Neurologic Outcomes and Quality of Life in Children After Extracorporeal Membrane Oxygenation.

RATIONALE: Use of life support with extracorporeal membrane oxygenation (ECMO) is associated with brain injury. However, the consequences of these injuries on subsequent neurologic development and health-related quality of life (HRQoL) are poorly described in children. OBJECTIVES: The aim of this preliminary study was to describe short- and long-term neurologic outcomes in survivors of ECMO, as well as their HRQoL. DESIGN: Retrospective identified cohort with contemporary evaluations. SETTING: Necker Children's Hospital academic PICU. PATIENTS: Forty survivors who underwent ECMO (October 2014 to January 2020) were included in follow-up assessments in May 2021. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We first reviewed the outcomes of ECMO at the time of PICU discharge, which included a summary of neurology, radiology, and Pediatric Overall/Cerebral Performance Category (POPC/PCPC) scores. Then, in May 2021, we interviewed parents and patients to assess HRQoL (Pediatric Quality of Life Inventory [PedsQL]) and POPC/PCPC for children 3 years old or older, and Denver II test (DTII) for younger children. An evaluation of DTII in the youngest patients 1 year after ECMO decannulation was also added. Median age at ECMO was 1.4 years (interquartile range [IQR], 0.4-6 yr). Thirty-five children (88%) underwent a venoarterial ECMO. At PICU discharge, 15 of 40 patients (38%) had neurologic impairment. Assessment of HRQoL was carried out at median of 1.6 years (IQR, 0.7-3.3 yr) after PICU discharge. PedsQL scores were over 70 of 100 for all patients (healthy peers mean results: 80/100), and scores were like those published in patients suffering with chronic diseases. In May 2021, seven of 15 patients had a normal DTII, and 36 of 40 patients had a POPC/PCPC score less than or equal to 3. CONCLUSIONS: None of our patients presented severe disability at long term, and HRQoL evaluation was reassuring. Considering the risk of neurologic impairment after ECMO support, a systematic follow-up of these high-risk survivor patients would be advisable.

Severe meningoencephalitis: epidemiology and outcomes.

PURPOSE OF REVIEW: This article aims to provide an updated review on the epidemiology and outcomes of severe meningoencephalitis. RECENT FINDINGS: Meningoencephalitis is a critical medical condition characterized by inflammation in both the meninges and brain parenchyma. Bacterial, viral, or fungal infections are common causes, although noninfectious factors, such as autoimmune causes, can also contribute. In patients requiring intensive care, meningoencephalitis is associated with a severe prognosis, including mortality rates ranging from 11 to 25% and functional disability in 15-25% of survivors. Recent multicenter studies have identified several parameters linked to poor outcomes, including older age, immunocompromised status, focal neurologic signs, abnormal brain imaging, and delayed administration of antimicrobials. The use of new multiplex PCR techniques for diagnosis has generated debate based on recent data. Investigation is still needed to determine the effectiveness of adjunctive therapies, including seizure prophylaxis, and adjunctive steroids for nonbacterial causes. SUMMARY: Recent multicenter studies have enhanced our understanding of the current epidemiology and outcomes of severe meningoencephalitis in adult patients.

The spectrum of sepsis-associated encephalopathy: a clinical perspective.

