Discriminative performance of pancreatic stone protein in predicting ICU mortality and infection severity in adult patients with infection: a systematic review and individual patient level meta-analysis.

BACKGROUND: Several studies suggested pancreatic stone protein (PSP) as a promising biomarker to predict mortality among patients with severe infection. The objective of the study was to evaluate the performance of PSP in predicting intensive care unit (ICU) mortality and infection severity among critically ill adults admitted to the hospital for infection. METHODS: A systematic search across Cochrane Central Register of Controlled Trials and MEDLINE databases (1966 to February 2022) for studies on PSP published in English using 'pancreatic stone protein', 'PSP', 'regenerative protein', 'lithostatin' combined with 'infection' and 'sepsis' found 46 records. The search was restricted to the five trials that measured PSP using the enzyme-linked immunosorbent assay technique (ELISA). We used Bayesian hierarchical regression models for pooled estimates and to predict mortality or disease severity using PSP, C-Reactive Protein (CRP) and procalcitonin (PCT) as main predictor. We used statistical discriminative measures, such as the area under the receiver operating characteristic curve (AUC) and classification plots. RESULTS: Among the 678 patients included, the pooled ICU mortality was 17.8% (95% prediction interval 4.1% to 54.6%) with a between-study heterogeneity (I-squared 87%). PSP was strongly associated with ICU mortality (OR = 2.7, 95% credible interval (CrI) [1.3-6.0] per one standard deviation increase; age, gender and sepsis severity adjusted OR = 1.5, 95% CrI [0.98-2.8]). The AUC was 0.69 for PSP 95% confidence interval (CI) [0.64-0.74], 0.61 [0.56-0.66] for PCT and 0.52 [0.47-0.57] for CRP. The sensitivity was 0.96, 0.52, 0.30 for risk thresholds 0.1, 0.2 and 0.3; respective false positive rate values were 0.84, 0.25, 0.10. CONCLUSIONS: We found that PSP showed a very good discriminative ability for both investigated study endpoints ICU mortality and infection severity; better in comparison to CRP, similar to PCT. Combinations of biomarkers did not improve their predictive ability.

Metformin's Role in Hyperlactatemia and Lactic Acidosis in ICU Patients: A Systematic Review.

INTRODUCTION: Metformin-treated patients may experience severe hyperlactatemia or lactic acidosis (LA). LA often requires intensive-care-unit (ICU) treatment, and mortality rates are high. Here, we investigate the impact of renal dysfunction and renal replacement therapy (RRT) on the outcomes of critically ill patients with metformin-associated LA (MALA). Furthermore, we assessed associations between mortality and metformin dose, metformin plasma/serum concentrations, lactate level, and arterial pH. Finally, we investigated whether the recommended classification in MALA, metformin-unrelated LA, metformin-induced LA, and LA in metformin therapy appears useful in this regard. METHODS: We performed a retrospective analysis based on a systematic PubMed search for publications on hyperlactatemia/LA in metformin-treated ICU patients from January 1995 to February 2020. Case-level data including demographics and clinical conditions were extracted, and logistic regression analyses were performed. RESULTS: A total of 92 ICU patients were reported. Two of these patients had no comorbidities interfering with lactate metabolism. In the overall group, arterial pH, lactate levels, and metformin plasma/serum concentrations were similar in survivors versus non-survivors. Ingested daily metformin doses and plasma/serum creatinine levels were significantly higher in survivors versus non-survivors (p = 0.007 vs. p = 0.024, respectively). Higher plasma/serum creatinine levels, higher lactate levels, and lower arterial pH were all associated with patients receiving RRT (all p < 0.05). Overall mortality was 22% (20 out of 92 patients) and did not differ between the RRT and non-RRT groups. CONCLUSION: Mortality is high in ICU patients with metformin-associated hyperlactatemia/LA. Unexpectedly, higher ingested metformin dose and plasma/serum creatinine were associated with a better outcome. Survival was similar in patients with or without need for RRT.

Dysphagia in the intensive care unit: epidemiology, mechanisms, and clinical management.

