Background This study aimed to assess a potential organ protective effect of volatile sedation in a scenario of severe inflammation with an early cytokine storm (in particular IL-6 elevation) in patients suffering from COVID-19-related lung injury with invasive mechanical ventilation and sedation. Methods This is a small-scale pilot multicenter randomized controlled trial from four tertiary hospitals in Switzerland, conducted between April 2020 and May 2021. 60 patients requiring mechanical ventilation due to severe COVID-19-related lung injury were included and randomized to 48-hour sedation with sevoflurane vs. continuous intravenous sedation (= control) within 24 h after intubation. The primary composite outcome was determined as mortality or persistent organ dysfunction (POD), defined as the need for mechanical ventilation, vasopressors, or renal replacement therapy at day 28. Secondary outcomes were the length of ICU and hospital stay, adverse events, routine laboratory parameters (creatinine, urea), and plasma inflammatory mediators. Results 28 patients were randomized to sevoflurane, 32 to the control arm. The intention-to-treat analysis revealed no difference in the primary endpoint with 11 (39%) sevoflurane and 13 (41%) control patients ( p = 0.916) reaching the primary outcome. Five patients died within 28 days in each group (16% vs. 18%, p = 0.817). Of the 28-day survivors, 6 (26%) and 8 (30%) presented with POD ( p = 0.781). There was a significant difference regarding the need for vasopressors (1 (4%) patient in the sevoflurane arm, 7 (26%) in the control one ( p = 0.028)). Length of ICU stay, hospital stay, and registered adverse events within 28 days were comparable, except for acute kidney injury (AKI), with 11 (39%) sevoflurane vs. 2 (6%) control patients ( p = 0.001). The blood levels of IL-6 in the first few days after the onset of the lung injury were less distinctly elevated than expected. Conclusions No evident benefits were observed with short sevoflurane sedation on mortality and POD. Unexpectedly low blood levels of IL-6 might indicate a moderate injury with therefore limited improvement options of sevoflurane. Acute renal issues suggest caution in using sevoflurane for sedation in COVID-19. Trial registration The trial was registered on ClinicalTrials.gov (NCT04355962) on 2020/04/21.

PurposeMultiple murine studies modelling the immuno-pathophysiological consequences of trauma, shock, burn or sepsis were performed during the last decades. Almost every animal model requires anesthesia for practical and ethical reasons. Furthermore, often, corresponding control groups involve untreated animals without or with a limited exposure to anesthetics. However, the influences of anesthetic drugs on immuno-pathophysiological reactions remain insufficiently investigated. Therefore, we aimed to closer characterize the anesthetic impact exemplified by sevoflurane on the organ performance in mice and thereby investigate the influence of anesthesia itself on major outcome parameters in animal studies.MethodsC57/BL6 mice were subjected either to 270 min of sevoflurane narcosis or directly euthanized. Plasma, BAL-fluids, lungs, kidneys, liver and intestine were collected and examined for immunological, functional and morphological changes.ResultsSystemic levels of the cytokine keratinocyte chemoattractant (KC) were raised in the narcosis group, while concentrations of high mobility group box protein 1 (HMGB-1) as a major inflammatory marker were reduced. In the lungs, levels of HMGB-1 and interleukin 6 (IL-6) were reduced. In contrast, systemic concentrations of intestinal fatty acid binding-protein (i-FABP) as an intestinal damage marker were elevated. Furthermore, liver-type fatty acid binding-protein (L-FABP) levels were lower in the narcosis animals, and inflammatory markers were reduced in liver tissues. Anesthesia also ameliorated the inflammatory reaction in renal tissues, while plasma levels of urea and creatinine were elevated, reflecting either dehydration and/or impaired renal function.ConclusionAs anesthesia with sevoflurane exhibited distinct effects in different organs, it is difficult to predict its specific impact on targets of interest in in vivo studies. Therefore, further studies are required to clarify the effects of different anesthetic drugs. Overall, the inclusion of a control group subjected to the same anesthesia protocol as the experimental groups of interest seems helpful to precisely define the inherent impact of the anesthetic when investigating immuno-pathophysiologic conditions in vivo.

