Inhaled Epoprostenol Compared With Nitric Oxide for Right Ventricular Support After Major Cardiac Surgery.

BACKGROUND: Right ventricular failure (RVF) is a leading driver of morbidity and death after major cardiac surgery for advanced heart failure, including orthotopic heart transplantation and left ventricular assist device implantation. Inhaled pulmonary-selective vasodilators, such as inhaled epoprostenol (iEPO) and nitric oxide (iNO), are essential therapeutics for the prevention and medical management of postoperative RVF. However, there is limited evidence from clinical trials to guide agent selection despite the significant cost considerations of iNO therapy. METHODS: In this double-blind trial, participants were stratified by assigned surgery and key preoperative prognostic features, then randomized to continuously receive either iEPO or iNO beginning at the time of separation from cardiopulmonary bypass with the continuation of treatment into the intensive care unit stay. The primary outcome was the composite RVF rate after both operations, defined after transplantation by the initiation of mechanical circulatory support for isolated RVF, and defined after left ventricular assist device implantation by moderate or severe right heart failure according to criteria from the Interagency Registry for Mechanically Assisted Circulatory Support. An equivalence margin of 15 percentage points was prespecified for between-group RVF risk difference. Secondary postoperative outcomes were assessed for treatment differences and included: mechanical ventilation duration; hospital and intensive care unit length of stay during the index hospitalization; acute kidney injury development including renal replacement therapy initiation; and death at 30 days, 90 days, and 1 year after surgery. RESULTS: Of 231 randomized participants who met eligibility at the time of surgery, 120 received iEPO, and 111 received iNO. Primary outcome occurred in 30 participants (25.0%) in the iEPO group and 25 participants (22.5%) in the iNO group, for a risk difference of 2.5 percentage points (two one-sided test 90% CI, -6.6% to 11.6%) in support of equivalence. There were no significant between-group differences for any of the measured postoperative secondary outcomes. CONCLUSIONS: Among patients undergoing major cardiac surgery for advanced heart failure, inhaled pulmonary-selective vasodilator treatment using iEPO was associated with similar risks for RVF development and development of other postoperative secondary outcomes compared with treatment using iNO. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03081052.

Heated Humidified Breathing Circuit Rewarming in Hypothermic Patients Post-Cardiopulmonary Bypass-Pilot Study.

OBJECTIVES: Hypothermia on intensive care unit (ICU) admission after cardiac surgery and cardiopulmonary bypass is common. It contributes to postoperative complications including shivering, coagulopathy, increased blood loss and transfusion requirements, morbid cardiac events, metabolic acidosis, increased wound infections, and prolonged hospital length of stay. The current standard of care for rewarming ICU patients is forced air warming blankets. However, high-quality evidence on additional benefit rendered by other warming methods, such as heated humidified breathing circuits (HHBC), is lacking. Therefore, the authors conducted a pilot study to examine whether the addition of HHBC to standard forced air warming blankets in hypothermic patients (≤35°C) admitted to the ICU after cardiac surgery using cardiopulmonary bypass reduced time to normothermia. DESIGN: Prospective study conducted at a single large academic medical center. PARTICIPANTS: The study group was composed of 14 patients who were enrolled prospectively between April 1 and June 14, 2019. The study group was compared with a 2:1 matched retrospective control group. The matched group consisted of 28 patients from a 12-month period from July 1, 2018 June 30, 2019. INTERVENTIONS: Study patients received warming via forced air warming blankets and HHBC and were compared with patients in a control group who received only warming blankets. Time to normothermia, time to extubation, time to normal pH, blood loss, blood transfusions, and coagulation profile laboratory values were compared between the study and control groups. MEASUREMENTS AND MAIN RESULTS: The present study found no statistical difference in time to normothermia, for which the standard-of-care retrospective group achieved normothermia after a median (Q1-Q3) 4.8 (4.0-6.0) hours compared with 4.4 (3.5-5.5) hours in the prospective group receiving HHBC. All secondary outcomes, including time to extubation, time to normal pH, ICU blood product transfusion, chest tube output, and coagulation profile, were similar. CONCLUSIONS: The present pilot study detected a similar time to normothermia, extubation, and normal pH when HHBC were added to standard forced air warming blankets in hypothermic patients (≤35°C) admitted to the ICU after cardiac surgery using cardiopulmonary bypass. A future larger prospective study designed to detect smaller, but clinically meaningful, reductions in the time to key clinical events for patients treated with HHBC is feasible and warranted.

Inhaled Pulmonary Vasodilator Therapy in Adult Lung Transplant: A Randomized Clinical Trial.

