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BackgroundThe investigation of CO2reactivity (CO2-CVR) is used in the setting of, e.g., traumatic brain injury (TBI). Transcranial color-coded duplex sonography (TCCD) is a promising bedside tool for monitoring cerebral hemodynamics. This study used TCCD to investigate CO2-CVR in volunteers, in sedated and mechanically ventilated patients without TBI and in sedated and mechanically ventilated patients in the acute phase after TBI.MethodsThis interventional investigation was performed between March 2013 and February 2016 at the surgical ICU of the University Hospital of Zurich. Ten volunteers (group 1), ten sedated and mechanically ventilated patients (group 2), and ten patients in the acute phase (12–36 h) after severe TBI (group 3) were included. CO2-CVR to moderate hyperventilation (∆ CO2-5.5 mmHg) was assessed by TCCD.ResultsCO2-CVR was 2.14 (1.20–2.70) %/mmHg in group 1, 2.03 (0.15–3.98) %/mmHg in group 2, and 3.32 (1.18–4.48)%/mmHg in group 3, without significant differences among groups.ConclusionOur data did not yield evidence for altered CO2-CVR in the early phase after TBI examined by TCCD.Trial registrationPart of this trial was performed as preparation for the interventional trial in TBI patients (clinicaltrials.govNCT03822026, 30.01.2019, retrospectively registered).

Background and Purpose: There is an increasing number of evidence-based indications for pharmacogenetic (PGx) tests and a growing demand for PGx screening. We aimed to evaluate clinical relevance of a 16-gene panel test for PGx-guided pharmacotherapy. Experimental Approach: Observational cohort study of subjects tested with a PGx panel for variants of ABCB1, COMT, CYP1A2, CYP2B6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, CYP4F2, DPYD, OPRM1, POR, SLCO1B1, TPMT and VKORC1. Specialized clinical pharmacology consultations with PGx-guided pharmacotherapy management were supported by the PGx expert system SONOGEN XP. Study outcomes were PGx-based changes and recommendations regarding current and potential future medication. Key Results: PGx-testing was triggered by specific drug-gene pairs in 102 subjects, whereas screening was performed in 33. Based on PHARMGKB expert guidelines the 16-gene panel identified at least one “actionable” variant relevant for current or potential future medication in all 135 (100%) tested patients. Drugs that triggered PGx-testing were clopidogrel in 60, tamoxifen in 15, polypsychopharmacotherapy in 9, opioids in 7, and other in 11 patients. Among those, PGx variants resulted in clinical recommendations to change PGx-triggering drugs in 33 (32.4 %), and other current pharmacotherapy in 23 (22.5%). Conclusion and Implications: The 16-gene PGx panel detected clinically relevant variants in a high proportion of tested patients, and SONOGEN XP supported their interpretation based on latest evidence. Additional costs of panel vs. single gene tests are moderate, and the efficiency of PGx panel testing challenges traditional cost-benefit calculations for single drug-gene pairs. However, PGx-guided pharmacotherapy requires specialized consultations with interdisciplinary collaborations.

Population-based, cross-sectional. To determine pain prevalence and identify factors associated with chronic pain in individuals with spinal cord injury (SCI) living in Switzerland. Swiss SCI Cohort Study (SwiSCI). Pain characteristics were assessed using an adapted version of the International SCI Pain Basic Data Set, adding one item of the SCI Secondary Conditions Scale to address chronic pain. Pain prevalence was calculated using stratification over demographic, SCI-related and socioeconomic characteristics; odds ratios (adjusted for non-response) for determinants of severity of chronic pain were calculated using stereotype logistic regressions. Pain (in the past week) was reported by 68.9% and chronic pain by 73.5% (significant 36.9%) of all participants (N=1549; 28% female). Most frequently reported pain type was musculoskeletal (71.1%). Back/spine was the most frequently reported pain location (54.6%). Contrasting the 'significant' to the 'none/mild' category of chronic pain, adjusted odds ratios were 1.54 (95% CI: 1.18–2.01; P

Objectives The speed of intrathecal drug administration (slow continuous infusion vs. rapid bolus application) might influence the efficacy of therapy despite the equal daily dose in both administration patterns. We tested this hypothesis in a small prospective single-centre pilot study in a population of chronic pain patients with intrathecal opioid therapy. Methods Ten patients receiving intrathecal opioids for chronic pain assessed their pain four times daily on a numeric rating scale (NRS), more than the time course of six weeks divided into three blocks of two weeks each: Baseline evaluation (intrathecal pumps with previously established continuous infusion settings), followed by two blinded trial blocks of continuous (same pump parameters as during evaluation) and bolus (40% of daily dose split into four equal boli applied every six hours, with the remaining 60% as background continuous infusion) regimes. Patients were randomized in a crossover fashion. Results 6/10 patients reported significantly lower NRS-scores during bolus as compared to continuous trial blocks while only one patient showed the opposite effect. Overall, bolus trial blocks were associated with a small but significant reduction of NRS-scores (mean −0.56; p

OBJECTIVES Primary graft dysfunction (PGD) is a major cause of mortality within the first year following lung transplantation. Pulmonary hypertension, elevated body mass index (BMI), prolonged ischaemic time of the graft, intraoperative blood transfusions >1000 ml and the use of cardiopulmonary bypass or extracorporeal membrane oxygenation increase the risk for PGD. We aimed to evaluate whether dyslipidaemia is an additional risk factor for the development of PGD. METHODS We retrospectively analysed demographic and clinical data of 264 patients who received their first bilateral lung transplantation between March 2000 and October 2013 at our institution. The endpoint was PGD grade 3 at any time, defined according to the International Society for Heart and Lung Transplantation (ISHLT) criteria. Fasting lipid profiles at listing time or just before transplantation (baseline) were documented and dyslipidaemia was defined as any of the parameters being out of range. Comparisons of continuous variables between patients with PGD grade 3 and patients without were performed with the Mann-Whitney U-test, whereas proportions were compared with the χ2 test. Continuous variables were presented as arithmetic means with standard deviation for ease of comparison, but levels of statistical significance were computed using the appropriate non-parametric statistical test. To identify PGD risk factors, a forward stepwise logistic regression model was used. RESULTS PGD occurred in 63 recipients (24%). Pretransplant dyslipidaemia was documented in 153 recipients (58%) and was significantly more prevalent among recipients developing PGD (45 vs 108, P < 0.013). Despite various underlying pulmonary pathologies, higher triglyceride (TG) levels (1.41 ± 0.78 vs 1.16 ± 0.78, P < 0.012), lower high-density lipoprotein-cholesterol (HDL-C) concentrations (1.24 ± 0.55 vs 1.57 ± 0.71, P < 0.0005) and higher cholesterol/HDL-C values (3.80 ± 2.02 vs 3.00 ± 0.92, P < 0.0005) were associated with a lower incidence of PGD. Patients with PGD had significantly longer ischaemic time (350 ± 89 vs 322 ± 91, P = 0.017) and higher BMI (23 ± 5 vs 21 ± 4.4, P < 0.007). CONCLUSIONS Dyslipidaemia seems to be an independent risk factor for PGD after lung transplantation: low circulating levels of HDL-C and hypertriglyceridaemia increase the incidence of PGD. Even if HDL-C levels are difficult to alter today, triglyceride and cholesterol levels can be addressed therapeutically and may have a positive influence on the development of PGD.

