Background: Children with pulmonary hypertension routinely undergo pulmonary vascular resistance studies to assess the disease severity and vasodilator responsiveness. It is vital that results are accurate and reliable and are not influenced by the choice of anaesthetic agent. However, there are anecdotal data to suggest that propofol and inhalational agents have different effects on pulmonary vascular resistance. Methods: A total of 10 children with pulmonary hypertension were selected sequentially to be included in the study. To avoid confounding because of baseline anatomic or demographic details, a crossover protocol was implemented, using propofol or isoflurane, with time for washout in between each agent and blinding of the interventionalist. Results: Pulmonary and systemic vascular resistance were not significantly different when using propofol or isoflurane. However, the calculated resistance fraction – ratio of pulmonary resistance to systemic resistance – was significantly lower when using propofol than when using isoflurane. Conclusions: Although no difference in pulmonary vascular resistance was demonstrated, this pilot study suggests that the choice of anaesthetic agent may affect the calculation of relative pulmonary and systemic vascular resistance, and provides some preliminary evidence to favour propofol over isoflurane. These findings require replication in a larger study, and thus they should be considered in future calculations to make informed decisions about the management of children with pulmonary hypertension.

Background and objective: Isoflurane is a chiral, volatile anaesthetic with low metabolic rate (0.17%) that is routinely administered in its racemic form. Knowledge about the distribution of the enantiomers in human beings may give some important information about the understanding of the mechanisms of volatile anaesthetics.

Methods: Blood samples were drawn immediately after tracheal extubation and daily up to 8 days postoperatively from patients undergoing general anaesthesia with isoflurane racemate. The enantiomer enrichment of isoflurane was determined by headspace gas chromatography-mass spectrometry.

Results: At all time points, there was a statistically significant accumulation of the S(+) enantiomer in blood, especially at days 2 (52.01%) and 7 (52.1%). Separate analysis of obese patients or in a small group of patients with co-existing lung disease did not show any difference to the total population. In addition, duration of anaesthesia did not influence the enantiomer concentrations.

Conclusions: We suggest that a slower association and dissociation rate is responsible for the S(+) enrichment.

Background and objective We investigated whether glibenclamide (glyburide) affects myocardial metabolism and hydroxyl radical formation in the rat heart–lung preparation with or without inhalation anaesthetics.

Methods Thirty-seven male Wistar rats were allocated to four groups: (a) control group (C), received vehicle only; (b) group G, received glibenclamide 10 μM L−1; (c) group I, received glibenclamide 10 μM L−1 and 1.4% isoflurane during perfusion; (d) group S, received glibenclamide 10 μM L−1 and 2.7% sevoflurane during perfusion. Glibenclamide was administered 7 min after the start of perfusion. Ten minutes later, the heart was rendered globally ischaemic for 10 min by reducing the preload and afterload to zero, and then the heart was reperfused for 10 min. The formation of hydroxyl radicals in perfusate blood and heart was measured with high performance liquid chromatography using salicylic acid. Hydroxyl radicals react with salicylic acid, yielding dihydroxybenzoic acids.

Results The recovery time from ischaemia in group G was significantly longer than the other groups. However, there were no differences in myocardial metabolites and dihydroxybenzoic acids concentrations in the perfusate and heart among the four groups.

Conclusions Glibenclamide prolonged recovery time from ischaemia, but did not affect hydroxyl radical formation in the postischaemic reperfused heart. In addition, isoflurane and sevoflurane shortened this time. These facts suggest that mechanisms other than effects of volatile anaesthetics on hydroxyl radical formation are responsible for their protective effects in this model.

Background and objective This study investigates the interaction of sevoflurane and nitrous oxide on EEG median power frequency of 2.5 Hz during surgery.

Methods Sevoflurane concentrations required for electroencephalographic median power frequency between 2 and 3 Hz were measured in 25 patients during gynaecological laparotomies. Nitrous oxide was randomly administered at 0, 20, 40, 60 and 75 vol%, subsequently two different concentrations in each patient. The data were analysed using isobolographic analysis together with previously published data on nitrous oxide-isoflurane, -enflurane, or -desflurane interaction.

Results The interaction is described by the equation: C volatile anaesthetic/C0 volatile anaesthetic + C N2O/C0 N2O = 1 (C is the concentrations for a drug combination to achieve the desired effect; C0 is the concentration for single drug use). The parameters are C0 isoflurane = 1.11 vol% (95% CI 1.03–1.19), C0 enflurane = 1.64 (1.52–1.77), C0 desflurane = 5.31 (4.92–5.73), C0 sevoflurane = 2.12 (1.96–2.29), C0 N2O = 174 (153–202). These parameters decrease by 6% (2.5–10) for every 10 years of patients’ age > 40 years.

