"With Great Responsibility Comes Great Uncertainty".

BACKGROUND: Uncertainty is inherent in medicine, and trainees are particularly exposed to the adverse effects of uncertainty. Previous work suggested that junior residents seek to leverage the support of supervisors to regulate the uncertainty encountered in clinical placements. However, a broader conceptual framework addressing uncertainty experience, from the sources of uncertainty to residents' responses, is still needed. OBJECTIVE: To capture the spectrum of uncertainty experiences in medical residents, providing an integrative framework that considers the influence of specialties and training stages on their experience with clinical uncertainty. DESIGN: We used Hillen's uncertainty tolerance framework to conduct a thematic template analysis of individual and focus group interviews, identifying themes and subthemes reflecting residents' experience of clinical uncertainty. PARTICIPANTS: Medical residents from diverse medical specialty training programs, across five French medical schools. APPROACH: Qualitative study driven by an interpretivist research paradigm. RESULTS: Twenty residents from all years of medical residency and diverse medical specialties were interviewed during three focus groups and five individual interviews. They described managing treatments, making ethical decisions, and communicating uncertainty, as their major sources of uncertainty. We identified residents' delayed response to uncertainty as a key theme, fostering the development of experiential learnings. Prior clinical experience was a key determinant of uncertainty tolerance in medical residents. Entrusting residents with responsibilities in patient management promoted their perception of self-efficacy, although situations of loneliness resulted in stress and anxiety. CONCLUSION: Residents face significant uncertainty in managing treatments, ethical decisions, and communication due to limited clinical experience and growing responsibilities. Scaffolding their responsibilities and clearly defining their roles can improve their comfort with uncertainty. To that extent, effective supervision and debriefing are crucial for managing emotional impacts and fostering reflection to learn from their uncertain experiences.

Antithrombin Levels and Heparin Responsiveness during Venoarterial Extracorporeal Membrane Oxygenation: A Prospective Single-center Cohort Study.

BACKGROUND: Unfractionated heparin, administered during venoarterial extracorporeal membrane oxygenation to prevent thromboembolic events, largely depends on plasma antithrombin for its antithrombotic effects. Decreased heparin responsiveness seems frequent on extracorporeal membrane oxygenation; however, its association with acquired antithrombin deficiency is poorly understood. The objective of this study was to describe longitudinal changes in plasma antithrombin levels during extracorporeal membrane oxygenation support and evaluate the association between antithrombin levels and heparin responsiveness. The hypothesis was that extracorporeal membrane oxygenation support would be associated with acquired antithrombin deficiency and related decreased heparin responsiveness. METHODS: Adults receiving venoarterial extracorporeal membrane oxygenation were prospectively included. All patients received continuous intravenous unfractionated heparin using a standardized protocol (target anti-Xa 0.3 to 0.5 IU/ml). For each patient, arterial blood was withdrawn into citrate-containing tubes at 11 time points (from hour 0 up to day 7). Anti-Xa (without dextran or antithrombin added) and antithrombin levels were measured. The primary outcome was the antithrombin plasma level. In the absence of consensus, antithrombin deficiency was defined as a time-weighted average of antithrombin less than or equal to 70%. Data regarding clinical management and heparin dosage were collected. RESULTS: Fifty patients, including 42% postcardiotomy, were included between April 2020 and May 2021, with a total of 447 samples. Median extracorporeal membrane oxygenation duration was 7 (interquartile range, 4 to 12) days. Median antithrombin level was 48% (37 to 60%) at baseline. Antithrombin levels significantly increased throughout the follow-up. Time-weighted average of antithrombin levels was 63% (57 to 73%) and was less than or equal to 70% in 32 (64%) of patients. Overall, 45 (90%) patients had at least one antithrombin value less than 70%, and 35 (70%) had at least one antithrombin value less than 50%. Antithrombin levels were not significantly associated with heparin responsiveness evaluated by anti-Xa assay or heparin dosage. CONCLUSIONS: Venoarterial extracorporeal membrane oxygenation support was associated with a moderate acquired antithrombin deficiency, mainly during the first 72 h, that did not correlate with heparin responsiveness.

Prevalence and risk factors of significant persistent pain symptoms after critical care illness: a prospective multicentric study.

