Background:Thyroid hormone alterations are common in critical illness and may reflect disease severity. Their prognostic significance in infarct-related cardiogenic shock remains incompletely defined. Methods:In this prospective cohort study from a cardiogenic shock registry, 41 patients with acute myocardial infarction complicated by cardiogenic shock underwent serial measurements of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) at baseline and 24, 48, 72, and 96 h after percutaneous coronary intervention. Associations between hormone trajectories and in-hospital mortality were assessed using longitudinal and small-sample-robust methods. Results:Thyroid trajectories diverged by outcome. Survivors maintained higher TSH concentrations over time, whereas non-survivors showed progressive suppression. fT3 declined in both groups early after presentation, with a steeper overall decline in non-survivors and outcome separation becoming most apparent later in the observation period. Lower fT3 was associated with greater illness severity and higher mortality risk. fT4 decreased over time in both groups without consistent between-group differences. Conclusions:In conclusion, dynamic alterations in thyroid hormone levels, particularly reductions in fT3, were associated with greater illness severity and adverse outcomes in cardiogenic shock. Serial thyroid function assessment may improve risk stratification in acute cardiovascular critical illness and warrants further evaluation in larger prospective studies.

QuestionDoes individualized perioperative blood pressure management based on preoperative nighttime mean arterial pressure (MAP) improve outcomes in patients undergoing abdominal surgery who are considered at high risk of postoperative complications?FindingsIn this randomized clinical trial that included 1272 participants, the incidence of a composite primary outcome (acute kidney injury, acute myocardial injury, nonfatal cardiac arrest, or death within the first 7 postoperative days) was not significantly different between patients assigned to individualized MAP targets and patients assigned to routine blood pressure management with a MAP target of 65 mm Hg or higher.MeaningThis trial does not support individualizing blood pressure targets based on preoperative nighttime MAP in high-risk patients undergoing abdominal surgery. ImportanceIntraoperative hypotension is associated with organ injury. However, it remains unknown if targeted blood pressure management during surgery can improve clinical outcomes.ObjectiveTo evaluate whether individualized vs routine perioperative blood pressure management during major abdominal surgery improves clinical outcomes in patients considered at high risk of postoperative complications.Design, Setting, and ParticipantsThis randomized single-blind clinical trial enrolled patients 45 years or older undergoing elective major abdominal surgery with general anesthesia expected to last 90 minutes or longer who had at least 1 additional high-risk criterion between February 26, 2023, and April 25, 2024, at 15 German university hospitals. The date of last follow-up was July 25, 2024.InterventionPatients were randomized in a 1:1 ratio to individualized perioperative blood pressure management (with mean arterial pressure [MAP] targets based on preoperative mean nighttime MAP assessed using automated blood pressure monitoring) or routine blood pressure management with a MAP target of 65 mm Hg or higher.Main Outcomes and MeasuresThe primary outcome was the incidence of a composite outcome of acute kidney injury, acute myocardial injury, nonfatal cardiac arrest, or death within the first 7 postoperative days. There were 22 secondary outcomes, including infectious complications within the first 7 postoperative days and a composite outcome of need for kidney replacement therapy, myocardial infarction, nonfatal cardiac arrest, or death within 90 days after surgery.ResultsOf the 1272 patients enrolled, 1142 were randomized (571 patients to each group), and 1134 were included in the primary analysis (median age, 66 years [IQR, 59-73 years]; 34.1% female). The primary outcome occurred in 190 of 567 patients (33.5%) assigned to individualized blood pressure management and 173 of 567 patients (30.5%) assigned to routine blood pressure management (relative risk, 1.10 [95% CI, 0.93-1.30]; P = .31). None of the 22 secondary outcomes were significantly different, including infectious complications within the first 7 postoperative days (90/567 [15.9%] vs 97/567 [17.1%]; P = .63) and a composite outcome of need for kidney replacement therapy, myocardial infarction, nonfatal cardiac arrest, or death within 90 days after surgery (32/566 [5.7%] vs 20/567 [3.5%]; P = .12).Conclusions and RelevanceAmong patients at high risk of postoperative complications undergoing major abdominal surgery, individualized perioperative blood pressure management with MAP targets based on preoperative mean nighttime MAP did not decrease the composite outcome of acute kidney injury, acute myocardial injury, nonfatal cardiac arrest, or death within the first 7 postoperative days compared with routine blood pressure management with a MAP target of 65 mm Hg or higher.Trial RegistrationClinicalTrials.gov Identifier: NCT05416944 This randomized trial evaluates whether individualized (mean arterial pressure [MAP] targets based on preoperative mean nighttime MAP assessed using automated blood pressure monitoring) vs routine perioperative blood pressure management during major abdominal surgery improves clinical outcomes in patients considered at high risk of postoperative complications.

