PROACTIVE SCREENING ALGORITHM FOR EARLY-ONSET PNEUMONIA IN PATIENTS WITH OUT-OF-HOSPITAL CARDIAC ARREST: A BEFORE-AFTER IMPLEMENTATION STUDY.

ABSTRACT: Introduction : Early-onset pneumonia (EOP) occurs in around 50% of critically ill patients with out-of-hospital cardiac arrest (OHCA) and is associated with increased morbidity. Prompt diagnosis of EOP in these patients is difficult because of targeted temperature management and the postcardiac arrest syndrome. We hypothesized that an algorithm for proactive screening of EOP would improve patient outcomes. Methods : We conducted a single-center observational study comparing the outcomes of mechanically ventilated adult patients with OHCA, before (study period 1) and after (study period 2) implementation of an algorithm for proactive diagnosis of EOP, including an early distal pulmonary specimen. An inverse probability treatment weighted multivariable regression was performed to identify independent parameters associated with duration of mechanical ventilation. A subgroup analysis was conducted in patients alive on day 5 after intensive care unit admission. Results : Over the 4-year study period, 190 patients (99 and 91 for study periods 1 and 2, respectively) were enrolled. The overall incidence of EOP was 57.4% and was similar between both study periods. Although there was no difference in the time interval to antibiotic initiation, study period 2 was independently associated with higher SpO 2 /FiO 2 ratios on days 3 and 4. We also observed a decrease in mechanical ventilation time in study period 2 (4.5 [1-11.3] vs. 3 [2-5.8] days; P = 0.07), and this reached statistical significance in the subgroup analysis of patients alive at day 5 (10 [5-17] vs. 5 [3-9] days, P = 0.01). Conclusion: In critically ill patients with OHCA, proactive diagnosis of EOP was not associated with a significant change in the time to antibiotic initiation. Further research is warranted to better define optimal diagnosis and management of EOP in this setting.

Prevention of post-operative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: a pragmatic, randomized, double-blind, placebo-controlled trial.

BACKGROUND: After cardiac surgery, post-operative delirium (PoD) is acknowledged to have a significant negative impact on patient outcome. To date, there is no valuable and specific treatment for PoD. Critically ill patients often suffer from poor sleep condition. There is an association between delirium and sleep quality after cardiac surgery. This study aimed to establish whether promoting sleep using an overnight infusion of dexmedetomidine reduces the incidence of delirium after cardiac surgery. METHODS: Randomized, pragmatic, multicentre, double-blind, placebo controlled trial from January 2019 to July 2021. All adult patients aged 65 years or older requiring elective cardiac surgery were randomly assigned 1:1 either to the dexmedetomidine group or the placebo group on the day of surgery. Dexmedetomidine or matched placebo infusion was started the night after surgery from 8 pm to 8 am and administered every night while the patient remained in ICU, or for a maximum of 7 days. Primary outcome was the occurrence of postoperative delirium (PoD) within the 7 days after surgery. RESULTS: A total of 348 patients provided informed consent, of whom 333 were randomized: 331 patients underwent surgery and were analysed (165 assigned to dexmedetomidine and 166 assigned to placebo). The incidence of PoD was not significantly different between the two groups (12.6% vs. 12.4%, p = 0.97). Patients treated with dexmedetomidine had significantly more hypotensive events (7.3% vs 0.6%; p < 0.01). At 3 months, functional outcomes (Short-form 36, Cognitive failure questionnaire, PCL-5) were comparable between the two groups. CONCLUSION: In patients recovering from an elective cardiac surgery, an overnight infusion of dexmedetomidine did not decrease postoperative delirium. Trial registration This trial was registered on ClinicalTrials.gov (number: NCT03477344; date: 26th March 2018).

Anti-Factor-Xa and Activated Partial Thromboplastin Time Concordance and Outcomes in Adults Undergoing Extracorporeal Membrane Oxygenation: A Secondary Analysis of the Pilot Low-Dose Heparin in Critically Ill Patients Undergoing Extracorporeal Membrane Oxygenation Randomized Trial.

