Marc-Alexander Burmeister

Präoperative Hämodilution mit bovinem Hämoglobin Akute hämodynamische Auswirkungen bei Patienten in der Leberchirurgie

ZusammenfassungHämoglobinlösungen sind kolloidale Volumenersatzpräparate, die Sauerstoff transportieren und damit eine Alternative zur homologen Transfusion von Erythrozyten darstellen können. Ziel der vorliegenden klinischen Studie war es, ein polymerisiertes ultragereinigtes Rinderhämoglobin (HBOC-201) im Vergleich zu Hydroxyäthylstärke (HES) auf Veränderungen der Hämodynamik und der O2-Transportparameter während und nach Hämodilution zu untersuchen. Material und Methoden: Nach Zustimmung durch die Ethikkommission wurden 12 Patienten (6 m. u. 6 w., Alter 59±10 J., ASA I–II, die sich einer Leberteilresektion unterziehen mußten, randomisiert auf 2 Gruppen verteilt. In Gruppe 1 erhielten die Patienten im Anschluß an eine präoperative Eigenblutspende von 1 l eine Infusion von 3 ml·kg−1 6% HES 70000/0,5 über 30 min sowie 2 l Ringerlaktat. Patienten der Gruppe 2 erhielten 2 l Ringerlaktat und über 30 min 0,4 g·kg−1 HBOC-201. Blutgasanalysen, Hämodynamik und Parameter des O2-Transports wurden vor und nach Eigenblutspende, während und nach Infusion, bei Operationsbeginn und auf der Intensivstation gemessen. Ergebnisse: Der arterielle Mitteldruck stieg unter Infusion von HBOC-201 im Gegensatz zu HES um maximal 18% gegenüber der Ausgangsmessung an. Während der pulmonale Gefäßwiderstand in der HBOC-201-Gruppe einen Trend zu höheren Werten als in der HES-Gruppe zeigte, stieg der systemische Gefäßwiderstand unter Infusion von HBOC-201 im Vergleich zum Ausgangswert um maximal 42% und war doppelt so hoch wie in der HES-Gruppe. Der Cardiac-Index lag in der HBOC-201-Gruppe unter den Werten der HES-Gruppe. Gemischt-venöse O2-Konzentrationen und -Sättigung sowie das errechnete O2-Angebot waren während und nach HBOC-201 Applikation niedriger als in der HES-Gruppe, während die O2-Extraktion nach Infusion von HBOC-201 höher war als nach HES. Die maximale Plasmakonzentration von HBOC-201 betrug 1,0±0,2 g·dl−1, die intravasale Halbwertszeit im Mittel 8,5 h. Im Urin war kein freies Hämoglobin nachweisbar. Schlußfolgerung. Die Ergebnisse zeigen bei guter Verträglichkeit der HBOC-201-Lösung einen vasokonstriktorischen Nebeneffekt, der zu einer Steigerung insbesondere des systemischen Gefäßwiderstands führt.AbstractHaemoglobin solutions can be an alternative to allogeneic red-cell transfusions because they combine colloid osmotic with oxygen transport properties. Since severe toxic side effects have been overcome by ultrapurification, clinical interest has been focused on haemodynamics changes during application of haemoglobin preparations. The present clinical study examines changes of haemodynamic and oxygen transport parameters during and after haemodilution with ultrapurified polymerized bovine haemoglobin (HBOC-201) in comparison to hydroxyethyl starch (HES). Methods: After approval of the Ethics Committee, 12 patients (6 males and 6 females, mean age 59±10 years, ASA 1-2) undergoing elective liver resection were randomly allocated to receive either 3 ml·kg−1 6% HES 70000/0.5 (group 1) or 0.4 g· kg−1 HBOC-201 (group 2) within 30 min following autologous blood donation of 1 l and substitution with 2 l Ringer’s lactate. Measurements of blood gases, haemodynamics, and oxygen transport parameters were performed after induction of general anaesthesia, prior to and after blood donation, during and after infusion, at the beginning of surgery, and in the intensive care unit. Results: Demographic characteristics did not differ between groups. In contrast to the HES group, mean arterial pressure increased by 18% over baseline measurements in group 2. While pulmonary vascular resistance showed a trend to higher values in group 2, systemic vascular resistance increased to a maximum of 42% over baseline in group 2 and was twice as high as in the HES group. The cardiac index was lower in the HBOC-201 group than in the HES group. During and after HBOC-201 infusion, mixed-venous oxygen saturation and content and calculated oxygen delivery were lower in group 2 in comparison to group 1, while the oxygen extraction ratio was higher in group 2. Free haemoglobin reached a maximal concentration of 1.0±0.2 g·dl−1 30 min after the HBOC-201 infusion was started, but was not detectable in urine over time. The mean intravascular half-life of HBOC-201 was 8.5 h. Conclusions: Patients did not show any severe complications during and after infusion of HBOC-201. However, vasoconstrictive side effects resulted in increased systemic but not pulmonary resistance. Ongoing studies with higher doses of HBOC-201 applied in a larger number of patients will probably reveal potential clinical consequences of the demonstrated haemodynamic changes.