Conclusions The interaction is compatible with additivity. The potency of nitrous oxide to substitute the volatile anaesthetics is less than anticipated from previously reported MAC values.

Background and objective Late postoperative hypoxaemia after upper abdominal surgery is common even among cardiopulmonary healthy patients. Atelectasis may develop after intubation and persist into or reveal a disposition for atelectasis in the postoperative period. Positive end–expiratory pressure (PEEP) eliminates peroperative atelectasis but the effect on perioperative oxygenation is controversial. This study evaluated the effect of peroperative PEEP optimized pulmonary compliance on perioperative oxygenation and complications.

Methods Forty patients assessed by electrocardiography, spirometry, functional residual capacity and diffusion capacity were randomly assigned to receive positive end–expiratory pressure (PEEP) or zero endexpiratory pressure (ZEEP) during surgery. PaO2, SPO2 and complications in the postoperative period were evaluated without knowledge of peroperative PEEP or ZEEP application.

Results Peroperative arterial oxygenation improved for all patients receiving PEEP, mean 2.1 kPa (0.7–3.5 kPa). There was no difference in postoperative median PaO2 between the groups. The differences in the incidence of late prolonged postoperative hypoxaemia and complications were 25% (−5% to 55%) and −1% (−31% to 29%) between the ZEEP and the PEEP group, but were not statistically significant.

Background and objective Volatile anaesthetic effects on altering tone after blocking nitric oxide synthase, cyclo-oxygenase-prostaglandin synthase and KATP channel pathways are controversial. We examined in isolated guinea pig hearts whether anaesthetics alter bradykinin and 5-hydroxytryptamine-induced effects on coronary flow and percentage oxygen extraction after blocking these pathways.

Methods Before and during exposure to sevo-flurane, halothane or isoflurane, hearts were infused with 10−13–10−8 M bradykinin, or 10−8–10−6 M 5-hydroxytryptamine (serotonin), with either L-NAME, indomethacin, or glibenclamide. Bradykinin or 5-hydroxytryptamine alone increased flow and decreased percentage oxygen extraction in a concentration-dependent manner; these effects were largely blocked by L-NAME (nitro-L-arginine methylester), which also decreased basal flow and increased basal percentage oxygen extraction.

Results The anaesthetics restored bradykinin and 5-hydroxytryptamine-induced increases in flow or decreases in percentage oxygen extraction after inhibition by L-NAME. Indomethacin or glibenclamide alone had little effect on basal flow and percentage oxygen extraction. The anaesthetics restored bradykinin and 5-hydroxytryptamine-induced increases in flow or decreases in percentage oxygen extraction after inhibition by L-NAME. Indomethacin or glibenclamide alone had little effect on basal flow and percentage oxygen extraction. Drug-induced increases in flow and decreases in percentage oxygen extraction in the absence or presence of glibenclamide or indomethacin were not altered at either of the two concentrations of anaesthetics.

Conclusions Endothelium-dependent vasodilatation is not affected by blocking prostaglandin release or KATP channels in the intact heart even in the presence of an anaesthetic. However, the diminished responses to vasodilators after nitric oxide synthase inhibition is largely restored or enhanced by anaesthetics.

Background and objective We studied the influence of systemic (aortic) blood flow velocity on changes of cerebral blood flow velocity under isoflurane or sevoflurane anaesthesia.

Methods Forty patients (age: isoflurane 24–62 years; sevoflurane 24–61 years; ASA l–lll) requiring general anaesthesia undergoing routine spinal surgery were randomly assigned to either group. Cerebral blood flow velocity was measured in the middle cerebral artery by transcranial Doppler sonography (depth: 50–60 mm). Systemic blood flow velocity was determined by transthoracic Doppler sonography at the aortic valve. Heart rate, arterial pressure, arterial oxygen saturation and body temperature were monitored. After standardized anaesthesia induction (propofol, remifentanil, vecuronium) sevoflurane or isoflurane were used as single agent anaesthetics. Cerebral blood flow velocity and systemic blood flow velocity were measured in the awake patient (baseline) and repeated 5 min after reaching a steady state of inspira-tory and end-expiratory concentrations of 0.75, 1.00, nd 1.25 mean alveolar concentrations of either anaesthetic. To calculate the influence of systemic blood flow velocity on cerebral blood flow velocity, we defined the cerebral-systemic blood flow velocity index (CSvl). CSvl of 100% indicates a 1:1 relationship of changes of cerebral blood flow velocity and systemic blood flow velocity.

Results Isoflurane and sevoflurane reduced both cerebral blood flow velocity and systemic blood flow velocity. The CSvl decreased significantly at all three concentrations vs. 100% (isoflurane/sevoflurane: 0.75 MAC: 85 ± 25%/81 ± 23%, 1.0 MAC: 79 ± 19%/74 ± 16%, 1.25 MAC: 71 ± 16%/79 ± 21%; [mean ±SD] P% 0.0001). Conclusions The reduction of the CSvl vs. 100% indicates a direct reduction of cerebral blood flow velocity caused by isoflurane/sevoflurane, independently of systemic blood flow velocity.

