Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial.

BACKGROUND: The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. METHODS: In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8-1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data. CONCLUSION: Ethics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04475666 . Registered on July 17, 2020.

Early administration of umbilical cord blood cells following brief high tidal volume ventilation in preterm sheep: a cautionary tale.

BACKGROUND: Umbilical cord blood (UCB) cells are a promising treatment for preterm brain injury. Access to allogeneic sources of UCB cells offer the potential for early administration to optimise their therapeutic capacities. As preterm infants often require ventilatory support, which can contribute to preterm brain injury, we investigated the efficacy of early UCB cell administration following ventilation to reduce white matter inflammation and injury. METHODS: Preterm fetal sheep (0.85 gestation) were randomly allocated to no ventilation (SHAM; n = 5) or 15 min ex utero high tidal volume ventilation. One hour following ventilation, fetuses were randomly allocated to i.v. administration of saline (VENT; n = 7) or allogeneic term-derived UCB cells (24.5 ± 5.0 million cells/kg; VENT + UCB; n = 7). Twenty-four hours after ventilation, lambs were delivered for magnetic resonance imaging and post-mortem brain tissue collected. Arterial plasma was collected throughout the experiment for cytokine analyses. To further investigate the results from the in vivo study, mononuclear cells (MNCs) isolated from human UCB were subjected to in vitro cytokine-spiked culture medium (TNFα and/or IFNγ; 10 ng/mL; n = 3/group) for 16 h then supernatant and cells collected for protein and mRNA assessments respectively. RESULTS: In VENT + UCB lambs, systemic IFNγ levels increased and by 24 h, there was white matter neuroglial activation, vascular damage, reduced oligodendrocytes, and increased average, radial and mean diffusivity compared to VENT and SHAM. No evidence of white matter inflammation or injury was present in VENT lambs, except for mRNA downregulation of OCLN and CLDN1 compared to SHAM. In vitro, MNCs subjected to TNFα and/or IFNγ displayed both pro- and anti-inflammatory characteristics indicated by changes in cytokine (IL-18 & IL-10) and growth factor (BDNF & VEGF) gene and protein expression compared to controls. CONCLUSIONS: UCB cells administered early after brief high tidal volume ventilation in preterm fetal sheep causes white matter injury, and the mechanisms underlying these changes are likely dysregulated responses of the UCB cells to the degree of injury/inflammation already present. If immunomodulatory therapies such as UCB cells are to become a therapeutic strategy for preterm brain injury, especially after ventilation, our study suggests that the inflammatory state of the preterm infant should be considered when timing UCB cells administration.

Perioperative Challenges and Outcome After Surgical Correction of Post-myocardial Infarction Ventricular Septal Rupture: A Retrospective Single Center Study.

BACKGROUND: Ventricular septal rupture (VSR) is a rare but grave complication of acute myocardial infarction (AMI). It is a mechanical complication of myocardial infarction where patients may present either in a compensated state or in cardiogenic shock. The aim of the study is to determine the in-hospital mortality. The study also aims to identify the predictors of outcomes (in-hospital mortality, vasoactive inotrope score (VIS), duration of ICU stay and mechanical ventilation in the postoperative period) and compare the clinical and surgical parameters between survivors and non-survivors. METHODS: This is a retrospective study. The data of 90 patients was collected from the medical records and the data comprising of 13 patients who underwent VSR closure by single patch technique, or septal occluder, and those who expired before receiving the treatment, was excluded. The data of 77 patients diagnosed with post-AMI VSR and who underwent surgical closure of VSR by double patch technique was included in this study. Clinical findings and echocardiography parameters were recorded from the perioperative period. The statistical software used was SPSS version 27. The primary outcome was determining the in-hospital mortality. The secondary outcome was identifying the clinical parameters that are significantly more in the non-survivors, and the factors predicting the in-hopsital mortality and morbidity (increased duration of ICU stay, and of mechanical ventilation, postoperative requirement of high doses of vasopressors and inotropes). Subgroup analysis was done to identify the relation of various clinical parameters with the postoperative complications. The factors predicting the in-hospital mortality were illustrated by a forest plot. RESULTS: The mean age of the patients was 60.35 (±9.9) years, 56 (72.7%) were males, and 21 (27.3%) were females. Requirement of mechanical ventilation preoperatively (OR 3.92 [CI 2.91-6.96]), cardiogenic shock at presentation (OR 4 [CI 2.33 - 6.85]), requirement of IABP (OR 2.05 [CI 1.38-3.94]), were predictors of mortality. The apical location of VSR had been favorable for survival. The EUROScore II at presentation correlated with the postoperative VIS (level of significance [LS] 0.0011, R 0.36. The in-hospital mortality in this study was 33.76%. CONCLUSION: The in-hospital mortality of VSR is 33.76%. Cardiogenic shock at presentation, non-apical site of VSR, preoperative requirement of mechanical ventilation, high VIS preoperatively, perioperative utilization of IABP, prolonged CPB time, postoperative duration of mechanical ventilation, and high postoperative VIS were the factors associated with increased odds of in-hospital mortality.

