Neuromuscular Blockade Monitoring in Acute Respiratory Distress Syndrome: Randomized Controlled Trial of Clinical Assessment Alone or With Peripheral Nerve Stimulation.

BACKGROUND: Whether train-of-four (TOF) monitoring is more effective than clinical monitoring to guide neuromuscular blockade (NMB) in patients with acute respiratory distress syndrome (ARDS) is unclear. We compared clinical monitoring alone or with TOF monitoring to guide atracurium dosage adjustment with respect to drug dose and respiratory parameters. METHODS: From 2015 to 2016, we conducted a randomized controlled trial comparing clinical assessments every 2 hours with or without corrugator supercilii TOF monitoring every 4 hours in patients who developed ARDS (Pao2/Fio2 <150 mm Hg) in a cardiothoracic intensive care unit. The primary outcome was the cumulative atracurium dose (mg/kg/h). Secondary outcomes included respiratory parameters during the neuromuscular blockade. RESULTS: A total of 38 patients in the clinical + TOF (C + TOF) group and 39 patients in the clinical (C) group were included in an intention-to-treat (ITT) analysis. The cumulative atracurium dose was higher in the C + TOF group (1.06 [0.75-1.30] vs 0.65 [0.60-0.89] mg/kg/h in the C group; P < .001) compared to C group, as well as the atracurium daily dose (C + TOF - C group mean difference = 0.256 mg/kg/h [95% confidence interval {CI}, 0.099-0.416], P = .026). Driving pressures during neuromuscular blocking agent (NMBA) administration did not differ between groups (P = .653). Intensive care unit (ICU) mortality was 22% in the C group and 27% in the C + TOF group (P = .786). Days on ventilation were 17 (8-26) in the C group and 16 (10-35) in the C + TOF group. CONCLUSIONS: In patients with ARDS, adding TOF to clinical monitoring of neuromuscular blockade did not change ICU mortality or days on mechanical ventilation (MV) but did increase atracurium consumption when compared to clinical assessment alone. TOF monitoring may not be needed in all patients who receive neuromuscular blockade for ARDS.

Ultrasound Assessment of Respiratory Workload With High-Flow Nasal Oxygen Versus Other Noninvasive Methods After Chest Surgery.

OBJECTIVE: To compare the respiratory workload using the diaphragm thickening fraction (DTf) determined by sonography during high-flow nasal oxygen (HFNO), standard oxygen therapy (SOT), and noninvasive bilevel positive airway pressure support (BIPAP) in patients with acute respiratory failure (ARF) after cardiothoracic surgery. DESIGN: Prospective controlled clinical trial. SETTING: A French 23-bed cardiothoracic surgical intensive care unit. PARTICIPANTS: Nonintubated patients with ARF after cardiothoracic surgery or while awaiting lung transplantation. INTERVENTIONS: HFNO (50 L/min), SOT via a standard facemask, and BIPAP (pressure support, 4 cmH2O; positive end-expiratory pressure [PEEP], 4 cmH2O), with FIO2 kept constant were successively applied and compared. With BIPAP, pressure support or PEEP increments up to 8 cmH2O were compared with baseline settings. Each measurement was made after stable breathing for 5 minutes. MEASUREMENTS AND MAIN RESULTS: Fifty patients aged 60.0 ± 12.2 years were enrolled, including 14 (28%) with obesity. Mean PaO2/FIO2 was 153 ± 55 mmHg. DTf was lower with HFNO and BIPAP than with SOT (respectively 21.2% ± 15.1% v 30.9% ± 21.1% and 17.8% ± 19.1% v 30.9% ± 21.1%, p < 0.001) and was not different with HFNO versus BIPAP (p = 0.22). With BIPAP, increasing pressure support to 8 cmH2O decreased DTf (21.0% ± 14.3% v 28.8% ± 19.8%, p = 0.009), whereas increasing PEEP to 8 cmH2O did not (25.2% ± 17.2% v 28.8% ± 19.8%, p = 0.79). Tidal volume increased to 10.6 ± 3.4 mL/kg with 8 cmH2O pressure support v 8.8 ± 2.7 mL/kg with 4 cmH2O pressure support (p < 0.001). CONCLUSION: HFNO provides a comparable respiratory workload decrease compared with BIPAP at lower levels of pressure support and PEEP compared with SOT. Increasing BIPAP pressure support may provide higher levels of assistance but carries a risk of overdistension.