Sepsis-associated encephalopathy is a severe neurologic syndrome characterized by a diffuse dysfunction of the brain caused by sepsis. This review provides a concise overview of diagnostic tools and management strategies for SAE at the acute phase and in the long term. Early recognition and diagnosis of SAE are crucial for effective management. Because neurologic evaluation can be confounded by several factors in the intensive care unit setting, a multimodal approach is warranted for diagnosis and management. Diagnostic tools commonly employed include clinical evaluation, metabolic tests, electroencephalography, and neuroimaging in selected cases. The usefulness of blood biomarkers of brain injury for diagnosis remains limited. Clinical evaluation involves assessing the patient's mental status, motor responses, brainstem reflexes, and presence of abnormal movements. Electroencephalography can rule out non-convulsive seizures and help detect several patterns of various severity such as generalized slowing, epileptiform discharges, and triphasic waves. In patients with acute encephalopathy, the diagnostic value of non-contrast computed tomography is limited. In septic patients with persistent encephalopathy, seizures, and/or focal signs, magnetic resonance imaging detects brain injury in more than 50% of cases, mainly cerebrovascular complications, and white matter changes. Timely identification and treatment of the underlying infection are paramount, along with effective control of systemic factors that may contribute to secondary brain injury. Upon admission to the ICU, maintaining appropriate levels of oxygenation, blood pressure, and metabolic balance is crucial. Throughout the ICU stay, it is important to be mindful of the potential neurotoxic effects associated with specific medications like midazolam and cefepime, and to closely monitor patients for non-convulsive seizures. The potential efficacy of targeted neurocritical care during the acute phase in optimizing patient outcomes deserves to be further investigated. Sepsis-associated encephalopathy may lead to permanent neurologic sequelae. Seizures occurring in the acute phase increase the susceptibility to long-term epilepsy. Extended ICU stays and the presence of sepsis-associated encephalopathy are linked to functional disability and neuropsychological sequelae, underscoring the necessity for long-term surveillance in the comprehensive care of septic patients.

Incidence, risk factors and treatment of central nervous system immune reconstitution inflammatory syndrome in non-HIV patients with tuberculous meningitis: a multicentre observational study.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) affecting the central nervous system (CNS) is associated with poor outcomes. AIMS: To report on risk factors for CNS-IRIS following tuberculous meningitis (TBM) in HIV-negative patients. METHODS: In this retrospective multicentre study, all HIV-negative adult patients admitted between 2003 and 2021 with microbiologically proven TBM were included. The primary outcome measure was IRIS onset over follow-up. Characteristics of patients who developed IRIS were described. Factors associated with IRIS were identified using a multivariable logistic regression procedure. RESULTS: Fifty-six patients (33.0 (27.0-44.3) years, 39 (69.6%) men) with microbiologically proven TBM were studied. All patients received antituberculosis treatment and 48 (n = 48/56; 85.7%) steroids at TBM diagnosis. During a median follow-up of 18.0 (12.0-27.3) months, IRIS occurred in 28 (n = 28/56, 50.0%) patients, at a median time of 2.0 (1.0-3.0) months after antituberculosis treatment was started. IRIS involved the CNS in all but one case. Imaging revealed new (n = 23/28, 82.1%) and/or worsening (n = 21/28; 75.0%) of previously recognised lesions. Multivariable analysis showed that meningeal enhancement on brain magnetic resonance imaging (MRI) (odds ratio (OR): 15.3; 95% confidence interval (CI): (1.19-1193.5)) at TBM diagnosis and high blood albumin level (OR: 1.21; 95% CI: (1.02-1.60)) were associated with the occurrence of CNS-IRIS during follow-up. CONCLUSION: CNS-IRIS following TBM in non-HIV patients appears frequent and severe. Meningeal enhancement on brain MRI at tuberculosis diagnosis is a risk factor for CNS-IRIS.

Piperacillin Population Pharmacokinetics and Dosing Regimen Optimization in Critically Ill Children Receiving Continuous Renal Replacement Therapy.

