ICU- and ventilator-free days with isoflurane or propofol as a primary sedative - A post- hoc analysis of a randomized controlled trial.

PURPOSE: To compare ICU-free (ICU-FD) and ventilator-free days (VFD) in the 30 days after randomization in patients that received isoflurane or propofol without receiving the other sedative. MATERIALS AND METHODS: A recent randomized controlled trial (RCT) compared inhaled isoflurane via the Sedaconda® anaesthetic conserving device (ACD) with intravenous propofol for up to 54 h (Meiser et al. 2021). After end of study treatment, continued sedation was locally determined. Patients were eligible for this post-hoc analysis only if they had available 30-day follow-up data and never converted to the other drug in the 30 days from randomization. Data on ventilator use, ICU stay, concomitant sedative use, renal replacement therapy (RRT) and mortality were collected. RESULTS: Sixty-nine of 150 patients randomized to isoflurane and 109 of 151 patients randomized to propofol were eligible. After adjusting for potential confounders, the isoflurane group had more ICU-FD than the propofol group (17.3 vs 13.8 days, p = 0.028). VFD for the isoflurane and propofol groups were 19.8 and 18.5 respectively (p = 0.454). Other sedatives were used more frequently (p < 0.0001) and RRT started in a greater proportion of patients in the propofol group (p = 0.011). CONCLUSIONS: Isoflurane via the ACD was not associated with more VFD but with more ICU-FD and less concomitant sedative use.

Clinical risk factors for increased respiratory drive in intubated hypoxemic patients.

BACKGROUND: There is very limited evidence identifying factors that increase respiratory drive in hypoxemic intubated patients. Most physiological determinants of respiratory drive cannot be directly assessed at the bedside (e.g., neural inputs from chemo- or mechano-receptors), but clinical risk factors commonly measured in intubated patients could be correlated with increased drive. We aimed to identify clinical risk factors independently associated with increased respiratory drive in intubated hypoxemic patients. METHODS: We analyzed the physiological dataset from a multicenter trial on intubated hypoxemic patients on pressure support (PS). Patients with simultaneous assessment of the inspiratory drop in airway pressure at 0.1-s during an occlusion (P0.1) and risk factors for increased respiratory drive on day 1 were included. We evaluated the independent correlation of the following clinical risk factors for increased drive with P0.1: severity of lung injury (unilateral vs. bilateral pulmonary infiltrates, PaO2/FiO2, ventilatory ratio); arterial blood gases (PaO2, PaCO2 and pHa); sedation (RASS score and drug type); SOFA score; arterial lactate; ventilation settings (PEEP, level of PS, addition of sigh breaths). RESULTS: Two-hundred seventeen patients were included. Clinical risk factors independently correlated with higher P0.1 were bilateral infiltrates (increase ratio [IR] 1.233, 95%CI 1.047-1.451, p = 0.012); lower PaO2/FiO2 (IR 0.998, 95%CI 0.997-0.999, p = 0.004); higher ventilatory ratio (IR 1.538, 95%CI 1.267-1.867, p < 0.001); lower pHa (IR 0.104, 95%CI 0.024-0.464, p = 0.003). Higher PEEP was correlated with lower P0.1 (IR 0.951, 95%CI 0.921-0.982, p = 0.002), while sedation depth and drugs were not associated with P0.1. CONCLUSIONS: Independent clinical risk factors for higher respiratory drive in intubated hypoxemic patients include the extent of lung edema and of ventilation-perfusion mismatch, lower pHa, and lower PEEP, while sedation strategy does not affect drive. These data underline the multifactorial nature of increased respiratory drive.

Lung Transplantation for End-Stage Respiratory Failure After Severe COVID-19: A Report of 2 Cases.

We report 2 cases of bilateral lung transplantation for nonresolving coronavirus disease 2019 associated respiratory failure. In the first patient, the severe acute respiratory syndrome coronavirus 2 infection caused acute respiratory distress syndrome requiring prolonged extracorporeal membrane oxygenation support; in the second patient, coronavirus disease 2019 resulted in irreversible pulmonary fibrosis requiring only ventilatory support. The 2 cases represent the 2 ends of the spectrum showing significant differences in preoperative and postoperative courses.

Inhaled isoflurane via the anaesthetic conserving device versus propofol for sedation of invasively ventilated patients in intensive care units in Germany and Slovenia: an open-label, phase 3, randomised controlled, non-inferiority trial.

