Summary

In adults, a number of measures to reduce perioperative blood loss have been established. These techniques serve to reduce patients' exposure to homologous blood. Most adults are concerned with this issue especially since many patients became infected with human immunodeficiency virus (HIV) during the 1980s through exposure to blood components. While blood-saving strategies are widely used in adults, they are mostly neglected in infants. However, it is these young patients with their whole life in front of them who, it could be argued, would benefit especially from any potentially avoidable infection (HIV, hepatitis, etc.) or immunological complications. In infants and small children, these blood-sparing techniques may not be as effective as in adults and technical limitations may prevent their application. However, some of these measures can be used and may serve to prevent or reduce exposure to homologous blood. In the following review, blood-saving techniques established in adults are described and their applicability for paediatric patients discussed.

Summary

Background and objective: We studied the pharmacokinetics and pharmacodynamics of GPI 15715 (Aquavan® injection), a new water-soluble prodrug metabolized to propofol by hydrolysis.

Methods: Nine adult male Sprague–Dawley rats (398 ± 31 g) received a bolus dose of 40 mg GPI 15715. The plasma concentrations of GPI 15715 and propofol were determined from arterial blood samples, and the pharmacokinetics of both compounds were investigated using compartment models whereby the elimination from the central compartment of GPI 15715 was used as drug input for the central compartment of propofol. Pharmacodynamics were assessed using the median frequency of the EEG power spectrum.

Results: A maximum propofol concentration of 7.1 ± 1.7 μg mL−1 was reached 3.7 ± 0.2 min after bolus administration. Pharmacokinetics were best described by two-compartment models. GPI 15715 showed a short half-life (2.9 ± 0.2 and 23.9 ± 9.9 min), an elimination rate constant of 0.18 ± 0.01 min−1 and a central volume of distribution of 0.25 ± 0.02 L kg−1. For propofol, the half-life was 1.9 ± 0.1 and 45 ± 7 min, the elimination rate constant was 0.15 ± 0.02 min−1 and the central volume of distribution was 2.3 ± 0.6 L kg−1. The maximum effect on the electroencephalogram (EEG) – EEG suppression for >4 s – occurred 6.5 ± 1.2 min after bolus administration and baseline values of the EEG median frequency were regained 30 min later. The EEG effect could be described by a sigmoid Emax model including an effect compartment (E0 = 16.9 ± 7.9 Hz, EC50 = 2.6 ± 0.8 μg mL−1, ke0 = 0.35 ± 0.04 min−1).

Conclusions: Compared with known propofol formulations, propofol from GPI 15715 showed a longer half-life, an increased volume of distribution, a delayed onset, a sustained duration of action and a greater potency with respect to concentration.

Summary

Background and objective: The effect of propofol on myocardial dysfunction during ischaemia and reperfusion is controversial yet important because of its frequent use in cardiac anaesthesia. Although animal studies suggest a free radical-scavenging potential, the cardioprotective properties of propofol have not been demonstrated consistently in vivo. Previous studies focused on systolic function while diastolic function may be a more sensitive marker of ischaemic injury. The main aim was to document the effect of propofol on diastolic function in isolated, blood perfused rabbit hearts subjected to moderate global ischaemia and reperfusion.

Methods: Propofol 168 μmol L−1, or the equivalent of its vehicle, Intralipid®, was administered to 34 paced parabiotic Langendorff blood-perfused isolated rabbit hearts before and after 30 min of global normothermic ischaemia. Recovery of systolic function was quantified with the maximum rate of rise of left ventricular pressure. Diastolic performance was assessed using the time constant of the decline in left ventricular pressure (τ) and chamber stiffness (VdP/dV at 12 mmHg).

Results: Recovery of systolic function during reperfusion was comparable in the two groups. There was no difference in left ventricular pressure between the two groups at any time during the experiments. Chamber stiffness increased significantly during ischaemia and reperfusion in the control group (from 34 ± 9 to 54 ± 8 mmHg during ischaemia, and 43 ± 5 mmHg after 30 min reperfusion; mean ±95% confidence interval) but not in the propofol-treated group (29 ± 5, 36 ± 8 and 30 ± 8 at baseline, ischaemia and 30 min reperfusion, respectively).