Dysphagia may present in all critically ill patients and large-scale clinical data show that e.g. post-extubation dysphagia (PED) is commonly observed in intensive care unit (ICU) patients. Recent data demonstrate that dysphagia is mostly persisting and that its presence is independently associated with adverse patient-centered clinical outcomes. Although several risk factors possibly contributing to dysphagia development were proposed, the underlying exact mechanisms in ICU patients remain incompletely understood and no current consensus exists on how to best approach ICU patients at risk.From a clinical perspective, dysphagia is well-known to be associated with an increased risk of aspiration and aspiration-induced pneumonia, delayed resumption of oral intake/malnutrition, decreased quality of life, prolonged ICU and hospital length of stay, and increased morbidity and mortality. Moreover, the economic burden on public health care systems is high.In light of high mortality rates associated with the presence of dysphagia and the observation that dysphagia is not systematically screened for on most ICUs, this review describes epidemiology, terminology, and potential mechanisms of dysphagia on the ICU. Furthermore, the impact of dysphagia on affected individuals, health care systems, and society is discussed in addition to current and future potential therapeutic approaches.

A randomized trial of the effects of the noble gases helium and argon on neuroprotection in a rodent cardiac arrest model.

BACKGROUND: The noble gas xenon is considered as a neuroprotective agent, but availability of the gas is limited. Studies on neuroprotection with the abundant noble gases helium and argon demonstrated mixed results, and data regarding neuroprotection after cardiac arrest are scant. We tested the hypothesis that administration of 50% helium or 50% argon for 24 h after resuscitation from cardiac arrest improves clinical and histological outcome in our 8 min rat cardiac arrest model. METHODS: Forty animals had cardiac arrest induced with intravenous potassium/esmolol and were randomized to post-resuscitation ventilation with either helium/oxygen, argon/oxygen or air/oxygen for 24 h. Eight additional animals without cardiac arrest served as reference, these animals were not randomized and not included into the statistical analysis. Primary outcome was assessment of neuronal damage in histology of the region I of hippocampus proper (CA1) from those animals surviving until day 5. Secondary outcome was evaluation of neurobehavior by daily testing of a Neurodeficit Score (NDS), the Tape Removal Test (TRT), a simple vertical pole test (VPT) and the Open Field Test (OFT). Because of the non-parametric distribution of the data, the histological assessments were compared with the Kruskal-Wallis test. Treatment effect in repeated measured assessments was estimated with a linear regression with clustered robust standard errors (SE), where normality is less important. RESULTS: Twenty-nine out of 40 rats survived until day 5 with significant initial deficits in neurobehavioral, but rapid improvement within all groups randomized to cardiac arrest. There were no statistical significant differences between groups neither in the histological nor in neurobehavioral assessment. CONCLUSIONS: The replacement of air with either helium or argon in a 50:50 air/oxygen mixture for 24 h did not improve histological or clinical outcome in rats subjected to 8 min of cardiac arrest.

Therapy Intensity Level Scale for Traumatic Brain Injury: Clinimetric Assessment on Neuro-Monitored Patients Across 52 European Intensive Care Units.

Intracranial pressure (ICP) data from traumatic brain injury (TBI) patients in the intensive care unit (ICU) cannot be interpreted appropriately without accounting for the effect of administered therapy intensity level (TIL) on ICP. A 15-point scale was originally proposed in 1987 to quantify the hourly intensity of ICP-targeted treatment. This scale was subsequently modified-through expert consensus-during the development of TBI Common Data Elements to address statistical limitations and improve usability. The latest 38-point scale (hereafter referred to as TIL) permits integrated scoring for a 24-h period and has a five-category, condensed version (TIL(Basic)) based on qualitative assessment. Here, we perform a total- and component-score analysis of TIL and TIL(Basic) to: 1) validate the scales across the wide variation in contemporary ICP management; 2) compare their performance against that of predecessors; and 3) derive guidelines for proper scale use. From the observational Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study, we extract clinical data from a prospective cohort of ICP-monitored TBI patients (n = 873) from 52 ICUs across 19 countries. We calculate daily TIL and TIL(Basic) scores (TIL24 and TIL(Basic)24, respectively) from each patient's first week of ICU stay. We also calculate summary TIL and TIL(Basic) scores by taking the first-week maximum (TILmax and TIL(Basic)max) and first-week median (TILmedian and TIL(Basic)median) of TIL24 and TIL(Basic)24 scores for each patient. We find that, across all measures of construct and criterion validity, the latest TIL scale performs significantly greater than or similarly to all alternative scales (including TIL(Basic)) and integrates the widest range of modern ICP treatments. TILmedian outperforms both TILmax and summarized ICP values in detecting refractory intracranial hypertension (RICH) during ICU stay. The RICH detection thresholds which maximize the sum of sensitivity and specificity are TILmedian ≥ 7.5 and TILmax ≥ 14. The TIL24 threshold which maximizes the sum of sensitivity and specificity in the detection of surgical ICP control is TIL24 ≥ 9. The median scores of each TIL component therapy over increasing TIL24 reflect a credible staircase approach to treatment intensity escalation, from head positioning to surgical ICP control, as well as considerable variability in the use of cerebrospinal fluid drainage and decompressive craniectomy. Since TIL(Basic)max suffers from a strong statistical ceiling effect and only covers 17% (95% confidence interval [CI]: 16-18%) of the information in TILmax, TIL(Basic) should not be used instead of TIL for rating maximum treatment intensity. TIL(Basic)24 and TIL(Basic)median can be suitable replacements for TIL24 and TILmedian, respectively (with up to 33% [95% CI: 31-35%] information coverage) when full TIL assessment is infeasible. Accordingly, we derive numerical ranges for categorising TIL24 scores into TIL(Basic)24 scores. In conclusion, our results validate TIL across a spectrum of ICP management and monitoring approaches. TIL is a more sensitive surrogate for pathophysiology than ICP and thus can be considered an intermediate outcome after TBI.