BACKGROUND: Previous studies indicate that isoflurane could be useful for the sedation of patients in the intensive care unit (ICU), but prospective studies evaluating isoflurane's efficacy have been small. The aim of this study was to test whether the sedation with isoflurane was non-inferior to sedation with propofol. METHODS: This phase 3, randomised, controlled, open-label non-inferiority trial evaluated the efficacy and safety of up to 54 h of isoflurane compared with propofol in adults (aged ≥18 years) who were invasively ventilated in ICUs in Germany (21 sites) and Slovenia (three sites). Patients were randomly assigned (1:1) to isoflurane inhalation via the Sedaconda anaesthetic conserving device (ACD; Sedana Medical AB, Danderyd, Sweden; ACD-L [dead space 100 mL] or ACD-S [dead space 50 mL]) or intravenous propofol infusion (20 mg/mL) for 48 h (range 42-54) using permuted block randomisation with a centralised electronic randomisation system. The primary endpoint was percentage of time in Richmond Agitation-Sedation Scale (RASS) range -1 to -4, assessed in eligible participants with at least 12 h sedation (the per-protocol population), five or more RASS measurements, and no major protocol violations, with a non-inferiority margin of 15%. Key secondary endpoints were opioid requirements, spontaneous breathing, time to wake-up and extubation, and adverse events. Safety was assessed in all patients who received at least one dose. The trial is complete and registered with EudraCT, 2016-004551-67. FINDINGS: Between July 2, 2017, and Jan 12, 2020, 338 patients were enrolled and 301 (89%) were randomly assigned to isoflurane (n=150) or propofol (n=151). 146 patients (97%) in each group completed the 24-h follow-up. 146 (97%) patients in the isoflurane group and 148 (98%) of patients in the propofol group were included in the per-protocol analysis of the primary endpoint. Least-squares mean percentage of time in RASS target range was 90·7% (95% CI 86·8-94·6) for isoflurane and 91·1% (87·2-95·1) for propofol. With isoflurane sedation, opioid dose intensity was 29% lower than with propofol for the overall sedation period (0·22 [0·12-0·34] vs 0·32 [0·21-0·42] mg/kg per h morphine equivalent dose, p=0·0036) and spontaneous breathing was more frequent on day 1 (odds ratio [OR] 1·72 [1·12-2·64], generalised mixed linear model p=0·013, with estimated rates of 50% of observations with isoflurane vs 37% with propofol). Extubation times were short and median wake-up was significantly faster after isoflurane on day 2 (20 min [IQR 10-30] vs 30 min [11-120]; Cox regression p=0·0011). The most common adverse events by treatment group (isoflurane vs propofol) were: hypertension (ten [7%] of 150 vs two [1%] of 151), delirium (eight [5%] vs seven [5%]), oliguria (seven [5%] vs six [4%]), and atrial fibrillation (five [3%] vs four [3%]). INTERPRETATION: These results support the use of isoflurane in invasively ventilated patients who have a clinical need for sedation. FUNDING: Sedana Medical AB.

Sigh in Patients With Acute Hypoxemic Respiratory Failure and ARDS: The PROTECTION Pilot Randomized Clinical Trial.

BACKGROUND: Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. RESEARCH QUESTION: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? STUDY DESIGN AND METHODS: We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. RESULTS: Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, -7%; 95% CI, -18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group. INTERPRETATION: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03201263; URL: www.clinicaltrials.gov.

Cardiopulmonary Resuscitation with Extracorporeal Membrane Oxygenation in a Patient with Profound Accidental Hypothermia and Refractory Ventricular Fibrillation.

We describe a patient with severe accidental hypothermia (≤25.4°C) and prolonged refractory ventricular fibrillation, lasting at least 4 hours and 8 minutes, who underwent cardiopulmonary resuscitation with extracorporeal membrane oxygenation and survived without neurologic deficit.

Pressure support ventilation + sigh in acute hypoxemic respiratory failure patients: study protocol for a pilot randomized controlled trial, the PROTECTION trial.