Assess optimal equation to noninvasively estimate intracranial pressure (eICP) and cerebral perfusion pressure (eCPP) following severe traumatic brain injury (TBI) using transcranial color-coded duplex sonography (TCCDS). This is an observational clinical study in a university hospital. A total of 45 continuously sedated (BIS 35 mmHg), and non-febrile TBI patients. eICP and eCPP based on TCCDS-derived flow velocities and arterial blood pressure values using three different equations were compared to actually measured ICP and CPP in severe TBI patients subjected to standard treatment. Optimal equation was assessed by Bland–Altman analysis. The equations: $$ {\hbox{ICP}} = {1}0.{927} \times {\hbox{PI}}\left( {{\hbox{pulsatility}}\,{\hbox{index}}} \right) - {1}.{284} $$ and $$ {\hbox{CPP}} = {89}.{646} - {8}.{258} \times {\hbox{PI}} $$ resulted in eICP and eCPP similar to actually measured ICP and CPP with eICP 10.6 ± 4.8 vs. ICP 10.3 ± 2.8 and eCPP 81.1 ± 7.9 vs. CPP 80.9 ± 2.1 mmHg, respectively. The other two equations, $$ {\hbox{eCPP}} = \left( {{\hbox{MABP}} \times {\hbox{EDV}}} \right)/{\hbox{mFV}} + {14} $$ and $$ {\hbox{eCPP}} = \left[ {{\hbox{mFV}}/\left( {{\hbox{mFV}} - {\hbox{EDV}}} \right)} \right] \times \left( {{\hbox{MABP}} - {\hbox{RRdiast}}} \right) $$ , resulted in significantly decreased eCPP values: 72.9 ± 10.1 and 67 ± 19.5 mmHg, respectively. Superiority of the first equation was confirmed by Bland–Altman revealing a smallest standard deviations for eCPP and eICP. TCCDS-based equation $$ \left( {{\hbox{ICP}} = {1}0.{927} \times {\hbox{PI}} - {1}.{284}} \right) $$ allows to screen patients at risk of increased ICP and decreased CPP. However, adequate therapeutic interventions need to be based on continuously determined ICP and CPP values.

Grade 3 primary graft dysfunction (PGD3) represents the most important risk factor for patient mortality during the first year after lung transplantation (LTX). We investigated whether pretransplant pulmonary hypertension (PH) is a risk factor for the development of PGD3. This retrospective, single-center cohort study included 96 candidates undergoing right heart catheterization (RHC) prior to being listed for LTX between March 2000 and October 2015. Based on their mean pulmonary artery pressure (mPAP) levels, the patients were classified into 3 groups: (1)25 mm Hg, (2) 25-34 mm Hg and (3) ≥35 mm Hg. Forty-seven patients were classified in group 1, 31 in group 2, and 18 in group 3. Fifteen recipients (16%, 95%-CI 8-23) developed PGD3. In the univariate analysis, the diagnosis of interstitial lung disease (ILD) compared to COPD (OR: 7.06, P = .005), blood transfusion1000 mL during surgery (OR: 5.25, P = .005), the need for intra-operative cardio-pulmonary bypass (CPB) or extra-corporeal membrane oxygenation (ECMO) (OR: 4, P = .027), mPAP (OR 1.06, P = .007) and serum high density lipoprotein-cholesterol (HDL-C) (OR 0.09, P = .005) were associated with PGD3. In the multivariable logistic regression analysis, only HDL-C (OR 0.10, P = .016) was associated with PGD3 based on our single-center cohort data analysis.

There is a lack of data regarding use of ECMO in children undergoing lung transplantation. We evaluated our experience of ECMO in pediatric lung transplant recipients. All patients (

We analyzed the first 100 patients who underwent liver transplantation by Model for End-Stage Liver Disease (MELD) allocation, and compared the outcome of patients on the waiting list and after orthotopic liver transplantation with the last 100 patients who underwent transplantation prior to the introduction of the MELD system in July 2007. MELD allocation resulted in decreased waiting list mortality (386 versus 242 deaths per 1000 patient-years, P < 0.0001) and the transplantation of sicker recipients (uncorrected median MELD score 13.5 versus 20, P ¼ 0.003). Recipient posttransplant morbidity was significantly higher, mainly caused by increased percentage of renal failure requiring renal replacement therapy (13 versus 46%, P < 0.0001). However, kidney function recovered in most cases within 6 months after OLT. Hospital mortality remained similar in both groups (6% versus 9%). Patient 1-year survival was 91% versus 83% (pre-MELD versus MELD era, P ¼ 0.2154), graft 1year survival was 88% versus 78% (P ¼ 0.1013), respectively. Costs accumulated were significantly higher after introduction of the MELD policy (US $81,967 versus US $127,453, a 55% increase, P ¼ 0.02) with a strong correlation with the individual MELD score (P < 0.0001). The MELD system addresses the goal of fairness well. However, the postoperative course appears more difficult in the MELD era with increased financial burden, but reasonable patient and graft survival. This is the inevitable price to balance justice and utility in liver graft allocation. Liver Transpl 17:674-684, 2011. V C 2011 AASLD.