Management of swallowing disorders in ICU patients - A multinational expert opinion.

BACKGROUND: Dysphagia is common in intensive care unit (ICU) patients, yet it remains underrecognized and often unmanaged despite being associated with life-threatening complications, prolonged ICU stays and hospitalization. PURPOSE: To propose an expert opinion for the diagnosis and management of dysphagia developed from evidence-based clinical recommendations and practitioner insights. METHODS: A multinational group of dysphagia and critical care experts conducted a literature review using a modified ACCORD methodology. Based on a fusion of the available evidence and the panel's clinical experience, an expert opinion on best practice management was developed. RESULTS: The panel recommends adopting clinical algorithms intended to promote standardized, high-quality care that triggers timely systematic dysphagia screening, assessment, and treatment of extubated and tracheostomized patients in the ICU. CONCLUSIONS: Given the lack of robust scientific evidence, two clinical management algorithms are proposed for use by multidisciplinary teams to improve early systematic detection and effective management of dysphagia in ICU patients. Additionally, emerging therapeutic options such as neurostimulation have the potential to improve the quality of ICU dysphagia care.

The effect of duration of antimicrobial treatment for bacteremia in critically ill patients on in-hospital mortality - Retrospective double center analysis.

PURPOSE: Excessive duration of antibiotic treatment is a major factor for inappropriate antibiotic consumption. Although in some instances shorter antibiotic courses are as efficient as longer ones, no specific recommendations as to the duration of antimicrobial treatment for bloodstream infections currently exist. In the present study, we investigated the effect of antibiotic treatment duration on in-hospital mortality using retrospective data from two cohorts that included patients with bacteremia at two Swiss tertiary Intensive Care Units (ICUs). MATERIALS AND METHODS: Overall 8227 consecutive patients requiring ICU admission were screened for bacteremia between 01/2012-12/2013 in Lausanne and between 07/2016-05/2017 in Bern. Patients with an infection known to require prolonged treatment or having single positive blood culture with common contaminant pathogens were excluded. The primary outcome of interest was the time from start of antimicrobial treatment to in-hospital death or hospital discharge, whichever comes first. The predictor of interest was adequate antimicrobial treatment duration, further divided into shorter (≤10 days) and longer (>10 days) durations. A time-dependent Cox model and a cloning approach were used to address immortality bias. The secondary outcomes were the median duration of antimicrobial treatment for patients with bacteremia overall and stratified by underlying infectious syndrome and pathogens in the case of secondary bacteremia. RESULTS: Out of the 707 patients with positive blood cultures, 382 were included into the primary analysis. Median duration of antibiotic therapy was 14 days (IQR, 7-20). Most bacteremia (84%) were monomicrobial; 18% of all episodes were primary bacteremia. Respiratory (28%), intra-abdominal (23%) and catheter infections (17%) were the most common sources of secondary bacteremia. Using methods to mitigate the risk of confounding associated with antibiotic treatment durations, shorter versus longer treatment groups showed no differences in in-hospital survival (time-dependent Cox-model: HR 1.5, 95% CI (0.8, 2.7), p = 0.20; Cloning approach: HR 1.0, 95% CI (0.7,1.5) p = 0.83). Sensitivity analyses showed that the interpretation did not change when using a 7 days cut-off. CONCLUSIONS: In this restrospective study, we found no evidence for a survival benefit of longer (>10 days) versus shorter treatment course in ICU patients with bacteremia. TRIAL REGISTRATION: The study was retrospectively registered on clinicatrials.gov (NCT05236283), 11 February 2022. The respective cantonal ethics commission (KEK Bern # 2021-02302) has approved the study.

