Erythropoietin to treat anaemia in critical care patients: a multicentre feasibility study.

Anaemia is common and associated with poor outcomes during and after critical illness. The use of erythropoietin to treat such anaemia is controversial with older studies showing mixed results. In this study, we aimed to evaluate the feasibility of performing a large multicentre randomised controlled trial of erythropoietin in this setting. We randomly allocated patients staying in the ICU for ≥ 72 h with haemoglobin ≤ 120 g.l-1 to either a weekly injection of erythropoietin (40,000 iu, maximum of five injections) or placebo (saline). The primary endpoint was feasibility (as measured by recruitment, randomisation and follow-up rates, and protocol compliance). Secondary endpoints included biological efficacy and clinical outcomes. Forty-two participants were recruited and randomly allocated, all participants received the allocated intervention, but one withdrew their consent and refused the use of their data, leaving 20 in the erythropoietin group and 21 in placebo group. Follow-up was completed for all patients who survived. The overall recruitment rate was 73.7% with 8.4 participants recruited on average per month. The last haemoglobin measured before hospital discharge (or death) was similar between the groups with a mean (SD) haemoglobin of 107 (21) vs. 95 (25) g.l-1 , mean difference (95%CI) 11 (-4-26), g.l-1 , p = 0.154. A large, multicentre randomised controlled trial of erythropoietin to treat anaemia in ICU patients is feasible and necessary to determine effects of erythropoietin on mortality in ICU anaemic patients.

Factors associated with an unfavourable outcome in elderly intensive care traumatic brain injury patients. a retrospective multicentre study.

BACKGROUND: Changes in the epidemiology of traumatic brain injury (TBI) in older patients have received attention, but limited data are available on the outcome of these patients after admission to intensive care units (ICUs). The aim of this study was to evaluate the outcomes of patients over 65 years of age who were admitted to an ICU for TBI. METHODS: This was a multicentre, retrospective, observational study conducted from January 2013 to February 2019 in the surgical ICUs of 5 level 1 trauma centres in France. Patients aged ≥ 65 years who were hospitalized in the ICU for TBI with or without extracranial injuries were included. The main objective was to determine the risk factors for unfavourable neurological outcome at 3 months defined as an Extended Glasgow Outcome Scale (GOSE) score < 5. RESULTS: Among the 349 intensive care patients analysed, the GOSE score at 3 months was ≤ 4 and ≥ 5 in 233 (67%) and 116 (33%) patients, respectively. The mortality rate at 3 months was 157/233 (67%), and only 7 patients (2%) fully recovered or had minor symptoms. Withdrawal or withholding of life-sustaining therapies in the ICU was identified in 140 patients (40.1%). Multivariate analysis showed that age (OR 1.09, CI 95% 1.04-1.14), male sex (OR 2.94, CI95% 1.70-5.11), baseline Glasgow Coma Scale score (OR 1.20, CI95% 1.13-1.29), injury severity score (ISS; OR 1.04, CI95% 1.02-1.06) and use of osmotherapy (OR 2.42, CI95% 1.26-4.65) were associated with unfavourable outcomes (AUC = 0.79, CI 95% [0.74-0.84]). According to multivariate analysis, the variables providing the best sensitivity and specificity were age ≥ 77 years, Glasgow Coma Scale score ≤ 9 and ISS ≥ 25 (AUC = 0.79, CI 95% [0.74-0.84]). CONCLUSIONS: Among intensive care patients aged ≥ 65 years suffering from TBI, age (≥ 77 years), male sex, baseline Glasgow coma scale score (≤ 9), ISS (≥ 25) and use of osmotherapy were predictors of unfavourable neurological outcome. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04651803. Registered 03/12/2020. Retrospectively registered.

Factors associated with time to defecate and outcomes in critically ill patients: a prospective, multicentre, observational study.