Conclusions: Propofol has no protective effect on active relaxation or on systolic function in the present model, but it reduces ischaemic and postischaemic chamber stiffness.

Summary

Background and objective: The effects of sevoflurane on bupivacaine cardiotoxicity are mainly attributed to systemic effects. The purpose of this study was to investigate the direct myocardial effects of sevoflurane on bupivacaine toxicity.

Methods: Hearts of 30 Wistar albino rats were isolated and mounted on a Langendorff apparatus perfused by modified Tyrode solution. Experimental groups were: a sevoflurane group (Group S, n = 10) – following baseline and 20 min (Stage 1) recordings, sevoflurane was added in doses of 1.4% (1 MAC) and 2.8% (2 MAC). In the two bupivacaine groups, bupivacaine 5 μmol (Group B5, n = 10) and bupivacaine 10 μmol (Group B10, n = 10) was added to the solution at Stage 1, and sevoflurane was added to the system as in Group S. Haemodynamic variables, i.e. heart rate, PR interval, QRS duration, left ventricular systolic pressure, contractility (+dp/dtmax), relaxation, time to reach peak systolic pressure, change in left ventricular diastolic pressure from baseline, and rate–pressure product were recorded.

Results: In Group S, there was no change in cardiac rhythm. In bupivacaine groups, severe rhythm disturbances occurred and both the PR intervals and QRS complexes were prolonged significantly. All contractility variables deteriorated and the rate–pressure product decreased by 67–90% with the addition of bupivacaine. In all groups, 2 MAC sevoflurane lowered +dp/dtmax further.

Conclusions: Sevoflurane does not have any untoward effect on bupivacaine-induced cardiotoxicity in clinically relevant doses in the isolated rat heart.

Summary

Background and objective: This study was designed to compare the haemodynamic, electrophysiological and pharmacodynamic effects of three selective inhibitors of the different isoenzyme forms of phosphodiesterase (PDE) on ischaemia-induced dysrhythmias in the anaesthetized rat. The drugs used were pimobendan, a selective PDE III inhibitor, rolipram, a selective PDE IV inhibitor, and zaprinast, a selective PDE V inhibitor.

Methods: The coronary artery was occluded 15 min after commencing drug administration, and myocardial ischaemia was maintained for 30 min during which the heart rate and mean arterial pressure were recorded. cAMP and cGMP were determined by radioimmunoassay.

Results: Pretreatment with rolipram decreased the duration of ventricular tachycardia without any change in the incidences of dysrhythmias or the mortality rate. This drug did not modify ventricular content of adenosine 3′,5′-cyclic monophosphate (cAMP) or guanosine 3′,5′-cyclic monophosphate (cGMP). Pimobendan (1 mg kg−1 + 0.1 mg kg−1 min) decreased the duration of ventricular tachycardia. This dose of pimobendan and zaprinast (1 mg kg−1 + 0.1 mg kg−1 min−1) increased the incidence rate of ventricular fibrillation following coronary artery ligation and the mortality rate. Moreover, both drugs increased cGMP in the ventricle.

Conclusions: The results demonstrated that pimobendan and zaprinast increased the incidence of dysrhythmias and the mortality rate, which was accompanied by an increase in the ventricular content of cGMP. Rolipram decreased the duration of ventricular tachycardia without a change in the cyclic nucleotide content or in the mortality rate.

Summary

Background and objective: The aim was to determine the effect of acute and chronic administration of 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, on the righting reflex ED50 and the minimum alveolar concentration during sevoflurane anaesthesia in rats.

Methods: 7-Nitroindazole was acutely (0, 50 and 100 mg kg−1) and chronically (0 and 150 mg kg−1 day−1, 4 days) administered to rats. After the preparation, the minimum alveolar concentration and the righting reflex ED50 were measured. The concentration of cGMP in the brain, cerebellum and spinal cord was also measured.

