Clinical Effectiveness of Transversus Abdominis Plane (TAP) Block versus Local Anesthesia Wound Infiltration for Postoperative Pain Relief After Laparoscopic Appendicectomy in Children: A Study Protocol for a Multicenter Double-Blind Randomized Controlled Phase III Trial.

Purpose: Postoperative pain relief after laparoscopic appendicectomy is a key determinant of early rehabilitation in children. Recent guidelines recommend performing either a transversus abdominis plane (TAP) block or local anesthesia (LA) wound infiltration as part of multimodal postoperative analgesia after appendectomy. To date, the clinical effectiveness of TAP block versus LA wound infiltration has never been compared. The hypothesis of this study is that the TAP block may provide a greater opioid-sparing effect after laparoscopic appendicectomy in children than LA wound infiltration. Study Design and Methods: We designed a multicenter double-blind randomized controlled phase III trial and aim to include 110 children who undergo laparoscopic appendicectomy. Children are randomized to receive either TAP block (TAP group) or LA wound infiltration (infiltration group). Multimodal analgesia is standardized in the two groups using the same protocol, which includes the stepwise prescription of paracetamol, phloroglucinol, ketoprofene, and nalbuphine according to the hetero-evaluation of pain performed by the nurses who were blinded to the treatment allocated using the validated FLACC scale. The primary outcome is the total dose of nalbuphine administered within 24 hours after surgery. Discussion: No study has specifically compared the clinical effectiveness of TAP block versus LA wound infiltration for postoperative pain relief after laparoscopic appendectomy in children. This paper describes the protocol for a randomized trial that addresses this issue. The results of this trial will be useful for editing guidelines with a higher level of evidence on this topic.

Oxygenation management during veno-arterial ECMO support for cardiogenic shock: a multicentric retrospective cohort study.

BACKGOUND: Hyperoxemia is common and associated with poor outcome during veno-arterial extracorporeal membrane oxygenation (VA ECMO) support for cardiogenic shock. However, little is known about practical daily management of oxygenation. Then, we aim to describe sweep gas oxygen fraction (FSO2), postoxygenator oxygen partial pressure (PPOSTO2), inspired oxygen fraction (FIO2), and right radial arterial oxygen partial pressure (PaO2) between day 1 and day 7 of peripheral VA ECMO support. We also aim to evaluate the association between oxygenation parameters and outcome. In this retrospective multicentric study, each participating center had to report data on the last 10 eligible patients for whom the ICU stay was terminated. Patients with extracorporeal cardiopulmonary resuscitation were excluded. Primary endpoint was individual mean FSO2 during the seven first days of ECMO support (FSO2 mean (day 1-7)). RESULTS: Between August 2019 and March 2022, 139 patients were enrolled in 14 ECMO centers in France, and one in Switzerland. Among them, the median value for FSO2 mean (day 1-7) was 70 [57; 79] % but varied according to center case volume. Compared to high volume centers, centers with less than 30 VA-ECMO runs per year were more likely to maintain FSO2 ≥ 70% (OR 5.04, CI 95% [1.39; 20.4], p = 0.017). Median value for right radial PaO2 mean (day 1-7) was 114 [92; 145] mmHg, and decreased from 125 [86; 207] mmHg at day 1, to 97 [81; 133] mmHg at day 3 (p < 0.01). Severe hyperoxemia (i.e. right radial PaO2 ≥ 300 mmHg) occurred in 16 patients (12%). PPOSTO2, a surrogate of the lower body oxygenation, was measured in only 39 patients (28%) among four centers. The median value of PPOSTO2 mean (day 1-7) value was 198 [169; 231] mmHg. By multivariate analysis, age (OR 1.07, CI95% [1.03-1.11], p < 0.001), FSO2 mean (day 1-3)(OR 1.03 [1.00-1.06], p = 0.039), and right radial PaO2 mean (day 1-3) (OR 1.03, CI95% [1.00-1.02], p = 0.023) were associated with in-ICU mortality. CONCLUSION: In a multicentric cohort of cardiogenic shock supported by VA ECMO, the median value for FSO2 mean (day 1-7) was 70 [57; 79] %. PPOSTO2 monitoring was infrequent and revealed significant hyperoxemia. Higher FSO2 mean (day 1-3) and right radial PaO2 mean (day 1-3) were independently associated with in-ICU mortality.

