Summary

The mitochondrial myopathies consist of a heterogeneous group of disorders caused by structural and functional abnormalities in mitochondria leading to involvement of the nervous system and muscles as well as other organ systems. The peculiar genetic characteristics of mitochondrial DNA impart distinctive properties to these disorders. The pathophysiology is presented. The methods employed in making the correct diagnosis, the preoperative patient assessment and correction of metabolic dysfunctions and anaesthetic techniques used, are highlighted. The conditions are briefly reviewed and suggestions are made for the safe anaesthetic management of affected patients.

Summary

Background and objective: The clinical practice of spinal morphine administration for pain relief is based on observations in animals that opioid receptors exist in the spinal cord and intrathecal injections of opioids in those species (mostly rats) lead to antinociceptive effects. Clinicians are well aware that administration of spinal opioids is associated with side-effects, such as nausea and respiratory depression, that indicate supraspinal spread of the drug administered. Those observations call into question how much of the observed pain relief is due to action of the drug in the brain. This study investigated the spinal cord actions of morphine given intrathecally to rats in a model that allows investigation of drug–receptor interaction at the spinal cord level. Experiments were performed on male Wistar rats with chronically implanted lumbar subarachnoid catheters.

Methods: Nociceptive thresholds were measured in rats given morphine intrathecally alone and in combination with intrathecal injections of selective opioid receptor antagonists: β-funaltrexamine (μ), naltrindole (δ) and nor-binaltorphimine (κ).

Results: Intrathecal morphine caused dose-related antinociceptive effects that were reversed totally by naloxone. Intrathecal β-funaltrexamine and naltrindole did not reverse the effects of intrathecal morphine. However, intrathecal nor-binaltorphimine did reverse the electrical current threshold effects of morphine but not tail flick latency.

Conclusions: Antinociception following intrathecal morphine involves spinal and supraspinal opioid receptors. The tail flick effect described in rat experiments involves actions at opioid receptors in the brain that override any action that may be caused by combination of morphine with μ-opioid receptors in the spinal cord.

Summary

Background and objective: Combined spinal–epidural is an alternative technique to epidural analgesia for labour, but its benefits are not clearly identified.

Methods: A prospective, blinded, randomized study was undertaken involving 113 women attending a university hospital obstetric department. Analgesia was initiated with intrathecal bupivacaine 0.25% 1 mL + sufentanil 5 μg in the combined spinal–epidural group (n = 54), and with bupivacaine 0.125% + epinephrine 2.5 μg mL−1 + sufentanil 7.5 μg in the epidural group (n = 59). In both cases this was followed by patient-controlled epidural analgesia with bupivacaine 0.125% (+sufentanil 0.25 μg mL−1). Duration of labour, quality of analgesia and side-effects were compared between groups.

Results: In the combined spinal–epidural group, the onset of analgesia was faster (5 vs. 15 min, P < 0.001), the consumption of bupivacaine was lower (7.5 vs. 11.3 mg h−1, P = 0.003) and there was less unilateral analgesia (14.8% vs. 40.7%, P = 0.002) than in the epidural group. The characteristics of labour were similar in both groups. However, in the combined spinal–epidural group, there was a higher incidence of posterior presentation (25.9% vs. 10%, P = 0.03), pruritus (P < 0.001), hypotension (P = 0.002), somnolence (P = 0.01), nausea (P = 0.02) and one case of meningitis.

Conclusions: The combined spinal–epidural technique provided more effective analgesia during labour than epidural analgesia alone but offered no other advantage. It induced more adverse effects and this should be considered before routinely using the combined spinal–epidural technique.

Summary

Background and objective: Intrathecal ketamine as the sole anaesthetic agent has demonstrated a lack of cardiovascular depression that should be of advantage in an elderly population. S(+) ketamine has three-times the analgesic potency of R(−) ketamine and its antinociceptive effects after intrathecal administration in rats are known. We decided to evaluate the effects of intrathecal S(+) ketamine added to a small dose of spinal bupivacaine in elderly patients undergoing transurethral prostate surgery.

