Cardiac index-guided therapy to maintain optimised postinduction cardiac index in high-risk patients having major open abdominal surgery: the multicentre randomised iPEGASUS trial.

BACKGROUND: It is unclear whether optimising intraoperative cardiac index can reduce postoperative complications. We tested the hypothesis that maintaining optimised postinduction cardiac index during and for the first 8 h after surgery reduces the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. METHODS: In three German and two Spanish centres, high-risk patients having elective major open abdominal surgery were randomised to cardiac index-guided therapy to maintain optimised postinduction cardiac index (cardiac index at which pulse pressure variation was <12%) during and for the first 8 h after surgery using intravenous fluids and dobutamine or to routine care. The primary outcome was the incidence of a composite outcome of moderate or severe complications within 28 days after surgery. RESULTS: We analysed 318 of 380 enrolled subjects. The composite primary outcome occurred in 84 of 152 subjects (55%) assigned to cardiac index-guided therapy and in 77 of 166 subjects (46%) assigned to routine care (odds ratio: 1.87, 95% confidence interval: 1.03-3.39, P=0.038). Per-protocol analyses confirmed the results of the primary outcome analysis. CONCLUSIONS: Maintaining optimised postinduction cardiac index during and for the first 8 h after surgery did not reduce, and possibly increased, the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. Clinicians should not strive to maintain optimised postinduction cardiac index during and after surgery in expectation of reducing complications. CLINICAL TRIAL REGISTRATION: NCT03021525.

Impaired Cell Viability and Functionality of Hepatocytes After Incubation With Septic Plasma-Results of a Second Prospective Biosensor Study.

Liver dysfunction (LD) and liver failure are associated with poor outcome in critically ill patients. In patients with severe sepsis or septic shock, LD occurred in nearly 19% of patients. An early diagnosis of LD at time of initial damage of the liver can lead to a better prognosis of these patients because an early start of therapy is possible. We performed a second prospective study with septic patients to test a new cell-based cytotoxicity device (biosensor) to evaluate clinical relevance for early diagnosis of LD and prognostic capacity. In the clinical study, 99 intensive care unit patients were included in two groups. From the patients of the septic group (n = 51, SG), and the control (non-septic) group [n = 49, control group (CG)] were drawn 20 ml blood at inclusion, after 3, and 7 days for testing with the biosensor. Patients' data were recorded for hospital survival, organ function, and demographic data, illness severity [acute physiology and chronic health evaluation (APACHE) II-, sepsis-related organ failure assessment (SOFA) scores], cytokines, circulating-free deoxyribonucleic acid/neutrophil-derived extracellular traps (cf-DNA/NETs), microbiological results, and pre-morbidity. For the developed cytotoxicity test, the human liver cell line HepG2/C3A was used. Patients' plasma was incubated in a microtiter plate assay with the test cells and after 6 days incubation the viability (trypan blue staining, XTT-test) and functionality (synthesis of albumin, cytochrome 1A2 activity) was analyzed. An impairment of viability and functionality of test cells was only seen in the SG compared with the CG. The plasma of non-survivors in the SG led to a more pronounced impairment of test cells than the plasma of survivors at inclusion. In addition, the levels of cf-DNA/NETs were significantly higher in the SG at inclusion, after 3, and after 7 days compared with the CG. The SG showed an in-hospital mortality of 24% and the values of bilirubin, APACHE II-, and SOFA scores were markedly higher at inclusion than in the CG. Hepatotoxicity of septic plasma was already detected with the liver cell-based biosensor at inclusion and also in the course of disease. The biosensor may be a tool for early diagnosis of LD in septic patients and may have prognostic relevance.

