R. Waurick

Inhaled prostaglandin E1 for treatment of acute lung injury in severe multiple organ failure

Acute lung injury is characterized by hypoxemia due to pulmonary ventilation/perfusion-mismatching. IV administered prostaglandin E1 (PGE1), a vasodilator with a high pulmonary clearance, has been studied in acute lung injury. Inhalation of the vasodilators nitric oxide and prostacyclin improved oxygenation by selective dilation of the pulmonary vasculature in ventilated lung areas. In the present study, PGE1 inhalation was used for treatment of acute lung injury. Fifteen patients with acute lung injury defined as PaO2/fraction of inspired oxygen (FIO2) <160 mm Hg were treated with PGE1 inhalation in addition to standard intensive care. The drug was continuously delivered via a pneumatic nebulizer. Acute physiology and chronic health evaluation system II and multiple organ failure scores were (mean +/- SEM) 33 +/- 2 and 10 +/- 0.3, respectively. Inhaled PGE1 was administered for 103 +/- 17 h at a dose of 41 +/- 2 [micro sign]g/h. The PaO2/FIO2 ratio increased from 105 +/- 9 to 160 +/- 17 mm Hg (P < 0.05) and to 189 +/- 25 mm Hg (P < 0.05) after 4 h and 24 h, respectively. PGE1 inhalation decreases in mean pulmonary artery pressure and central venous pressure were not statistically significant. Mean arterial pressure, pulmonary capillary wedge pressure, cardiac output, and heart rate remained unchanged. Intensive care unit mortality was 40%. The present data suggest that inhaled PGE (1) is an effective therapeutic option for improving oxygenation in patients with acute lung injury. Whether inhaled PGE1 will increase survival in acute lung injury should be investigated in a controlled prospective trial. Implications: In patients with severe acute lung injury and multiple organ failure, inhaled prostaglandin E1 improved oxygenation and decreased venous admixture without affecting systemic hemodynamic variables. Controlled clinical trials are warranted. (Anesth Analg 1998;86:753-8)

Comparison of the haemodynamic effects of nitric oxide synthase inhibition and nitric oxide scavenging in endotoxaemic sheep

Objective: The present study compared the effects of nitric oxide (NO) synthase inhibition and NO scavenging with haemoglobin in endotoxaemic sheep. Design: 12 sheep were instrumented for chronic study. Six sheep received lG-nitro-arginine-methylester (l-NAME, 2.5 mg/kg bolus followed by a continuous infusion of 0.5 mg/kg per h), the other 6 sheep received pyridoxalated haemoglobin polyoxyethylene conjugate (PHP, 100 mg/kg bolus followed by a continuous infusion of 20 mg/kg per h). Measurements and results: Haemodynamic and oxygenation parameters were measured in healthy sheep, after infusion of Salmonella typhosa endotoxin (10 ng/kg per min) for 24 h and after infusion of l-NAME or PHP. The infusion of endotoxin resulted in a hypotensive, hyperdynamic circulation. Infusion of l-NAME increased mean arterial pressure (MAP) from 76.1 ± 4.2 mmHg to normal values of 95.8 ± 5.7 mmHg (p < 0.05). PHP increased MAP from 73.0 ± 3.0 to 88.6 ± 4.7 mmHg (p < 0.05). This increase in MAP was associated in the l-NAME group with a more prominent drop in cardiac index (from 10.2 ± 0.4 to 7.0 ± 0.5 l · min–1· m–2; p < 0.05) than in the PHP group (from 10.7 ± 0.2 to 9.3 ± 0.6 l · min–1· m–2). During the first 90 min of infusion, cardiac index remained lower in the l-NAME group than in the PHP group. The increase in pulmonary vascular resistance was also higher in the l-NAME group. Conclusion: These results suggest, that at the doses used in the experiment, NO scavenging with PHP has smaller effects on cardiac index and pulmonary vascular resistance than NO synthase inhibition with l-NAME. Therefore, the concept of NO scavenging in hyperdynamic sepsis should be further evaluated.

Effect of 2,3-butanedione monoxime on force of contraction and protein phosphorylation in bovine smooth muscle

Abstract The aim of the study was to investigate the effects of the putative protein phosphatase (PP) activator 2,3-butanedione monoxime (BDM) in vascular smooth muscle. BDM concentration-dependently increased PP activity in homogenates of bovine coronary arteries and led to dephosphorylation of various smooth muscle proteins in 32P-labelled bovine aortic smooth muscle cells. In isolated bovine coronary artery rings (CARs) the effects of 10 mmol/l BDM on force of contraction (FOC) under conditions of depolarization by 75 mmol/l KCl and PP inhibition by 100 μmol/l cantharidin were investigated. At the end of contraction experiments CARs were freeze-clamped and myosin light chain (MLC20) phosphorylation was determined by two-dimensional gel electrophoresis. Pretreatment of CARs with BDM reduced KCl-induced FOC to 42 ± 4% vs. 118 ± 1% (no BDM) and cantharidin-induced FOC to 102 ± 2% vs. 120 ± 7% (no BDM) compared to a former KCl contraction (= 100%). Moreover, BDM increased the amount of unphosphorylated MLC20 up to 56 ± 2% vs. 36 ± 5% (no BDM) and 28 ± 2% vs. 21 ± 1% (no BDM), respectively, demonstrating the central role of MLC20 phosphorylation in initiating smooth muscle contraction. In KCl precontracted CARs BDM decreased FOC to 47 ± 4% vs. 100 ± 1% (no BDM) but did not affect MLC20 phosphorylation, suggesting an uncoupling of force maintenance and MLC20 phosphorylation. In contrast, BDM neither affected FOC nor MLC20 phosphorylation in CARs precontracted with cantharidin. These results strengthen the hypothesis that PP activation by BDM only occurs on the holoenzyme level, e.g. by affecting regulatory subunits.