Delayed defecation is common in patients on intensive care. We aimed to determine factors associated with time to defecation after admission to intensive care and in turn its association with length of stay and mortality. We studied 396 adults admitted to one of five intensive care units in whom at least 2 days' invasive ventilation was anticipated during an expected stay of at least 3 days. The median (IQR [range]) time to defecate by the 336 out of 396 (84%) patients who did so before intensive care discharge was 6 (4-8 [1-18]) days. Defecation was independently associated with five factors, hazard ratio (95%CI), higher values indicating more rapid defecation: alcoholism, 1.32 (1.05-1.66), p = 0.02; laxatives before admission, 2.35 (1.79-3.07), p < 0.001; non-invasive ventilation, 0.54 (0.36-0.82), p = 0.004; duration of ventilation, 0.78 (0.74-0.82), p < 0.001; laxatives after admission, 1.67 (1.23-2.26), p < 0.001; and enteral nutrition within 48 h of admission, 1.43 (1.07-1.90), p = 0.01. Delayed defecation was associated with prolonged intensive care stay but not mortality.

Patient blood management during the COVID-19 pandemic: a narrative review.

As COVID-19 disease escalates globally, optimising patient outcome during this catastrophic healthcare crisis is the number one priority. The principles of patient blood management are fundamental strategies to improve patient outcomes and should be given high priority in this crisis situation. The aim of this expert review is to provide clinicians and healthcare authorities with information regarding how to apply established principles of patient blood management during the COVID-19 pandemic. In particular, this review considers the impact of the COVID-19 pandemic on blood supply and specifies important aspects of donor management. We discuss how preventative and control measures implemented during the COVID-19 crisis could affect the prevalence of anaemia, and highlight issues regarding the diagnosis and treatment of anaemia in patients requiring elective or emergency surgery. In addition, we review aspects related to patient blood management of critically ill patients with known or suspected COVID-19, and discuss important alterations of the coagulation system in patients hospitalised due to COVID-19. Finally, we address special considerations pertaining to supply-demand and cost-benefit issues of patient blood management during the COVID-19 pandemic.

Multicentre, prospective, double-blind, randomised controlled clinical trial comparing different non-opioid analgesic combinations with morphine for postoperative analgesia: the OCTOPUS study.

BACKGROUND: Head-to-head comparisons of combinations of more than one non-opioid analgesic (NOA) with morphine alone, for postoperative analgesia, are lacking. The objective of this multicentre, randomised, double-blind controlled trial was to compare the morphine-sparing effects of different combinations of three NOAs-paracetamol (P), nefopam (N), and ketoprofen (K)-for postoperative analgesia. METHODS: Patients from 10 hospitals were randomised to one of eight groups: control (C) received saline as placebo, P, N, K, PN, PK, NK, and PNK. Treatments were given intravenously four times a day during the first 48 h after surgery, and morphine patient-controlled analgesia was used as rescue analgesia. The outcome measures were morphine consumption, pain scores, and morphine-related side-effects evaluated 24 and 48 h after surgery. RESULTS: Two hundred and thirty-seven patients undergoing a major surgical procedure were included between July 2013 and November 2016. Despite a failure to reach a calculated sample size, 24 h morphine consumption [median (inter-quartile range)] was significantly reduced in the PNK group [5 (1-11) mg] compared with either the C group [27 (11-42) mg; P<0.05] or the N group [21 (12-29) mg; P<0.05]. Results were similar 48 h after surgery. Patients experienced less pain in the PNK group compared with the C, N, and P groups. No difference was observed in the incidence of morphine-related side-effects. CONCLUSIONS: Combining three NOAs with morphine allows a significant morphine sparing for 48 h after surgery associated with superior analgesia the first 24 h when compared with morphine alone. CLINICAL TRIAL REGISTRATION: EudraCT: 2012-004219-30; NCT01882530.

SmartPilot® view-guided anaesthesia improves postoperative outcomes in hip fracture surgery: a randomized blinded controlled study.