Comparison of limited driving pressure ventilation and low tidal volume strategies in adults with acute respiratory failure on mechanical ventilation: a randomized controlled trial.

BACKGROUND: Ventilator-induced lung injury (VILI) presents a grave risk to acute respiratory failure patients undergoing mechanical ventilation. Low tidal volume (LTV) ventilation has been advocated as a protective strategy against VILI. However, the effectiveness of limited driving pressure (plateau pressure minus positive end-expiratory pressure) remains unclear. OBJECTIVES: This study evaluated the efficacy of LTV against limited driving pressure in preventing VILI in adults with respiratory failure. DESIGN: A single-centre, prospective, open-labelled, randomized controlled trial. METHODS: This study was executed in medical intensive care units at Siriraj Hospital, Mahidol University, Bangkok, Thailand. We enrolled acute respiratory failure patients undergoing intubation and mechanical ventilation. They were randomized in a 1:1 allocation to limited driving pressure (LDP; ⩽15 cmH2O) or LTV (⩽8 mL/kg of predicted body weight). The primary outcome was the acute lung injury (ALI) score 7 days post-enrolment. RESULTS: From July 2019 to December 2020, 126 patients participated, with 63 each in the LDP and LTV groups. The cohorts had the mean (standard deviation) ages of 60.5 (17.6) and 60.9 (17.9) years, respectively, and they exhibited comparable baseline characteristics. The primary reasons for intubation were acute hypoxic respiratory failure (LDP 49.2%, LTV 63.5%) and shock-related respiratory failure (LDP 39.7%, LTV 30.2%). No significant difference emerged in the primary outcome: the median (interquartile range) ALI scores for LDP and LTV were 1.75 (1.00-2.67) and 1.75 (1.25-2.25), respectively (p = 0.713). Twenty-eight-day mortality rates were comparable: LDP 34.9% (22/63), LTV 31.7% (20/63), relative risk (RR) 1.08, 95% confidence interval (CI) 0.74-1.57, p = 0.705. Incidences of newly developed acute respiratory distress syndrome also aligned: LDP 14.3% (9/63), LTV 20.6% (13/63), RR 0.81, 95% CI 0.55-1.22, p = 0.348. CONCLUSIONS: In adults with acute respiratory failure, the efficacy of LDP and LTV in averting lung injury 7 days post-mechanical ventilation was indistinguishable. CLINICAL TRIAL REGISTRATION: The study was registered with the ClinicalTrials.gov database (identification number NCT04035915).

Limited breathing pressure or low amount of air given to the lung; which one is better for adults who need breathing help by ventilator machineWe conducted this research at Siriraj Hospital in Bangkok, Thailand, aiming to compare two ways of helping patients with breathing problems. We studied 126 patients who were randomly put into two groups. One group received a method where the pressure during breathing was limited (limited driving pressure: LDP), and the other group got a method where the amount of air given to the lungs was kept low (low tidal volume: LTV). We checked how bad the lung injury was at seven days later. The results showed that there was no difference between the two methods. Both ways of helping patients breathe had similar outcomes, and neither was significantly better than the other in preventing lung problems. The study suggests that both approaches work about the same for patients who need help with breathing using a machine.

