Difference In Ventilator-free Days Research Articles

High-Flow Nasal Cannula Versus Noninvasive Ventilation as Initial Treatment in Acute Hypoxia: A Propensity Score-Matched Study.

Patients presenting to the emergency department (ED) with hypoxemia often have mixed or uncertain causes of respiratory failure. The optimal treatment for such patients is unclear. Both high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) are used. We sought to compare the effectiveness of initial treatment with HFNC versus NIV for acute hypoxemic respiratory failure. We conducted a retrospective cohort study of patients with acute hypoxemic respiratory failure treated with HFNC or NIV within 24 hours of arrival to the University of Michigan adult ED from January 2018 to December 2022. We matched patients 1:1 using a propensity score for odds of receiving NIV. The primary outcome was major adverse pulmonary events (28-d mortality, ventilator-free days, noninvasive respiratory support hours) calculated using a win ratio. A total of 1154 patients were included. Seven hundred twenty-six (62.9%) received HFNC and 428 (37.1%) received NIV. We propensity score matched 668 of 1154 (57.9%) patients. Patients on NIV versus HFNC had lower 28-day mortality (16.5% vs. 23.4%, p = 0.033) and required noninvasive treatment for fewer hours (median 7.5 vs. 13.5, p < 0.001), but had no difference in ventilator-free days (median [interquartile range]: 28 [26, 28] vs. 28 [10.5, 28], p = 0.199). Win ratio for composite major adverse pulmonary events favored NIV (1.38; 95% CI, 1.15-1.65; p < 0.001). In this observational study of patients with acute hypoxemic respiratory failure, initial treatment with NIV compared with HFNC was associated with lower mortality and fewer composite major pulmonary adverse events calculated using a win ratio. These findings underscore the need for randomized controlled trials to further understand the impact of noninvasive respiratory support strategies.

Oxygen-Saturation Targets and Cognitive and Functional Outcomes in Mechanically Ventilated Adults.

Rationale: Among mechanically ventilated critically ill adults, the PILOT (Pragmatic Investigation of Optimal Oxygen Targets) trial demonstrated no difference in ventilator-free days among lower, intermediate, and higher oxygen-saturation targets. The effects on long-term cognition and related outcomes are unknown.Objectives: To compare the effects of lower (90% [range, 88-92%]), intermediate (94% [range, 92-96%]), and higher (98% [range, 96-100%]) oxygen-saturation targets on long-term outcomes.Methods: Twelve months after enrollment in the PILOT trial, blinded neuropsychological raters conducted assessments of cognition, disability, employment status, and quality of life. The primary outcome was global cognition as measured using the Telephone Montreal Cognitive Assessment. In a subset of patients, an expanded neuropsychological battery measured executive function, attention, immediate and delayed memory, verbal fluency, and abstraction.Measurements and Main Results: A total of 501 patients completed follow-up, including 142 in the lower, 186 in the intermediate, and 173 in the higher oxygen target groups. Median (interquartile range) peripheral oxygen saturation values in the lower, intermediate, and higher target groups were 94% (91-96%), 95% (93-97%), and 97% (95-99%), respectively. Telephone Montreal Cognitive Assessment score did not differ between lower and intermediate (adjusted odds ratio [OR], 1.36 [95% confidence interval (CI), 0.92-2.00]), intermediate and higher (adjusted OR, 0.90 [95% CI, 0.62-1.29]), or higher and lower (adjusted OR, 1.22 [95% CI, 0.83-1.79]) target groups. There was also no difference in individual cognitive domains, disability, employment, or quality of life.Conclusions: Among mechanically ventilated critically ill adults who completed follow-up at 12 months, oxygen-saturation targets were not associated with cognition or related outcomes.

