Thomas Standl

Use of perflubron emulsion to decrease allogeneic blood transfusion in high-blood-loss non-cardiac surgery: results of a European phase 3 study.

Background This single-blind randomized study in general surgery evaluated the efficacy of perflubron emulsion (PFC) as an artificial oxygen carrier being used to augment preoperative acute normovolemic hemodilution to reduce and avoid transfusion of both allogeneic erythrocytes and erythrocytes from preoperative autologous donation compared with standard of care. Methods Subjects (N = 492) with hemoglobin concentrations of 12–15 g/dl undergoing noncardiac surgical procedures with 20 ml/kg or greater expected blood loss were randomized into two groups. Control patients were transfused intraoperatively at a hemoglobin concentration less than 8.0 ± 0.5 g/dl or at protocol-defined, physiologic triggers. PFC-treated patients first underwent acute normovolemic hemodilution to hemoglobin of 8.0 ± 0.5 g/dl, followed by dosing with perflubron emulsion (1.8 g/kg). When hemoglobin reached less than 6.5 ± 0.5 g/dl, an additional 0.9-g/kg dose was given. PFC patients were transfused at hemoglobin less than 5.5 ± 0.5 g/dl or at predefined physiologic triggers. After surgery, hemoglobin was maintained at 8.5 ± 0.5 g/dl or greater in all patients until discharge. Efficacy endpoints included the number of allogeneic and preoperative autologous donation units transfused and the percentage of subjects avoiding transfusion. Results Both groups had similar hemoglobin concentrations at screening (13.5 ± 1.0 g/dl) and at discharge: 10.8 ± 1.2 g/dl (PFC) and 11.1 ± 1.3 g/dl (control). At 24 h, more patients in the PFC group avoided allogeneic and preoperative autologous donation erythrocyte transfusions (53%vs. 43%, P < 0.05), and fewer erythrocytes were transfused (1.5 ± 4.8 vs. 2.1 ± 3.9 units; median, 0 vs. 1 unit;P = 0.013). By day of discharge, these differences were not significant in the intent-to-treat population, but overall there were less allogeneic and preoperative autologous donation erythrocyte transfusions in the PFC group (696 vs. 846 units). In the protocol-defined target population (n = 330 subjects with blood loss ≥ 20 ml/kg), significantly greater avoidance of any erythrocyte transfusion was maintained through day of hospital discharge (26%vs. 16% in the PFC and control groups, respectively;P < 0.05), and there was also a significant reduction in the number of erythrocyte units transfused (3.4 ± 2.9 vs. 4.9 ± 2.4 units; median 2 vs. 4 units;P < 0.001). Adverse events rates were similar in the PFC (86%) and control (81%) groups; however, more serious adverse events were reported in the PFC group (32%) than in controls (21%;P < 0.05). Overall mortality was 3%, and the difference between groups (PFC, 4%vs. controls, 2%) was not statistically significant. Conclusions Augmented acute normovolemic hemodilution with PFC reduces transfusion needs in patients undergoing noncardiac surgical procedures with blood loss 20 ml/kg or greater.

Comparative evaluation of the Datex-Ohmeda S/5 Entropy Module and the Bispectral Index monitor during propofol-remifentanil anesthesia.