Respiratory Support Practices for Bronchiolitis in the Pediatric Intensive Care Unit.

Importance: Admissions to the pediatric intensive care unit (PICU) due to bronchiolitis are increasing. Whether this increase is associated with changes in noninvasive respiratory support practices is unknown. Objective: To assess whether the number of PICU admissions for bronchiolitis between 2013 and 2022 was associated with changes in the use of high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) and to identify factors associated with HFNC and NIV success and failure. Design, Setting, and Participants: This cross-sectional study examined encounter data from the Virtual Pediatric Systems database on annual PICU admissions for bronchiolitis and ventilation practices among patients aged younger than 2 years admitted to 27 PICUs between January 1, 2013, and December 31, 2022. Use of HFNC and NIV was defined as successful if patients were weaned to less invasive support (room air or low-flow nasal cannula for HFNC; room air, low-flow nasal cannula, or HFNC for NIV). Main Outcomes and Measures: The main outcome was the number of PICU admissions for bronchiolitis requiring the use of HFNC, NIV, or IMV. Linear regression was used to analyze the association between admission year and absolute numbers of encounters stratified by the maximum level of respiratory support required. Multivariable logistic regression was used to analyze factors associated with HFNC and NIV success and failure (defined as not meeting the criteria for success). Results: Included in the analysis were 33 816 encounters for patients with bronchiolitis (20 186 males [59.7%]; 1910 patients [5.6%] aged ≤28 days and 31 906 patients [94.4%] aged 29 days to <2 years) treated at 27 PICUs from 2013 to 2022. A total of 7615 of 15 518 patients (49.1%) had respiratory syncytial virus infection and 1522 of 33 816 (4.5%) had preexisting cardiac disease. Admissions to the PICU increased by 350 (95% CI, 170-531) encounters annually. When data were grouped by the maximum level of respiratory support required, HFNC use increased by 242 (95% CI, 139-345) encounters per year and NIV use increased by 126 (95% CI, 64-189) encounters per year. The use of IMV did not significantly change (10 [95% CI, -11 to 31] encounters per year). In all, 22 381 patients (81.8%) were successfully weaned from HFNC to low-flow oxygen therapy or room air, 431 (1.6%) were restarted on HFNC, 3057 (11.2%) were escalated to NIV, and 1476 (5.4%) were escalated to IMV or extracorporeal membrane oxygenation (ECMO). Successful use of HFNC increased from 820 of 1027 encounters (79.8%) in 2013 to 3693 of 4399 encounters (84.0%) in 2022 (P = .002). In all, 8476 patients (81.5%) were successfully weaned from NIV, 787 (7.6%) were restarted on NIV, and 1135 (10.9%) were escalated to IMV or ECMO. Success with NIV increased from 224 of 306 encounters (73.2%) in 2013 to 1335 of 1589 encounters (84.0%) in 2022 (P < .001). In multivariable logistic regression, lower weight, higher Pediatric Risk of Mortality III score, cardiac disease, and PICU admission from outside the emergency department were associated with greater odds of HFNC and NIV failure. Conclusions and Relevance: Findings of this cross-sectional study of patients aged younger than 2 years admitted for bronchiolitis suggest there was a 3-fold increase in PICU admissions between 2013 and 2022 associated with a 4.8-fold increase in HFNC use and a 5.8-fold increase in NIV use. Further research is needed to standardize approaches to HFNC and NIV support in bronchiolitis to reduce resource strain.

Effect of immediate initiation of invasive ventilation on mortality in acute hypoxemic respiratory failure: a target trial emulation.

PURPOSE: Invasive ventilation is a fundamental treatment in intensive care but its precise timing is difficult to determine. This study aims at assessing the effect of initiating invasive ventilation versus waiting, in patients with hypoxemic respiratory failure without immediate reason for intubation on one-year mortality. METHODS: Emulation of a target trial to estimate the benefit of immediately initiating invasive ventilation in hypoxemic respiratory failure, versus waiting, among patients within the first 48-h of hypoxemia. The eligible population included non-intubated patients with SpO2/FiO2 ≤ 200 and SpO2 ≤ 97%. The target trial was emulated using a single-center database (MIMIC-IV) which contains granular information about clinical status. The hourly probability to receive mechanical ventilation was continuously estimated. The hazard ratios for the primary outcome, one-year mortality, and the secondary outcome, 30-day mortality, were estimated using weighted Cox models with stabilized inverse probability weights used to adjust for measured confounding. RESULTS: 2996 Patients fulfilled the inclusion criteria of whom 792 were intubated within 48 h. Among the non-invasive support devices, the use of oxygen through facemask was the most common (75%). Compared to patients with the same probability of intubation but who were not intubated, intubation decreased the hazard of dying for the first year after ICU admission HR 0.81 (95% CI 0.68-0.96, p = 0.018). Intubation was associated with a 30-day mortality HR of 0.80 (95% CI 0.64-0.99, p = 0.046). CONCLUSION: The initiation of mechanical ventilation in patients with acute hypoxemic respiratory failure reduced the hazard of dying in this emulation of a target trial.

Postexchange transfusion-related acute lung injury in a term neonate.

We report a successful case where a newborn with transfusion-related acute lung injury following an exchange transfusion was effectively treated using conservative methods, eliminating the need for surfactant therapy. Very few instances of this complication have been documented globally. A low birth weight, small for gestational age, term neonate, diagnosed with hyperbilirubinaemia due to Rh incompatibility, experienced sudden respiratory distress in the form of severe retractions, tachypnoea and cyanosis 3 hours after the procedure. Neonate required mechanical ventilation on the grounds of mixed acidosis and diffuse alveolar infiltrates on the chest radiograph. The medical team suspected and treated the baby for transfusion-related acute lung injury through conservative measures. Transfusion-related acute lung injury, an acute life-threatening complication of blood component transfusion, can exhibit symptoms in neonates that are frequently misinterpreted as sepsis. The baby was discharged in good health after successful management after 19 days.

Effect of cortisol and glycosylated-hemoglobin levels on mortality in intensive care unit.

OBJECTIVES: To research the effects of blood cortisol and hemoglobinA1c (HBA1C) levels on mortality in patients admitted to the intensive care unit (ICU) and whether these factors could be used as reliable indicators for mortality risk assessment in these patients. METHODS: After receiving approval from the ethics committee, 79 patients admitted to ICU were included in the study. From patient files, we collected data on demographics (age, gender), presence of diabetes mellitus, and levels of cortisol, HbA1C, glucose, and lactate measured during hospitalization, along with acute physiology and chronic health evaluation (APACHE) II scores calculated within the first 24 hours. In our study, we planned to investigate the relationship between patients' cortisol and HbA1C levels and mortality. RESULTS: A total of 79 patients were included in the study. The mortality rate of the patients included in the study was 65.8%. In the model established with all variables, only cortisol level (p=0.017) and APACHE II score (p=0.005) were defined to affect mortality. CONCLUSION: Cortisol levels at the time of admission to the ICU were found to affect mortality and can be considered a predictive factor, while HBA1C levels showed no such effect. Our findings indicate that neither cortisol nor HBA1C levels had an impact on the duration of mechanical ventilation or length of stay in the ICU.

Management of severe tetanus in Afghanistan: lessons from the field.