Sigh Ventilation in Patients With Trauma

Among patients receiving mechanical ventilation, tidal volumes with each breath are often constant or similar. This may lead to ventilator-induced lung injury by altering or depleting surfactant. The role of sigh breaths in reducing ventilator-induced lung injury among trauma patients at risk of poor outcomes is unknown. To determine whether adding sigh breaths improves clinical outcomes. A pragmatic, randomized trial of sigh breaths plus usual care conducted from 2016 to 2022 with 28-day follow-up in 15 academic trauma centers in the US. Inclusion criteria were age older than 18 years, mechanical ventilation because of trauma for less than 24 hours, 1 or more of 5 risk factors for developing acute respiratory distress syndrome, expected duration of ventilation longer than 24 hours, and predicted survival longer than 48 hours. Sigh volumes producing plateau pressures of 35 cm H2O (or 40 cm H2O for inpatients with body mass indexes >35) delivered once every 6 minutes. Usual care was defined as the patient's physician(s) treating the patient as they wished. The primary outcome was ventilator-free days. Prespecified secondary outcomes included all-cause 28-day mortality. Of 5753 patients screened, 524 were enrolled (mean [SD] age, 43.9 [19.2] years; 394 [75.2%] were male). The median ventilator-free days was 18.4 (IQR, 7.0-25.2) in patients randomized to sighs and 16.1 (IQR, 1.1-24.4) in those receiving usual care alone (P = .08). The unadjusted mean difference in ventilator-free days between groups was 1.9 days (95% CI, 0.1 to 3.6) and the prespecified adjusted mean difference was 1.4 days (95% CI, -0.2 to 3.0). For the prespecified secondary outcome, patients randomized to sighs had 28-day mortality of 11.6% (30/259) vs 17.6% (46/261) in those receiving usual care (P = .05). No differences were observed in nonfatal adverse events comparing patients with sighs (80/259 [30.9%]) vs those without (80/261 [30.7%]). In a pragmatic, randomized trial among trauma patients receiving mechanical ventilation with risk factors for developing acute respiratory distress syndrome, the addition of sigh breaths did not significantly increase ventilator-free days. Prespecified secondary outcome data suggest that sighs are well-tolerated and may improve clinical outcomes. ClinicalTrials.gov Identifier: NCT02582957.

Effect of propranolol and clonidine after severe traumatic brain injury: a pilot randomized clinical trial

ObjectiveTo evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI).BackgroundAdministration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit.MethodsThis phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16–64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study.ResultsDose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (− 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes.ConclusionDespite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI.Trial Registration Number NCT01322048.

Implementation of Lung-Protective Ventilation in Patients With Acute Respiratory Failure.

We implemented a computerized protocol for low tidal volume ventilation (LTVV) to improve management and outcomes of mechanically ventilated patients with, and without, the acute respiratory distress syndrome (ARDS). Pragmatic, nonrandomized stepped wedge type II hybrid implementation/effectiveness trial. Twelve hospitals in an integrated healthcare system over a 2-year period. Patients greater than or equal to 18 years old who had initiation of mechanical ventilation in the emergency department or ICU. We excluded patients who died or transitioned to comfort care on the day of admission to the ICU. We defined a subgroup of patients with ARDS for analysis. Implementation of ventilator protocols for LTVV in the ICU. Our primary clinical outcome was ventilator-free days (VFDs) to day 28. Our primary process outcome was median initial set tidal volume. We included 8,692 mechanically ventilated patients, 3,282 (38%) of whom had ARDS. After implementation, set tidal volume reported as mL/kg predicted body weight decreased from median 6.1 mL/kg (interquartile range [IQR], 6.0-6.8 mL/kg) to 6.0 mL/kg (IQR, 6.0-6.6 mL/kg) ( p = 0.009). The percent of patients receiving LTVV (tidal volume ≤ 6.5 mL/kg) increased from 69.8% ( n = 1,721) to 72.5% ( n = 1,846) ( p = 0.036) after implementation. The percent of patients receiving greater than 8 mL/kg initial set tidal volume was reduced from 9.0% ( n = 222) to 6.7% ( n = 174) ( p = 0.005) after implementation. Among patients with ARDS, day 1 positive end-expiratory pressure increased from 6.7 to 8.0 cm H 2 O ( p < 0.001). We observed no difference in VFD (adjusted odds ratio, 1.06; 95% CI, 0.91-1.24; p = 0.44), or in secondary outcomes of length of stay or mortality, either within the main cohort or the subgroup of patients with ARDS. We observed improved adherence to optimal ventilator management with implementation of a computerized protocol and reduction in the number of patients receiving tidal volumes greater than 8 mL/kg. We did not observe improvement in clinical outcomes.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