Background.The Molecular Adsorbent Recirculating System (MARS) has been shown to clear albumin-bound toxins from patients with liver failure but might cause bleeding complications potentially obscuring survival benefits. We hypothesized that monitoring clotting parameters and bed-side thromboelastography allows to reduce bleeding complications.Methods. Retrospective analysis of 25 MARS sessions during which clotting parameters were monitored by a standardized protocol.Results. During MARS therapy median INR increased significantly from 1.7 to 1.9 platelet count and fibrinogen content decreased significantly from 57 fL−1to 42 fL−1and 2.1 g/L to 1.5 g/L. Nine relevant complications occurred: the MARS system clotted 6 times 3 times we observed hemorrhages. Absent thrombocytopenia and elevated plasma fibrinogen predicted clotting of the MARS system (ROC 0.94 and 0.82). Fibrinolysis, detected by thromboelastography, uniquely predicted bleeding events.Conclusion. Bed-side thromboelastography and close monitoring of coagulation parameters can predict and, therefore, help prevent bleeding complications during MARS therapy.

This study was undertaken as the first national single-center analysis to assess the impact of the new Swiss transplantation law on patient selection, intensive care unit (ICU) complications, outcome, and, in particular, costs in liver transplant recipients treated in our surgical ICU. The first 35 consecutive liver transplant recipients following the new act were compared with the last 35 liver transplant recipients preceding July 1, 2007. Following execution of the new law, recipients were in poorer condition, reflected by significant higher Model for End-Stage Liver Disease (MELD) scores (12 vs. 22; p = 0.006). Furthermore, the MELD group obtained more renal replacement therapies (40.0% vs. 14.3%; p = 0.015). Cumulative one-yr patient survival was comparable in both groups (91.4% vs. 80.1%, p = 0.22). Finally, the additional costs per single case increased 27 000 Euros after the adoption of the new law. Our data serve as an example that political decisions influence patient's selection, and, in turn, complications, finally leading to higher costs of medical treatment. Liver graft allocation according to the MELD system may save lives at the price of increased intensive care efforts.

BackgroundEarly prediction of outcome would be useful for an optimal intensive care management of liver transplant recipients. Indocyanine green clearance can be measured non-invasively by pulse spectrophometry and is closely related to liver function.MethodsThis study was undertaken to assess the predictive value of a combination of the model of end stage liver disease (MELD) score and early indocyanine plasma disappearance rates (ICG-PDR) for length of stay in the intensive care unit (ICU), length of stay in the hospital and hospital mortality in liver transplant recipients.ResultsFifty consecutive liver transplant recipients were included in this post Hoc single-center study. ICG-PDR was determined within 6 hours after ICU admission. Endpoints were length of stay in the ICU, length of hospital stay and hospital mortality. The combination of a high MELD score (MELD >25) and a low ICG-PDR clearance (ICG-PDR ConclusionThe combination of MELD scores and a singular ICG-PDR measurement in the early postoperative phase is an accurate predictor for outcome in liver transplant recipients. This easy-to-assess tool might be valuable for an optimal intensive care management of those patients.

Background— There is an ongoing debate as to whether the gastrointestinal safety of COX-2 inhibition compared with nonsteroidal antiinflammatory drugs (NSAIDs) may come at the cost of increased cardiovascular events. In view of the large number of patients at cardiovascular risk requiring chronic analgesic therapy with COX-2 inhibitors for arthritic and other inflammatory conditions, the effects of selective COX-2 inhibition on clinically useful surrogates for cardiovascular disease, particularly endothelial function, need to be determined. Methods and Results— Fourteen male patients (mean age, 66±3 years) with severe coronary artery disease (average of 2.6 vessels with stenosis >75%) undergoing stable background therapy with aspirin and statins were included. The patients received celecoxib (200 mg BID) or placebo for a duration of 2 weeks in a double-blind, placebo-controlled, crossover fashion. After each treatment period, flow-mediated dilation of the brachial artery, high-sensitivity C-reactive protein, oxidized LDL, and prostaglandins were measured. Celecoxib significantly improved endothelium-dependent vasodilation compared with placebo (3.3±0.4% versus 2.0±0.5%, P =0.026), whereas endothelium-independent vasodilation, as assessed by nitroglycerin, remained unchanged (9.0±1.6% versus 9.5±1.3%, P =0.75). High-sensitivity C-reactive protein was significantly lower after celecoxib (1.3±0.4 mg/L) than after placebo (1.8±0.5 mg/L, P =0.019), as was oxidized LDL (43.6±2.4 versus 47.6±2.6 U/L, P =0.028), whereas prostaglandins did not change. Conclusions— This is the first study to demonstrate that selective COX-2 inhibition improves endothelium-dependent vasodilation and reduces low-grade chronic inflammation and oxidative stress in coronary artery disease. Thus, selective COX-2 inhibition holds the potential to beneficially impact outcome in patients with cardiovascular disease.

Background— Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality. Striking similarities exist in the inflammatory and immunologic response in RA and atherosclerosis. Indeed, adhesion molecules and cytokines, tumor necrosis factor (TNF)-α in particular, are key mediators of joint inflammation and of vascular dysfunction and progression of atherosclerotic vascular disease. Hence, the aim of the present study was to assess the effect of chronic antiinflammatory treatment with the anti-TNF-α antibody infliximab on disease activity and endothelial function in patients with active RA. Methods and Results— Eleven RA patients (mean age 46±5 years; disease duration 9±2 years) with high disease activity despite treatment with stable doses of methotrexate (≤25 mg/wk) and prednisone (≤10 mg/d) were investigated. Clinical status and endothelium-dependent and -independent vasodilation of the brachial artery as assessed by high-resolution ultrasound were measured before and after 12 weeks of infliximab therapy. Flow-mediated vasodilation improved from 3.2±0.4% to 4.1±0.5% ( P =0.018), whereas endothelium-independent vasodilation with nitroglycerin and baseline diameter remained unchanged (13.6±1.2% versus 12.8±1.4%, P =0.98, and 3.74±0.15 versus 3.66±0.11 mm, P =0.54, respectively). Disease activity score (DAS28) was significantly reduced, from 5.6±0.3 to 3.5±0.6 ( P =0.002). Erythrocyte sedimentation rate and C-reactive protein were lowered from 34±7 to 19±5 mm/h ( P =0.04) and from 38±11 to 15±10 mg/L ( P =0.08), respectively. Conclusions— This is the first study to show that anti-TNF-α treatment improves endothelial function in RA. The data suggest that in RA, endothelial dysfunction is part of the disease process and is mediated by TNF-α.

