The influence of nifedipine induced hypotension on intracranial pressure (ICP) and intracranial compliance (ICC) was investigated in dogs without (group I, n = 8) and with (group II, n = 8) intracranial hypertension. ICP in group II was raised by gradual inflation of an epidurally placed balloon catheter. A volume-pressure-response curve (VPR) was established before and during the administration of nifedipine. In group II dogs angiotensin was infused before and during infusion of nifedipine in a dose sufficient to raise mean arterial pressure (MAP) by 30-40 mm Hg. An infusion of nifedipine (2 micrograms X kg-1 X min-1) subsequent to a bolus injection of nifedipine (10 micrograms X kg-1) resulted in a significant and sustained decrease in MAP (p less than 0.05) by 25% and 35% resp. due to a significant reduction in total peripheral resistance (p less than 0.05). ICP increased from 8.7 +/- 3.0 mm Hg to a maximum of 12.5 +/- 5.2 mm Hg in group I animals (p less than 0.05) and from 19.8 +/- 2.6 mm Hg to 24.8 +/- 7.2 mm Hg not significantly in group II dogs. The pressure-volume-index revealed a slight reduction of ICC in group I and a slight increase of ICC in group II resp. during nifedipine as compared to before nifedipine. When angiotensin was being administered in group II dogs before nifedipine was given, MAP increased by 40 +/- 5.8 mm Hg while ICP did not change significantly (+2 +/- 2.4 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)
Intrinsic cholinergic inhibitory pathways present a key modulating system in pain perception.The use of intrathecal (IT) acetylcholinesterase-inhibitors, such as neostigmine, result in analgesia in both preclinical and clinical models. However, whether IT neostigmine suppresses tonic persistent pain or has peripheral sites of antinociceptive action has not been determined. Thus, we studied central (IT) and peripheral (intraarticular; IA) neostigmine in a rat inflamed knee joint model. Inhibition of thermal and mechanical hyperalgesia was assessed over 28 h using a modified Hargreaves box and von Frey hairs, respectively. IT neostigmine resulted in a dose-dependent thermal analgesia (50% of maximal effective dose [ED50] 0-4 h: 6.6 [micro sign]g, 24-28 h: 9.4 [micro sign]g) and mechanical analgesia (ED (50) 0-4 h: 3.5 [micro sign]g, 24-28 h: 4.3 [micro sign]g). IT atropine reversed analgesia by IT neostigmine. IA neostigmine also resulted in an IA atropine reversible dose-dependent increase of thermal analgesia, although it did not exceed 60% of a maximal possible analgesic effect with the largest applied dose (ED50 0-4 h: 76.2 [micro sign]g, 24-28 h: 140.1 [micro sign]g). Partial suppression of mechanical hyperalgesia was observed after IA neostigmine. We conclude that centrally administered neostigmine modulates thermal and mechanical antinociception in this animal model of inflammatory pain. These data suggest a peripheral site of muscarinic antinociception. Implications: This animal study shows that administration of the acetylcholinesteraseinhibitor neostigmine results in enhanced levels of the endogenous neurotransmitter acetylcholine, which seems to act as one of a group of analgesia-modulating compounds at central and peripheral sites in inflammatory pain. (Anesth Analg 1998;86:1027-32)
The use of sufentanil in neuroanesthesia has been questioned because of a potential increase in intracranial pressure (ICP) in dogs and humans. The effect of sufentanil administration on ICP was studied in 6 dogs with normal and elevated baseline ICP, anesthetized with nitrous oxide and an intravenous piritramide infusion. No significant change in ICP could be demonstrated over a 30 minute observation period after administration of 2 micrograms/kg of sufentanil. The results indicate that this dose of sufentanil does not increase ICP in moderately hyperventilated dogs under stable anesthetic conditions.