Individualized, perioperative, hemodynamic goal-directed therapy in major abdominal surgery (iPEGASUS trial): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative morbidity and mortality in patients undergoing surgery is high, especially in patients who are at risk of complications and undergoing major surgery. We hypothesize that perioperative, algorithm-driven, hemodynamic therapy based on individualized fluid status and cardiac output optimization is able to reduce mortality and postoperative moderate and severe complications as a major determinant of the patients' postoperative quality of life, as well as health care costs. METHODS/DESIGN: This is a multi-center, international, prospective, randomized trial in 380 patients undergoing major abdominal surgery including visceral, urological, and gynecological operations. Eligible patients will be randomly allocated to two treatment arms within the participating centers. Patients of the intervention group will be treated perioperatively following a specific hemodynamic therapy algorithm based on pulse-pressure variation (PPV) and individualized optimization of cardiac output assessed by pulse-contour analysis (ProAQT© device; Pulsion Medical Systems, Feldkirchen, Germany). Patients in the control group will be treated according to standard local care based on established basic hemodynamic treatment. The primary endpoint is a composite comprising the occurrence of moderate or severe postoperative complications or death within 28 days post surgery. Secondary endpoints are: (1) the number of moderate and severe postoperative complications in total, per patient and for each individual complication; (2) the occurrence of at least one of these complications on days 1, 3, 5, 7, and 28 in total and for every complication; (3) the days alive and free of mechanical ventilation, vasopressor therapy and renal replacement therapy, length of intensive care unit, and hospital stay at day 7 and day 28; and (4) mortality and quality of life, assessed by the EQ-5D-5L™ questionnaire, after 6 months. DISCUSSION: This is a large, international randomized controlled study evaluating the effect of perioperative, individualized, algorithm-driven ,hemodynamic optimization on postoperative morbidity and mortality. TRIAL REGISTRATION: Trial registration: NCT03021525 . Registered on 12 January 2017.

Effects of Bioreactor-Oxygenation During Extracorporeal Granulocytes Treatment in Septic Patients.

A granulocyte bioreactor for the extracorporeal treatment was developed to enhance the immune cell function in patients with severe sepsis. The influence of oxygenation on the used cells was tested in a prospective clinical study. Ten patients with severe sepsis were treated twice with the granulocyte bioreactor. The used cells were screened for functionality; values of blood gases, glucose and lactate were obtained from the recirculating bioreactor circuit. Five patients were treated with an oxygenator setup (Oxy group), five without oxygenator (Non-Oxy group). The overall in-hospital mortality was 50%. Significantly lower values of oxygen saturation, partial oxygen pressure, lactate, oxyburst and phagocytosis were seen in the Non-Oxy group compared with the Oxy group in the bioreactor circuit. Further studies with this approach are encouraged and should focus on the influence of oxygenation on production of reactive oxygen species and cytokines of used cells.

Comparison of the trapezius and the adductor pollicis muscle as predictor of good intubating conditions: a randomized controlled trial.

BACKGROUND: Adequate muscle relaxation is important for ensuring optimal conditions for intubation. Although acceleromyography of the adductor pollicis muscle is commonly used to assess conditions for intubation, we hypothesized that acceleromyography of the trapezius is more indicative of optimal intubating conditions. The primary outcome was the difference between both measurement sites with regard to prediction of good or acceptable intubating conditions. METHODS: Neuromuscular blockade after injection of rocuronium 0.3 mg/kg IV was measured simultaneously with acceleromyography of the adductor pollicis muscle and the trapezius muscle in sixty female patients, American Society of Anesthesiologists physical status I to III, undergoing general anesthesia for gynecologic surgery. Exclusion criteria were: expected difficult tracheal intubation (e.g. history of difficult intubation, reduced mouth opening (< 2 cm) and/or Mallampati Score 4), increased risk of pulmonary aspiration (e.g. gastroesophageal reflux or delayed gastric emptying) allergies to drugs used during the study, pregnancy, neuromuscular diseases, medication with potential to influence neuromuscular function (e.g. furosemide, magnesium, cephalosporins) and hepatic or renal insufficiency (serum bilirubin >26 µmol/L, serum creatinine >90 µmol/l). Patients were randomized to 2 groups: group A (n = 30): endotracheal intubation after onset of the neuromuscular block at the adductor pollicis muscle. Group B (n = 30): endotracheal intubation after onset at the trapezius muscle. Intubating conditions were compared between both groups by means of a standardised score (the Copenhagen score) with Fisher's exact test. RESULTS: Onset of the block after rocuronium injection was observed at the adductor pollicis muscle compared to the trapezius with 2.8 (1.1) versus 2.5 (1.1) min (mean ± SD; P = 0.006). Intubating conditions were poor in 2 patients (7%) of group A, and in 1 patient (3%) of group T. They were acceptable (either excellent or good) in 28 patients (93%) in group A, and in 1 patient (97%) in group T (P = 0.82). CONCLUSIONS: Performing acceleromyography at the trapezius muscle reduced the time between injection of neuromuscular blocking agents and intubation by 18 s (11%). Thus, trapezius muscle acceleromyography is an acceptable alternative to adductor pollicis muscle acceleromyography in predicting acceptable intubating conditions, which allows for earlier indication of adequate intubating conditions. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT01849198 . Registered April 29, 2013.