Background:Different analytical concepts were introduced to quantify the changes of the electroencephalogram. The Datex-Ohmeda S/5 Entropy Module (Datex-Ohmeda Division, Instrumentarium Corp., Helsinki, Finland) was the first commercial monitor based on the entropy generating two indices, the state entropy (SE) and the response entropy (RE). The aim of the current study was to compare the accuracy of SE and RE with the Bispectral Index® monitor (BIS®; Aspect Medical Systems, Newton, MA) during propofol–remifentanil anesthesia. Methods:The authors investigated 20 female patients during minor gynecologic surgery. SE, RE, BIS, mean arterial blood pressure, heart rate, and sedation level were recorded every 20 s during stepwise increase (target-controlled infusion, 0.5 &mgr;g/ml) of propofol until the patients lost response. Five minutes after loss of response, remifentanil infusion (0.4 &mgr;g · kg−1 · min−1) was started. Spearman correlation coefficient and prediction probability were calculated for sedation levels with SE, RE, BIS, mean arterial blood pressure, and heart rate. The ability of the investigated parameters to distinguish between the anesthesia steps awake versus loss of response, awake versus anesthesia, anesthesia versus first reaction, and anesthesia versus extubation was analyzed with the prediction probability. Results:SE correlates best with sedation levels, but no significant differences of the prediction probability values among SE, RE, and BIS were found. The prediction probability for all investigated steps of anesthesia did not show significant differences among SE, RE, and BIS. SE, RE, and BIS were superior to mean arterial blood pressure and heart rate. Conclusion:SE, RE, and BIS revealed similar information about the level of sedation and allowed the authors to distinguish between different steps of anesthesia. Both monitors provided useful additional information for the anesthesiologist.

Physostigmine Prevents Postanesthetic Shivering As Does Meperidine or Clonidine

BackgroundPostanesthetic shivering develops in as many as one half of patients recovering from isoflurane anesthesia. Cholinergic stimulation of the hypothalamic-pituitary-adrenal axis and adrenal medulla by physostigmine enhances secretion of arginine vasopressin, epinephrine, and norepinephrine. B

Continuous Wound Infiltration with Ropivacaine Reduces Pain and Analgesic Requirement After Shoulder Surgery

After achieving a reduction of pain scores for 10 h with a single dose wound infiltration after shoulder surgery, we examined in a prospective, placebo-controlled and double-blinded study the analgesic effects of continuous wound infiltration with different concentrations of ropivacaine. Forty-five patients undergoing shoulder surgery were randomly assigned into three groups to receive single dose wound infiltration with 30 mL saline (group S) or ropivacaine 7.5 mg/mL (groups R2 and R3.75) after skin closure. Postoperatively, patients received a continuous wound infiltration with saline (group S), ropivacaine 2 mg/mL (group R2) or ropivacaine 3.75 mg/mL (group R3.75) for 48 h. Supplemental pain relief was provided by IV patient-controlled analgesia with the opioid piritramide. At 1, 2, 3, 4, 24, and 48 h postoperatively visual analogue scale (VAS) values (0–100 mm), piritramide requirements and side effects were registered. Plasma levels of ropivacaine were measured preoperatively and at 24 h and 48 h after surgery. Until 48 h VAS values were smaller in group R3.75 compared with group S (group R3.75, 8 ± 9 mm; group S, 31 ± 14 mm; P < 0.005), whereas 4 h and 48 h postoperatively VAS values were even smaller in group R3.75 compared with group R2 (P < 0.05). Cumulative piritramide consumption was always smaller in groups R2 and R3.75 compared with group S (1–24 h, P < 0.005; 48 h, P < 0.05). Plasma ropivacaine levels remained less than the toxic threshold. We conclude that continuous postoperative wound infiltration with ropivacaine, especially using 3.75 mg/mL, provides smaller VAS values and opioid requirement in comparison with saline after shoulder surgery.

Patient-controlled epidural analgesia reduces analgesic requirements compared to continuous epidural infusion after major abdominal surgery.

