Andreas Zollinger

Preconditioning by Sevoflurane Decreases Biochemical Markers for Myocardial and Renal Dysfunction in Coronary Artery Bypass Graft Surgery: A Double-blinded, Placebo-controlled, Multicenter Study

Background Preconditioning by volatile anesthetics is a promising therapeutic strategy to render myocardial tissue resistant to perioperative ischemia. It was hypothesized that sevoflurane preconditioning would decrease postoperative release of brain natriuretic peptide, a biochemical marker for myocardial dysfunction. In addition, several variables associated with the protective effects of preconditioning were evaluated. Methods Seventy-two patients scheduled for coronary artery bypass graft surgery under cardioplegic arrest were randomly assigned to preconditioning during the first 10 min of complete cardiopulmonary bypass with either placebo (oxygen–air mixture only) or sevoflurane 4 vol% (2 minimum alveolar concentration). No other volatile anesthetics were administered at any time during the study. Treatment was strictly blinded to anesthesiologists, perfusionists, and surgeons. Biochemical markers of myocardial dysfunction and injury (brain natriuretic peptide, creatine kinase–MB activity, and cardiac troponin T), and renal dysfunction (cystatin C) were determined. Results of Holter electrocardiography were recorded perioperatively. Translocation of protein kinase C was assessed by immunohistochemical analysis of atrial samples. Results Sevoflurane preconditioning significantly decreased postoperative release of brain natriuretic peptide, a sensitive biochemical marker of myocardial contractile dysfunction. Pronounced protein kinase C &dgr; and &egr; translocation was observed in sevoflurane-preconditioned myocardium. In addition, postoperative plasma cystatin C concentrations increased significantly less in sevoflurane-preconditioned patients. No differences between groups were found for perioperative ST-segment changes, arrhythmias, or creatine kinase–MB and cardiac troponin T release. Conclusions Sevoflurane preconditioning preserves myocardial and renal function as assessed by biochemical markers in patients undergoing coronary artery bypass graft surgery under cardioplegic arrest. This study demonstrated for the first time translocation of protein kinase C isoforms &dgr; and &egr; in human myocardium in response to sevoflurane.

Assessment of stroke volume variation for prediction of fluid responsiveness using the modified FloTrac™ and PiCCOplus™ system

IntroductionStroke volume variation (SVV) has repeatedly been shown to be a reliable predictor of fluid responsiveness. Various devices allow automated clinical assessment of SVV. The aim of the present study was to compare prediction of fluid responsiveness using SVV, as determined by the FloTrac™/Vigileo™ system and the PiCCOplus™ system.MethodsIn patients who had undergone elective cardiac surgery, SVVFloTrac was determined via radial FloTrac sensor, and SVVPiCCO and pulse pressure variation were assessed via a femoral PiCCO catheter. Stroke volume was assessed by transpulmonary thermodilution. All variables were recorded before and after a volume shift induced by a change in body positioning (from 30° head-up position to 30° head-down position). Pearson correlation, t-test, and Bland-Altman analysis were performed. Area under the curve was determined by plotting receiver operating characteristic curves for changes in stroke volume in excess of 25%. P < 0.05 was considered statistically significant.ResultsBody positioning resulted in a significant increase in stroke volume; SVVFloTrac and SVVPiCCO decreased significantly. Correlations of SVVFloTrac and SVVPiCCO with change in stroke volume were similar. There was no significant difference between the areas under the curve for SVVFloTrac and SVVPiCCO; the optimal threshold values given by the receiver operating characteristic curves were 9.6% for SVVFloTrac (sensitivity 91% and specificity 83%) and 12.1% for SVVPiCCO (sensitivity 87% and specificity 76%). There was a clinically acceptable agreement and strong correlation between SVVFloTrac and SVVPiCCO.ConclusionSVVs assessed using the FloTrac™/Vigileo™ and the PiCCOplus™ systems exhibited similar performances in terms of predicting fluid responsiveness. In comparison with SVVPiCCO, SVVFloTrac has a lower threshold value.

Bilateral volume reduction surgery for diffuse pulmonary emphysema by video-assisted thoracoscopy.

