Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis

Background

It is unknown whether a conservative approach to fluid administration or deresuscitation (active removal of fluid using diuretics or renal replacement therapy) is beneficial following haemodynamic stabilisation of critically ill patients.

Purpose

To evaluate the efficacy and safety of conservative or deresuscitative fluid strategies in adults and children with acute respiratory distress syndrome (ARDS), sepsis or systemic inflammatory response syndrome (SIRS) in the post-resuscitation phase of critical illness.

Methods

We searched Medline, EMBASE and the Cochrane central register of controlled trials from 1980 to June 2016, and manually reviewed relevant conference proceedings from 2009 to the present. Two reviewers independently assessed search results for inclusion and undertook data extraction and quality appraisal. We included randomised trials comparing fluid regimens with differing fluid balances between groups, and observational studies investigating the relationship between fluid balance and clinical outcomes.

Results

Forty-nine studies met the inclusion criteria. Marked clinical heterogeneity was evident. In a meta-analysis of 11 randomised trials (2051 patients) using a random-effects model, we found no significant difference in mortality with conservative or deresuscitative strategies compared with a liberal strategy or usual care [pooled risk ratio (RR) 0.92, 95 % confidence interval (CI) 0.82–1.02, I2 = 0 %]. A conservative or deresuscitative strategy resulted in increased ventilator-free days (mean difference 1.82 days, 95 % CI 0.53–3.10, I2 = 9 %) and reduced length of ICU stay (mean difference −1.88 days, 95 % CI −0.12 to −3.64, I2 = 75 %) compared with a liberal strategy or standard care.

Conclusions

In adults and children with ARDS, sepsis or SIRS, a conservative or deresuscitative fluid strategy results in an increased number of ventilator-free days and a decreased length of ICU stay compared with a liberal strategy or standard care. The effect on mortality remains uncertain. Large randomised trials are needed to determine optimal fluid strategies in critical illness.

Adaptações cardio-respiratorias em atletas : estudo em diferentes fases do treinamento fisico

Universidade Estadual de Campinas. Faculdade de Educação Física

Positive end expiratory pressure during resuscitation of premature lambs rapidly improves blood gases without adversely affecting arterial pressure

Positive end expiratory pressure (PEEP) is important for neonatal ventilation but is not considered in guidelines for resuscitation. Our aim was to investigate the effects of PEEP on cardiorespiratory parameters during resuscitation of very premature lambs delivered by hysterotomy at similar to125 d gestation (term similar to147 d). Before delivery, they were intubated and lung fluid was drained. Immediately after delivery, they were ventilated with a Drager Babylog plus ventilator in volume guarantee mode with a tidal volume of 5 mL/kg. Lambs were randomized to receive 0, 4, 8, or 12 cm H2O of PEEP. They were ventilated for a 15-min resuscitation period followed by 2 h of stabilization at the same PEEP. Tidal volume, peak inspiratory pressure, PEEP, arterial pressure, oxygen saturation, and blood gases were measured regularly, and respiratory system compliance and alveolar/ arterial oxygen differences were calculated. Lambs that received 12 cm H2O of PEEP died from pneumothoraces; all others survived without pneumothoraces. Oxygenation was significantly improved by 8 and 12 cm H2O of PEEP compared with 0 and 4 cm H2O of PEEP. Lambs with 0 PEEP did not oxygenate adequately. The compliance of the respiratory system was significantly higher at 4 and 8 cm H2O of PEEP than at 0 PEEP. There were no significant differences in partial pressure of carbon dioxide in arterial blood between groups. Arterial pressure was highest with 8 cm H2O of PEEP, and there was no cardiorespiratory compromise at any level of PEEP. Applying PEEP during resuscitation of very premature infants might be advantageous and merits further investigation.

