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The aim of the present study was to develop a physiologically compatible inhalation solution of delta-9-tetrahydrocannabinol (THC), and to compare the pharmacokinetic and analgesic properties of pulmonal THC versus pulmonal placebo and intravenous (iv) THC, respectively. Eight healthy volunteers were included in this randomized, double-blind, crossover study. The aqueous THC formulations were prepared by using a solubilization technique. iv THC (0.053 mg/kg body weight), pulmonal THC (0.053 mg/kg), or a placebo inhalation solution was administered as single dose. At defined time points, blood samples were collected, and somatic and psychotropic side effects as well as vital functions monitored. An ice water immersion test was performed to measure analgesia. Using a pressure-driven nebulizer, the pulmonal administration of the THC liquid aerosol resulted in high THC peak plasma levels within minutes. The bioavailability of the pulmonal THC was 28.7 +/- 8.2% (mean +/- SEM). The side effects observed after pulmonal THC were coughing and slight irritation of the upper respiratory tract, very mild psychotropic symptoms, and headache. The side effects after iv THC were much more prominent. Neither pulmonal nor iv THC significantly reduced experimentally induced pain.

SUMMARY One hundred and fifty years after the first general anaesthetic in 1846 our knowledge about the mechanisms of general anaesthetics is still very sparse. The concept ‘depth of anaesthesia’ was introduced by John Snow (1847). He described ‘5° of narcotism’. Because one single agent had to provide all the components of general anaesthesia, the main problem for the anaesthetist was to avoid morbidity and mortality associated with excessively deep anaesthesia. The introduction of curare in 1942 allowed muscle relaxation required for surgery during a lighter level of anaesthesia, but also changed the emphasis from the problem of too deep anaesthesia and death, to too light anaesthesia and litigation. The problem of awareness during general anaesthesia with muscle relaxants provided the main impetus for monitoring depth of anaesthesia. During daily clinical practice the anaesthesiologist relies on clinical signs to evaluate anaesthetic depth, although several studies have shown a poor correlation between the 2 (Cullen et al. 1972; Evans and Davies 1984; Russell 1993). Different methods have been used in attempts to measure anaesthetic depth (Evans and Davies 1984; Stanski 1994), but none have been developed to a state where they can be used routinely in the operating theatre. This review will cover some of the parameters used to evaluate anaesthetic depth.

The analgesic effect of subanaesthetic concentrations of ether, trichloroethylene, methoxyflurane and halothane has been investigated previously using either clinical assessment or pain threshold measurements, but with conflicting results. The purpose of the present study was to evaluate the analgesic effect of isoflurane using experimental pain models. We studied 12 healthy volunteers at three randomly chosen subanaesthetic isoflurane concentrations: low (0.10-0.14 vol%), middle (0.16-0.20 vol%) and high (0.22-0.26 vol%). We used thermal pain detection and pain tolerance thresholds to argon laser stimulation, pressure pain detection and pain tolerance thresholds, immersion of the hand in ice water, and the nociceptive reflex to single and repeated (temporal summation) electrical stimulations, as experimental models to assess analgesia. There were no significant changes in the response to heat, cold or mechanical pressure at any of the subanaesthetic concentrations of isoflurane used. The nociceptive reflex thresholds to single stimulations, but not the thresholds for repeated stimulations, were significantly increased in all three isoflurane groups compared with baseline values. The difference between the different isoflurane concentrations was not statistically significant. In experimental pain models, subanaesthetic isoflurane concentrations have little or no analgesic potency.

We present a case of a probably unnecessary Caesarean section due to misinterpretation of the cardiotocography (CTG) trace during general anaesthesia. A 27‐yr‐old patient in her 30th week of an uneventful, normal first pregnancy presented with a deep venous thrombosis in the pelvic region. She was to undergo an emergency thrombectomy under general anaesthesia. During the operation, the CTG showed a lack of beat‐to‐beat heart rate variation (silent pattern CTG) with normal fetal heart rate. This silent CTG pattern was probably a result of the effect of general anaesthesia on the fetus. The CTG pattern was interpreted as indicating fetal distress, and an emergency Caesarean section was performed after the thrombectomy. The infant was apnoeic and had to be resuscitated and admitted to the neonatal intensive care unit. The pH at delivery was 7.23 and the baby was extubated 2 days later. Mother and child recovered without short‐term sequelae. In the absence of alternative explanations, reduced fetal beat‐to‐beat variability with a normal baseline heart rate during general anaesthesia is probably normal. Br J Anaesth 2001; 87: 791-3

Pain has been defined by the International Asso­ ciation for the Study of Pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." The definition clearly stresses that pain is a subjective conscious feeling. It is therefore a question whether one can speak of pain during a general anesthesia where the patient is uncon­ scious; however, the activity of the nociceptive system can be assessed during general anesthesia by direct measurements (eg, dorsal horn recording in animals) and ind irect measurements or observations (eg, move­ ment or withdrawal reflexes, and hemodynamic or hor­ monal responses to painful stimuli in animals and hu­ mans). Problems may arise when extrapolating to humans results obtained in animals. Different species may not show the same reactions. In animals, microelectrode recordings of events in the spinal cord can be made, and isolation of the spinal cord from higher central nervous system centers can be achieved through spinal cord transection. Obviously, this is not possible in humans. For human research , we have to rely on responses (psychophysical and/or electrophysiologic) evoked by activation of dorsal horn neurons through stimulation of peripheral receptors.