Fluid Overload Phenotypes in Critical Illness-A Machine Learning Approach.

BACKGROUND: The detrimental impact of fluid overload (FO) on intensive care unit (ICU) morbidity and mortality is well known. However, research to identify subgroups of patients particularly prone to fluid overload is scarce. The aim of this cohort study was to derive "FO phenotypes" in the critically ill by using machine learning techniques. METHODS: Retrospective single center study including adult intensive care patients with a length of stay of ≥3 days and sufficient data to compute FO. Data was analyzed by multivariable logistic regression, fast and frugal trees (FFT), classification decision trees (DT), and a random forest (RF) model. RESULTS: Out of 1772 included patients, 387 (21.8%) met the FO definition. The random forest model had the highest area under the curve (AUC) (0.84, 95% CI 0.79-0.86), followed by multivariable logistic regression (0.81, 95% CI 0.77-0.86), FFT (0.75, 95% CI 0.69-0.79) and DT (0.73, 95% CI 0.68-0.78) to predict FO. The most important predictors identified in all models were lactate and bicarbonate at admission and postsurgical ICU admission. Sepsis/septic shock was identified as a risk factor in the MV and RF analysis. CONCLUSION: The FO phenotypes consist of patients admitted after surgery or with sepsis/septic shock with high lactate and low bicarbonate.

Dysphagia Post-Extubation Affects Long-Term Mortality in Mixed Adult ICU Patients-Data From a Large Prospective Observational Study With Systematic Dysphagia Screening.

Data on long-term effects of post-extubation dysphagia is lacking. We investigate mid- and long-term clinical outcomes in a large sample of ICU patients with systematic dysphagia screening. DESIGN: Outcome analysis with a follow-up of 6 years or death (whichever occurred earlier) of ICU patients from a prospective observational trial (Dysphagia in Mechanically Ventilated ICU Patients study) with systematic dysphagia screening. SETTING: ICU of a tertiary care academic center. PATIENTS: Nine-hundred thirty-three mixed medical-surgical ICU patients (median age, 66 yr; interquartile range [IQR], 54-74, Acute Physiology and Chronic Health Evaluation II score 19 [IQR, 14-24], 71% male). INTERVENTIONS: ICU patients were followed up for a mean follow-up period of 1,731 ± 772 days (4.7 ± 2.1 yr). Primary outcome measures were 180-day and 360-day all-cause mortality in ICU patients with versus without dysphagia. MEASUREMENTS AND MAIN RESULTS: Two-hundred seventy-three patients died (29.3%) during the observational interval (n = 76 lost to follow-up). In dysphagia screening positive versus negative ICU patients, mortality at 180 days was 16% versus 5.8% (excess mortality 10.2%), whereas mortality at 360 days was 25% versus 9.1% (excess mortality 15.9%). Adjustment for confounders in a Cox model revealed a significant association of dysphagia with all-cause mortality in a time-dependent manner. The risk of death in ICU patients with versus without post-extubation dysphagia declined from about 2.5 times higher to about equal risk for both groups over the first year (i.e. 1.03 yr) post-ICU admission (at 360 d: hazard ratio [HR], 1.03; 95% CI, 0.42-3.70). The mean mortality HR for the first year post-ICU admission was HR 2.09 (95% CI, 1.34-3.24; p = 0.0009). CONCLUSIONS: Long-term follow-up of a large cohort of medical-surgical adult ICU patients systematically screened for dysphagia showed that dysphagia is associated with increased hazards for death for up to 1 year after ICU admission. Our data underline effects of post-extubation dysphagia on long-term clinical outcomes in affected critically ill patients.

Granulomatosis with polyangiitis (Wegener's) complicated by splenic rupture and severe acute respiratory distress syndrome: A case report.

Even in the absence of disease-specific radiological signs of granulomatosis with polyangiitis (GPA), severe intrapulmonary GPA may be present. Rapidly establishing the diagnosis with a confirmatory biopsy is key to initiate lifesaving therapy.

Risk Factors for Dysphagia in ICU Patients After Invasive Mechanical Ventilation.