The effect of tidal volume and peep on CO2 and oxygenation during resuscitation of very premature lambs

Background: Over-ventilation causing low arterial carbon dioxide levels (PaCO2) has been associated with the development of neonatal chronic lung disease and adverse outcomes. This may occur very soon after birth. Aim: To investigate the effect on PaCO2 and oxygenation of very premature lambs resuscitated with different tidal volumes and PEEP. Methods: Anaesthetised lambs delivered at 126 days gestation were randomised to 15 min resuscitation with 3 regimes: (1) Laerdal resuscitation bag (B) with 100% oxygen and no PEEP, (2) fixed tidal volume (VT) of 5 mL/kg, or (3) VT of 10 mL/kg, both delivered with a Babylog 8000 ventilator in volume guarantee mode with 8 cm H2O PEEP and variable FiO2. Frequent blood gases were measured and VT, mean airway pressure (Paw), minute volume (MV), ventilation rate (VR), respiratory system compliance (Crs) and alveolar/arterial oxygen difference (AaDO2) were recorded. Results: Twenty lambs were studied. B (1) was associated with more variable VT and peak inspiratory pressures (PIP) compared to fixed tidal volumes (2 and 3). The lambs ventilated with 10 mL/kg were over-ventilated, those ventilated with 5 mL/kg were slightly under-ventilated. Those ventilated with the Laerdal bag had a mean VT of 7.5 mL/kg and were normocarbic. The different tidal volumes had little effect on oxygenation. PEEP improved oxygenation. The table shows the values at 15 minutes expressed as mean and SEM. TABLE. No caption av... TABLE. No caption av... Image Tools Conclusion: Very premature lambs can be effectively resuscitated from birth using volume guarantee ventilation. Within minutes of birth different tidal volumes had a large effect on PaCO2 and no effect on oxygenation. Studies are needed to determine the appropriate tidal volume for resuscitating very premature infants to maintain acceptable levels of PaCO2. © International Pediatrics Research Foundation, Inc. 2004. All Rights Reserved.

Effects of tidal volume and positive end-expiratory pressure during resuscitation of very premature lambs

Background: Guidelines recommend neonatal resuscitation without controlling tidal volume or positive end-expiratory pressure (PEEP). However, these may improve gas exchange, lung volume and outcome. Aim: To investigate resuscitation of very premature lambs with a Laerdal bag without PEEP versus volume guarantee ventilation with PEEP. Methods: Anaesthetized lambs (n = 20) delivered at 125 d gestation were randomized to three groups receiving 15 min resuscitation: (1) Laerdal bag and no PEEP; (2) ventilation with a tidal volume of 5 ml/kg and 8 cm H2O PEEP; (3) ventilation with 10 ml/kg and 8 cm H2O PEEP. They were then all ventilated for 2 h with tidal volumes of 5 or 10 ml/kg, and 8 cm H2O PEEP. Ventilation parameters and blood gases were recorded. Results: Different tidal volumes affected PaCO2 within minutes, with 10 ml/kg causing severe hypocarbia. PEEP had little effect on PaCO2. Oxygenation improved significantly with PEEP of 8 cm H2O, irrespective of tidal volume. Conclusion: Very premature lambs can be resuscitated effectively using volume-guarantee ventilation and PEEP. Tidal volumes affected PaCO2 within minutes but had little effect on oxygenation. PEEP halved the oxygen requirement compared with no PEEP. Resuscitating premature babies with controlled tidal volumes and PEEP might improve their outcome.

A Comparison Between Pulse Pressure Variation and Right End Diastolic Volume Index as Guides to Resuscitation in a Model of Hemorrhagic Shock in Pigs

Background: Different hemodynamic parameters including static indicators of cardiac preload as right ventricular end-diastolic volume index (RVEDVI) and dynamic parameters as pulse pressure variation (PPV) have been used in the decision-making process regarding volume expansion in critically ill patients. The objective of this study was to compare fluid resuscitation guided by either PPV or RVEDVI after experimentally induced hemorrhagic shock. Methods: Twenty-six anesthetized and mechanically ventilated pigs were allocated into control (group I), PPV (group II), or RVEDVI (group III) group. Hemorrhagic shock was induced by blood withdrawal to target mean arterial pressure of 40 mm Hg, maintained for 60 minutes. Parameters were measured at baseline, time of shock, 60 minutes after shock, immediately after resuscitation with hydroxyethyl starch 6% (130/0.4), 1 hour and 2 hours thereafter. The endpoint of fluid resuscitation was determined as the baseline values of PPV and RVEDVI. Statistical analysis of data was based on analysis of variance for repeated measures followed by the Bonferroni test (p < 0.05). Results: Volume and time to resuscitation were higher in group III than in group II (group III = 1,305 +/- 331 mL and group II = 965 +/- 245 mL, p < 0.05; and group III = 24.8 +/- 4.7 minutes and group II = 8.8 +/- 1.3 minutes, p < 0.05, respectively). All static and dynamic parameters and biomarkers of tissue oxygenation were affected by hemorrhagic shock and nearly all parameters were restored after resuscitation in both groups. Conclusion: In the proposed model of hemorrhagic shock, resuscitation to the established endpoints was achieved within a smaller amount of time and with less volume when guided by PPV than when guided by pulmonary artery catheter-derived RVEDVI.