Results: Acute administration reduced the minimum alveolar concentration (50 mg kg−1, 58.8% (95% CI: 50.3–67.3%) of the baseline value, P < 0.01; 100 mg kg−1, 55.8 (46.9–64.7), P < 0.01) and the righting reflex ED50 (50 mg kg−1, 27.2 (17.2–37.2), P < 0.01; 100 mg kg−1, 14.3 (6.6–22.0), P < 0.01). Chronic administration did not reduce the minimum alveolar concentration; however, it reduced the righting reflex ED50 (65.3 (52.9–77.7), P < 0.01). Overall, the reduction in minimum alveolar concentration in the acute and chronic protocol did not correlate with that of the righting reflex ED50. 7-Nitroindazole (100 mg kg−1, acute) reduced the cGMP concentration within the cerebellum by 55.4%; however, it did not decrease concentrations in the brain or spinal cord.

Conclusions: Different mechanisms are responsible for the observed alterations to the minimum alveolar concentration and the righting reflex ED50 following treatment with 7-nitroindazole. The nitric oxide–cGMP pathway might play a less important role in the determination of minimum alveolar concentration than the righting reflex ED50.

Summary

Background and objective: Propofol is a phenol derivative (2,6 di-isopropylphenol) with a unique effect profile including activating effects on GABAA and blocking effects on voltage-operated sodium channels. If the substituents in the 2- and the 6-positions are replaced by tert-butyl groups, the resulting phenol derivative, 2,6 di-tert-butylphenol, despite being a close structural propofol analogue, completely lacks GABAA receptor effects. The aim of this in vitro study was to investigate the effects of 2,6 di-tert-butylphenol on voltage-operated neuronal sodium channels in order to determine whether and, if so, how these structural changes alter the sodium channel-blocking effect seen with propofol.

Methods: Whole-cell sodium inward currents through heterologously expressed rat type IIA sodium channels were recorded in the absence and presence of definite concentrations of 2,6 di-tert-butylphenol and propofol.

Results: When applied at concentrations ≥30 μmol, 2,6 di-tert-butylphenol completely and irreversibly blocked sodium inward currents. The blockade equilibrium time was about 2 min. A partial washout was possible only if the application was stopped before the equilibrium of the blockade was achieved.

Conclusions: 2,6 Di-tert-butylphenol exerts a high-affinity block of neuronal sodium channels. Apparently, the slight structural differences of 2,6 di-tert-butylphenol in comparison with propofol – which account for the lack of GABAA receptor effects – enhance its voltage-operated sodium channel-blocking effects. As 2,6 di-tert-butylphenol is much more potent than most sodium channel blockers in clinical use, it might be of interest in the development of local anaesthetics.

Summary

Background and objective: The study was designed to identify those factors associated with early tracheal extubation following cardiac surgery. Previous studies have tended to concentrate on surgery for coronary artery bypass or on other selected cohorts.

Methods: Sequential cohort analysis of 296 unselected adult cardiac surgery patients was performed over 3 months.

Results: In total, 39% of all patients were extubated within 6 h, 89% within 24 h and 95% within 48 h. Delayed extubation (>6 h after surgery) appeared unrelated to age, gender, body mass index, a previous pattern of angina or myocardial infarction, diabetes, preoperative atrial fibrillation, and preoperative cardiovascular assessment, as well as other factors. Delayed tracheal extubation was associated with poor left ventricular, renal and pulmonary function, a high Euroscore, as well as the type, duration and urgency of surgery. Early extubation (<6 h) was not associated with a reduced length of stay in either the intensive care unit or in hospital compared with patients who were extubated between 6 and 24 h. In these groups, it is presumed that organizational and not clinical factors appear to be responsible for a delay in discharge from intensive care. Patients who were extubated after 24 h had a longer duration of hospital stay and a greater incidence of postoperative complications. Postoperative complications were not adversely affected by early tracheal extubation.

Conclusions: In an unselected sequential cohort, both patient- and surgery-specific factors may be influential in determining the duration of postoperative ventilation of the lungs following cardiac surgery. In view of the changing nature of the surgical population, regular re-evaluation is useful in reassessing performance.

Summary

Background and objective: The reported incidence of shoulder tip pain following laparoscopic surgery varies from 35 to 63%. This study evaluated the analgesic efficacy of either performing a prophylactic suprascapular nerve block with bupivacaine or applying a piroxicam patch to the skin over both shoulders for the relief of shoulder tip pain after laparoscopy.