Prospective randomized double-blind study to evaluate the superiority of Vasopressin versus Norepinephrine in the management of the patient at renal risk undergoing cardiac surgery with cardiopulmonary bypass (NOVACC trial).

BACKGROUND: Cardiac surgery-associated acute kidney injury (CS-AKI) affects up to 30% of patients, increasing morbidity and healthcare costs. This condition results from complex factors like ischemia-reperfusion injury and renal hemodynamic changes, often exacerbated by surgical procedures. Norepinephrine, commonly used in cardiac surgeries, may heighten the risk of CS-AKI. In contrast, vasopressin, a noncatecholaminergic agent, shows potential in preserving renal function by favorably affecting renal hemodynamic. Preliminary findings, suggest vasopressin could reduce the incidence of CS-AKI compared to norepinephrine. Additionally, vasopressin is linked to a lower incidence of postoperative atrial fibrillation, another factor contributing to longer hospital stays and higher costs. This study hypothesizes that vasopressin could effectively reduce CS-AKI occurrence and severity by optimizing renal perfusion during cardiac surgeries. STUDY DESIGN: The NOVACC trial (NCT05568160) is a multicenter, randomized, double blinded superiority-controlled trial testing the superiority of vasopressin over norepinephrine in patients scheduled for cardiac surgery with cardiopulmonary bypass (CPB). The primary composite end point is the occurrence of acute kidney injury and death. The secondary end points are neurological, cardiologic, digestive, and vasopressor related complications at day 7, day 30, day 90, hospital and intensive care unit lengths of stay, medico-economic costs at day 90. CONCLUSION: The NOVACC trial will assess the effectiveness of vasopressin in cardiac surgery with CPB in reducing acute kidney injury, mortality, and medical costs. CLINICAL TRIAL REGISTRATION: NCT05568160.

Protocol Study for the Evaluation of Non-Opioid Balanced General Anaesthesia in Cardiac Surgery with Cardiopulmonary Bypass: A Randomised, Controlled, Multicentric Superiority Trial (OFACAR Study).

Opioid-free anaesthesia (OFA) is general anaesthesia based on the use of several non-opioid molecules that aim to have an analgesic effect, decrease the sympathetic response, decrease hormonal stress, and decrease the inflammatory response during surgery. Although this approach to anaesthesia is regularly used in clinical practice, it remains a novel approach. The literature on this anaesthesia modality finds a number of positive effects on cardiac, respiratory, and cognitive function but no randomised study evaluated these effects during cardiac surgery where there is a high incidence of postoperative complications. The main aim of the study is to compare OFA vs. standard balanced opioid general anaesthesia on the incidence of postoperative complications and the length of stay in intensive care and hospital. OFACAR is a multicentric, randomised, controlled, superiority, single-blind, two parallel-arm clinical trial in patients undergoing cardiac surgery with cardiopulmonary bypass. We compared a balanced general anaesthesia without opioids (OFA group) vs. a balanced opioid general anaesthesia with sufentanil (control group). One hundred and sixty patients will be enrolled in each treatment group. The primary endpoint is a composite one which corresponds to the occurrence of at least one of the postoperative complications, defined according to European standards within 30 days after surgery. Recruitment started in September 2019, and data collection is expected to end in November 2024.

Short-term mortality prediction using a combination of clinical and CT features: Refining the prognosis of critically ill patients in shock.