BACKGROUND: Dysphagia is common and independently predicts death in ICU patients. Risk factors for dysphagia are largely unknown, with sparse data available from mostly small cohorts without systematic dysphagia screening. RESEARCH QUESTION: What are the key risk factors for dysphagia in ICU patients after invasive mechanical ventilation? STUDY DESIGN AND METHODS: Post hoc analysis of data from a monocentric prospective observational study (Dysphagia in Mechanically Ventilated ICU Patients [DYnAMICS]) using comprehensive statistical models to identify potential risk factors for postextubation dysphagia. A total of 933 primary admissions of adult medical-surgical ICU patients (median age, 65 years; interquartile range, 54-73; 666 [71%] men) were investigated in a tertiary care academic center. Patients received systematic bedside screening for dysphagia within 3 h postextubation. Dysphagia screening positivity (n = 116) was followed within 24 h by a confirmatory examination. RESULTS: After adjustment for confounders, baseline neurologic disease (OR, 4.45; 95% CI, 2.74-7.24; P < .01), emergency admission (OR, 2.04; 95% CI, 1.15-3.59; P < .01), days on mechanical ventilation (OR, 1.19; 95% CI, 1.06-1.34; P < .01), days on renal replacement therapy (OR, 1.1; 95% CI, 1-1.23; P = .03), and disease severity (Acute Physiology and Chronic Health Evaluation II score within first 24 h; OR, 1.03; 95% CI, 0.99-1.07; P < .01) remained independent risk factors for dysphagia postextubation. Increased BMI reduced the risk for dysphagia (6% per step increase; OR, 0.94; 95% CI, 0.9-0.99; P = .03). INTERPRETATION: In ICU patients, baseline neurologic disease, emergency admission, and duration of invasive mechanical ventilation appeared as prominent independent risk factors for dysphagia. Because all ICU patients after mechanical ventilation should be considered at risk for dysphagia, systematic screening for dysphagia is recommended in respective critically ill patients. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02333201; URL: www.clinicaltrials.govclinicaltrials.gov.

Hypertonic saline for fluid resuscitation in ICU patients post-cardiac surgery (HERACLES): a double-blind randomized controlled clinical trial.

PURPOSE: Recent evidence questions a liberal approach to fluid resuscitation in intensive care unit (ICU) patients. Here, we assess whether use of hypertonic saline applied as single infusion at ICU admission after cardiac surgery can reduce cumulative perioperative fluid volume. METHODS: Prospective randomized double-blind single-center clinical trial investigates effects of a single infusion of hypertonic saline (HS) versus normal saline (comparator). Primary endpoint was the cumulative amount of fluid administered in patients in the hypertonic saline versus the 0.9% saline groups (during ICU stay). Upon ICU admission, patients received a single infusion of 5 ml/kg body weight of 7.3% NaCl (or 0.9% NaCl) over 60 min. Patients undergoing cardiac surgery for elective valvular and/or coronary heart disease were included. Patients with advanced organ dysfunction, infection, and/or patients on chronic steroid medication were excluded. RESULTS: A total of 101 patients were randomized to receive the study intervention (HS n = 53, NS n = 48). Cumulative fluid intake on the ICU (primary endpoint) did not differ between the HS and the NS groups [median 3193 ml (IQR 2052-4333 ml) vs. 3345 ml (IQR 2332-5043 ml)]. Postoperative urinary output until ICU discharge was increased in HS-treated patients [median 2250 ml (IQR 1640-2690 ml) vs. 1545 ml (IQR 1087-1976 ml)], and ICU fluid balance was lower in the HS group when compared to the NS group [296 ml (IQR - 441 to 1412 ml) vs. 1137 ml (IQR 322-2660 ml)]. CONCLUSION: In a monocentric prospective double-blind randomized clinical trial, we observed that hypertonic saline did not reduce the total fluid volume administered on the ICU in critically ill cardiac surgery patients. Hypertonic saline infusion was associated with timely increase in urinary output. Variations in electrolyte and acid-base homeostasis were transient, but substantial in all patients.

The PhINEST study - Pharyngeal ICU Novel Electrical Stimulation Therapy: Study protocol of a prospective, multi-site, randomized, sham-controlled, single-blind (outcome assessor-blinded) study.