Haemodynamic effects of dopexamine and nitric oxide synthase inhibition in healthy and endotoxaemic sheep.

Chronically instrumented awake healthy sheep (n = 6) received the synthetic catecholamine, dopexamine, during or without a background infusion of the nitric oxide synthase inhibitor. L-nitro-arginine-methylester (L-NAME). Three days later, hypotensive-hyperdynamic circulation was induced and maintained by continuous infusion of Salmonella typhosa endotoxin (10 ng/kg per min). After 24 h of continuous endotoxin infusion, the dopexamine L-NAME protocol was repeated. In healthy and endotoxaemic animals with and without nitric oxide synthase inhibition dopexamine caused the same haemodynamic changes: heart rate and cardiac output increased, mean arterial pressure and systemic vascular resistance decreased. L-NAME infusion induced normalisation of the hypotonic-hyperdynamic circulation in endotoxaemic animals. Dopexamine reduced some adverse effects of L-NAME treatment, like increased pulmonary vascular resistance and decreased oxygen delivery. In conclusion the haemodynamic effects of dopexamine are independent of the amount of nitric oxide production. Dopexamine may attenuate some of the adverse effects of nitric oxide synthase inhibition.

Effects of sympathetic nerve blockade on vasoconstrictive properties of nitric oxide synthase inhibition in sheep

OBJECTIVE Inhibition of nitric oxide synthase causes intense vasoconstriction. This effect is thought to be dependent on sympathetic nerve activity. Thus, we investigated the vasoconstrictive effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in sheep, in which a reversible sympathetic block was established by thoracic epidural anesthesia. METHODS Sheep (n = 11) were surgically prepared for chronic study. After at least 5 days of recovery, L-NAME was continuously administered and hemodynamics were monitored. This was done in sheep with and without sympathetic blockade in randomized order. RESULTS The vasoconstrictive effects of L-NAME were similar in sheep with and without sympathetic blockade. CONCLUSION The obtained results suggest that the vasoconstrictive properties of nitric oxide synthase inhibitors are independent of sympathetic tone.

Therapeutic administration of thoracic epidural anesthesia reduces cardiopulmonary deterioration in ovine pulmonary embolism.

Objective:It was hypothesized that sympathetic blockade restricted to the thoracic levels and achieved by thoracic epidural anesthesia might be capable of reducing hemodynamic deterioration after pulmonary artery embolism and that this might represent a potential method of treatment in patients with pulmonary embolism. Cardiopulmonary function after pulmonary embolism was therefore studied in sheep, either without a sympathetic blockade (the control group) or with sympathetic blockade. Design:Prospective, randomized laboratory investigation. Setting:University research laboratory. Subjects:Twelve adult, chronically instrumented Blackhead ewes. Interventions:Pulmonary embolization was achieved by injecting autologous blood clots (0.75 mL/kg) intravenously into an external jugular vein. The treatment group (n = 6) received 6 mL of 0.175% bupivacaine and the control group (n = 6) received 6 mL of 0.9% NaCl 90 mins after the embolization procedure. The injections were made via an epidural catheter (at the level of T3). Results were considered to be statistically significant (with analysis of variance) at p < .05. Measurements and Main Results:After epidural administration of bupivacaine in the thoracic epidural anesthesia group, the mean pulmonary artery pressure and heart rate were significantly reduced and the stroke volume index was significantly higher in comparison with the control group, in which the animals received epidural injections of saline. Conclusions:Thoracic epidural anesthesia administered after the occurrence of pulmonary artery embolism thus significantly reduces hemodynamic deterioration in awake, spontaneously breathing sheep and may represent an additional option in the treatment of pulmonary embolism.