PURPOSE: To assess the predictive value of combining CT and clinical findings for predicting 10-day mortality in critically ill patients in shock. MATERIALS AND METHODS: From January 1, 2018, to December 31, 2021, 289 consecutives critically ill patients in shock who underwent a contrast enhanced CT were included. Variables at the time of the CT were retrospectively extracted from medical charts. CT examinations were blindly analyzed by two independent radiologists. Multivariable analysis was performed, combining clinical and CT features. A simple survival score for 10-day mortality prediction was built and validated in a further independent external cohort of 70 patients. RESULTS: 10-day mortality rate was 135/289 (47%) in the study sample. At multivariate analysis, catecholamine infusion (OR = 2.11; 95%CI [1.21-4.18], P = 0.011), lactates level > 5 mmol/l (OR = 3.54; 95%CI [1.94-6.54], P < 0.001); total bilirubin > 50 mg/l (OR = 1.79 CI 95% [1.03-3.13], P = 0.039); small bowel dilation (OR = 1.82; 95%CI [1.01-3.32], P = 0.047); diffuse kidney infarction (OR = 2.76; 95%CI [1.26-6.37], P = 0.013) and superior mesentery artery < 5 mm (OR = 1.96; 95%CI [1.10-3.49], P = 0.021) were associated with 10-days mortality. The AUC of the combined model was 0.79; 95%CI [0.74-0.85] in the study sample and 0.87; 95%CI [0.71-0.91] in the validation cohort. CONCLUSION: The combination of CT imaging features and clinical data should emerge as a novel approach to predict short-term mortality in critically ill patients in shock.

Impact of early postoperative blood glucose variability on serum endocan level in cardiac surgery patients: a sub study of the ENDOLUNG observational study.

BACKGROUND: Early postoperative glycemic variability is associated with worse outcome after cardiac surgery, but the underlying mechanisms remain unknown. This study aimed to describe the relationship between postoperative glycemic variability and endothelial function, as assessed by serum endocan level in cardiac surgery patients. METHODS: We performed a post hoc analysis of patients included in the single-center observational ENDOLUNG study. Adult patients who underwent planned isolated coronary artery bypass graft surgery were eligible. Postoperative glycemic variability was assessed by calculating the coefficient of variability (CV) of blood glucose measured within 24 (CV24) and 48 (CV48) hours after surgery. Serum endocan level was measured at 24 (Endocan24) and 48 (Endocan48) hours after surgery. Pearson's correlation coefficient with 95% confidence interval (95% CI) was calculated between CV24 and Endocan24, and between CV48 and Endocan48. RESULTS: Data from 177 patients were analyzed. Median CV24 and CV48 were 18% (range 7 to 39%) and 20% (range 7 to 35%) respectively. Neither CV48 nor CV24 were significantly correlated to Endocan48 and Endocan24 respectively (r (95% CI) = 0.150 (0.001 to 0.290; and r (95% CI) = 0.080 (-0.070 to 0.220), respectively). CONCLUSIONS: Early postoperative glycemic variability within 48 h after planned cardiac surgery does not appear to be correlated with postoperative serum endocan level. CLINICAL TRIAL REGISTRATION NUMBER: NCT02542423.

Abdominal atherosclerosis is not a risk factor of nonocclusive mesenteric ischemia among critically ill patients: a propensity matching study.

BACKGROUND: Although risk factors of occlusive acute mesenteric ischemia are well known, triggering factors of nonocclusive mesenteric ischemia (NOMI) remain unclear. Alongside to the known risk factors for NOMI, the role of atherosclerosis is not fully elucidated. The purpose of our study was to evaluate whether abdominal atherosclerosis is a risk factor for NOMI. METHODS: From January 2018 to December 2021, all consecutive patients admitted to the intensive care unit who underwent contrast-enhanced CT for suspicion of NOMI were evaluated for inclusion. Clinical and biological data at the time of the CT scan were retrospectively extracted from medical charts and reviewed by a single radiologist. The cohorts were matched by a 1:1 propensity score based on the patient clinical, biological data, and abdominal CT features associated with NOMI. Noncontrast CT acquisitions were used to calculate calcium scores of the abdominal aorta, celiac trunk, superior mesenteric artery (SMA), and common iliac artery according to the Agatston method. Analyses were performed before and after propensity score matching. RESULTS: Among the 165 critically ill patients included, 59 (36%) had NOMI. Before matching analysis, the SMA and total abdominal Agatston calcium scores were not different between patients without and with NOMI (52.00 [IQR = 0, 473] vs. 137.00 [IQR = 0, 259], P = 0.857, respectively, and 7253 [IQR = 1220, 21738] versus 5802 [IQR = 2075, 15,084]; P = 0.723). The results were similar after matching 38 patients with NOMI and 38 without: 153 [IQR = 0, 665] versus 85 [IQR = 0, 240] (P = 0.312) for the SMA calcium score, and 7915 [IQR = 1812, 21561] versus 4139 [IQR = 1440, 9858] (P = 0.170) for the total abdominal Agatston calcium score. CONCLUSION: Our results suggest that atherosclerosis is not a risk factor for NOMI in critically ill patients.