BACKGROUND: Prevalence, risk factors and medical management of persistent pain symptoms after critical care illness have not been thoroughly investigated. METHODS: We performed a prospective multicentric study in patients with an intensive care unit (ICU) length of stay ≥ 48 h. The primary outcome was the prevalence of significant persistent pain, defined as a numeric rating scale (NRS) ≥ 3, 3 months after admission. Secondary outcomes were the prevalence of symptoms compatible with neuropathic pain (ID-pain score > 3) and the risk factors of persistent pain. RESULTS: Eight hundred fourteen patients were included over a 10-month period in 26 centers. Patients had a mean age of 57 (± 17) years with a SAPS 2 score of 32 (± 16) (mean ± SD). The median ICU length of stay was 6 [4-12] days (median [interquartile]). At 3 months, the median intensity of pain symptoms was 2 [1-5] in the entire population, and 388 (47.7%) patients had significant pain. In this group, 34 (8.7%) patients had symptoms compatible with neuropathic pain. Female (Odds Ratio 1.5 95% CI [1.1-2.1]), prior use of anti-depressive agents (OR 2.2 95% CI [1.3-4]), prone positioning (OR 3 95% CI [1.4-6.4]) and the presence of pain symptoms on ICU discharge (NRS ≥ 3) (OR 2.4 95% CI [1.7-3.4]) were risk factors of persistent pain. Compared with sepsis, patients admitted for trauma (non neuro) (OR 3.5 95% CI [2.1-6]) were particularly at risk of persistent pain. Only 35 (11.3%) patients had specialist pain management by 3 months. CONCLUSIONS: Persistent pain symptoms were frequent in critical illness survivors and specialized management remained infrequent. Innovative approaches must be developed in the ICU to minimize the consequences of pain. TRIAL REGISTRATION: NCT04817696. Registered March 26, 2021.

A Deep Learning-Based Automated Framework for Subpeak Designation on Intracranial Pressure Signals.

The intracranial pressure (ICP) signal, as monitored on patients in intensive care units, contains pulses of cardiac origin, where P1 and P2 subpeaks can often be observed. When calculable, the ratio of their relative amplitudes is an indicator of the patient's cerebral compliance. This characterization is particularly informative for the overall state of the cerebrospinal system. The aim of this study is to develop and assess the performances of a deep learning-based pipeline for P2/P1 ratio computation that only takes a raw ICP signal as an input. The output P2/P1 ratio signal can be discontinuous since P1 and P2 subpeaks are not always visible. The proposed pipeline performs four tasks, namely (i) heartbeat-induced pulse detection, (ii) pulse selection, (iii) P1 and P2 designation, and (iv) signal smoothing and outlier removal. For tasks (i) and (ii), the performance of a recurrent neural network is compared to that of a convolutional neural network. The final algorithm is evaluated on a 4344-pulse testing dataset sampled from 10 patient recordings. Pulse selection is achieved with an area under the curve of 0.90, whereas the subpeak designation algorithm identifies pulses with a P2/P1 ratio > 1 with 97.3% accuracy. Although it still needs to be evaluated on a larger number of labeled recordings, our automated P2/P1 ratio calculation framework appears to be a promising tool that can be easily embedded into bedside monitoring devices.

Clinical Benefit of Extubation in Patients on Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: Although patients on venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock are usually supported with mechanical ventilation, it is not clear whether sedation cessation and extubation might improve outcomes. DESIGN: Retrospective cohort study with propensity score overlap weighting analysis. SETTING: Three ICUs in a 1,500-bed tertiary university hospital. PATIENTS: From an overall cohort of 641 patients with venoarterial-extracorporeal membrane oxygenation support, the primary analysis was performed in 344 patients who had been successfully decannulated in order to reduce immortal time bias. MEASUREMENTS AND MAIN RESULTS: Seventy-five patients (22%) were extubated during extracorporeal membrane oxygenation support and were subsequently decannulated alive. Forty-nine percent received noninvasive ventilation, and 25% had emergency reintubation for respiratory, neurologic, or hemodynamic reasons. Higher Simplified Acute Physiology Score II at admission (odds ratio, 0.97; 95% CI [0.95-0.99]; p = 0.008) was associated with a lower probability of extubation, whereas cannulation in cardiac surgery ICU (odds ratio, 3.14; 95% CI [1.21-8.14]; p = 0.018) was associated with an increased probability. Baseline characteristics were well balanced after propensity score overlap weighting. The number of ICU-free days within 30 days of extracorporeal membrane oxygenation decannulation was significantly higher among extubated patients compared with nonextubated patients (22 d [11-26 d] vs 18 d [7-25 d], respectively; p = 0.036). There were no differences in other outcomes including ventilator-associated pneumonia (odds ratio, 0.96; 95% CI [0.51-1.82]; p = 0.90) and all-cause mortality within 30 days of extracorporeal membrane oxygenation decannulation (5% vs 17%; hazard ratio, 0.54; 95% CI [0.19-1.59]; p = 0.27).As a secondary analysis, outcomes were compared in the overall cohort of 641 venoarterial extracorporeal membrane oxygenation-supported patients. Results were consistent with the primary analysis as extubated patients had a higher number of ICU-free days (18 d [0-24 d] vs 0 d [0-18 d], respectively; < 0.001) and a lower risk of death within 30 days of extracorporeal membrane oxygenation cannulation (hazard ratio, 0.45; 95% CI [0.29-0.71]; p = 0.001). CONCLUSIONS: Extubation during venoarterial-extracorporeal membrane oxygenation support is safe, feasible, and associated with greater ICU-free days.