We aimed to develop a piperacillin population pharmacokinetic (PK) model in critically ill children receiving continuous renal replacement therapy (CRRT) and to optimize dosing regimens. The piperacillin plasma concentration was quantified by high-performance liquid chromatography. Piperacillin PK was investigated using a nonlinear mixed-effect modeling approach. Monte Carlo simulations were performed to compute the optimal scheme of administration according to the target of 100% interdose interval time in which concentration is one to four times above the MIC (100% fT > 1 to 4× MIC). A total of 32 children with a median (interquartile range [IQR]) postnatal age of 2 years (0 to 11), body weight (BW) of 15 kg (6 to 38), and receiving CRRT were included. Concentration-time courses were best described by a one-compartment model with first-order elimination. BW and residual diuresis (Qu) explained some between-subject variabilities on volume of distribution (V), where [Formula: see text], and clearance (CL), where [Formula: see text], where CLpop and Vpop are 6.78 L/h and 55.0 L, respectively, normalized to a 70-kg subject and median residual diuresis of 0.06 mL/kg/h. Simulations with intermittent and continuous administrations for 4 typical patients with different rates of residual diuresis (0, 0.1, 0.25, and 0.5 mL/kg/h) showed that continuous infusions were appropriate to attain the PK target for patients with residual diuresis higher than 0.1 mL/kg/h according to BW and MIC, while for anuric patients, less frequent intermittent doses were mandatory to avoid accumulation. Optimal exposure to piperacillin in critically ill children on CRRT should be achieved by using continuous infusions with escalating doses for high-MIC bacteria, except for anuric patients who require less frequent intermittent doses.

Brain abscess in immunocompetent patients: recent findings.

PURPOSE OF REVIEW: We conducted a systematic review of the literature to update findings on the epidemiology and the management of cerebral abscesses in immunocompetent patients. RECENT FINDINGS: Observational studies suggest that the overall prognosis has improved over the last decades but mortality rates remain high. Several parameters may contribute to a better prognosis, including the identification of common risk factors for brain abscess, the systematic use of brain MRI at diagnosis, the implementation of appropriate neurosurgical and microbiological techniques for diagnosis, the optimization of the antibacterial treatment based on epidemiology and pharmacokinetic/pharmacodynamic studies, and a long-term follow-up for detection of secondary complications. Outcome research on brain abscess is mainly based on observational studies. Randomized controlled trials have yet to be performed to identify clinically relevant interventions associated with improved patient-centered outcomes. SUMMARY: Our review highlights the importance of a multidisciplinary approach to optimize brain abscess management both at the acute phase and in the long-term. Randomized controlled studies are urgently needed to identify interventions associated with improved outcomes.

Novel mutations in antiviral multiresistant HSV-2 genital lesion: A case report.

HSV-2 antiviral resistance mainly occurs in immunocompromised patients and especially in HIV-positive individuals receiving long-term antiviral treatment. Those situations can be challenging as few alternatives are available for HSV infection management. To describe clinical and virological significance of two novel potential HSV-2 resistance mutations after treating an obese patient with a pseudotumoral genital HSV-related lesion. Consecutive different antiviral treatments were used: valacyclovir (VACV) then foscarnet (FOS) then topical cidofovir (CDV) and finally imiquimod. Under VACV, genotypic resistance testing revealed a novel mutation within viral thymidine kinase (TK, gene UL23) not previously reported but probably accounting for antiviral resistance: W89G, similar to W88R mutation reported in HSV-1 TK, known to be associated with ACV resistance for HSV-1. Under FOS, while initial mutations were still present, a second genotypic resistance testing performed on persisting lesions showed a novel mutation within viral DNA polymerase (DNA pol, gene UL30): C625R. All three antivirals used in this case are small molecules and pharmacokinetics of VACV, FOS, and CDV have not been evaluated in animals and there are very few studies in human. As small molecules are poorly bound to proteins and distribution volume is increased in obese patients, there is risk of underdosage. This mechanism is suspected to be involved in emergence of resistance mutation and further data is needed to adapt, closely to patient profile, antiviral dosage. This report describes a chronic HSV-2 genital lesion, with resistance to current antivirals and novel mutations within viral TK and DNA pol which may confer antiviral resistance.

Critical care management of meningitis and encephalitis: an update.