Evaluation of Reperfusion Pulmonary Edema by Extravascular Lung Water Measurements After Pulmonary Endarterectomy.

OBJECTIVES: Reperfusion pulmonary edema is a specific complication of pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Extravascular lung water measurement may be valuable for diagnosing reperfusion pulmonary edema. The primary objective of this study was to describe and assess the clinical significance of extravascular lung water variations after pulmonary endarterectomy. DESIGN: Prospective observational study. SETTING: Nineteen-bed cardiothoracic ICU. PATIENTS: Consecutive patients who were hemodynamically stable after pulmonary endarterectomy were divided into two groups based on whether their preoperative pulmonary vascular resistance indicated severe or nonsevere chronic thromboembolic pulmonary hypertension (> 900 or ≤ 900 dynes·s/cm, respectively). INTERVENTIONS: Hemodynamic variables obtained by right heart catheterization and transpulmonary thermodilution measurements were recorded 1 hour, 1 day, and 2 days after pulmonary endarterectomy. Extravascular lung water was indexed to predicted body weight (EVLWPBW). MEASUREMENTS AND MAIN RESULTS: We studied 31 patients. Overall, 26 patients (84%) experienced reperfusion pulmonary edema during the first 72 hours after pulmonary endarterectomy. EVLWPBW significantly increased between the first hour after pulmonary endarterectomy and day 2 (10.2 ± 2.6 vs 11.4 ± 3.6; p = 0.03). EVLWPBW measured at the first hour after pulmonary endarterectomy is closely associated with reperfusion pulmonary edema occurrence in the next 48 hours (area under the receiver-operating characteristics curve = 0.88 ± 0.07). EVLWPBW correlated with duration of mechanical ventilation (ρ = 0.59; p < 0.0001) and ICU stay (ρ = 0.52; p < 0.0001). Patients with severe chronic thromboembolic pulmonary hypertension (n = 15) had higher EVLWPBW values at day 2 compared with those without (n = 16) (13.2 ± 3.6 vs 9.7 ± 2.7 mL/kg; p = 0.004). Cardiac output was measured simultaneously by pulmonary artery catheter and aortic transpulmonary thermodilution on 92 occasions; agreement was good, with a bias of 0.50 ± 0.95 L/min (95% CI, -1.36-2.36). CONCLUSIONS: Accurate extravascular lung water measurements were obtained after pulmonary endarterectomy. Extravascular lung water may prove valuable for diagnosing reperfusion pulmonary edema after pulmonary endarterectomy and had prognostic value. Extravascular lung water values were significantly higher in patients with severe compared with nonsevere chronic thromboembolic pulmonary hypertension.

Metabolomic profiling of cardiac allografts after controlled circulatory death.

BACKGROUND: Assessment of myocardial viability during ex situ heart perfusion (ESHP) is based on the measurement of lactate concentrations. As this provides with limited information, we sought to investigate the metabolic signature associated with donation after circulatory death (DCD) and the impact of ESHP on the myocardial metabolome. METHODS: Porcine hearts were retrieved either after warm ischemia (DCD group, N = 6); after brain-stem death (BSD group, N = 6); or without DCD nor BSD (Control group, N = 6). Hearts were perfused using normothermic oxygenated blood for 240 minutes. Plasma and myocardial samples were collected respectively every 30 and 60 minutes, and analyzed by an untargeted metabolomic approach using liquid chromatography coupled to high-resolution mass spectrometry. RESULTS: Median duration of warm ischemia was 23 minutes [19-29] in DCD animals. Lactate level within myocardial biopsies was not significantly different between groups at T0 (p = 0.281), and remained stable over the 4-hour period of ESHP. More than 300 metabolites were detected in plasma and heart biopsy samples. Compared to BSD animals, metabolomics changes involving energy and nucleotide metabolisms were observed in plasma samples of DCD animals before initiation of ESHP, whereas 2 metabolites (inosine monophosphate and methylbutyrate) exhibited concentration changes in biopsy samples. Normalization of DCD metabolic profile was remarkable after 4 hours of ESHP. CONCLUSION: A specific metabolic profile was observed in DCD hearts, mainly characterized by an increased nucleotide catabolism. DCD and BSD metabolomes proved normalized during ESHP. Complementary investigations are needed to correlate these findings to cardiac performances.