PurposeTo compare the quality of pain relief and incidence of side effects between 24-hr postoperative continuous epidural infusion (CEI) and subsequent patient-controlled epidural analgesia (PCEA) with different analgesics after major abdominal surgery.MethodsTwenty-eight women undergoing extended gynecological tumour surgery received postoperative CEI with 0.15 ml·kg−1hr−10.2% ropivacaine (R:n = 14) or 0.125% bupivacaine plus 0.5 μg · mL−1 sufentanil (BS:n = 14) during 24 postoperative hours. Twenty-four hours later, postoperative pain management was switched to PCEA without background infusion and 5 mL single bolus application of R or BS every 20 min at most. Visual analogue scales (VAS; 1–100 mm) were assessed by patients at rest and on coughing after 24 hr of CEI and PCEA. Side effects, doses of local anesthetics and opioids were recorded and plasma concentrations of total and unbound ropivacaine and bupivacaine were measured.ResultsPatients required lower doses of each respective analgesic medication with PCEA (R: 108 ± 30 mL; BS: 110 ± 28 mL) than with CEI (R: 234 ± 40; BS: 260 ± 45;P < 0.01). Ropivacaine plasma concentrations were lower 24 hr after PCEA when compared with CEI (P < 0.01). No patient after PCEA but two after CEI (n = 4; NS) presented motor block. PCEA with R provided better postoperative pain relief than CEI (37 ± 32vs 59 ±27,P < 0.05). No difference in parenteral opioid rescue medication between CEI and PCEA was seen.ConclusionPCEA in comparison to preceding CEI provides equivalent analgesia with lower local anesthetic doses and plasma levels, and without motor blocking side effects, irrespective of the applied drug regimen.RésuméObjectifComparer la qualité de l’analgésie et l’incidence d’effets secondaires entre une perfusion postopératoire péridurale continue (PPC) de 24 h et une analgésie péridurale auto-contrôlée (APAC) ultérieure, réalisée avec différents analgésiques après une intervention chirurgicale majeure.MéthodeVingt-huit femmes, devant subir l’ablation élargie d’une tumeur gynécologique, ont reçu une PPC postopératoire avec 0,15 mL · kg−1hr−1 de ropivacaine à 0,2 % (R: n = 14) ou de bupivacaïne à 0,125% plus 0,5 μg · mL−1 de sufentanil (BS:n = 14) pendant 24 h après l’opération. La PPC a été ensuite remplacée par une APAC, sans perfusion d’appoint, et avec l’application d’un unique bolus de 5 mL de R ou de BS toutes les 20 min au plus. L’échelle visuelle analogique (EVA; 1–100 mm) a été évaluée par les patientes au repos et pendant la toux après 24 h de PPC et d’APAC. Les effets secondaires, les doses d’anesthésiques locaux et d’opidides ont été notées et les concentrations plasmatiques de ropivacaïne et de bupivacaïne totales et libres, mesurées.RésultatsLes patientes ont demandé de plus faibles doses de chacun des analgésiques avec l’APAC (R: 108 ± 30 mL; BS: 110 ± 28 mL) qu’avec la PPC (R: 234 ± 40; BS: 260 ± 45; P < 0,01). Les concentrations plasmatiques de ropivacaïne étaient plus faibles 24 h après l’APAC, comparée à la PPC (P < 0,01). Aucune patiente n’a présenté de bloc moteur après l’administration d’APAC, mais deux après la PPC (n = 4; NS). L’APAC avec R s’est révélée meilleure que la PPC comme analgésique postopératoire (31 ± 32 vs 59 ± 27, P < 0,05). Nous n’avons observé aucune différence de médication de secours, avec opioïde parentéral, entre la PPC et l’APAC.ConclusionLAPAC, comparée à la PPC qui a précédé, fournit une analgésie équivalente pour des doses d’anesthésique local et des niveaux plasmatiques plus faibles et sans les effets secondaires de bloc moteur, peu importe le régime médicamenteux appliqué.

Bovine hemoglobin increases skeletal muscle oxygenation during 95% artificial arterial stenosis