INTRODUCTION: Tetanus is a rather rare disease in the Western countries thanks to widespread vaccination programs and the availability of prophylactics for patients with tetanus-prone injuries. The few cases that do occur are promptly managed in intensive care units (ICUs). However, tetanus is not so rare in developing countries, where access to a suitable level of care is limited. An unstable political situation can be a significant factor influencing patient outcomes. CASE REPORT: A ten-year-old boy presented at the EMERGENCY hospital in Lashkar-Gah (southern Afghanistan) with generalized tetanus after falling off his bicycle. In response to his rapidly deteriorating general conditions - respiratory failure and hemodynamic instability - the patient was urgently transferred by ambulance to the ICU at the EMERGENCY hospital in Kabul (northern Afghanistan). The patient was placed on mechanical ventilation while receiving intravenous sedation and pharmacologic paralysis for almost four weeks. A prolonged infusion of a high dose of magnesium sulphate and labetalol was also given to counteract autonomic dysfunction. Multiple complications related to the long stay in the ICU were observed and promptly addressed. During this period, several mass casualties took place in Kabul, which stretched the hospital's surge capacity. The patient was discharged and accompanied back to Lashkar-Gah three months after his admission to the hospital. CONCLUSION: This case report shows some of the many difficulties that arise when managing a patient with severe tetanus in a war zone where resources are limited.

First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study.

BACKGROUND: Inhaled nitric oxide (iNO) has a beneficial effect on hypoxemic respiratory failure. The increased use of concurrent iNO and milrinone was observed. We aimed to report the trends of iNO use in the past 15 years in Taiwan and compare the first-year outcomes of combining iNO and milrinone to the iNO alone in very low birth weight preterm (VLBWP) infants under mechanical ventilation. METHODS: This nationwide cohort study enrolled preterm singleton infants with birth weight <1500g treated with iNO from 2004 to 2019. Infants were divided into two groups, with a combination of intravenous milrinone (Group 2, n = 166) and without milrinone (Group 1, n = 591). After propensity score matching (PSM), each group's sample size is 124. The primary outcomes were all-cause mortality and the respiratory condition, including ventilator use and duration. The secondary outcomes were preterm morbidities within one year after birth. RESULTS: After PSM, more infants in Group 2 needed inotropes. The mortality rate was significantly higher in Group 2 than in Group 1 from one month after birth till 1 year of age (55.1% vs. 13.5%) with the adjusted hazard ratio of 4.25 (95%CI = 2.42-7.47, p <0.001). For infants who died before 36 weeks of postmenstrual age (PMA), Group 2 had longer hospital stays compared to Group 1. For infants who survived after 36 weeks PMA, the incidence of moderate and severe bronchopulmonary dysplasia (BPD) was significantly higher in Group 2 than in Group 1. For infants who survived until one year of age, the incidence of pneumonia was significantly higher in Group 2 (28.30%) compared to Group 1 (12.62%) (p = 0.0153). CONCLUSION: Combined treatment of iNO and milrinone is increasingly applied in VLBWP infants in Taiwan. This retrospective study did not support the benefits of combining iNO and milrinone on one-year survival and BPD prevention. A future prospective study is warranted.

Clinical and immunological comparison of COVID-19 disease between critical and non-critical courses: a systematic review and meta-analysis.

Introduction: Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which appeared in 2019, has been classified as critical and non-critical according to clinical signs and symptoms. Critical patients require mechanical ventilation and intensive care unit (ICU) admission, whereas non-critical patients require neither mechanical ventilation nor ICU admission. Several factors have been recently identified as effective factors, including blood cell count, enzymes, blood markers, and underlying diseases. By comparing blood markers, comorbidities, co-infections, and their relationship with mortality, we sought to determine differences between critical and non-critical groups. Method: We used Scopus, PubMed, and Web of Science databases for our systematic search. Inclusion criteria include any report describing the clinical course of COVID-19 patients and showing the association of the COVID-19 clinical courses with blood cells, blood markers, and bacterial co-infection changes. Twenty-one publications were eligible for full-text examination between 2019 to 2021. Result: The standard difference in WBC, lymphocyte, and platelet between the two clinical groups was 0.538, -0.670, and -0.421, respectively. Also, the standard difference between the two clinical groups of CRP, ALT, and AST was 0.482, 0.402, and 0.463, respectively. The odds ratios for hypertension and diabetes were significantly different between the two groups. The prevalence of co-infection also in the critical group is higher. Conclusion: In conclusion, our data suggest that critical patients suffer from a suppressed immune system, and the inflammation level, the risk of organ damage, and co-infections are significantly high in the critical group and suggests the use of bacteriostatic instead of bactericides to treat co-infections.