Extubation Failure Prediction by Echography of the Diaphragm After Cardiothoracic Surgery: The EXPEDIA Study.

BACKGROUND: Successful extubation is difficult to predict. Ultrasound measurement of the diaphragm thickening fraction (DTF) might help predict weaning failure after cardiothoracic surgery. METHODS: We assessed the predictive performance of diaphragm ultrasound in a derivation cohort of 50 prospectively included cardiothoracic surgery subjects ready for a weaning trial and in a validation cohort of 39 subjects ventilated for ≥ 48 h. DTF was assessed by ultrasound during pressure support ventilation (PSV) then during a T-piece spontaneous breathing trial (SBT). DTF was the percentage change in diaphragm thickness between expiration and inspiration and DTFmax, the higher DTF value of the 2 hemidiaphragms. DTFmax during SBT (static study) and the difference in DTFmax between PSV and SBT (dynamic study) were analyzed. RESULTS: In the derivation cohort, DTFmax during SBT was 25.6 ± 17.3% in subjects with successful extubation and 65.2 ± 17.3% in those with weaning failure (difference 39.7 [95% CI 27.4-51.9], P < .01). During SBT, DTFmax ≥ 50% was associated with weaning failure (area under the receiver operating characteristic curve [AUC] 0.94 ± 0.05). In the dynamic study, a ≥ 40% DTFmax increase was associated with weaning failure (AUC 0.91 ± 0.06). In the validation cohort, DTFmax during SBT was 20.3 ± 17.1% in subjects with successful extubation and 82.0 ± 51.6% in those with weaning failure (difference 61.8 [95% CI 41.6-82.0], P < .01). During SBT, DTFmax ≥ 50% predicted weaning failure (AUC 0.99 ± 0.02). In the dynamic study, a ≥ 40% increase in DTFmax predicted weaning failure (AUC 0.81 ± 0.09). CONCLUSIONS: Measuring DTFmax during SBT and the DTFmax change when switching from PSV to SBT may help predict weaning failure after cardiothoracic surgery. The study was registered on ANZCTR. CLINICAL TRIAL REGISTRATION NUMBER: U1111-1180-1999.

Effect of Recruitment Maneuvers and PEEP on Respiratory Failure After Cardiothoracic Surgery in Obese Subjects: A Randomized Controlled Trial.

BACKGROUND: Obesity may increase the risk of respiratory failure after cardiothoracic surgery. A recruitment maneuver followed by PEEP might decrease the risk of respiratory failure in obese subjects. We hypothesized that the routine use after heart surgery of a recruitment maneuver followed by high or low PEEP level would decrease the frequency of respiratory failure in obese subjects. METHODS: In a pragmatic, randomized controlled trial, we assigned obese subjects (ie, with body mass index [BMI] ≥ 30 kg/m2) in the immediate postoperative period of cardiothoracic surgery to either volume control ventilation with 5 cm H2O of PEEP (control group) or a recruitment maneuver followed by 5 or 10 cm H2O of PEEP in the intervention arms (RM5 and RM10 groups, respectively). The primary outcome was the proportion of subjects with postextubation respiratory failure, defined as the need for re-intubation, bi-level positive airway pressure, or high-flow nasal cannula within the first 48 h. RESULTS: The study included 192 subjects: 65 in the control group (BMI 33.5 ± 3.2 kg/m2), 66 in the RM5 group (BMI 34.5 ± 3.2 kg/m2, and 61 in RM10 group (BMI 33.8 ± 4.8 kg/m2). Postextubation respiratory failure occurred in 14 subjects in the control group (21.5% [95% CI 13.3-35.3]), 21 subjects in the RM5 group (31.8% [95% CI 21.2-44.6]), and 9 subjects in the RM10 group (14.7% [95% CI 7.4-26.7]) (P = .07). The recruitment maneuver was stopped prematurely due to severe hypotension in 8 (12.1%) RM5 subjects and in 4 (6.6%) RM10 subjects (P = .28). There were no significant differences between the 3 groups for the frequencies of atelectasis, pneumonia, and death in the ICU. CONCLUSIONS: The routine use after heart surgery of a recruitment maneuver followed by 5 or 10 cm H2O of PEEP did not decrease the frequency of respiratory failure in obese subjects. A recruitment maneuver followed by 5 cm H2O of PEEP is inappropriate.