Perioperative blood glucose variability and autonomic nervous system activity in on-pump cardiac surgery patients: Study protocol of a single-center observational study.

INTRODUCTION: On-pump coronary artery bypass graft (CABG) and surgical valve replacement (SVR) are high-risk procedures. Several studies reported that perioperative blood glucose (BG) variability was independently associated with impaired postoperative outcome. However, the underlying mechanisms contributing to increased perioperative BG variability and to its deleterious impact remain unknown. The hypothesis of the study is that perioperative BG variability could be related to perioperative alteration of the autonomic nervous system (ANS) activity and to preoperative BG variability. METHODS AND ANALYSIS: We designed a prospective observational single-center study. Four groups of 30 patients will be studied: group 1, including insulin-requiring type 2 diabetic patients undergoing on-pump CABG; group 2, including non-insulin-requiring type 2 diabetic patients undergoing on-pump CABG; group 3, including non-diabetic patients undergoing aortic SVR; and group 4, including non-diabetic patient undergoing on-pump CABG. Preoperative (baseline) and postoperative BG variability will be quantified using the Abbott's Freestyle Libre Pro sensor allowing for continuous subcutaneous BG monitoring. Preoperative (baseline) and postoperative ANS activity will be measured using noninvasive continuous heart rate monitoring (Mooky HR memory®). Blood level and urinary concentration of inflammatory and endothelial dysfunction biomarkers will be measured from blood and urinary samples at the end of the surgery and on postoperative day 1 and 2. The primary objective is to describe the relationship between baseline BG variability and postoperative BG variability. The secondary objectives are to describe the relationship: between baseline and postoperative BG variability according to the diabetes phenotype and to the type of surgery; between the ANS activity and the BG variability; and between postoperative BG variability and, urinary and blood biomarkers.

Clinical effectiveness of hypertonic sodium lactate infusion for intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection: A study protocol of a single center double-blind randomized controlled phase II pilot trial.

INTRODUCTION: Hyperosmolar solutions are prescribed in neurosurgery patients to provide satisfactory intraoperative brain relaxation and to lower cerebral injuries related to surgical retractors. Mannitol is traditionally considered as the first-choice solution for brain relaxation in neurosurgery patients. Hypertonic sodium lactate infusion was reported to provide a higher and longer osmotic effect compared to mannitol in severely brain-injured patients and to prevent impaired cerebral energetics related to brain injuries. To date, the clinical effectiveness of hypertonic sodium lactate infusion has never been studied in neurosurgery patients. The hypothesis of the study is that hyperosmolar sodium lactate infusion may provide satisfactory intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection. METHODS AND ANALYSIS: We designed a phase II randomized, controlled, double-blind, single-center pilot trial, and aim to include 50 adult patients scheduled for craniotomy for supratentorial brain tumor resection under general anesthesia. Patients will be randomized to receive either mannitol (conventional group) or hypertonic sodium lactate (intervention group) infusion at the time of skin incision. Brain relaxation (primary outcome) will be assessed immediately after opening the dura by the neurosurgeon blinded to the treatment allocated using a validated 4-point scale. The primary outcome is the proportion of satisfactory brain relaxation, defined as brain relaxation score of 3 or 4. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee (Comité de Protection des Personnes Est III) and authorized by the French Health Authority (Agence Nationale de Sécurité des Médicaments, Saint-Denis, France). The University Hospital of Besancon is the trial sponsor and the holder of all data and publication rights. Results of the study will be submitted for publication in a peer-review international medical journal and for presentation in abstract (oral or poster) in international peer-reviewed congresses. REGISTRATION: The trial is registered with ClinicalTrials.gov (Identifier: NCT04488874, principal investigator: Prof Guillaume Besch, date of registration: July 28, 2020).