We studied the effects of mild hypothermia on cardiac contractility in isolated rabbit hearts perfused with Krebs-Henseleit solution according to the technique of Langendorff. Isovolumetric left ventricular pressure (LVP) was measured with a fluid-filled balloon. Hearts were paced after induction of atrioventricular block. At low heart rates (< 30 bpm) mild hypothermia (cooling to 30 degrees C) induced a 32% increase in LVP (146.5 +/- 10 mm Hg at 30 degrees C vs 110.7 +/- 13 mm Hg at 37 degrees C) but this positive inotropic response was progressively lost by increasing heart rate. At pacing rates >or=to90 bpm, lower systolic LVP, higher diastolic LVP, and lower positive and negative LV dP/dt were obtained in hypothermic (93 +/- 12 mm Hg, 55 +/- 18 mm Hg, 584 +/- 137 mm Hg/s, and 323 +/- 57 mm Hg/s at 210 bpm, respectively) compared to normothermic hearts (123 +/- 4 mm Hg, 10 +/- 4 mm Hg, 1705 +/- 145.5 mm Hg/s, and 1155 +/- 78 mm Hg/s at 210 bpm, respectively). The duration of mechanical diastole was reduced or suppressed in these hearts. Exposure to the beta-adrenoceptor agonist, isoproterenol, improved this diastolic dysfunction during hypothermia and pacing at high rates, suggesting that the sarcoplasmic reticulum Ca2+ uptake might be involved. Our data are also consistent with an increase in myofilament Ca (2+) sensitivity that is opposed by isoproterenol during hypothermia. (Anesth Analg 1996;82:975-81)
To determine the efficacy and safety of intravascular volume augmentation with a hypertonic saline-hyperoncotic HES solution prior to CABG.Randomized, double-blind, clinical trial.Consecutive sample of 37 patients scheduled for elective CABG; mean age 64.5 (41-80; range) years and weight 74 (51-111) kg.Continuous, central-venous infusion of either 250 ml (approx. 3.5 ml/kg) HES (0.9% NaCl/10% hydroxyethyl starch 200.000/0.5) or HT-HES (7.5% NaCl/10% hydroxyethyl starch 200.000/0.5) in 15 minutes, following induction of anesthesia.Groups were similar with respect to age, weight, and sex. 15 min. after fluid loading, cardiac index, pulmonary artery pressure, and wedge pressure had increased from baseline in both groups (p < 0.05), with a greater increase in the HT-HES-group (p < 0.05). In eight out of 18 patients, who had received HT-HES, transient drops in arterial blood pressure (mean 20% from baseline, range 10-35%) were observed during the first 5 minutes of infusion. Seven of the HT-HES-group patients developed transient left ventricular failure, predominantly 5-20 min. after infusion. No incidence of initial hypotension or LVF was observed in the HES-group.In patients with coronary artery disease, volume augmentation with hypertonic-hyperoncotic solutions may induce transient hypotension and post-infusion hypervolemic left heart failure.
S252 Remifentanil is a new ultrashort-acting anilidopiperidine with a [micro sign]-specific opioid action. Remifentanil with its unique properties could be of particular use for fetal and maternal analgesia during fetal surgery. However, the hemodynamic changes and pharmacokinetic behavior of remifentanil in the pregnant patient have not been studied in depth. METHODS: Using the chronic maternal-fetal sheep preparation, a continuous infusion of remifentanil 0.33 [micro sign]g/kg/min was administered intravenously over 60 min. Fetal and maternal arterial blood samples were obtained for remifentanil levels before and at 5, 15, 30, 60, 65, 75 and 120 min following start of the infusion. At regular intervals, arterial blood samples were drawn to determine blood gases and acid-base status of mother and fetus. Maternal mean arterial pressure (MMAP), uterine bloodflow (UBF), maternal heart rate (MHR), fetal mean arterial pressure (FMAP) and fetal heart rate (FHR) were recorded continuously. Statistical analyses were performed using repeated measures of ANOVA followed by Dunnett t-testing. A p value < 0.05 was considered significant. RESULTS: Eight experiments were performed in eight ewes. MMAP, MHR FHR, FMAP and UBF or blood-gases and acid-base status in mother or fetus did not change significantly during remifentanil infusion. Peak levels of remifentanil were detected in maternal plasma after 30 min. and reached 3.5 ng/ml. Peak fetal plasma levels of 0.36 ng/ml were attained after 60 min. (Figure 1)Figure 1CONCLUSION: This study indicates that intravenous aplication of remifentanil has not any significant effect on maternal and fetal cardiovascular and acid-base status in the pregnant ewe. Peak fetal plasma concentration of remifentanil reached 14% of the peak maternal placental concentration.
Background and aim Compound A generation and accumulation in sevoflurane anaesthesia is dependent on fresh gas flow. We investigated the extent of generation of compund A. Methods After Institutional Review Board approval and informed consent, patients with normal renal function were randomized to receive either sevoflurane (n = 33) or isoflurane (n = 43) minimal flow anaesthesia (0.5 L min−1) for at least 2 h under standardized conditions. Compound A concentrations were quantified and blood and urine samples were taken to assess renal involvement. Both groups were comparable. Results No significant differences concerning blood chemistry and urine measurements were found. The maximum mean compound A concentration was observed 90 min after flow reduction being 40 ± 9 p.p.m. at a corresponding mean sevoflurane concentration of 2.1 ± 0.5 vol%. Mean inspiratory compound A exposure was 102 ± 33 p.p.m h−1. Conclusion Compound A concentrations using 0.5 L min−1 fresh gas flow and a heated absorber were higher than previously published values using an inflow of 1 L min−1. Compound A exposure was similar to other clinical studies which did not show changes in renal and hepatic function.