Ex vivo perfusion of the donor heart: Preliminary experience in high-risk transplantations.

BACKGROUND: The number of heart transplantations (HTs) has decreased in France since 2017 (-5%/year) despite a stable rate of patients referred on the waiting list. Ex vivo heart perfusion (EVHP) is an innovative approach for organ preservation, reducing graft ischaemic time and facilitating continuous organ monitoring before transplantation. AIM: To report our preliminary experience of seven donor hearts preserved with EVHP, including the first heart resuscitated after circulatory-determined death in France. METHODS: Seven hearts were procured from donation after brain death (DBD) for HT or donation after circulatory-determined death (DCD) for research purposes (Protocol PFS20-004, Agence de la Biomédecine, La Plaine Saint-Denis, France). All grafts were preserved using the Organ Care System® (TransMedics Inc., Andover, MA, USA) for normothermic EVHP. Perfusion parameters were adjusted to achieve stable or decreasing arterial lactate trend consistent with suitability for organ transplantation. RESULTS: Indications for EVHP were assessment of a marginal graft in four cases, prolonged preservation in two cases (anticipated duration for retrieval of recipient's heart>3hours) and resuscitation after circulatory-determined death in one case. Median duration of EVHP was 270 (interquartile range 216-343) minutes. five were transplanted, with a median ex situ preservation time (ischaemic time+EVHP time) of 334 (interquartile range 326-444) minutes. The two other grafts were discarded for HT. Three recipients had extracorporeal life support after HT, and presented complete cardiac recovery within a week after HT. One patient died at day 11 because of septic shock. The 3-month survival rate was 75% among recipients. Three months after HT, the left ventricular ejection fraction was>60% in all cases. CONCLUSIONS: EVHP enabled safe prolonged preservation and assessment of marginal grafts. This approach provides an opportunity to expand the donor pool by resuscitating grafts from donors with extended criteria, including controlled DCD.

Lung and heart-lung transplantation for children with PAH: Dramatic benefits from the implementation of a high-priority allocation program in France.

PURPOSE: Pulmonary arterial hypertension (PAH) is rare but remains fatal in infants and children despite the advance of targeted therapies. Lung transplantation (LTx), first performed in pediatric patients in the 1980s, is, with the Potts shunt, the only potentially life-extending option in patients with end-stage PAH but is possible only in tightly selected patients. Size-matching challenges severely restrict the donor organ pool, resulting-together with peculiarities of PAH in infants-in high waitlist mortality. We aimed to investigate survival when using a high-priority allocation program (HPAP) in children with PAH listed for double-LTx or heart-LTx. METHODS: We conducted a single-center, retrospective, before-after study of consecutive children with severe Group 1 PAH listed for double-LTx or heart-LTx between 1988 and 2019. The HPAP was implemented in France in 2006 and 2007 for heart-LTx and double-LTx, respectively. RESULTS: Fifty-five children with PAH were listed for transplantation. Mean age at transplantation was 15.8±2.8 years and 72% had heart-lung transplantation. PAH was usually idiopathic (65%) or due to congenital heart disease (25%). HPAP implementation resulted in the following significant benefits: Decreased cumulative incidence of waitlist death within 1 and 2 years (p < 0.0001); increased cumulative incidence of transplantation within 6 months, from 44% to 67% (p < 0.01); and improved survival after listing (at 1, 3, and 5 years: 61%, 50%, and 44% vs. 92%, 84%, and 72% before and after HPAP implementation, respectively; p = 0.02). CONCLUSION: HPAP implementation was associated with significant improvements in access to transplantation and in survival after listing in children with end-stage PAH.