Subarachnoid Sufentanil for early postoperative pain management in orthopedic patients : A placebo-controlled, double-blind study using spinal microcatheters

BackgroundContinuous spinal anesthesia is frequently used for intraoperative anesthesia but rarely for postoperative pain management. Because even small doses of local anesthetics can be associated with motor deficits, subarachnoid opioid injection may be an alternative. MethodsEighty patients randomly received a subarachnoid injection of 10 &mgr;g sufentanil, 5 mg bupivacaine, 2.5 &mgr;g sufentanil plus 2.5 mg bupivacaine, or saline through 28-gauge spinal microcatheters for early postoperative pain relief after major lower-limb surgery (n = 20 in each group). Hemodynamic and respiratory parameters, pain scores, and motor function were monitored, and sufentanil concentrations in plasma and cerebrospinal fluid were measured. Ten additional patients received up to three repetitive injections of 10 &mgr;g sufentanil over 24 h. ResultsAll drugs provided excellent pain relief within 15 min after injection, lasting 128 ± 61 min with sufentanil, 146 ± 74 min with bupivacaine, and 167 ± 78 min with the mixture. Patients receiving bupivacaine showed the highest cephalad extension of sensory block (median, T6) and the most intense motor block, whereas patients given only sufentanil had no motor deficit. The duration of analgesia was shorter after subsequent sufentanil injection (100–115 min) than after the first injection (198 ± 70 min). Six of 50 patients with sufentanil experienced a short episode of respiratory depression within 30 min after the first injection. Cerebrospinal fluid concentrations of sufentanil peaked at 5 min after injection (183 ± 167 ng/ml) but were at the level of detection in the plasma. ConclusionsSufentanil injected through microspinal catheters provided profound pain relief without impairing motor function when compared with bupivacaine. However, close monitoring remains mandatory in this setting.

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 μg/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 μg/mL−1 sufentanil and may therefore represent an alternative in epidural pain management.

Effects of a prophylactic or therapeutic application of perflubron emulsion on myocardial ischaemia-reperfusion injury in rats.

Background and objective: The efficacy of administering a perfluorochemical‐based oxygen therapeutic such as perflubron emulsion (OxygentTM) 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 6 g 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 O2 (FiO2) 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.

Safety and efficacy of spinal vs general anaesthesia in bone marrow harvesting.

Bone marrow harvesting (BMH) can be performed with either general (GA) or spinal anaesthesia (SPA). Whether SPA is advantageous in BMH and if this technique is safe for procedures performed in the prone position is still controversial. To evaluate the safety and efficacy of both anaesthetic techniques in BMH, 37 allogeneic donors (nine female, 28 male; 34.3 ± 9 years; ASA class 1–2) received either spinal (group 1, n = 20) or general anaesthesia (group 2, n = 17) according to their personal wishes. Under standardised harvesting conditions, haematology parameters, cell counts (MNC, CD34+), haemodynamic parameters, adverse reactions and patient satisfaction were registered. No differences were seen between groups with respect to demographic data, harvesting time (55 ± 17 vs 60 ± 16 min) and bone marrow cell counts (MNC: 6.68 ± 2.1 vs 5.7 ± 1.7 ml/106). The incidence of hypotension was higher in group 1 (45 vs 10.8%; P = 0.042). Postoperative analgesic requirement and emesis were increased in group 2 (P < 0.04) in comparison to group 1. in conclusion, the present study failed to show superiority of spinal over general anaesthesia with regard to the quality of the harvested bone marrow. however, the lower incidence of complaints after spinal anaesthesia appears to offer an advantage over ga in healthy allogeneic bone marrow donors.