OBJECTIVES: To determine the concordance between activated partial thromboplastin time (aPTT) and anti-factor-Xa (anti-Xa) in adults undergoing extracorporeal membrane oxygenation (ECMO) and to identify the factors associated with discordant paired aPTT/anti-Xa. DESIGN: Pre-planned secondary analysis of the Low-Dose Heparin in Critically Ill Patients Undergoing Extracorporeal Membrane Oxygenation pilot randomized unblinded, parallel-group controlled trial. SETTING: Two ICUs in two university hospitals. PATIENTS: Thirty-two critically ill patients who underwent ECMO and who had at least one paired aPTT and anti-Xa assay performed at the same time. INTERVENTIONS: We analyzed the concordance between aPTT and anti-Xa and identified factors associated with discordant paired aPTT/anti-Xa based on their respective therapeutic ranges. We also compared biological parameters between heparin resistance episode and no heparin resistance. MEASUREMENTS AND MAIN RESULTS: Of the 32 patients who were included in this study, 24 (75%) had at least one discordant paired aPTT/anti-Xa. Of the 581 paired aPTT/anti-Xa that were analyzed, 202 were discordant. The aPTT was relatively lower than anti-Xa in 66 cases (32.7%) or relatively higher than anti-Xa in 136 cases (67.3%). Thirty-three heparin resistance episodes were identified in six patients (19%). CONCLUSIONS: In these critically ill patients undergoing ECMO, one third of paired aPTT/anti-Xa measures was discordant. Coagulopathy and heparin resistance might be the reasons for discordance. Our results support the potential importance of routinely monitoring both tests in this setting.

Postoperative transfusion hemoglobin threshold and functional recovery after high-risk oncologic surgery: A randomized controlled pilot study.

BACKGROUND: Robust evidence to inform best transfusion management after major oncologic surgery, where postoperative recovery might impact treatment regimens for cancer, is lacking. We conducted a study to validate the feasibility of a larger trial comparing liberal versus restrictive red blood cells (RBC) transfusion strategies after major oncologic surgery. STUDY DESIGN AND METHODS: This was a two-center, randomized, controlled, study of patients admitted to the intensive care unit after major oncologic surgery. Patients whose hemoglobin level dropped below 9.5 g/dL, were randomly assigned to immediately receive a 1-unit RBC transfusion (liberal) or delayed until the hemoglobin level dropped below 7.5 g/dL (restrictive). The primary outcome was the median hemoglobin level between randomization to day 30 post-surgery. Disability-free survival was evaluated by the WHODAS 2.0 questionnaire. RESULTS: 30 patients were randomized (15 patients/group) in 15 months with a mean recruitment rate of 1.8 patients per month. The median hemoglobin level was significantly higher in the liberal group than in the restrictive group: 10.1 g/dL (IQR 9.6-10.5) versus 8.8 g/dL (IQR 8.3-9.4), p < .001, and RBC transfusion rates were 100% versus 66.7%, p = .04. The disability-free survival was similar between groups: 26.7% versus 20%, p = 1. DISCUSSION: Our results support the feasibility of a phase 3 randomized controlled trial comparing the impact of liberal versus restrictive transfusion strategies on the functional recovery of critically ill patients following major oncologic surgery.

Impact of continuous hypertonic (NaCl 20%) saline solution on renal outcomes after traumatic brain injury (TBI): a post hoc analysis of the COBI trial.

BACKGROUND: To evaluate if the increase in chloride intake during a continuous infusion of 20% hypertonic saline solution (HSS) is associated with an increase in the incidence of acute kidney injury (AKI) compared to standard of care in traumatic brain injury patients. METHODS: In this post hoc analysis of the COBI trial, 370 patients admitted for a moderate-to-severe TBI in the 9 participating ICUs were enrolled. The intervention consisted in a continuous infusion of HSS to maintain a blood sodium level between 150 and 155 mmol/L for at least 48 h. Patients enrolled in the control arm were treated as recommended by the latest Brain Trauma foundation guidelines. The primary outcome of this study was the occurrence of AKI within 28 days after enrollment. AKI was defined by stages 2 or 3 according to KDIGO criteria. RESULTS: After exclusion of missing data, 322 patients were included in this post hoc analysis. The patients randomized in the intervention arm received a significantly higher amount of chloride during the first 4 days (intervention group: 97.3 ± 31.6 g vs. control group: 61.3 ± 38.1 g; p < 0.001) and had higher blood chloride levels at day 4 (117.9 ± 10.7 mmol/L vs. 111.6 ± 9 mmol/L, respectively, p < 0.001). The incidence of AKI was not statistically different between the intervention and the control group (24.5% vs. 28.9%, respectively; p = 0.45). CONCLUSIONS: Despite a significant increase in chloride intake, a continuous infusion of HSS was not associated with AKI in moderate-to-severe TBI patients. Our study does not confirm the potentially detrimental effect of chloride load on kidney function in ICU patients. TRIAL REGISTRATION: The COBI trial was registered on clinicaltrial.gov (Trial registration number: NCT03143751, date of registration: 8 May 2017).

Management of urgent invasive procedures in patients treated with direct oral anticoagulants: An observational registry analysis.

