We also used AUC test, likelihood ratio test, and net reclassification index (NRI) to compare the predictive performance between competing models (ie, fHb ratio versus neutrophil gelatinase-associated lipocalin [NGAL], N-acetyl-ß-d-glucosaminidase [NAG], and kidney injury molecule-1 [KIM-1], respectively, and incorporation of fHb ratio with NGAL, NAG, and KIM-1 versus urinary biomarkers alone), if applicable. RESULTS: Data stratified by median fHb ratio showed that subjects with an fHb ratio >2.23 presented higher incidence of AKI (80.0% vs 49.1%; P = .001), more need of renal replacement therapy (10.9% vs 0%; P = .036), and higher in-hospital mortality (10.9% vs 0%; P = .036) than subjects with an fHb ratio ≤2.23. fHb ratio was associated with AKI after adjustment for preestablished factors. fHb ratio outperformed urinary biomarkers with the highest AUC of 0.704 (95% confidence interval [CI], 0.592-0.804) and accuracy of 0.714 (95% CI, 0.579-0.804). Incorporation of fHb ratio achieved better discrimination (AUC test, P = .012), calibration (likelihood ratio test, P < .001; accuracy, 0.740 [95% CI, 0.617-0.832] vs 0.632 [95% CI, 0.477-0.748]), and significant prediction increment (NRI, 0.638; 95% CI, 0.269-1.008; P < .001) at an early stage, compared with prediction using urinary biomarkers alone. CONCLUSIONS: Results from this exploratory, hypothesis-generating retrospective, observational study shows that fHb ratio at the end of CPB might be used as a novel, widely applicable biomarker for AKI. The use of fHb ratio might help for an early detection of AKI, compared with prediction based only on urinary biomarkers.

In-hospital airway management of COVID-19 patients.

Those involved in the airway management of COVID-19 patients are particularly at risk. Here, we describe a practical, stepwise protocol for safe in-hospital airway management in patients with suspected or confirmed COVID-19 infection.

Comparison of published guidelines for management of coagulopathy and thrombosis in critically ill patients with COVID 19: implications for clinical practice and future investigations.

Critically ill patients with COVID-19 are at increased risk for thrombotic complications which has led to an intense debate surrounding their anticoagulation management. In the absence of data from randomized controlled clinical trials, a number of consensus guidelines and recommendations have been published to facilitate clinical decision-making on this issue. However, substantive differences exist between these guidelines which can be difficult for clinicians. This review briefly summarizes the major societal guidelines and compares their similarities and differences. A common theme in all of the recommendations is to take an individualized approach to patient management and a call for prospective randomized clinical trials to address important anticoagulation issues in this population.

A lung rescue team improves survival in obesity with acute respiratory distress syndrome.

BACKGROUND: Limited data exist regarding ventilation in patients with class III obesity [body mass index (BMI) > 40 kg/m2] and acute respiratory distress syndrome (ARDS). The aim of the present study was to determine whether an individualized titration of mechanical ventilation according to cardiopulmonary physiology reduces the mortality in patients with class III obesity and ARDS. METHODS: In this retrospective study, we enrolled adults admitted to the ICU from 2012 to 2017 who had class III obesity and ARDS and received mechanical ventilation for > 48 h. Enrolled patients were divided in two cohorts: one cohort (2012-2014) had ventilator settings determined by the ARDSnet table for lower positive end-expiratory pressure/higher inspiratory fraction of oxygen (standard protocol-based cohort); the other cohort (2015-2017) had ventilator settings determined by an individualized protocol established by a lung rescue team (lung rescue team cohort). The lung rescue team used lung recruitment maneuvers, esophageal manometry, and hemodynamic monitoring. RESULTS: The standard protocol-based cohort included 70 patients (BMI = 49 ± 9 kg/m2), and the lung rescue team cohort included 50 patients (BMI = 54 ± 13 kg/m2). Patients in the standard protocol-based cohort compared to lung rescue team cohort had almost double the risk of dying at 28 days [31% versus 16%, P = 0.012; hazard ratio (HR) 0.32; 95% confidence interval (CI95%) 0.13-0.78] and 3 months (41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16-0.74), and this effect persisted at 6 months and 1 year (incidence of death unchanged 41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16-0.74). CONCLUSION: Individualized titration of mechanical ventilation by a lung rescue team was associated with decreased mortality compared to use of an ARDSnet table.