Dexmedetomidine for analgesia and sedation in newborn infants receiving mechanical ventilation.

BACKGROUND: Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are drugs currently used for analgesia and sedation in newborn infants. Dexmedetomidine is increasingly being used in children and infants despite not being licenced for analgesia in this group. OBJECTIVES: To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety. AUTHORS' CONCLUSIONS: Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.

Prone positioning does not improve outcomes of intubated patients with pneumocystis pneumonia and moderate-severe acute respiratory distress syndrome: a single-center, retrospective, observational, cohort study.

BACKGROUND: Pneumocystis pneumonia is an uncommon precipitant of acute respiratory distress syndrome and is associated with high mortality. Prone positioning ventilation has been proven to reduce mortality in patients with moderate-severe acute respiratory distress syndrome. We investigated the effect of prone positioning on oxygenation and mortality in intubated patients with pneumocystis pneumonia comorbid with moderate-severe acute respiratory distress syndrome. METHODS: In this single-center, retrospective, observational, cohort study, eligible patients were enrolled at West China Hospital of Sichuan University from January 1, 2017, to December 31, 2021. Data on demographics, clinical features, ventilation parameters, arterial blood gas, and outcomes were collected. Patients were assigned to the prone cohort or supine cohort according to whether they received prone positioning ventilation. The main outcome was 28-day mortality. FINDINGS: A total of 79 patients were included in the study. Sixty-three patients were enrolled in the prone cohort, and 16 patients were enrolled in the supine cohort. The 28-day mortality was 61.9% in the prone cohort and 68.8% in the supine cohort (P = 0.26), and 90-day mortality was 66.7% in the prone cohort and 68.8% in the supine cohort (P = 0.55). Patients in the supine cohort had fewer invasive mechanical ventilation days and more ventilator-free days. The incidence of complications was higher in the prone cohort than in the supine cohort. CONCLUSIONS: In patients with pneumocystis pneumonia and moderate-severe acute respiratory distress syndrome, prone positioning did not decrease 28-day or 90-day mortality. Trial registration ClinicalTrials.gov number, ChiCTR2200063889. Registered on 20 September 2022, https://www.chictr.org.cn/showproj.html?proj=174886 .

Correlation Between Early Serum Myoglobin Levels and the Incidence and Prognosis of Intensive Care Unit-Acquired Weakness (ICU-AW) in Septic Shock Patients: A Comparative Study.

Intensive Care Unit-acquired weakness (ICU-AW) is a common complication that significantly impedes patient recovery. In the study, we investigated the correlation between early serum myoglobin levels in patients with septic shock due to pneumonia, and the incidence of ICU-AW, duration of mechanical ventilation, and prognosis. Patients were classified based on the development of ICU-AW within the first 10 days of ICU admission. We measured serum myoglobin levels upon ICU entry, and analyzed demographic data, APACHE II scores, use of mechanical ventilation, and clinical outcomes, including mortality and duration of mechanical ventilation. The results indicated significantly elevated serum myoglobin levels in the ICU-AW group, correlated with prolonged mechanical ventilation and increased mortality. ROC analysis revealed myoglobin as a promising biomarker for predicting ICU-AW, with an area under the curve of 0.843 (95% CI: 0.819~0.867), demonstrating a sensitivity of 76.00% and specificity of 82.30%. These findings underscored serum myoglobin as a predictive biomarker for early ICU-AW in septic shock patients, highlighting its potential to guide clinical decision-making.

Driving pressure, as opposed to tidal volume based on predicted body weight, is associated with mortality: results from a prospective cohort of COVID-19 acute respiratory distress syndrome patients.

