BACKGROUNDThe concept of pre-emptive analgesia remains controversial. This prospective, randomized, and double-blind study compared epidural administration of ropivacaine 2 mg ml(-1), sufentanil 0.5 microg ml(-1), clonidine 3 microg ml(-1), and S(+)-ketamine 0.25 mg ml(-1) (study solution) given before incision with the same combination started at the end of the operation.METHODSAfter testing the stability of the solution using high performance liquid chromatography (HPLC) and examining 12 patients for possible side-effects in comparison with the epidural infusion of ropivacaine 2 mg ml(-1) and sufentanil 0.5 microg ml(-1), 30 patients undergoing major pancreatic surgery were recruited into the study. Before induction of anaesthesia, an epidural catheter was inserted (TH6-8). Patients in Group 1 received a bolus of 8 ml followed by a continuous infusion (8 ml h(-1)) of the study solution before induction of anaesthesia. In Group 2, patients received the same volume of saline before operation, the study solution was started at the end of surgery. After operation, the infusion was maintained for at least 96 h using a patient-controlled epidural analgesia (PCEA) pump in both groups. Patients were evaluated up to the seventh postoperative day for pain and side-effects.RESULTSVisual analogue scale (VAS) values at rest were as follows: G1 vs G2: 24 h, 19 (sd 23) vs 6 (13); 48 h, 4 (10) vs 11 (21); and 72 h, 12 (22) vs 13 (21). VAS values during coughing and mobilization were also comparable. Total volume of epidural infusion was 904 (114) ml in G1 vs 892 (154) ml in G2. The incidence of side-effects (nausea, vomiting, and motor block) was low and not different between the groups.CONCLUSIONSPre-incisional epidural analgesic infusion did not provide pre-emptive analgesia compared with administration started at the end of surgery, but both groups had low pain scores.

Background and objective: The efficacy of administering a perfluorochemical-based oxygen therapeutic such as perflubron emulsion (Oxygent (TM) ) prior to ischaemia is currently unknown, although there is evidence for potential beneficial effects for the perioperative treatment in cardiac risk patients. This experimental study investigated the efficacy of perflubron emulsion in preventing reperfusion injury and myocardial infarction size after coronary ischaemia and reperfusion. The perflubron emulsion was given either in a prophylactic manner, prior to induction of myocardial ischaemia, or as a therapeutic agent given during ischaemia. Methods: Thirty-two anaesthetized and mechanically ventilated rats were subjected to 25 min occlusion of the left coronary artery followed by 120 min reperfusion. Animals were randomized to one of four groups: Group 1 was treated with administration of 6g kg(-1) intravenous perflubron emulsion 25 min before occlusion; Group 2 received the same dose 10 min after occlusion; and Groups 3 and 4 received no perflubron emulsion. Inspired O-2 (FiO(2)) concentration was maintained at 1.0 in Groups 1, 2 and 3 and at 0.35 in Group 4. Results: Neither prophylactic nor therapeutic perflubron emulsion treatment reduced infarct size measurements by triphenyltetrazolium-chloride staining or severity of cardiac arrhythmias in comparison to the hyperoxic control group. However, prophylactic application of perflubron emulsion reduced areas of impaired perfusion vs. Group 3 assessed by in vivo staining with Thioflavin-S while no significant effect was seen in Groups 2 and 4 vs. 3. Density of DNA single-strand breaks in the ventricle was increased in all groups ventilated with 100% oxygen. Conclusion: Although administration of perflubron emulsion did not reduce infarct size, areas of impaired perfusion were significantly mitigated when perflubron emulsion was administered prior to coronary occlusion. However, a high oxygen concentration may provoke DNA strand breaks during reperfusion after ischaemia. Further studies must clarify whether enhanced oxidative stress outweighs the advantage of improved areas of impaired perfusion following perflubron emulsion.

Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Knappschaftskrankenhaus Bochum Langendreer, University Hospital Bochum, In der Schornau 23-25, 44892 Bochum, Germany. Department of Anaesthesiology, Department of Surgery, and Pharmacy, University Hospital Hamburg Eppendorf, Hamburg, Germany. Department of Anaesthesiology and Critical Care Medicine, Academic Hospital Solingen, Germany

Background. The concept of pre-emptive analgesia remains controversial. This prospective, randomized, and double-blind study compared epidural administration of ropivacaine 2 mg ml(-1), sufentanil 0.5 mu g ml(-1), clonidine 3 mu g ml(-1), and S(+)-ketamine 0.25 mg ml(-1) (study solution) given before incision with the same combination started at the end of the operation.Methods. After testing the stability of the solution using high performance liquid chromatography (HPLC) and examining 12 patients for possible side-effects in comparison with the epidural infusion of ropivacaine 2 mg ml(-1) and sufentanil 0.5 mu g ml(-1), 30 patients undergoing major pancreatic surgery were recruited into the study. Before induction of anaesthesia, an epidural catheter was inserted (TH6-8). Patients in Group 1 received a bolus of 8 ml followed by a continuous infusion (8 ml h(-1)) of the study solution before induction of anaesthesia. In Group 2, patients received the same volume of saline before operation, the study solution was started at the end of surgery. After operation, the infusion was maintained for at least 96 h using a patient-controlled epidural analgesia (PCEA) pump in both groups. Patients were evaluated up to the seventh postoperative day for pain and side-effects.Results. Visual analogue scale (VAS) values at rest were as follows: G1 vs G2: 24 h, 19 (SD 23) vs 6 (13); 48 h, 4 (10) vs 11 (21); and 72 h, 12 (22) vs 13 (21). VAS values during coughing and mobilization were also comparable. Total volume of epidural infusion was 904 (114) ml in G1 vs 892 (154) ml in G2. The incidence of side-effects (nausea, vomiting, and motor block) was low and not different between the groups.Conclusions. Pre-incisional epidural analgesic infusion did not provide pre-emptive analgesia compared with administration started at the end of surgery, but both groups had low pain scores.

Amputations of extremities, especially in the childhood, impose high demands on the perioperative management. Apart from the intraoperative care of these children, the postoperative pain therapy has to do one's utmost in the avoidance of the development of phantom limb pain, which can, especially in the childhood, be associated with far reaching psychological consequences. We report the case of a 3-year old boy who had to undergo exarticualtion of his left arm due to an osteosarcoma of the humerus. The perioperative pain management was performed by a preoperatively placed interscalene catheter and infusion of 0.2 % ropivacaine. Within the first six days postoperatively complete pain relief could be ensured with this analgetic regimen.

Vertebroplasty consists of percutaneous injection of acrylic cement--polymethylmethacrylate (PMMA)--into a partially collapsed vertebral body in order to obtain pain relief and augment mechanical stability of the vertebral body. Although vertebroplasty is an efficient treatment it is not free of complications. Our present case report describes a woman with pulmonary polymethylmethacrylate embolism during percutaneous vertebroplasty who presented with hypotension, arrhythmia and hypocapnia.

A rare though extremely harmful complication in neuraxial anaesthesia is an epidural hematoma which can be associated with deleterious consequences for the patient, e. g. persistent paraplegia. The risk of epidural haematomas after neuraxial blockade is dependent on abnormal anatomy of the spine, difficult and multiple punctures and coagulation disorders. Especially when patients undergo therapy with anticoagulants like low molecular heparin or platelet inhibitors (tyclopidine) or a combination of them, the indication for neuraxial blockade must strictly outweigh risk of spinal bleeding. In this context, the precautions and contraindications are the same for spinal puncture and catheter insertion as for catheter removal. We describe the case of a patient who underwent emergency coronary angioplasty in combination with coronary stent implantation due to acute postoperative myocardial infarction following knee replacement in continuous epidural anaesthesia. Under the symptoms of a beginning local infection at the puncture site the epidural catheter had to be removed in spite of ongoing antithrombotic therapy. A possible management of such cases is discussed with regard to risk minimization.