BACKGROUND: Adding cyclic short sustained inflations (sigh) to assisted ventilation yields optimizes lung recruitment, decreases heterogeneity and reduces inspiratory effort in patients with acute hypoxemic respiratory failure (AHRF). These findings suggest that adding sigh to pressure support ventilation (PSV) might decrease the risk of lung injury, shorten weaning and improve clinical outcomes. Thus, we conceived a pilot trial to test the feasibility of adding sigh to PSV (the PROTECTION study). METHODS: PROTECTION is an international randomized controlled trial that will be conducted in 23 intensive care units (ICUs). Patients with AHRF who have been intubated from 24 h to 7 days and undergoing PSV from 4 to 24 h will be enrolled. All patients will first undergo a 30-min sigh test by adding sigh to clinical PSV for 30 min to identify early oxygenation responders. Then, patients will be randomized to PSV or PSV + sigh until extubation, ICU discharge, death or day 28. Sigh will be delivered as a 3-s pressure control breath delivered once per minute at 30 cmH2O. Standardized protocols will guide ventilation settings, switch back to controlled ventilation, use of rescue treatments, performance of spontaneous breathing trial, extubation and reintubation. The primary endpoint of the study will be to verify the feasibility of PSV + sigh evaluated through reduction of failure to remain on assisted ventilation during the first 28 days in the PSV + sigh group versus standard PSV (15 vs. 22%). Failure will be defined by switch back to controlled ventilation for more than 24 h or use of rescue treatments or reintubation within 48 h from elective extubation. Setting the power to 80% and first-risk order to 5%, the computed size of the trial is 129 patients per arm. DISCUSSION: PROTECTION is a pilot randomized controlled trial testing the feasibility of adding sigh to PSV. If positive, it will provide physicians with an effective addition to standard PSV for lung protection, able to reduce failure of assisted ventilation. PROTECTION will provide the basis for a future larger trial aimed at verifying the impact of PSV + sigh on 28-day survival and ventilator-free days. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03201263 . Registered on 28 June 2017.

Pregnancy complicated by influenza A ARDS requiring consecutive VV-ECMO treatment with successful vaginal delivery.

A 29-year-old woman presented with influenza A ARDS at 23+0 weeks of gestation. Mechanical ventilation failed and VV-ECMO was started in a non-ECMO hospital. Transportation was performed on ECMO. Within 5 days ECMO weaning was successful. Fetal condition was stable, and decision to continue pregnancy was taken. However, second VV-ECMO was needed due to ventilator-associated pneumonia. At 25+6 weeks, the patient spontaneously delivered a neonate vaginally. Patient's condition improved, and ECMO could be removed 10 days postpartum. 2-year follow-up showed no severe consequences in the mother and the child.

Prophylactic versus clinically-driven antibiotics in comatose survivors of out-of-hospital cardiac arrest-A randomized pilot study.

AIM: To investigate benefits of prophylactic antibiotics in comatose survivors of out-of-hospital cardiac arrest (OHCA). METHODS: Patients without evidence of tracheobronchial aspiration on admission bronchoscopy were randomized to prophylactic Amoxicillin-Clavulanic acid 1.2g every 8h (P) or clinically-driven antibiotics (C) administered if signs of infection developed during initial 7days of intensive care unit (ICU) stay. RESULTS: Among 83 patients enrolled between September 2013 and February 2015, tracheobronchial aspiration was documented in 23 (28%). Accordingly, 60 patients were randomized. Percentage of patients on antibiotics between days 1-5 was significantly greater in P group. White blood count, C-reactive protein, procalcitonin (PCT) and CD 64 significantly increased during the postresuscitation phase. Except for lower CRP and PCT in group P on day 6 (p<0.05), there was no significant differences. Mini BAL on day 3 was less often positive in group P (7% vs. 42%; p<0.01). There was no significant difference in other microbiological samples and X-ray signs of pneumonia cumulatively documented in 50% in both groups. Use of vasopressors/inotropes (93% in both groups), duration of mechanical ventilation (5.4±3.7 vs. 5.2±3.1 days), tracheal intubation (6.5±4.6 vs. 5.9±4.3 days), ICU stay (7.7±5.2 vs. 6.9±4.5 days), survival (73% vs. 73%) and survival with good neurological outcome (50% vs. 40%) were also comparable between P and C groups. CONCLUSION: Bronchoscopy on admission documented tracheobronchial aspiration in 28% of comatose survivors of OHCA. In the absence of aspiration, prophylactic antibiotics did not significantly alter systemic inflammatory response, postresuscitation pneumonia, ICU treatment and outcome (ClinicalTrials.gov Identifier: NCT02899507).

Emergency percutaneous implantation of veno-arterial extracorporeal membrane oxygenation in the catheterisation laboratory.