Clevidipine is a new lipophilic, ultra-short acting 1,4-dihydropyridine calcium channel antagonist for intraoperative use. Because sarcolemnal calcium currents are involved in the mechanism of action of anaesthetics we questioned whether clevidipine alters the potency of volatile anaesthetics. We studied the effects of clevidipine on minimal alveolar concentration and the time to awaken from isoflurane anaesthesia. Sprague-Dawley rats were anaesthetized with isoflurane, and were allocated to one of four treatments prior to minimal alveolar concentration determination: (a) saline control; (b) clevidipine 20 nmol kg−1 min−1; (c) clevidipine 40 nmol kg−1 min−1; (d) clonidine 1 μg kg−1 – positive control. Ten mongrel dogs were anaesthetized with isoflurane and received a continuous infusion of clevidipine 6 nmol kg−1 min−1 or the solvent (Intralipid 20% – control). After 2 h of steady-state anaesthesia, minimal alveolar concentration awake and the time to awakening were recorded. Clevidipine reduced minimal alveolar concentration to a small but statistically significant extent (from 1.40±0.16 control to 1.23±0.13 vol% with 20 nmol kg−1 min−1 and to 1.27±0.12 vol% with 40 nmol kg−1 min−1; mean±SD; P < 0.05) in rats. Clonidine reduced minimal alveolar concentration to 0.90±0.17 vol% (mean± SD; P < 0.05). Minimal alveolar concentration awake and the duration of sleep were not affected by clevidipine in dogs. Clevidipine mildly reduces miinimal alveolar concentration of isoflurane but does not prolong the duration of sleep and does not affect minimal alveolar concentration awake after a 2-h steady-state isoflurane anaesthesia.

Anaesthetic agents have been implicated in the development of postoperative pneumonia, but the direct effect of volatile anaesthetics on bacterial growth has given contradictory results. The effects of isoflurane on the growth of Staphylococcus aureus and Escherichia coli were investigated under conditions similar to those of clinical practice, using standardized microbiological methods. An open anaesthetic circuit was adjusted to the normal ventilatory settings of an adult patient. A spray, installed on the inspiratory side of the circuit, ensured the delivery of isoflurane at 1.5 minimal alveolar concentration. The bacterial strains studied were both wild-type and reference strains. Bacterial inoculums were prepared to obtain a bacterial exponential growth of 103 colony-forming units per mL in 10mL of nutritive broth. Each strain was studied with and without exposure to isoflurane and measured by the usual criteria of bacterial growth, and by bacterial regrowth after exposure to isoflurane. Under experimental conditions close to clinical practice, exposure to isoflurane did not alter bacterial growth of S aureus and E. coli, or their bacterial regrowth when isoflurane exposure is over.

The effects of inhalational anaesthetic agents on renal sympathetic nerve activity (RSNA) were compared in anaesthetized rabbits. Concentrations of 6% desflurane, 1.2% isoflurane, and 2.4% enflurane increased mean RSNA up to 32, 36 and 44% while higher concentrations, of 12, 2.4 and 3.2% depressed it by 42, 83 and 5%, respectively. For halothane RSNA was unchanged up to 0.8% and decreased by 36% at 1.6% concentration. Nitrous oxide increased RSNA up to 28% at 50% concentration. Maximum reductions in mean arterial pressure (MAP) were 60% for both 2.4% isoflurane and 3.2% enflurane, 50% for 12% desflurane and 1.6% halothane, while 70% nitrous oxide increased MAP by 22%. In conclusion, unlike the entirely depressive effects of halothane, the effects of desflurane, isoflurane and enflurane were biphasic involving excitation at lower concentrations and depression of RSNA and a reduction in MAP at higher concentrations. Nitrous oxide caused increases in both RSNA and MAP.