PURPOSE OF REVIEW: Meningitis and encephalitis represent severe neurological syndromes associated with encephalopathy, seizures, focal deficits, and neurological sequelae in survivors. We update on the critical care management of adult patients with severe meningitis and encephalitis. RECENT FINDINGS: Large multicenter studies conducted in the adult population improved current knowledge on the epidemiology and outcomes of patients with severe meningitis and encephalitis. An early multimodal diagnostic workup (including CSF analysis, brain MRI, EEG, and serum studies) is mandatory for diagnosis and prognostication in those patients.New diagnostic methods, including multiplex PCR and next-generation sequencing techniques, allow for a faster differential diagnosis of infectious causes that may require specific antimicrobial therapy. Autoimmune causes of encephalitis, which may require urgent immunotherapy, are also increasingly recognized in the ICU setting. Although observational data suggest that early combined immunotherapy is associated with better neurological outcomes in patients with autoimmune encephalitis, randomized clinical trials have yet to be performed. SUMMARY: Our review highlights the importance of an early multimodal approach for diagnosing severe meningitis and encephalitis. Randomized clinical trials are needed to identify pharmacological interventions that may improve patients' outcomes.

Impact of prior antibiotic therapy on severe necrotizing soft-tissue infections in ICU patients: results from a French retrospective and observational study.

Necrotizing soft-tissue infection (NSTI) is a life-threatening pathology that often requires management in intensive care unit (ICU). Therapies consist of early diagnosis, adequate surgical source control, and antimicrobial therapy. Whereas guidelines underline the need for appropriate routine microbiological cultures before starting antimicrobial therapy in patients with suspected sepsis or septic shock, delaying adequate therapy also strongly increases mortality. The aim of the present study was to compare the characteristics and outcomes of patients hospitalized in ICU for NSTI according to their antimicrobial therapy exposure > 24 h before surgery (called the exposed group) or not (called the unexposed group) before surgical microbiological sampling. We retrospectively included 100 consecutive patients admitted for severe NSTI. The exposed group consisted of 23(23%) patients, while 77(77%) patients belonged to the unexposed group. The demographic and underlying disease conditions were similar between the two groups. Microbiological cultures of surgical samples were positive in 84 patients and negative in 16 patients, including 3/23 (13%) patients and 13/77 (17%) patients in the exposed and unexposed groups, respectively (p = 0.70). The distribution of microorganisms was comparable between the two groups. The main antimicrobial regimens for empiric therapy were also similar, and the proportions of adequacy were comparable (n = 60 (84.5%) in the unexposed group vs. n = 19 (86.4%) in the exposed group, p = 0.482). ICU and hospital lengths of stay and mortality rates were similar between the two groups. In conclusion, in a population of severe ICU NSTI patients, antibiotic exposure before sampling did not impact either culture sample positivity or microbiological findings.

Increased risk of severe COVID-19 in hospitalized patients with SARS-CoV-2 Alpha variant infection: a multicentre matched cohort study.

BACKGROUND: The impact of the variant of concern (VOC) Alpha on the severity of COVID-19 has been debated. We report our analysis in France. METHODS: We conducted an exposed/unexposed cohort study with retrospective data collection, comparing patients infected by VOC Alpha to contemporaneous patients infected by historical lineages. Participants were matched on age (± 2.5 years), sex and region of hospitalization. The primary endpoint was the proportion of hospitalized participants with severe COVID-19, defined as a WHO-scale > 5 or by the need of a non-rebreather mask, occurring up to day 29 after admission. We used a logistic regression model stratified on each matched pair and accounting for factors known to be associated with the severity of the disease. RESULTS: We included 650 pairs of patients hospitalized between Jan 1, 2021, and Feb 28, 2021, in 47 hospitals. Median age was 70 years and 61.3% of participants were male. The proportion of participants with comorbidities was high in both groups (85.0% vs 90%, p = 0.004). Infection by VOC Alpha was associated with a higher odds of severe COVID-19 (41.7% vs 38.5%-aOR = 1.33 95% CI [1.03-1.72]). CONCLUSION: Infection by the VOC Alpha was associated with a higher odds of severe COVID-19.

Renal Replacement Therapy for Patients Requiring Extracorporeal Membrane Oxygenation: A Multicenter International Survey.