Methods: Forty males over 60 yr old, scheduled for transurethral prostate resection under spinal anaesthesia, were studied in a prospective, double-blinded, randomized way. Patients were allocated to receive either bupivacaine 10 mg or bupivacaine 7.5 mg combined with S(+) ketamine 0.1 mg kg−1. Spinal block onset time, maximum sensory level, duration of blockade, haemodynamic variables, postoperative analgesic requirements and adverse events were recorded.

Results: Onset times of motor and sensory block were shorter in the bupivacaine plus S(+) ketamine group. Incomplete motor block of the lower extremities was seen in 80% of the patients in bupivacaine plus S(+) ketamine group. Duration of complete motor block and spinal analgesia was shorter in the bupivacaine plus S(+) ketamine group. There was no significant difference in arterial pressure. Heart rate decreased after spinal anaesthesia in the bupivacaine plus S(+) ketamine group and was significantly lower until the end of anaesthesia. The incidence of adverse effects was not different between groups.

Conclusions: Intrathecal S(+) ketamine administered with a low dose of bupivacaine provides shorter motor and sensory block onset time, shorter duration of action and less motor blockade in elderly males.

Summary

Background and objective: The addition of clonidine to local anaesthetics enhances pain relief after peripheral nerve block, but the site of action is unproven.

Methods: Seven healthy volunteers underwent three brachial block procedures using bupivacaine 0.25% 1 mg kg−1 + epinephrine 1 : 200 000 (=local analgesic) in a randomized, double-blind cross-over fashion: (a) control treatment: local analgesic with 0.9% sodium chloride solution for the block and an intramuscular injection of saline; (b) intramuscular treatment: local analgesic with 0.9% NaCl for block and an intramuscular injection of clonidine 2 μg kg−1 and (c) block treatment: local analgesic with clonidine 2 μg kg−1 for block and an intramuscular injection of saline.

Results: The onset and duration of complete blockade (sensory/motor/temperature) was evaluated in the four nerve regions of the hand and forearm. Additionally, sedation score, blood pressure, heart rate and plasma clonidine concentrations were determined. The median duration of complete sensory blockade was 270 min (range 0–600) for block treatment compared to 0 min (range 0–480) for intramuscular treatment (P < 0.05) and 0 min (range 0–180) for control treatment (P < 0.05). Motor and temperature blockade exhibited similar results. Administration of clonidine was associated with sedation and a decrease in heart rate and blood pressure independent of the route of administration. Plasma clonidine concentrations were lower for block compared to the intramuscular treatment.

Conclusions: The admixture of clonidine to bupivacaine plus epinephrine prolongs and enhances brachial plexus blockade. Lower clonidine plasma concentrations for block treatment strongly suggest a local effect.

Summary

Background and objective: Clonidine has cardiac and systemic effects that can modify the potentially lethal cardiovascular effects of local anaesthetics. We evaluated the effects of clonidine pre-treatment on cardiotoxicity induced by an infusion of bupivacaine or ropivacaine and the success rate of resuscitation in anaesthetized rats.

Methods: Thirty-two Sprague–Dawley rats (250–300 g) were anaesthetized with thiopental and ketamine. Lung ventilation was maintained mechanically, and the electrocardiograph and invasive blood pressure were recorded continuously. Two separate groups of rats were treated with intravenous clonidine 5 μg kg−1 (n = 16) or saline (n = 16) in a randomized fashion. Fifteen minutes later, each group was randomly subdivided into two equal groups and an infusion of bupivacaine or ropivacaine, 3 mg kg−1 min−1, was given until cardiac arrest (asystole) occurred. The times when the cardiotoxic events (25%, 50% and 75% reduction of arterial pressure and heart rate, first dysrhythmia and asystole, respectively), induced by the local anaesthetic, occurred and the resuscitation outcome scores were recorded.

Results: Clonidine reduced heart rate and arterial pressure (P < 0.01). Clonidine did not alter cardiotoxicity or the success rate of resuscitation in bupivacaine-treated rats. In the ropivacaine group, clonidine increased the 25%, 50% and 75% reduction times of arterial pressure and the 50% and 75% reduction times of heart rate, times to first dysrhythmia and asystole (P < 0.05). Clonidine also increased the success rate of resuscitation in ropivacaine-treated rats (P < 0.05).