ABSTRACT Abdominal trauma (AT) is of major global importance, particularly because the civil, terroristic, and military traumatic potential of blast injuries has increased. The consequences of blunt abdominal injuries are highly variable and frequently underestimated or even overlooked. However, the underlying path mechanisms and subsequent innate immune response remain poorly understood. Therefore, we investigated the spatiotemporal local and systemic effects of a standardized blast-induced blunt AT on the intestine and innate immune response. In an established AT model, 66 male C57Bl6 mice were anesthetized and exposed to either a single blast wave centered on the epigastrium or control treatment (sham). At 2, 6, or 24 hours after trauma induction, animals were sacrificed. In 16 of 44 (36%) AT animals, one or more macroscopically visible injuries of the intestine were observed. Epithelial damage was detected by histological analysis of jejunum and ileum tissue samples, quantified by the Chiu score and by increased plasma concentrations of the intestinal fatty acid–binding protein, an enterocyte damage marker. Moreover, in the early posttraumatic period, elevated syndecan-1, claudin-5, and mucin-2 plasma levels also indicated alterations in the gut-blood barrier. Increased levels of pro-inflammatory cytokines such as TNF and macrophage inflammatory protein 2 in tissue homogenates and plasma indicate a systemic immune activation after blunt AT. In conclusion, we detected early morphological intestinal damage associated with high, early detectable intestinal fatty acid–binding protein plasma levels, and a considerable time- and dose-dependent impairment of the gut-blood barrier in a newly established mouse model of blunt AT. It appears to be a sufficient model for further studies of the intestinal immunopathophysiological consequences of AT and the evaluation of novel therapeutic approaches.

Background and objectives: The coronavirus disease 2019 (COVID-19) pandemic and the shortage of intravenous sedatives has led to renewed interest in inhaled sedation for patients with acute respiratory distress syndrome (ARDS). We hypothesized that inhaled sedation would be associated with improved clinical outcomes in COVID-19 ARDS patients. Methods: Retrospective international study including mechanically ventilated patients with COVID-19 ARDS who required sedation and were admitted to 10 European and US intensive care units. The primary endpoint of ventilator-free days through day 28 was analyzed using zero-inflated negative binomial regression, before and after adjustment for site, clinically relevant covariates determined according to the univariate results, and propensity score matching. Results: A total of 196 patients were enrolled, 78 of whom died within 28 days. The number of ventilator-free days through day 28 did not differ significantly between the patients who received inhaled sedation for at least 24 h (n = 111) and those who received intravenous sedation only (n = 85), with medians of 0 (interquartile range [IQR] 0–8) and 0 (IQR 0–17), respectively (odds ratio for having zero ventilator-free days through day 28, 1.63, 95% confidence interval [CI], 0.91–2.92, p = 0.10). The incidence rate ratio for the number of ventilator-free days through day 28 if not 0 was 1.13 (95% CI, 0.84–1.52, p = 0.40). Similar results were found after multivariable adjustment and propensity matching. Conclusion: The use of inhaled sedation in COVID-19 ARDS was not associated with the number of ventilator-free days through day 28.

BACKGROUND: Postoperative complications in surgery are a significant burden, not only for the patients but also economically. While several predicting factors have already been identified, it is still not well known if increased levels of inflammatory markers in the immediate perioperative phase correlate with a higher incidence of postoperative complications. This study aimed to evaluate which patient characteristics and intraoperative parameters correlate with increased plasma values of monocyte chemoattractant protein 1 (MCP-1) and interleukin 6 (IL-6) of thoracic surgery patients. A second goal was to explore whether MCP-1 and IL-6 are associated with the incidence of postoperative complications. We hypothesized that there is a positive association between inflammatory markers and the occurrence of complications within 6 months after surgery. METHODS: This is a substudy of a recent randomized controlled trial, which defined the effect of desflurane versus propofol anesthesia on morbidity and mortality in patients undergoing thoracic surgery. MCP-1 and IL-6 were determined in plasma obtained before and 30 minutes after 1-lung ventilation, 6 hours after surgery, and on postoperative days 1 and 2. Complications were recorded for 6 months. Mixed linear models were used to examine factors associated with MCP-1 and IL-6 levels. Logistic regression models and receiver operating characteristic curves were used to determine the association between MCP-1 and IL-6 and postoperative complications. RESULTS: In the original study, 460 patients were included, MCP-1 and IL-6 levels were determined in 428 patients. MCP-1 was positively associated with the duration of surgery ( P = .016), whereas IL-6 levels increased with both the length ( P < .001) and invasiveness of lung surgery (thoracoscopic wedge resection or lobectomy versus open lobectomy, P = .005; thoracoscopic wedge resection or lobectomy versus pneumonectomy, P = .021). In an exploratory approach, elevated IL-6 plasma peaks were associated with the occurrence of severe complications defined as Clavien-Dindo score grade ≥IVa during the postoperative phase up to 6 months after thoracic surgery ( P = .006). CONCLUSIONS: In summary, this substudy reveals factors, which correlate with high MCP-1 and IL-6 values. Moreover, higher IL-6 seems to be associated with postoperative severe complications. Perioperative IL-6 monitoring might be helpful for risk estimation in the perioperative setting of patients after lung surgery.