BACKGROUND: Both under-dosage and over-dosage of general anaesthetics can harm frail patients. We hypothesised that computer-assisted anaesthesia using pharmacokinetic/pharmacodynamic models guided by SmartPilot® View (SPV) software could optimise depth of anaesthesia and improve outcomes in patients undergoing hip fracture surgery. METHODS: This prospective, randomized, single-centre, blinded trial included patients undergoing hip fracture surgery under general anaesthesia. In the intervention group, anaesthesia was guided using SPV with predefined targets. In the control group, anaesthesia was delivered by usual practice using the same agents (propofol, sufentanil and desflurane). The primary endpoint was the time spent in the "appropriate anaesthesia zone" defined as bispectral index (BIS) (blinded to the anaesthetist during surgery) of 45-60 and systolic arterial pressure of 80-140 mm Hg. Postoperative complications were recorded for one month in a blinded manner. RESULTS: Of 100 subjects randomised, 97 were analysed (n=47 in SPV and 50 in control group). Anaesthetic drug consumption was reduced in the SPV group (for propofol and desflurane). Intraoperative duration of low BIS (<45) was similar, but cumulative time of low systolic arterial pressure (<80 mm Hg) was significantly shorter in the SPV group (median (Q1-Q3); 3 (0-40) vs 5 (0-116) min, P=0.013). SPV subjects experienced fewer moderate or major postoperative complications at 30-days (8 (17)% vs 18 (36)%, P=0.035) and shorter length of hospitalisation (8 (2-20) vs 8 (2-60) days, P=0.017). CONCLUSIONS: SmartPilot® View-guided anaesthesia reduces intraoperative hypotension duration, occurrence of postoperative complications and length of stay in hip fracture surgery patients. CLINICAL TRIAL REGISTRATION: NCT 02556658.

International consensus statement on the peri-operative management of anaemia and iron deficiency.

Despite current recommendations on the management of pre-operative anaemia, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in surgical patients. A number of experienced researchers and clinicians took part in an expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the peri-operative period. These statements include: a diagnostic approach for anaemia and iron deficiency in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up. We urge anaesthetists and peri-operative physicians to embrace these recommendations, and hospital administrators to enable implementation of these concepts by allocating adequate resources.

Impact of imipenem and amikacin pharmacokinetic/pharmacodynamic parameters on microbiological outcome of Gram-negative bacilli ventilator-associated pneumonia.

OBJECTIVES: Despite recent advances, antibiotic therapy of ventilator-associated pneumonia (VAP) in ICU patients is still challenging. We assessed the impact of imipenem and amikacin pharmacokinetic and pharmacodynamic parameters on microbiological outcome in these patients. PATIENTS AND METHODS: Patients with Gram-negative bacilli (GNB) VAP were prospectively included. Blood samples for pharmacokinetic analysis were collected after empirical administration of a combination of imipenem three times daily and one single dose of amikacin. MICs were estimated for each GNB obtained from respiratory samples. Microbiological success was defined as a ≥10(3) cfu/mL decrease in bacterial count in quantitative cultures between baseline and the third day of treatment. RESULTS: Thirty-nine patients [median (min-max) age = 60 years (28-84) and median SAPS2 at inclusion = 40 (19-73)] were included. Median MICs of imipenem and amikacin were 0.25 mg/L (0.094-16) and 2 mg/L (1-32), respectively. Median times over MIC and over 5× MIC for imipenem were 100% (8-100) and 74% (3-100), respectively. The median C1/MIC ratio for amikacin was 23 (1-76); 34 patients (87%) achieved a C1/MIC ≥10. Microbiological success occurred in 29 patients (74%). No imipenem pharmacodynamic parameter was significantly associated with the microbiological success. For amikacin, C1/MIC was significantly higher in the microbiological success group: 26 (1-76) versus 11 (3-26) (P = 0.004). CONCLUSIONS: In ICU patients with VAP, classic imipenem pharmacodynamic targets are easily reached with usual dosing regimens. In this context, for amikacin, a higher C1/MIC ratio than previously described might be necessary.

Tranexamic acid for the prevention and treatment of postpartum haemorrhage.

Postpartum haemorrhage (PPH) is a major cause of maternal mortality, accounting for one-quarter of all maternal deaths worldwide. Uterotonics after birth are the only intervention that has been shown to be effective for PPH prevention. Tranexamic acid (TXA), an antifibrinolytic agent, has therefore been investigated as a potentially useful complement to this for both prevention and treatment because its hypothesized mechanism of action in PPH supplements that of uterotonics and because it has been proved to reduce blood loss in elective surgery, bleeding in trauma patients, and menstrual blood loss. This review covers evidence from randomized controlled trials (RCTs) for PPH prevention after caesarean (n=10) and vaginal (n=2) deliveries and for PPH treatment after vaginal delivery (n=1). It discusses its efficacy and side effects overall and in relation to the various doses studied for both indications. TXA appears to be a promising drug for the prevention and treatment of PPH after both vaginal and caesarean delivery. Nevertheless, the current level of evidence supporting its efficacy is insufficient, as are the data about its benefit:harm ratio. Large, adequately powered multicentre RCTs are required before its widespread use for preventing and treating PPH can be recommended.