Preoperative respiratory muscle dysfunction is a predictor of prolonged invasive mechanical ventilation in cardiorespiratory complications after heart valve surgery

Objective: To verify whether preoperative respiratory muscle strength and ventilometric parameters, among other clinically relevant factors, are associated with the need for prolonged invasive mechanical ventilation (PIMV) due to cardiorespiratory complications following heart valve surgery. Methods: Demographics, preoperative ventilometric and manometric data, and the hospital course of 171 patients, who had undergone heart valve surgery at Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, were prospectively collected and subjected to univariate analysis for identifying the risk factors for PIMV. Results: The hospital mortality was 7%. About 6% of the patients, who had undergone heart valve surgery required PIMV because of postoperative cardiorespiratory dysfunction. Their hospital mortality was 60% (vs 4%, p < 0.001). Univariate analysis revealed that preoperative respiratory muscle dysfunction, characterized by maximal inspiratory and expiratory pressure below 70% of the predicted values combined with respiratory rate above 15 rpm during ventilometry, was associated with postoperative PIMV (p = 0.030, odds ratio: 50, 95% confidence interval (CI): 1.2-18). Postoperative PIMV was also associated with: (1) body mass index (BMI) < 18.5 (odds ratio: 7.2, 95% CI: 1.5-32), (2) body weight < 50 kg (odds ratio: 6.5, 95% CI: 1.6-25), (3) valve operation due to acute endocarditis (odds ratio: 5.5, 95% CI: 0.98-30), and (4) concomitant operation for mitral and tricuspid valve dysfunction (p = 0.047, odds ratio: 5.0, 95% CI: 1.1-22). Conclusion: Our results have demonstrated that respiratory muscle dysfunction, among other clinical factors, is associated with the need for PIMV due to cardiovascular or pulmonary dysfunction after heart valve surgery. (C) 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B. V. All rights reserved.

Increasing respiratory dead space improves sleep disordered breathing and hypoxemia in patients with chronic mountain sickness

Background: Chronic mountain sickness (CMS), which is characterised by hypoxemia, erythrocytosis and pulmonary hypertension, is a major public health problem in high-altitude dwellers. The only existing treatment is descent to low altitude, an option that for social reasons almost never exists. Sleep disordered breathing may represent an underlying mechanism. We recently found that in mountaineers increasing the respiratory dead space markedly improves sleep disordered breathing. The aim of the present study was to assess the effects of this procedure on sleep disordered breathing in patients with CMS. Methods: In 10 male Bolivian high-altitude dwellers (mean ± SD age, 59 ± 9 y) suffering from CMS (haemoglobin >20 g/L) full night sleep recordings (Embletta, RespMed) were obtained in La Paz (3600 m). In random order, one night was spent with a 500 ml increase in dead space through a custom designed full face mask and the other night without it. Exclusion criteria were: secondary erythrocytosis, smoking, drug intake, acute infection, cardio- pulmonary or neurologic disease and travelling to low altitude in the preceding 6 months. Results: The major new finding was that added dead space dramatically improved sleep disordered breathing in patients suffering from CMS. The apnea/hypopnea index decreased by >50% (from 34.5 ± 25.0 to 16.8 ± 14.9, P = 0.003), the oxygen desaturation index decreased from 46.2 ± 23.0 to 27.2 ± 20.0 (P = 0.0004) and hypopnea index from 28.8 ± 20.9 to 16.3 ± 14.0 (P = 0.01), whereas nocturnal oxygen saturation increased from 79.8 ± 3.6 to 80.9 ± 3.0% (P = 0.009). The procedure was easily accepted and well tolerated. Conclusion: Here, we show for the very first time that an increase in respiratory dead space through a fitted mask dramatically improves nocturnal breathing in high-altitude dwellers suffering from CMS. We speculate that when used in the long-term, this procedure will improve erythrocytosis and pulmonary hypertension and offer an inexpensive and easily implementable treatment for this major public health problem.