A rare though extremely harmful complication in neuraxial anaesthesia is an epidural hematoma which can be associated with deleterious consequences for the patient, e.g. persistent paraplegia. The risk of epidural haernatomas after neuraxial blockade is dependent on abnormal anatomy of the spine, difficult and multiple punctures and coagulation disorders. Especially when patients undergo therapy with anticoagulants like low molecular heparin or platelet inhibitors (tyclopidine) or a combination of them, the indication for neuraxial blockade must strictly outweigh risk of spinal bleeding. In this context, the precautions and contrainclications are the same for spinal puncture and catheter insertion as for catheter removal. We describe the case of a patient who underwent emergency coronary angioplasty in combination with coronary stent implantation due to acute postoperative myocardial infarction following knee replacement in continuous epidural anaesthesia. Under the symptoms of a beginning local infection at the puncture site the epidural catheter had to be removed in spite of ongoing antithrombotic therapy. A possible management of such cases is discussed with regard to risk minimization.

Amputations of extremities, especially in the childhood, impose high demands on the perioperative management. Apart from the intraoperative care of these children, the postoperative pain therapy has to do one's utmost in the avoidance of the development of phantom limb pain, which can, especially in the childhood, be associated with far reaching psychological consequences. We report the case of a 3-year old boy who had to undergo exarticualtion of his left arm due to an osteosarcoma of the humerus. The perioperative pain management was performed by a preoperatively placed interscalene catheter and infusion of 0.2% ropivacaine. Within the first six days postoperatively complete pain relief could be ensured with this analgetic regimen.

Background and objective: To compare the anaesthetic characteristics in terms of onset and offset times of the sensory and motor blocks of prilocaine 1% and ropivacaine 0.75% alone and in different combinations when used for brachial plexus anaesthesia in axillary perivascular blocks. Methods: After informed consent 96 ASA I–III patients undergoing forearm or hand surgery participated in this prospective, randomized, double‐blind study. Patients received either prilocaine 1% 40 mL (G1), prilocaine 1% 30 mL and ropivacaine 0.75% 10 mL (G2), prilocaine 1% 20 mL and ropivacaine 0.75% 20 mL (G3) or ropivacaine 0.75% 40 mL (G4) for axillary perivascular brachial plexus anaesthesia. Onset and duration of sensory and motor blocks in the distribution of the musculocutaneous, radial, median and ulnar nerves were assessed. Results: The onset time of the sensory and motor blocks of the whole brachial plexus differed only between patients in G4 with ropivacaine 0.75% 40 mL demonstrating a later motor onset in comparison to all other groups and a later sensory onset in comparison to G1 and G2 (P < 0.01). The addition of ropivacaine resulted in longer offset times of the sensory and motor blocks. The median offset time of the motor block was 179.5 min in G1, 262 min in G2, 389.5 min in G3 and 745 min in G4 (P < 0.01). The median offset time of the sensory block was 163.5 min in G1, 277 min in G2, 383.5 min in G3 and 784 min in G4 (P < 0.01). There was no difference in onset and offset times between sensory and motor blocks within the groups. Conclusions: For axillary perivascular brachial plexus block prilocaine 1% alone and in combination with ropivacaine 0.75% was similar in terms of onset of sensory and motor blocks but different in duration of sensory and motor blocks without a differential sensory and motor offset.