New colistin population pharmacokinetic data in critically ill patients suggesting an alternative loading dose rationale.

Colistin is an old antibiotic that has recently gained a considerable renewal of interest as the last-line defense therapy against multidrug-resistant Gram-negative bacteria. It is administered as colistin methanesulfonate (CMS), an inactive prodrug, and it was shown that due to slow CMS conversion, colistin plasma concentrations increase very slowly after treatment initiation, which constitutes the rationale for a loading dose in critically ill patients. However, faster CMS conversion was observed in healthy volunteers but using a different CMS brand, which may also have a major impact on colistin pharmacokinetics. Seventy-three critically ill patients not undergoing dialysis received multiple doses of CMS. The CMS concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and a pharmacokinetic analysis was conducted using a population approach. We confirmed that CMS renal clearance and colistin concentrations at steady state are mostly governed by creatinine clearance, but we predict a typical maximum concentration of drug in serum (Cmax) of colistin close to 2 mg/liter, occurring 3 h after an initial dose of 2 million international units (MIU) of CMS. Accordingly, the estimated colistin half-life (t1/2) was relatively short (3.1 h), with rapid attainment of steady state. Our results are only partially consistent with other recently published results. We confirm that the CMS maintenance dose should be adjusted according to renal function in critically ill patients. However, much higher than expected colistin concentrations were observed after the initial CMS dose, with rapid steady-state achievement. These discrepancies challenge the pharmacokinetic rationale for a loading dose, which may still be appropriate for rapid bacterial eradication and an improved clinical cure rate.

Evaluation of pulse pressure variation validity criteria in critically ill patients: a prospective observational multicentre point-prevalence study.

BACKGROUND: Respiratory variation in pulse pressure (ΔPP) is commonly used to predict the fluid responsiveness of critically ill patients. However, some researchers have demonstrated that this measurement has several limitations. The present study was designed to evaluate the proportion of patients satisfying criteria for valid application of ΔPP at a given time-point. METHODS: A 1 day, prospective, observational, point-prevalence study was performed in 26 French intensive care units (ICUs). All patients hospitalized in the ICUs on the day of the study were included. The ΔPP validity criteria were recorded prospectively and defined as follows: (i) mechanical ventilation in the absence of spontaneous respiration; (ii) regular cardiac rhythm; (iii) tidal volume ≥8 ml kg(-1) of ideal body weight; (iv) a heart rate/respiratory rate ratio >3.6; (v) total respiratory system compliance ≥30 ml cm H2O(-1); and (vi) tricuspid annular peak systolic velocity ≥0.15 m s(-1). RESULTS: The study included 311 patients with a Simplified Acute Physiology Score II of 41 (39-43). Overall, only six (2%) patients satisfied all validity criteria. Of the 170 patients with an arterial line in place, only five (3%) satisfied the validity criteria. During the 24 h preceding the study time-point, fluid responsiveness was assessed for 79 patients. ΔPP had been used to assess fluid responsiveness in 15 of these cases (19%). CONCLUSIONS: A very low percentage of patients satisfied all criteria for valid use of ΔPP in the evaluation of fluid responsiveness. Physicians must consider limitations to the validity of ΔPP before using this variable.

Probabilistic estimation of the source component of seismic hazard in North-Eastern Brazil.

Stable continental regions pose unique challenges for conducting Probabilistic Seismic Hazard Analysis because the earthquake activity driving mechanisms are poorly understood. For instance, the lower seismicity (hence the paucity of data) and the absence of well-defined active fault systems complicate accurately determining seismic source parameters. Northeastern Brazil is a stable continental region exhibiting moderate-size events recorded with significant seismic intensities and provoking the collapse of poorly constructed buildings in the last century. Thus, assessing the seismic hazard is critical for seismic risk mitigation. The seismic hazard depends on three components: source, path, and site, and here, we present the probabilistic seismic hazard analysis of the source component for NE Brazil. Spatial aggregation of earthquake sources outlined four areal seismic zones. A goodness-of-fit test rejected the Gutenberg-Richter model of magnitude frequency distribution in one of the studied seismic zones. For this reason, we estimated the magnitude probability distribution function in that zone using a nonparametric adaptive kernel estimator. In other zones the Gutenberg-Richter magnitude frequency model was applied. In either way of the magnitude probability distribution modelling we considered the upper bound for magnitude equal to 6.6 mR, based on the upper bound of a 95 % confidence interval for the standard normal distribution of palaeoearthquake sizes. Our findings suggests that potentially damaging events are likely to occur, and we cannot neglect chances for the occurrence of earthquakes exceeding 5.2 mR. The calculated mean return periods indicate significantly shorter intervals between consecutive large events than palaeoseismic records.

