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Background In mechanically ventilated patients, an increase in cardiac index during an end-expiratory-occlusion test predicts fluid responsiveness. To identify this rapid increase in cardiac index, continuous and instantaneous cardiac index monitoring is necessary, decreasing its feasibility at the bedside. Our study was designed to investigate whether changes in velocity time integral and in peak velocity obtained using transthoracic echocardiography during an end-expiratory-occlusion maneuver could predict fluid responsiveness. Methods This single-center, prospective study included 50 mechanically ventilated critically ill patients. Velocity time integral and peak velocity were assessed using transthoracic echocardiography before and at the end of a 12-sec end-expiratory-occlusion maneuver. A third set of measurements was performed after volume expansion (500 mL of saline 0.9% given over 15 minutes). Patients were considered as responders if cardiac output increased by 15% or more after volume expansion. Results Twenty-eight patients were responders. At baseline, heart rate, mean arterial pressure, cardiac output, velocity time integral and peak velocity were similar between responders and non-responders. End-expiratory-occlusion maneuver induced a significant increase in velocity time integral both in responders and non-responders, and a significant increase in peak velocity only in responders. A 9% increase in velocity time integral induced by the end-expiratory-occlusion maneuver predicted fluid responsiveness with sensitivity of 89% (95% CI 72% to 98%) and specificity of 95% (95% CI 77% to 100%). An 8.5% increase in peak velocity induced by the end-expiratory-occlusion maneuver predicted fluid responsiveness with sensitivity of 64% (95% CI 44% to 81%) and specificity of 77% (95% CI 55% to 92%). The area under the receiver operating curve generated for changes in velocity time integral was significantly higher than the one generated for changes in peak velocity (0.96 ± 0.03 versus 0.70 ± 0.07, respectively, P  = 0.0004 for both). The gray zone ranged between 6 and 10% (20% of the patients) for changes in velocity time integral and between 1 and 13% (62% of the patients) for changes in peak velocity. Conclusions In mechanically ventilated and sedated patients in the neuro Intensive Care Unit, changes in velocity time integral during a 12-sec end-expiratory-occlusion maneuver were able to predict fluid responsiveness and perform better than changes in peak velocity.

Keywords: Augmented renal clearance, Piperacillin, Critical care

The main objective was to assess the performance of the neutrophil-lymphocyte ratio (NLR) for early prediction of delayed neurological impairment and cerebral contusion worsening in patients with mild-to-moderate traumatic brain injury (TBI). Over a 3-year period, every adult patient triaged to our level 1 trauma center with brain contusion and Glasgow Coma Scale (GCS) of 10 or greater were retrospectively included. The main study outcome was the occurrence of delayed clinical deterioration, defined as a GCS < 10 and/or a secondary need for mechanical ventilation, within 5 days after TBI. The performance of NLR for prediction of delayed clinical deterioration was assessed by receiver operating characteristic (ROC) curve. Overall, 115 patients were included and 16 (14%) presented a delayed clinical deterioration. Overall, the NLR at ED admission was higher in patients who developed a delayed clinical deterioration (18 [12–29] vs 8 [5–13], p = 0.0003). The area under the ROC curves for NLR at ED admission in predicting delayed clinical deterioration was 0.79 [0.65–0.93] and NLR > 15 was found to be independently associated with the occurrence of delayed clinical deterioration (adjusted OR = 10.1 [95%CI: 2.3–45.6]). The NLR at ED admission was independently associated with the occurrence of delayed clinical deterioration, although limited by a poor discriminative value by itself. Further studies are needed to test the predictive value of composite scoring systems including NLR for prevention of under-triage of patients with mild-to-moderate TBI.

Background Augmented renal clearance (ARC) is recognized as a leading cause of β-lactam subexposure when conventional dosing regimens are used. The main objective was to compare the clinical outcome of ARC patients treated by conventional or increased β-lactam dosing regimens for a first episode of hospital or ventilator-acquired pneumonia (HAP-VAP). Methods In this single-center, retrospective study, every ARC patient treated by β-lactam for a first episode of HAP-VAP was included during two 15-month periods, before ( Control period ) and after ( Treatment period ) the modification of a local antibiotic therapy protocol. ARC was defined by a 24-h measured creatinine clearance ≥ 150 ml/min. The primary endpoint was defined as a therapeutic failure of the antimicrobial therapy or a HAP-VAP relapse within 28 days. Inverse probability of treatment weight (IPTW) was derived from a propensity score model. Cox proportional hazard models were used to evaluate the association between treatment period and clinical outcome. Results During the study period, 177 patients were included ( control period , N  = 88; treatment period , N  = 89). Therapeutic failure or HAP-VAP relapse was significantly lower in the treatment period (10 vs. 23%, p = 0.019 ). The IPTW-adjusted hazard ratio of poor clinical outcome in the treatment period was 0.35 (95% CI 0.15–0.81), p = 0.014 . No antibiotic side effect was reported during the treatment period. Conclusions Higher than licensed dosing regimens of β-lactams may be safe and effective in reducing the rate of therapeutic failure and HAP-VAP recurrence in critically ill augmented renal clearance (ARC) patients.