Accurate identification of patients at risk of blood transfusion can reduce complications and improve institutional resource allocation. Probabilistic models are used to detect risk factors and formulate patient blood management strategies. Whether these predictors vary among institutions is unclear. We aimed to identify risk factors among our patients who underwent total hip (THA) or knee (TKA) arthroplasty, and combine these predictors to improve our model. We retrospectively assessed risk factors among 531 adults who underwent elective THA or TKA from January 2016 to November 2018. Using relevant surgical and patient characteristics gathered from electronic medical records, we conducted univariable and multivariable analyses. For our logistic regression model, we measured the impact of independent variables (age, gender, operation type (THA or TKA) and preoperative hemoglobin concentration) on the need for a transfusion. Of the 531 patients, 321 had THA (uncemented) and 210 had TKA. For the selected period, our transfusion rate of 8.1% (10.6% THA and 4.3% TKA) was low. Univariable analyses showed that lower BMI (p < 0.001) was associated with receiving a transfusion. Important factors identified through logistic regression analyses were age (estimated effect of an interquartile range increase in age: OR 3.89 [CI 95% 1.96–7.69]), TKA (OR − 0.77 [CI 95% − 1.57–0.02]), and preoperative hemoglobin levels (estimated effect of interquartile range increase in hemoglobin: OR 0.47 [CI 95% 0.31–0.71]). Contrary to findings from previous reports, gender was not associated with transfusion. Previously published predictors such as advanced age, low preoperative hemoglobin, and procedure type (THA) were also identified in our analysis. However, gender was not a predictor, and BMI showed the potential to influence risk. We conclude that, when feasible, the determination of site-specific transfusion rates and combined risk factors can assist practitioners to customize care according to the needs of their patient population. Level 3, retrospective cohort study

Purpose Complement is activated in hemorrhagic shock and protective effects by specific complement inhibition were shown. However, it remains unclear if complement activation contributes to the local tissue damage and organ failure. Zonulin is known to activate complement and affect organ failure. Therefore, local and systemic complement activation during hemorrhagic shock and its consequences on zonulin were examined. Methods Porcine hemorrhagic shock (n = 9) was initiated with mean arterial blood pressure maintained constant for 4 h before retransfusion. Before, 4 h after hemorrhage and 12 and 22 h after resuscitation, central and renal blood samples were drawn. Analysis included HMGB-1, C3a, and zonulin (blood and kidney homogenisates) as well as terminal complement complex (TCC) and CH50 (blood). Organ samples were taken for histological and immunohistochemical analyses (C3c). Results HMGB-1 was significantly elevated in plasma 4 h after hemorrhagic shock and in homogenized kidneys. TCC after 12 h was significantly elevated centrally, while renal levels were not altered. In contrast, CH50 showed diminished renal values, while normal central levels were observed. Local complement activation was observed with enhanced C3c deposition in kidneys. Zonulin showed significantly diminished levels at 12 and 22 h after hemorrhagic shock (central and renal) and significantly correlated with levels of CH50 and neutrophil gelatinase-associated lipocalin (NGAL). Conclusion The more pronounced complement activation centrally might indicate consumption of complement products in kidney tissue, which is underlined by C3c staining. Together with diminished levels of zonulin in both systemic and local samples, results could indicate the involvement of complement as well as zonulin in acute kidney failure.