Rocuronium is more hepatotoxic than succinylcholine in vitro.

BACKGROUND: The development of liver failure is a major problem in critically ill patients. The hepatotoxicity of many drugs, as one important reason for liver failure, is poorly screened for in human models. Rocuronium and succinylcholine are neuromuscular blocking agents used for tracheal intubation and for rapid-sequence induction. OBJECTIVE: We used an in-vitro test with a permanent cell line and compared rocuronium and succinylcholine for hepatotoxicity. DESIGN: In-vitro study. SETTING: A basic science laboratory, University Hospital Rostock, Germany. MATERIAL/(PATIENTS): The basic test compound is the permanent human liver cell line HepG2/C3A. In a standardised microtitre plate assay the toxicity of different concentrations of rocuronium, succinylcholine and plasma control was tested. INTERVENTIONS: After two incubation periods of 3 days, the viability of cells (XTT test, lactate dehydrogenase release and trypan blue staining), micro-albumin synthesis and the cytochrome 1A2 activity (metabolism of ethoxyresorufin) were measured. MAIN OUTCOME MEASURES: Differences between rocuronium and succinylcholine were assessed using the Kruskal-Wallis one-way test and two-tailed Mann-Whitney U test. RESULTS: Rocuronium, but not succinylcholine, led to a significant dose-dependent decrease of viability, albumin synthesis and cytochrome 1A2 activity of test cells. CONCLUSION: An in-vitro test with a cell line showed hepatotoxicity of rocuronium that was dose-dependent. Further studies are needed to investigate the underlying mechanisms of the effects of rocuronium on hepatic cellular integrity. TRIAL REGISTRATION: Not suitable.

Sevoflurane at 1.0 MAC together with remifentanil and propofol produces clinically acceptable intubation conditions at the vocal cords: A prospective randomized study.

Objective The overall intubation conditions after tracheal intubation with remifentanil, propofol, and sevoflurane at 1.0 minimum alveolar concentration (MAC) are worse than with rocuronium at 0.45 mg/kg. Therefore, we compared the intubation conditions and laryngeal morbidity (vocal cord injuries, hoarseness, and sore throat) with sevoflurane at 1.2 and 1.4 MAC versus 1.0 MAC. Methods In this prospective clinical trial, 90 patients were randomized to 3 groups: the sevoflurane 1.0, 1.2, and 1.4 MAC groups. At 3 min, tracheal intubation was performed and the patients' intubation conditions were assessed. The vocal cords were examined for injury by videolaryngoscopy. Additionally, the incidence and severity of laryngeal morbidity were compared between women and men. Results Acceptable intubation conditions were seen in 72% of the patients without significant differences between the groups. Overall, vocal cord injuries (oedema) occurred in three (4%) patients. Women reported sore throat more often than men (51% vs. 21%, respectively). Conclusions Intubation conditions were not improved with higher sevoflurane concentrations. The incidence and severity of sore throat were greater in women than men. TRIAL REGISTRATION: ClinicalTrials.Gov: NCT 01896245.

Procalcitonin Impairs Liver Cell Viability and Function In Vitro: A Potential New Mechanism of Liver Dysfunction and Failure during Sepsis?