BACKGROUND: Patients treated with direct oral anticoagulants (DOACs) may require urgent procedures. Managing these patients is challenging due to different bleeding risks and may include laboratory testing, procedural delays, or haemostatic/reversal agent administration. OBJECTIVE: We evaluated management strategies and outcomes of urgent, non-haemostatic invasive procedures in patients treated with DOACs. METHODS AND RESULTS: In a descriptive cohort study, we prospectively evaluated 478 patients in the GIHP-NACO registry, from June 2013 to November 2015. Hospitalised patients receiving dabigatran (n = 160), rivaroxaban (n = 274), or apixaban (n = 44) requiring urgent, procedural interventions were evaluated, of which 384/478 (80 %) were surgical procedures. Orthopaedic surgery included 216/384 patients (56 %), while gastrointestinal surgery included 75/384 (20 %) patients. On admission, the median age was 79 (70-85), and creatinine clearance was <60 mL·min-1 in 316/478 (66 %) patients. DOAC concentration was determined in 277 (58 %) patients and was 85 ng·mL-1 (median; range 0-764), 61 ng·mL-1 (3-541), and 81 ng·mL-1 (26-354) for dabigatran, rivaroxaban, and apixaban, respectively. Procedures were delayed in 194/455 (43 %) of the cases. Excessive bleeding was observed in 62/478 (13 %) procedures, and haemostatic agents were administered in 76/478 (16 %) procedures. By day 30, major cerebral and cardiovascular events were observed in 38/478 (7.9 %) patients, and mortality was 28/478 (5.9 %). CONCLUSIONS: In the GIHP-NACO registry, before specific antidotes were available, DOAC treated patients undergoing urgent invasive procedures were delayed in nearly half of the cases, and showed a low rate of excessive bleeding, suggesting that most urgent procedures can be performed safely without DOAC reversal. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov. Identifier: NCT02185027.

Detection of cerebral hypoperfusion with a dynamic hyperoxia test using brain oxygenation pressure monitoring.

INTRODUCTION: Brain multimodal monitoring including intracranial pressure (ICP) and brain tissue oxygen pressure (PbtO2) is more accurate than ICP alone in detecting cerebral hypoperfusion after traumatic brain injury (TBI). No data are available for the predictive role of a dynamic hyperoxia test in brain-injured patients from diverse etiology. AIM: To examine the accuracy of ICP, PbtO2 and the oxygen ratio (OxR) in detecting regional cerebral hypoperfusion, assessed using perfusion cerebral computed tomography (CTP) in patients with acute brain injury. METHODS: Single-center study including patients with TBI, subarachnoid hemorrhage (SAH) and intracranial hemorrhage (ICH) undergoing cerebral blood flow (CBF) measurements using CTP, concomitantly to ICP and PbtO2 monitoring. Before CTP, FiO2 was increased directly from baseline to 100% for a period of 20 min under stable conditions to test the PbtO2 catheter, as a standard of care. Cerebral monitoring data were recorded and samples were taken, allowing the measurement of arterial oxygen pressure (PaO2) and PbtO2 at FiO2 100% as well as calculation of OxR (= ΔPbtO2/ΔPaO2). Regional CBF (rCBF) was measured using CTP in the tissue area around intracranial monitoring by an independent radiologist, who was blind to the PbtO2 values. The accuracy of different monitoring tools to predict cerebral hypoperfusion (i.e., CBF < 35 mL/100 g × min) was assessed using area under the receiver-operating characteristic curves (AUCs). RESULTS: Eighty-seven CTPs were performed in 53 patients (median age 52 [41-63] years-TBI, n = 17; SAH, n = 29; ICH, n = 7). Cerebral hypoperfusion was observed in 56 (64%) CTPs: ICP, PbtO2 and OxR were significantly different between CTP with and without hypoperfusion. Also, rCBF was correlated with ICP (r = - 0.27; p = 0.01), PbtO2 (r = 0.36; p < 0.01) and OxR (r = 0.57; p < 0.01). Compared with ICP alone (AUC = 0.65 [95% CI, 0.53-0.76]), monitoring ICP + PbO2 (AUC = 0.78 [0.68-0.87]) or ICP + PbtO2 + OxR (AUC = 0.80 (0.70-0.91) was significantly more accurate in predicting cerebral hypoperfusion. The accuracy was not significantly different among different etiologies of brain injury. CONCLUSIONS: The combination of ICP and PbtO2 monitoring provides a better detection of cerebral hypoperfusion than ICP alone in patients with acute brain injury. The use of dynamic hyperoxia test could not significantly increase the diagnostic accuracy.

Does Chloride Intake at the Early Phase of Septic Shock Resuscitation Impact on Renal Outcome?