Effects of isovolaemic haemodilution on oxygenation of liver and skeletal muscle.

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 Ringers 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.

Fast-track regional anaesthesia.

Regional anaesthesia plays an important role in day case surgery because it combines reliable effects with low risk and the possibility of local postoperative analgesia without systemic side-effects. Fast-track regional anaesthesia allows short-term postoperative surveillance or even bypassing the post-anaesthesia care unit. Peripheral nerve blocks provide long-lasting pain relief, and can accelerate timely discharge if a persisting motor block is accepted. Multiple peripheral nerve stimulation and injection techniques may help to realize differential blockades with a pronounced analgesic rather than a motor blocking effect. Nerve blocks with local anaesthetics in combination with alpha2-adrenoceptor agonists or non-steroidal anti-inflammatory drugs and short-acting parenteral opioids represent an effective multimodal concept for ambulatory surgery.

Subarachnoid Sufentanil for Early Postoperative Pain Management in Orthopedic Patients: More Disadvantages Than Benefits?

Background: Continuous spinal anesthesia is frequently used for intraoperative anesthesia but rarely for postoperative pain management. Because even small doses of local anesthetics can be associated with motor deficits, subarachnoid opioid injection may be an alternative. Methods: Eighty patients randomly received a subarachnoid injection of 10 mg sufentanil, 5 mg bupivacaine, 2.5 mg sufentanil plus 2.5 mg bupivacaine, or saline through 28-gauge spinal microcatheters for early postoperative pain relief after major lower-limb surgery (n 5 20 in each group). Hemodynamic and respiratory parameters, pain scores, and motor function were monitored, and sufentanil concentrations in plasma and cerebrospinal fluid were measured. Ten additional patients received up to three repetitive injections of 10 mg sufentanil over 24 h. Results: All drugs provided excellent pain relief within 15 min after injection, lasting 128 6 61 min with sufentanil, 146 6 74 min with bupivacaine, and 167 6 78 min with the mixture. Patients receiving bupivacaine showed the highest cephalad extension of sensory block (median, T6) and the most intense motor block, whereas patients given only sufentanil had no motor deficit. The duration of analgesia was shorter after subsequent sufentanil injection (100–115 min) than after the first injection (198 6 70 min). Six of 50 patients with sufentanil experienced a short episode of respiratory depression within 30 min after the first injection. Cerebrospinal fluid concentrations of sufentanil peaked at 5 min after injection (183 6 167 ng/ml) but were at the level of detection in the plasma. Conclusions: Sufentanil injected through microspinal catheters provided profound pain relief without impairing motor function when compared with bupivacaine. However, close monitoring remains mandatory in this setting.

Long-term follow-up study in liver resection patients receiving a haemoglobin-based oxygen carrier

Since improvement in purification of stroma-free haemoglobin solutions enables the production of cell-free oxygen carriers which are free of toxic side-effects on liver and kidneys, clinical interest in such material has been aroused during the last years. Animal models have shown that ultrapurified polymerized bovine haemoglobin (HBOC-201) is free of severe hepato-renal side-effects and provides excellent tissue oxygenation [1,2,3]. The present prospective study was designed to examine safety and tolerance of HBOC-201 applied during haemodilution in patients prior to liver resection.

Peri-operative changes of haemodynamics and oxygen transport in patients undergoing haemodilution with bovine haemoglobin

Haemodynamic reactions following infusions of haemoglobin solutions have been shown in several animal experiments and may be of clinical concern. There is some evidence that vasoconstriction is a function of impurities of haemoglobin solutions. As a consequence, purification and chemical modification of haemoglobin should reduce adverse circulatory reactions. In animal models, ultrapurified polymerized bovine haemoglobin (HBOC-201) appears to be free of severe side effects. The present prospective study investigates haemodynamic changes and oxygen transport parameters in patients undergoing pre-operative haemodilution with HBOC-201 in comparison to hetastarch.