Oberarmkorrekturosteotomie bei einem Patienten mit McCune-Albright-Syndrom unter perivaskulärer axillärer Plexusanästhesie nach Weber

We report on a 20-year-old patient with McCune-Albright syndrome suffering from global respiratory insufficiency who required continuous mask ventilation and where intubation had to be avoided. Perivascular axillary anesthesia according to Weber was performed for a double corrective osteotomy of the humerus. During plexus anesthesia the patient was positioned on the non-anesthesized side in a 15 degrees Trendelenburg position. An extension of analgesia was observed up to the complete upper arm region. Using the modified positioning an extension of brachial plexus anesthesia is possible.ZusammenfassungBei einem 20-jährigen Patienten mit McCune-Albright-Syndrom und respiratorischer Globalinsuffizienz mit Dauermaskenbeatmung musste eine Intubationsnarkose vermieden werden. Zur operativen Korrektur einer schwergradigen Oberarmfehlstellung erfolgte eine perivaskuläre axilläre Plexusanästhesie nach Weber. Mit der Lagerung des Patienten auf die nichtbetroffene Seite und Kopftieflagerung von 15° (modifizierte Lagerungstechnik) konnte eine Ausbreitung der Analgesie bis auf die Oberarmregion erreicht werden.AbstractWe report on a 20-year-old patient with McCune-Albright syndrome suffering from global respiratory insufficiency who required continuous mask ventilation and where intubation had to be avoided. Perivascular axillary anesthesia according to Weber was performed for a double corrective osteotomy of the humerus. During plexus anesthesia the patient was positioned on the non-anesthesized side in a 15° Trendelenburg position. An extension of analgesia was observed up to the complete upper arm region. Using the modified positioning an extension of brachial plexus anesthesia is possible.

Oberarmkorrekturosteotomie bei einem Patienten mit McCune-Albright-Syndrom unter perivaskulärer axillärer Plexusanästhesie nach Weber@@@Corrective osteotomy of the humerus using perivascular axillary anesthesia according to Weber in a patient suffering from McCune-Albright syndrome

We report on a 20-year-old patient with McCune-Albright syndrome suffering from global respiratory insufficiency who required continuous mask ventilation and where intubation had to be avoided. Perivascular axillary anesthesia according to Weber was performed for a double corrective osteotomy of the humerus. During plexus anesthesia the patient was positioned on the non-anesthesized side in a 15 degrees Trendelenburg position. An extension of analgesia was observed up to the complete upper arm region. Using the modified positioning an extension of brachial plexus anesthesia is possible.ZusammenfassungBei einem 20-jährigen Patienten mit McCune-Albright-Syndrom und respiratorischer Globalinsuffizienz mit Dauermaskenbeatmung musste eine Intubationsnarkose vermieden werden. Zur operativen Korrektur einer schwergradigen Oberarmfehlstellung erfolgte eine perivaskuläre axilläre Plexusanästhesie nach Weber. Mit der Lagerung des Patienten auf die nichtbetroffene Seite und Kopftieflagerung von 15° (modifizierte Lagerungstechnik) konnte eine Ausbreitung der Analgesie bis auf die Oberarmregion erreicht werden.AbstractWe report on a 20-year-old patient with McCune-Albright syndrome suffering from global respiratory insufficiency who required continuous mask ventilation and where intubation had to be avoided. Perivascular axillary anesthesia according to Weber was performed for a double corrective osteotomy of the humerus. During plexus anesthesia the patient was positioned on the non-anesthesized side in a 15° Trendelenburg position. An extension of analgesia was observed up to the complete upper arm region. Using the modified positioning an extension of brachial plexus anesthesia is possible.

Periphere Nervenblockaden: mehr Fragen als Antworten?

Mehrere Faktoren haben in den vergangenen Jahren zu einem neu erwachten Interesse an der Regionalanästhesie und an peripheren Nervenblockaden geführt. Abgesehen von ihrem humanitären Charakter hat die Schmerztherapie durch das erweiterte Wissen um die Bedeutung des Schmerzes bzw. der Schmerzfreiheit für kardiovaskuläre Komplikationen und das Outcome operativer Patienten einen neuen Stellenwert erfahren; die Schmerztherapie ist mehr denn je integraler Bestandteil unseres Fachgebietes. Die Vorteile der peripheren Nervenblockaden gegenüber der Allgemeinanästhesie bestehen in einer besseren Analgesie, dem Vermeiden von postoperativer Übelkeit und fehlender Schläfrigkeit. Für Eingriffe an der unteren Extremität lassen sich gegenüber rückenmarknahen Regionalanästhesieverfahren die geringeren hämodynamischen Auswirkungen, die fehlende Blasenentleerungsstörung und die Umgehung der Gefahr von schwerwiegenden Komplikationen (epidurales Hämatom, epiduraler Abszess) aufführen. Die peripheren Nervenblockaden in Kathetertechnik können eine effektive und sichere perioperative Schmerztherapie ermöglichen. Modifikationen der Punktionstechniken und die obligate Verwendung des Nervenstimulators haben die Komplikationsund Versagerquote vermindert. In der eigenen Klinik haben wir vor etwa zwei Jahren begonnen, vermehrt periphere Nervenblockaden, zumeist in Kathetertechnik, durchzuführen. In der täglichen Praxis tauchen immer neue Fragen auf, die durch die publizierten und die durch den eigenen Schmerztherapiedienst erhobenen Daten noch nicht sicher beantwortet werden konnten. Zum einen Fragen zur Technik der Katheteranlage und -pflege: