The effect of hydroxyethyl starches (HES 130/0.42 and HES 200/0.5) on activated renal tubular epithelial cells.

BACKGROUND: Acute renal failure is a frequent complication of sepsis. Hydroxyethyl starch (HES) is widely used in the treatment of such patients. However, the effect of HES on renal function during sepsis remains controversial. We established an in vitro model of tumor necrosis factor-alpha (TNF-alpha)-stimulated human proximal tubular epithelial (HK-2) cells to assess the possible effects of HES 130/0.42 and HES 200/0.5 on these activated cells. METHODS: HK-2 cells were stimulated with TNF-alpha in the presence or absence of HES 130/0.42 or 200/0.5. After 4, 10, and 18 h of incubation, monocyte chemoattractant protein-1 (MCP-1), a key chemoattractant for neutrophils and macrophages, was measured. In addition, viability and cytotoxicity assays were performed. RESULTS: MCP-1 expression was doubled upon TNF-alpha exposure. In the presence of 2% and 4% HES 200/0.5 in 98% (96%) medium over a stimulation time period of 10 h and 18 h, the MCP-1 concentration was decreased between 26% and 56% (P < 0.05). TNF-alpha stimulation resulted in a significant decrease of viability by 53%-63%, whereas viability decreased by only 32%-40% in coincubation with HES 130/0.42 (P < 0.005) and remained even less affected by TNF-alpha in the presence of HES 200/0.5 (P < 0.001). The TNF-alpha-induced cell death rate was attenuated in the presence of HES 200/0.5 (P < 0.05). CONCLUSIONS: This in vitro study shows that both HES products modulate cell injury upon inflammatory stimulation. The effect was more pronounced in the HES 200/0.5 group than for HES 130/0.42, suggesting a possible biological difference between the HES types.

Transdermal resorption of an ethanol- and 2-propanol-containing skin disinfectant.

BACKGROUND AND AIMS: Ethanol- or 2-propanol-containing disinfectant agents are widely used in medical practice, particularly in the surgical environment. It was the primary objective of this phase I study to comparatively investigate the transdermal resorption of ethanol and 2-propanol within 1 h after dermal application of the two agents as single preparations and a commercial product containing both alcohols in combination, respectively. The secondary objective was to examine whether a mutual influence of the two alcohols in combination exists. MATERIALS AND METHODS: Following the double-blind, randomized, three-times cross-over design for this clinical trial, 20 ml of three different alcohol-containing disinfectants were applied on a 200-cm(2) gauze swab on skin areas, identical in size and location, of 14 healthy volunteers for 10 min to investigate the absorption rate of ethanol and 2-propanol with special focus on the question whether the two alcohols might influence each other's absorption rate when being applied in combination. RESULTS: No clinically relevant enhancement of dermal absorption, with respect to ethanol and 2-propanol, could be observed within 1 h after application, neither when used as single preparations, nor in combination. CONCLUSION: Therefore, the use of ethanol- and 2-propanol-containing disinfectants in the medical environment can be considered as safe.

Propofol anesthesia in children does not induce sister chromatid exchanges in lymphocytes.

BACKGROUND: Propofol is frequently used for general anesthesia in children although little is known about possible genotoxic effects in humans. We investigated the formation of sister chromatid exchanges (SCE) in metaphase chromosomes of T-lymphocytes of children as a marker for possible genotoxocity following total intravenous anesthesia with propofol for minor surgical procedures. METHODS: 40 children ASA classification I-III were included (ASA I n=34, ASA II n=5, ASA III n=1) in the study. Anesthesia was induced by propofol (3mg/kg) and alfentanil. Succinylcholine or rocuronium were administered for muscle relaxation. After tracheal intubation anesthesia was maintained by continuous propofol infusion at 12 mg/(kgh). Blood samples were drawn before induction and after termination of anesthesia. Following a 72 h cell culture period, 25 T-lymphocyte metaphases per blood sample for all children were analyzed for SCE frequencies. RESULTS: Total intravenous anesthesia with propofol on children did not influence SCE rates in metaphase chromosomes of T-lymphocytes. No SCE differences could be detected between blood samples before initiation and after termination of anesthesia (Wilcoxon signed rank test). Slightly elevated SCE rates were obtained in T-lymphocytes of girls compared to boys, but these differences did not reach statistical significance. CONCLUSIONS: Propofol anesthesia under the chosen conditions did not induce the formation of SCE in children in vivo. No genotoxic effect of a short term exposure to propofol during pediatric anesthesia had been observed.

Patient-controlled thoracic epidural infusion with ropivacaine 0.375% provides comparable pain relief as bupivacaine 0.125% plus sufentanil after major abdominal gynecologic tumor surgery.