UNLABELLED We prospectively studied the surgical aspects, functional results, and complications of video-assisted bilateral thoracoscopic volume reduction surgery in patients with severe diffuse pulmonary emphysema. METHODS Fifteen men and five women with a mean age of 64 years (range 42 to 78 years) whose daily activity was substantially impaired by severe airflow obstruction and hyperinflation underwent thoracoscopic volume reduction surgery. The prospective preoperative assessment and postoperative assessment at 3 months included (1) pulmonary function studies, (2) grading of dyspnea, and (3) exercise performance; pulmonary function tests were also performed immediately before discharge from the hospital. RESULTS There was no perioperative mortality. All patients left the hospital after a median stay of 15 days (6 to 27 days). Only seven patients had a prolonged chest tube drainage time (>7 days). At 3 months the mean (+/- standard deviation) forced expiratory volume in 1 second had improved by 42% (+/-3.8%), from 0.80 L (+/-0.23) to 1.09 L (+/-0.28) (p < 0.001); residual volume had decreased from 5.8 L (+/-1.5) to 4.4 L (+/-1.0) (p < 0.001). Shortly before discharge the forced expiratory volume in 1 second was already 1.10 L (+/-0.26). The median 12-minute walking distance increased from 495 m (35 to 790 m) to 688 m (175 to 1035 m) (p < 0.001) and the mean maximal oxygen consumption from 10 ml/kg per minute (+/-2.5) to 13 ml/kg per minute (+/-2.3) (p < 0.0005). The patients reported a substantial relief of dyspnea with a mean decrease in the Medical Research Council score from 3.4 to 1.8.

Adrenergic receptor genotype but not perioperative bisoprolol therapy may determine cardiovascular outcome in at-risk patients undergoing surgery with spinal block: the Swiss Beta Blocker in Spinal Anesthesia (BBSA) study: a double-blinded, placebo-controlled, multicenter trial with 1-year follow-up

Background:Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block. Methods:The authors performed a double-blinded, placebo-controlled, multicenter trial to compare the effect of bisoprolol with that of placebo on 1-yr composite outcome including cardiovascular mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and cerebrovascular insult. Bisoprolol was given orally before and after surgery for a maximum of 10 days. Adrenergic receptor polymorphisms and safety outcome measures of bisoprolol therapy were also determined. Results:A total of 224 patients were enrolled. Spinal block could not be established in 5 patients. One hundred ten patients were assigned to the bisoprolol group, and 109 patients were assigned to the placebo group. The mean duration of treatment was 4.9 days in the bisoprolol group and 5.1 days in the placebo group. Bisoprolol therapy reduced mean heart rate by 10 beats/min. The primary outcome was identical between treatment groups and occurred in 25 patients (22.7%) in the bisoprolol group and 24 patients (22.0%) in the placebo group during the 1-yr follow-up (hazard ratio, 0.97; 95% confidence interval, 0.55–1.69; P = 0.90). However, carriers of at least one Gly allele of the β1-adrenergic receptor polymorphism Arg389Gly showed a higher number of adverse events than Arg homozygous (32.4% vs. 18.7%; hazard ratio, 1.87; 95% confidence interval, 1.04–3.35; P = 0.04). Conclusions:Perioperative bisoprolol therapy did not affect cardiovascular outcome in these elderly at-risk patients undergoing surgery with spinal block.

Prospective, randomized comparison of extrapleural versus epidural analgesia for postthoracotomy pain

BACKGROUND Thoracic epidural analgesia is considered the method of choice for postthoracotomy analgesia, but it is not suitable for every patient and is associated with some risks and side effects. We therefore evaluated the effects of an extrapleural intercostal analgesia as an alternative to thoracic epidural analgesia. METHODS In a prospective, randomized study, pain control, recovery of ventilatory function, and pulmonary complications were analyzed in patients undergoing elective lobectomy or bilobectomy. Two groups of 15 patients each were compared: one received a continuous extrapleural intercostal nerve blockade (T3 through T6) with bupivacaine through an indwelling catheter, the other was administered a combination of local anesthetics (bupivacaine) and opioid analgesics (fentanyl) through a thoracic epidural catheter. RESULTS Both techniques were safe and highly effective in terms of pain relief and recovery of postoperative pulmonary function. However, minor differences were observed that, together with practical benefits, would favor extrapleural intercostal analgesia. CONCLUSIONS These results led us to suggest that extrapleural intercostal analgesia might be a valuable alternative to thoracic epidural analgesia for pain control after thoracotomy and should particularly be considered in patients who do not qualify for thoracic epidural analgesia.