PurposeTo assess the impact of delayed hemothorax on outcomes in blunt chest trauma patients without life-threatening condition at admission and characterize the predictive value of predefined anatomical factors for delayed hemothorax.MethodsIn a single-centre retrospective study, every spontaneous breathing patient admitted for a blunt chest trauma without significant pleural effusion at ICU admission was included. A multivariable regression model was used to determine the covariate-adjusted odd of secondary respiratory complications in patients with delayed hemothorax ≥ 500 ml. The characteristics of rib fractures (number, location and displacement) were integrated into a logistic regression model to determine variables associated with delayed hemothorax in multivariate analysis.ResultsOver the study period, 109 patients were included and the rate of delayed hemothorax ≥ 500 ml was 36%. Patients with delayed hemothorax had higher rates of pulmonary infections (OR 4.8 [1.6–16.4]) but no statistical association between delayed hemothorax and secondary respiratory failure (OR 2.0 [0.4–9.4]). A posterior location and a displaced rib fracture were independent predictors of delayed hemothorax (OR 3.4 [1.3–8.6] and OR 2.3 [1.1–5.1], respectively). At least one displaced rib fracture was more specific of delayed hemothorax than the commonly used threshold of three or more rib fractures (81.3 vs. 51.5%).ConclusionDelayed hemothorax is a frequent complication associated with increased risk of pulmonary infection. The posterior location and the displacement of at least one rib fracture in the initial CT scan were independent risk factors for predicting the occurrence of delayed hemothorax.

* Letter * Open Access The kinetic glomerular filtration rate is not interchangeable with measured creatinine clearance for prediction of piperacillin underexposure in critically ill patients with augmented renal clearance * Cédric Carrié1, 6Email author, * Sébastien Rubin2, * Pierre Sioniac1, * Dominique Breilh3, 4 and * Matthieu Biais1, 5 Critical Care2018 22:177 https://doi.org/10.1186/s13054-018-2117-7 © The Author(s). [...]the area under the ROC curve generated for KeGFR was significantly lower than the one generated for measured CrCL for prediction of piperacillin underdosing (0.76 [0.68–0.83] vs 0.85 [0.79–0.91], p = 0.03; Fig. 2). The importance of empiric antibiotic dosing in critically ill trauma patients: are we under-dosing based on augmented renal clearance and inaccurate renal clearance estimates? J Trauma Acute Care Surg. 2016;81(6):1115–21.View ArticlePubMedGoogle Scholar Carrié C, Petit L, d'Houdain N, Sauvage N, Cottenceau V, Lafitte M, Foumenteze C, Hisz Q, Menu D, Legeron R, Breilh D, Sztark F. Association between augmented renal clearance, antibiotic exposure and clinical outcome in critically ill septic patients receiving high doses of β-lactams administered by continuous infusion: a prospective observational study.

Background The benefit–risk ratio of prophylactic non-invasive ventilation (NIV) and high-flow nasal oxygen therapy (HFNC-O 2 ) during the early stage of blunt chest trauma remains controversial because of limited data. The main objective of this study was to compare the rate of endotracheal intubation between two NIV strategies in high-risk blunt chest trauma patients. Methods The OptiTHO trial was a randomized, open-label, multicenter trial over a two-year period. Every adult patients admitted in intensive care unit within 48 h after a high-risk blunt chest trauma (Thoracic Trauma Severity Score ≥ 8), an estimated PaO 2 /FiO 2 ratio < 300 and no evidence of acute respiratory failure were eligible for study enrollment (Clinical Trial Registration: NCT03943914). The primary objective was to compare the rate of endotracheal intubation for delayed respiratory failure between two NIV strategies: i) a prompt association of HFNC-O 2 and “early” NIV in every patient for at least 48 h with vs. ii) the standard of care associating COT and “late” NIV, indicated in patients with respiratory deterioration and/or PaO 2 /FiO 2 ratio ≤ 200 mmHg. Secondary outcomes were the occurrence of chest trauma-related complications (pulmonary infection, delayed hemothorax or moderate-to-severe ARDS). Results Study enrollment was stopped for futility after a 2-year study period and randomization of 141 patients. Overall, 11 patients (7.8%) required endotracheal intubation for delayed respiratory failure. The rate of endotracheal intubation was not significantly lower in patients treated with the experimental strategy (7% [5/71]) when compared to the control group (8.6% [6/70]), with an adjusted OR = 0.72 (95%IC: 0.20–2.43), p  =  0.60 . The occurrence of pulmonary infection, delayed hemothorax or delayed ARDS was not significantly lower in patients treated by the experimental strategy (adjusted OR = 1.99 [95%IC: 0.73–5.89], p  =  0.18, 0.85 [95%IC: 0.33–2.20], p  =  0.74 and 2.14 [95%IC: 0.36–20.77], p  =  0.41 , respectively). Conclusion A prompt association of HFNC-O 2 with preventive NIV did not reduce the rate of endotracheal intubation or secondary respiratory complications when compared to COT and late NIV in high-risk blunt chest trauma patients with non-severe hypoxemia and no sign of acute respiratory failure. Clinical Trial Registration : NCT03943914, Registered 7 May 2019.