BACKGROUND AND OBJECTIVES: We tested the hypothesis that an opioid-free local anesthetic alone is able to provide comparable analgesia to the opioid supplemented epidural application of local anesthetics using thoracic epidural catheters after major abdominal surgery. METHODS: In a prospective, randomized, and double-blind study, we have compared the analgesic efficacy and side effects of ropivacaine 0.375% (group R) versus bupivacaine 0.125% in combination with sufentanil 0.5 microg/mL(-1) (group B/S) via a thoracic epidural catheter for a duration of 96 hours after major abdominal surgery in 30 gynecologic tumor patients. Piritramide was given for breakthrough pain. Assessments were performed every 12 hours after start of the epidural infusion using continuous (first 24 hours) and patient-controlled epidural analgesia (PCEA) (24 to 96 hours). RESULTS: No differences were seen in demographic and perioperative data. Dynamic pain scores (visual analog scale [VAS] values) were comparable between groups during mobilization (group R v group B/S: 24 hours: 40 +/- 30 v 36 +/- 14, P =.9; 48 hours: 46 +/- 33 v 42 +/- 25, P =.93; 72 hours: 42 +/- 24 v 48 +/- 26, P =.78; 96 hours: 42 +/- 25 v 29 +/- 28, P =.49) and on coughing during the whole study period. Hemodynamics, intensity of motor block (Bromage scale), and side effects like nausea, vomiting, pruritus, and bladder disfunction also did not differ between groups. CONCLUSION: The present study shows that thoracic epidural infusion of ropivacaine 0.375% provides comparable pain relief and incidence of side effects after major abdominal gynecologic surgery as bupivacaine 0.125% in combination with 0.5 microg/mL(-1) sufentanil and may therefore represent an alternative in epidural pain management.

Impact of the C2/C6 ratio of high-molecular-weight hydroxyethyl starch on pharmacokinetics and blood coagulation in pigs.

BACKGROUND: High-molecular-weight, low-substituted hydroxyethyl starch (HES) may not affect blood coagulation more than low-molecular-weight, low-substituted HES. The authors assessed in vivo the effect of a lowered C2/C6 ratio on pharmacokinetic characteristics and the impact on blood coagulation of high-molecular-weight, low-substituted HES. METHODS: A prospective, randomized, parallel study in 30 pigs compared HES 650/0.42/2.8 with HES 650/0.42/5.6. Before, during, and after infusion of 30 ml/kg body weight HES, blood samples were collected over 630 min to measure HES concentrations and plasmatic coagulation and to assess blood coagulation in whole blood by Thrombelastography (TEG; Haemoscope Corporation, Niles, IL). Pharmacokinetic parameters were estimated using a two-compartment model. RESULTS: The elimination constant was 0.009 +/- 0.001 min(-1) for HES 650/0.42/2.8 and 0.007 +/- 0.001 min(-1) for HES 650/0.42/5.6 (P < 0.001); the area under the plasma concentration-time curve was 1,374 +/- 340 min x g/l for HES 650/0.42/2.8 and 1,697 +/- 411 min x g/l for HES 650/0.42/5.6 (P = 0.026). The measured plasma HES concentrations were not different between HES 650/0.42/2.8 and HES 650/0.42/5.6. Both HES solutions equally affected blood coagulation: Thrombelastographic coagulation index decreased similarly at the end of infusion of HES 650/0.42/2.8 and at the end of infusion of HES 650/0.42/5.6 (P = 0.293). Also, activated partial thromboplastin and prothrombin times increased similarly for HES 650/0.42/2.8 and HES 650/0.42/5.6 (P = 0.831). CONCLUSION: Reducing the C2/C6 ratio in high-molecular, low-substituted HES solutions results in a slightly faster HES elimination. However, the blood coagulation compromising effect was unaffected.

Effect of high- and low-molecular-weight low-substituted hydroxyethyl starch on blood coagulation during acute normovolemic hemodilution in pigs.

BACKGROUND: Hydroxyethyl starches (HES) with lower impact on blood coagulation but longer intravascular persistence are of clinical interest. The current study aimed to investigate in vivo the isolated effect of molecular weight on blood coagulation during progressive acute normovolemic hemodilution. METHODS: Twenty-four pigs were normovolemically hemodiluted up to a total exchange of 50 ml . kg . body weight of HES 650/0.42 or HES 130/0.42. Serial blood sampling was performed to measure HES plasma concentration and to assess blood coagulation. Concentration-effect relations were analyzed by linear regression, followed by the Student t test on regression parameters. RESULTS: Blood coagulation was increasingly compromised toward hypocoagulability by acute normovolemic hemodilution with both treatments (P < 0.01). Significantly greater impact on activated partial thromboplastin time (P = 0.04) and significantly stronger decrease of maximal amplitude (P = 0.04), angle alpha (P = 0.02), and coagulation index (P = 0.02) was seen after acute normovolemic hemodilution with HES 650/0.42 as compared with HES 130/0.42. Except for factor VIII (P = 0.04), no significant differences between both treatments were observed when relating antihemostatic effects to HES plasma concentrations (P > 0.05). A significantly lesser decrease of hemoglobin concentration has been found with HES 650/0.42 as compared with HES 130/0.42 (P < 0.01) in relation to HES plasma concentrations. CONCLUSION: High-molecular-weight HES (650/0.42) shows a moderately greater antihemostatic effect than low-molecular-weight HES (130/0.42) during acute normovolemic hemodilution. However, similar effects on hemostasis were observed with both treatments when observed antihemostatic effects were related to measured HES plasma concentrations. In addition, HES 650/0.42 may have a lower efficacy in immediately restoring plasma volume.