Cardiogenic shock (CS) following myocardial infarction remains highly fatal. The prognostic value of dynamic metabolic markers—particularly glucose and cortisol—remains incompletely understood. In this prospective cohort study, 41 patients with infarction-related CS underwent serial blood sampling over 96 h. Plasma glucose and serum cortisol levels were measured repeatedly. Primary endpoint was in-hospital mortality. Admission glucose levels stratified as < 10, 10–15, and > 15 mmol/L were associated with rising mortality (36.4

Importance:Intraoperative hypotension is associated with organ injury. However, it remains unknown if targeted blood pressure management during surgery can improve clinical outcomes. Objective:To evaluate whether individualized vs routine perioperative blood pressure management during major abdominal surgery improves clinical outcomes in patients considered at high risk of postoperative complications. Design, Setting, and Participants:This randomized single-blind clinical trial enrolled patients 45 years or older undergoing elective major abdominal surgery with general anesthesia expected to last 90 minutes or longer who had at least 1 additional high-risk criterion between February 26, 2023, and April 25, 2024, at 15 German university hospitals. The date of last follow-up was July 25, 2024. Intervention:Patients were randomized in a 1:1 ratio to individualized perioperative blood pressure management (with mean arterial pressure [MAP] targets based on preoperative mean nighttime MAP assessed using automated blood pressure monitoring) or routine blood pressure management with a MAP target of 65 mm Hg or higher. Main Outcomes and Measures:The primary outcome was the incidence of a composite outcome of acute kidney injury, acute myocardial injury, nonfatal cardiac arrest, or death within the first 7 postoperative days. There were 22 secondary outcomes, including infectious complications within the first 7 postoperative days and a composite outcome of need for kidney replacement therapy, myocardial infarction, nonfatal cardiac arrest, or death within 90 days after surgery. Results:Of the 1272 patients enrolled, 1142 were randomized (571 patients to each group), and 1134 were included in the primary analysis (median age, 66 years [IQR, 59-73 years]; 34.1% female). The primary outcome occurred in 190 of 567 patients (33.5%) assigned to individualized blood pressure management and 173 of 567 patients (30.5%) assigned to routine blood pressure management (relative risk, 1.10 [95% CI, 0.93-1.30]; P = .31). None of the 22 secondary outcomes were significantly different, including infectious complications within the first 7 postoperative days (90/567 [15.9%] vs 97/567 [17.1%]; P = .63) and a composite outcome of need for kidney replacement therapy, myocardial infarction, nonfatal cardiac arrest, or death within 90 days after surgery (32/566 [5.7%] vs 20/567 [3.5%]; P = .12). Conclusions and Relevance:Among patients at high risk of postoperative complications undergoing major abdominal surgery, individualized perioperative blood pressure management with MAP targets based on preoperative mean nighttime MAP did not decrease the composite outcome of acute kidney injury, acute myocardial injury, nonfatal cardiac arrest, or death within the first 7 postoperative days compared with routine blood pressure management with a MAP target of 65 mm Hg or higher. Trial Registration:ClinicalTrials.gov Identifier: NCT05416944.