Continuous Transversus Abdominis Plane Infusion via Surgically Inserted Catheter for Postoperative Analgesia After Abdominal Aortic Surgery by Retroperitoneal Approach: TAPCACAO Study.

BACKGROUND: The purpose of our study was to evaluate the analgesic properties of continuous transversus abdominis plane (TAP) infusion with ropivacaine compared to placebo for postoperative analgesia in elective surgery of the abdominal aorta by retroperitoneal exposure. METHODS: We conducted a prospective, single-center, randomized, double-blind study comparing a group of patients with a TAP catheter undoing ropivacaine infusion with a placebo group. Patients received a left retroperitoneal pararectal exposure for abdominal aortic surgery. A continuous infusion catheter was placed under visual control by the surgeon before closure and removed after 48 hr. All patients had postoperative patient-controlled analgesia with morphine. The primary endpoint was morphine consumption during the first 24 hr. RESULTS: The analysis included 25 patients in the placebo group and 24 in the ropivacaine group. The average morphine consumption during the first 24 hr was significantly different, with 31 ± 16 mg in the ropivacaine group and 41 ± 17 mg in the placebo group (P = 0.019). At 48 hr, morphine consumption was still lower in the ropivacaine group (42 ± 26 mg) than in the placebo group (64 ± 25 mg) (P = 0.003). The opioid narcotic-related side effects of opioid infusion (postoperative nausea and vomiting, constipation) and length of hospital stay were similar in both populations. CONCLUSIONS: Our study showed that continuous TAP block with ropivacaine via surgically inserted catheter significantly decreased morphine consumption at 24 and 48 hr after elective abdominal aortic surgery by retroperitoneal exposure.

Treatment of Hyperlactatemia in Acute Circulatory Failure Based on CO2-O2-Derived Indices: Study Protocol for a Prospective, Multicentric, Single, Blind, Randomized, Superiority Study (The LACTEL Study).

Background: Hyperlactatemia is a biological marker of tissue hypoperfusion with well-known diagnostic, prognostic, and therapeutic implications in shock states. In daily clinical practice, it is difficult to find out the exact mechanism underlying hyperlactatemia. Central venous to arterial CO2 difference (pCO2 gap) is a better parameter of tissue hypoperfusion than the usual ones (clinical examination and mixed venous saturation). Furthermore, the ratio between the pCO2 gap and p(v-a)CO2/C(a-v)O2 may be a promising indicator of anaerobic metabolism, allowing for the identification of different causes of tissue hypoxia and hyperlactatemia. The main aim of the study is to demonstrate that initial hemodynamic resuscitation based on an algorithm integrating the pCO2 gap and p(v-a)CO2/C(a-v)O2 ratio vs. usual clinical practice in acute circulatory failure improves lactate clearance. Methods: LACTEL is a randomized, prospective, multicentric, controlled study. It compares the treatment of hyperlactatemia using an algorithm based on the pCO2 gap and P(v-a)CO2/C(a-v)O2 ratio vs. usual clinical practice in acute circulatory failure. A total of 90 patients were enrolled in each treatment group. The primary endpoint is the number of patients with a lactate clearance of more than 10% 2 h after inclusion. Lactate levels were monitored during the first 48 h of treatment as hemodynamic parameters, biological markers of organ failure, and 28-day mortality. Discussion: pCO2 derivate indices may be of better interest than routine clinical indices to differentiate causes of hyperlactatemia and diagnose anaerobiosis. LACTEL results will provide clinical insights into the role of these indices in the early hemodynamic management of acute circulatory failure in the ICU. Clinical Trial Registration: www.clinicaltrials.gov; identifier: NCT05032521.

