Doppler cardiac output (CO) determination is discussed as a non-invasive alternative to CO estimation by thermodilution. This study was designed to compare the accuracy of a new transoesophageal Doppler device with the thermodilution technique. In 24 patients undergoing coronary artery bypass surgery, CO was determined simultaneously by the oesophageal Doppler (OD) and thermodilution (TD) method in triplicate for three sample episodes: after induction of anaesthesia during clinical steady-state conditions (A), after start of surgery (B), and after sternotomy (C). The agreement between ODCO and TDCO estimations was assessed by analysing the mean difference, indicating the systematic error, and analysing the distribution of differences between the two methods. The bias between ODCO and TDCO estimations was 0.38 (−0.06 to +0.81) L min−1 (mean and 95% confidence interval) for sample episode A, 0.48 (−0.11 to +1.1) L min−1 for sample episode B, and 0.69 (+0.08 to +1.3) L min−1 (P < 0.05 vs. zero) for sample episode C. Bias analysis of the log-transformed data revealed that 95% of the ODCO values differed from TDCO values by 43% below to 50% above for sample episode A, by 39% below to 95% above for sample episode B, and by 32% below to 96% above for sample episode C. Analysis of the changes in CO from sample episode A to B and from sample episode B to C, expressed as percentage values, showed a non-significant bias between the methods, but the 2 SD limits were ±44% and ±36% respectively. Our findings suggest that CO estimation by OD cannot replace estimation by the TD method.

In order to assess if a mixture of phenylephrine/lignocaine is as effective as cocaine for local analgesia and vasoconstriction during nasal fibreoptic intubation, 99 patients receiving topical nasal analgesia either with cocaine 10% or a mixture of phenylephrine 1% and lignocaine 4% were studied in a randomized double-blind investigation. After topical analgesia a flexible fibreoptic endoscope was advanced through a nostril. Larynx, glottis and trachea were endoscopically sprayed with lignocaine. Following induction of anaesthesia a nasotracheal tube was inserted fibreoptically. Pain intensity and amount of epistaxis during endoscopy were assessed.Blood pressure, heart rate and ECG-ST segment were determined before and after topical nasal analgesia, after induction of anaesthesia and after nasotracheal intubation. There were no significant differences in painintensity or epistaxis between groups during endoscopy, nor significant alterations in haemodynamic parameters or ST-segment. It is concluded that the mixture of phenylephrine and lignocaine is a useful alternative to cocaine for local analgesia and vasoconstriction during nasal fibreoptic intubation.

Subarachnoid haemorrhage (SAH) following cerebral aneurysm rupture or trauma can result in the induction of secondary ischaemic brain damage via a decrease in microvascular perfusion, a disruption of the blood-brain barrier and consequent vasogenic oedema, and the delayed spasm of the major cerebral arteries (i.e. vasospasm). It is increasingly apparent that oxygen radical-induced, iron-catalyzed lipid peroxidation (LP) within the subarachnoid blood and vascular wall plays a key role in the occurrence of these secondary events. Tirilazad mesylate is a potent cytoprotective inhibitor of LP that works by a combination of radical scavenging and membrane stabilizing properties. It has been demonstrated to attenuate the acute and delayed vascular consequences of SAH and to protect the brain against ischaemic insults. Much of its action is mediated by an effect on the vascular endothelium, although it also appears to exert some direct neuroprotection and to inhibit LP in the subarachnoid blood. These actions of tirilazad in experimental SAH are reviewed.

Etomidate-induced suppression of cortisol biosynthesis is a result of a blockade of 11-beta-hydroxylation in the adrenal gland, mediated by the imidazol radical of etomidate. Since the generation of steroids requires reductive and energy rich equivalents, the present study examined whether supplementation with ascorbic acid or xylitol, a major source of NADPH, could attenuate adrenal suppression by etomidate in human subjects by promoting the turnover rate of 11-beta-hydroxylase. During continuous etomidate/alfentanil anaesthesia for pelviscopic surgery 30 female patients received either Ringer's lactate, xylitol (0.25 g kg−1 h−1) or ascorbic acid (0.5 g h−1) intravenously (i.v.). The plasma concentrations of cortisol, aldosterone and dehydroepiandrosterone (DHEA) were recorded for 5 h after end of surgery and a stimulation with synthetic ACTH was performed. The results showed no evidence of a clinically relevant attenuating effect of ascorbic acid or xylitol on etomidate-induced adrenocortical suppression. However, the observed suppression of cortisol levels was not enough to allow an attenuating affect to be measured.