BACKGROUND This study investigates the effect of a stroma-free ultrapurified bovine hemoglobin solution (HBOC) on skeletal muscle tissue oxygenation in comparison with hetastarch during nearly complete arterial stenosis. METHODS Fourteen foxhounds were intravenously anesthetized and mechanically ventilated with 30% oxygen in air. Catheters were inserted into the right femoral artery and vein for measurements of hemodynamic parameters and blood gas sampling. Arterial blood flow of the left popliteal artery was measured by means of an electromagnetic flow probe. Skeletal muscle tissue oxygen tension (tpO2) was measured in the left gastrocnemius muscle by using a stepwise driven polarographic needle probe creating histograms from 200 single tpO2 measurements. After isovolemic hemodilution with Ringers lactate solution to a hematocrit of 25%, a 95% artificial stenosis of the popliteal artery was established. The animals then randomly received two applications of either 50 ml HBOC (molecular weight, 32,000 to 500,000; hemoglobin, 13 +/- 1 gm/dl-1) or 200 ml 6% hetastarch 200,000/0.5. Variables were measured at baseline, after hemodilution, 30 minutes after stenosis, and 15 minutes after two applications of the respective compound. RESULTS Demographic data, muscle temperature, and arterial blood gases did not differ between groups. With the exception of higher mean arterial and mean pulmonary artery pressures in HBOC-treated animals, hemodynamics did not differ between groups. In both groups oxygen delivery and oxygen consumption of the muscle decreased in parallel to the decreasing blood flow during arterial stenosis. In contrast, oxygen extraction ratio increased after infusion of HBOC and was higher after the second application when compared with hetastarch-treated animals (p < 0.05). During stenosis tpO2 was decreased in both groups when compared with baseline (p < 0.001). Mean tpO2 remained at decreased levels after administration of hetastarch but increased to nearly baseline values after HBOC treatment (p < 0.001). CONCLUSIONS The data suggest that increased oxygen extraction in the HBOC group is associated with improved skeletal muscle tissue oxygenation during severe arterial stenosis.

Effect of Different Cost Drivers on Cost per Anesthesia Minute in Different Anesthesia Subspecialties

Background:Little is known about differences in costs to provide anesthesia care for different surgical subspecialties and which factors influence the subspecialty-specific costs. Methods:In this retrospective study, the authors determined main cost components (preoperative visit, intraoperative personnel costs, material and pharmaceutical costs, and others) for 10,843 consecutive anesthesia cases from a 6-month period in the 10 largest anesthesia subspecialties in their university hospital: ophthalmology; general surgery; obstetrics and gynecology; ear, nose, and throat surgery; oral and facial surgery; neurosurgery; orthopedics; cardiovascular surgery; traumatology; and urology. Using regression analysis, the effect of five presumed cost drivers (anesthesia duration, emergency status, American Society of Anesthesiologists physical status of III or higher, patient age younger 6 yr, and placement of invasive monitoring) on subspecialty-specific costs per anesthesia minute were analyzed. Results:Both personnel costs for anesthesiologists and total costs calculated per anesthesia minute were inversely correlated with the duration of anesthesia (adjusted R2 = 0.75 and 0.69, respectively), i.e., they were higher for subspecialties with short cases and lower for subspecialties with longer cases. The multiple regression model showed that differences in anesthesia duration alone accounted for the majority of the cost differences, whereas the other presumed cost drivers added only little to explain subspecialty-specific cost differences. Conclusions:Different anesthesia subspecialties show significant and financially important differences regarding their specific costs. Personnel costs and total costs are highest for subspecialties with the shortest cases. Other analyzed cost drivers had little effect on subspecialty-specific costs. In the light of these cost differences, a detailed cost analysis seems necessary before the profitability of an anesthesia subspecialty can be assessed.

Quality of Postoperative Pain Using an Intraoperatively Placed Epidural Catheter after Major Lumbar Spinal Surgery