Optimizing PO2 during peripheral veno-arterial ECMO: a narrative review.

During refractory cardiogenic shock and cardiac arrest, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used to restore a circulatory output. However, it also impacts significantly arterial oxygenation. Recent guidelines of the Extracorporeal Life Support Organization (ELSO) recommend targeting postoxygenator partial pressure of oxygen (PPOSTO2) around 150 mmHg. In this narrative review, we intend to summarize the rationale and evidence for this PPOSTO2 target recommendation. Because this is the most used configuration, we focus on peripheral VA-ECMO. To date, clinicians do not know how to set the sweep gas oxygen fraction (FSO2). Because of the oxygenator's performance, arterial hyperoxemia is common during VA-ECMO support. Interpretation of oxygenation is complex in this setting because of the dual circulation phenomenon, depending on both the native cardiac output and the VA-ECMO blood flow. Such dual circulation results in dual oxygenation, with heterogeneous oxygen partial pressure (PO2) along the aorta, and heterogeneous oxygenation between organs, depending on the mixing zone location. Data regarding oxygenation during VA-ECMO are scarce, but several observational studies have reported an association between hyperoxemia and mortality, especially after refractory cardiac arrest. While hyperoxemia should be avoided, there are also more and more studies in non-ECMO patients suggesting the harm of a too restrictive oxygenation strategy. Finally, setting FSO2 to target strict normoxemia is challenging because continuous monitoring of postoxygenator oxygen saturation is not widely available. The threshold of PPOSTO2 around 150 mmHg is supported by limited evidence but aims at respecting a safe margin, avoiding both hypoxemia and severe hyperoxemia.

Identification of Heparin-Induced Thrombocytopenia in Surgical Critically Ill Patients by Using the HIT Expert Probability Score: An Observational Pilot Study.

Background: Heparin-induced thrombocytopenia (HIT) remains a challenging diagnosis especially in surgical intensive care unit (SICU) patients. The aim of the study was to evaluate for the first time the diagnostic accuracy of the HIT Expert Probability (HEP) score in the early identification of HIT in SICU patients. Methods: The HEP and 4Ts scores were calculated in all patients with suspected HIT during their stay in our SICU. The diagnosis of HIT was finally confirmed (HIT+ group) or excluded (HIT− group) by an independent committee blinded to the HEP and 4Ts score values. The primary outcome was the sensitivity and specificity of a HEP score ≥ 5 for the diagnosis of HIT. The secondary outcome was the area under the ROC curve (AUC) of the HEP and 4Ts scores in the diagnosis of HIT. Results: Respectively 6 and 113 patients were included in the HIT+ and HIT− groups. A HEP score value ≥ 5 had a sensitivity (95% confidence interval (95% CI)) of 1.00 (0.55−1.00), and a specificity (95% CI) of 0.92 (0.86−0.96). The AUC (95% CI) was significantly higher for the HEP score versus for the 4Ts score (0.967 (0.922−1.000) versus 0.707 (0.449−0.965); p = 0.035). Conclusions: A HEP score value < 5 could be helpful to rule out HIT in SICU patients.

Extracorporeal Membrane Oxygenation Cannula-Related Infections: Epidemiology and Risk Factors.