Background Prognostic abilities of medical parameters, which are scoring systems, measurements and biomarkers, are important for stratifying critically ill patients. Indocyanine green plasma disappearance (ICG-PDR) is an established clinical tool for the assessment of liver perfusion and function. Copeptin, MR-proANP and pro-ADM are biomarkers whose prognostic value is still unclear. The goal of this prospective study was to evaluate ICG-PDR, copeptin, MR-proANP and pro-ADM to predict prolonged length of stay (pLOS) in the ICU. Methods This study was conducted as a prospective single center study including 110 consecutively admitted ICU patients. Primary endpoint was prolonged length of stay (pLOS) in the ICU, defined as more than three days of stay there. Results ROC analysis showed an AUC of 0.73 for ICG-PDR, 0.70 for SAPS II, 0.65 for MR-proANP, 0.64 for pro-ADM and 0.54 for copeptin for pLOS in the ICU. Conclusions The prediction of pLOS in the ICU might be better by means of ICG-PDR than with the new biomarkers copeptin, MR-proANP or pro-ADM. Nevertheless, there is more need for research to evaluate whether ICG-PDR is an overall prognostic marker for pLOS. Trial registration (ClinicalTrials.gov number, NCT01126554).

Introduction Major abdominal surgery leads to a postoperative systemic inflammatory response, making it difficult to discriminate patients with systemic inflammatory response syndrome from those with a beginning postoperative infectious complication. At present, physicians have to rely on their clinical experience to differentiate between the two. Pancreatic stone protein (PSP) and pancreatitis-associated protein (PAP), both secretory proteins produced by the pancreas, are dramatically increased during pancreatic disease and have been shown to act as acute-phase proteins. Increased levels of PSP have been detected in polytrauma patients developing sepsis and PSP has shown a high diagnostic accuracy in discriminating the severity of peritonitis and in predicting death in intensive care unit patients. However, the prognostic value of PSP/PAP for infectious complications among patients undergoing major abdominal surgery is unknown. Methods and analysis 160 patients undergoing major abdominal surgery will be recruited preoperatively. On the day before surgery, baseline blood values are attained. Following surgery, daily blood samples for measuring regular inflammatory markers (c-reactive protein, procalcitonin, interleukin-6, tumour necrosis factor-α and leucocyte counts) and PSP/PAP will be acquired. PSP/PAP will be measured using a validated ELISA developed in our research laboratory. Patient9s discharge marks the end of his/her trial participation. Complication grade including mortality and occurrence of infectious postoperative complications according to validated diagnostic criteria will be correlated with PSP/PAP values. Total intensive care unit days and total length of stay will be recorded as further outcome parameters. Ethics and dissemination The PSP trial is a prospective monocentric cohort study evaluating the prognostic value of PSP and PAP for postoperative infectious complications. In addition, a comparison with established inflammatory markers in patients undergoing major abdominal surgery will be performed to help evaluate the role of these proteins in predicting and diagnosing infectious and other postoperative complications. Institution ethics board approval ID KEKZH-Nr. STV 11-2009. Trial registration ClinicalTrials.gov: NCT01258179.

Background The Swiss organ allocation system for donor lungs was implemented on 1 July 2007. The effects of this implementation on patient selection, intensive care unit course, outcomes and intensive care costs are unknown. Methods The first 37 consecutive lung transplant recipients following the implementation of the new act were compared with the previous 42 lung transplant recipients. Results Following implementation of the new law, baseline characteristics and cumulative one-year patient survival were comparable in both groups (88.1% vs 83.8%, P = 0.58). The costs for each case increased by 35,000 euros after adoption of the new law. Stratifying patients after implementation of the law according to urgency status shows that urgent patients required longer mechanical ventilation (P = 0.04), a longer ICU stay (P = 0.045) and a longer hospital stay (P = 0.04) and ICU costs (median 64,050 euros) were higher compared to regular patients. Conclusion The new transplantation law has increased ICU costs with the implementation of the Swiss organ allocation system. Patients listed as ‘urgent’ contribute significantly to the increase in ICU costs.

Das fruhe Lungenversagen nach schwerem Trauma wird zum einen direkt durch Verletzungen der Lunge und indirekt durch Freisetzung von Entzundungsmediatoren initiiert. Scheitern alle Beatmungsstrategien mit persistierender schwerer Hypoxie, kann die ECMO (extrakorporale Membranoxygenierung) eine suffiziente Oxygenierung aufrechterhalten.

Lung transplantation is an accepted therapy in selected patients with end-stage lung disease. However, there is a shortage of suitable donor organs, in particular for small or pediatric patients. Simultaneous bilateral lobar lung transplantation derived from one large donor into two small recipients is reported. The upper lobes were transplanted into the smaller female recipient, and the middle and right lower lobe and left lower lobe were transplanted into the male recipient.

Introduction 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. Methods In this randomized, controlled, double-blind trial, 48 patients with severe burn injury were assigned to receive either lactated Ringer’s solution plus 6% HES 130/0.4 in a ratio of 2:1 or lactated Ringer’s solution with no colloid supplement for the first 72 hours. Primary outcome parameter was the group difference of administered total fluid from intensive care unit (ICU) admission up to day 3. Secondary outcomes included kidney and lung injury and failure, length of stay, and mortality. Results Three-day totals of administered resuscitation fluid (medians) were 21,190 mL in the lactated Ringer’s group and 19,535 mL in the HES group (HES: −1,213 mL; P = 0.39). Creatinine levels from day 1 to 3 (HES: +0.4 μmol/L; 95% confidence interval (CI) −18.7 to 19.5; P = 0.97) and urinary outputs from day 1 to 3 (HES: −58 mL; 95% CI −400 to 283; P = 0.90) were not different. Six patients in each group developed acute respiratory distress syndrome (ARDS) (risk ratio 0.96; 95% CI 0.35 to 2.64; P = 0.95). Length of ICU stay (HES vs. lactated Ringer’s: 28 vs. 24 days; P = 0.80) and length of hospital stay (31 vs. 29 days; P = 0.57) were similar. Twenty-eight-day mortality was 4 patients in each group (risk ratio 0.96; 95% CI 0.27 to 4.45; P = 0.95), and in-hospital mortality was 8 in the HES group vs. 5 patients in the lactated Ringer’s group (hazard ratio 1.86; 95% CI 0.56 to 6.19; P = 0.31). Conclusions There was no evidence that early fluid resuscitation with balanced HES 130/0.4 (6%) in addition to lactated Ringer’s solution would lead to a volume-sparing effect in severe burn injury. Together with the findings that early renal function, incidence of ARDS, length of stay, and mortality were not negatively influenced by HES in this setting, balanced HES 130/0.4 (6%) plus lactated Ringer’s solution could not be considered superior to lactated Ringer’s solution alone. Trial registration ClinicalTrials.gov NCT01012648

Background: The optimal daptomycin dosing regimen for critically ill patients undergoing continuous renal replacement therapy (CRRT) has still to be established. Methods: Daptomycin pharmacokinetics was determined in 9 patients after administration of 6 mg/kg/day over 5 days. Results: At steady state, which was reached by day 3, the area under the curve over 24 h (AUC24h) was 667.4 ± 356.6 mg·h/l, and the maximum concentration (Cmax) was 66.9 ±25.3 mg/l. Mean CRRT clearance accounted for 48% (range 32-67%) of total clearance (mean 10.2 ml/min, range 6.1-18 ml/min). Significant correlations were observed between Cmax, minimum concentration (Cmin) and AUC24h (R2 = 0.91, p < 0.001, and R2 = 0.94, p < 0.001) and between albumin plasma concentration and free daptomycin (R2 = 0.7, p = 0.009). Conclusion: No significant accumulation occurred with a daily daptomycin dose of 6 mg/kg in patients undergoing CRRT with an effluent flow rate of >30 ml/kg/h. The quantification of trough concentrations (Cmin) appears to be a good surrogate to estimate AUC24h and to monitor daptomycin treatment in patients undergoing CRRT.

We analyzed the first 100 patients who underwent liver transplantation by Model for End-Stage Liver Disease (MELD) allocation, and compared the outcome of patients on the waiting list and after orthotopic liver transplantation with the last 100 patients who underwent transplantation prior to the introduction of the MELD system in July 2007. MELD allocation resulted in decreased waiting list mortality (386 versus 242 deaths per 1000 patient-years, P0.0001) and the transplantation of sicker recipients (uncorrected median MELD score 13.5 versus 20, P = 0.003). Recipient posttransplant morbidity was significantly higher, mainly caused by increased percentage of renal failure requiring renal replacement therapy (13 versus 46%, P0.0001). However, kidney function recovered in most cases within 6 months after OLT. Hospital mortality remained similar in both groups (6% versus 9%). Patient 1-year survival was 91% versus 83% (pre-MELD versus MELD era, P = 0.2154), graft 1-year survival was 88% versus 78% (P = 0.1013), respectively. Costs accumulated were significantly higher after introduction of the MELD policy (US $81,967 versus US $127,453, a 55% increase, P = 0.02) with a strong correlation with the individual MELD score (P0.0001). The MELD system addresses the goal of fairness well. However, the postoperative course appears more difficult in the MELD era with increased financial burden, but reasonable patient and graft survival. This is the inevitable price to balance justice and utility in liver graft allocation.

Iron deficiency is known to cause symptoms such as fatigue, depression and restless legs syndrome resulting in impaired quality of life and working capacity. We sought to examine the iron status of reportedly healthy individuals by a framed study design in 58 highly educated Swiss hospital employees and to compare the use of non invasive tests for assessing iron deficiency (ID). A structured interview was used to assess health status, nutritional intake and potential blood loss, blood counts as well as parameters proposed to diagnose iron deficiency were determined. All subjects felt well and were working at their maximum capacity. The male subjects were neither anaemic nor had decreased iron parameters however 50% (23/46) of the women had a serum ferritin of below 22 μg/L, still 33% (15/46) of the women had a ferritin value below the more stringent cut off value of 15 μg/L. In 15% (7/46) of the women we diagnosed iron deficient anaemia. Red meat consumption correlated with ferritin values as did the menstrual blood loss which was estimated by asking the amount of tampons used. Of the additionally analysed iron parameters only the percentage of hypochromic erythrocytes, soluble transferrin receptor and transferrin values were significantly correlated with ferritin and reached an AUCROC of ≥0.7 indicating good predictive tests. Nevertheless neither soluble transferrin receptor nor transferrin showed diagnostic advantages for the diagnosis of ID compared to ferritin alone or together with erythrocyte parameters. Working in a hospital environment and having access to health education does not seem to correlate with prevention of ID or ID anaemia in female hospital employees.

This study was undertaken as the first national single-center analysis to assess the impact of the new Swiss transplantation law on patient selection, intensive care unit (ICU) complications, outcome, and, in particular, costs in liver transplant recipients treated in our surgical ICU. The first 35 consecutive liver transplant recipients following the new act were compared with the last 35 liver transplant recipients preceding July 1, 2007. Following execution of the new law, recipients were in poorer condition, reflected by significant higher Model for End-Stage Liver Disease (MELD) scores (12 vs. 22; p = 0.006). Furthermore, the MELD group obtained more renal replacement therapies (40.0% vs. 14.3%; p = 0.015). Cumulative one-yr patient survival was comparable in both groups (91.4% vs. 80.1%, p = 0.22). Finally, the additional costs per single case increased 27 000 Euros after the adoption of the new law. Our data serve as an example that political decisions influence patient's selection, and, in turn, complications, finally leading to higher costs of medical treatment. Liver graft allocation according to the MELD system may save lives at the price of increased intensive care efforts.

The strong inverse relationship between plasma high-density lipoprotein (HDL)-cholesterol and atherosclerotic cardiovascular disease provides the epidemiological basis that HDL is atheroprotective. Since HDL enhances cholesterol efflux and exhibits potent antiinflammatory properties, the aim of the present study was to investigate whether infusion of reconstituted HDL (rHDL) impacts on vascular function, a well-established surrogate of atherosclerotic vascular disease, as well as markers of inflammation and oxidative stress in patients with acute coronary syndromes (ACS).Twenty-nine patients with ACS were randomized to double-blind treatment with rHDL or albumin. Endothelium-dependent and independent vasodilatation to intraarterial acetylcholine and sodium nitroprusside were measured by forearm venous occlusion plethysmography. In addition, oxidized LDL and high-sensitivity C-reactive protein were determined as markers of oxidative stress and vascular inflammation.rHDL infusion increased plasma HDL (P0.0001) and decreased LDL (P0.0001). Oxidized LDL (P= 0.11), high-sensitivity C-reactive protein (P= 0.12) and the response to endothelium-dependent and -independent vasodilatators remained unchanged after rHDL compared to albumin infusion (14.9 ± 9.2 versus 14.5 ± 12.4, P= 0.93 and 12.8 ± 7.1 versus 13.2 ± 9.6, P= 0.27, respectively).An increase of HDL and a reduction of LDL notwithstanding, human rHDL did not improve vascular function in patients with ACS thus further challenging the clinical benefit of interventions, which rapidly raise HDL in ACS, particularly with the infusion of reconstituted HDL.

Background 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. Findings Bland-Altman analysis for repeated measurements showed a good correlation with a bias of +1.39% and 2 SD of ± 3.12%. The 24%-hematocrit-group showed a correlation of r2 = 0.87. With a kappa of 0.56, 22.7% of the cases would have been transfused differently. In the-28%-hematocrit group with a similar correlation (r2 = 0.8) and a kappa of 0.58, 21% of the cases would have been transfused differently. Conclusions Despite a good agreement between the two methods used to determine hematocrit in clinical routine, the calculated difference of 1.4% might substantially influence transfusion triggers depending on the employed method.

Background: To prevent iatrogenic damage, transfusions of red blood cells should be avoided. For this, specific and reliable transfusion triggers must be defined. To date, the optimal hematocrit during the initial operating room (OR) phase is still unclear in patients with severe traumatic brain injury (TBI). We hypothesized that hematocrit values exceeding 28%, the local hematocrit target reached by the end of the initial OR phase, resulted in more complications, increased mortality, and impaired recovery compared to patients in whom hematocrit levels did not exceed 28%. Methods: Impact of hematocrit (independent variable) reached by the end of the OR phase on mortality and morbidity determined by the extended Glasgow outcome scale (eGOS; dependent variables) was investigated retrospectively in 139 TBI patients. In addition, multiple logistic regression analysis was performed to identify additional important variables. Findings: Following severe TBI, mortality and morbidity were neither aggravated by hematocrit above 28% reached by the end of the OR phase nor worsened by the required transfusions. Upon multiple logistic regression analysis, eGOS was significantly influenced by the highest intracranial pressure and the lowest cerebral perfusion pressure values during the initial OR phase. Conclusions: Based on this retrospective observational analysis, increasing hematocrit above 28% during the initial OR phase following severe TBI was not associated with improved or worsened outcome. This questions the need for aggressive transfusion management. Prospective analysis is required to determine the lowest acceptable hematocrit value during the OR phase which neither increases mortality nor impairs recovery. For this, a larger caseload and early monitoring of cerebral metabolism and oxygenation are indispensable

Background Monitoring of cardiac output and blood pressure are standard procedures in critical care medicine. Traditionally, invasive techniques like pulmonary artery catheter (PAC) and arterial catheters are widely used. Invasiveness bears many risks of deleterious complications. Therefore, a noninvasive reliable cardiac output (CO) and blood pressure monitoring system could improve the safety of cardiac monitoring. The aim of the present study was to compare a noninvasive versus a standard invasive cardiovascular monitoring system. Methods Nexfin HD is a continuous noninvasive blood pressure and cardiac output monitor system and is based on the development of the pulsatile unloading of the finger arterial walls using an inflatable finger cuff. During continuous BP measurement CO is calculated. We included 10 patients with standard invasive cardiac monitoring system (pulmonary artery catheter and arterial catheter) comparing invasively obtained data to the data collected noninvasively using the Nexfin HD. Results Correlation between mean arterial pressure measured with the standard arterial monitoring system and the Nexfin HD was r2 = 0.67 with a bias of -2 mmHg and two standard deviations of ± 16 mmHg. Correlation between CO derived from PAC and the Nexfin HD was r2 = 0.83 with a bias of 0.23 l/min and two standard deviations of ± 2.1 l/min; the percentage error was 29%. Conclusion Although the noninvasive CO measurement appears promising, the noninvasive blood pressure assessment is clearly less reliable than the invasively measured blood pressure. Therefore, according to the present data application of the Nexfin HD monitoring system in the ICU cannot be recommended generally. Whether such a tool might be reliable in certain critically ill patients remains to be determined.

Anxiolytic therapy with the benzodiazepine alprazolam is an established therapy in patients with panic disorder. Normally, panic-like anxiety and its concomitant physical symptoms quickly disappear under such treatment. Therefore we investigated whether there is a difference in sympathetic nervous system in patients with panic disorder compared to healthy controls. Three groups of subjects were included: ten patients with panic disorder, who received alprazolam and 20 healthy control subjects who were given either alprazolam (n=10) or matching placebo (n=10). Muscle sympathetic nerve activity (MSNA) and heart rate did not differ at baseline but significantly increased both in patients and healthy controls after intake of alprazolam (1 mg). However, in both groups both MSNA and heart rate were significantly elevated when compared to both baseline and the placebo control group. This study demonstrates (1) that anxiolytic therapy with alprazolam increases muscle sympathetic nerve activity and heart rate not only in patients with panic disorder but also in healthy controls and (2) that a significant difference in sympathetic nervous system activity between patients and controls, at baseline and during the therapy with alprazolam could not be demonstrated.