Hemodilution Tolerance in Elderly Patients Without Known Cardiac Disease

Hemodilution tolerance is not well defined in elderly patients.In 20 patients older than 65 yr and free from known cardiovascular disease, hemodynamic variables, ST segment deviation, and O2 consumption were determined prior to and after 6 and after 12 mL/kg isovolemic exchange of blood for 6% hydroxyethyl starch. The mean age of the patients was 76 +/- 2 yr (mean +/- SEM, range 66-88 yr). During hemodilution, hemoglobin decreased from 11.6 +/- 0.4 to 8.8 +/- 0.3 g/dL (P < 0.05). With stable filling pressures, cardiac index increased from 2.02 +/- 0.11 to 2.19 +/- 0.10 L centered dot min-1 centered dot m-2 (P < 0.05) while systemic vascular resistance decreased from 1796 +/- 136 to 1568 +/- 126 dynes centered dot s centered dot cm-5 (P < 0.05) and O2 extraction increased from 28.0% +/- 0.9% to 33.0% +/- 0.8% (P < 0.05) resulting in a stable O2 consumption during hemodilution. No alterations in ST segments were observed in lead II during hemodilution. In lead V5, ST segment deviation became slightly less negative during hemodilution from -0.03 +/- 0.01 to -0.02 +/- 0.01 mV (P < 0.05). The moderate decrease in hemoglobin was fully compensated by both an increase in cardiac index and in O2 extraction. Electrocardiographic signs of myocardial ischemia were not observed in this population. In conclusion, isovolemic hemodilution to a hemoglobin value of 8.8 +/- 0.3 g/dL is well tolerated in elderly patients free from known cardiac disease at the ages of 65-88 yr. (Anesth Analg 1996;82:681-6)

Compromised blood coagulation: an in vitro comparison of hydroxyethyl starch 130/0.4 and hydroxyethyl starch 200/0.5 using thrombelastography.

UNLABELLED We compared the effects of progressive in vitro hemodilution (30% and 60%) on blood coagulation in 80 patients receiving one of two different 6% hydroxyethyl starch (HES) solutions using thrombelastography (TEG). The newly developed solution has a mean molecular weight of 130 kD and a degree of substitution, defined as the average number of hydroxyethyl groups per glucose moiety, of 0.4 (HES 130/0.4); the conventional solution has a mean molecular weight of 200 kD and a degree of substitution of 0.5 (HES 200/0.5). Both HES solutions significantly compromised blood coagulation, as seen by an increase in reaction time and coagulation time and a decrease in angle alpha, maximal amplitude, and coagulation index (all P 0.05 for all TEG variables). When analyzing the intrinsic HES effect by taking hemodilution with 0.9% saline into account, progressive hemodilution with both HES solutions resulted in an increasing clot lysis (P < 0.05 after 60 min). Again, there was no difference between HES 130/0.4 and HES 200/0.5 diluted blood. We conclude that HES 130/ 0.4 and HES 200/0.5 compromise blood coagulation to the same degree. IMPLICATIONS Progressive in vitro hemodilution using hydroxyethyl starch (HES) compromises blood coagulation. We observed similar effects of a new HES solution with a mean molecular weight of 130 kD and a degree of substitution of 0.4 (HES 130/0.4), compared with the conventional HES 200/0.5.

Low- and medium-molecular-weight hydroxyethyl starches: comparison of their effect on blood coagulation.