Background:Major spinal surgery is associated with high postoperative pain scores and opioid requirement. The aim of the current prospective, randomized, placebo-controlled, double-blind study was to assess the reduction of opioid requirement and pain scores using an intraoperatively placed epidural catheter with infusion of 0.1% ropivacaine during the postoperative period. Methods:Thirty patients undergoing major lumbar spinal surgery from a dorsal approach were included in this study. Before wound closure, the orthopedic surgeon inserted an epidural catheter. Postoperatively, patients were randomly assigned to receive an infusion of 12 ml/h ropivacaine, 0.1% (group R), or 12 ml/h saline (group N) after an initial bolus of 10 ml of the respective study solution. Additional pain relief was provided using an intravenous patient-controlled analgesia pump with the opioid piritramide. Patients were assessed with respect to pain scores (visual analog scale of 0–100), cumulative opioid requirement, side effects, and satisfaction with pain management. Results:Demographic data, duration of surgery, and type of surgery were comparable between groups. Pain scores were assessed as follows (group R vs. group N: 6 h: 24 ± 20 vs. 51 ± 20, P = 0.002; 24 h: 33 ± 19 vs. 53 ± 27, P = 0.04; 48 h: 21 ± 17 vs. 40 ± 26, P = 0.04; 72 h: 14 ± 13 vs. 38 ± 25, P = 0.02). The cumulative piritramide requirement after 72 h was 97 ± 23 mg in group R and 157 ± 72 mg in group N (P = 0.03). The incidence of side effects was comparable between groups, and patient satisfaction was always higher in group R (P < 0.05). Conclusion:Continuous epidural infusion of 0.1% ropivacaine results in lower pain scores and opioid consumption and higher patient satisfaction when compared with placebo. Application of ropivacaine using an epidural catheter seems to be a highly effective treatment for postoperative pain after major lumbar spinal surgery.

Narcotrend and Bispectral Index monitor are superior to classic electroencephalographic parameters for the assessment of anesthetic states during propofol-remifentanil anesthesia

Background A new electroencephalogram monitor, the Narcotrend®, was developed to measure anesthetic depth. The authors compared the Narcotrend®, the Bispectral Index®, and classic electroencephalographic and hemodynamic parameters during anesthesia with propofol and remifentanil. Methods The authors investigated 25 patients undergoing laminectomy at different anesthetic states: awake, steady state anesthesia, first reaction during emergence, and extubation. Narcotrend® value; BIS; relative power (percent) in &dgr;, &thgr;, &agr;, and &bgr;; median frequency; spectral edge frequency; and hemodynamic parameters were recorded simultaneously. The ability of the classic and processed electroencephalographic and hemodynamic parameters to predict the clinically relevant anesthetic states of awake, steady state anesthesia, first reaction, and extubation was tested using prediction probability. Results Only the Narcotrend® was able to differentiate between awake versus steady state anesthesia and steady state anesthesia versus first reaction/extubation with a prediction probability value of more than 0.90. Conclusions Modern electroencephalographic parameters, especially Narcotrend®, are more reliable indicators for the clinical assessment of anesthetic states than classic parameters.

Comparative evaluation of Narcotrend, Bispectral Index, and classical electroencephalographic variables during induction, maintenance, and emergence of a propofol/remifentanil anesthesia.

In the present study, we sought to compare the abilities of Narcotrend™ (NT) with the Bispectral Index™ (BIS™) electroencephalographic system to monitor depth of consciousness immediately before induction of anesthesia until extubation during a standardized anesthetic. We investigated 26 patients undergoing laminectomy. Investigated states of anesthesia were: awake, loss of response, loss of eyelash reflex, steady-state anesthesia, first reaction, and extubation during emergence. NT, BIS™, spectral edge frequency, median frequency, relative power in δ, &thetas;, &agr;, β, and hemodynamics were recorded simultaneously. The ability of all variables to distinguish between awake versus loss of response, awake versus loss of eyelash reflex, awake versus steady-state anesthesia, steady-state anesthesia versus first reaction and extubation were analyzed with the prediction probability. Effects of remifentanil during propofol infusion were investigated with Fried-man’s and post hoc with Wilcoxon’s test. Only NT and BIS™ were able to distinguish all investigated states accurately with a prediction probability >0.95. After start of remifentanil infusion, only hemodynamics changed statistically significantly (P < 0.05). NT and BIS™ are more reliable indicators for the assessment of anesthetic states than classical electroencephalographic variables and hemodynamics, whereas the analgesic potency of depth of anesthesia could not be detected by NT and BIS™.