Specific Considerations for Venovenous Extracorporeal Membrane Oxygenation During Coronavirus Disease 2019 Pandemic.

Extracorporeal membrane oxygenation (ECMO) is recognized as organ support for potentially reversible acute respiratory distress syndrome (ARDS). However, limited resource during the outbreak and the coagulopathy associated with coronavirus disease 2019 (COVID-19) make the utilization of venovenous (VV) ECMO highly challenging. We herein report specific considerations for cannulation configurations and ECMO management during the pandemic. High blood flow and anticoagulation at higher levels than usual practice for VV ECMO may be required because of thrombotic hematologic profile of COVID-19. Among our first 24 cases (48.8 ± 8.9 years), 17 patients were weaned from ECMO after a mean duration of 19.0 ± 10.1 days and 16 of them have been discharged from ICU.

Connection of a Renal Replacement Therapy or Plasmapheresis Device to the ECMO Circuit.

In patients under extracorporeal membrane oxygenation (ECMO) support requiring renal replacement therapy or plasmapheresis, connecting such extracorporeal therapy device to the ECMO circuit provides many advantages compared with central venous catheterization. However, high pressures of the ECMO circuit limit the usefulness of this technique. We propose a new approach to connect extracorporeal therapy lines to the ECMO circuit. Inlet line is connected to the oxygenator, and outlet line is connected either to the femoral artery antegrade perfusion cannula in case of venoarterial ECMO or to the lateral vent of the return cannula in case of venovenous ECMO. We report the successful management of 21 patients using this connection, with much longer hemofilter average lifetime than previously reported.

Fiber optic bronchoscopy and remifentanil target-controlled infusion in critically ill patients with acute hypoxaemic respiratory failure: A descriptive study.

INTRODUCTION: Sedation optimizes patient comfort and ease of execution during fiber optic bronchoscopy (FOB). Our objective was to describe the safety and efficacy of remifentanil-TCI during FOB in non-intubated, hypoxaemic, thoracic surgery ICU patients. METHODS: Consecutive spontaneously breathing adults requiring FOB after thoracic surgery were included if they had hypoxaemia (PaO2/FiO2<300mmHg or need for non-invasive ventilation [NIV]) and prior FOB failure under topical anaesthesia. The remifentanil initial target was chosen at 1ng/mL brain effect-site concentration (Cet), then titrated to 0.5ng/mL Cet increments according to patient comfort and coughing. Outcomes were patient-reported pain and discomfort (Visual Analogue Scale scores), ventilatory support intensification within 24hours after bronchoscopy, and ease of FOB execution. RESULTS: Thirty-nine patients were included; all had a successful FOB. Their median PO2/FiO2 before starting FOB was 187±84mmHg and 24 patients received NIV. Median [interquartile range] pain scores were not different before and after FOB (1.0 [0.0-3.0] and 0.0 [0.0-2.0], respectively). Discomfort was reported as absent or minimal by 27 patients (69%; 95% confidence interval [95% CI], 54-81%) and as bothersome but tolerable by 12 patients (31%; 95% CI, 19-46%). Mean FiO2 returned to baseline within 2hours after FOB in 30 patients; the remaining 9 patients (23%; 95% CI, 13-38%) received ventilatory support intensification. Ease of execution was good or very good in 34 patients (87%; 95% CI, 73-94%), acceptable in 4 patients, and poor in 1 patient (persistent cough). CONCLUSION: Sedation with remifentanil-TCI during FOB with prior failure under topical anaesthesia alone was effective and acceptably safe in non-intubated hypoxaemic thoracic surgery patients.