Long-term survival of traumatic brain injury and intra-cerebral haemorrhage patients: A multicentric observational cohort.

PURPOSE: Mortality is often assessed during ICU stay and early after, but rarely at later stage. We aimed to compare the long-term mortality between TBI and ICH patients. MATERIALS AND METHODS: From an observational cohort, we studied 580 TBI patients and 435 ICH patients, admitted from January 2013 to February 2021 in 3 ICUs and alive at 7-days post-ICU discharge. We performed a Lasso-penalized Cox survival analysis. RESULTS: We estimated 7-year survival rates at 72.8% (95%CI from 67.3% to 78.7%) for ICH patients and at 84.9% (95%CI from 80.9% to 89.1%) for TBI patients: ICH patients presenting a higher mortality risk than TBI patients. Additionally, we identified variables associated with higher mortality risk (age, ICU length of stay, tracheostomy, low GCS, absence of intracranial pressure monitoring). We also observed anisocoria related with the mortality risk in the early stage after ICU stay. CONCLUSIONS: In this ICU survivor population with a prolonged follow-up, we highlight an acute risk of death after ICU stay, which seems to last longer in ICH patients. Several variables characteristic of disease severity appeared associated with long-term mortality, raising the hypothesis that the most severe patients deserve closer follow-up after ICU stay.

Patient blood management in Europe.

Preoperative anaemia is common in patients undergoing orthopaedic and other major surgery. Anaemia is associated with increased risks of postoperative mortality and morbidity, infectious complications, prolonged hospitalization, and a greater likelihood of allogeneic red blood cell (RBC) transfusion. Evidence of the clinical and economic disadvantages of RBC transfusion in treating perioperative anaemia has prompted recommendations for its restriction and a growing interest in approaches that rely on patients' own (rather than donor) blood. These approaches are collectively termed 'patient blood management' (PBM). PBM involves the use of multidisciplinary, multimodal, individualized strategies to minimize RBC transfusion with the ultimate goal of improving patient outcomes. PBM relies on approaches (pillars) that detect and treat perioperative anaemia and reduce surgical blood loss and perioperative coagulopathy to harness and optimize physiological tolerance of anaemia. After the recent resolution 63.12 of the World Health Assembly, the implementation of PBM is encouraged in all WHO member states. This new standard of care is now established in some centres in the USA and Austria, in Western Australia, and nationally in the Netherlands. However, there is a pressing need for European healthcare providers to integrate PBM strategies into routine care for patients undergoing orthopaedic and other types of surgery in order to reduce the use of unnecessary transfusions and improve the quality of care. After reviewing current PBM practices in Europe, this article offers recommendations supporting its wider implementation, focusing on anaemia management, the first of the three pillars of PBM.

Comparison of neonatal outcomes of cesarean sections performed under primary or secondary general anesthesia: a retrospective study.

BACKGROUND: The conversion of neuraxial anesthesia (NA) to general anesthesia (GA) during a cesarean section (CS) may be associated with a higher risk of neonatal morbidity by adding the undesirable effects of both these anesthesia techniques. We aimed to compare the neonatal morbidity of non-elective CS performed after conversion from NA to GA (secondary GA) vs. that after GA from the outset (primary GA). METHODS: We performed a monocentric retrospective study at the Angers University Hospital (France). All non-elective CSs performed under GA between January 2015 and December 2019 were included. The CSs were classified using a three-color coding system (green for non-urgent delivery, orange for urgent CS, and red for very urgent CS). The primary neonatal outcome was a composite of umbilical artery pH <7.10 or 5-min Apgar score <7. The crude and adjusted odds ratios (OR) for the risk of neonatal morbidity associated with secondary GA were estimated. RESULTS: We included 247 patients, of whom 101 (41.3%) had a secondary GA and 146 (58.7%) had primary GA. In the secondary GA group, 86.1% (87/101) had epidural anesthesia and 13.9% (14/101) had spinal anesthesia. Multivariate analysis showed no difference in neonatal morbidity between the two groups (adjusted odds ratio 1.18, 95% CI 0.56 to 2.51). CONCLUSIONS: Our study found insufficient evidence to identify a difference in neonatal outcomes between secondary compared with primary GA for CS, regardless of the level of emergency. However, our study is underpowered and additional studies are needed to confirm these data.