Introduction of anti-retroviral combination therapy has profoundly altered both the course and prognosis of the disease in HIV infected persons. Recent data, however, have raised concerns that anti-retroviral combination therapy is associated with premature manifestation of coronary artery disease.1 In particular, protease inhibitors have been linked to metabolic changes such as insulin resistance, abnormalities in lipid metabolism and lipodystrophy, and increased coronary artery calcification. While previous studies have reached conflicting conclusions about the incidence of myocardial infarction, the most substantial database recently provided by Friis-Moller and co-workers demonstrated an increased incidence in HIV infected persons receiving protease inhibitors or non-nucleoside reverse transcriptase inhibitor-containing therapy.2 One of the postulated mechanisms of pro-atherogenic effects of protease inhibitors is the promotion of atherosclerotic lesion formation by an increase in CD36-dependent cholesteryl ester accumulation in macrophages. Additionally, hypercholesterolaemia promotes a CD36-dependent and endothelial nitric oxide synthase mediated endothelial dysfunction. Endothelial dysfunction is associated with future risk of adverse cardiovascular events.3 Impaired endothelial function was previously shown in HIV infected persons receiving protease inhibitor therapy.4 The effect of statins (hydroxy-methyl-glutaryl coenzyme A reductase inhibitors) in anti-retroviral combination therapy associated dyslipidaemia remains to be determined. As most statins are metabolised by the cytochrome P450 3A4 isoform, and thus interfere with the metabolism of many anti-retroviral drugs, resulting in increased toxicity, cytochrome P450 independent statins, such as pravastatin, may be advantageous. Hence, the present study aimed to evaluate the effects of pravastatin on endothelial function and plasma lipid profile in …

In hypertension baroreceptor-mediated modulation of heart rate is impaired, resulting in a decreased vagal control. Reactive oxygen species produced locally in the vasculature decrease baroreceptor sensitivity. Folic acid has antioxidant properties. Therefore, the aim of this study was to test whether folic acid improves baroreceptor function in hypertension. Twenty-one male patients with hypertension not taking any drugs for 2 weeks participated in the study and were randomized to folic acid 5 mg or matching placebo. Cardiac and vascular sympathetic baroreceptor functions were tested before and after a single dose of folic acid or placebo with two different methods: the alpha-coefficient method and the phenylephrine (PE) and sodium nitroprusside (SNP) bolus method. In the folic acid group both methods showed significantly improved cardiac and vascular sympathetic baroreceptor sensitivity compared with placebo. This study provides evidence that folic acid improves cardiac and vascular sympathetic baroreceptor sensitivity in hypertensive patients, which suggests an improved vagal control and an enhanced baroreceptor modulation of sympathetic vasomotor tone. Thus, folic acid may represent a novel treatment for prevention of orthostatic dysregulation and/or arrhythmic complications resulting from baroreceptor dysfunction.

Angiotensin II directly stimulates muscle sympathetic nerve activity and facilitates adrenergic sympathetic transmission. The hypotheses that the chronic blockade of angiotensin II receptors (AT(1) type) reduces muscle sympathetic activity and that there is an interaction with baroreceptor function in patients with mild to moderate hypertension were investigated. Muscle sympathetic nerve activity decreased from 51.7 +/- 3.5 to 45.9 +/- 4.2 bursts/min (p = 0.022), and cardiac baroreceptor sensitivity increased from 3.2 +/- 1.3 to 4.9 +/- 1.8 ms/mm Hg (p = 0.007). This study for the first time demonstrates that in hypertensive patients, chronic AT(1) receptor antagonism inhibits muscle sympathetic nerve activity and that baroreceptor function is improved under these conditions.

Background— The interplay of resting muscle sympathetic nerve activity (MSA) and the baroreceptor reflex in patients with vasovagal syncope remains elusive. Hence, the aim of the present study was to investigate MSA, baroreceptor sensitivity, heart rate, and blood pressure under resting conditions and during orthostatic stress in patients with a history of vasovagal syncope. Methods and Results— MSA was measured using microneurography at rest and during lower body negative pressure (LBNP) to mimic orthostatic stress in patients with a history of vasovagal syncope (n=10) and in age-matched healthy controls (n=8). Heart rate and blood pressure were simultaneously recorded. Cardiac baroreceptor sensitivity was calculated with the spectral technique (α coefficient). Resting MSA in the patients with syncope was significantly increased as compared with controls (42.4±2.3 versus 26.5±3.6 bursts/min, P =0.001), whereas activation of MSA during orthostatic stress in the patient group was significantly blunted (5.1±1.6 versus 15.2±2.1 bursts/min at LBNP −50 mm Hg, P =0.002). In the patients with syncope, cardiac baroreceptor sensitivity was significantly reduced under supine resting conditions (8.5±0.7 versus 13.0±1.1 ms/mm Hg, P =0.001), as well as under orthostatic stress (7.3±0.7 versus 13.4±1.5 ms/mm Hg, P =0.003). Conclusions— This study shows that in patients with vasovagal syncope, resting MSA is increased and baroreflex regulation during orthostatic stress is blunted, thus leading to impaired MSA adaptation. These results provide new insights into mechanisms of vasovagal syncope and suggest that pharmacological modulation of baroreceptor sensitivity may represent a promising treatment of neuromediated syncope.

The leading cause of aortic valve morbidity in industrialised nations is degenerative calcified aortic stenosis. A convincing body of evidence suggests the concept that degenerative aortic stenosis represents a form of atherosclerotic vascular disease.1 Endothelial dysfunction promoting abnormal vasomotion, increased leucocyte adhesion, platelet dysfunction and vascular inflammation, which have been shown extensively in atherosclerosis, was recently found in degenerative aortic valve disease.2 Decreased nitric oxide (NO) bioavailability has a pivotal role in this process, and is largely determined by the expression of endothelial nitric oxide synthase (eNOS). Interestingly, eNOS expression is markedly influenced by haemodynamic factors, as shear stress is the main physiological trigger to enhance eNOS expression and activity.3 In the study by Poggianti et al,2 the effects of haemodynamic parameters have not been discussed as only patients with aortic valve sclerosis but without relevant haemodynamic stenosis were studied. We hypothesised that altered haemodynamics in aortic stenosis may at least partly be responsible for endothelial dysfunction and thus potentially normalise after aortic-valve replacement. Increased low-grade systemic inflammation has also been shown in aortic stenosis4 and consequently would be expected to influence vascular function similar to that described in coronary artery disease. Thus, we investigated endothelial dysfunction and signs of inflammation in haemodynamically relevant degenerative aortic stenosis before and after valve replacement. Patients …