SARS-CoV-2-Induced ARDS Associates with MDSC Expansion, Lymphocyte Dysfunction, and Arginine Shortage.

PURPOSE: The SARS-CoV-2 infection can lead to a severe acute respiratory distress syndrome (ARDS) with prolonged mechanical ventilation and high mortality rate. Interestingly, COVID-19-associated ARDS share biological and clinical features with sepsis-associated immunosuppression since lymphopenia and acquired infections associated with late mortality are frequently encountered. Mechanisms responsible for COVID-19-associated lymphopenia need to be explored since they could be responsible for delayed virus clearance and increased mortality rate among intensive care unit (ICU) patients. METHODS: A series of 26 clinically annotated COVID-19 patients were analyzed by thorough phenotypic and functional investigations at days 0, 4, and 7 after ICU admission. RESULTS: We revealed that, in the absence of any difference in demographic parameters nor medical history between the two groups, ARDS patients presented with an increased number of myeloid-derived suppressor cells (MDSC) and a decreased number of CD8pos effector memory cell compared to patients hospitalized for COVID-19 moderate pneumonia. Interestingly, COVID-19-related MDSC expansion was directly correlated to lymphopenia and enhanced arginase activity. Lastly, T cell proliferative capacity in vitro was significantly reduced among COVID-19 patients and could be restored through arginine supplementation. CONCLUSIONS: The present study reports a critical role for MDSC in COVID-19-associated ARDS. Our findings open the possibility of arginine supplementation as an adjuvant therapy for these ICU patients, aiming to reduce immunosuppression and help virus clearance, thereby decreasing the duration of mechanical ventilation, nosocomial infection acquisition, and mortality.

Association between perioperative normal saline and delayed graft function in deceased-donor kidney transplantation: a retrospective observational study.

PURPOSE: Isotonic 0.9% sodium chloride (normal saline; NS) solution use is common, but its high chloride content has been shown to contribute to acid-base disturbances and acute kidney injury (AKI). As kidney transplant recipients are at high risk of postoperative AKI and renal replacement therapy, we aimed to evaluate the impact of perioperative NS administration on graft function after kidney transplantation. METHODS: All adult patients undergoing deceased-donor kidney transplantation between January 2010 and December 2014 at the Rennes University Hospital were included. Logistic regression models were constructed to evaluate the association of hyperchloremia and hyperchloremic acidosis on delayed graft function (DGF), defined as the need for renal replacement therapy within the first week after transplantation. RESULTS: Three hundred and fifty-nine patients were included, 20% developed DGF. The mean (standard deviation) volume of NS infused in the operating room and in the standard postoperative intensive care unit stay was 4,832 (2,242) mL. In the first 24 postoperative hours, 11% of patients developed hyperchloremia and 11% developed hyperchloremic acidosis. These outcomes were not associated with significantly higher total volumes of NS administration or with DGF. In contrast, multivariable analysis showed that cold ischemia time, donor terminal creatinine, and perioperative NS volume were all independent predictors of DGF. CONCLUSION: Perioperative NS infusion volume was associated with DGF in deceased-donor kidney transplant recipients. Conversely, postoperative hyperchloremia and hyperchloremic acidosis were not associated with an increased risk of DGF, suggesting other mechanisms than a chloride effect.

Impact of age on outcomes of patients assisted by veno-arterial or veno-venous extra-corporeal membrane oxygenation: 403 patients between 2005 and 2015.

INTRODUCTION: To assess the impact of age on early outcomes and mortality in veno-arterial extra-corporeal membrane oxygenation and veno-venous extra-corporeal membrane oxygenation recipients, and to investigate predictors of mortality. METHODS: Single-center retrospective study on prospectively collected data including all patients treated by veno-venous extra-corporeal membrane oxygenation and veno-arterial extra-corporeal membrane oxygenation (January 2005-July 2015). Outcomes were compared among two subgroups: aged less than 65 years (Group 1) versus more than 65 years (Group 2) and by type of support (veno-arterial extra-corporeal membrane oxygenation or veno-venous extra-corporeal membrane oxygenation). RESULTS: Among 403 patients, 20.3% were treated by veno-venous extra-corporeal membrane oxygenation and 79.7% by veno-arterial extra-corporeal membrane oxygenation. Veno-arterial extra-corporeal membrane oxygenation group: 76.6% were included in Group 1 and were more severe (pH 7.30 ± 0.19 vs. 7.35 ± 0.13 in Group 2, p = 0.003; lactates 7.5 ± 5.6 mmol/L vs. 5.8 ± 4.5 mmol/L in Group 2, p = 0.003). Weaning rate was higher in Group 1 (63.8% vs. 45.3%, p = 0.0043). The 30-day survival was higher in Group 1 (52.0% vs. 25.3%, p < 0.001). Univariate analysis identified higher Simplified Acute Physiology Score II (p = 0.02) and noradrenaline (p = 0.04) to be associated with mortality. Veno-venous extra-corporeal membrane oxygenation group: 80.5% were in Group 1. Mean PaO2 was 73.5 ± 42.9 mm Hg versus 100.8 ± 80.3 mm Hg (p = 0.24); FiO2 90.1% ± 18% versus 89.4% ± 16.4% (p = 0.89); and 30-day survival 56.1% versus 25.0% (p = 0.048). CONCLUSION: Patients older than 65 years have higher mortality after veno-arterial extra-corporeal membrane oxygenation or veno-venous extra-corporeal membrane oxygenation. This therapeutic strategy is feasible in the elderly, but comorbidities and clinical presentation have a major impact on prognosis and need to be seriously considered to avoid futile treatment.

Population pharmacokinetics of daptomycin in critically ill patients with various degrees of renal impairment.

Objectives: The objective of this study was to characterize the pharmacokinetics of unbound and total concentrations of daptomycin in infected ICU patients with various degrees of renal impairment. From these results, the probability of attaining antimicrobial efficacy and the risks of toxicity were assessed. Methods: Twenty-four ICU patients with various renal functions and requiring treatment of complicated skin and soft-tissue infections, bacteraemia, or endocarditis with daptomycin were recruited. Daptomycin (Cubicin®) at 10 mg/kg was administered every 24 h for patients with creatinine clearance (CLCR) ≥30 mL/min and every 48 h for patients with CLCR <30 mL/min. Total and unbound plasma concentrations and urine concentrations of daptomycin were analysed simultaneously following a population pharmacokinetic approach. Simulations were conducted to estimate the probability of attaining efficacy (unbound AUCu/MIC >40 or >80) or toxicity (Cmin >24.3 mg/L) targets. Results: Exposure to unbound daptomycin increased when the renal function decreased, thus increasing the probability of reaching the efficacy targets, but also the risk of toxicity. Modifications of the unbound fraction (fu) of daptomycin did not affect the pharmacokinetics of unbound daptomycin, but did affect the pharmacokinetics of total daptomycin. Conclusions: Daptomycin at 10 mg/kg q24h allowed efficacy pharmacokinetic/pharmacodynamic targets for ICU patients with CLCR ≥30 mL/min to be reached. For patients with CLCR <30 mL/min, halving the rate of drug administration, i.e. 10 mg/kg q48h, was sufficient to reach these targets. No adverse events were observed, but the toxicity of the 10 mg/kg q24h dosing regimen should be further assessed, particularly for patients with altered renal function.

Impact of Low-Dose Hydrocortisone on the Incidence of Atrial Fibrillation in Patients With Septic Shock: A Propensity Score-Inverse Probability of Treatment Weighting Cohort Study.