INTRODUCTION: Patients receiving extracorporeal membrane oxygenation (ECMO) often require renal replacement therapy (RRT). The challenge of inserting a dialysis catheter (DC) could be solved by direct connection of RRT lines on an ECMO circuit (DCRE) without published guidelines. This study aimed to describe the practice of RRT in patients on ECMO, including the DCRE as well as the perception and concerns related to this technique. METHODS: An international survey was worldwide sent via email to professionals involved in the management of ECMO. Respondents always or often performing RRT via the ECMO circuit were classified in the ECMO group, and those using a DC were classified in the DC group. RESULTS: From March 2019 to October 2019, 298 participants answered the questionnaire from 46 different countries. Only 28% were working in pediatric departments. Among the 165 participants commonly performing RRT in patients on ECMO, 100 (61%) performed mainly RRT via the ECMO circuit, and 65 (39%) performed RRT via DC. Pediatric practice and a longer experience were the only noticeable characteristics of the ECMO group. The most reported concern regarding DCRE was the risk of air embolism (n = 84, 28%), but the most encountered problem was unmanageable pressure alarms in RRT devices. CONCLUSION: The present study showed significant heterogeneity in RRT practices in patients on ECMO. The lower experience of the DC group, the high rates of concerns toward DCRE, and pressure alarm issues suggested that protocols and training may overcome reluctance and technical difficulties.

Clinical impact of rapid susceptibility testing on Mueller-Hinton Rapid-SIR directly from urine specimens.

Urinary tract infection diagnosis and management generally involves a 48-h microbiological delay to obtain the antibiotic susceptibility test (AST) results. In the context of multidrug resistance, reducing the time to obtain AST results is an essential factor, allowing for more timely appropriate treatment. We conducted a single-centre prospective study on urinary samples meeting two criteria: significant leukocyturia > 50/mm3 and exclusive presence of Gram-negative bacilli on direct examination. AST were performed by direct inoculation on Mueller-Hinton Rapid-SIR (MHR-SIR) agar. We evaluated the time to antibiotic adaptation by the antimicrobial stewardship team according to rapid AST results. Patients were subsequently excluded from the study if asymptomatic bacteria were confirmed, or in the absence of clinical data. Seventy patients were included. Mean age of patients was 68.8 years (± 21.3). Empirical antibiotic treatment were mainly based on third generation cephalosporins (n = 33), fluoroquinolones (n = 15), beta-lactamin/beta-lactamase inhibitors (n = 7), fosfomycin and nitrofurantoin (n = 5, each). The average time to obtain results was 7.2 h (± 1.6 h). Adaptation of therapy following MHR-SIR was performed for 29 patients (41%) with early switch to oral antibiotics, de-escalation or escalation in respectively 72.3%, 30%, and 11% of cases. Time saving of MHR-SIR compared with the standard technique was 42.6 (± 16.7) h. This study showed that rapid antibiotic susceptibility test results, using MHR-SIR method directly from urine, can be obtained 40 h earlier than conventional AST. The study also demonstrated significant clinical impact on the selection and reduction of the antibiotic therapy spectrum.

How and why do French medical students choose the specialty of infectious and tropical diseases? A national cross-sectional study.

BACKGROUND: Infectious and tropical diseases (ID) physicians are needed now more than ever to tackle existing and emerging global threats. However, in many countries, ID is not recognized as a qualifying specialty. The creation of ID residency in 2017 in France offers the opportunity to know how and why the specialty is chosen by medical students. METHODS: We first analyzed the choice of specialty of all French medical students in 2017 and 2018 according to their rank at the national exam that ends medical studies. A web questionnaire was then sent in January 2019 to all ID residents in France (n = 100) to assess the factors influencing their choice of specialty and their career plan. RESULTS: We analyzed the choice of 17,087 medical students. ID was the first-chosen specialty with a median national rank of 526/8539, followed by plastic surgery and ophthalmology. The questionnaire was completed by 90% of the French ID residents (n = 100). The most encouraging factors to choose ID were the multi-system approach of the specialty, the importance of diagnostic medicine and having done an internship in ID during medical school. The potential deterrents were the work-life balance, the workload and the salary. CONCLUSIONS: The recent recognition of ID as a qualifying specialty in France can be considered a success insofar as the specialty is the most popular among all medical and surgical specialties. Individuals who choose ID are attracted by the intellectual stimulation of the specialty but express concerns about the working conditions and salaries.

