Minimal flow sevoflurane and isoflurane anaesthesia and impact on renal function.

BACKGROUND AND AIM: Compound A generation and accumulation in sevoflurane anaesthesia is dependent on fresh gas flow. We investigated the extent of generation of compound 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.

Functional reorganization of the human primary somatosensory cortex after acute pain demonstrated by magnetoencephalography.

The somatosensory system is capable of functional reorganization following peripheral denervation or training. Studies on human amputees with phantom limb pain provided evidence that these reorganizational changes are modulated through nociceptive input. In the present study we used magnetoencephalographic recordings of six healthy volunteers to assess whether acute pain by itself causes a reorganization of the primary somatosensory cortex. After the induction of an intense experimental pain at the thenar of the left hand by intradermal injection of capsaicin, the extent of the cortical hand representation and the distance between the hand representation and the localization of the lip decreased. A likely mechanism for this acute reorganization is that pain induced hyperresponsiveness of the left thenar to tactile input from neighboring body sites.

Thermal and mechanical antinociceptive action of spinal vs peripherally administered clonidine in the rat inflamed knee joint model.

It has been demonstrated recently that in addition to its spinal analgesic actions, the alpha 2 adrenoreceptor agonist clonidine also has peripheral analgesic activity. Few data are available regarding the antinociceptive effects of spinal vs peripherally delivered clonidine in inflammatory pain. Thus we have studied spinal (intrathecal = i.t.) and peripheral (intra-articular = i.a.) administration of clonidine in the rat inflamed knee joint model. Thermal and mechanical antinociception was assessed in rats over 28 h using a modified Hargreaves box and von Frey hairs after induction of tonic persistent inflammatory pain by injection of a kaolin-carrageenan mixture into the right knee joint. Thirty minutes after injection of kaolin-carrageenan, clonidine was administered via an i.t. catheter or by i.a. injection into the right inflamed knee joint or by subcutaneous injection (s.c.) (highest effective intra-articular dose). The specific site of action was assessed using the alpha 2 antagonist yohimbine i.t., i.a. or s.c. Clonidine i.t. resulted in thermal and mechanical antinociception during ongoing inflammation, which was not enhanced by inflammation. In contrast, i.a. delivery of clonidine, which also produced a dose-dependent thermal and mechanical antinociceptive effect, revealed a leftward shift in the antinociceptive activity produced by ongoing inflammation. Yohimbine inhibited the antinociceptive action of clonidine at the site of delivery. We suggest that clonidine produces potent thermal and mechanical antinociception regardless of the route of administration. However, chronic inflammatory processing appears to enhance the antinociceptive efficacy of the peripheral alpha 2 agonist.

Central and peripheral analgesia mediated by the acetylcholinesterase-inhibitor neostigmine in the rat inflamed knee joint model.

UNLABELLED: Intrinsic cholinergic inhibitory pathways present a key modulating system in pain perception. The use of intrathecal (i.t.) acetylcholinesterase-inhibitors, such as neostigmine, result in analgesia in both preclinical and clinical models. However, whether i.t. neostigmine suppresses tonic persistent pain or has peripheral sites of antinociceptive action has not been determined. Thus, we studied central (i.t.) and peripheral (intraarticular; i.a.) 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. I.t. neostigmine resulted in a dose-dependent thermal analgesia (50% of maximal effective dose [ED50] 0-4 h: 6.6 microg, 24-28 h: 9.4 microg) and mechanical analgesia (ED50 0-4 h: 3.5 microg, 24-28 h: 4.3 microg). I.t. atropine reversed analgesia by i.t. neostigmine. I.a. neostigmine also resulted in an i.a. 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 microg, 24-28 h: 140.1 microg). Partial suppression of mechanical hyperalgesia was observed after i.a. 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 acetylcholinesterase-inhibitor 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.

Interaction of heart rate and hypothermia on global myocardial contraction of the isolated rabbit heart.

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 = 90 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-adrenoreceptor 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 Ca2+ sensitivity that is opposed by isoproterenol during hypothermia.

[Hypertonic-hyperoncotic volume replacement (7.5% NaCl/10% hydroxyethyl starch 200.000/0.5) in patients with coronary artery stenoses]. / Hyperton-hyperonkotischer Volumenersatz (7.5% NaCl/10% Hydroxyethylstärke 200.000/0.5) bei Patienten mit Koronararterienstenosen.

OBJECTIVES: To determine the efficacy and safety of intravascular volume augmentation with a hypertonic saline-hyperoncotic HES solution prior to CABG. DESIGN: Randomized, double-blind, clinical trial. PATIENTS: Consecutive sample of 37 patients scheduled for elective CABG; mean age 64.5 (41-80; range) years and weight 74 (51-111) kg. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: In patients with coronary artery disease, volume augmentation with hypertonic-hyperoncotic solutions may induce transient hypotension and post-infusion hypervolemic left heart failure.

[Effect of nifedipine and urapidil on autoregulation of cerebral circulation in the presence of an intracranial space occupying lesion]. / Der Einfluss von Nifedipin und Urapidil auf die Autoregulation der zerebralen Durchblutung in Gegenwart einer intrakraniellen Raumforderung.

We investigated in dogs with an intracranial space occupying lesion the effects of the antihypertentive agents nifedipine and urapidile on intracranial pressure (ICP) and intracerebral autoregulation. During the application of nifedipine the ICP rose significantly whereas urapidile had no influence on the ICP. By continuous angiotensin infusion the mean arterial pressure was raised by 50% by which a simultaneous increase of the ICP could be seen in the nifedipine group, whereas the urapidile group remained unaffected.

The effect of sufentanil on intracranial pressure (ICP) in anesthetized dogs.

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.

[The behavior of intracranial pressure and intracranial compliance in nifedipine-induced hypotension]. / Das Verhalten von intrakraniellem Druck und intrakranieller Compliance während Nifedipin-induzierter Hypotension.

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)

Permeation of the blood-brain barrier by urapidil and its influence on intracranial pressure in man in the presence of compromised intracranial dynamics.

We studied eight patients undergoing craniotomy for intracerebral tumour surgery requiring monitoring of intracranial pressure. All these patients showed significantly increased systolic arterial pressure, during anaesthesia. Following an average dose of 0.8 +/- 0.22 mg/kg urapidil, systolic arterial pressure returned to baseline values without a significant change in intracranial pressure. In nine patients, urapidil concentrations in plasma and cerebrospinal fluid were assayed following an intravenous injection of urapidil. Urapidil was found in the cerebrospinal fluid in concentrations between 5 and 99 ng/ml after total cumulative bolus injections of 10-75 mg. There is evidence that in clinically applied doses urapidil permeates the blood-brain barrier and reaches cerebrospinal fluid concentrations that allow an interaction with central 5-hydroxytryptamine-1A receptors.