Importance: Inhaled nitric oxide (iNO) is commonly administered for selectively inhaled pulmonary vasodilation and prevention of oxidative injury after lung transplant (LT). Inhaled epoprostenol (iEPO) has been introduced worldwide as a cost-saving alternative to iNO without high-grade evidence for this indication. Objective: To investigate whether the use of iEPO will lead to similar rates of severe/grade 3 primary graft dysfunction (PGD-3) after adult LT when compared with use of iNO. Design, Setting, and Participants: This health system-funded, randomized, blinded (to participants, clinicians, data managers, and the statistician), parallel-designed, equivalence clinical trial included 201 adult patients who underwent single or bilateral LT between May 30, 2017, and March 21, 2020. Patients were grouped into 5 strata according to key prognostic clinical features and randomized per stratum to receive either iNO or iEPO at the time of LT via 1:1 treatment allocation. Interventions: Treatment with iNO or iEPO initiated in the operating room before lung allograft reperfusion and administered continously until cessation criteria met in the intensive care unit (ICU). Main Outcomes and Measures: The primary outcome was PGD-3 development at 24, 48, or 72 hours after LT. The primary analysis was for equivalence using a two one-sided test (TOST) procedure (90% CI) with a margin of 19% for between-group PGD-3 risk difference. Secondary outcomes included duration of mechanical ventilation, hospital and ICU lengths of stay, incidence and severity of acute kidney injury, postoperative tracheostomy placement, and in-hospital, 30-day, and 90-day mortality rates. An intention-to-treat analysis was performed for the primary and secondary outcomes, supplemented by per-protocol analysis for the primary outcome. Results: A total of 201 randomized patients met eligibility criteria at the time of LT (129 men [64.2%]). In the intention-to-treat population, 103 patients received iEPO and 98 received iNO. The primary outcome occurred in 46 of 103 patients (44.7%) in the iEPO group and 39 of 98 (39.8%) in the iNO group, leading to a risk difference of 4.9% (TOST 90% CI, -6.4% to 16.2%; P = .02 for equivalence). There were no significant between-group differences for secondary outcomes. Conclusions and Relevance: Among patients undergoing LT, use of iEPO was associated with similar risks for PGD-3 development and other postoperative outcomes compared with the use of iNO. Trial Registration: ClinicalTrials.gov identifier: NCT03081052.

Rapid Ventilator Splitting During COVID-19 Pandemic Using 3D Printed Devices and Numerical Modeling of 200 Million Patient Specific Air Flow Scenarios.

There has been a pressing need for an expansion of the ventilator capacity in response to the recent COVID19 pandemic. To address this need, we present a system to enable rapid and efficacious splitting between two or more patients with varying lung compliances and tidal volume requirements. Reserved for dire situations, ventilator splitting is complex, and has been limited to patients with similar pulmonary compliances and tidal volume requirements. Here, we report a 3D printed ventilator splitter and resistor system (VSRS) that uses interchangeable airflow resistors to deliver optimal tidal volumes to patients with differing respiratory physiologies, thereby expanding the applicability of ventilator splitting to a larger patient pool. We demonstrate the capability of the VSRS using benchtop test lungs and standard-of-care ventilators, which produced data used to validate a complementary, patient-specific airflow computational model. The computational model allows clinicians to rapidly select optimal resistor sizes and predict delivered pressures and tidal volumes on-demand from different patient characteristics and ventilator settings. Due to the inherent need for rapid deployment, all simulations for the wide range of clinically-relevant patient characteristics and ventilator settings were pre-computed and compiled into an easy to use mobile app. As a result, over 200 million individual computational simulations were performed to maximize the number of scenarios for which the VSRS can provide assistance. The VSRS will help address the pressing need for increased ventilator capacity by allowing ventilator splitting to be used with patients with differing pulmonary physiologies and respiratory requirements, which will be particularly useful for developing countries and rural communities with a limited ventilator supply.

Analysis of radial artery catheter placement by respiratory therapists using ultrasound guidance.

BACKGROUND: The use of ultrasound (US) guidance for radial artery cannulation has been shown to improve first attempt success rate, reduce time to successful cannulation, and reduce complications. We sought to determine whether properly trained respiratory therapists (RTs) could utilize US guidance for the placement of radial artery catheters. Primary outcome measurements were successful cannulation and first attempt success rate. Secondary outcomes included the effect of systolic blood pressure, prior attempts, palpable pulse strength, and gender in relation to US-guided radial artery cannulation success rates. METHODS: RTs certified in arterial catheter insertion were trained in radial artery catheterization using US by emergency medicine physicians. Subjects were enrolled based on the need for an arterial catheter placement. The catheters and US devices used were standardized. Data recorded included pulse strength, systolic and diastolic blood pressure, number of attempts, and successful/unsuccessful artery cannulation. All catheterization attempts were performed according to institutional policy and procedure. RESULTS: One hundred twenty-two radial artery catheter insertion attempts were made between December of 2008 and October of 2011, in patients in whom the treating physician requested RT radial artery cannulation. The overall success rate was 86.1%, whereas the first attempt success rate was 63.1%. There was no difference found between the overall mean success rate for weak or absent pulses, age, systolic blood pressure, gender, or prior attempts. CONCLUSION: RTs can effectively utilize US technology to place radial artery catheters. Systolic blood pressure, prior attempts, and gender are not reliable predictors of success for US-guided radial artery cannulation. Training on the use of US should be strongly encouraged for all practitioners who place radial artery catheters.

Noninvasive ventilation in severe acute asthma.

Noninvasive ventilation (NIV) in severe acute asthma is controversial but may benefit this population by preventing intubation. We report on a 35-year-old male asthma patient who presented to our emergency department via emergency medical services. The patient was responsive, diaphoretic, and breathing at 35 breaths/min on 100% oxygen with bag-mask assistance, with S(pO2) 88%, heart rate 110-120 beats/min, blood pressure 220/110 mm Hg, and temperature 35.8 °C. NIV at 12/5 cm H2O and FIO2 0.40 was applied, and albuterol at 40 mg/h was initiated. Admission arterial blood gas revealed a pH of 6.95, P(aCO2) 126 mm Hg, and P(aO2) 316 mm Hg. After 90 min of therapy, P(aCO2) was 63 mm Hg. Improvement continued, and NIV was stopped 4 h following presentation. NIV tolerance was supported with low doses of lorazepam. The patient was transferred to the ICU, moved to general care the next morning, and discharged 3 days later. We attribute our success to close monitoring in a critical care setting and the titration of lorazepam.