Clinical impact of rapid susceptibility testing on MHR-SIR directly from blood cultures.

BACKGROUND: In a previous study, we demonstrated that rapid antibiotic susceptibility tests (ASTs) can be performed directly on blood culture samples tested on Mueller-Hinton Rapid agar (MHR-SIR) with a time delay of 6-8 h. OBJECTIVES: Using this rapid disc diffusion method, we analysed the clinical impact associated with rapid reporting of results in our hospital setting. METHODS: All patients with bloodstream infections (BSIs) related to Enterobacteriaceae or Staphylococcus aureus were prospectively included in the study. The rapid ASTs were performed by incubation of positive blood cultures on MHR-SIR for 6-8 h by direct inoculation according to BSAC recommendations. RESULTS: One hundred and sixty-seven patients with BSIs were included as MHR-guided adaptation therapy cases. Eighty percent had Enterobacteriaceae-related BSIs, of which 12 (9%) were ESBL producers and 20% were S. aureus-related BSIs. A urinary or intra-abdominal infection was observed in 44.3% and 19.8%, respectively, of Enterobacteriaceae-related infections. The most frequent sources of infections for S. aureus BSIs were cutaneous and endovascular, in 43% and 23% of cases, respectively. Forty-four percent of the patients benefited from therapeutic modification according to the results of the MHR-SIR AST. Thus, empirical antibiotic therapy was modified by using antibiotic therapy that had too wide a spectrum or was unsuitable in 26% and 18% of cases, respectively. Compared with the 24 h required for the reference method, the median length of time to provision of susceptibility test results by MHR-SIR was 7 h. CONCLUSIONS: This study showed a significant time saving (17 h) on the appropriateness of antibiotic prescription and demonstrated a significant impact regarding the choice and reduction of the spectrum of antibiotic therapy.

Robotic-assisted unilateral adrenalectomy: risk factors for perioperative complications in 303 consecutive patients.

BACKGROUND: There is no consensus about the utility of using the robotic platform to perform a unilateral lateral transabdominal adrenalectomy in comparison with conventional laparoscopy. In some groups, obese patients (Body Mass Index > 30 kg/m2) and patients with tumor size > 5 cm have been considered as good candidates for robotic adrenalectomy. However, evaluation of incidence and risk factors for perioperative complications is currently lacking in large series of patients. The aim of this study was to evaluate incidence and predictive factors for intraoperative (conversion and capsular rupture) and postoperative complications (morbidity) after unilateral robotic-assisted transabdominal lateral adrenalectomy. METHODS: From 2001 to 2016, consecutive patients undergoing unilateral lateral transabdominal robotic adrenalectomy were included in a prospectively maintained database and analyzed retrospectively (clinicaltrials.gov NCT03410394). RESULTS: A total of 303 consecutive patients were analyzed. Between the first and last 100 of patients, mean tumor size increased from 2.9 to 4.2 cm (p < 0.001) and mean operating time decreased from 99 to 77 min (p < 0.001). Postoperative complications occurred in 28 patients (9.2%) and no postoperative death was observed. Nine patients (3%) were converted to open laparotomy and capsular rupture was observed in nine patients (3%). BMI was not a significant risk factor for conversion, capsular rupture, or postoperative complication. Tumor size > 5 cm remained the only predictive factor for conversion to laparotomy (OR 7.47, 95% CI 1.81-30.75; p = 0.005). History of upper gastrointestinal surgery was the only predictive factor for capsular rupture (OR 13.6, 95% CI 2.33-80.03; p = 0.004). Conversion to laparotomy (OR 8.35, 95% CI 1.99-35.05; p = 0.003) and patient age (OR 1.039, 95% CI 1.006-1.072; p = 0.019) remained independent predictive factors for postoperative complications. CONCLUSIONS: This study identified independent risk factors for perioperative complications after robotic-assisted unilateral adrenalectomy. These factors should be taken into account when evaluating robotic-assisted transabdominal lateral adrenalectomy.