INTRODUCTION: Post-extubation dysphagia is commonly observed in ICU patients and associated with increased aspiration rates, delayed resumption of oral intake/ malnutrition, prolonged ICU and hospital length of stay, decreased quality of life, and increased mortality. Conventional therapeutic approaches are limited. Pharyngeal electrical stimulation (PES) was previously shown to improve swallowing function and airway safety in severely dysphagic tracheostomised stroke patients. METHODS: In a multi-center, single-blind, 1:1 randomized controlled study, up to 400 (360 evaluable) mixed emergency adult ICU patients with recent extubation following mechanical ventilation and confirmed oropharyngeal dysphagia will be enrolled at investigational academic ICUs. Primary objective is to evaluate the effectiveness of PES in reducing the severity of unsafe swallows. Patients will be randomized to receive PES (or sham) treatment on 3 consecutive days in addition to best supportive care. Primary endpoint is a composite of 2 endpoints with hierarchy based on clinical priorities: DISCUSSION:: This study will evaluate the effects of PES on swallowing safety in critically ill ICU patients post mechanical ventilation with oropharyngeal dysphagia.

Dysphagia in the intensive care unit in Switzerland (DICE) - results of a national survey on the current standard of care.

INTRODUCTION: Oropharyngeal dysphagia (OD) is often observed in critically ill patients. In most affected patients OD persists throughout hospital stay and negatively impacts on clinical outcomes. Here we systematically explore routine clinical practice standards for recognition/screening, diagnosis and treatment of OD in accredited Swiss ICUs. METHODS: An online, 23-item questionnaire-based survey was performed to investigate current standards of care for OD in Switzerland (DICE). All (n = 49) accredited Swiss teaching hospitals providing specialist training for adult intensive care medicine were contacted. Senior intensivists were interviewed on how they would screen for, diagnose and treat OD in the ICU. RESULTS: The total response rate was 75.5%, with information available on all tertiary care academic centres. 67.6% (25/37) of institutions stated that they have established standard operating procedures for OD using a mostly sequential diagnostic approach (86.5%, 32/37). In 75.7% (28/37) of institutions, OD confirmation is performed without the use of instrumental techniques such as flexible (or fibre-endoscopic) evaluation of swallowing (FEES). Presumed key risk factors for OD were admission for acute neurological illness, long-term mechanical ventilation, ICU-acquired weakness and pre-existing neurological disease. Reported presumed OD-related complications typically include aspiration-induced pneumonia, increased rates of both reintubation and tracheostomy and increased ICU readmission rates. CONCLUSIONS: Many Swiss ICUs have established standard operating procedures, with most using sequential clinical approaches to assess ICU patients at risk of dysphagia. OD confirmation is mostly performed using non-instrumental techniques. In general, it appears that awareness of OD and ICU educational curricula can be further optimised.

Hypertonic saline for fluid resuscitation after cardiac surgery (HERACLES): study protocol for a preliminary randomised controlled clinical trial.

BACKGROUND: Intraoperative and postoperative management of cardiac surgery patients is complex, involving the application of differential vasopressors and volume therapy. It has been shown that a positive fluid balance has a major impact on postoperative outcome. Today, the advantages and disadvantages of buffered crystalloid solutes are a topic of controversy, with no consensus being reached so far. The use of hypertonic saline (HS) has shown promising results with respect to lower total fluid balance and postoperative weight gain in critically ill patients in preliminary studies. However, collection of more data on HS in critically ill patients seems warranted. This preliminary study aims to investigate whether fluid resuscitation using HS in patients following cardiac surgery results in less total fluid volume being administered. METHODS: In a prospective double-blind randomised controlled clinical trial, we aim to recruit 96 patients undergoing elective cardiac surgery for ischaemic and/or valvular heart disease. After postoperative admission to the intensive care unit (ICU), patients will be randomly assigned to receive 5 ml/kg ideal body weight HS (7.3% NaCl) or normal saline (NS, 0.9% NaCl) infused within 60 min. Blood and urine samples will be collected preoperatively and postoperatively up to day 6 to assess changes in renal, cardiac, inflammatory, acid-base, and electrolyte parameters. Additionally, we will perform renal ultrasonography studies to assess renal blood flow before, during, and after infusion, and we will measure total body water using preoperative and postoperative body composition analysis (bioimpedance). Patients will be followed up for 90 days. DISCUSSION: The key objective of this study is to assess the cumulative amount of fluid administered in the intervention (HS) group versus control (NS) group during the ICU stay. In this preliminary, prospective, randomised controlled clinical trial we will test the hypothesis that use of HS results in less total fluids infused and less postoperative weight gain when compared to the standard of intensive care in cardiac surgery patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03280745 . Registered on 12 September 2017.