Cardiogenic shock (CS) is a life-threatening complication of acute myocardial infarction (AMI) with high mortality. Hormonal alterations during CS may offer prognostic insights. While growth hormone (GH) dynamics have been studied in heart failure, the role of insulin-like growth factor-1 (IGF-1) in CS remains unclear. IGF-1 exerts cardioprotective effects, including reducing myocardial apoptosis after ischemia-reperfusion injury. This study examines temporal changes in GH and IGF-1 levels in CS and their prognostic value. The Halle-Cardiogenic Shock Registry included 41 AMI patients with CS. GH and IGF-1 levels were measured at admission and on day 1, 2 and 4 post-percutaneous coronary intervention. Differences were analyzed between survivors and non-survivors, as well as by age (<70 vs ≥70 years) and sex. We found that at admission, GH levels (2.86 ± 0.78 μg/L) were within the normal range in 75.6% of patients and showed no significant differences between survivors and non-survivors. IGF-1 levels (76.23 ± 5.67 μg/L) were at the lower end of normal and declined to 66.8 μg/L at 48–72 h (P = 0.14). Non-survivors had a more rapid IGF-1 decline, while survivors maintained stable levels. IGF-1 was higher in younger and male patients, while older and female patients showed a greater decline. We conclude that GH levels remained stable and lacked prognostic value, while IGF-1 decline correlated with disease severity and possible hepatic dysfunction. IGF-1 may serve as a biomarker for risk stratification and a therapeutic target for metabolic regulation and recovery in CS, warranting further investigation.

AbstractObjectiveThe course of sedation during drug‐induced sleep endoscopy (DISE) depends on the application pattern of the sedative drug. The depth of sedation should imitate light and deep sleep as well. Moreover, there should be as many breathing cycles as possible available for observation during light and deep sedation. The aim of the study was to evaluate different rates of propofol application with respect to the achieved depth and length of the course of sedation.MethodsSixty‐three consecutive patients with obstructive sleep apnea and/or snoring undergoing DISE were randomly sedated by propofol perfusion at seven different application patterns: 14, 16, 18, 19, 20, 22 mg/kg/h (0.233, 0.267, 0.3, 0.317, 0.333, 0.367 mg/kg/min) per perfusor and individual bolus application 10 mg each. Sedation depth was monitored by BiSpectral Index™ (BIS). The influence of baseline parameters and the courses of sedation were analyzed.ResultsThe application rate was the only factor that influenced the depth of sedation. Basic parameters (gender, age, body mass index, apnea‐hypopnea index) had no influence on the depth of sedation. The sedation depth was dependent on the rate of propofol application. Regimes at 14 and 16 mg/kg/h as well as bolus application did not reach BIS levels below 50 representing deep sleep. Propofol doses of more than 20 mg/kg/h led to rapid decreases of sedation levels below deep sleep niveau. Propofol rates between 18 and 20 mg/kg/h enable BIS levels below 50 representing deep sleep and providing enough breathing cycles for observation.ConclusionLower application rates of propofol provide slower courses of sedation and shallower depths of sedation. A rate of 14 mg/kg/h might be appropriate to reach a sedation plateau at light sleep. A rate of 18 mg/kg/h leads to a sedation, corresponding to deep sleep. The combination of both rates might be a suitable pattern for performing sedation‐controlled DISE.Level of evidence2: Randomized trial.