Alveolar fibroblasts in acute lung injury: biological behaviour and clinical relevance.

Although fibroblasts are key cells in the lung repair/fibrosis process, their characteristics are poorly studied in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The aims of our study were to: 1) determine the biological behaviour of alveolar fibroblasts during ALI; and 2) to evaluate the clinical relevance of positive alveolar fibroblast culture from patients with ALI/ARDS. Cells were cultured from bronchoalveolar lavage (BAL) obtained from 68 critically ill, ventilated patients: ALI n = 17; ARDS n = 31; and ventilated controls n = 20. Patients were followed for 28 days and clinical data was recorded. We studied proliferation, migration and collagen-1 synthesis capacities of fibroblasts. Cells expressing fibroblast markers were cultured from BAL obtained in six (35%) ALI patients and six (19%) ARDS patients, but never from ventilated controls. Alveolar fibroblasts exhibited a persistent activated phenotype with enhanced migratory and collagen-1 production capacities, with hyporesponsiveness to prostaglandin E(2) compared to normal lung fibroblasts (p< or =0.04). Positive fibroblast culture was associated with both an increased collagen-1 concentration and monocyte/macrophage percentage in BAL fluid (p< or =0.01), and with a reduced duration of mechanical ventilation (p<0.001). We conclude that activated alveolar fibroblasts can be cultured either in ALI or ARDS and that their presence might reflect the initiation of the organising phase of ALI.

Extended-spectrum ß-lactamase Enterobacteriaceae (ESBLE) in intensive care units: strong correlation with the ESBLE colonization pressure in patients but not same species.

Sink drains of six intensive care units (ICUs) were sampled for screening contamination with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBLE). A high prevalence (59.4%) of sink drain contamination was observed. Analysing the data by ICU, the ratio 'number of ESBLE species isolated in sink drains/total number of sink drains sampled' was highly correlated (Spearman coefficient: 0.87; P = 0.02) with the ratio 'number of hospitalization days for patients with ESBLE carriage identified within the preceding year/total number of hospitalization days within the preceding year'. Concurrently, the distribution of ESBLE species differed significantly between patients and sink drains.

Use, timing and factors associated with tracheal intubation in septic shock: a prospective multicentric observational study.

BACKGROUND: No recommendation exists about the timing and setting for tracheal intubation and mechanical ventilation in septic shock. PATIENTS AND METHODS: This prospective multicenter observational study was conducted in 30 ICUs in France and Spain. All consecutive patients presenting with septic shock were eligible. The use of tracheal intubation was described across the participating ICUs. A multivariate analysis was performed to identify parameters associated with early intubation (before H8 following vasopressor onset). RESULTS: Eight hundred and fifty-nine patients were enrolled. Two hundred and nine patients were intubated early (24%, range 4.5-47%), across the 18 centers with at least 20 patients included. The cumulative intubation rate during the ICU stay was 324/859 (38%, range 14-65%). In the multivariate analysis, seven parameters were significantly associated with early intubation and ranked as follows by decreasing weight: Glasgow score, center effect, use of accessory respiratory muscles, lactate level, vasopressor dose, pH and inability to clear tracheal secretions. Global R-square of the model was only 60% indicating that 40% of the variability of the intubation process was related to other parameters than those entered in this analysis. CONCLUSION: Neurological, respiratory and hemodynamic parameters only partially explained the use of tracheal intubation in septic shock patients. Center effect was important. Finally, a vast part of the variability of intubation remained unexplained by patient characteristics. Trial registration Clinical trials NCT02780466, registered on May 23, 2016. https://clinicaltrials.gov/ct2/show/NCT02780466?term=intubatic&draw=2&rank=1.