PURPOSE: Atrial fibrillation (AF) is common in the intensive care unit (ICU), notably in patients with septic shock for whom inflammation is an already identified risk factor. The aim of this study was to evaluate the effect of low-dose hydrocortisone on AF occurrence in patients with septic shock. METHODS: We performed a prospective nonrandomized observational study in 5 academic ICUs in France. From November 2012 to June 2014, all patients ≥16 years having septic shock were included, except those who had a history of AF, had a pacemaker, and/or experienced AF during hospitalization before the onset of shock or in whom the onset of shock occurred prior to admission to the ICU. Hydrocortisone was administered at the discretion of the attending physician. The incidence of AF was compared among patients who received hydrocortisone, and the effect of low-dose hydrocortisone on AF was estimated using the inverse probability treatment weighting method based on propensity scores. RESULTS: A total of 261 patients were included (no-hydrocortisone group, n = 138; hydrocortisone group, n = 123). Atrial fibrillation occurred in 57 (22%) patients. Atrial fibrillation rates were 33 (24%) and 24 (19%) in no-hydrocortisone patients and hydrocortisone patients, respectively. In the weighted sample, the proportion of patients who developed AF was 28.8% in the no-hydrocortisone group and 16.8% in the hydrocortisone group (difference: -11.9%; 95% confidence interval: -23.4% to -0.5%; P = .040). CONCLUSION: In patients with septic shock, low-dose hydrocortisone was associated with a lower risk of developing AF during the acute phase.

Prognostic value of high-sensitivity troponin T in aneurysmal subarachnoid hemorrhage: a prospective observational study.

Objective: To evaluate the prognostic value of high-sensitivity troponin (hsT) in severe aneurysmal subarachnoid hemorrhage (aSAH). Methods: This prospective non-interventional study was performed at a surgical intensive care unit (ICU) from 2012 to 2015. Consecutive patients who had severe aSAH were included. A modified Rankin Scale score ≥ 4 or death within 3 months defined a poor outcome. hsT levels were measured at ICU admission and 72 hours following symptom onset. Results: A total of 137 patients were analyzed. The median hsT level was 29 ng/L (range: 7-4485). The best threshold level of hsT for predicting a poor outcome was 22 ng/L. At this threshold, the sensitivity was 71% (95% confidence interval [CI]: 58%-81%) and the specificity was 58% (95%CI: 46%-70%). The area under the ROC curve was 0.61 (95%CI: 0.52-0.71). Based on a multivariate analysis, the independent factors for a poor neurological prognosis were a World Federation of Neurologic Surgeons (WFNS) score ≥ 4 (odds ratio [OR]: 2.61; 95%CI: 1.04-6.56) and an hsT level > 22 ng/L (OR: 2.80; 95%CI: 1.18-6.64). Conclusion: In patients with severe aSAH, with regard for the severity of disease (assessed by the WFNS score), an hsT level > 22 ng/L at ICU admission was associated with poor outcomes.

Patient factors and outcomes associated with the withdrawal or withholding of life-sustaining therapies in mechanically ventilated brain-injured patients: An observational multicentre study.

BACKGROUND: Knowledge of the factors associated with the decision to withdraw or withhold life support (WWLS) in brain-injured patients is limited. However, most deaths in these patients may involve such a decision. OBJECTIVES: To identify factors associated with the decision to WWLS in brain-injured patients requiring mechanical ventilation who survive the first 24 h in the ICU, and to analyse the outcomes and time to death. DESIGN: A retrospective observational multicentre study. SETTINGS: Twenty French ICUs in 18 university hospitals. PATIENTS: A total of 793 mechanically ventilated brain-injured adult patients. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Decision to WWLS within 3 months of ICU admission, and death or Glasgow Outcome Scale (GOS) score at day 90. RESULTS: A decision to WWLS was made in 171 patients (22%), of whom 89% were dead at day 90. Out of the 247 deaths recorded at day 90, 153 (62%) were observed after a decision to WWLS. The median time between admission and death when a decision to WWLS was made was 10 (5 to 20) days vs. 10 (5 to 26) days when no end-of-life decision was made (P < 0.924). Among the 18 patients with a decision to WWLS who were still alive at day 90, three patients (2%) had a GOS score of 2, nine patients (5%) had a GOS score of 3 and five patients (3%) a GOS score of 4. Older age, presence of one nonreactive and dilated pupil, Glasgow Coma Scale less than 7, barbiturate use, acute respiratory distress syndrome and worsening lesions on computed tomography scans were each independently associated with decisions to WWLS. CONCLUSION: Using a nationwide cohort of brain-injured patients, we observed a high proportion of deaths associated with an end-of-life decision. Older age and several disease severity factors were associated with the decision to WWLS.