Purpose. Liver dysfunction and failure are severe complications of sepsis and result in poor outcome and increased mortality. The underlying pathologic mechanisms of hepatocyte dysfunction and necrosis during sepsis are only incompletely understood. Here, we investigated whether procalcitonin, a biomarker of sepsis, modulates liver cell function and viability. Materials and Methods. Employing a previously characterized and patented biosensor system evaluating hepatocyte toxicity in vitro, human hepatocellular carcinoma cells (HepG2/C3A) were exposed to 0.01-50 ng/mL procalcitonin for 2 × 72 h and evaluated for proliferation, necrosis, metabolic activity, cellular integrity, microalbumin synthesis, and detoxification capacity. Acetaminophen served as positive control. For further standardization, procalcitonin effects were confirmed in a cellular toxicology assay panel employing L929 fibroblasts. Data were analyzed using ANOVA/Tukey's test. Results. Already at concentrations as low as 0.25 ng/mL, procalcitonin induced HepG2/C3A necrosis (P < 0.05) and reduced metabolic activity, cellular integrity, synthesis, and detoxification capacity (all P < 0.001). Comparable effects were obtained employing L929 fibroblasts. Conclusion. We provide evidence for procalcitonin to directly impair function and viability of human hepatocytes and exert general cytotoxicity in vitro. Therapeutical targeting of procalcitonin could thus display a novel approach to reduce incidence of liver dysfunction and failure during sepsis and lower morbidity and mortality of septic patients.

Bioartificial Therapy of Sepsis: Changes of Norepinephrine-Dosage in Patients and Influence on Dynamic and Cell Based Liver Tests during Extracorporeal Treatments.

Purpose. Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. A granulocyte bioreactor for the extracorporeal treatment of sepsis was tested in a prospective clinical study focusing on the dosage of norepinephrine in patients and influence on dynamic and cell based liver tests during extracorporeal therapies. Methods and Patients. Ten patients with severe sepsis were treated twice within 72 h with the system containing granulocytes from healthy donors. Survival, physiologic parameters, extended hemodynamic measurement, and the indocyanine green plasma disappearance rate (PDR) were monitored. Plasma of patients before and after extracorporeal treatments were tested with a cell based biosensor for analysis of hepatotoxicity. Results. The observed mortality rate was 50% during stay in hospital. During the treatments, the norepinephrine-dosage could be significantly reduced while mean arterial pressure was stable. In the cell based analysis of hepatotoxicity, the viability and function of sensor-cells increased significantly during extracorporeal treatment in all patients and the PDR-values increased significantly between day 1 and day 7 only in survivors. Conclusion. The extracorporeal treatment with donor granulocytes showed promising effects on dosage of norepinephrine in patients, liver cell function, and viability in a cell based biosensor. Further studies with this approach are encouraged.

Monitoring recovery from rocuronium-induced neuromuscular block using acceleromyography at the trapezius versus the adductor pollicis muscle: an observational trial.

PURPOSE: Positioning for surgery can restrict access to the patient's hand, thereby limiting assessment of the response at the adductor pollicis muscle to ulnar nerve stimulation. We evaluated a novel site to assess neuromuscular block by stimulating the accessory nerve and measuring the acceleromyographic response at the trapezius muscle. METHODS: In this prospective non-blinded observational study, we assessed neuromuscular transmission in anesthetized adult female patients undergoing elective laparoscopic gynecological surgery. We performed the assessment by simultaneous recording acceleromyographic responses with the TOF-Watch(®) SX monitor at both the right adductor pollicis and left trapezius muscles. The neuromuscular block was achieved using rocuronium 0.3 mg·kg(-1), and the repeatability, time course, and limits of agreement (Bland-Altman) of responses were compared at the two recording sites. The primary endpoint was the 90% train-of-four (TOF) recovery time with other endpoints included the onset time of the block, maximum T1 depression, time to 25% T1 recovery, and recovery time course of the T1 response and TOF ratio. RESULTS: Thirty-six patients were enrolled with responses obtained from 27 subjects. The variability of baseline responses recorded at the trapezius muscle was larger than that recorded at the adductor pollicis muscle, as determined by their mean (SD) repeatability coefficients [twitch height T1, 6.1 (1.9)% and 4.2 (1.6)%, respectively; P = 0.001; TOF ratio, 6.2 (2.1)% and 4.3 (1.7)%, respectively; P = 0.001]. The recorded responses showed relatively narrow limits of agreement. The onset time of the block was 0.3 min earlier at the trapezius muscle than at the adductor pollicis muscle [2.3 (0.8) min and 2.6 (0.7) min, respectively; P = 0.007], with limits of agreement ranging from 1.6 min earlier to 1.0 min later. The time to 25% T1 recovery was 1.8 min earlier at the trapezius muscle than at the adductor pollicis muscle [18.2 (5.7) min and 20.0 (5.2) min, respectively; P = 0.039], with limits of agreement ranging from 11.1 min earlier to 7.5 min later. Additionally, the time to achieve 90% TOF ratio was 4.4 min earlier at the trapezius muscle than at the adductor pollicis muscle [32.6 (7.9) min and 37 (9.1) min, respectively; P = 0.004], with limits of agreement ranging from 18.4 min earlier to 9.7 min later. CONCLUSIONS: We conclude that recording evoked acceleromyographic responses at the trapezius muscle is an acceptable alternative when monitoring from the adductor pollicis muscle is compromised. Nevertheless, we caution that recording a 90% TOF response at the trapezius muscle may overestimate functional recovery from the neuromuscular blockade. This trial was registered at ClinicalTrials.gov identifier, NCT01849198.