Neuroprotection with the P53-Inhibitor Pifithrin-µ after Cardiac Arrest in a Rodent Model.

BACKGROUND: The small molecule pifithrin-µ reversibility inhibits the mitochondrial pathway of apoptosis. The neuronal effects of pifithrin-µ applied after cardiac arrest are unknown. We hypothesized that pifithrin-µ reduces neuronal damage in the most vulnerable brain region, the hippocampus, after cardiac arrest. METHODS: In two randomized controlled series we administered pifithrin-µ or control in 109 rats resuscitated after 8 or 10 min of cardiac arrest. Neuronal damage was blindly assessed with histology (Fluoro Jade B: FJB, cresyl violet: CV) in the most vulnerable brain region (CA1 segment of hippocampus) and with a series of neurobehavioral tests (Open Field Task, Tape-Removal Test, Morris Water Maze test). Mixed ANOVA was used to combine both series, simple comparisons were done with t tests or Mann-Whitney U test. RESULTS: Pifithrin-µ reduced the number of degenerating, FJB-positive neurons by 25% (mixed ANOVA p group = 0.014). This was more prominent after 8 min cardiac arrest (8 min arrest pifithrin-µ 94 ±â€Š47 vs control 128 ±â€Š37; n = 11 each; 10 min arrest pifithrin-µ 78 ±â€Š44, n = 15 vs control 101 ±â€Š31, n = 18; p group* arrest length interaction = 0.622). The reduction of ischemic CV-positive neurons in pifithrin-µ animals was not significant (ANOVA p group = 0.063). No significant group differences were found in neurobehavioral testing. CONCLUSION: Temporarily inhibition of apoptosis with pifithrin-µ after cardiac arrest decreases the number of injured neurons in the CA1 segment of hippocampus in a cardiac arrest rat model, without clinical correlate. Further studies should elucidate the role of this neuroprotective agent in different settings and with longer cardiac arrest.

Calypso's spell: accidental near-fatal thiacloprid intoxication.

Acute life-threatening intoxications with insecticides are rare. We report a case of accidental near-fatal thiacloprid intoxication with mass spectrometry-based analytical confirmation. The initial clinical presentation resembled imminent brain death and/or severe postanoxic encephalopathy. Prolonged supportive treatment resulted in full recovery underlining intoxication as an important differential diagnosis in unclear coma.

Reliability and Validity of the Therapy Intensity Level Scale: Analysis of Clinimetric Properties of a Novel Approach to Assess Management of Intracranial Pressure in Traumatic Brain Injury.

We aimed to assess the reliability and validity of the Therapy Intensity Level scale (TIL) for intracranial pressure (ICP) management. We reviewed the medical records of 31 patients with traumatic brain injury (TBI) in two European intensive care units (ICUs). The ICP TIL was derived over a 4-day period for 4-h (TIL4) and 24-h epochs (TIL24). TIL scores were compared with historical schemes for TIL measurement, with each other, and with clinical variables. TIL24 scores in ICU patients with TBI were compared with two control groups: patients with extracranial trauma necessitating intensive care (Trauma_ICU; n = 20) and patients with TBI not needing ICU care (TBI_WARD; n = 19), to further determine the discriminative validity of the TIL for ICP-related ICU interventions. Interrater and intraobserver agreement were excellent for TIL4 and TIL24 (Cohen κ: 0.98-0.99; intraclass correlation coefficient: 0.99-1; p < 0.0005). The mean + standard deviation (SD) TIL24 in the ICU TBI cohort was significantly higher than the Trauma_ICU patients and the TBI_WARD patients (8.2 ± 3.2 vs. 2.2 ± 0.9 and 0.1 ± 0.1, respectively; p < 0.005 for both comparisons). Correlations between the TIL scale scores and historical TIL scores, between TIL24 and the Glasgow Coma Scale, and between a range of TIL metrics and summary measures of ICP over the 4-day period, were all highly significant (p < 0.01). The results were consistent with the expected direction. A linear mixed effect analysis, accounting for within-subjects repeated measures, showed strong correlation between TIL4 and 4-h ICP (p < 0.0000005). The TIL scale is a reliable measurement instrument with a high degree of validity for assessing the therapeutic intensity level of ICP management in patients with TBI.