To evaluate arterial (PaCO2), end-tidal (PETCO2) and carbon dioxide tension difference during mechanical ventilation with extratracheal airways, 60 patients ASA physical status I-II, receiving general anaesthesia for minor extra-abdominal procedures were randomly allocated to receive either a cuffed oropharyngeal airway (group COPA, n=30) or a laryngeal mask (group LMA, n=30). The lungs were mechanically ventilated by IPPV using a 60% nitrous oxide and 1–1.5% isoflurane in oxygen mixture (VT8 mL kg−1; RR=12 b min−1; I/E=1/2). After PETCO2 had been stable for at least 10 min after airway placement, haemodynamic variables and PETCO2 were recorded and an arterial blood sample was obtained for measurement of PaCO2. No differences in anthropometric parameters, smoking habit, haemodynamic variables and incidence of untoward events were observed between the two groups. Airway manipulation, to maintain adequate ventilation, was required in only nine patients in the cuffed oropharyngeal airway group (30%)(P < 0.0005); however,in no case was it necessary to remove the designated extratracheal airway due to unsuccessful mechanical ventilation. The mean difference between arterial and end-tidal carbon dioxide partial pressure was 0.4±0.3 KPa in the laryngeal mask group (95% confidence intervals: 0.3–0.5 KPa) and 0.3±0.26 KPa in the cuffed oropharyngeal airway group (95% confidence intervals: 0.24–0.4 KPa) (P =NS). We conclude that in healthy adults who are mechanically ventilated via the cuffed oropharyngeal airway, the end-tidal carbon dioxide determination is as accurate an indicator of PaCO2 as that measured via the laryngeal mask, allowing capnometry to be reliably used to evaluate the adequacy of ventilation.

There is disagreement concerning the role of nitric oxide (NO) in general anaesthesia. The present study was conducted to determine whether the anaesthetic drug isoflurane alters levels of NO metabolites, NOx (NO2 and NO3), in the hippocampus of rats during and after anaesthesia. Results showed resting hippocampal NOx levels of about 20 pmol in freely moving control rats. Five minutes after the induction of isoflurane anaesthesia (4.72%=4 minimum alveolar concentrations, detected by righting reflex), there was loss of the righting reflex coincident with a significant elevation in hippocampal NOx levels. During isoflurane anaesthesia, the maximum NOx concentration rose ≈2.4-fold higher than control levels; the NO3 level increased about 5-fold higher than resting levels. NOx levels returned to control levels following discontinuation of the anaesthetic. When rats were pre-treated with L-NG-nitro arginine methyl ester, an NO synthase-inhibitor, the isoflurane-induced increases in NOx were markedly suppressed. D-NG-nitro arginine methyl ester was ineffective in preventing these neurochemical changes, thus indicating the stereoselective nature of the inhibition by L-NG-nitro arginine methyl ester. Furthermore, L-NG-nitro arginine methyl ester pre-treatment likewise prevented increases in both NO2 and NO3 levels. When rats were exposed to 80% nitrous oxide in oxygen, there was loss of the righting reflex but no change in hippocampal NOx levels. These findings indicate that isoflurane increases production of hippocampal NO and that this may be pertinent to general anaesthetic drug effects.

Sevoflurane has been reported to generate oxygen free radicals. We have investigated whether sevoflurane or isoflurane enhances oxygen free radical formation in the post-ischaemic reperfused heart. An isolated rat heart–lung preparation was used. Thirty male Wistar rats were allocated to four groups: control, no drug, 2.5% sevoflurane and 1.4% isoflurane. The heart was perfused initially at a cardiac output of 30 mL min−1 and a mean arterial pressure of 70 mmHg. Ten minutes after the start of perfusion, the heart was rendered globally ischaemic for 10 min by reducing the preload and afterload to zero. Then, the heart was reperfused for 10 min. At the end of reperfusion, the heart was freeze dried for 6 days. The perfusate blood was collected just before and just after ischaemia and at the end of reperfusion. The formation of hydroxyl radicals in perfusate blood and heart was measured with high-performance liquid chromatography using salicylic acid. Hydroxyl radicals react with salicylic acid, yielding 2,3-, 2,4-, 2,5- and 3,4-dihydroxybenzoic acid (DHBA). Before and after ischaemia, there were no significant differences in cardiac output, systolic pressure, heart rate and right arterial pressure among the groups. The concentrations of 2,3-, 2,4-, 2,5- and 3,4-DHBA in the perfusate blood after ischaemia and reperfusion were significantly higher than those before ischaemia in all groups. However, there were no differences in the DHBA levels among groups. This study indicates that sevoflurane and isoflurane do not enhance hydroxyl radical formation in the post-ischaemic reperfused heart.

The isoflurane-saving and CO2-retaining effects of a charcoal filter were compared with a Siemens standard heat and moisture (HME) exchanger and an emptied specimen (dummy). Isoflurane was delivered during the inspiratory phase and consumption investigated at 10, 15 and 25 cycles min−1. The investigation was performed by ventilation with humidified air with a constant end-tidal CO2 and temperature. For a comparison, isoflurane was delivered in a conventional manner via the ventilator. The arrangement with a charcoal filter reduced the isoflurane consumption by a factor of 2.0−2.6, depending on ventilatory rate. Most of the saving was a result of the method of isoflurane delivery (factor 1.4−2.0), while adding the reflector gave a further reduction (factor 1.3−1.5). One circumstance that reduced the net efficiency of the charcoal filter was that it also reflected CO2; consequently, total minute ventilation had to be increased to maintain constant end-tidal CO2.