These in vitro results demonstrate that hydroxythyl starches especially compromise clot polymerisation. The new preparation HES 130/0.4 seems to inhibit platelet function to a lesser extent than hydroxyethyl starch preparations with a higher molecular weight and degree of substitution.

We have investigated the effects of isoflurane and desflurane on neurological outcome in a rat model of incomplete cerebral ischaemia. We studied 40 non-fasted male Sprague-Dawley rats, anaesthetized, intubated and ventilated mechanically with isoflurane and nitrous oxide in oxygen (FlO2 0.3). Arterial and venous catheters were inserted for measurement of arterial pressure, drug administration and blood sampling. A biparietal electroencephalogram (EEG) was recorded continuously using subdermal platinum electrodes. At completion of surgery, administration of isoflurane was discontinued (with the exception of those animals receiving isoflurane as treatment) and rats were allowed an equilibration period of 30 min according to the following procedure: group 1 (n = 10), 66% nitrous oxide in oxygen and fentanyl (bolus 10 micrograms kg-1 i.v. followed by infusion at a rate of 25 micrograms kg-1 h-1); group 2 (n = 10), 1.0 MAC of isoflurane in oxygen (FlO2 0.3) and air; groups 3 and 4 (n = 10 per group), 1.0 MAC or 1.5 MAC of desflurane in oxygen (FlO2 0.3) and air, respectively. Ischaemia was produced by combined unilateral common carotid artery ligation and haemorrhagic hypotension to 35 mm Hg for 30 min. Functional neurological deficit was evaluated for 3 days after cerebral ischaemia. At baseline, brain electrical activity was higher with fentanyl-nitrous oxide, 1.0 MAC of isoflurane and 1.0 MAC of desflurane (groups 1-3) compared with 1.5 MAC of desflurane (group 4). Neurological outcome was improved in isoflurane and desflurane anaesthetized animals (groups 2-4), regardless of the concentration used compared with fentanyl-nitrous oxide anaesthesia (group 1). The increase in plasma epinephrine and norepinephrine concentrations during ischaemia was significantly higher in fentanyl-nitrous oxide anaesthetized animals (group 1) compared with animals who received volatile anaesthetics (groups 2-4). These data suggest that cerebral protection produced by isoflurane and desflurane appears to be related to reduction in sympathetic activity rather than suppression of cerebral metabolic rate.

No abstract

572CAN J ANESTH 2000 / 47: 6 / pp [572][573][574][575][576][577][578] Purpose: To determine the effects of the non-competitive NMDA-receptor antagonist S(+)-ketamine on neurological outcome in a rat model of incomplete cerebral ischemia. Methods: Thirty rats were anesthetized, intubated and mechanically ventilated with isoflurane, O 2 30% and nitrous oxide 70%. Following surgery animals were randomly assigned to one of the following treatment groups: Rats in group 1 (n=10, control) received fentanyl (bolus: 10 µg·kg -1 iv; infusion 25 µg·kg -1 ·h -1 ) and N 2 O 70% / O 2 . Rats in group 2 (n=10) received O 2 30% in air and low-dose S(+)-ketamine (infusion: 0.25 mg·kg -1 ·min -1 ). Rats in group 3 (n=10) received O 2 30% in air and high-dose S(+)-ketamine (infusion: 1.0 mg·kg -1 ·min -1 ). Following 30 min equilibration period ischemia was induced by combined unilateral common carotid artery ligation and hemorrhagic hypotension to 35 mmHg for 30 min. Plasma catecholamines were assayed before and at the end of ischemia. Neurological deficit was evaluated for three postischemic days. Results: Neurological outcome was improved with high-dose S(+)-ketamine when compared to fentanyl / N 2 O -anesthetized controls (9 vs 1 stroke related deaths, P < 0.05). Increases in plasma catecholamine concentrations were higher in fentanyl / N 2 O -anesthetized (adrenaline baseline 105.5 ± 92.1 pg·ml -1 , during ischemia 948 ± 602.8 pg·ml -1 , P < 0.05; noradrenaline baseline 407± 120.2 pg·ml -1 , ischemia 1267 ± 422.2 pg·ml -1 , P < 0.05) than in high-dose S(+)-ketamine-treated animals (adrenaline baseline 71 ± 79.5 pg·ml -1 , ischemia 237 ± 131.9; noradrenaline baseline 317.9 ± 310.5 pg·ml -1 , ischemia 310.5 ± 85.7 pg·ml -1 ). Conclusion: Neurological outcome is improved following incomplete cerebral ischemia with S(+)-ketamine. Decreases in neuronal injury may be related to suppression of sympathetic discharge. Résultats : L'évolution neurologique a été meilleure avec de fortes doses de S(+)-kétamine qu'avec l'alfentanyl / N 2 O (9 vs 1 décès reliés à un accident ischémique cérébral, P < 0,05). L'augmentation des concentrations plasmatiques de catécholamines a été plus marquée avec l'alfentanyl / N 2 O (l'adrénaline de base à 105,5 ± 92,1 pg·ml -1 ; pendant l'ischémie, 948 ± 602,8 pg·ml -1 , P < 0,05; la noradrénaline de base à 407± 120,2 pg·ml -1 ; pendant l'ischémie, 1267 ± 422,2 pg·ml -1 , P < 0,05) qu'avec de fortes doses de S(+)-kétamine (l'adrénaline de base à 71 ± 79,5 pg·ml -1 ; pendant l'ischémie, 237 ± 131,9; la noradrénaline de base à 317,9 ± 310,5 pg·ml -1 ; pendant l'ischémie, 310,5 ± 85,7 pg·ml -1 ). Conclusion : L'utilisation de S(+)-kétamine permet une évolution neurologique supérieure après une ischémie cérébrale incomplète. Cette situation peut être reliée à la suppression de décharge sympathique.

