T. Standl

Bovine haemoglobin is more potent than autologous red blood cells in restoring muscular tissue oxygenation after profound isovolaemic haemodilution in dogs

PurposeThis study compares the effects of stored red cells, freshly donated blood and ultrapurified polymerized bovine haemoglobin (HBOC) on haemodynamic variables, oxygen transport capacity and muscular tissue oxygenation after acute and almost complete isovolaemic haemodilution in a canine model.MethodsFollowing randomization to one of three groups, 24 anaesthetized Foxhounds underwent isovolaemic haemodilution with 6% hetastarch to haematocrit levels of 20%, 15% and 10% before they received isovolaemic stepwise augmentation of 1 g · dl−1 haemoglobin. In Group 1, animals were given autologous stored red cells which they had donated three weeks before. In Group 2, animals received freshly donated blood harvested during haemodilution. In Group 3, animals were infused with HBOC. Skeletal muscle tissue oxygen tension was measured with a polarographic 12 μ needle probe.ResultsIn all groups, heart rate and cardiac index were increased with decreasing vascular resistance during haemodilution (P < 0.05). Haemodynamic variables showed a reversed trend during transfusion when compared to haemodilution but remained below baseline (P < 0.05). Arterial and venous oxygen content were changed in parallel to changes of haematocrit and haemoglobin concentrations but were lower in Group 3 than in Groups 1 and 2 (P < 0.05) during transfusion. In contrast, the oxygen extraction ratio was higher in Group 3 (59 ± 8%, P < 0.01) at the end of transfusion than in Group 1 (37 ± 13%) and 2 (32 ± 5%). In Group 3, mean tissue oxygen tension increased from 16 ± 5 mmHg after haemodilution to 56 ± 11 mmHg after transfusion (P < 0.01) and was higher than in Group 1 (41 ± 9, P < 0.01) and Group 2 (29 ± 11, P < 0.01). While in Group 3 an augmentation of 0.7 g · dl−1 haemoglobin resulted in restoring baseline tissue oxygenation, higher doses of 2.7 g · dl−1 and 2.1 g · dl−1 were needed in Groups 1 and 2 to reach this level (P < 0.01).ConclusionThe results show a higher oxygenation potential of HBOC than with autologous stored red cells because of a more pronounced oxygen extraction.RésuméObjectifCette étude compare les effets des hématies conservées, du sang fraîchement prélevé et de l’hémoglobine bovine polymérisée ultrapurifiée (HBOC) sur les variables hémodynamiques, la capacité de transport en oxygène et l’oxygénation du tissu musculaire après hémodilution isovolémique aiguë et presque complète sur un modèle canin.MéthodesAprès randomisation en trois groupes, 24 fox-hounds ont subi, une hémodilution isovolémique en paliers avec de l’hétastarch à 6% pour réaliser des hématocrites de 20%, 15% et 10% avant de recevoir une augmentation iso-volémique en paliers de 1 g · dl−1 d’hémoglobine. Dans le groupe 1, les chiens ont reçu les hématies autologues conservées prélevées trois semaines auparavant. Dans le groupe 2, les animaux ont reçu de sang frais recueilli au moment de l’hémodilution. Dans le groupe 3, les animaux ont été perfusés avec HBCO. La tension en oxygène du tissus musculaire a été mesurée avec une sonde polarographique.RésultatsDans tous les groupes, la fréquence et l’index cardiaques ont augmenté avec la baisse de la résistance vasculaire pendant l’hémodilution (P < 0,05). Pendant la transfusion, les variables hémodynamiques ont révélé une tendance inverse de celle de l’hémodilution mais sont demeurées sous la ligne de base (P < 0,05). Pendant la transfusion, les contenus artériels et veineux eh oxygène ont changé parallèlement aux changements de l’hématocrite et de la concentration de l’hémoglobine mais étaient plus bas dans le groupe 3 que dans les groupes 1 et 2 (P < 0,05). Par contre, à la fin de la transfusion, l’extraction de l’oxygène a été plus grande dans le groupe 3 (59 ± 8%, P < 0,01) que dans les groupes 1 (37 ±13%) et 2 (31 ± 5%). Dans le groupe 3, après la transfusion, la tension tissulaire moyenne en oxygène a augmenté de 16 ±5 mmHg à 56 ± 11 mmHg (P < 0,01) et était plus élevée que dans les groupes 1(41 ± 9, P < 0,01) et 2 (29 ± 11,P < 0,01). Alors que dans le groupe 3, une augmentation de 0,7 g · dl−1 a permis de ramener l’oxygénation tissulaire à la ligne de base, des quantités plus grandes (2,7 g · dl−1 et de 2,2 g · dl−1) ont été requises pour atteindre ce niveau dans les groupes 1 et 2.ConclusionCes résultats montrent un potentiel d’oxygénation plus élevé avec HBCO qu ’avec des hématies autologues conservées en raison d’une extraction plus prononcée de l’oxygène.

