Lars Hüter

Hydroxyethylstarch impairs renal function and induces interstitial proliferation, macrophage infiltration and tubular damage in an isolated renal perfusion model

IntroductionThe aim of the study was to evaluate some of the underlying pathomechanisms of hydroxyethylstarch (HES) induced adverse effects on renal function using 24 porcine kidneys in an isolated perfusion model over six hours.MethodsInfusion of either 10% HES 200/0.5, 6% HES 130/0.42 or Ringers lactate (RL) was performed to achieve an haematocrit of 20% in eight kidneys from four animals per group. Physiological and pathophysiological parameters were determined (including N-acetyl-beta-aminoglucosidase as a marker for lysosomal tubular damage). Histological investigations and immunohistological stainings of the kidneys were performed.ResultsInitially after haemodilution, HES 130/0.42 and HES 200/0.5 reduced urine output compared with RL (P < 0.01). After six hours, N-acetyl-beta-aminoglucosidase was significantly higher in HES 200/0.5 (81 ± 23 U/L) compared with HES 130/0.42 (38 ± 12 U/L) and RL (21 ± 13 U/L; P < 0.001). Osmotic nephrosis-like lesions (OL) of the tubuli were present in all groups showing a significantly lower number of OL in RL (1.1 ± 0.4; P = 0.002) compared with both HES groups (HES 200/0.5 = 2.1 ± 0.6; HES 130/0.42 = 2.0 ± 0.5). Macrophage infiltration was significantly higher in HES 200/0.5 compared with HES 130/0.42 (1.3 ± 1.0 vs. 0.2 ± 0.04; P = 0.044). There was a significant increase in interstitial cell proliferation in the HES 200/0.5 group vs. HES 130/0.42 (18.0 ± 6.9 vs. 6.5 ± 1.6; P = 0.006) with no significant difference in RL (13.5 ± 4.0).ConclusionsWe observed impaired diuresis and sodium excretion by HES and identified renal interstitial proliferation, macrophage infiltration and tubular damage as potential pathological mechanisms of HES-induced adverse effects on renal function using an isolated porcine renal perfusion model. Furthermore, we demonstrated that 10% HES 200/0.5 had more of a pro-inflammatory effect compared with 6% HES 130/0.42 and caused more pronounced tubular damage than 6% HES 130/0.42 and RL. OL were present in all groups, but to a lesser degree after RL administration.

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial

Importance Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial. Objective To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock. Design, Setting, and Participants Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock. Interventions Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190). Main Outcomes and Measures The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]). Results The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, -1.8%; 95% CI, -10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, -5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, -5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, -4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia. Conclusions and Relevance Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients. Trial Registration clinicaltrials.gov Identifier: NCT00670254.

Low-Dose Intravenous Midazolam Reduces Etomidate-Induced Myoclonus: A Prospective, Randomized Study in Patients Undergoing Elective Cardioversion

BACKGROUND:Myoclonic movements are a common problem in unpremedicated patients during induction of anesthesia with etomidate. METHODS:In a double-blind fashion, 40 patients (ASA physical status III–IV) scheduled for elective cardioversion were randomly assigned to receive either 0.015 mg/kg midazolam or placebo 90 s before the injection of 0.3 mg/kg etomidate. Myoclonic movements and sedation were recorded on a scale between 0 and 3. Pulse oximetry, noninvasive arterial blood pressure, and heart rate were recorded during the study period. RESULTS:Two patients (10%) in the midazolam group had myoclonic movements after the administration of etomidate, whereas 10 of the 20 patients (50%) receiving placebo experienced such movements (P = 0.006). No other differences were found between the groups; in particular, there was no difference in recovery 5 min after the administration of etomidate. CONCLUSIONS:IV midazolam 0.015 mg/kg administered 90 s before induction of anesthesia with etomidate is effective in reducing myoclonic movements and does not prolong recovery in unpremedicated patients after short procedures.