Although being a potential major source of infection in extracorporeal membrane oxygenation (ECMO) patients, data regarding cannula-related infections (CRI) remain scarce. We therefore aimed at describing the epidemiology of CRI among critically ill patients supported by ECMO. Between October 2017 and November 2019, adult patients supported by either venoarterial (VA), venopulmonary arterial, or venovenous (VV) ECMO for more than 24 hours were prospectively enrolled. When CRI was suspected, cannula swab and subcutaneous needle aspirate samples were obtained for microbiological culture. Cannula tips were systematically sent for culture at the time of ECMO removal. Primary end-point was CRI, which was defined by sepsis or local sign of cannula infection and at least one positive culture among swab, subcutaneous needle aspirate or tip. Multivariate analysis was performed to identify risk factors of CRI. Hundred patients were included, including 77 VA, 12 venopulmonary arterial, and 11 VV ECMO. Cannula-related infections were diagnosed after a median duration of ECMO of 10 [7-13] days. Rate of CRI was 24%, including 10% with bacteremia. Most frequent involved pathogens were Enterobacteriaceae (n = 14), Enterococci (n = 8), and coagulase-negative Staphylococci (n = 7). By multivariate analysis, diabetes and ECMO duration were independently associated with CRI.

ß-lactam dosing at the early phase of sepsis: Performance of a pragmatic protocol for target concentration achievement in a prospective cohort study.

PURPOSE: We hypothesized that a protocol of standardized fixed dose using prolonged infusion during the early phase of sepsis may avoid insufficient ß-lactam concentrations. METHODS: In this single center prospective study, patients with sepsis and vasopressors were enrolled if they were treated by either piperacillin-tazobactam, meropenem or cefepime. Βeta-lactams were administered at fixed dose by prolonged infusion. Targeted plasma concentrations for piperacillin, meropenem and cefepime were above 80 mg/L, 8 mg/L and 38 mg/L respectively. Three blood samples were collected per patient over the first 48 h of treatment. Primary endpoint was target concentration achievement during the 48 first hours, defined as all plasma concentrations above the targeted threshold. RESULTS: Among the 89 patients completing the three samples, target concentrations were achieved for 61 (69%). Target concentrations were achieved in 20 (53%), 32 (89%), and 9 (60%) of the patients treated with piperacillin, meropenem and cefepime, respectively. By multivariate analysis, lower APACHE 2 score, higher baseline MDRD creatinine clearance, and piperacillin use were independently associated with insufficient ß-lactam concentrations. CONCLUSION: Despite a fixed dose antibiotic administration protocol with prolonged infusion insufficient ß-lactam concentration was frequent at the early phase of sepsis, especially in less severe patients, without renal failure, and treated with piperacillin. In septic patients with vasopressors, piperacillin dosing higher than 16 g may be needed to achieve the recommended target concentration. TRIAL REGISTRATION: NCT02820987.

French multicentre observational study on SARS-CoV-2 infections intensive care initial management: the FRENCH CORONA study.

AIM: Describing acute respiratory distress syndrome patterns, therapeutics management, and outcomes of ICU COVID-19 patients and indentifying risk factors of 28-day mortality. METHODS: Prospective multicentre, cohort study conducted in 29 French ICUs. Baseline characteristics, comorbidities, adjunctive therapies, ventilatory support at ICU admission and survival data were collected. RESULTS: From March to July 2020, 966 patients were enrolled with a median age of 66 (interquartile range 58-73) years and a median SAPS II of 37 (29-48). During the first 24 h of ICU admission, COVID-19 patients received one of the following respiratory supports: mechanical ventilation for 559 (58%), standard oxygen therapy for 228 (24%) and high-flow nasal cannula (HFNC) for 179 (19%) patients. Overall, 721 (75%) patients were mechanically ventilated during their ICU stay. Prone positioning and neuromuscular blocking agents were used in 494 (51%) and 460 (48%) patients, respectively. Bacterial co-infections and ventilator-associated pneumonia were diagnosed in 79 (3%) and 411 (43%) patients, respectively. The overall 28-day mortality was 18%. Age, pre-existing comorbidities, severity of respiratory failure and the absence of antiviral therapy on admission were identified as independent predictors of 28-day outcome. CONCLUSION: Severity of hypoxaemia on admission, older age (> 70 years), cardiovascular and renal comorbidities were associated with worse outcome in COVID-19 patients. Antiviral treatment on admission was identified as a protective factor for 28-day mortality. Ascertaining the outcomes of critically ill COVID-19 patients is crucial to optimise hospital and ICU resources and provide the appropriate intensity level of care.