[The use of arginine vasopressin during cardiopulmonary resuscitation. An analysis of experimental and clinical experience and a view of the future]. / Der Einsatz von Arginin Vasopressin bei der kardiopulmonalen Reanimation. Eine Analyse der experimentellen und klinischen Erfahrungen sowie ein Ausblick in die Zukunft.

The risks and benefits of epinephrine given during cardiopulmonary resuscitation (CPR) are controversially discussed. Animal experiments revealed beta-receptor-mediated adverse effects of epinephrine such as increased myocardial oxygen consumption, ventricular arrhythmia, ventilation-perfusion defects, and cardiac failure in the postresuscitation phase. In clinical studies, high-dose vs. standard-dose epinephrine was unable to improve resuscitation success. During CPR in patients, endogenous arginine vasopressin (AVP) levels were increased and surviving vs. non-surviving patients had significantly higher AVP levels. This may indicate that the human body discharges AVP during life-threatening situations as an additional vasopressor to catecholamines in order to maintain cardiocirculatory homeostasis. In different experimental CPR models, AVP compared with epinephrine given during CPR significantly improved vital organ blood flow, coronary perfusion pressure, resuscitability, and long-term survival. During prolonged CPR with repeated drug administration, AVP but not epinephrine maintained coronary perfusion pressure on a level that ensured return of spontaneous circulation. Also, AVP can be administered successfully in the intravenous dose into the endobronchial tree, and also intraosseously. When given during CPR, AVP induces a transient splanchnic hypoperfusion, and an increase in systemic vascular resistance, both of which normalized spontaneously; furthermore, an oligo-anuric state was not observed. In two clinical studies, AVP vs. epinephrine improved 24-h survival during out-of-hospital CPR, and comparable CPR outcome during in-hospital CPR. The new CPR guidelines of both the American Heart Association and the European Resuscitation Council assign a given CPR intervention into classes of recommendation [class 1 (definitely recommended), class 2 A (intervention of choice), class 2B (alternative intervention), class X (neutral), or class 3 (not recommended)]. For CPR of adults with shock-refractory ventricular fibrillation, 40 units AVP or 1 mg epinephrine is recommended (class 2B); patients with asystole or pulseless electrical activity should be resuscitated with epinephrine. AVP is not recommended for adult cardiac arrest patients with asystole or pulseless electrical activity; or pediatric cardiac arrest patients due to a lack of clinical data. Until definitive data about AVP vs. epinephrine effects during CPR are available, the present state of knowledge should be interpreted that two vasopressors are available for use instead of one.

Smoking does not alter the dose-requirements and the pharmacodynamics of rocuronium.

PURPOSE: Controversial data about the effect of smoking on the dose-requirements and the pharamcodynamics of rocuronium have been reported recently. This study was conducted to evaluate the dose-requirements and the pharmacodynamics of rocuronium in smokers using target controlled infusion. METHODS: The dose-requirements of rocuronium for 60 min relaxation, using target controlled infusion, given under intravenous anaesthesia with propofol, fentanyl and nitrous oxide was studied in 37 smokers and 37 non-smokers. Initially 450 microg x kg(-1) rocuronium were administered, neuromuscular effects were quantified by recording the single twitch response of the adductor pollicis muscle after ulnar nerve stimulation using a force transducer, and the neuromuscular block was kept at 80% by target controlled infusion throughout the procedure. RESULTS: The dose-requirements for one hour relaxation were 867 +/- 116 microg x kg(-1) x hr(-1) for smokers (S) and 839 +/- 149 microg x kg(-1) x hr(-1) for non-smokers (NS). The duration to 10% and the spontaneous recovery from 25% to 75% of the control twitch response also showed no differences between S (17.2 +/- 3.4 min, 10.6 +/- 0.9 min) and NS (18.9 +/- 4.3 min, 10.9 +/- 3.2 min), as well as maximum block, onset time and infusion rate. CONCLUSION: Smoking does not alter the dose-requirements for rocuronium and no effects on the onset time, degree of block, time to maximum block, duration 10% and spontaneous recovery index were observed.

[The effect of different priming doses on the pharmacodynamics of cisatracurium]. / Die Wirkung unterschiedlicher Primingdosierungen auf die Pharmakodynamik von Cisatracurium.