Percutaneous transtracheal ventilation: effects of a new oxygen flow modulator on oxygenation and ventilation in pigs compared with a hand triggered emergency jet injector

The application of percutaneous transtracheal jet ventilation for emergency ventilation depends on special equipment which is often not available outside the operating room. The oxygen flow modulator is a new specially designed device for emergency ventilation using a low pressure oxygen supply. We studied the effects of the new device in comparison with a hand triggered emergency jet injector on oxygenation and ventilation in six pigs (21+/-1 kg). The animals were anaesthetized, tracheally intubated, and mechanically ventilated. Following central venous and pulmonary artery catheterization, a Paratrend 7 sensor was placed in the left femoral artery for continuous measurements of PaO(2) and PaCO(2). Then an emergency transtracheal airway catheter was inserted into the trachea after surgical exposure. In randomized order each animal was ventilated via the transtracheal airway catheter with the hand triggered emergency jet injector (inspiratory/expiratory (I/E) ratio of 1:1; respiratory rate of 60 min(-1); driving pressure 1.5 bar; FjetO(2) 1.0) and the oxygen flow modulator (FiO(2) 1.0 at an oxygen flow of 15 l min(-1); respiratory rate of 60 min(-1); I/E ratio of approximately 1:1) for 15 min each. After each phase of the experiment respiratory and hemodynamic variables were measured. Whereas PaO(2) was not significantly different between the two devices, PaCO(2) was higher during the hand-triggered jet ventilation. Thus, the efficacy of the oxygen flow modulator during the experiment was comparable with the efficacy of the hand triggered emergency jet injector.

Impairment of renal function using hyperoncotic colloids in a two hit model of shock: a prospective randomized study

IntroductionOne of the therapeutic essentials in severe sepsis and septic shock is an adequate fluid replacement to restore and maintain circulating plasma volume, improve organ perfusion and nutritive microcirculatory flow. The type of solution to be used as a fluid replacement remains under discussion. The aim of the study was to evaluate the effects of clinically used fluid replacement solutions on renal function and inflammatory response.MethodsA total of 23 anesthetized and ventilated female German Landrace pigs were investigated over 19 hours using a two-hit model that combined hemorrhagic and septic shock. The septic shock was induced using an Escherichia coli laden clot placed into the abdominal cavity. Infusions of 6% hydroxyethylstarch 130/0.42 in acetate (6% HES 130), 4% gelatin in acetate (4% gelatin) and 10% hydroxyethylstarch 200/0.5 in saline (10% HES200) compared to Ringers acetate (RAc) were used for fluid replacement to maintain a central venous pressure of 12 mmHg. Ringers acetate was also used in the sham-treated group (SHAM).ResultsAt study end the cardiac output (10% HES200 143 ± 48 ml/kgBW; 6% HES130 171 ± 47 ml/kgBW; RAc 137 ± 32 ml/kgBW; 4% gelatin 160 ± 42 ml/kgBW), as well as mean arterial pressure did not differ between groups. N-acetyl-beta-D-glucosamidase was significantly higher in the hydroxyethylstarch 200 (157 ± 115 U/g creatinine; P < 0.05) group compared to hydroxyethylstarch 130 (24 ± 9 U/g creatinine), Ringers acetate (2 ± 3 U/g creatinine) and SHAM (21 ± 15 U/g creatinine) at the studys end. Creatinine significantly increased by 87 ± 84 percent of baseline in the 10% HES200 group compared to RAc and 6% HES130. We demonstrated in the histology of the kidneys a significant increase in osmotic-nephrosis like lesions for 4% gelatin compared to RAc, 6% HES130 and SHAM. Urine output was lowest in the 10% HES200 and 4% gelatin group, however not significantly.Interleukin(IL)-6 levels were significantly elevated in the 10% HES200 group (3,845 ± 1,472 pg/ml) two hours after sepsis induction compared to all other groups (6% HES130 1,492 ± 604 pg/ml; RAc 874 ± 363 pg/ml; 4% gelatin 1,623 ± 1,242 pg/ml).ConclusionsDespite similar maintenance of macrocirculation 6% hydroxyethylstarch 130/0.42 and Ringers acetate significantly preserve renal function and attenuate tubular damage better than 10% hydroxyethylstarch 200/0.5 in saline.