No abstract

Acute normovolemic hemodilution (ANH) may help to reduce demand for homologous blood but requires extra time and apparatus. A more simple procedure is acute hypervolemic hemodilution (HHD), where hydroxyethylstarch is administered preoperatively without removal of blood. In a prospectively randomized study we compared ANH (preoperatively 15 mL/kg autologous blood removal and replacement with 15 mL/kg of hydroxyethylstarch with HHD (15 mL/kg of hydroxyethylstarch administered preoperatively) in 49 patients undergoing hip arthroplasty. To avoid excessive intravascular volume, we used the vasodilating effect of isoflurane. No significant differences were found between groups (ANH, n = 23; HHD, n = 26) for intraoperative blood loss (ANH versus HHD, median [minimum-maximum]); 545 [295-785] mL versus 520 [315-825] mL) and postoperative blood loss (730 [525-945] mL versus 780 [495-895] mL), postoperative hemoglobin, hemotocrit, platelet count or coagulation variables, and transfusion requirements (ANH 43% versus HHD 35% of patients received homologous blood) (P > 0.05). Heart rate did not change significantly in either group. In the ANH group mean arterial blood pressure (MAP) decreased after hemodilution (P < 0.05) while in the HHD group MAP did not change over time. Mean time required to perform ANH was 58 (46-62) min versus HHD 16 (12-19) min (P < 0.05). Costs for ANH were $63.60 USD and for HHD $32.75 USD (labor costs not included). In orthopedic patients undergoing hip replacement with a predicted blood loss of about 1000 mL, HHD seems to be a simple as well as time- and cost-saving alternative for ANH.

Gamma-hydroxybutyric acid (GHB) is a naturally occurring transmitter in the mammalian brain, related to sleep regulation and possibly to energy balance in diving or hibernating animals. It has been used for almost 35 years as an intravenous agent for induction of anaesthesia and for long-term sedation. Its convincing pharmacological properties, without serious adverse effects on circulation or respiration, are compromised by its unpredictable duration of action. This is not a major problem with long-term sedation during ICU treatment. GHB has been used with good results for sedation of patients with severe brain injury, where it compares favourably with barbiturates. In animal studies, it seems to possess a protective action against hypoxia on a cellular and whole organ level. However, in some experimental animals GHB has been shown to produce seizure-like activities, and the compound is being used to produce absence-like seizures. GHB has been used in our ICU for years to provide adequate sedation for patients under controlled ventilation or for patients fighting the respirator during spontaneous respiration. No serious side effects were observed in these patients, while in some patients under haemodialysis hypernatraemia and metabolic alkalosis developed; both were reversible after discontinuation of GHB and restriction of additional sodium input (Somsanit, the commercially available GHB preparation in Germany, contains 9.2 mmol sodium/g; the daily dose averages 20-40 g GHB, i.e. 180-370 mmol sodium). PATIENTS AND METHODS. In 31 patients after major abdominal surgery, sedation was established with GHB 50 mg/kg BW injected via perfusion pump over a 20-min period. No centrally acting medication had been given for at least 2 h. A computer-based multichannel EEG system (CATEEM, MediSyst, Linden) was used, allowing for fast Fourier transformation, spectral analysis and topographical brain mapping. EEG during induction of sedation was followed after a baseline EEG (10 min) had been recorded. Patients receiving long-term sedation were studied daily for an additional 15-min period. Corresponding well to the clinical findings, EEG pattern changed to a slow delta-theta or delta-only rhythm within 10 min of the start of injection. Alpha and beta power decreased, while delta activity exhibited an increase. All changes were most obvious in frontal and central areas of the brain. In about one out of three patients, a burst--suppression pattern developed. Since automatic processing of EEG may fail to detect special patterns like the looked-for 3/s spikes and waves, the raw EEG was analysed visually by an expert neurologist. Both processed and conventionally analysed EEG were free of any seizure-like electrical activity. CONCLUSION. We conclude that animal data may not apply to the use of GHB in humans, provided the dose is limited to the clinical needs. GHB is used in clinical practice in doses twice as high, or even higher, than the one we use for induction, without obvious side effects. However, the suppression of theta rhy...

No abstract