Objectives: Stasis of the pancreatic microcirculation initiates and aggravates acute pancreatitis. Bovine hemoglobin has been shown to improve microcirculation in acute pancreatitis if prophylactically infused 15 minutes after initiation of acute pancreatitis. The purpose of this study was to evaluate the therapeutic effectiveness of bovine hemoglobin on pancreatic microcirculation and tissue damage later in the course of experimental acute rodent pancreatitis.Methods: In Wistar rats, severe acute pancreatitis was induced by administration of glyco-deoxycholic-acid intraductally and cerulein intravenously. Pancreatic microcirculation was continuously monitored by intravital microscopy. Three hours after the initiation of acute pancreatitis, animals received either 0.8 mL bovine hemoglobin (Oxyglobin), hydroxyethyl starch (HES), or 2.4 mL 0.9% NaCl intravenously at random. After 6 hours, animals were killed, and histopathological damage of the pancreas was assessed using a validated histology score.Results: Pancreatic microcirculation assessed by leukocyte adherence was significantly improved by the administration of bovine hemoglobin in comparison with normal saline over time ( mean difference, 51.6 +/- 9.2; P < 0.001) and HES (mean difference, 24.1 +/- 9.2; P = 0.037). This result was paralleled by decreased tissue damage in the bovine hemoglobin group as opposed to NaCl (6.75 vs. 12; range, 5.25-7.75 vs. 8.25-14; P < 0.001) and HES (6.75 vs. 9; range, 5.25-7.75 vs. 7.5-10.75; P < 0.001).Conclusion: Therapeutic intravenous infusion of bovine hemoglobin improves pancreatic microcirculation and reduces pancreatic tissue damage in severe acute rodent pancreatitis but is not as effective as early (prophylactic) administration.

Background: Disturbed microcirculation and as a consequence decreased tissue oxygenation is a crucial effect in the cascade from the self limiting mild edematous to the often fatal form of acute hemorrhagic necrotizing pancreatitis.The aim of this study was to evaluate the therapeutic approach of volume therapy with HBOC-301 with and without IHD with regard to pancreatic tissue oxygenation, pancreatic microcirculation and survival in pigs suffering from acute necrotizing pancreatitis. Methods: After approval of the local ethics committee 39 pigs were anesthetized, endotracheally intubated and normoventilated (FIO2:0.3). After laparotomy and splenectomy the pancreatic duct was canulated. Pancreatic tissue oxygen tensions (tpO2) were measured using a silicon catheter (Licox Medical Systems, Germany). Pancreatic microcirculation was assessed by a laser-doppler perfusion imager (Perimed, Sweden). After 30 min. equilibration (M0) AP was induced by a combination of intravenous cerulein and intraductal glycodeoxycholic acid. Fifteen min. and 75 min. after induction of AP animals were randomized to isovolemic (PAOP-constant) hemodilution with 10% HES 200,000/0.5 plus HBOC-301 (+0.6 g dl-1 plasmatic Hb; Oxyglobin®, Biopure, USA) (IHD+HBOC) or to HBOC-301 (+0.6 g dl-1 plasmatic Hb) (HBOC), or to hemodilution with Ringer's solution (IHD RINGER) to a hematocrit (Hct) of 15%. TpO2 and microcirculation were measured every hour. After six hours catheters were removed, the abdomen was closed and animals were extubated. After six days (144 hours) surviving animals were sacrified. Statistical analyses were performed using the Kolmogorov-Smirnov test for normal distribution, Kruskal-Wallis test for group differences, Student`s t-test for normally distributed data and Chi-square test for the survival rate (significance p < 0.05). Results: After induction of AP tpO2 decreased in all groups and increased significantly to normal levels after application of HBOC-301 with and without IHD compared to the IHD RINGER-group. The survival rate at the end of the observation period was higher in the IHD+HBOC group (10/13) (p < 0.001) and in the HBOC-group (9/13) (p < 0.001) compared to the Ringer group (2/13) (p = 0,001 Kruskal-Wallis Test). The extend of the microcirculatory impairment corresponded with these results. Conclusion: The therapeutic application of HBOC-301 was able to normalize pancreatic tissue oxygen and improve survival after induction of severe AP. The IHD had no additional effect.