The interaction of aprotinin with normal coagulation was studied in blood samples obtained from 10 healthy subjects. Each sample was simultaneously tested in four different preparations : NaCl-treated blood: 0.03 mL 0.9% NaCl in 0.33 mL blood; aprotinin treated blood : 0.33 mL blood+aprotinin in 0.03 mL in aliquots to obtain a final blood concentration of respectively 50 KIU mL−1; 100 KIU mL−1 and 200 KIU mL−1. The coagulation process was analysed by thromboelastography. R-time, reflecting intrinsic coagulation, increased in a dose dependent manner between NaCl-treated and aprotinin-treated blood. These findings suggest a dose dependent impairment of intrinsic coagulation by aprotinin.

The effects of different anaesthetics on the neutrophil oxidative response in vitro are compared. Neutrophils were stimulated with small amounts of the bacterial peptide N-formyl-L-methionyl-L-leucyl-phenylalanine as a physiological, receptor-dependent stimulus. A new flow cytometry-based method capable of detecting the small amounts of H2O2 generated by neutrophils in a heterogenous all-or-none response following submaximal stimulation with N-formyl-L-methionyl-L-leucyl-phenylalanine was used. Propofol and thiopentone suppressed the respiratory burst significantly (P < 0.05 and P < 0.01) in therapeutic concentrations, while midazolam and methohexitone inhibited significantly (P < 0.01) only at concentrations greater than the therapeutic range. Impairment of the neutrophil response was primarily because of a reduction in the number of neutrophils participating in the respiratory burst and not of a proportional decrease of the fluorescence of all neutrophils.

The present study was designed to determine the direct effects of halothane, isoflurane and sevoflurane on the bovine epicardial coronary artery as well as their mode of action. We chose serotonin as the vasoconstrictor because it also causes endothelium-dependent relaxation of coronary arteries. Isolated spiral strips of bovine epicardial coronary artery with and without endothelium were suspended for isotonic contraction recordings in Tyrode's solution. KCl (80.4 mm) solution induced maximal contraction, regarded as the reference value (100%). The muscle strips were then exposed to increasing concentrations of serotonin from 10−8 to 10−4 m in the presence and absence of 1.5 MAC halothane, isoflurane or sevoflurane. All three drugs attenuated serotonin-evoked contraction in the coronary artery strips both those strips with and without endothelium (P < 0.05−0.001). However, there were no significant differences in the attenuation of serotonin-induced contraction of the strips, both with and without endothelium, in each drug group. The attenuation potency of halothane was more than that of isoflurane and sevoflurane. The results demonstrate that halothane, isoflurane and sevoflurane attenuate contractile responses evoked by serotonin in bovine epicardial coronary artery both with and without endothelium.

We have examined the effect of propofol on the neutrophil respiratory burst. Chemiluminescence was used as a measure of the respiratory burst following stimulation with 10−5m N-formyl-L-methionyl-L-leucyl-L-phenylalanine.Propofol 1.25, 2.5 and 5.0 × 10−5m inhibited neutrophil chemiluminescence by 29.6, 43.0 and 57.6%, respectively, in neutrophils prepared from healthy adult volunteers, and by 25.5, 37.4 and 54.7% in cells from patients with severe sepsis. We conclude that propofol interferes with the ability of human neutrophils to generate reactive oxygen species.

The occurrence of a pneumothorax in a 4-week-old infant is described. The cause of the problem is believed to have been a kink in the silastic reservoir tube. The failure of the monitors to detect the event and methods of improving safety are discussed. Difficulties may occur even with familiar equipment; the value of full monitoring and constant vigilance are stressed.

The precise mechanisms underlying secondary brain damage after traumatic injury to the central nervous system (CNS) are not well understood, and delayed neuronal injury may result from pathological changes in neurotransmitter release, synthesis or generation of endogenous autodestructive neurochemicals and/or inflammatory mediators, or alterations in endogenous protective or trophic factors. Recent identification of such factors and the elucidation of the timing of the neurochemical cascade following CNS injury provides a window of opportunity for therapeutic intervention with pharmacological compounds which modify synthesis, release, receptor binding or physiological activity of neurotoxic factors. A number of recent experimental studies have reported that pharmacological modification of the post-traumatic neurochemical milieu can promote functional recovery in a variety of animal models of CNS trauma. This paper summarizes recent work suggesting that pharmacological manipulation of several key neurotransmitter and neurochemical systems can attenuate neuronal damage and improve functional outcome associated with traumatic brain injury.