Background To explore the underlying mechanisms leading to the occurrence of hyponatremia and enhanced urinary sodium excretion in brain trauma patients using sodium balance and urinary biochemical analysis. Methods We conducted a retrospective analysis of a local database prospectively collected in 60 brain trauma patients without chronic renal dysfunction. Metabolic and hemodynamic parameters were averaged over three consecutive periods over the first seven days after admission. The main outcome investigated in this study was the occurrence of at least one episode of hyponatremia. Results Over the study period, there was a prompt decrease in sodium balance (163 ± 193 vs. -12 ± 154 mmol/day, p < 0.0001 ) and free water clearance (− 0.7 ± 0.7 vs. -1.8 ± 2.3 ml/min, p < 0.0001 ). The area under the ROC curves for sodium balance in predicting the occurrence of hyponatremia during the next period was 0.81 [95% CI: 0.64–0.97]. Variables associated with averaged urinary sodium excretion were sodium intake (R 2  = 0.26, p < 0.0001 ) and fractional excretion of urate (R 2  = 0.15, p = 0.009 ). Urinary sodium excretion was also higher in patients with sustained augmented renal clearance over the study period (318 ± 106 vs. 255 ± 135 mmol/day, p = 0.034 ). Conclusion The decreased vascular volume resulting from a negative sodium balance is a major precipitating factor of hyponatremia in brain trauma patients. Predisposing factors for enhanced urinary sodium excretion were high sodium intake, high fractional excretion of urate and augmented renal clearance over the first seven days after ICU admission.

Background Analgesia Nociception Index (ANI) is a device based on analysis of the R-R interval and respiratory sinus arrhythmia to assess the balance between sympathetic and parasympathetic activity. The autonomic system is directly affected by load changes. Therefore, monitoring sympathetic tone and its change could theoretically allow tracking of load changes during volume expansion. The aim of the present study was to determine whether changes in ANI are able to track the increase in stroke volume caused by volume expansion (SV). Methods This prospective observational study included mechanically ventilated patients undergoing neurosurgery and benefiting from SV monitoring. Exclusion criteria were cardiac dysfunction, arrhythmias, beta-blockade therapy, and dysautonomia. SV was optimized by fluid administration of 250 ml of crystalloid fluid. A positive fluid increase was defined as a SV increase of 10% or more from baseline. Changes in SV and medium ANI (ANIm) were recorded before and 4 to 5 min after volume expansion. Results Sixty-nine patients had 104 fluid challenges (36 positive and 68 negative). Volume expansion resulted in a greater ANI increase in responders than in nonresponders. The change in ANIm > 5 predicted fluid responsiveness with a sensitivity of 68.4% (95% CI: 67.4% to 69.5%) and a specificity of 51.2% (95% CI: 50.1% to 52.3%). The area under the receiver operating characteristic curve was 0.546 (95% CI: 0.544 to 0.549) and appeared to be affected by remifentanil dose and baseline ANI. Conclusion Changes in ANIm induced by fluid challenge is not able to predict fluid responsiveness in mechanically ventilated patients undergoing neurosurgery. Trial registration Clinical trial registration: NCT04223414.

Background: Open abdomen with vacuum-assisted wound closure therapy (OA/VAC) is frequently used in critically ill patients although the impact of OA/VAC on antibiotics pharmacokinetics (PK) remains unknown. We thus aimed to characterize the PK of piperacillin–tazobactam (PTZ) in critically ill patients with OA/VAC and assess the optimal dosing regimens based on pharmacodynamics (PD) target attainment. Methods: Over a 15-month study period, 45 patients with OA/VAC treated with PTZ administered continuously and adapted to 24 h creatinine clearance (CLCR) underwent measurements of free concentrations in their plasma, urine, VAC exudate, and peritoneal fluid. Population PK modeling was performed considering the effect of covariates, and Monte Carlo simulations were employed to determine the probability of target attainment (PTA) for the PK/PD targets (100% fT > 16 mg/L) in the plasma and at the peritoneal site at steady state. Results: Piperacillin concentrations were described using a two-compartment model, with age and total body weight as significant covariates for central volume of distribution (V1) and estimated renal function for clearance (CL). Tazobactam concentrations were described using a two-compartment model with estimated renal function as a significant covariate. The central volume of distributions V1 of piperacillin and tazobactam were 21.2 and 23.2 L, respectively. The VAC-induced peritoneal clearance was negligible compared to renal clearance. Most patients achieved the desirable PK/PD target when using a CLCR-pondered PTZ dosing regimen from 12 g/1.5 g/day to 20 g/2.5 g/day. Conclusions: Despite a wide inter-individual variability, the influence of OA/VAC on piperacillin and tazobactam PK parameters is not straightforward. The use of a CLCR-pondered PTZ dosing regimen from 12 g/1.5 g/day to 20 g/2.5 g/day is needed to reach a PTA > 85%.