Conclusions: Although pre-treatment with clonidine protects the effects of ropivacaine cardiotoxicity and increases the success rate of resuscitation, it does not affect bupivacaine toxicity.

Summary

Background and objective: Eutectic mixture of local anaesthetic cream and lidocaine iontophoresis are effective in providing analgesia for peripheral venous cannulation with small gauge cannulae in adults and children. The objective of this study was to compare the analgesic efficacy of the two techniques directly in patients using larger cannulae.

Methods: In a double-blind, randomized, controlled study we compared the two techniques directly. Twenty-eight patients had the eutectic mixture of local anaesthetic cream applied to the dorsum of one hand for 60 min followed by sham iontophoresis (group EMLA); the other hand had a sham cream applied for 60 min followed by 10 min of 2 mA iontophoresis with lidocaine 4% and epinephrine 1 in 50 000 (group iontophoresis). Within 5 min of completion of iontophoresis an anaesthetist, unaware of treatment allocation, inserted 18-G venous cannulae into veins of both hands. The patient then scored the amount of pain on cannulation using a 10 point verbal rating scale.

Results: Eight patients were excluded from analysis due to failed cannulation (two group EMLA, two group iontophoresis), intolerable burning sensation from iontophoresis (one), protocol violation (one), and changes in surgical schedule (two). Pain scores were lower for the EMLA treated hand than for the iontophoresis side (median (range) 1 (0–7) vs. 3 (0–6); P = 0.023). Erythema and paraesthesia were common but short lived on the iontophoresis side.

Conclusions: Although lidocaine iontophoresis is effective more quickly than the eutectic mixture of local anaesthetic cream, the superior quality of analgesia produced by the eutectic mixture in this study should be borne in mind if these treatments are used electively.

Summary

Background and objective: This randomized, prospective study was performed to evaluate the efficacy of a subcutaneous local anaesthetic infiltration prior to venepuncture using different cannula sizes.

Methods: Three-hundred-and-one patients were included in the study, 150 received mepivacaine 1% (0.25 mL) subcutaneously, 151 were cannulated without local analgesia. Patients were further allocated to one of five cannula size groups (standard wire gauge (G)): 20-, 18-, 17-, 16- and 14-G. They were asked to quantify the pain experienced using a four-point rating scale.

Results: In the group without local anaesthetics, 28.8% complained about pain compared to 12% receiving local analgesia. The incidence of pain for 14-G (10%) and 16-G (12.9%) cannulae was significantly reduced in the local analgesia group (P < 0.01) compared to no local analgesia (77.4% and 45.1%). Other cannula sizes showed no difference in pain whether using local analgesia or not.

Conclusions: Patients profit from a subcutaneous infiltration with mepivacaine 1% prior to intravenous cathetherization only when cannulae of size ≥16-G are inserted.

Summary

Background and objective: To compare the effects of sevoflurane and desflurane anaesthesia on lipid peroxidation.

Methods: We studied 40 healthy patients undergoing elective laparoscopic cholecystectomy. Patients were randomly allocated to be anaesthetized either with sevoflurane (n = 20) or desflurane (n = 20). Anaesthesia was maintained with inspiratory concentrations of sevoflurane 1–1.5 MAC (n = 20) or desflurane (n = 20). Samples were taken for plasma malondialdehyde and superoxide dismutase assays before induction of anaesthesia, before skin incision and at the end of surgery. Alveolar cell samples were obtained from the lungs using the technique of protective blind bronchoalveolar lavage, after induction of anaesthesia and at the end of surgery for malondialdehyde and superoxide dismutase concentrations.

Results: Plasma malondialdehyde increased more after the administration of desflurane than after sevoflurane: after induction 5.9 ± 0.6 nmol mL−1 for desflurane vs. 3.8 ± 0.5 nmol L−1 for sevoflurane (P < 0.001); at the end of the surgery: 6.7 ± 0.4 nmol mL−1 for desflurane vs. 4.2 ± 0.3 nmol mL−1 for sevoflurane (P < 0.001). There was a small but significant increase in plasma superoxide dismutase concentration after desflurane – from 24.2 ± 1.2 to 24.9 ± 0.9U mL−1 after induction and 25 ± 1U mL−1 at the end of the surgery (P < 0.01) but no increase with sevoflurane. Malondialdehyde concentrations increased significantly in the cells obtained by protective blind bronchoalveolar lavage at the end of surgery in the desflurane group (from 0.3 ± 0.1 to 1.7 ± 0.2 nmol mL−1 (P < 0.001)), but not in the sevoflurane group. There were no significant differences between the two anaesthetics in the amounts of superoxide dismutase in the samples obtained by protective blind bronchoalveolar lavage.