OBJECTIVE: To evaluate the association between driving pressure and tidal volume based on predicted body weight and mortality in a cohort of patients with acute respiratory distress syndrome caused by COVID-19. METHODS: This was a prospective, observational study that included patients with acute respiratory distress syndrome due to COVID-19 admitted to two intensive care units. We performed multivariable analyses to determine whether driving pressure and tidal volume/kg predicted body weight on the first day of mechanical ventilation, as independent variables, are associated with hospital mortality. RESULTS: We included 231 patients. The mean age was 64 (53 - 74) years, and the mean Simplified Acute and Physiology Score 3 score was 45 (39 - 54). The hospital mortality rate was 51.9%. Driving pressure was independently associated with hospital mortality (odds ratio 1.21, 95%CI 1.04 - 1.41 for each cm H2O increase in driving pressure, p = 0.01). Based on a double stratification analysis, we found that for the same level of tidal volume/kg predicted body weight, the risk of hospital death increased with increasing driving pressure. However, changes in tidal volume/kg predicted body weight were not associated with mortality when they did not lead to an increase in driving pressure. CONCLUSION: In patients with acute respiratory distress syndrome caused by COVID-19, exposure to higher driving pressure, as opposed to higher tidal volume/kg predicted body weight, is associated with greater mortality. These results suggest that driving pressure might be a primary target for lung-protective mechanical ventilation in these patients.

Risk factors and clinical prediction models for prolonged mechanical ventilation after heart valve surgery.

OBJECTIVES: Prolonged mechanical ventilation (PMV) is a common complication following cardiac surgery linked to unfavorable patient prognosis and increased mortality. This study aimed to search for the factors associated with the occurrence of PMV after valve surgery and to develop a risk prediction model. METHODS: The patient cohort was divided into two groups based on the presence or absence of PMV post-surgery. Comprehensive preoperative and intraoperative clinical data were collected. Univariate and multivariate logistic regression analyses were employed to identify risk factors contributing to the incidence of PMV. Based on the logistic regression results, a clinical nomogram was developed. RESULTS: The study included 550 patients who underwent valve surgery, among whom 62 (11.27%) developed PMV. Multivariate logistic regression analysis revealed that age (odds ratio [OR] = 1.082, 95% confidence interval [CI] = 1.042-1.125; P < 0.000), current smokers (OR = 1.953, 95% CI = 1.007-3.787; P = 0.047), left atrial internal diameter index (OR = 1.04, 95% CI = 1.002-1.081; P = 0.041), red blood cell count (OR = 0.49, 95% CI = 0.275-0.876; P = 0.016), and aortic clamping time (OR = 1.031, 95% CI = 1.005-1.057; P < 0.017) independently influenced the occurrence of PMV. A nomogram was constructed based on these factors. In addition, a receiver operating characteristic (ROC) curve was plotted, with an area under the curve (AUC) of 0.782 and an accuracy of 0.884. CONCLUSION: Age, current smokers, left atrial diameter index, red blood cell count, and aortic clamping time are independent risk factors for PMV in patients undergoing valve surgery. Furthermore, the nomogram based on these factors demonstrates the potential for predicting the risk of PMV in patients following valve surgery.

Monitoring CO2 kinetics as a marker of cardiopulmonary efficiency.

PURPOSE OF REVIEW: To describe current and near future developments and applications of CO2 kinetics in clinical respiratory and cardiovascular monitoring. RECENT FINDINGS: In the last years, we have witnessed a renewed interest in CO2 kinetics in relation with a better understanding of volumetric capnography and its derived parameters. This together with technological advances and improved measurement systems have expanded the monitoring potential of CO2 kinetics including breath by breath continuous end-expiratory lung volume and continuous noninvasive cardiac output. Dead space has slowly been gaining relevance in clinical monitoring and prognostic evaluation. Easy to measure dead space surrogates such as the ventilatory ratio have demonstrated a strong prognostic value in patients with acute respiratory failure. SUMMARY: The kinetics of carbon dioxide describe many relevant physiological processes. The clinical introduction of new ways of assessing respiratory and circulatory efficiency based on advanced analysis of CO2 kinetics are paving the road to a long-desired goal in clinical monitoring of critically ill patients: the integration of respiratory and circulatory monitoring during mechanical ventilation.