Purpose Temperature monitoring in the perioperative setting often represents a compromise between accuracy, invasiveness of probe placement, and patient comfort. Transcutaneous sensors using the Zero-Heat-Flux (ZHF) and Double-Sensor (DS) technology have been developed and evaluated in a variety of clinical settings. The present study is the first to compare the performance of both sensors simultaneously with temperature measured by a Swan-Ganz catheter (PAC) in patients admitted to the intensive care unit (ICU) after cardiac surgery. Methods In this monocentric prospective observational study patients were postoperatively transferred to the ICU and both sensors were placed on the patients’ foreheads. Core body temperature measured by intraoperatively placed PAC served as gold standard. Measurements were recorded at 5-minute intervals and up to 40 data sets per patient were recorded. Bland and Altman’s method for repeated measurements was used to analyse agreement. Subgroup analyses for gender, body-mass-index, core temperature, airway status and different time intervals were performed. Lin’s concordance correlation coefficient (LCCC) was calculated, as well as sensitivity and specificity for detecting hyperthermia (≥ 38 °C) and hypothermia (< 36 °C). Results Over a period of six month, we collected 1600 sets of DS, ZHF, and PAC measurements, from a total of 40 patients. Bland-Altman analysis revealed a mean bias of -0.82 ± 1.27 °C (average ± 95% Limits-of-Agreement (LoA)) and − 0.54 ± 1.14 °C for DS and ZHF, respectively. The LCCC was 0.5 (DS) and 0.63 (ZHF). Mean bias was significantly higher in hyperthermic and hypothermic patients. Sensitivity and specificity were 0.12 / 0.99 (DS) and 0.35 / 1.0 (ZHF) for hyperthermia and 0.95 / 0.72 (DS) and 1.0 / 0.85 (ZHF) for hypothermia. Conclusion Core temperature was generally underestimated by the non-invasive approaches. In our study, ZHF outperformed DS. In terms of agreement, results for both sensors were outside the range that is considered clinically acceptable. Nevertheless, both sensors might be adequate to detect postoperative hypothermia reliably when more invasive methods are not available or appropriate. Trial Registration German Register of Clinical Trials (DRKS-ID: DRKS00027003), retrospectively registered 10/28/2021.

Background Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Mortality of patients with sepsis is high and largely unchanged throughout the past decades. Animal models have been widely used for the study of sepsis and septic shock, but translation into effective treatment regimes in the clinic have mostly failed. Pigs are considered as suitable research models for human diseases due to their high comparability and similarity to human anatomy, genetics, and the immune system. We here evaluated the previously reported models of septic shock in pigs and established a novel model of polymicrobial sepsis that meets the clinical criteria of septic shock in pigs. Materials and methods The literature search was performed using the keywords “pig”, “sepsis” and “septic shock”. For the establishment of septic shock in n = 10 German landrace pigs, mechanical ventilation was initiated, central venous and arterial lines and invasive hemodynamic monitoring via pulse contour cardiac output measurement (PiCCO) established. Peritoneal polymicrobial faecal sepsis was induced by application of 3 g/kg body weight faeces into the abdominal cavity. Septic shock was defined according to the third international consensus definitions (Sepsis-3). Upon shock, pigs underwent the 1-h bundle for the treatment of human sepsis. Cytokine levels were measured by ELISA. Results Published porcine sepsis models exhibited high methodological variability and did not meet the clinical criteria of septic shock. In our model, septic shock developed after an average of 4.8 ± 0.29 h and was associated with a reproducible drop in blood pressure (mean arterial pressure 54 ± 1 mmHg) and significant hyperlactatemia (3.76 ± 0.65 mmol/L). Septic shock was associated with elevated levels of interleukin-6 (IL6) and initial cardiac depression followed by a hyperdynamic phase with significant loss of systemic vascular resistance index after initial resuscitation. In addition, organ dysfunction (acute kidney injury) occurred. Conclusions We here established a model of septic shock in pigs that meets the clinical criteria of septic shock utilized in human patients. Our model may thus serve as a reference for clinically relevant sepsis research in pigs.