Effect of Continuous versus Intermittent Subglottic Suctioning on Tracheal Mucosa by the Mallinckrodt TaperGuard Evac Oral Tracheal Tube in Intensive Care Unit Ventilated Patients: A Prospective Randomized Study.

BACKGROUND AND AIMS: A risk of tracheal mucosa injury induced by subglottic suctioning has been raised. Therefore, this prospective randomized study aims to compare the effect of continuous suctioning of subglottic secretions versus intermittent suctioning of subglottic secretions (CSSS vs. ISSS) secretions on tracheal mucosa in front of the suctioning port of the endotracheal tube. PATIENTS AND METHODS: Patients requiring intubation or reintubation in Intensive Care Unit with an expected ventilation duration > 24 h were eligible. Participants received CSSS at -20 mmHg or ISSS at -100 mmHg during 15 s and no suction during 8 s. The effect on tracheal mucosa in front of the suction port was assessed after intubation (T0) and before extubation (T1) using bronchoscopy. Tracheal mucosa damages were graded into five categories (no injury, erythema, edema, ulceration, or necrosis). The occurrence (no injury observed at T0 but present at T1) or the worsening (injury observed at T0 exacerbating at T1) was studied. RESULTS: Seventy-three patients were included and 53 patients (CSSS, n = 26 and ISSS, n = 27) were evaluable on the primary endpoint. The occurrence or worsening of tracheal mucosal damages did not differ between the two groups (CSSS, n = 7 [27%] vs. ISSS, n = 5 [17%], P = 0.465). Daily average volume of suctioned secretion was higher with ISSS (74 ± 100 ml vs. 20 ± 25 ml, P < 0.001). Impossibility to aspirate was higher with CSSS (0.14 ± 0.16 per day vs. 0.03 ± 0.07 per day, P < 0.001). CONCLUSIONS: Our results suggest that tracheal mucosal damages did not differ between CSSS and ISSS. The aspirated volume was higher and impossibility to aspirate was lower with ISSS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01555229.

Extubation Success Prediction in a Multicentric Cohort of Patients with Severe Brain Injury.

BACKGROUND: Patients with brain injury are at high risk of extubation failure. METHODS: We conducted a prospective observational cohort study in four intensive care units of three university hospitals. The aim of the study was to create a score that could predict extubation success in patients with brain injury. RESULTS: A total of 437 consecutive patients with brain injury were included, and 338 patients (77.3%) displayed successful extubation. In the multivariate analysis, four features were associated with success the day of extubation: age less than 40 yr, visual pursuit, swallowing attempts, and a Glasgow coma score greater than 10. In the score, each item counted as one. A score of 3 or greater was associated with 90% extubation success. The area under the receiver-operator curve was 0.75 (95% CI, 0.69 to 0.81). After internal validation by bootstrap, the area under the receiver-operator curve was 0.73 (95% CI, 0.68 to 0.79). Extubation success was significantly associated with shorter duration of mechanical ventilation (11 [95% CI, 5 to 17 days] vs. 22 days [95% CI, 13 to 29 days]; P < 0.0001), shorter intensive care unit length of stay (15 [95% CI, 9 to 23 days] vs. 27 days [95% CI, 21 to 36 days]; P < 0.0001), and lower in-intensive care unit mortality (4 [1.2%] vs. 11 [11.1%]; P < 0.0001). CONCLUSIONS: Our score exploring both airway functions and neurologic status may increase the probability of successful extubation in patients with severe brain injury.

Ex Vivo Model to Decipher the Impact of Extracorporeal Membrane Oxygenation on Beta-lactam Degradation Kinetics.