OBJECTIVE: The aim of the study was to evaluate the effect of two different priming regimen on the onset time of 100 micrograms/kg cisatracurium, when compared to bolus administration. METHODS: 51 patients were randomly assigned and received either a bolus of 100 micrograms/kg cisatracurium, or a priming dose of 10 micrograms/kg cisatracurium followed after 4 min by 90 micrograms/kg cisatracurium, or a priming dose of 15 micrograms/kg cisatracurium followed after 4 min by 85 micrograms/kg cisatracurium. The neuromuscular monitoring was performed using a mechanomyograph (Groningen II Monitor). Anaesthesia was induced with propofol and fentanyl and maintained by continuous infusion of propofol. RESULTS: The priming combination of 15 micrograms/kg cisatracurium followed after 4 min by 85 micrograms/kg cisatracurium produced a statistically significant reduction in the onset time (95% block) (180 +/- 60 s) and time to complete block (210 +/- 48 s), when compared to the bolus group (240 +/- 60 s and 288 +/- 66 s) (p < 0.05). CONCLUSION: Our data indicate that the "priming principle" is an appropriate technique to shorten the onset time of cisatracurium. To achieve a maximum effect the priming combination of 15 micrograms/kg cisatracurium followed after 4 min by 85 micrograms/kg cisatracurium is recommended.

Bacterial contamination of needles used for spinal and epidural anaesthesia.

We have investigated prospectively the incidence of bacterial contamination of 114 spinal and 20 epidural needles collected immediately after lumbar puncture of the subarachnoid or epidural space. Bacteriological examination revealed bacterial contamination of 24 (17.9%) of the needles, mainly coagulase-negative staphylococci (21; 15.7%) followed by yeasts (2; 1.5%), enterococcus (1; 0.8%), pneumococcus (1; 0.8%) and micrococcus (1; 0.8%). Our results suggest that even during aseptic puncture for lumbar anaesthesia, there is a significant rate of needle contamination.

Establishment of a pneumococcal septicemia model in the miniature swine.

Human pneumococcal septicemia, the prominent postsplenectomy complication, was as yet difficult to study in the porcine model, since this species appeared to be fairly resistant against pneumococcal infections. We have used two strains of pneumococci (serotype 1 and 6B) both of which had been isolated from patients with systemic infection and both of which were maintained in a virulent state by regular mouse passage. After challenge with 10(9) type 1 pneumococci, however, only one of the 5 pigs developed fever, none showed profound hematological alterations and each animal exhibited a rapid clearance of bacteria from peripheral blood. By contrast, challenge of 7 animals with type 6B pneumococci resulted in a slower and incomplete bacterial clearance with persistent bacteremia for up to 24 hours. All animals developed fever and a profound leukopenia with less than 5,000 leukocytes/ml and 3 of the 7 animals died after injection of type 6B pneumococci. The results show that potentially the type 6B pneumococci can be successfully employed for studies of gram positive septicemia in the miniature swine.

Splenectomy does not influence outcome of pneumococcal septicemia in a porcine model.

The existence of the overwhelming postsplenectomy infection syndrome in adults after traumatic splenectomy is controversial. Due to the similarity of the porcine immune system to man we chose the pig to study subsets of peripheral mononuclear cells after splenectomy and resistance to experimental Pneumococcal infection after splenic surgery and specific immunization. Female miniature pigs were assigned to four operative groups: sham operation, splenectomy, splenic resection, and heterotopic splenic autotransplantation. Hematologic and flow cytometric analysis of mononuclear cells and their subsets revealed a marked leukocytosis following splenectomy and autotransplantation but no significant shift in monocyte and B-cell numbers. Response of leukocytes to septicemia, bacterial elimination from peripheral blood, and mortality were not affected by splenectomy or spleen-preserving operations. Mortality of splenectomized animals was 18%, compared to 42% in sham-operated controls (difference not significant). Immunization protected animals from development of leukopenia, and led to an enhanced bacterial elimination, and a significantly decreased mortality of 5%, compared to 48% in nonimmune animals. Thus our data do not show significant effects of splenectomy on subsets of porcine mononuclear cells or on resistance to experimental Pneumococcal septicemia.

Beneficial effect of liposome-encapsulated muramyl tripeptide in experimental septicemia in a porcine model.

In a porcine model of pneumococcal septicemia, animals were pretreated with 1 mg of liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (MTP-PE) or with liposomes alone. After 24 h each animal received an injection of either 10(9) or 10(10) pneumococcal serotype 6B cells. MTP-PE pretreatment resulted in less pronounced leukocytopenia, with a nadir of 6,700 (versus 4,100) leukocytes per mm3 after injection of 10(9) bacteria and a nadir of 4,400 (versus 3,800) leukocytes per mm3 after injection of 10(10) bacteria. At the same time bacterial clearance was substantially improved by MTP-PE pretreatment. Finally, pretreatment with MTP-PE dramatically reduced mortality; the average death rates for both series of animals used were 55% for liposome-pretreated animals and 3% for animals pretreated with MTP-PE-containing liposomes. These results in a preclinical model suggest that treatment with MTP-PE-containing liposomes might be beneficial in controlling septicemia in patients at risk.