1206: BETA-LACTAM DOSING IN PATIENTS WITH SEPSIS AND AKI: A MULTICENTER OBSERVATIONAL STUDY

Introduction: Beta-lactam antibiotics are the backbone of therapy for critically ill patients with sepsis; however, these patients experience pharmacokinetic changes that alter beta-lactam exposure. Adjusting doses for acute kidney injury during the first 48 hours of admission to the ICU may result in suboptimal drug exposure and subject patients to inadequate therapy. We evaluated the association of beta-lactam antibiotic dose adjustment within the first 48 hours of therapy, on shock-free days in critically ill patients with acute kidney injury and septic shock secondary to gram-negative bloodstream infections. Methods: Multi-center, retrospective, observational cohort study of adult ICU patients with septic shock secondary to gram-negative bloodstream infections who received empiric, in vitro active cefepime, piperacillin-tazobactam, or meropenem. Primary outcome was shock-free days at 28 days which was modeled with linear regression. Secondary outcomes were ventilator-free days at 28 days, ICU mortality, and analysis of outcomes in patients with CrCL < 50ml/min at the time of beta-lactam initiation. Results: A total of 179 patients were included in the final analysis (103 in the adjusted group, 76 in the unadjusted group). Dose adjusting the beta-lactam was not associated with a difference in shock-free days at 28 days (β 2.25, [95% CI -2.04, 6.54], p=0.30. There was no difference in ventilator-free days at 28 days, or overall mortality. Conclusions: In patients with gram negative bacteremia and shock, there was no difference in clinical outcomes in patients who had their beta-lactams renally dose adjusted verses those who did not. Prospective, randomized interventional studies are needed to test if renal dose adjustments impact outcomes in patients with septic shock.

Clinical Outcomes of Acute Respiratory Failure Associated With Noninvasive and Invasive Ventilation in a Pediatric ICU.

It remains unknown if pediatric patients failing initial noninvasive ventilation (NIV) experience worse clinical outcomes than those successfully treated with NIV or those primarily intubated. This was a single-center, retrospective review of patients admitted with acute respiratory failure to the University of Michigan pediatric intensive care or cardiothoracic ICUs and receiving NIV or invasive mechanical ventilation as first-line therapy. One hundred seventy subjects met inclusion criteria and were enrolled: 65 NIV success, 55 NIV failure, and 50 invasive mechanical ventilation alone. Of those failing NIV, median time to intubation was 1.8 (interquartile range [IQR] < 1-7) h. On multivariable regression, ICU-free days were significantly different between groups (NIV success: 22.9 ± 6.9 d; NIV failure: 13.0 ± 6.6 d; invasive ventilation: 12.5 ± 6.9 d; P < .001 across all groups). Multivariable regression revealed no difference in ventilator-free days between NIV failure and invasive ventilation groups (15.4 ± 10.1 d vs 15.9 ± 9.7 d, P = .71). Of 64 subjects (37.6%) meeting Pediatric Acute Lung Injury Consensus Conference pediatric ARDS criteria, only 14% were successfully treated with NIV. Ventilator-free days were similar between the NIV failure and invasive ventilation groups (11.6 vs 13.2 d, P = .47). On multivariable analysis, ICU-free days were significantly different across pediatric ARDS groups (P < .001): NIV success: 20.8 + 31.7 d; NIV failure: 8.3 + 23.8 d; invasive alone: 8.9 + 23.9 d, yet no significant difference in ventilator-free days between those with NIV failure versus invasive alone (11.6 vs 13.2 d, P = .47). We demonstrated that critically ill pediatric subjects unsuccessfully trialed on NIV did not experience increased ICU length of stay or fewer ventilator-free days when compared to those on invasive mechanical ventilation alone, including in the pediatric ARDS subgroup. Our findings are predicated on a median time to intubation of < 2 h in the NIV failure group and the provision of adequate monitoring while on NIV.

