Sepsis-related Organ Failure Assessment Score is a strong predictor of survival in acute-on-chronic liver failure.

INTRODUCTION: The mortality of patients with an exacer-bation of decompensated liver cirrhosis is high even if treated in the intensive care unit (ICU), and the criteria for referral to ICU are not well defined. The objective of this study was to identify variables associated with mortality. METHODS: A single-centre retrospective cohort analysis was conducted in a university-affiliated ICU. A total of 53 adult patients with decompensated alcoholic liver cirrhosis were admitted from January 2012 to June 2015. Variables associated with survival were identified using Cox regression analysis. RESULTS: The ten-day, 30-day, 90-day, and one-year mortality were 36%, 57%, 66%, and 80%, respectively. Univariate Cox regression analysis showed that mortality was significantly associated with a low oxygen saturation, low diastolic blood pressure, terlipressin treatment, high Acute Physiology And Chronic Health Evaluation II score, high Simplified Acute Physiology Score II score, high Sepsis-related Organ Failure Assessment (SOFA) score and high Model For End-Stage Liver Disease score, but only a high SOFA score and old age were independently associated with increased mortality. These two variables were combined to the Age-SOFA index to predict the probability of surviving a given period. CONCLUSIONS: The mortality was high in these severely ill patients, even when they received optimum supportive therapy in the ICU. The finding that the SOFA score and age best predicted mortality shows that the increased mortality was caused mainly by insufficiency of organs other than the liver. FUNDING: none. TRIAL REGISTRATION: not relevant.

Association between biomarkers of endothelial injury and hypocoagulability in patients with severe sepsis: a prospective study.

INTRODUCTION: Patients with severe sepsis often present with concurrent coagulopathy, microcirculatory failure and evidence of vascular endothelial activation and damage. Given the critical role of the endothelium in balancing hemostasis, we investigated single-point associations between whole blood coagulopathy by thrombelastography (TEG) and plasma/serum markers of endothelial activation and damage in patients with severe sepsis. METHODS: A post-hoc multicenter prospective observational study in a subgroup of 184 patients from the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial. Study patients were admitted to two Danish intensive care units. Inclusion criteria were severe sepsis, pre-intervention whole blood TEG measurement and a plasma/serum research sample available from baseline (pre-intervention) for analysis of endothelial-derived biomarkers. Endothelial-derived biomarkers were measured in plasma/serum by enzyme-linked immunosorbent assay (syndecan-1, thrombomodulin, protein C (PC), tissue-type plasminogen activator and plasminogen activator inhibitor-1). Pre-intervention TEG, functional fibrinogen (FF) and laboratory and clinical data, including mortality, were retrieved from the trial database. RESULTS: Most patients presented with septic shock (86%) and pulmonary (60%) or abdominal (30%) focus of infection. The median (IQR) age was 67 years (59 to 75), and 55% were males. The median SOFA and SAPS II scores were 8 (6 to 10) and 56 (41 to 68), respectively, with 7-, 28- and 90-day mortality rates being 21%, 39% and 53%, respectively. Pre-intervention (before treatment with different fluids), TEG reaction (R)-time, angle and maximum amplitude (MA) and FF MA all correlated with syndecan-1, thrombomodulin and PC levels. By multivariate linear regression analyses, higher syndecan-1 and lower PC were independently associated with TEG and FF hypocoagulability at the same time-point: 100 ng/ml higher syndecan-1 predicted 0.64 minutes higher R-time (SE 0.25), 1.78 mm lower TEG MA (SE 0.87) and 0.84 mm lower FF MA (SE 0.42; all P < 0.05), and 10% lower protein C predicted 1.24 mm lower TEG MA (SE 0.31). CONCLUSIONS: In our cohort of patients with severe sepsis, higher circulating levels of biomarkers of mainly endothelial damage were independently associated with hypocoagulability assessed by TEG and FF. Endothelial damage is intimately linked to coagulopathy in severe sepsis. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT00962156. Registered 13 July 2009.

[Central venous oxygen saturation as a resuscitation goal for patients with severe sepsis should be examined closely]. / Central venøs saturation som behandlingsmål hos patienter med svær sepsis bør undersøges nærmere.