BackgroundHigh-molecular-weight hydroxyethyl starch (HES) compromises blood coagulation more than medium-molecular-weight HES. The authors compared medium molecular weight HES (200 kd [HES200]) and low-molecular-weight HES (70 kd [HES70]). MethodsIn a prospective, double-blind, randomized-sequence crossover study, 22 male volunteers received 15 ml/kg HES200 and HES70. Blood samples were taken before and 5 min, 30 min, 1 h, 2 h, 4 h, 8 h, and 24 h after infusion. The following parameters were analyzed at all time points: prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII, antigenetic and functional von Willebrand factor, platelets, Thrombelastograph® analysis parameters (reaction time, coagulation time, maximum amplitude, angle &agr;, and clot lysis 30 and 60 min after maximum amplitude), ionized calcium, hematocrit, HES plasma concentration, molecular weight (weight average and number average), molar substitution, and polydispersity (weight average/number average). Repeated-measures analysis of variance (P < 0.05) was used to compare the response of the aforementioned parameters to the infusion of HES70 and HES200. ResultsBoth HES solutions had a significant impact on all parameters. A slightly greater compromise with HES200 was found in activated partial thromboplastin time (P = 0.010), factor VIII (P = 0.009), antigenetic von Willebrand factor (P = 0.041), functional von Willebrand factor (P = 0.026), maximum amplitude (P = 0.008), and angle &agr; (P = 0.003). No difference was established with the other parameters. HES concentration (P < 0.001), weight average (P < 0.001), number average (P < 0.001), and polydispersity (P < 0.001) were higher with HES200. There was no difference with molar substitution (P = 0.091). ConclusionsLow-molecular-weight hydroxyethyl starch (70 kd) compromises blood coagulation slightly less than HES200, but it is unclear whether this is clinically relevant.

Therapeutic impact of intra‐operative transoesophageal echocardiography during noncardiac surgery*

The impact of transoesophageal echocardiography on haemodynamic management during elective noncardiac surgery was assessed during this observational prospective database analysis. Ninety‐nine consecutive patients were studied, who were at risk of intra‐operative myocardial ischaemia or haemodynamic instability (Class II indications) and were undergoing vascular, visceral or chest surgery. A total of 165 new echocardiographic findings were recorded. Based on these findings changes in drug therapy were made in 47% and changes in fluid therapy in 24% of patients. Left ventricular wall motion abnormalities were seen in 32% and other relevant diagnoses made in 10%. Echocardiography showed a significant impact on drug therapy in patients with pre‐operative systolic wall motion abnormalities (vasodilators: OR = 7.1, CI 95% = 2.1/24.0; vasopressors: OR = 3.3, CI 95% = 1.2/9.1) and patients with a history of left heart failure (vasodilators: OR = 5.2, CI 95% = 1.0/31.4). Fluid therapy was significantly influenced by echocardiographic findings during liver and lung transplantation (50% compared with 24% during other surgical interventions, p < 0.05).

Assessment of cardiac output changes using a modified FloTrac/Vigileo™ algorithm in cardiac surgery patients

IntroductionThe FloTrac/Vigileo™ (Edwards Lifesciences, Irvine, CA, USA) allows pulse pressure-derived cardiac output measurement without external calibration. Software modifications were performed in order to eliminate initially observed deficits. The aim of this study was to assess changes in cardiac output determined by the FloTrac/Vigileo™ system (FCO) with an initially released (FCOA) and a modified (FCOB) software version, as well as changes in cardiac output from the PiCCOplus™ system (PCO; Pulsion Medical Systems, Munich, Germany). Both devices were compared with cardiac output measured by intermittent thermodilution (ICO).MethodsCardiac output measurements were performed in patients after elective cardiac surgery. Two sets of data (A and B) were obtained using FCOA and FCOB in 50 patients. After calibration of the PiCCOplus™ system, triplicate FCO and PCO values were recorded and ICO was determined in the supine position and cardiac output changes due to body positioning were recorded 15 minutes later (30° head-up, 30° head-down, supine). Students t test, analysis of variance and Bland-Altman analysis were calculated.ResultsSignificant changes of FCO, PCO and ICO induced by body positioning were observed in both data sets. For set A, ΔFCOA was significantly larger than ΔICO induced by positioning the head down. For set B, there were no significant differences between ΔFCOB and ΔICO. For set A, increased limits of agreement were found for FCOA-ICO when compared with PCO-ICO. For set B, mean bias and limits of agreement were comparable for FCOB-ICO and PCO-ICO.ConclusionsThe modification of the FloTrac/Vigileo™ system resulted in an improved performance in order to reliably assess cardiac output and track the related changes in patients after cardiac surgery.