Background: Volatile anesthetics are becoming increasingly used for sedation in ICU but the evidence for long-term use is still low. We conducted a randomized controlled trial comparing sevoflurane with intravenous sedation with particular focus on efficacy and safety. Methods: In this prospective, randomized-controlled phase-IIb monocentric clinical trial ICU patients requiring at least 48h of sedation were randomized to receive sevoflurane (S) or propofol (P). Sedation quality was controlled using the Richmond Agitation Sedation Scale. Following termination of sedation, time to spontaneous breathing or extubation and opioid consumption, hemodynamics, ICU and hospital length of stay (LOS) as well as adverse events were recorded.Results: 79 patients were eligible to randomization. Use of sevoflurane (n=39) was associated with comparable sedation quality as use of propofol (n=40) and resulted in shortened times to spontaneous breathing (26min vs. 375min, P<0.001). Patients sedated with propofol had lower opioid requirements (remifentanil:400µg/h vs. 500µg/h, P=0.007 and sufentanil:40µg/h vs. 30µg/h, P=0.007) while hemodynamics, LOS or the occurrence of adverse events did not differ.Conclusion: Long-term sedated ICU patients under use of sevoflurane awaken more quickly and exhibit comparable sedation quality as patients sedated with propofol. Use of sevoflurane for long-term sedation is safe and non-inferior compared to use of propofol in ICU.

Background Airway management in case of acute tracheal injury is a challenging situation where the use of Extracorporeal Membrane Oxygenation (ECMO) has recently gained more importance.Case Description We report the case of a 60-year old women with aspiration of a large blister pack tablet causing acute tracheal obstruction with asphyxia as well as tracheal perforation with tension pneumothorax. As bronchoscopy failed to retrieve the blister pack, emergency tracheal reconstruction with Extracorporeal Membrane Oxygenation (ECMO) support was carried out.Conclusion The application of ECMO instantly alleviated the acute situation and provided excellent conditions for technically demanding emergency tracheal repair.

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.

Abstract Background  Not much is known about the results of nonelective anatomical lung resections in coronavirus disease 2019 (COVID-19) patients put on extracorporeal membrane oxygenation (ECMO). The aim of this study was to analyze the outcome of lobectomy under ECMO support in patients with acute respiratory failure due to severe COVID-19. Methods  All COVID-19 patients undergoing anatomical lung resection with ECMO support at a German university hospital were included into a prospective database. Study period was April 1, 2020, to April 30, 2021 (first, second, and third waves in Germany). Results  A total of nine patients (median age 61 years, interquartile range 10 years) were included. There was virtually no preexisting comorbidity (median Charlson score of comorbidity 0.2). The mean interval between first positive COVID-19 test and surgery was 21.9 days. Clinical symptoms at the time of surgery were sepsis (nine of nine), respiratory failure (nine of nine), acute renal failure (five of nine), pleural empyema (five of nine), lung artery embolism (four of nine), and pneumothorax (two of nine). Mean intensive care unit (ICU) and ECMO days before surgery were 15.4 and 6, respectively. Indications for surgery were bacterial superinfection with lung abscess formation and progressive septic shock (seven of nine) and abscess formation with massive pulmonary hemorrhage into the abscess cavity (two of nine). All patients were under venovenous ECMO with femoral-jugular configuration. Operative procedures were lobectomy (eight) and pneumonectomy (one). Weaning from ECMO was successful in four of nine. In-hospital mortality was five of nine. Mean total ECMO days were 10.3 ± 6.2 and mean total ICU days were 27.7 ± 9.9. Mean length of stay was 28.7 ± 8.8 days. Conclusion  Emergency surgery under ECMO support seems to open up a perspective for surgical source control in COVID-19 patients with bacterial superinfection and localized pulmonary abscess.