OBJECTIVES Surgical repair of aneurysmal disease involving the ascending aorta, aortic arch and eventually the descending aorta is generally associated with significant morbidity and mortality. A less invasive approach with the ascending wrapping technique (WT), supra-aortic vessel debranching (SADB) and thoracic endovascular aneurysm repair (TEVAR) in zone 0 was developed to reduce the associated risk in these patients. METHODS During a 10-year period, consecutive patients treated by the ascending WT, SADB and TEVAR in zone 0 were included. All patients were considered at high risk for conventional surgery. Measured outcomes included perioperative deaths and morbidity, maximal aortic transverse diameter (TD) and its postoperative evolution, endoleak, survival, freedom from cardiovascular reinterventions, SADB freedom from occlusion and aortic valve function during follow-up. Median follow-up was 37.4 [mean = 34; range, 0-65; standard deviation (SD) = 20] months. RESULTS Twenty-six cases were included with a mean age of 71.88 ( r  = 56-87; SD = 8) years. A mean of 2.9 supra-aortic vessels (75) per patient was debranched from the ascending aorta. The mean time interval from WT/SADB and TEVAR was 29 ( r  = 0-204; SD = 48) days. TEVAR was associated with chimney and/or periscope grafts in 6 (23%) patients, and extra-anatomical supra-aortic bypasses were performed in 6 (23%) patients. Perioperative mortality was 7.7% (2/26). Neurological events were registered in 3 (11.5%) cases, and a reintervention was required in 3 (11.5%) cases. After the WT, the ascending diameter remained stable during the follow-up period in all cases. At mean follow-up, significant shrinkage of the arch/descending aorta diameter was observed. A type I/III endoleak occurred in 3 cases. At 5 years, the rates of survival, freedom from cardiovascular reinterventions and SADB freedom from occlusion were 71.7, 82.3 and 96%, respectively. CONCLUSIONS The use of the ascending WT, SADB and TEVAR in selected patients with complex thoracic aorta disease is safe and shows promising mid-term results at 3 years. The combination of these techniques could represent an alternative to the standard open surgical repair, especially in older patients or in patients unfit for cardiopulmonary bypass.

Chronic foot and leg ulcers are a common health problem worldwide. A mainstay of chronic ulcer therapy is sharp mechanical wound debridement requiring potent analgesia. In this prospective, controlled, single-centre, crossover design study, patients were assigned to either the administration of topical analgesia with 5% lidocaine/prilocaine cream or the inhalation of an analgesic 50% N2 O/O2 gas premix. Primary outcome parameter was level of pain at maximum wound depth during debridement as measured by a visual analogue scale. Secondary outcomes included level of pain after debridement, overall duration of treatment session, duration and completeness of debridement, and the patient's subjective perception of analgesic quality during debridement. Pain level increased from 0·60/0·94 (first/second debridement; baseline) to 1·76/2·50 (debridement) with 5% lidocaine/prilocaine and from 1·00/1·35 (baseline) to 3·95/3·29 (debridement) with 50% N2 O/O2 gas premix. Patient satisfaction was 90·48%/94·44% (first/second debridement) with topical 5% lidocaine/prilocaine analgesia and 90·48%/76·47% with the inhalation of 50% N2 O/O2 gas premix. Debridement was completed in a significantly higher percentage of 85·71%/88·89% (first/second debridement) with 5% lidocaine/prilocaine than with 50% N2 O/O2 gas premix (42·86%/58·82%) (odds ratio 6·7; P = 0·001). This study provides sound evidence that analgesia with topically administered 5% lidocaine/prilocaine cream is superior to the use of inhaled 50% N2 O/O2 gas premix in chronic leg ulcer debridement.