Conclusions: Desflurane may cause more systemic and regional lipid peroxidation than sevoflurane during laparoscopic cholecystectomy in healthy human beings.

Summary

Background and objective: The P2X receptor is responsible for fast excitatory neurotransmission in the central nervous system. This receptor is suggested as one of the targets of volatile anaesthetics. The study was undertaken to examine the site of action of volatile anaesthetics, especially for P2X purinoceptor-mediated neurotransmission.

Methods: The effect of sevoflurane and isoflurane on [3H] α,β-methylene ATP binding was investigated in rat crude synaptic membranes. The crude synaptic membranes were prepared from Sprague-Dawley rat brains by centrifugation and then incubated with volatile anaesthetics or P2 receptor antagonists.

Results: [3H] α,β-methylene ATP binding was unchanged by either sevoflurane or isoflurane at clinically relevant concentrations. Suramin, a P2 antagonist, significantly (P < 0.05) decreased the binding of [3H] α,β-methylene ATP in a dose-dependent manner (68.7 ± 14.7% at 10 μmol, 49.5 ± 6.4% at 50 μmol, 24.3 ± 5.7% at 100 μmol, n = 10, mean ± SD), whereas pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), another P2 antagonist, did not affect the binding.

Conclusions: The suppressive effect of volatile anaesthetics on ATP-mediated excitatory synaptic transmission could be one site of action. However, the blockade of ATP binding to P2X receptors is not a mechanism of action of volatile anaesthetics.

Summary

Background and objective: Propofol may cause undesirable hypotension due to vasodilation. The underlying mechanisms are not completely understood. We investigated the mechanisms by which propofol relaxes vascular segments.

Methods: We studied the effect of propofol on isolated porcine coronary artery rings precontracted with potassium chloride or prostaglandin F2α.

Results: Propofol, in a concentration-dependent manner, relaxed all segments at concentrations of 5 μg mL−1 and above. This relaxation was unaltered in the presence of Nω-nitro-L-arginine, indomethacin, diltiazem and glibenclamide. Tetraethylammonium chloride, an inhibitor of the BKCa K+ channel (a high conductance Ca2+-sensitive K+ channel), dose-dependently attenuated the vasodilating effect of propofol (P < 0.001).

Conclusions: Our results suggests that the activation of the BKCa channel may contribute to the vasodilating effect of propofol, hereby causing hyperpolarization of the smooth muscle membrane and reduction of smooth muscle tone.

Summary

Background and objective: To investigate the effects of moderate hyponatraemia, induced by intravenous application of an electrolyte-free irrigation fluid, as a model of the human transurethral prostate resection syndrome and of its rapid correction by hypertonic saline infusion in rats.

Methods: Experimental animals received irrigation fluid (Purisole SM®) 20 mL kg−1 body weight, intravenously. In one group, hyponatraemia was subsequently rapidly corrected by infusion of hypertonic saline (NaCl 5.85%), while rats of group two were ‘sham-corrected’ by infusion of a balanced salt crystalloid solution. Plasma sodium concentrations were analysed during and at the end of the experiments. After 10 days, experimental and untreated control animals were killed humanely, fixed by perfusion and the brains were prepared for electron microscopic investigation of myelin sheets and glial cell numbers in the striatum and pons.

Results: The myelin appearance was unaltered in experimental groups compared to controls, but glial cell numbers were distinctly altered in the pons but not in the striatum. In the pons, oligodendrocytes were significantly reduced in number upon rapid correction of hyponatraemia, while astrocyte numbers were increased in rats with uncorrected hyponatraemia.

Conclusions: Our electron microscopic data demonstrate that the effects of hyponatraemia and of its rapid correction are multifarious in animals. This may also apply for human patients during transurethral prostate resection.