Active warming during cesarean delivery.

We tested the hypothesis that 15 min of forced-air prewarming, combined with intraoperative warming, prevents hypothermia and shivering in patients undergoing elective cesarean delivery. We simultaneously tested the hypothesis that maintaining maternal normothermia increases newborn temperature, umbilical vein pH, and Apgar scores. Thirty patients undergoing elective cesarean delivery were randomly assigned to forced-air warming or to passive insulation. Warming started 15 min before the induction of epidural anesthesia. Core temperature was measured at the tympanic membrane, and shivering was graded by visual inspection. Patients evaluated their thermal sensation with visual analog scales. Rectal temperature and umbilical pH were measured in the infants after birth. Results were compared with unpaired, two-tailed Student’s t-tests and &khgr;2 tests. Core temperatures after 2 h of anesthesia were greater in the actively warmed (37.1°C ± 0.4°C) than in the unwarmed (36.0°C ± 0.5°C;P < 0.01) patients. Shivering was observed in 2 of 15 warmed and 9 of 15 unwarmed mothers (P < 0.05). Babies of warmed mothers had significantly greater core temperatures (37.1°C ± 0.5°C vs 36.2°C ± 0.6°C) and umbilical vein pH (7.32 ± 0.07 vs 7.24 ± 0.07).

Wound Infiltration and Drain Lavage with Ropivacaine After Major Shoulder Surgery

UNLABELLED Subcutaneous infiltration and wound lavage with ropivacaine is an alternative to opioids after major shoulder surgery. However, the efficacy and potential toxicity of this method remain unclear. We therefore evaluated plasma ropivacaine concentrations after shoulder infiltration and wound lavage. We subsequently quantified the efficacy of two ropivacaine concentrations. Patients undergoing major shoulder surgery were anesthetized with alfentanil and propofol. The initial patients (n = 18) received ropivacaine 7.5 mg/mL and ropivacaine plasma concentrations were measured in 15-min intervals. The subsequent 45 patients were randomly assigned to: 1) isotonic saline, 2) 3.75 mg/mL ropivacaine, or 3) 7.5 mg/mL ropivacaine. Ten milliliters of each solution was administered subcutaneously and 20 mL was injected into the wound drain which was clamped for 10 min. Supplemental postoperative pain relief was provided by patient-controlled anesthesia using the opioid piritramid (3.5-mg boluses, 6-min lock-out). Postoperative pain scores were recorded on a 100-mm visual analog scale for 4 h in the initial patients and for 10 h in the second part of the study. Unbound ropivacaine plasma concentrations peaked after 15 min at 0.08+/-0.09 microg/mL; the maximum was 0.30 microg/mL, compared with a toxic threshold of 0.6 microg/mL. In the second part of the study, pain scores were significantly lower after 3.75 mg/mL (20+/-15 mm) or 7.5 mg/mL (10+/-9 mm) ropivacaine than saline (35+/-10 mm). Piritramid requirements differed significantly in the three groups, being highest with saline and lowest with ropivacaine 7.5 mg/mL. We conclude that wound infiltration and lavage with 30 mL ropivacaine 7.5 mg/mL after major shoulder surgery resulted in very low pain scores and opioid requirement. IMPLICATIONS Wound infiltration and lavage with 30 mL ropivacaine 7.5 mg/mL after major shoulder surgery resulted in very low pain scores and opioid requirement.

Pulmonary embolism caused by polymethylmethacrylate during percutaneous vertebroplasty in orthopaedic surgery

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.

Haemodynamic changes and skeletal muscle oxygen tension during complete blood exchange with ultrapurified polymerized bovine haemoglobin.