Proportion of out-of-hospital adult non-traumatic cardiac or respiratory arrest among calls for seizure.

OBJECTIVES: To measure the proportion of adult non-traumatic cardiac or respiratory arrest among calls for seizure to an emergency medical dispatch centre and to record whether known epileptic patients present cardiac or respiratory arrest together with seizure. METHODS: This 2-year prospective observational investigation involved the collection of tape recordings of all incoming calls to the emergency medical dispatch centre, in which an out-of-hospital non-traumatic seizure was the chief complaint in patients >18 years, in addition to the paramedics' records of all patients who presented with respiratory or cardiac arrest. The authors also recorded whether the bystander spontaneously mentioned to the dispatcher that the victim was known to have epilepsy. RESULTS: During the 24-month period, the call centre received 561 incoming calls for an out-of-hospital non-traumatic seizure in an adult. Twelve cases were classified as cardiac or respiratory arrest by paramedics. In one case, the caller spontaneously mentioned that the victim had a history of epilepsy. The proportion of cardiac or respiratory arrest among calls for seizure was 2.1%. CONCLUSION: Although these cases are rare, dispatchers should closely monitor seizure patients with the help of bystanders to exclude an out-of-hospital cardiac or respiratory arrest, in which case the dispatcher can offer telephone cardiopulmonary resuscitation advice until the paramedics arrive. Whenever the activity of the centre allows it and no new incoming call is on hold, this can be achieved by staying on the line with the caller or by calling back. A history of epilepsy should not modify the type of monitoring performed by the dispatcher as those patients may also have an arrest together with seizure.

Surréanimation liquidienne pré et intrahospitatière des patients brûlés: fréquente et néfaste [Pre- and intra-hospital over-resuscitation in burns: frequent and deleterious].

Major burns are characterized by an initial capillary leak which requires fluid resuscitation for hemodynamic stabilisation. While under-resuscitation was the major cause of death until the 80ies, over-resuscitation has become an important source of complications: abdominal compartment syndrome, escharotomies, impaired gas exchange and prolonged mechanical ventilation and hospital stay. The fluid creep started in the 90ies with an increasing proportion of the first 24 hours' fluid delivery above the 4 ml/kg/% BSA Parkland prediction. The first alerts were published under the form of case reports of increased mortality due to abdominal compartment syndrome and respiratory failure. The paper analyses the causes of this fluid creep, and the ways to prevent it, which includes rationing prehospital fluid delivery, avoiding early colloids and permissive hypovolemia.

Patients' characteristics associated with the decision of "do not attempt cardiopulmonary resuscitation" order in a Swiss hospital

Présentation En accord avec la loi suisse, seul le patient peut décider de la notification, dans son dossier, d'un ordre de «non réanimation » (DNACPR) en cas d'arrêt cardio-respiratoire. L'équipe médicale peut exceptionnellement prendre une telle décision, si elle juge qu'une réanimation n'a aucune chance d'aboutir. Les mécanismes menant à ce processus de décision n'ont pas encore été complètement investigués, en particulier en Suisse. Enjeu Notre étude vise à déterminer la prévalence de l'ordre de «non réanimation» après l'admission, l'auteur de cette décision, ainsi que son association avec certaines caractéristiques propres aux patients : le sexe, l'âge, la situation familiale, la nationalité, la religion, le nombre et le type de comorbidités. Nous cherchons ainsi à mieux définir quels sont les facteurs importants dans ce processus décisionnel complexe où le jugement médical, ainsi que l'information apportée aux patients sont primordiaux. Contexte de recherche Nous avons effectué une étude observationnelle sur une durée de 6 semaines, en analysant les formulaires d'admission de 194 patients hospitalisés dans le service de médecine interne du CHUV, dans les 72 heures après leur admission. Résultats L'étude montre que plus de la moitié des 194 dossiers de patients analysés ont un ordre de « non réanimation » (DNACPR) (53%). 27% de ces décisions ont été prises par les patients eux-mêmes, 12% par leur représentant thérapeutique/famille et 61% par les équipes médicales. Nous trouvons une association statistiquement significative entre l'ordre DNACPR et l'âge, avec un âge moyen de 80.7 +-10.8 ans dans le groupe « non réanimation » versus 67.5 +- 15.1 ans dans le groupe « réanimation », entre l'ordre DNACPR et une pathologie oncologique, quel que soit le stade de cette dernière, ainsi qu'entre l'ordre DNACPR et la religion protestante. Une analyse de sous-groupe montre que l'âge, ainsi que la pathologie oncologique sont statistiquement significatifs lors de l'analyse des décisions prises par les équipes médicales. La religion protestante est, quant à elle, significative lors de l'analyse des décisions prises par le patient ou son représentant. Perspectives Contrairement aux publications passées, cette étude montre une prédominance de l'ordre de «non réanimation » (DNACPR) à l'admission dans un service de médecine interne, principalement sur décision médicale. La plupart des patients ont été jugés incapables de discernement sur la question ou n'ont tout simplement pas été impliqués dans le processus décisionnel. Une réflexion doit avoir lieu afin de prendre des mesures de sensibilisation auprès des équipes médicales et d'approfondir la formation médicale et éthique sur le sujet de la détermination de l'attitude de réanimation. D'autres études qualitatives permettraient de mieux comprendre les motivations ayant mené à ces nombreuses décisions médicales, ainsi que les critères importants pour les patients.