BACKGROUND: As a consequence of drug sequestration, increase in volume of distribution, or alteration of elimination, extracorporeal membrane oxygenation (ECMO) might lead to inadequate plasma concentrations of vital drugs. The aim of this experimental study was to develop an ex vivo model to better characterize the impact of ECMO procedure on beta-lactam antibiotics pharmacokinetics. METHODS: Plasma concentrations of cefotaxime, ceftazidime, cefepime, piperacillin, oxacillin, amoxicillin, and ceftriaxone were measured in an ex vivo ECMO circuit primed with whole human blood and compared with controls stored in glass tubes and polyvinyl chloride tubing. Serial blood samples were collected over 48 hours, and the concentrations of beta-lactam antibiotics were quantified using a validated high-performance liquid chromatography assay. The concentrations' decay rate over time was compared between the ECMO circuits and controls using nonlinear mixed-effect modeling. RESULTS: Cefotaxime concentrations decreased markedly: 86% of the initial concentration remained after 4 hours and only 21% after 48 hours (P < 0.05 for the comparison in rate of decrease with both glass and polyvinyl chloride controls). There was no difference in the rate of decrease between ECMO circuit and controls for the other beta-lactam antibiotics. The average drug recoveries from the ECMO circuits at 48 hours were as follows: ceftazidime, 73%; cefepime, 67%; piperacillin, 71%; oxacillin, 46%; and amoxicillin, 72%. Concentrations of ceftriaxone remained stable throughout the 48-hour study both in ECMO circuits and in controls. CONCLUSIONS: Significant losses of cefotaxime were observed, whereas ceftazidime, cefepime, piperacillin, oxacillin, and amoxicillin decrease was moderate and similar to that of the control group, and ceftriaxone concentrations remained unchanged. These results are reassuring for the use of beta-lactam antibiotics in critically ill patients treated with ECMO.

Empiric antimicrobial therapy for ventilator-associated pneumonia after brain injury.

Issues regarding recommendations on empiric antimicrobial therapy for ventilator-associated pneumonia (VAP) have emerged in specific populations.To develop and validate a score to guide empiric therapy in brain-injured patients with VAP, we prospectively followed a cohort of 379 brain-injured patients in five intensive care units. The score was externally validated in an independent cohort of 252 brain-injured patients and its extrapolation was tested in 221 burn patients.The multivariate analysis for predicting resistance (incidence 16.4%) showed two independent factors: preceding antimicrobial therapy ≥48 h (p<0.001) and VAP onset ≥10 days (p<0.001); the area under the receiver operating characteristic curve (AUC) was 0.822 (95% CI 0.770-0.883) in the learning cohort and 0.805 (95% CI 0.732-0.877) in the validation cohort. The score built from the factors selected in multivariate analysis predicted resistance with a sensitivity of 83%, a specificity of 71%, a positive predictive value of 37% and a negative predictive value of 96% in the validation cohort. The AUC of the multivariate analysis was poor in burn patients (0.671, 95% CI 0.596-0.751).Limited-spectrum empirical antimicrobial therapy has low risk of failure in brain-injured patients presenting with VAP before day 10 and when prior antimicrobial therapy lasts <48 h.

The Accuracy of Temperature Measurements Provided by the Edwards Lifesciences Pulmonary Artery Catheter.

BACKGROUND: Pulmonary artery catheters (PACs) are frequently used for monitoring patient temperatures in the intensive care unit. Nevertheless, data regarding the accuracy of these measurements are lacking, and few data testify to the accuracy of temperatures recorded after the PAC has been in place for several days. The absolute values of such measurements are relevant for critical care because patient temperatures are often used as diagnostic criteria for sepsis and antibiotic therapy. We thus hypothesized that the Edwards Lifesciences PAC would accurately measure blood temperature. To test our hypothesis, we compared temperature measurements obtained from PACs inserted in patients for different lengths of time with measurements of a reference platinum resistance thermometer (PRT). METHODS: PACs were removed and analyzed in 39 patients in whom PACs were inserted for 0 to 5 days. The PACs were placed in calibration baths, and 10 consecutive measurements at each of 7 different temperatures were obtained (36°C, 36.5°C, 37°C, 38°C, 38.3°C, 39°C, and 40°C). The temperature measurements obtained using PACs were compared with measurements obtained using a PRT. Bland-Altman statistical analyses were performed. Outliers, defined as PAC temperature measurements that varied more than ±0.3°C from PRT measurements, were identified. We considered a catheter unfit for clinical diagnostic or therapeutic use if ≥15% of data pairs were outliers. RESULTS: A total of 2730 data pairs were analyzed. Overall, the bias was -0.15°C; the precision was +0.13°C; and the limits of agreement were -0.45°C to +0.13°C. The bias and limits of agreement did not differ according to the age of the catheter or the temperature tested. One hundred fourteen data pairs (4.2% [95% confidence interval, 2.0%-6.4%]), involving 13 PACs and mostly from 4 PACs, were outliers. CONCLUSIONS: We conclude that temperature measurements obtained using the Edwards Lifesciences PACs are thus sufficiently accurate to be used for clinical temperature monitoring in critically ill patients.