The effect of intermittent pneumatic compression on deep-vein thrombosis and ventilation-free days in critically ill patients with heart failure

There are contradictory data regarding the effect of intermittent pneumatic compression (IPC) on the incidence of deep-vein thrombosis (DVT) and heart failure (HF) decompensation in critically ill patients. This study evaluated the effect of adjunctive use of IPC on the rate of incident DVT and ventilation-free days among critically ill patients with HF. In this pre-specified secondary analysis of the PREVENT trial (N = 2003), we compared the effect of adjunctive IPC added to pharmacologic thromboprophylaxis (IPC group), with pharmacologic thromboprophylaxis alone (control group) in critically ill patients with HF. The presence of HF was determined by the treating teams according to local practices. Patients were stratified according to preserved (≥ 40%) versus reduced (< 40%) left ventricular ejection fraction, and by the New York Heart Association (NYHA) classification. The primary outcome was incident proximal lower-limb DVT, determined with twice weekly venous Doppler ultrasonography. As a co-primary outcome, we evaluated ventilation-free days as a surrogate for clinically important HF decompensation. Among 275 patients with HF, 18 (6.5%) patients had prevalent proximal lower-limb DVT (detected on trial day 1 to 3). Of 257 patients with no prevalent DVT, 11/125 (8.8%) patients in the IPC group developed incident proximal lower-limb DVT compared to 6/132 (4.5%) patients in the control group (relative risk, 1.94; 95% confidence interval, 0.74–5.08, p = 0.17). There was no significant difference in ventilator-free days between the IPC and control groups (median 21 days versus 25 days respectively, p = 0.17). The incidence of DVT with IPC versus control was not different across NYHA classes (p value for interaction = 0.18), nor across patients with reduced and preserved ejection fraction (p value for interaction = 0.15). Ventilator-free days with IPC versus control were also not different across NYHA classes nor across patients with reduced or preserved ejection fraction. In conclsuion, the use of adjunctive IPC compared with control was associated with similar rate of incident proximal lower-limb DVT and ventilator-free days in critically ill patients with HF.Trial registration: The PREVENT trial is registered at ClinicalTrials.gov, ID: NCT02040103 (registered on 3 November 2013, https://clinicaltrials.gov/ct2/show/study/NCT02040103) and Current controlled trials, ID: ISRCTN44653506 (registered on 30 October 2013).

The Impact of Pneumonia PCR Panel Testing in the PICU: A Quality Improvement Study

AbstractInappropriate antibiotic usage can contribute to the promotion of resistant bacteria. In an effort to reduce antibiotic length of therapy (LOT), we initiated a performance improvement project utilizing pneumonia polymerase chain reaction (PCR) testing in ventilated pediatric intensive care unit (PICU) patients suspected of tracheitis or pneumonia. This is a single-center cohort intervention study that compared pre- and postimplementation patients. The intervention was the use of a pneumonia PCR panel on all PICU patients undergoing an evaluation for acute tracheitis or pneumonia during the postimplementation period. The inclusion criteria were either acute or acute on chronic respiratory failure. After an 8-month period, the charts were reviewed from both cohorts and baseline data, and outcome data were compared by statistical analysis. A total of 41 preimplementation and 30 postimplementation patients were compared, and no baseline differences were found except postimplementation patients being slightly older (133 vs. 56 months, p-value = 0.040). Analysis of the primary outcome measures found that the time to identification of organism (5 vs. 67 hours) and LOT (5 vs. 9 days, p &lt; 0.001) were shorter in postimplementation patients compared with preimplementation patients. Antibiotics were changed based on the results of the pneumonia PCR on 18 of 30 patients (60%). There was no difference in ventilator-free days, PICU length of stay, or mortality. In conclusion, pneumonia PCR panel testing leads to more rapid results and is associated with reduced antibiotic LOT.