Background There is little knowledge about the effect of dyslipidaemia on the outcome after lung transplantation. Thus, the aim of this retrospective single centre study was to analyse the impact of the plasma lipid profile on mortality in lung transplant recipients. From January 2000 to December 2008 the charts of 172 consecutive lung transplantation recipients were analysed. At baseline and after one year lipid profiles were routinely collected. During the follow-up major cardiovascular events (MCE; beginning of dialysis, cerebrovascular insult or myocardial infarction) were recorded. The follow-up period ended December 2010. Findings Over all total cholesterol (4.3 ± 1.6 vs. 5.4 ± 1.3 mmol/l, p During the observational period 6.9% (10 patients) suffered a major cardiac event. In univariate analysis MCE was associated with baseline TC: on average the event-group had a 33% higher baseline TC (5.6 vs. 4.2 mmol/l, OR 1.6, CI 1.1 – 2.2, p = 0.02). The total mortality in the observational period was 25% (36 patients overall). In univariate analysis mortality was associated with increased TC/HDL ratio. The non-survivors had on average a 22% higher baseline TC/HDL ratio (3.6 vs. 2.8, HR 2.8, CI 1.2 – 3.5, p = 0.001). There was no association between mortality and TC (p = 0.33), triglycerides (p = 0.34), HDL (p = 0.78) and creatinine (p = 0.73). In a multivariate model the hazard ratio was 1.5 (1.2 – 1.9, p = 0.001) per increase of 0.4 TC/HDL ratio. Conclusions This study shows that the total cholesterol before transplantation is associated with the incidence of MCE and the cholesterol/HDL ratio with mortality in lung transplanted recipients.

Introduction The optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism. Methods In twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 μl/min, collecting samples at 60 minute intervals. Occult metabolic alterations were determined by calculating the lactate- pyruvate (L/P), lactate- glucose (L/Glc), and lactate- glutamate (L/Glu) ratios. Results Brain glucose was influenced by arterial blood glucose. Elevated L/P and L/Glc were significantly reduced at brain glucose above 1 mM, reaching lowest values at blood and brain glucose levels between 6-9 mM (P < 0.001). Lowest cerebral glutamate was measured at brain glucose 3-5 mM with a significant increase at brain glucose below 3 mM and above 6 mM. While L/Glu was significantly increased at low brain glucose levels, it was significantly decreased at brain glucose above 5 mM (P < 0.001). Insulin administration increased brain glutamate at low brain glucose, but prevented increase in L/Glu. Conclusions Arterial blood glucose levels appear to be optimal at 6-9 mM. While low brain glucose levels below 1 mM are detrimental, elevated brain glucose are to be targeted despite increased brain glutamate at brain glucose >5 mM. Pathogenity of elevated glutamate appears to be relativized by L/Glu and suggests to exclude insulin- induced brain injury.

Introduction The impact of model of end stage liver disease (MELD) score on postoperative morbidity and mortality is still elusive, especially for high MELD. There are reports of poorer patient outcome in transplant candidates with high MELD score, others though report no influence of MELD score on outcome and survival. Methods We retrospectively analyzed data of 144 consecutive liver transplant recipients over a 72-month period in our transplant unit, from January 2003 until December 2008 and performed uni- and multivariate analysis for morbidity and mortality, in particular to define the influence of MELD to these parameters. Results This study identified MELD score greater than 23 as an independent risk factor of morbidity represented by intensive care unit (ICU) stay longer than 10 days (odds ratio 7.0) but in contrast had no negative impact on mortality. Furthermore, we identified transfusion of more than 7 units of red blood cells as independent risk factor for mortality (hazard ratio 7.6) and for prolonged ICU stay (odds ratio [OR] 7.8) together with transfusion of more than 10 units of fresh frozen plasma (OR 11.6). Postoperative renal failure is a strong predictor of morbidity (OR 7.9) and postoperative renal replacement therapy was highly associated with increased mortality (hazard ratio 6.8), as was hepato renal syndrome prior to transplantation (hazard ratio 13.2). Conclusions This study identified MELD score greater than 23 as an independent risk factor of morbidity represented by ICU stay longer than 10 days but in contrast had no negative impact on mortality. This finding supports the transplantation of patients with high MELD score but only with knowledge of increased morbidity.

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.

Transfusions of allogeneic red blood cells (RBC) are associated with viral and bacterial infections, activation of inflammatory pathways, transfusion-related acute lung injury and transfusion-associated circulatory overload. To reduce and prevent such harmful consequences, a clear indication for transfusion of RBC is required. However, our clinical experience shows that the method of assessing hematocrit is of crucial importance when implementing a strict trigger-dependent transfusion practice with the aim of preventing unnecessary transfusions, especially in non-bleeding critically ill patients. The aims of the present study were therefore to compare two different hematocrit-assessing methods used in clinical routine and to determine whether the results obtained by these two methods would influence our RBC transfusion management.

INTRODUCTION: Maintaining arterial blood glucose within tight limits is beneficial in critically ill patients. Upper and lower limits of detrimental blood glucose levels must be determined. METHODS: In 69 patients with severe traumatic brain injury (TBI), cerebral metabolism was monitored by assessing changes in arterial and jugular venous blood at normocarbia (partial arterial pressure of carbon dioxide (paCO2) 4.4 to 5.6 kPa), normoxia (partial arterial pressure of oxygen (paO2) 9 to 20 kPa), stable haematocrit (27 to 36%), brain temperature 35 to 38 degrees C, and cerebral perfusion pressure (CPP) 70 to 90 mmHg. This resulted in a total of 43,896 values for glucose uptake, lactate release, oxygen extraction ratio (OER), carbon dioxide (CO2) and bicarbonate (HCO3) production, jugular venous oxygen saturation (SjvO2), oxygen-glucose index (OGI), lactate-glucose index (LGI) and lactate-oxygen index (LOI). Arterial blood glucose concentration-dependent influence was determined retrospectively by assessing changes in these parameters within pre-defined blood glucose clusters, ranging from less than 4 to more than 9 mmol/l. RESULTS: Arterial blood glucose significantly influenced signs of cerebral metabolism reflected by increased cerebral glucose uptake, decreased cerebral lactate production, reduced oxygen consumption, negative LGI and decreased cerebral CO2/HCO3 production at arterial blood glucose levels above 6 to 7 mmol/l compared with lower arterial blood glucose concentrations. At blood glucose levels more than 8 mmol/l signs of increased anaerobic glycolysis (OGI less than 6) supervened. CONCLUSIONS: Maintaining arterial blood glucose levels between 6 and 8 mmol/l appears superior compared with lower and higher blood glucose concentrations in terms of stabilised cerebral metabolism. It appears that arterial blood glucose values below 6 and above 8 mmol/l should be avoided. Prospective analysis is required to determine the optimal arterial blood glucose target in patients suffering from severe TBI.