High-dose continuous oxacillin infusion results in achievement of pharmacokinetics targets in critically ill patients with deep sternal wound infections following cardiac surgery.

Knowledge regarding antimicrobial therapy strategies in deep sternal wound infections (DSWI) following cardiac surgery is limited. Therefore, we aimed to determine the steady-state plasma and mediastinal concentrations of oxacillin administered by continuous infusion in critically ill patients with DSWI and to compare these concentrations with the susceptibility of staphylococci recovered. A continuous infusion of oxacillin (150 to 200 mg/kg of body weight/24 h) was administered after a loading dose (50 mg/kg). Plasma and mediastinal concentrations of total and unbound oxacillin were determined 4 h after the loading dose (H4) and then at day 1 (H24) and day 2 (H48). Twelve patients were included. Nine patients exhibited bacteremia, 5 were in septic shock, 8 were positive for Staphylococcus aureus, and 4 were positive for coagulase-negative staphylococci. The median MIC (first to third interquartile range) was 0.25 (0.24 to 0.41) mg/liter. Median plasma concentrations of total and unbound oxacillin at H4, H24, and H48 were, respectively, 64.4 (41.4 to 78.5) and 20.4 (12.4 to 30.4) mg/liter, 56.9 (31.4 to 80.6) and 21.7 (6.5 to 27.3) mg/liter, and 57.5 (32.2 to 85.1) and 20 (14.3 to 35.7) mg/liter. The median mediastinal concentrations of total and unbound oxacillin at H4, H24, and H48 were, respectively, 2.3 (0.7 to 25.9) and 0.9 (<0.5 to 15) mg/liter, 29.1 (19.7 to 38.2) and 12.6 (5.9 to 19.8) mg/liter, and 31.6 (14.9 to 42.9) and 17.1 (6.7 to 26.7) mg/liter. High-dose oxacillin delivered by continuous infusion is a valuable strategy to achieve our pharmacokinetic target (4× MIC) at the site of action at H24. But concerns remain in cases of higher MICs, emphasizing the need for clinicians to obtain the MICs for the bacteria and to monitor oxacillin concentrations, especially the unbound forms, at the target site.

Effect of a fever control protocol-based strategy on ventilator-associated pneumonia in severely brain-injured patients.

INTRODUCTION: Fever is associated with a poor outcome in severely brain-injured patients, and its control is one of the therapies used in this condition. But, fever suppression may promote infection, and severely brain-injured patients are frequently exposed to infectious diseases, particularly ventilator-associated pneumonia (VAP). Therefore, we designed a study to explore the role of a fever control protocol in VAP development during neuro-intensive care. METHODS: An observational study was performed on severely brain-injured patients hospitalized in a university ICU. The primary goal was to assess whether fever control was a risk factor for VAP in a prospective cohort in which a fever control protocol was applied and in a historical control group. Moreover, the density of VAP incidence was compared between the two groups. The statistical analysis was based on a competing risk model multivariate analysis. RESULTS: The study included 189 brain-injured patients (intervention group, n = 98, and historical control group, n = 91). The use of a fever control protocol was an independent risk factor for VAP (hazard ratio 2.73, 95% confidence interval (1.38, 5.38; P = 0.005)). There was a significant increase in the incidence of VAP in patients treated with a fever control protocol (26.1 versus 12.5 VAP cases per 1000 days of mechanical ventilation). In cases in which a fever control protocol was applied for > 3 days, we observed a higher rate of VAP in comparison with the rate among patients treated for ≤ 3 days. CONCLUSIONS: Fever control in brain-injured patients was a major risk factor for VAP occurrence, particularly when applied for > 3 days.

Management of spontaneous septic hypothermia in intensive care. A national survey of French intensive care units.

The benefit of temperature control in sepsis or septic shock is still under debate in the literature. We developed a national survey to assess the current state of knowledge and the practical management of spontaneous septic hypothermia in French intensive care units. Out of more 764 intensivists who were contacted, 436 responded to the survey. The majority of doctors (52.4%) considered spontaneous septic hypothermia to be a frequently encountered situation in intensive care, and 62.1% were interested in this problem. Definition of spontaneous septic hypothermia among French intensivists was not consensual. More than half of the doctors questioned (57.1%) stated that they did not actively rewarm patients suffering from spontaneous septic hypothermia.