Eleven adult patients with severe head injuries caused by blunt trauma, (Glasgow Coma Score of eight or less after resuscitation), were studied while being mechanically ventilated and sedated in the intensive care unit (ICU). In a double blind randomized cross over trial each patient received a bolus of suxamethonium (1 mg kg−1) or an equal volume of saline(0.02 mL kg−1) before planned physiotherapy. Intracranial pressure (ICP) and mean arterial pressure(MAP) were measured continuously for 10 min after each injection. There were no significant changes in intracranial pressure or cerebral perfusion pressure(CPP) following the administration of suxamethonium or saline. Suxamethonium appears to be a safe drug to use on sedated persons with severe head injuries following blunt trauma.

In a randomized double-blind study 60 children, undergoing the extraction of carious deciduous teeth under day-case general anaesthesia, were assigned to receive either intravenous nalbuphine hydrochloride 0.3 mg kg−1 (n = 21), one or more diclofenac suppositories 12.5 mg to a dose of 1–2 mg kg−1 (n = 19), or no analgesia (n = 20). The duration of anaesthesia was longer in the diclofenac group (9.6 min, SD 3.5) compared with control (7.2 min, SD 2.6) and nalbuphine (6.9 min, SD 3.0) groups respectively (P < 0.05). There were no statistically significant differences in post-operative pain scores during the 45 min post-operative period studied between the three groups using an objective pain score. We conclude that using this methodology we were unable to demonstrate any statistically significant differences between the analgesic effects of either intravenous (i.v.) nalbuphine or diclofenac suppositories compared with control.

Intrathecal midazolam for use as a post-operative analgesic when given alone and in conjunction with intrathecal diamorphine was assessed. Fifty-two patients scheduled for elective Caesarean section under spinal anaesthesia were randomly allocated to receive either bupivacaine (B), bupivacaine with diamorphine (BD), bupivacaine with midazolam (BM) or all three (BMD) by intrathecal injection. Post-operatively, no differences in visual analogue score (VAS), sedation or post-operative nausea and vomiting (PONV) could be demonstrated between groups. Patient-controlled analgesia system (PCAS) usage was significantly greater in group B when compared with the other groups. Pruritus was commoner in patients receiving diamorphine (BMD & BD). No side effects attributable to midazolam were identified. Intrathecal midazolam at this dose appears safe and has clinically detectable analgesic properties. The duration of useful analgesia appears to be short-lived.

Prolongation of the QT interval may produce potentially hazardous arrhythmias. The effects of midazolam or propofol, followed by suxamethonium on the QT interval have been investigated. Thirty patients, ASA I or II, without cardiovascular disease, electrolyte abnormalities or receiving any medication were studied. All patients were premedicated with midazolam 0.08 mg kg−1 i.m., 30–60 min prior to surgery. Anaesthesia was induced with either midazolam 0.4 mg kg−1 i.v., (15 patients) or propofol 1 mg kg−1 i.v. bolus, followed by a continuous infusion (15 patients). ECG, heart rate and arterial pressure were measured before induction of anaesthesia and at 1 and 3 min after the bolus of midazolam or propofol. Further recordings were obtained at 1 and 3 min after a bolus of suxamethonium 1.5 mg kg−1 i.v. and also immediately after tracheal intubation and 1 min later. Neither midazolam nor propofol had any significant effect on QTc interval. Prolongation of QTc was observed in both groups after suxamethonium and this was further prolonged following intubation. Heart rate and arterial pressure were also increased significantly in both groups following intubation.

The use of adrenaline added to bupivacaine during epidural analgesia for labour is controversial. The effects of epidural analgesia with bupivacaine containing adrenaline on maternal blood pressure and heart rate, uterine activity, progress of labour, fetal heart rate and Apgar scores, were assessed using visual analogue pain scores, upper level of sensory block and motor blockade in 60 parturients who were allocated randomly to receive: 10 mL of bupivacaine 0.25% plain (group I) or with adrenaline 5 μg mL−1 (group II) or with adrenaline 1.66 μg mL−1 (group III).

The first stage of labour was significantly longer in group II than in group I [414 ± 49 vs. 296 ± 24 min (± SD)]. There were no other significant differences. It is concluded that adrenaline at 5 μg mL−1 significantly prolongs the first stage of labour. Neither adrenaline 5 μg mL−1 nor 1.66 μg mL−1 has any beneficial effect.