Students insert the laryngeal tube quicker and more often successful than the esophageal-tracheal combitube in a manikin

BACKGROUND Endotracheal intubation remains the standard of airway management. Because intubation skills are difficult to acquire, for medical students teaching of easier to learn techniques should be considered. METHODS We retrospectively analyzed data that were collected in a University teaching facility. 264 medical students were taught how to use laryngeal tube (LT) and Esophageal Tracheal Combitube((R)) (ETC) in a manikin. The students underwent one of two different types of extraglottic airway management training consisting of either long lecture (30min) and intensive training (2h) (group IT, n=48), or brief (10min) lecture and 20min of training (group BT, n=216). Both groups underwent a test 6 weeks after training, group IT had an additional test 24h after training. RESULTS After 24h students in group IT were faster using the LT than the ETC (31.7s+/-2.1 vs. 51.9s+/-5.8, p<0.001). Up to 6 weeks after training students were able to place the LT significantly faster than the ETC in both groups (26.5s+/-2.1 vs. 53.9s+/-5.8 group IT and 43.4s+/-1.6 vs. 103.8s+/-4.4 group BT, p<0.001). At 24h and 6 weeks following intensive training, there was no statistical difference in the time required for insertion of either device. CONCLUSION Following different training scenarios in a manikin, students were able to place the LT much faster than the ETC. Even brief training was sufficient to generate short insertion times for the LT.

Present-day prehospital airway management in the former Eastern German state of Thuringia: equipment and education of emergency physicians.

We describe the condition of education and equipment regarding prehospital airway management in the German federal state of Thuringia, representing a part of former Eastern Germany. In 2006 a postal survey of the 39 emergency medical stations (EMS) in Thuringia was carried out. The response rate was 100%. In 72% of the EMS, a device for extraglottic airway management and in all EMS a device for cricothyrotomy was available. A device to monitor end-tidal CO2 was available in 41%. Difficulties in airway management in the past two years were reported from 74% of the EMS. Ongoing training and education in airway management is provided in 82% of the emergency districts. This survey reveals wide variations in the equipment for airway management available to prehospital emergency physicians in Thuringia. Given the reported difficulties in airway management, availability of a more standardized set of airway management devices in Thuringia may be helpful.

Predictors of Successful Fast Track Protocol in Transfemoral Transcatheter Aortic Valve Implantation Under General Anaesthesia

Objectives: There is no consensus about the optimal length of hospital stay in patients undergoing elective transfemoral TAVR under general anesthesia. Our study tried to find predictors of failure of early discharge strategy in those patients. Methods and results: We included retrospectively 135 high risk TAVI patients (mean Log. EuroSCORE 30.8 ± 6) operated under general anaesthesia between June 2017 and January 2018 in central hospital, Bad Berka, Germany. Focus on the preoperative factors was established in favor to find possible predictors of longer hospital stay in this group of patients. Uni- and multivariate analysis were performed to identify independent preoperative predictors of fast-track protocol failure, defined as inability to discharge the patient from the hospital five days after surgery. Independent predictors of fast-track protocol failure were NYHA IV (OR 4.3; CI 95% 2.3-25, p-Value 0.017), ejection fraction (EF) ≤ 30% (OR 3.5; CI 95% 2-12.5, p-Value 0.006), right bundle branch block (OR 4.7; CI 95% 1.25-25, p-Value 0.03) and stroke with residual disability (OR 4.5; CI 95% 1.1-16, p-Value 0.025). Conclusion: NYHA IV, severely reduced ejection fraction, right bundle branch block and stroke with residual disability might be considered potential predictors of failure of fast track protocol in patient undergoing TAVI under general anesthesia.