BACKGROUND:One-lung ventilation during thoracic surgery is associated with hypoxia-reoxygenation injury in the deflated and subsequently reventilated lung. Numerous studies have reported volatile anesthesia-induced attenuation of inflammatory responses in such scenarios. If the effect also extends to clinical outcome is yet undetermined. We hypothesized that volatile anesthesia is superior to intravenous anesthesia regarding postoperative complications. METHODS:Five centers in Switzerland participated in the randomized controlled trial. Patients scheduled for lung surgery with one-lung ventilation were randomly assigned to one of two parallel arms to receive either propofol or desflurane as general anesthetic. Patients and surgeons were blinded to group allocation. Time to occurrence of the first major complication according to the Clavien-Dindo score was defined as primary (during hospitalization) or secondary (6-month follow-up) endpoint. Cox regression models were used with adjustment for prestratification variables and age. RESULTS:Of 767 screened patients, 460 were randomized and analyzed (n = 230 for each arm). Demographics, disease and intraoperative characteristics were comparable in both groups. Incidence of major complications during hospitalization was 16.5% in the propofol and 13.0% in the desflurane groups (hazard ratio for desflurane vs. propofol, 0.75; 95% CI, 0.46 to 1.22; P = 0.24). Incidence of major complications within 6 months from surgery was 40.4% in the propofol and 39.6% in the desflurane groups (hazard ratio for desflurane vs. propofol, 0.95; 95% CI, 0.71 to 1.28; P = 0.71). CONCLUSIONS:This is the first multicenter randomized controlled trial addressing the effect of volatile versus intravenous anesthetics on major complications after lung surgery. No difference between the two anesthesia regimens was evident.

Introduction In a recent randomized controlled trial our group has demonstrated in 102 patients that late post-conditioning with sevoflurane performed in the intensive care unit after surgery involving extracorporeal circulation reduced damage to cardiomyocytes exposed to ischemia reperfusion injury. On the first post-operative day the sevoflurane patients presented with lower troponin T values when compared with those undergoing propofol sedation. In order to assess possible clinical relevant long-term implications in patients enrolled in this study, we performed the current retrospective analysis focusing on cardiac and non-cardiac events during the first 6 months after surgery. Methods All patients who had successfully completed the late post-conditioning trial were included into this follow-up. Our primary and secondary endpoints were the proportion of patients experiencing cardiac and non-cardiac events, respectively. Additionally, we were interested in assessing therapeutic interventions such as initiation or change of drug therapy, interventional treatment or surgery. Results Of 102 patients analyzed in the primary study 94 could be included in this follow-up. In the sevoflurane group (with 41 patients) 16 (39%) experienced one or several cardiac events within 6 months after cardiac surgery, in the propofol group (with 53 patients) 19 (36%, p=0.75). Four patients (9%) with sevoflurane vs. 7 (13%) with propofol sedation had non-cardiac events (p=0.61). While a similar percentage of patients suffered from cardiac and/or non-cardiac events, only 12 patients in the sevoflurane group compared to 20 propofol patients needed a therapeutic intervention (OR: 0.24, 95% CI: 0.04-1.43, p=0.12). A similar result was found for hospital admissions: 2 patients in the sevoflurane group had to be re-admitted to the hospital compared to 8 in the propofol group (OR 0.23, 95% CI: 0.04-1.29, p=0.10). Conclusions Sevoflurane does not seem to provide protection with regard to the occurrence of cardiac and non-cardiac events in the 6-month period following cardiac surgery with the use of extracorporeal circulation. However, there was a clear trend towards fewer interventions (less need for treatment, fewer hospital admissions) associated with sevoflurane post-conditioning in patients experiencing any event. Such results might encourage launching large multicenter post-conditioning trials with clinical outcome defined as primary endpoint.