Methods: Sixty healthy informed female patients were randomly assigned to one of three groups: (a) a control group (n = 20), no treatment; (b) a suprascapular nerve block group (n = 20) in which a bilateral suprascapular nerve block was performed before induction of anaesthesia with 5 mL 0.5% bupivacaine with epinephrine; and (c) a piroxicam patch group (n = 20) in which a 48 mg piroxicam patch on the skin of each shoulder was applied before induction of anaesthesia. All patients received a total intravenous anaesthesia technique with propofol, fentanyl and vecuronium. Shoulder tip and wound pain were recorded on a visual analogue pain scale at five time intervals for 24 h after surgery.

Results: A total of 80% of patients in the control group, 75% in the suprascapular nerve block group and 45% in the piroxicam patch group complained of shoulder tip pain during the recording period (P < 0.05). The scores for shoulder tip pain in the piroxicam patch group were significantly lower compared with the control group at 3, 6 and 12 h, and compared with the suprascapular nerve block group at 6 and 12 h. The need for analgesics was also significantly lower in the piroxicam patch group compared with the other two groups.

Conclusions: Prophylactic piroxicam patches are effective and safe for the relief of shoulder tip pain after laparoscopy. Bilateral suprascapular nerve block is not effective in this setting.

Summary

Background and objective: Acute hiccup is a minor complication that can occur during sedation or general anaesthesia. The disorder can disturb the surgical field, might interfere with lung ventilation or could hamper diagnostic procedures. The objective was to perform a systematic search for interventions aimed at treating hiccup occurring during anaesthesia or sedation.

Methods: A systematic search for reports describing interventions to treat hiccup in conjunction with anaesthesia was carried out (MEDLINE, EMBASE, Cochrane-Library, manual screening of reference lists and review articles, up to December 2001). Search terms were ‘hiccup’, ‘singultus’ or ‘hiccough’.

Results: Twenty-six reports involving approximately 581 patients focused on hiccup remedies in the anaesthesia setting. Only one report was substantiated by a randomized controlled trial. This investigated methylphenidate 10 mg intravenously in 51 patients, which did not show a beneficial effect compared with placebo. Hiccup was a self-limiting phenomenon. Case series and case reports focused on various systemically applied drugs in 12 reports, stimulating techniques (e.g. pharyngeal stimulation) in seven, topical applied remedies (e.g. intranasal ice-cold water) in four, and ventilation techniques (e.g. continuous positive pressure ventilation) in two.

Conclusions: A large variety of interventions have been proposed for the treatment of hiccup during anaesthesia and sedation. However, perioperative treatment is still based on empirical findings and no treatment is ‘evidence-based’. Thus, no valid recommendations for the treatment of hiccup can be derived. Uncontrolled observations are inadequate to establish treatment efficacy.

Summary

Background and objective: Rocuronium and, to a lesser extent, vecuronium can induce burning sensations associated with withdrawal reactions during administration. Dermal microdialysis in human and electrophysiological recordings of nociceptors in mouse skin were used to elucidate the underlying mechanisms of pain induction.

Methods: Microdialysis catheters were inserted intradermally into the forearm of 10 volunteers and were perfused with two different concentrations of rocuronium and vecuronium (1 and 10 mg mL−1) or a control. Dialysis samples were taken every 15 min and analysed for protein, histamine, tryptase and bradykinin content. Pain intensity was rated on a numerical scale of 0–10. In a parallel design, activation of cutaneous nociceptors was assessed directly in a skin–nerve in vitro preparation of the mouse hind paw. The receptive fields of identified single C-nociceptors (n = 12) were superfused with rocuronium or vecuronium solutions (10 mg mL−1) at physiological pH.

Results: In accordance with clinical observations, microdialysis of rocuronium (10 mg mL−1) induced sharp burning pain (NRS 4.1 ± 1.8), whereas vecuronium given in the usual clinical concentration (1 mg mL−1) induced only minor pain sensations (NRS 0.6 ± 1.3). At equimolar concentrations, pain sensation and concomitant mediator release evoked by both drugs were similar. No correlations were found between pain rating and mediator release. In the in vitro preparation, C-fibres showed a consistent excitatory response with rapid onset after stimulation with vecuronium as well as rocuronium (differences not significant).

Conclusions: The algogenic effect of aminosteroidal neuromuscular blocking drugs can be attributed to a direct activation of C-nociceptors.