Application of Lung Ultrasound During the COVID-19 Pandemic: A Narrative Review.

This review highlights the ultrasound findings reported from a number of studies and case reports and discusses the unifying findings from coronavirus disease (COVID-19) patients and from the avian (H7N9) and H1N1 influenza epidemics. We discuss the potential role for portable point-of-care ultrasound (PPOCUS) as a safe and effective bedside option in the initial evaluation, management, and monitoring of disease progression in patients with confirmed or suspected COVID-19 infection.

The Presence of Scarring and Associated Morbidity in the Burn Model System National Database.

INTRODUCTION: Postburn scarring is common, but the risk factors, natural history, and consequences of such scars are still poorly understood. This study aims to describe the frequency of scar-related morbidity for up to 2 years after injury and to analyze the impact of burn scars on long-term functional, psychosocial, and reintegration outcomes. METHODS: Analysis was conducted on data collected between January 2006 and May 2014 from 960 patients (2440 anatomic burn sites) using the Burn Model System (BMS) database. Study population demographics were analyzed and odds ratios for the development of raised or thick scarring were determined. Regression analyses were used to evaluate the impact of hypertrophic scarring (HTS) on psychosocial outcomes, including the Community Integration Questionnaire, Satisfaction with Life Scale, Distress, and the Short Form 12. Symptoms associated with scarring were analyzed at discharge and 6, 12, and 24 months after burn using a set of questions on scarring developed by the BMS. Mixed-effect modeling was used to determine linear change over time and the significance of symptoms. RESULTS: The study population was primarily white (65.0%) and male (71.8%), with a mean (SD) age of 44.0 (15.2) years and mean total body surface area burned of 19.6% (17.9%). The incidence of raised or thick scars increased from 65% to 80% (P < 0.0001) for the 2-year follow-up period. The presence of scarring was not associated with Community Integration Questionnaire, Satisfaction with Life Scale, or Short Form 12 scores. Most patients reported symptoms associated with scarring at 2 years after burn, including dry or fragile skin, scars that restrict range of motion at a joint, issues with hand function, and scar pain and itch. CONCLUSIONS: In this large, longitudinal, multicenter cohort of burn survivors, nearly all patients noted the presence of scarring, and a majority noted additional symptoms and morbidity related to their scars even at 2 years after injury. This study demonstrates a need for the continued support of burn survivors to address scar-related morbidity. Furthermore, future studies examining the impact of novel treatments for scarring should use similar scar problem questionnaires and distress scores.

Evaluation of the Augmented Infant Resuscitator: A Monitoring Device for Neonatal Bag-Valve-Mask Resuscitation.

BACKGROUND: Annually, 6 million newborns require bag-valve-mask resuscitation, and providing live feedback has the potential to improve the quality of resuscitation. The Augmented Infant Resuscitator (AIR), a real-time feedback device, has been designed to identify leaks, obstructions, and inappropriate breath rates during bag-valve-mask resuscitation. However, its function has not been evaluated. METHODS: The resistance of the AIR was measured by attaching it between a ventilator and a ventilator tester. To test the device's reliability in training and clinical-use settings, it was placed in-line between a ventilation bag or ventilator and a neonatal manikin and a clinical lung model simulator. The lung model simulator simulated neonates of 3 sizes (2, 4, and 6 kg). Leaks, obstructions, and respiratory rate alterations were introduced. RESULTS: At a flow of 5 L/min, the pressure drop across the AIR was only 0.38 cm H2O, and the device had almost no effect on ventilator breath parameters. During the manikin trials, it was able to detect all leaks and obstructions, correctly displaying an alarm 100% of the time. During the simulated clinical trials, the AIR performed best on the 6-kg neonatal model, followed by the 4-kg model, and finally the 2-kg model. Over all 3 clinical models, the prototype displayed the correct indicator 73.5% of the time, and when doing so, took 1.6 ± 0.9 seconds. CONCLUSIONS: The AIR is a promising innovation that has the potential to improve neonatal resuscitation. It introduces only marginal resistance and performs well on neonatal manikins, but its firmware should be improved before clinical use.