Taux quotidiens d’inhalation et paramètres cardio-pulmonaires chez l’humain selon les données publiées en rapport au double marquage des molécules d’eau pour l’analyse du risque

L’objectif de cette étude est de déterminer certains paramètres respiratoires et cardiovasculaires chez des sujets de tous âges pour utilisation, à titre d’intrants physiologiques, en modélisation toxicocinétique et en analyse du risque toxique. La base de données utilisée est tirée de la littérature. Il s’agit de mesures portant sur la dépense d’énergie quotidienne de base et la dépense d’énergie quotidienne de totale obtenues, l’une par calorimétrie indirecte, l’autre par double marquage isotopique des molécules d’eau. Selon le type d’unité retenu, les valeurs les plus élevées au 99e centile des taux quotidiens d’inhalation sont obtenues chez des adolescentes et des femmes âgées de 11 à 55 ans souffrant d’embonpoint ou d’obésité, durant leur 36e semaine de grossesse (47,31 m³/jour), ainsi que chez des garçons de poids corporel normal âgés de 2,6 à moins de 6 mois (1,138 m³/kg-jour) et de 10 à moins de 16,5 ans (22,29 m³/m²-jour). Chez les enfants et les adolescents de poids corporel normal âgés de 5 à moins de 16.5 ans, les valeurs pour l’écart entre le 2,5e au 99e centile sont généralement plus élevées que celles obtenues chez les sujets plus âgés : taux de ventilation minute, 0,132 à 0,774 L/kg-min ou 4,42 à 21,69 L/m²-min versus 0,076 à 0,461 L/kg-min ou 2,80 à 16,99 L/m²-min; taux de ventilation alvéolaire, 0,093 à 0,553 L/kg-min ou 3,09 à 15,53 L/m²-min versus 0,047 à 0,312 L/kg-min ou 1,73 à 11,63 L/m²-min; débit cardiaque, 0,065 à 0,330 L/kg-min ou 2,17 à 9,46 L/m²-min versus 0,045 à 0,201 L/kg-min ou 1,63 à 7,24 L/m²-min; ratio de ventilation-perfusion, 1,12 à 2,16 versus 0,78 à 2,40. Il faut conclure que les apports inhalés en polluants, exprimés en ug/kg-min ou ug/m²-min sont plus élevés chez les enfants que chez les sujets plus âgés pour des concentrations d’exposition comparables. D’autres données montrent qu’il en est de même pour les apports inhalés par unité de poids corporel chez les femmes enceintes et les femmes qui allaitent par rapport à des sujets males d’âge comparable. L’ensemble des résultats obtenus suggère notamment que les valeurs des NOAELH de Santé Canada pourraient être abaissées par un facteur de 2,6 par utilisation du 99e centile le plus élevé des taux quotidiens d’inhalation chez les enfants; le taux de ventilation minute de 20,83 L/min approximé pour une journée de travail de 8 heures peut être considéré comme étant conservateur ; par contre, l’utilisation du taux quotidien d’inhalation de 0,286 m³/kg-jour (c.-à-d. 20 m³/jour pour un adulte de poids corporel de 70 kg) est inappropriée en analyse et gestion du risque lorsqu’appliquée à l’ensemble de la population.