Association of body mass index with morbidity in patients hospitalised with COVID-19

PurposeTo evaluate the association between body mass index (BMI) and clinical outcomes other than death in patients hospitalised and intubated with COVID-19.MethodsThis is a single-centre cohort study of adults with...

A Prospective Observational Study of High-Flow Nasal Oxygen Therapy and Noninvasive Positive Pressure Ventilation in Patients with Acute Hypoxemic Respiratory Failure

Background: Treatment for acute hypoxemic respiratory failure (AHRF) includes treating the underlying disease, conventional oxygen therapy (COT), noninvasive ventilation (NIV), high-flow nasal oxygen (HFNO), and invasive mechanical ventilation. Aim: The aim of this study was to compare the use of HFNO and NIV in patients with moderate-to-severe AHRF to the tertiary level intensive care unit (ICU) of a teaching hospital. Methods: All adult patients admitted to the ICU with AHRF and failed COT were included. Administration of HFNO or NIV was protocol-based and targeted improvement in oxygen saturation, respiratory rate, PaO2, and PaCO2. Demographic data, clinical details, vital parameters, and laboratory findings were noted at prespecified intervals. Acute Physiology and Chronic Health Evaluation II at 24 h of ICU admission and daily Sequential Organ Failure Assessment were noted. The primary outcome was failure of treatment modalities defined as need for intubation and invasive ventilation. The secondary outcomes measured at 28 days were differences in ventilator-free days, ICU and hospital length of stay, patient comfort, and mortality. Results: A total of 35 patients were included in the study. Treatment failure was 20.8% (5/24) in the NIV group and 36% (4/11) in the HFNO group (P = 0.32). The number of ventilator-free days at day 28 was 22.67 ± 9.92 and 19.36 ± 12.45 (P = 0.44) in the NIV and HFNO groups, respectively. Mortality at 28 days was 12.5% (3/24) and 27.2% (3/11) in the NIV and HFNO groups, respectively (P = 0.282). Conclusion: Treatment with HFNO is associated with nonsignificant increase in the need for intubation and 28-day mortality compared to NIV. Larger studies are required to assess the utility of HFNO in moderate-to-severe AHRF.

Incidence and clinical manifestation of iatrogenic opioid withdrawal syndrome in mechanically ventilated patients

Objective The incidence of iatrogenic opioid withdrawal syndrome (IOWS) in mechanically ventilated adults has been questioned in settings driven by analgosedation strategies. This study aimed to describe the incidence, risk factors and clinical impact of IOWS in mechanically ventilated adults. Methods This prospective, observational study was performed between 1 January and 31 August 2018. IOWS was identified based on the presence of at least three signs or symptoms according to the Diagnostic and Statistical Manual 5th edition (DSM-5) criteria after opioid discontinuation or rate reduction. Incidence of IOWS, patient characteristics, opioid administration, and the impact of IOWS on the duration of mechanical ventilator and length of stay in the intensive care unit (ICU) were collected. Results Thirteen out of 55 patients (23.6%) manifested withdrawal symptoms. Two patients in the non-withdrawal group also developed hypertensive urgency after opioid discontinuation. Patients who received rapid once-daily weaning, especially rate reduction more than 50 µg as fentanyl equivalent per hour, were associated with IOWS. However, there was no statistically significant difference in ventilator-free days and ICU-free days. Conclusions These findings showed that approximately one-fourth of mechanically ventilated patients who received opioid infusion experienced IOWS. Monitoring for IOWS is recommended especially in patients who received rapid weaning rate of opioids. Future studies to develop IOWS assessment tools with the change of hemodynamic parameters should be performed. Trial registration This trial was registered in ClinicalTrials.gov: identifier NCT03374722, date of registration 15 December 2018.