Conservative management of post-intubation tracheal tears-report of three cases.

Iatrogenic tracheal rupture is a rare complication after intubation. We present three patients with tracheal tears. In all of these patients, a common finding was a lesion of the posterior tracheal wall with postoperative subcutaneous and emphysema as the first clinical sign of the rupture. Diagnosis and follow-up were based on clinical and endoscopic findings and chest computed tomography (CT) scans. In our cases with progressive subcutaneous and mediastinal emphysema or dyspnea, we performed a tracheotomy and bypassed the lesion with a tracheostomy tube to avoid an increase in air leakage into the mediastinum. Under broad-spectrum antibiotic therapy, no mediastinitis occurred and all patients survived without sequelae. Closure of tracheostomy was scheduled for 1-2 months after tracheal injury. Analysis of surgical and anesthesiological procedures revealed no abnormalities and the accumulation of tracheal injuries was considered as accidental. We found that in clinically stable patients with spontaneous breathing and with no mediastinitis, a conservative management of tracheal tears is a safe procedure.

Intubating conditions and side effects of propofol, remifentanil and sevoflurane compared with propofol, remifentanil and rocuronium: a randomised, prospective, clinical trial.

BACKGROUND: Tracheal intubation without muscle relaxants is usually performed with remifentanil and propofol or sevoflurane. Remifentanil 1.0 to 4.0 µg·kg(-1) and propofol 2.0-3.0 mg·kg(-1) or sevoflurane up to 8.0 Vol% provide acceptable, i.e. excellent or good intubating conditions. We hypothesized that sevoflurane 1.0 MAC would provide acceptable intubating conditions when combined with propofol and remifentanil. METHODS: Eighty-three patients to be intubated were randomised to two groups. The SEVO group received propofol 1.5 mg kg(-1), remifentanil 0.30 µg kg min(-1) and sevoflurane 1.0 MAC; the MR group received the same doses of propofol and remifentanil plus rocuronium 0.45 mg kg(-1). We evaluated intubation and extubation conditions, mean arterial pressure (MAP), heart rate (HR) and bispectral index (BIS). The vocal cords were examined for injury by videolaryngoscopy before and 24 hours after surgery. RESULTS: ACCEPTABLE INTUBATING CONDITIONS WERE SEEN MORE FREQUENTLY WITH ROCURONIUM THAN WITH SEVOFLURANE: 97% versus 82%; p = 0.03; the subscore for vocal cords was comparable: 100% versus 98%. MAP before intubation decreased significantly compared with the MAP at baseline to the same extent in both groups; ephedrine IV was given in 15 (SEVO) versus 16 (MR) patients; p = 0.93. BIS at tracheal intubation was 27 (13-65) in the SEVO group, 29 (14-62) in the MR group; p = 0.07. Vocal cord injuries (oedema, haematoma) were similar: 4 patients in each group. CONCLUSIONS: Overall intubating conditions were better when rocuronium was used; the subscore for vocal cords was comparable. The incidence of side effects was the same in the two groups. TRIAL REGISTRATION: ClinicalTrials.Gov: NCT 01591031.