Objective: The study investigates the effect of continuous blood exchange with ultrapurified, polymerized bovine haemoglobin (UPBH) in comparison to hetastarch on haemodynamics, oxygen transport and skeletal muscle oxygen tension in a canine model. Design: Sixteen anaesthetized beagle dogs underwent haemodilution with lactated Ringers to a starting haematocrit of 20 % followed by progressive blood exchange with 6 % hetastarch 200,000/0.5 (HES, group 1) or UPBH (haemoglobin 13 ± 1 g · dl−1, molecular weight (MW) 32–500,000, group 2) to haematocrit target levels of 15 %, 10 % and 5 % or less. Measurements and results: Besides haemodynamics, skeletal muscle tissue oxygen tension (tPO2) was measured using a polarographic needle probe. In HES-treated animals, heart rate, cardiac output and blood flow were higher while systemic vascular resistance, systemic and regional arterio-venous oxygen difference (avDO2) and oxygen extraction ratios were lower when compared to the UPBH group. In spite of a higher final haematocrit of 5 % in group 1, in comparison to group 2 with 2 %, final muscular oxygen uptake (4.7 ± 4 vs 10.1 ± 2 ml · min−1) and mean tPO2 (11.8 ± 2.3 vs 51.1 ± 2.9 mm Hg) were lower in group 1 than in group 2. While tPO2 histograms were continuously shifted to lower oxygen tensions during progressive haemodilution with HES, UPBH-exchanged animals showed tPO2 histograms shifted to higher values than baseline. Conclusion: In spite of vasoconstriction, UPBH provided more haemodynamic stability and enhanced skeletal muscle tPO2 during progressive blood exchange when compared to HES.

Postoperative complaints after spinal and thiopentone-isoflurane anaesthesia in patients undergoing orthopaedic surgery Spinal versus general anaesthesia

Background. The present prospective study investigates the impact of a standardized technique of spinal and general anaesthesia on the incidence and consequences of postanaesthetic complaints dependent on age and sex of patients.

Haemoglobin-based erythrocyte transfusion substitutes.

Concerns about the infectious and immunosuppressive risks of allogeneic blood products persist, and the increased disproportion of blood donation and consumption has reinforced the search for alternative erythrocyte transfusion strategies in recent years. With the absence of problems such as nephro-toxicity, increased colloid osmotic pressure and sudden renal clearance, modern haemoglobin based oxygen carriers (HBOC) have shown their effectiveness and tolerability in numerous animal and several clinical studies. HBOC can be infused without prior cross-matching and are now available as stable formulations with long shelf-life. Most clinical studies have been performed with human cross-linked haemoglobin (DCLHb) but all trials were stopped two years ago because of an increased mortality in two clinical trials in patients who received DCLHb after stroke and multiple injury shock. However, experimental trials in animals are in progress with DCLHb and recombinant human haemoglobin. In contrast, Phase III studies with polymerised bovine haemoglobin (HBOC-201) are finished or currently under evaluation showing that infusion of HBOC-201 can avoid or reduce allogeneic blood transfusion needs in specific peri-operative settings. As a consequence, HBOC-2001 was actually approved for treatment of peri-operative anaemia in elective adult surgical patients in South Africa. Other human or bovine haemoglobin solutions are currently being investigated in different clinical studies in cardiac surgery patients, sepsis and tumour patients. More recent investigations have shown that HBOC are not only simple erythrocyte transfusion substitutes but highly effective oxygen donators in terms of tissue oxygenation. HBOC open the door for a new therapeutic strategy: plasmatic oxygen delivery with physiological concentrations of inspired oxygen. In specific situations (e.g., ischaemia or arterial stenosis) HBOC have advantages over red blood cells because they can reach post-stenotic or poorly perfused tissues with the plasma stream, where erythrocytes are not able to pass. In addition to significant plasmatic oxygen transport, HBOC also enhance tissue oxygenation because of the facilitated oxygen release by HBOC and from remaining erythrocytes. Further studies will show, if the outcome of patients with impaired perfusion (e.g., stroke or myocardial infarction) can be improved by prophylactic or therapeutic application of HBOC. Whenever these formulations are globally launched, they will find differential indications as potent oxygen-delivering drugs in addition to the globally recognised goal of red cell substitutes in cases of bleeding.