AIMS: Our aim was to describe our protocol for emergency percutaneous implantation of femoral veno-arterial extracorporeal membrane oxygenation (VA ECMO) in the catheterisation laboratory and to compare its effectiveness and safety with implantation in the intensive care unit and the operating room. METHODS AND RESULTS: Our retrospective observational study enrolled 56 consecutive patients undergoing VA ECMO implantation in the catheterisation laboratory (n=23), the intensive care unit (n=8) and the operating room (n=25). Among patients undergoing catheterisation laboratory implantation, 11 patients had profound cardiogenic shock but preserved arterial pulsations, and 12 patients had refractory cardiac arrest undergoing automated mechanical chest compression. Using our fluoroscopy-guided protocol, arterial and venous cannulas were successfully implanted and the desired ECMO flow obtained in each patient. There was no vessel perforation/dissection. Moderate/severe GUSTO or BARC 3 and 5 bleeding occurred in 13%. Ipsilateral limb ischaemia occurred in one of eight patients (13%) with upfront perfusion sheath implantation, and in two of three patients (75%) in whom this strategy was not used (p=0.15). There was no infection at the site of cannula implantation. Complications related to implantation in the catheterisation laboratory were comparable to surgical implantation in the operating room and percutaneous implantation in the intensive care unit using ultrasound guidance. CONCLUSIONS: Fluoroscopy-guided emergency implantation of femoral VA ECMO by an interventional cardiologist in the catheterisation laboratory is effective and safe for both patients in cardiogenic shock and those in refractory cardiac arrest.

Angiographic characteristics of coronary disease and postresuscitation electrocardiograms in patients with aborted cardiac arrest outside a hospital.

Postresuscitation electrocardiogram (ECG) in patients with aborted cardiac death may demonstrate ST-elevation myocardial infarction (STEMI), ST-T changes, intraventricular conduction delay, or other nonspecific findings. In the present study, we compared ECG to urgent coronary angiogram in 158 consecutive patients with STEMI and 54 patients not fulfilling criteria for STEMI admitted to our hospital from January 1, 2003 through December 31, 2008. At least 1 obstructive lesion was present in 97% of patients with STEMI and in 59% of patients without STEMI with ≥1 occlusion in 82% and 39%, respectively (p <0.001). Obstructive lesion was considered acute in 89% of patients with STEMI and in 24% of patients without STEMI (p <0.001). An acute lesion in STEMI had a higher thrombus score (2.6 vs 1.3, p = 0.05) and more often presented with Thrombolysis In Myocardial Infarction grade 0 to 1 flow (75% vs 36%, p <0.01). Percutaneous coronary intervention, which was attempted in 148 lesions in patients with STEMI and in 17 lesions in patients without STEMI, resulted in final Thrombolysis In Myocardial Infarction grade 3 flow in 87% and 71%, respectively (p = 0.34). In conclusion, STEMI on postresuscitation ECG is usually associated with the presence of an acute culprit lesion. However, in the absence of STEMI, an acute culprit lesion is still present in 1/4 of patients. An acute lesion in STEMI is more thrombotic and more often leads to complete occlusion. Urgent percutaneous coronary intervention is feasible and successful regardless of postresuscitation ECG.

Primary percutaneous coronary intervention and mild induced hypothermia in comatose survivors of ventricular fibrillation with ST-elevation acute myocardial infarction.

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for ST-elevation acute myocardial infarction (STEMI). In comatose survivors of cardiac arrest, mild induced hypothermia (MIH) improves neurological recovery. In the present study, we investigated feasibility and safety of combining primary PCI and MIH in comatose survivors of ventricular fibrillation with signs of STEMI after reestablishment of spontaneous circulation. Forty consecutive patients undergoing primary PCI and MIH from November 1, 2003 to December 31, 2005 were compared to 32 consecutive patients who underwent primary PCI but no MIH between January 1, 2000 and November 1, 2003. There were no significant differences between the MIH and no MIH groups in general characteristics, cardiac arrest circumstances and angiographic features. Except for decreases in heart rate during hypothermia interval, there was no difference between the MIH and no MIH groups in arterial pressure, peak arterial lactate (5.1 mmol/l versus 5.7 mmol/l; p = .56), need for vasopressors (65% versus 53%; p = .44), inotropes (48% versus 59%; p = .44), aortic balloon counterpulsation (20% versus 22%; p = .92), repeat cardioversion/defibrillation (30% versus 34%; p=.89) and use of antiarrhythmics (33% versus 53%; p = .13). There was also no difference in inspired oxygen requirements during mechanical ventilation and in renal function. Hospital survival with cerebral performance category 1 and 2 was significantly better in MIH group (55% versus 16%; p=.001). Our preliminary experience indicates that primary PCI and MIH are feasible and may be combined safely in comatose survivors of ventricular fibrillation with signs of STEMI. Such a strategy may improve survival with good neurological recovery.