Laryngeal injuries following endotracheal intubation in ENT surgery: predictive value of anatomical scores.

Endotracheal intubation has been associated with a threefold higher incidence of laryngopharyngeal complaints following anesthesia in comparison to laryngeal mask airway. Such complaints, including hoarseness and sore throat, have been reported in up to 90% of patients within 24 h of extubation. The purpose of this study was to determine which preoperatively documented clinical and anatomic parameters are predictive of laryngo-pharyngeal trauma resulting from elective endotracheal intubation. Fifty-three patients undergoing ENT procedures requiring general anesthesia with endotracheal intubation were recruited. Pre and postoperative laryngostroboscopic examination was performed and findings correlated to preoperative clinical and anatomic parameters. Readily assessed anatomic parameters including height (>180 cm) and weight (>80 kg) correlated significantly to the Eckerbom grade of intubation-associated acute laryngeal injury (rs = 0.374; p = 0.006 and rs = 0.278; p = 0.044, respectively). The mandibular protrusion test also correlated significantly to the Eckerbom grade (rs = 0.462, p = 0.001) while the upper-lip-bite test showed significant correlation to impaired vocal fold oscillation (rs = 0.288, p = 0.036), with injury prediction sensitivities of 37.5 and 39.4%, respectively. No parameters correlated to subjective complaints (n = 5, 9.2%). This study provides suggestions on how to improve the classification of intubation-associated laryngeal injuries as well as providing the basis for larger clinical trials in other surgical subspecialties.

Dexamethasone decreases the duration of rocuronium-induced neuromuscular block: a randomised controlled study.

BACKGROUND: Several drugs influence the time course of neuromuscular block during general anaesthesia. OBJECTIVE: To evaluate the effect of a single dose of dexamethasone 8 mg on the time course of a rocuronium-induced neuromuscular block. DESIGN: A randomised controlled, unblinded, monocentre trial. SETTING: Kreiskrankenhaus Dormagen, Dormagen, Germany. PATIENTS: One hundred and eight adult patients scheduled for elective gynaecological laparoscopic surgery allocated to three groups. INTERVENTIONS: Patients received dexamethasone 8 mg intravenously 2 to 3 h prior to surgery (Group A), during induction of anaesthesia (Group B) or after recovery of the neuromuscular block (Group C, control). MAIN OUTCOME MEASURES: The time course of the neuromuscular block of rocuronium 0.3 mg kg was assessed using acceleromyography. The primary end point was the time from start of injection of rocuronium until recovery to a train-of-four ratio of 0.9. RESULTS: The clinical duration was decreased in Group A (15.8 ±â€Š4.5 min) compared with Group B (18.7 ±â€Š5.8 min; P = 0.031). The recovery index was reduced in Group A (6.8 ±â€Š1.8 min) compared with Group B (8.1 ±â€Š2.6 min; P = 0.018) and Group C (8.3 ±â€Š2.8 min; P = 0.01). The recovery to a train-of-four ratio of 0.9 was shorter in Group A (30.4 ±â€Š6.9 min) than in Groups B (36.3 ±â€Š10.7 min; P = 0.031) and C (36.8 ±â€Š11.3 min; P = 0.02). CONCLUSION: A single dose of dexamethasone 8 mg attenuated rocuronium-induced block by 15 to 20% if administered 2 to 3 h prior to induction of anaesthesia. However, the administration of dexamethasone during induction of anaesthesia did not influence the time course of the neuromuscular block. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT01782820.

Anesthesia with Propofol versus Sevoflurane: Does the Longer Neuromuscular Block under Sevoflurane Anesthesia Reduce Laryngeal Injuries?