During experimental sepsis, excessive generation of the anaphylatoxin C5a results in reduction of the C5a receptor (C5aR) on neutrophils. These events have been shown to result in impaired innate immunity. However, the regulation and fate of C5aR on neutrophils during sepsis are largely unknown. In contrast to 30 healthy volunteers, 60 patients in septic shock presented evidence of complement activation with significantly increased serum levels of C3a, C5a, and C5b-9. In the septic shock group, the corresponding decrease in complement hemolytic activity distinguished survivors from nonsurvivors. Neutrophils from patients in septic shock exhibited decreased C5aR expression, which inversely correlated with serum concentrations of C-reactive protein (CRP) and clinical outcome. In vitro exposure of normal neutrophils to native pentameric CRP led to a dose- and time-dependent loss of C5aR expression on neutrophils, whereas the monomeric form of CRP, as well as various other inflammatory mediators, failed to significantly alter C5aR levels on neutrophils. A circulating form of C5aR (cC5aR) was detected in serum by immunoblotting and a flow-based capture assay, suggestive of an intact C5aR molecule. Levels of cC5aR were significantly enhanced during septic shock, with serum levels directly correlating with lethality. The data suggest that septic shock in humans is associated with extensive complement activation, CRP-dependent loss of C5aR on neutrophils, and appearance of cC5aR in serum, which correlated with a poor outcome. Therefore, cC5aR may represent a new sepsis marker to be considered in tailoring individualized immune-modulating therapy.

There are limited data on the efficacy of early fluid resuscitation with third-generation hydroxyethyl starch (HES 130) in burn injury. Adverse effects of HES on survival and organ function have been reported.

Background Renal failure with following continuous renal replacement therapy is a major clinical problem in liver transplant recipients, with reported incidences of 3% to 20%. Little is known about the significance of postoperative acute renal failure or acute-on-chronic renal failure to postoperative outcome in liver transplant recipients. Methods In this post hoc analysis we compared the mortality rates of 135 consecutive liver transplant recipients over 6 years in our center subject to their renal baseline conditions and postoperative RRT. We classified the patients into 4 groups, according to their preoperative calculated Cockcroft formula and the incidence of postoperative renal replacement therapy. Data then were analyzed in regard to mortality rates and in addition to pre- and peritransplant risk factors. Results There was a significant difference in ICU mortality (p=.008), hospital mortality (p=.002) and cumulative survival (p<.0001) between the groups. The highest mortality rate occurred in the group with RRT and normal baseline kidney function (20% ICU mortality, 26.6% hospital mortality and 50% cumulative 1-year mortality, respectively). The hazard ratio in this group was 9.6 (CI 3.2-28.6, p=.0001). Conclusion This study shows that in liver transplant recipient’s acute renal failure with postoperative RRT is associated with mortality and the mortality rate is higher than in patients with acute-on-chronic renal failure and postoperative renal replacement therapy.

INTRODUCTION:The aim of this randomized controlled trial was to investigate whether volatile anesthetics used for postoperative sedation have any beneficial effects on myocardial injury in cardiac surgery patients after on-pump valve replacement.METHODS:Anesthesia was performed with propofol. After arrival in the intensive care unit (ICU), 117 patients were randomized to be sedated for at least 4 hours with either propofol or sevoflurane. Sevoflurane was administered by using the anesthetic-conserving device. Troponin T, creatine kinase, creatine kinase from heart muscle tissue, myoglobin, and oxygenation index were determined on arrival at the ICU, 4 hours after sedation, and in the morning of the first postoperative day (POD1). Primary end points were cardiac injury markers on POD1. As secondary end points oxygenation, postoperative pulmonary complications, and ICU and hospital stay were documented.RESULTS:Fifty-six patients were analyzed in the propofol arm, and 46 patients in the sevoflurane arm. Treatment groups were comparable with regard to patient demographics and intraoperative characteristics. Concentration of troponin T as the most sensitive marker for myocardial injury at POD1 was significantly lower in the sevoflurane group compared with the propofol group (unadjusted difference, -0.4; 95% CI, -0.7 to -0.1; P < 0.01; adjusted difference, -0.2; 95% CI, -0.4 to -0.02; P = 0.03, respectively).CONCLUSIONS:The data presented in this investigation indicate that late postconditioning with the volatile anesthetic sevoflurane might mediate cardiac protection, even with a late, brief, and low-dose application.TRIAL REGISTRATION:ClinicalTrials.gov: NCT00924222.