A Randomized Trial of Mycobacterium w in Severe Presumed Gram-Negative Sepsis

Mycobacterium w (Mw), an immunomodulator, has been shown to resolve early organ failure in severe sepsis. Does Mw improve survival in patients with severe presumed gram-negative sepsis? This was a randomized, double-blind, placebo-controlled, parallel-group study conducted in ICUs of five tertiary care centers in India. We included consecutive patients (age≥ 18 years) with presumed gram-negative sepsis in the study within 48h of the first organ dysfunction. Patients in the treatment arm received 0.3mL/d of Mw intradermally for 3 consecutive days, whereas the control arm received matching placebo. The primary outcome was 28-day all-cause mortality. The secondary outcomes were ventilator-free days, days receiving vasopressor therapy, ICU and hospital length of stay, nosocomial infection rate, antibiotic use duration, and delta Sequential Organ Failure Assessment (SOFA) score. We included 202 patients with severe sepsis (101 Mw, 101 placebo). The use of Mw significantly reduced the mortality (9/101 vs20/101; estimate difference, 0.11 [95%CI, 0.01-0.21]; P= .04). We found no difference in ventilator-free days, days receiving vasopressor drugs, ICU length of stay, and the hospital length of stay. The time to mortality (median, 13days vs8.5days) was significantly longer in the Mw than in the placebo arm. The delta SOFA score, rate of nosocomial infections, and antibiotic use duration were similar in the two arms. We found Mw to reduce significantly the odds (OR, 0.37 [95%CI, 0.15-0.9]) of mortality after adjusting for culture-positive sepsis, baseline SOFA score, age, and sex. The use of Mw was associated with a significant reduction in mortality in patients with severe presumed gram-negative sepsis. Further studies are required to confirm our findings. ClinicalTrials.gov; No.: NCT02330432; URL: www.clinicaltrials.gov.

Implementation of an Analgesia-Sedation Protocol Is Associated With Reduction in Midazolam Usage in the PICU.

Examine the association of a revised analgesia-sedation protocol with midazolam usage in the PICU. A single-center nonrandomized before-after study. PICU at a quaternary pediatric hospital (Boston Children's Hospital, Boston, MA). Children admitted to the PICU who were mechanically ventilated for greater than 24 hours. The preimplementation cohort included 190 eligible patients admitted between July 29, 2017, and February 28, 2018, and the postimplementation cohort included 144 patients admitted between July 29, 2019, and February 28, 2020. Implementation of a revised analgesia-sedation protocol. Our primary outcome, total dose of IV midazolam administered in mechanically ventilated patients up to day 14 of ventilation, decreased by 72% (95% CI [61-80%]; p < 0.001) in the postimplementation cohort. Dexmedetomidine usage increased 230% (95% CI [145-344%]) in the postimplementation cohort. Opioid usage, our balancing metric, was not significantly different between the two cohorts. There were no significant differences in ventilator-free days, PICU length of stay, rate of unplanned extubations, failed extubations, cardiorespiratory arrest events, and 24-hour readmissions to the PICU. We successfully implemented an analgesia-sedation protocol that primarily uses dexmedetomidine and intermittent opioids, and it was associated with significant decrease in overall midazolam usage in mechanically ventilated patients in the PICU. The intervention was not associated with changes in opioid usage or prevalence of adverse events.