Background Acute hypoxemic respiratory failure (AHRF) is a leading concern in critically ill patients. Experimental and clinical data suggest that early sedation with volatile anesthestics may improve arterial oxygenation and reduce the plasma and alveolar levels of markers of alveolar epithelial injury and of proinflammatory cytokines. Methods An a priori hypothesis substudy of a multicenter randomized controlled trial (The Sedaconda trial, EUDRA CT Number 2016-004551-67). In the Sedaconda trial, 301 patients on invasive mechanical ventilation were randomized to 48 h of sedation with isoflurane or propofol in a 1:1 ratio. For the present substudy, patients with a ratio of arterial pressure of oxygen (PaO 2 ) to inspired fraction of oxygen (FiO 2 ), PaO 2 /FiO 2 , of ≤ 300 mmHg at baseline were included ( n = 162). The primary endpoint was the change in PaO 2 /FiO 2 between baseline and the end of study sedation. A subgroup analysis in patients with PaO 2 /FiO 2 ≤ 200 mmHg was performed ( n = 82). Results Between baseline and the end of study sedation (48 h), oxygenation improved to a similar extent in the isoflurane vs. the propofol group (isoflurane: 199 ± 58 to 219 ± 76 mmHg ( n = 70), propofol: 202 ± 62 to 236 ± 77 mmHg ( n = 89); p = 0.185). On day seven after randomization, PaO 2 /FiO 2 was 210 ± 79 mmHg in the isoflurane group ( n = 41) and 185 ± 87 mmHg in the propofol group ( n = 44; p = 0.411). In the subgroup of patients with PaO 2 /FiO 2 ≤ 200 mmHg, PaO 2 /FiO 2 increase between baseline and end of study sedation was 152 ± 33 to 186 ± 54 mmHg for isoflurane ( n = 37), and 150 ± 38 to 214 ± 85 mmHg for propofol ( n = 45; p = 0.029). On day seven, PaO 2 /FiO 2 was 198 ± 69 mmHg in patients randomized to isoflurane ( n = 20) and 174 ± 106 mmHg in patients randomized to propofol ( n = 20; p = 0.933). Both for the whole study population and for the subgroup with PaO 2 /FiO 2 ≤ 200 mmHg, no significant between-group differences were observed for PaCO 2 , pH and tidal volume as well as 30-day mortality and ventilator-free days alive. Conclusions In patients with AHRF, inhaled sedation with isoflurane for a duration of up to 48 h did not lead to improved oxygenation in comparison to intravenous sedation with propofol. Trial registration The main study was registered in the European Medicines Agency’s EU Clinical Trial register (EudraCT), 2016-004551-67, before including the first patient. The present substudy was registered at German Clinical Trials Register (DRKS, ID: DRKS00018959) on January 7th, 2020, before opening the main study data base and obtaining access to study results.

Background: Tumescent local anaesthesia with prilocain can lead to clinically significant methemoglobin levels. New generation multiple wavelength pulse oximeters (e. g. Masimo Radical 7®) can measure methemoglobin levels. Methods: In this prospective observational study we compared the venous methemoglobin levels and the corresponding pulse oximetric values of the Radical 7® in patients undergoing tumescent local anaesthesia for liposuction procedures. The measurements were performed in Hanseklinik, Luebeck, Germany between 2008 and 2011. Results: In 133 patients, we measured a maximum methemoglobin level of 18 per cent. In a Bland-Altman analysis we found a mean bias of +2.2 % (-4.1 to 8.4 limits of agreement) for pulse oximetric values compared to hemoximetry. Conclusion: Pulse oximetric measurement of methemoglobin is an early-warning tool for the detection of clinically significant methaemoglobinemia in patients with tumescent local anaesthesia.

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.