BACKGROUND:HBOC-201 is an ultra purified bovine hemoglobin solution. It has already been used in clinical phase II/III trials for emergency treatments. Animal experiments have shown that HBOC-201 is highly effective in tissue oxygenation. The study was performed in order to assess the potential of low dose HBOC-201 to improve tumor oxygenation. METHODS:30 rats with a subcutaneously growing rhabdomyosarcoma R1H tumor were randomly assigned either to be ventilated with carbogen (n = 10), or to receive an IV injection of 0.3 g/kg HBOC-201 (n = 10) or a combination of 0.3 g/kg HBOC-201 and carbogen breathing (n = 10). Under general anesthesia the effects of the respective treatment on the tissue oxygen tension (tpO2) of the tumor were determined using a flexible stationary probe at baseline (b) and 15 and 60 min after application of the respective medication. RESULTS:HBOC-201 alone failed to improve tumor tpO2 (b: 1.3 +/- 1.2mmHg; 15min: 1.4 +/- 1 mmHg; 60min: 1 +/- 1 mmHg). In combination with carbogen the mean tpO2 of the tumor raised in comparison to baseline values (b: 3.1 +/- 4.6 mmHg; mmHg; 15min: 8.5 +/- 11*mmHg; 60min: 4.8 +/- 5mmHg; *p < 0.05 vs. b), but this effect was less pronounced than the increase in tpO2 by carbogen alone (b: 3.4 +/- 3.4mmHg; 15min: 9 +/- 10* mmHg; 60 min: 13 +/- 19* mmHg; *p < 0.05 vs. b). CONCLUSION:The application of low dose hemoglobin solution HBOC-201 does not result in improvement of tissue oxygenation in the rat rhabdomyosarcoma R1H.

Background and objective: Hydroxyethyl starch is frequently used for volume substitution during surgical procedures and for isovolaemic haemodilution. Haemodilution has also been shown to improve tissue oxygen tension in skeletal muscle. However, effects of this volume substitute on tissue oxygen tension of the liver during haemodilution remains unknown. Methods: Fourteen foxhounds were anaesthetized with fentanyl/midazolam and mechanically ventilated with 30% oxygen. Following splenectomy animals were randomly assigned to a control group without haemodilution but fluid substitution with Ringer's lactate (Group C) or underwent isovolaemic haemodilution to a haematocrit of 25% with hydroxyethyl starch 70/0.5 (Group H). Haemodynamic parameters and oxygen transport during 100 min following isovolaemic haemodilution were measured. Liver oxygen tension was recorded using a flexible polarographic electrode tonometer, whereas in the muscle a polarographic needle probe was used. Results: Animal characteristics and baseline haematocrit were similar in both groups. At baseline the tissue oxygen tension of liver and skeletal muscle were not different between groups. Haemodilution with hydroxyethyl starch 70/0.5 provided augmentation of mean liver tissue oxygen tension (baseline: 46 ± 13 mmHg; 20 min: 60.3 ± 12 mmHg*; 60 min: 60 ± 16 mmHg*; 100 min: 63 ± 16 mmHg*; *P < 0.05 vs. baseline), while oxygen tensions in Group C remained unchanged (baseline: 48 ± 16 mmHg; 20 min: 52 ± 19 mmHg; 60 min: 49 ± 12 mmHg; 100 min: 52 ± 16 mmHg) and no differences could be detected between groups. Oxygen tension in skeletal muscle changed as follows: Group H - baseline: 24 ± 32 mmHg; 20 min: 32 ± 3 mmHg*†; 60 min: 33 ± 7 mmHg*†; 100 min: 33 ± 11 mmHg†. Group C - baseline: 22 ± 6 mmHg; 20 min: 21 ± 3 mmHg; 60 min: 24 ± 4 mmHg; 100 min: 18 ± 4 mmHg (*P < 0.05 vs. baseline, †P < 0.05 vs. Group C). Conclusion: In this animal model, isovolaemic haemodilution with hydroxyethyl starch 70/0.5 increased tissue oxygen tension in liver and skeletal muscle in comparison with baseline values. However, when compared between groups haemodilution only resulted in an increase of tissue oxygen tension in the muscle but not in the liver.

Introduction: Sufficient perioperative analgesia can reduce the development of chronic pain (1). It remains unclear, if a preemptive epidural application of different drugs, which can manage acute pain is able to reduce the intensity of postoperative pain as well as the incidence of chronic pain. Before evaluating the possible preemptive effect of an epidural combination of ropivacaine, sufentanil, clonidine and S( )ketamine the stability and tolerance of this solution has to be evaluated.

Rempf, C.; Ritter, A.; Lang, E.; Gottschalk, A.; Freitag, M.; Standl, T.; Schulte Esch, J. am Author Information