Safety and efficacy of peri-operative administration of hydroxyethyl starch in children undergoing surgery: A systematic review and meta-analysis.

BACKGROUND: Hydroxyethyl starch (HES) solutions have shown their efficiency for intravascular volume expansion. A safety recommendation limiting their use in adult patients has recently been made. OBJECTIVE: To assess the efficacy and adverse effects of HES when administered intra-operatively to paediatric patients. DESIGN: Systematic review with meta-analyses. Data were analysed using classical mean differences [and their 95% confidence intervals (CIs)] and trial sequential analysis. A Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification was performed for all outcomes. Reviewers extracted valid data, including perioperative total fluid intakes, mortality, renal function, coagulation tests, blood loss and length of hospital and ICU stay. DATA SOURCES: Searches were performed in databases (Pubmed, Embase, Cochrane central register of controlled trials), clinical trials register, and open access journals not indexed in major databases. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) published before December 2016 involving paediatric patients who received 6% low molecular weight HES. RESULTS: Nine RCTs involving 530 peri-operative paediatric patients were analysed. Compared with other fluids, HES did not significantly modify the amount of peri-operative fluid administered [mean difference 0.04; 95% CI (-1.76 to 1.84) ml kg], urine output [mean difference -33; 95% CI (-104 to 38) ml kg] or blood loss [mean difference -0.09; (-0.32 to 0.15) ml kg]. Trial sequential analysis determined that the outcomes for peri-operative fluid and urine output were underpowered. All results were graded as very low quality of evidence. CONCLUSION: Intravascular volume expansion with low molecular weight 6% HES did not appear to modify renal function, blood loss or transfusion when administered to children during the peri-operative period. However, given the lack of statistical power and the very low GRADE quality of evidence, more high-quality RCTs are needed to explore these outcomes.

Time Course of Septic Shock in Immunocompromised and Nonimmunocompromised Patients.

OBJECTIVES: To address the impact of underlying immune conditions on the course of septic shock with respect to both mortality and the development of acute infectious and noninfectious complications. DESIGN: An 8-year (2008-2015) monocenter retrospective study. SETTING: A medical ICU in a tertiary care center. PATIENTS: Patients diagnosed for septic shock within the first 48 hours of ICU admission were included. Patients were classified in four subgroups with respect to their immune status: nonimmunocompromised and immunocompromised distributed into hematologic or solid malignancies and nonmalignant immunosuppression. Outcomes were in-hospital death and the development of ischemic and hemorrhagic complications and ICU-acquired infections. The determinants of death and complications were addressed by multivariate competing risk analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eight hundred one patients were included. Among them, 305 (38%) were immunocompromised, distributed into solid tumors (122), hematologic malignancies (106), and nonmalignant immunosuppression (77). The overall 3-day, in-ICU, and in-hospital mortality rates were 14.1%, 37.3%, and 41.3%, respectively. Patients with solid tumors displayed increased in-hospital mortality (cause-specific hazard, 2.20 [95% CI, 1.64-2.96]; p < 0.001). ICU-acquired infections occurred in 211 of the 3-day survivors (33%). In addition, 95 (11.8%) and 70 (8.7%) patients exhibited severe ischemic or hemorrhagic complications during the ICU stay. There was no association between the immune status and the occurrence of ICU-acquired infections. Nonmalignant immunosuppression and hematologic malignancies were independently associated with increased risks of severe ischemic events (cause-specific hazard, 2.12 [1.14-3.96]; p = 0.02) and hemorrhage (cause-specific hazard, 3.17 [1.41-7.13]; p = 0.005), respectively. CONCLUSIONS: The underlying immune status impacts on the course of septic shock and on the susceptibility to ICU-acquired complications. This emphasizes the complexity of sepsis syndromes in relation with comorbid conditions and raises the question of the relevant endpoints in clinical studies.