Background: Small studies indicate that isoflurane may be useful for sedation during invasive ventilation of ICU patients. There are no published large prospective efficacy trials. Methods: This phase 3, non-inferiority trial evaluated the efficacy and safety of ≤54 hours of isoflurane via the anaesthetic conserving device (ACD) compared with propofol in invasively ventilated ICU patients (30-day follow-up). Primary endpoint was percentage of time in Richmond Agitation–Sedation Scale (RASS) range –1 to –4; the predefined non-inferiority margin was 15% below the propofol mean. Secondary endpoints: opioid requirements, spontaneous breathing during sedation, time to wake-up and extubation, adverse events, ventilator-, ICU-, coma- and delirium-free days, and 30-day mortality. Findings: 301 patients were randomized to isoflurane (n=150) or propofol (n=151). Least-squares mean percentage of time (95% CI) in RASS target range was 90·7% (86·8–94·6) for isoflurane and 91·1% (87·2–95·0) for propofol. With isoflurane, opioid requirements were reduced by 29% (ANOVA, p=0·004) throughout and spontaneous breathing more frequent on Day 1 (50·3% vs 37·0%, GLMM, p=0·013). Extubation and wake-up times were short, and wake-up time was significantly shorter after isoflurane on Day 2 (median [IQR]: 20 [10–30] vs 30 [11–120] minutes; Cox regression p=0·001). No significant differences in serious adverse events, ventilator-, ICU-, coma- and delirium-free days or mortality. Interpretation: Isoflurane via the ACD for sedation of ICU patients was efficacious, non-inferior to propofol, with lower opioid use, more spontaneous breathing, and shorter wake-up time. Trial Registration: EudraCT#: 2016-004551-67Funding . This study was funded by Sedana Medical AB. Funding: This study was funded by Sedana Medical AB. Declaration of Interest: AM: Consultancy fees: Sedana Medical AB. TV: Grant support: B Braun. UG: Lecture fees: MT Monitor Technik, Getinge; reimbursement of clinical study expenses: Bayer Healthcare. TB: Lecture fees and travel costs: Sedana, Lowenstein Medical, Drager Medical. PK: Personal fees: Sedana Medical AB. MD: Lecture fees and travel costs: Cytosorbents Europe GmbH. PS: Employee and shareholder: Sedana Medical AB. JW, HB, KS, RK, AF, SCT, JS, HV, MB: Nothing to declare. Ethical Approval: The study was conducted in accordance with International Conference on Harmonisation Good Clinical Practice standards and the Declaration of Helsinki. Ethical approval for this study was provided by the ethics committees in Germany (Ethikkommission der Arztekammer des Saarlandes

Thrombocytosis is a common phenomenon in critically ill patients. Although thrombocytosis is an independent risk factor for complications, it does not seem to influence mortality in intensive care (ICU) patients.

The present study aimed to test the hypothesis that cerebral oxygen saturation (ScO2) measurements with the INVOS-5100-C and the ForeSight-Elite cerebral oximeters vary in their correlation with mixed venous oxygen saturation (SvO2) upon changes in systemic oxygenation in extubated cardiac surgical patients. Additionally, we aimed to elucidate whether the ScO2 measurements of both devices can be used interchangeably to detect reduced SvO2.

Background Thrombocytosis is a common phenomenon in critically ill patients. Although thrombocytosis is an independent risk factor for complications, it does not seem to influence mortality in intensive care (ICU) patients. Objectives Our investigation aimed to evaluate the etiological and clinical relevance of a platelet count greater than 450 × 10 9 /l in ICU patients. Materials and methods Patients admitted for a minimum of 4 days to an interdisciplinary ICU during a 45-month period were enrolled in this retrospective observational study. Thrombocytopenic patients (platelet count <150 × 10 9 /l in at least one measurement) were excluded. The study patients were divided into two groups: thrombocytosis group (thrombocytes >450 × 10 9 /l in at least one measurement) and control group (thrombocytes = 150 − 450 × 10 9 /l during ICU stay). Univariate and multiple regression analysis were used to determine the influence of severe co-morbidities on the development of thrombocytosis and the association of elevated platelet count with thrombotic embolism, length of stay (LOS) in ICU, and mortality. Results A total of 307 patients were analyzed, of whom thrombocytosis was observed in 119 cases. Independent risk factors for the development of thrombocytosis included SIRS, mechanical ventilation, and acute bleeding. Increasing age reduced the risk of thrombocytosis. Thromboembolism occurred in 16 patients (13.4%) with an elevated platelet count and only in nine patients (4.7%) with physiological platelet values (OR: 3.1; 95% CI: 1.3–7.2; p = 0.009). Mean duration of LOS was significantly longer in patients with thrombocytosis (25.2 vs.11.7 days, p < 0.0001). Elevated platelet count showed a negative correlation with ICU mortality (OR: 0.32; 95%-CI: 0.12–0.83; p = 0.019). Conclusion In our retrospective analysis the occurrence of thrombocytosis in a cohort of interdisciplinary ICU patients was associated with a higher rate of complications and longer LOS in the ICU. Despite these findings, thrombocytosis seems to reduce mortality in critical ill patients.