Pipecuronium bromide, a long acting non-depolarizing neuromuscular blocking agent was administered to four groups of 10 patients using the priming technique.The effects of the combination of two different priming doses (0.01 or 0.015 mg kg−1) given at two different time intervals (3 or 4 min) before the ‘main’ intubating dose (0.07 or 0.065 mg kg−1) were investigated. Onset times were recorded and the intubation conditions were scored and compared with a group of patients receiving the same total amount of pipecuronium(0.08 mg kg−1) in a single bolus injection. Intubating conditions at 90 s after administration of the intubating dose were found to be significantly improved in all primed groups but the onset times, evaluated using the response of the adductor pollicis muscle to a single twitch stimulation, were similar to that observed after the single bolus injection. The optimal priming combination is considered to be 0.01 mg kg−1 of pipecuronium followed 3 to 4 min later by 0.07 mg kg−1.

The influence of haemodilution with colloids on somatosensory evoked potentials in non-premedicated volunteers is reported. In seven volunteers (randomized crossover design), blood (20 mL kg−1 within 30 min) was removed and simultaneously replaced by gelatin 3% or hydroxyethylstarch 6%. After 30 min, blood was retransfused within 30 min. Median and posterior tibial nerve somatosensory evoked potentials were recorded from the cortex, second cervical vertebra, Erb's point and 1st lumbar vertebra, respectively. One volunteer experienced a severe allergic reaction to gelatin, therefore only six gelatin trials were evaluated. Haemodilution decreased the haematocrit from 39.8 ± 1.6% (mean ± SD) to 31.1 ± 2.0% (gelatin) and from 40.7 ± 1.7% to 29.8 ± 1.5% (hydroxyethylstarch), respectively. Retransfusion increased haematocrit to 34.4 ± 0.9% (gelatin) and to 34.2 ± 1.3% (hydroxyethylstarch). Neither haemodilution with gelatin nor haemodilution with hydroxyethylstarch or retransfusion influenced evoked potentials. In conclusion, the treatment of blood loss up to 30% of estimated blood volume with gelatin or hydroxyethylstarch will not affect somatosensory evoked potential monitoring provided normovolaemic conditions are maintained.

One hundred and one women (ASA grades I and II) were anaesthetized for routine gynaecological surgery using an intravenous (i.v.) anaesthetic technique combining propofol and alfentanil. The patients were allocated randomly into groups. Group one received 33% oxygen in nitrous oxide and group two received 33% oxygen in air (total i.v. anaesthesia). The group receiving nitrous oxide required significantly less (P < 0.05) of the propofol and alfentanil mixture to maintain anaesthesia and this was found to reduce the mean cost of anaesthesia by £1.70, (P < 0.05). There was no significant difference in the incidence of post-operative complications between the two groups. We suggest that nitrous oxide may be used to reduce the cost of total i.v. anesthesia with propofol and alfentanil without causing any increase in post-operative morbidity in patients undergoing routine gynaecological surgery.

A 21-year-old female weighing 55 kg was anaesthetized for facial reconstruction. After an initial bolus of pancuronium 5 mg and top-up doses of 2 mg at 135 min and 1 mg at 290 min and 335 min, no further relaxant was given for 130 min at which time neuromuscular transmission appeared fully recovered with a full train-of-four twitches and a sustained response to 50 Hz stimulation of the posterior tibial nerve. Subsequently, a single dose of mivacurium 8 mg(2 X ED95) produced extended paralysis with no response to train-of-four stimulation for 85 min. The prolonged effect of mivacurium may have been because of inhibition of plasma cholinesterase by pancuronium. The serum cholinesterase activity 12 h after surgery was 0.38 units mL−1 (normal range 0.65–1.0 units mL−1). There was no evidence of atypical choylinesterase.

Ketamine 3–6 mg kg−1 given by mouth to paediatric patients for anaesthetic premedication was evaluated. Forty-three children, ages 2–9 years were randomly allocated to receive either ketamine (3 or 6mg kg−1) or placebo (cola 0.2 mL kg−1). Oral use of ketamine made separation from the families easier, gave an increased level of sedation, made acceptance of mask application easier and improved the emotional state in the recovery phase. These improvements were present with ketamine 3mg kg−1 and 6mg kg−1 in comparison with the placebo. We conclude that 3mg kg−1 ketamine given by mouth to premedicate paediatric patients is as effective as 6mg kg−1 but has a decreased incidence of side effects such as nystagmus and vomiting.