Hydroxyethyl starch has recently become the subject of renewed interest because of the introduction of a new specification, hydroxyethyl starch 130/0.4, as well as the clinical availability of a solution using a previous hydroxyethyl starch type (hydroxyethyl starch 670/0.75) with a carrier other than 0.9% saline. Various types of hydroxyethyl starch show different pharmacokinetic behaviour. Since hydroxyethyl starch is a polydisperse solution acting as a colloid, pharmacodynamic action depends on the number of oncotically active molecules, not on the plasma concentration alone; therefore, solutions with a lower in vivo molecular weight contain more molecules at similar plasma concentrations. On the other hand, high plasma concentrations as well as high in vivo molecular weight can affect blood coagulation, especially factor VIII and von Willebrand factor. Hydroxyethyl starch types with a molar substitution >0.4 accumulate in plasma after repetitive administration, most pronounced with hetastarch (hydroxyethyl starch 670/0.75). Correspondingly, tissue storage as measured by (14)C tracer studies in animals showed significantly higher values for hydroxyethyl starch 200/0.5 compared with hydroxyethyl starch 130/0.4 (about 4-fold at the latest timepoint after the last administration), and considerably higher values for hetastarch compared with both hydroxyethyl starch 130/0.4 and 200/0.5. Hydroxyethyl starch 130/0.4 does not accumulate in plasma after single- and multiple-dose administration in contrast to all other available hydroxyethyl starch specifications. Plasma clearance of hydroxyethyl starch 130/0.4 is at least 20-fold higher than that for hetastarch, and considerably higher than for pentastarch. In patients with renal insufficiency, pharmacokinetic data are only available for hydroxyethyl starch 130/0.4. Cumulative urinary excretion, even in the presence of severe non-anuric renal failure, is higher for hydroxyethyl starch 130/0.4 than values published for older hydroxyethyl starch specifications. Hydroxyethyl starch 130/0.4 may be given to patients with severe renal impairment as long as urine flow is preserved. The pharmacodynamics with respect to the volume effect does not directly mirror pharmacokinetics in the case of hydroxyethyl starch solutions. Equivalent volume efficacy has been proven for hydroxyethyl starch 130/0.4 compared with 200/0.5. Prolonged persistence of hydroxyethyl starch in plasma and tissues can be avoided by using rapidly metabolisable hydroxyethyl starch types with molar substitution <0.5. Influence on coagulation is minimal with hydroxyethyl starch 130/0.4, and no adverse effects on kidney function have been observed even with large repetitive doses when used according to the product information.

Less is known about the influence of hematocrit detection methodology on transfusion triggers. Therefore, the aim of the present study was to compare two different hematocrit-assessing methods. In a total of 50 critically ill patients hematocrit was analyzed using (1) blood gas analyzer (ABLflex 800) and (2) the central laboratory method (ADVIA® 2120) and compared.

INTRODUCTION:Despite large experience in the management of severe burn injury, there are still controversies regarding the best type of fluid resuscitation, especially during the first 24 hours after the trauma. Therefore, our study addressed the question whether hyperoncotic hydroxyethyl starch (HES) 200/0.5 (10%) administered in combination with crystalloids within the first 24 hours after injury is as effective as 'crystalloids only' in severe burn injury patients.METHODS:30 consecutive patients were enrolled to this prospective interventional open label study and assigned either to a traditional 'crystalloids only' or to a 'HES 200/0.5 (10%)' volume resuscitation protocol. Total amount of fluid administration, complications such as pulmonary failure, abdominal compartment syndrome, sepsis, renal failure and overall mortality were assessed. Cox proportional hazard regression analysis was performed for binary outcomes and adjustment for potential confounders was done in the multivariate regression models. For continuous outcome parameters multiple linear regression analysis was used.RESULTS:Group differences between patients receiving crystalloids only or HES 200/0.5 (10%) were not statistically significant. However, a large effect towards increased overall mortality (adjusted hazard ratio 7.12; P = 0.16) in the HES 200/0.5 (10%) group as compared to the crystalloids only group (43.8% versus 14.3%) was present. Similarly, the incidence of renal failure was 25.0% in the HES 200/0.5 (10%) group versus 7.1% in the crystalloid only group (adjusted hazard ratio 6.16; P = 0.42).CONCLUSIONS:This small study indicates that the application of hyperoncotic HES 200/0.5 (10%) within the first 24 hours after severe burn injury may be associated with fatal outcome and should therefore be used with caution.TRIAL REGISTRATION:NCT01120730.