9 Impact of Methadone Initiation in Intubated Burn Patients: A Retrospective Review

Abstract Introduction Methadone can be used to wean opiates and reduce length of mechanical ventilation (MV) in critical care and burn patients. The objective of this study was to assess the impact of methadone use on ventilator-free days and clinical outcomes in burned patients requiring MV. Methods This was a retrospective study of adult patients admitted to a burn center for initial management of burn injuries who required MV for at least 48 hours between September 2013 and November 2019. Patients were excluded from the study if they had prior methadone use, total body surface area (TBSA) of less than 5%, or expired within the first 28 days of admission. The primary endpoint was the difference in ventilator-free days among those who received methadone compared to those who did not. Secondary endpoints include length of stay, mortality, sedative agent and average daily dose, analgesic agent and average daily dose, and incidence of delirium. Baseline demographics were compared using descriptive statistics. Nominal data was compared using Chi-square test. Continuous data was analyzed using student’s t-test or Mann-Whitney U test, as appropriate. Multivariate regression was used to identify variables for possible association with MV duration. Results A total of 83 patients were included in the study; 52 received methadone and 31 were controls. Patients were generally well-matched between groups, however patients receiving methadone were younger (45.3 vs 56.2 years, p = 0.002) and had a larger TBSA (30.4 vs 19.1%, p = 0.001). Patients who received methadone had fewer ventilator free days of the first 28 (9.5 vs 15.0 days, p = 0.009) and a longer ICU stay (57.2 vs 35.8 days, p = 0.025). There was no difference between groups in terms of mortality, reintubations, and incidence of delirium. Patients who received methadone had longer duration of analgesia (20.7 vs 12.0 days, p = 0.011) and sedation (19.0 vs 12.4 days, p = 0.026) while on MV. Conclusions This study found that methadone use contributed to fewer ventilator-free days and longer ICU stays, which was unexpected but worth discussing. There are several limitations to this study. This study occurred during a time period in which the pain management and sedation strategies of this burn unit were evolving, and strategies may not have been consistent between providers. The study included a small sample size and baseline demographics demonstrated significant differences in age and TBSA between the two groups. Additionally, pain scores were not collected as part of this study, which would have provided better insight into the effectiveness of pain management. The use of methadone as an adjunct for pain control remains undetermined.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

P0344 / #1483: EPIDEMIOLOGY OF BLEEDING IN CRITICALLY ILL CHILDREN FOLLOWING CARDIOPULMONARY BYPASS

Aims & Objectives: To describe the epidemiology of bleeding in critically-ill children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: We conducted a retrospective cohort study of critically ill l children 1 month to 18 years of age who underwent cardiac surgery with CPB and admitted to New York-Presbyterian Hospital from 2011-2017. Children were excluded if they required ECMO, died within 6 hours of admission or had a known pre-existing bleeding disorder. Severe bleeding was defined by the Bleeding Assessment Scale in Critically Ill Children (BASIC). Intra-operative data, post-operative blood loss, post-operative medical management and outcome data were collected. Results: 137 patients were enrolled. Sixty-four percent (87/137) were male with median (IQR) age of 22 (5-80) months. Majority of surgeries were RACHS2 (51%, 70/137) or RACHS3 (31%, 43/137). Seven percent (10/137) experienced severe bleeding post-operatively. No differences existed between those with severe bleeding and those without with respect to gender (p=.260), RACHS score (p=0.178), age (p=0.336) or weight (p=0.336). Those with severe bleeding received more platelets (p=0.045), plasma (p=0.034) and cryoprecipitate intra-operatively, but not more RBCs (p=0.096). Patients with severe bleeding had significantly longer times on CPB (p=0.018) and cross-clamped (p=0.002). Ninety percent of those with severe bleeding received blood products post-operatively and many received multiple products. Those with severe bleeding had significantly less PICU-free days (p=0.043) but no difference in ventilator-free days (p=0.095). Conclusions: Seven percent of children who undergo cardiac surgery with CPB had a severe bleeding event post-operatively. These children received more blood products intra-operatively and experienced worse clinical outcomes.

Interleukin-6 Receptor Antagonists for Severe Coronavirus Disease 2019: A Meta-Analysis of Reconstructed Individual Participant Data from Randomised Controlled Trials