A directional needle improves effectiveness and reduces complications of microcatheter continuous spinal anaesthesia

The present prospective randomized study compares the impact of two different spinal needle designs — non-directional versus directional — on the effectiveness of continuous spinal anaesthesia provided via a microcatheter in orthopaedic patients. Using the midline approach, a 28-gauge spinal catheter was inserted either through a 22-gauge Quincke needle (nondirectional, Group 1, n = 21) or a 22-gauge Sprotte needle (directional, Group 2, n = 21) under standardized conditions. The incidence of technical difficulties and postoperative complaints, onset time of analgesia at the level of T10 and dose requirement of plain bupivacaine 0.5% were recorded. Postoperatively, the subarachnoid position of the catheters was radiographically evaluated. There was a higher incidence of technical problems during catheter insertion in Group 1 compared with Group 2 (71% vs 19%, P < 0.05). Onset time of analgesia was shorter (P < 0.05) and anaesthetic dose requirement was lower in patients in Group 2 than in Group 1. While 40% of the catheters were found in a caudal position in Group 1, all catheters were in a cranial position or at the level of the puncture site in Group 2 (P < 0.05). There was no difference in the incidence of postoperative complaints between the groups. The faster onset of analgesia and lower dose requirement of local anaesthetics associated with a lower incidence of technical problems suggest that there is greater effectiveness and safety when microcatheters are inserted using directional needles rather than non-directional needles.RésuméCette élude randomisée compare en chirurgie orthopédique l’impact de deux modèles d’aiguille rachidienne — non directionnel versus directionnel — au regard de l’efficacité de la rachianesthésie continue réalisée avec un microcathéter. Par approche médiane, une cathéter rachidien 28 G est inséré à travers une aiguille Quincke 22G (modèle non-directionnel, Groupe 1, n = 21) ou Sprotte 22G (modèle directionnel, Groupe 2, n = 21) sous des conditions standardisées. On enregistre l’incidence des difficultés d’ordre technique et des doléances postopératoires, le délai de l’installation de l’analgésie au niveau T10 et la dose requise de bupivacaïne 0,5%. Après la chirurgie, la position sous-arachnoïdienne du cathéter est déterminée par radiographie. L’incidence des problèmes d’ordre technique au moment de l’insertion du cathéter est plus élevée dans le Groupe 1 que dans le Groupe 2 (71% vs 19% P < 0,05). L’installation de l’analgésie est plus courte (P < 0,05) et la dose anesthésique requise est plus basse dans le Groupe 2 que dans le Groupe 1. Alors que 40% des cathéters se retrouvent en position caudale dans le Groupe 1, tous les cathéters du Groupe 2 se retrouvent en position céphalique ou au niveau de la ponction dans le Groupe 2 (P < 0,05). L’incidence des doléances postopératoires est la même pour les deux groupes. Le plus court délai d’installation de l’analgésie et la diminution de la dose nécessaire d’anesthésique local associés à l’incidence moindre de problèmes techniques suggèrent que la sécurité et l’efficacité sont supérieures quand des microcathéters sont insérés à l’aide d’aiguilles directionnelles plutôt que non directionnelles.

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.

Elevated plasma concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine predict adverse events in patients undergoing noncardiac surgery.

Objective:In patients with cardiovascular disease or organ failure, elevated plasma concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) are associated with an increased risk of future cardiovascular events. We aimed to investigate elevated plasma ADMA concentrations as a prospective risk marker for adverse events in patients undergoing noncardiac surgery. Design:Prospective observational study. Setting:Two tertiary care centers. Patients:Four hundred and two patients scheduled for elective noncardiac surgery. Interventions:None. Measurements and Main Results:Patients were followed for 30 days after surgery for a predefined composite end point (death, myocardial infarction/acute coronary syndrome, acute heart failure, severe arrhythmia, embolism, or thrombosis). Plasma ADMA concentrations at baseline were determined by high-performance liquid chromatography. ADMA was only weakly (−0.2 < &tgr; < 0.2) correlated with other risk markers and risk scores. In univariate logistic regression, per 0.1-&mgr;mol/L increment in plasma ADMA concentration, the odds ratio to experience the primary end point increased by 1.26 (95% confidence interval 1.10–1.45, p = .001). In a multivariate logistic regression model adjusting for age, gender, current smoking, plasma creatinine, hypertension, diabetes, ischemic heart disease, highly sensitive C-reactive protein, revised cardiac risk index, type of surgery, high-risk surgery, ASA class, and study center, ADMA was found to be an independent risk marker. The odds ratio to experience the primary end point was 1.33 (95% confidence interval 1.12–1.59, p = .001) per 0.1-&mgr;mol/L increase in the plasma ADMA concentration. Conclusions:Elevated plasma ADMA concentrations are independently associated with a higher risk for adverse events in the peri- and postoperative periods.