Le rôle de l’Oxygénation Extracorporelle par Membrane (ECMO) dans la réanimation cardio-pulmonaire

Rapport de stage présenté à la Faculté de médecine en vue de l'obtention du grade de Maître ès sciences appliquées (M.Sc.A.) en génie biomédical, option génie clinique.

TONOMETRY REVISITED: PERFUSION-RELATED, METABOLIC, AND RESPIRATORY COMPONENTS OF GASTRIC MUCOSAL ACIDOSIS IN ACUTE CARDIORESPIRATORY FAILURE

Mucosal pH (pHi) is influenced by local perfusion and metabolism (mucosal-arterial Pco2 gradient, DeltaPco2), systemic metabolic acidosis (arterial bicarbonate), and respiration (arterial Pco2). We determined these components of pHi and their relation to outcome during the first 24 h of intensive care. We studied 103 patients with acute respiratory or circulatory failure (age, 63 +/- 2 [mean +/- SEM]; Acute Physiology and Chronic Health Evaluation II score, 20 +/- 1; Sequential Organ Failure Assessment score, 8 +/- 0). pHi, and the effects of bicarbonate and arterial and mucosal Pco2 on pHi, were assessed at admission, 6, and 24 h. pHi was reduced (at admission, 7.27 +/- 0.01) due to low arterial bicarbonate and increased DeltaPco2. Low pHi (<7.32) at admission (n = 58; mortality, 29% vs. 13% in those with pHi >/=7.32 at admission; P = 0.061) was associated with an increased DeltaPco2 in 59% of patients (mortality, 47% vs. 4% for patients with low pHi and normal DeltaPco2; P = 0.0003). An increased versus normal DeltaPco2, regardless of pHi, was associated with increased mortality at admission (51% vs. 5%; P < 0.0001; n = 39) and at 6 h (34% vs. 13%; P = 0.016; n = 45). A delayed normalization or persistently low pHi (n = 47) or high DeltaPco2 (n = 25) was associated with high mortality (low pHi [34%] vs. high DeltaPco2 [60%]; P = 0.046). In nonsurvivors, hypocapnia increased pHi at baseline, 6, and 24 h (all P resuscitation suggests poor tissue perfusion and is associated with high mortality. Arterial bicarbonate contributes more to pHi than the DeltaPco2 but is not associated with mortality. Hyperventilation partly masks mucosal acidosis. Inadequate tissue perfusion may persist despite stable hemodynamics and contributes to poor outcome.

Effect of fluid resuscitation on mortality and organ function in experimental sepsis models

Introduction Several recent studies have shown that a positive fluid balance in critical illness is associated with worse outcome. We tested the effects of moderate vs. high-volume resuscitation strategies on mortality, systemic and regional blood flows, mitochondrial respiration, and organ function in two experimental sepsis models. Methods 48 pigs were randomized to continuous endotoxin infusion, fecal peritonitis, and a control group (n = 16 each), and each group further to two different basal rates of volume supply for 24 hours [moderate-volume (10 ml/kg/h, Ringer's lactate, n = 8); high-volume (15 + 5 ml/kg/h, Ringer's lactate and hydroxyethyl starch (HES), n = 8)], both supplemented by additional volume boli, as guided by urinary output, filling pressures, and responses in stroke volume. Systemic and regional hemodynamics were measured and tissue specimens taken for mitochondrial function assessment and histological analysis. Results Mortality in high-volume groups was 87% (peritonitis), 75% (endotoxemia), and 13% (controls). In moderate-volume groups mortality was 50% (peritonitis), 13% (endotoxemia) and 0% (controls). Both septic groups became hyperdynamic. While neither sepsis nor volume resuscitation strategy was associated with altered hepatic or muscle mitochondrial complex I- and II-dependent respiration, non-survivors had lower hepatic complex II-dependent respiratory control ratios (2.6 +/- 0.7, vs. 3.3 +/- 0.9 in survivors; P = 0.01). Histology revealed moderate damage in all organs, colloid plaques in lung tissue of high-volume groups, and severe kidney damage in endotoxin high-volume animals. Conclusions High-volume resuscitation including HES in experimental peritonitis and endotoxemia increased mortality despite better initial hemodynamic stability. This suggests that the strategy of early fluid management influences outcome in sepsis. The high mortality was not associated with reduced mitochondrial complex I- or II-dependent muscle and hepatic respiration.