INTRODUCTION: Fluid administration is one of the first lines of treatment for hemodynamic management of sepsis and septic shock. Studies investigating the effects of chloride-rich fluids including normal saline on renal function report controversial findings. METHODS: This is a prospective, observational, multicenter study. Patients with septic shock, defined according to Sepsis-2 definition, were eligible. A "high-dose" of chloride was defined as a chloride intake greater than 18 g administrated within the first 48 h of septic shock management. The purpose of this study was to investigate the impact of cumulative chloride infusion within the first 48 h of septic shock resuscitation on acute kidney injury (AKI). RESULTS: Two hundred thirty-nine patients with septic shock were included. Patients who received a "high-dose" of chloride had significantly higher Sequential Organ Failure Assessment score at the time of enrolment (P < 0.001). Cumulative chloride load was higher in patients requiring renal replacement therapy (RRT) (31.1 vs. 25.2 g/48 h; P < 0.005). Propensity score-weighted regression did not find any association between "high-dose" of chloride and AKI requiring RRT (OR: 0.97 [0.88-1.1]; P = 0.69). There was no association between "high-dose" of chloride and worsening kidney function at H48 (OR: 0.94 [0.83-1.1]; P = 0.42). There was also no association between "high-dose" of chloride and ICU length of stay (P = 0.61), 28-day mortality (P = 0.83), or hospital mortality (P = 0.89). CONCLUSION: At the early stage of resuscitation of critically ill patients with septic shock, administration of "high-dose" of chloride (> 18 g/48 h) was not associated with renal prognosis.

Is there an optimal trade-off between anaemia and red blood cell transfusion in surgical critically ill patients after oncologic surgery?

BACKGROUND AND OBJECTIVES: Equipoise remains on the optimal transfusion strategy in surgical oncologic patients. The primary objective of our study was to determine the impact of anaemia and red blood cells (RBCs) transfusion on severe postoperative complications in surgical oncologic critically ill patients. MATERIALS AND METHODS: Retrospective single-centre study. Adults admitted to intensive care unit after major oncologic surgery were eligible. Analyses to determine the independent risk factors, including anaemia or RBC transfusion, for postoperative complications and/or hospital mortality were performed. RESULTS: Of the 283 patients included, 246 patients (86.9%) had anaemia. Fifty-five patients (19·4%) were transfused. Patients exposed to moderate-to-severe anaemia or RBC transfusion had more often severe complications, especially acute kidney injury and infectious complications. Multivariate analysis found an independent association between moderate and severe anaemia and severe postoperative complications (moderate anaemia: OR 14·02 [2·52-264]; severe anaemia: OR 16·25 [2·62-318·5]; P < 0·05). Elderly, obese patients and patients operated from abdominal surgery appeared to be more vulnerable to anaemia than other patients. Transfusion was also an independent risk factor for postoperative complications (OR 4·19 [2·12-8·39]; P < 0·001). When considering moderate-to-severe anaemic patients, RBC transfusion was no longer associated with postoperative complications. CONCLUSIONS: Anaemia was associated with severe postoperative complications, and this association was stronger in elderly, obese patients and after abdominal surgery. RBC transfusion also negatively impacts on patients' prognosis. However, this association was not found in case of moderate-to-severe anaemia exposure (haemoglobin < 10 g/dl).

Association between fluid overload and SOFA score kinetics in septic shock patients: a retrospective multicenter study.

BACKGROUND: Fluid infusion represents one of the cornerstones of resuscitation therapies in order to increase oxygen delivery during septic shock. Fluid overload as a consequence of excessive fluid administration seems to be linked to worse long-term outcome. However, its immediate effect on patient's clinical state is poorly described. The goal of this study was to assess the impact of FO on SOFA score kinetics as a surrogate marker of organ dysfunction from day 0 to day 5. MATERIAL AND METHODS: Retrospective, multicenter, investigator-initiated study. All adult patients (> 18 years old) admitted from January 2012 to April 2017 in one of the three ICUs for septic shock, secondary to peritonitis or pulmonary infection and mechanically ventilated, were included. Univariate analysis was performed with Student's t and chi-square test, for continuous and categorical variables, respectively. A multivariate linear regression model evaluated the impact of FO on delta SOFA score from day 0 to day 5. Secondly, a multivariate mixed-model accounting for repeated measures analyzed the impact of FO on SOFA score kinetics. RESULTS: One hundred twenty-nine patients met the inclusion criteria and were assigned into FO and no FO groups. FO occurred in 39% of the patients. The difference between SOFA score at day 0 and day 5 was more than twofold higher in the no FO group than in the FO group with a difference of 2.37 between the two groups (4.52 vs. 2.15; p = 0.001). Cumulative fluid intake at day 5 was higher in the FO group (2738 vs. 8715 ml, p < 0.001). In multivariate analysis, FO was associated with delta SOFA score: aRR = 0.15 (95% CI 0.03-0.63; p = 0.009). In mixed model, the regression coefficient for fluid overload status (r 2 = 1.16; p = 0.014) indicated that the slope for SOFA score kinetic was less pronounced for patients with FO than for patients without FO. CONCLUSIONS: FO patients had a more prolonged multi-organ failure according to SOFA score kinetics during septic shock from resuscitation phase to day 5.