Fluids, vasopressors and inotropics are mainstays in the initial treatment of sepsis. Consensus guidelines recommend a central venous oxygen saturation (ScvO(2)) larger than 69% as a resuscitation goal for sepsis treatment. Several studies demonstrate that many patients with sepsis have normal or higher ScvO(2) and this may lead to inappropriate use of vasopressors or inotropics when the patient is still in need of fluid. We discuss the (patho)physiology of ScvO(2) in sepsis and propose individualized fluid therapy based on optimization of cardiac preload, e.g. by establishing a maximal ScvO(2).

Erythropoietin treatment enhances muscle mitochondrial capacity in humans.

Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s(-1)·mg(-1)) and ETS (107 ± 4 to 143 ± 14 pmol·s(-1)·mg(-1), p < 0.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

[Severe metabolic acidosis in an alcoholic]. / Svaer metabolisk acidose hos en kronisk alkoholiker.

Severe metabolic acidosis is associated with poor prognosis. We present a patient with profound alcohol and starvation-related combined lactic and keto acidosis (lactate = 29 mM; pH = 6.83) who made a good recovery following 18 hours of intensive care therapy. A brief summary of the proposed mechanism by which these metabolic derangements develop is presented.

Voluntary respiratory control and cerebral blood flow velocity upon ice-water immersion.

INTRODUCTION: In non-habituated subjects, cold-shock response to cold-water immersion causes rapid reduction in cerebral blood flow velocity (approximately 50%) due to hyperventilation, increasing risk of syncope, aspiration, and drowning. Adaptation to the response is possible, but requires several cold immersions. This study examines whether thorough instruction enables non-habituated persons to attenuate the ventilatory component of cold-shock response. METHODS: There were nine volunteers (four women) who were lowered into a 0 degrees C immersion tank for 60 s. Middle cerebral artery mean velocity (CBFV) was measured together with ventilatory parameters and heart rate before, during, and after immersion. RESULTS: Within seconds after immersion in ice-water, heart rate increased significantly from 95 +/- 8 to 126 +/- 7 bpm (mean +/- SEM). Immersion was associated with an elevation in respiratory rate (from 12 +/- 3 to 21 +/- 5 breaths, min(-1)) and tidal volume (1022 +/- 142 to 1992 +/- 253 ml). Though end-tidal carbon dioxide tension decreased from 4.9 +/- 0.13 to 3.9 +/- 0.21 kPa, CBFV was insignificantly reduced by 7 +/- 4% during immersion with a brief nadir of 21 +/- 4%. DISCUSSION: Even without prior cold-water experience, subjects were able to suppress reflex hyperventilation following ice-water immersion, maintaining the cerebral blood flow velocity at a level not associated with impaired consciousness. This study implies that those susceptible to accidental cold-water immersion could benefit from education in cold-shock response and the possibility of reducing the ventilatory response voluntarily.

[Survival in cold water. Physiological consequences of accidental immersion in cold water]. / Overlevelse i koldt vand. De fysiologiske konsekvenser af nedsaenkning i koldt vand.

This survey addresses the immediate physiological reactions to immersion in cold water: cold shock response, diving reflex, cardiac arrhythmias and hypothermia. Cold shock response is the initial sympathetic reaction to immersion in cold water. The diving reflex is elicited by submersion of the face. Afferent and efferent nerves are the trigeminal and vagal nerves. Cardiac arrhythmias occur immediately after immersion. If the immersion persists, hypothermia becomes an issue. Hypothermia is delayed by habituation to immersion in cold water as well as insulating garments, subcutaneous fat and a large lean body mass.

[Prolonged survival after accidental immersion in cold water]. / Uventet lang overlevelsestid efter accidentel nedsaenkning i koldt vand.

In a recent boat accident, a 25-year-old yachting enthusiast fell overboard and survived for 24 hours in 17 degrees C water. Existing survival models are discussed in this case report. There is a discrepancy regarding survival probability amongst the various models. The calculated survival time for the yachtsman ranges from 3 hours to more than 30 hours. A reliable survival-time model is needed to determine the appropriate search duration of rescue services. In this case, the majority of the models underestimated the actual survival time.