Background: Current evidence from randomised controlled trials (RCTs) and systematic reviews on the use of interleukin-6 receptor (IL-6R) antagonists among patients with severe coronavirus disease 2019 (COVID-19) have yielded equivocal results. We conducted a meta-analysis of reconstructed individual participant data (IPD) from RCTs, in order to test the hypothesis that IL-6R antagonists lower mortality in severe COVID-19. Methods: We searched PubMed, Embase, Cochrane, Scopus and medRXiv from 1st December 2019 to 15th April 2021 for RCTs reporting on IL-6R antagonists in patients with severe COVID-19. Survival of individual patients was reconstructed from published Kaplan-Meier curves using a plot digitiser. Weibull mixture “cure” survival models were fitted to compare the overall survival and the “cured” fractions of the IL-6R antagonist and control arms. As a sensitivity analysis, we stratified our analysis according to the type and maximum dose of the IL-6R antagonist, and pooled the aggregate odds ratio (OR) for a cure from COVID-19. Secondary outcomes were analysed using a conventional two-stage meta-analysis, and include the pooled relative risk (RR) for secondary infections, and the pooled mean difference in ventilator-free days. The risk of bias was assessed using the Cochrane Risk-of-Bias Tool for RCTs, and overall certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Findings: 9 RCTs (6831 patients) reported on survival outcomes in COVID-19, of which data from 6 RCTs (6278 patients) was used for the reconstructed IPD meta-analysis. The fractions of “cured” patients who survived were estimated to be 74·0% and 67·9% in the IL-6R antagonist and control arms respectively, which corresponds to an absolute percentage increase in the fraction of COVID-19 survivors of +6·7% (95%-CI: 4·3% to 9·4%, pInterpretation: IL-6R antagonists increase the chances of survival among patients with severe COVID-19 without the increased risk of secondary infections.Funding Statement: There was no funding source for this study.Declaration of Interests: All authors declare no competing interests.

Effect of a Lower vs Higher Positive End-Expiratory Pressure Strategy on Ventilator-Free Days in ICU Patients Without ARDS

It is uncertain whether invasive ventilation can use lower positive end-expiratory pressure (PEEP) in critically ill patients without acute respiratory distress syndrome (ARDS). To determine whether a lower PEEP strategy is noninferior to a higher PEEP strategy regarding duration of mechanical ventilation at 28 days. Noninferiority randomized clinical trial conducted from October 26, 2017, through December 17, 2019, in 8 intensive care units (ICUs) in the Netherlands among 980 patients without ARDS expected not to be extubated within 24 hours after start of ventilation. Final follow-up was conducted in March 2020. Participants were randomized to receive invasive ventilation using either lower PEEP, consisting of the lowest PEEP level between 0 and 5 cm H2O (n = 476), or higher PEEP, consisting of a PEEP level of 8 cm H2O (n = 493). The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for the difference in ventilator-free days at day 28 of -10%. Secondary outcomes included ICU and hospital lengths of stay; ICU, hospital, and 28- and 90-day mortality; development of ARDS, pneumonia, pneumothorax, severe atelectasis, severe hypoxemia, or need for rescue therapies for hypoxemia; and days with use of vasopressors or sedation. Among 980 patients who were randomized, 969 (99%) completed the trial (median age, 66 [interquartile range {IQR}, 56-74] years; 246 [36%] women). At day 28, 476 patients in the lower PEEP group had a median of 18 ventilator-free days (IQR, 0-27 days) and 493 patients in the higher PEEP group had a median of 17 ventilator-free days (IQR, 0-27 days) (mean ratio, 1.04; 95% CI, 0.95-∞; P = .007 for noninferiority), and the lower boundary of the 95% CI was within the noninferiority margin. Occurrence of severe hypoxemia was 20.6% vs 17.6% (risk ratio, 1.17; 95% CI, 0.90-1.51; P = .99) and need for rescue strategy was 19.7% vs 14.6% (risk ratio, 1.35; 95% CI, 1.02-1.79; adjusted P = .54) in patients in the lower and higher PEEP groups, respectively. Mortality at 28 days was 38.4% vs 42.0% (hazard ratio, 0.89; 95% CI, 0.73-1.09; P = .99) in patients in the lower and higher PEEP groups, respectively. There were no statistically significant differences in other secondary outcomes. Among patients in the ICU without ARDS who were expected not to be extubated within 24 hours, a lower PEEP strategy was noninferior to a higher PEEP strategy with regard to the number of ventilator-free days at day 28. These findings support the use of lower PEEP in patients without ARDS. ClinicalTrials.gov Identifier: NCT03167580.