Anesthesia can be maintained with propofol or sevoflurane. Volatile anesthetics increase neuromuscular block of muscle relaxants. We tested the hypothesis, that sevoflurane would cause less vocal cord injuries than an intravenous anesthesia with propofol. In this prospective trial, 65 patients were randomized in 2 groups: SEVO group, anesthesia with sevoflurane, and TIVA group, total intravenous anesthesia with propofol. Intubating and extubating conditions were evaluated. Vocal cord injuries were examined by stroboscopy before and 24 and 72 h after surgery; hoarseness and sore throat were assessed up to 72 h after surgery. Hoarseness and sore throat were comparable between both groups (not significant). Similar findings were observed for vocal cord injuries: 9 (SEVO) versus 5 (TIVA) patients; P = 0.36; the overall incidence was 24%. Type of vocal cord injuries: 9 erythema and 5 edema of the vocal folds. Neuromuscular block was significantly longer in the SEVO group compared with the TIVA group: 71 (range: 38-148) min versus 52 (range: 21-74) min; P < 0.001. Five patients (TIVA group) versus 11 patients (SEVO group) needed neostigmine to achieve a TOF ratio of 1.0 (P = 0.14). Under anesthesia with propofol laryngeal injuries were not increased; the risk for residual curarization, however, was lower compared with sevoflurane.

Role of different replacement fluids during extracorporeal treatment in a pig model of sepsis.

In an extracorporeal combination therapy, the impact of different replacement fluids on survival was tested in a bacterial sepsis model in pigs. In an animal study 19 pigs, weighing 7.5-11.1 kg, were included. All groups received an intravenous lethal dose of live Staphylococcus aureus over 1 h. The animals were treated by an extracorporeal circuit consisting of online centrifugation and subsequent plasma filtration for 4 h. The extracorporeal circuit was pre-filled with 400 mL replacement fluid. In the P0 group 100% hydroxyethyl starch 130/0.4 was used as replacement fluid; in the P30 group 30% pig plasma and 70% hydroxyethyl starch; and in the P100 group 100% pig plasma. The observation time was 7 days. All animals of the group P100 survived, while all animals of group P0 and five out of seven animals of the P30 group died during the observation time. Extracorporeal therapy consisting of online centrifugation and plasma filtration with 100% pig plasma as replacement fluid significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged.

Plasma separation by centrifugation and subsequent plasma filtration: impact on survival in a pig model of sepsis.

The impact on survival of a combination of plasma separation by centrifugation and subsequent plasma filtration was tested in a bacterial sepsis model in pigs. In this animal study 19 pigs were included. Groups II and III received an intravenous lethal dose of live Staphylococcus aureus over 1 h; group I received saline (non-septic control--NC). Groups I and II were treated by an extracorporeal circuit consisting of online centrifugation and subsequent plasma filtration (group II: treated group--TG) for 4 h; group III had no specific treatment (septic control, SC). The observation time was 7 days. All animals of group I (NC) and group II (TG) survived, while all animals of group III (SC) died during the observation time. Extracorporeal therapy with online centrifugation and plasma filtration significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged.

Impaired cell functions of hepatocytes incubated with plasma of septic patients.

OBJECTIVE AND DESIGN: The development of liver failure is a major problem in septic patients. In this prospective clinical experimental study the hepatotoxicity of plasma from septic and non-septic patients was tested. METHODS AND SUBJECTS: The basic test components consist of human liver cells (HepG2/C3A) used in a standardized microtiter plate assay. After incubation with patient's plasma viability of cells (XTT-test), the cytochrome 1A2 activity and synthesis of micro albumin were measured. Subjects (28) enrolled comprise the septic shock group (SSG, n=10), the non-septic group (NSG, n=5) and the healthy volunteers group (HVG, n=13). RESULTS: The 28-day mortality was 30% in the SSG. The APACHE II-, SOFA-, and SAPS-scores and the values of bilirubin and prothrombin time as INR were significantly higher in the SSG than in the NSG. The cytochrome 1A2 activity and the release of albumin were significantly reduced in HepG2/C3A cells incubated with plasma of the SSG (p<0.05). The cytochrome 1A2 activities were higher in survivors compared to non-survivors at the time point 0 and were increasing in survivors and decreasing in non-survivors within 54 h in the SSG. In the SSG there was a significant decrease in IL-10 and IL-8 between inclusion and 54 h. Values of IL-6, TNF alpha and IL-10 were significantly lower in the NSG compared with the values of the SSG at inclusion and after 54 h. CONCLUSION: The plasma of patients with septic shock impaired cellular functions of HepG2/C3A cells.