Continuous wound infiltration with ropivacaine reduces pain and analgesic requirement after shoulder surgery.

UNLABELLED: 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. IMPLICATIONS: The continuous postoperative wound infiltration after shoulder surgery with different concentrations of ropivacaine, 2 mg/mL and 3.75 mg/mL, results in lower pain scores and opioid requirement compared with infiltration with placebo. Plasma levels of ropivacaine remained less than the toxic threshold.

Spinal anesthesia performance conditions and side effects are comparable between the newly designed Ballpen and the Sprotte needle: results of a prospective comparative randomized multicenter study.

UNLABELLED: In this study, we examined the characteristics of a newly designed spinal needle (Ballpen [B]) with a pencil-like tip formed by a stylet that is withdrawn after penetration of the dura. The main goal was to examine whether the use of the B needle could reduce performance time by improved puncture conditions in comparison with the Sprotte (S) needle. Seven-hundred patients at 4 hospitals received single-dose spinal anesthesia with a 25-gauge B or S needle and 0.5% bupivacaine. The performance time of spinal anesthesia was defined as the time between insertion of the introducer needle and the first identification of cerebrospinal fluid in the hub of the spinal needle. Failed spinals were assessed when patients required general anesthesia. On postoperative Day 2-4, all patients were visited and interviewed. Groups did not differ with respect to demographics, puncture site, and dose of bupivacaine. Performance time was 98 +/- 145 s in Group B and 103 +/- 159 s in Group S (P = 0.68). The failure rate in Groups B and S was 3.8% and 3.9%, respectively, and the incidence of postdural puncture headache was 1.8% and 0.9% (P = 0.50), respectively. We conclude that there was no difference in technical variables or outcome between the B and S needles. IMPLICATIONS: This multicenter study examined characteristics of the newly designed Ballpen needle with the Sprotte needle in 700 patients undergoing lower abdominal or extremity surgery in single-dose spinal anesthesia. Technical variables and side effects were comparable between both noncutting spinal needles.

Hydroxyethyl starch (HES) 130/0.4 provides larger and faster increases in tissue oxygen tension in comparison with prehemodilution values than HES 70/0.5 or HES 200/0.5 in volunteers undergoing acute normovolemic hemodilution.

UNLABELLED: Stable hemodynamics and improved rheology are important effects of hemodilution with hydroxyethyl starch (HES) infusions. One clinical indicator of improved rheology is increased tissue oxygen tension (tpO(2)). In this prospective, randomized, double-blinded, crossover study, we examined the effects of acute normovolemic hemodilution with HES 130/0.4 on hemodynamics and skeletal muscle tpO(2) in comparison with conventional HES solutions. Twelve healthy volunteers were randomly enrolled in each group. At an interval of >8 days, volunteers donated 18% of their calculated blood volume within 30 min and randomly received 6% HES 130/0.4, 6% HES 70/0.5, or 6% HES 200/0.5 (crossover design) in a 1:1.2 ratio to their blood loss. Hemodynamic variables, tpO(2) in the quadriceps muscle, hematocrit, plasmatic HES concentrations, plasma viscosity, colloid osmotic pressures, and platelet aggregation were measured until 6 h after the infusion of HES. No differences were found among groups with respect to changes of hemodynamics, hematocrit, or platelet aggregation. With HES 200, colloid osmotic pressures and plasma viscosities were larger than after HES 70 (P < 0.05). HES 130 in comparison with HES 70 and 200 caused the fastest (30 min versus 90 min and 150 min after hemodilution; P < 0.05) and largest increase of tpO(2) in comparison to baseline (+93% versus +33% and 40%; P < 0.05). In healthy volunteers undergoing acute normovolemic hemodilution, the newly designed HES 130/0.4 showed a more pronounced and earlier increase of skeletal muscle tpO(2) in comparison with prehemodilution values than HES 70/0.5 or 200/0.5. IMPLICATIONS: The effects of three different hydroxyethyl starch (HES) solutions on hemodynamics, rheology, and skeletal muscle tissue tension after acute normovolemic hemodilution were examined in awake volunteers. With HES 130/0.4, increases of tissue oxygen tension in comparison to baseline were larger and more rapid than with HES 70/0.5 or HES 200/0.5.

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.

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

PURPOSE: To 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. METHODS: Twenty-eight women undergoing extended gynecological tumour surgery received postoperative CEI with 0.15 mL x kg(-1) x hr(-1) 0.2% ropivacaine (R: n = 14) or 0.125% bupivacaine plus 0.5 micro g x 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. RESULTS: Patients 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 +/- 32 vs 59+/-27, P < 0.05). No difference in parenteral opioid rescue medication between CEI and PCEA was seen. CONCLUSION: PCEA 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.