We used 20 ml ropivacaine 0.75% for ankle blocks before foot surgery in 90 participants who we allocated in equal numbers to: perineural dexamethasone 8 mg and intravenous saline 0.9%; perineural saline 0.9% and intravenous dexamethasone 8 mg; or perineural and intravenous saline 0.9%. Dexamethasone increased the median (IQR [range]) time for the return of some sensation or movement, from 14.6 (10.8-18.8 [5.5-38.0]) h with saline to 24.1 (19.3-29.3 [5.0-44.0]) h when given perineurally, p = 0.00098, and to 20.9 (18.3-27.8 [8.8-31.3]) h when given intravenously, p = 0.0067. Dexamethasone increased the median (IQR [range]) time for the return of normal neurology, from 17.6 (14.0-21.0 [9.5-40.5]) h with saline to 27.5 (22.0-36.3 [7.0-53.0]) h when given perineurally, p = 0.00016, and to 24.0 (20.5-32.3 [13.0-42.5]) h when given intravenously, p = 0.0022. Dexamethasone did not affect the rates of block success, postoperative pain scores, analgesic use, or nausea and vomiting. The route of dexamethasone administration did not alter its effects.

BACKGROUND Prospective data on the use of prilocaine for ambulatory spinal anaesthesia remain limited. We compared the behaviour and characteristics of subarachnoid block using prilocaine and fentanyl with that of bupivacaine and fentanyl. METHODS In a prospective, double-blind, randomized controlled trial, 50 patients undergoing elective ambulatory arthroscopic knee surgery received subarachnoid anaesthesia, with either prilocaine 20 mg and fentanyl 20 µg (Group P) or plain bupivacaine 7.5 mg and fentanyl 20 µg (Group B). Primary endpoints included times for onset of maximum sensory block level and regression of sensory block to L4, and also motor block at 1 and 2 h, and levels of haemodynamic stability. Comparisons between the groups were made by χ² test for proportions and the Mann-Whitney test for ordinal data. Time-to-event data were analysed by the Mann-Whitney test for uncensored data or the logrank test for censored data. RESULTS At 2 h, motor block in Group P had fully resolved in 86% of patients, compared with 27% in Group B (P<0.001). Median time to regression of sensory block to L4 was significantly shorter in Group P (97 min) than in Group B (280 min) (P<0.001). A clinically significant decrease in arterial pressure was more common in Group B (73%) than in Group P (32%) (P=0.004). Two patients in Group P required conversion to general anaesthesia, but for reasons unrelated to prilocaine itself. CONCLUSIONS The combination of prilocaine and fentanyl is a better alternative to that of low-dose bupivacaine and fentanyl, for spinal anaesthesia in ambulatory arthroscopic knee surgery.

AIM OF THE STUDY:Cricoid pressure is recommended during positive pressure ventilation CPR and during anaesthesia when there is a risk of regurgitation. Studies suggest that cricoid pressure is frequently applied incorrectly placing patients at risk of regurgitation. Simulation training has been shown to improve the performance of cricoid pressure on a simulator, but whether simulation training improves the clinical performance of cricoid pressure was unknown. The aim of our study was to determine if simulator training improved the clinical performance of cricoid pressure. METHODS:101 medical students and nursing staff were recruited and randomised to receive cricoid pressure simulator training with or without force feedback. Subjects then applied cricoid pressure to an anaesthetised patient while standing on a force plate. The main outcome measure was the number of subjects who applied a mean force of 20-30N during their trial. RESULTS:Significantly more subjects (20/53, 38%) in the feedback group applied force in the appropriate range (20-30N) compared to the control group (9/48, 19%) (p=0.035, chi square test). The feedback group applied significantly higher forces than did the control group (p=0.029, Mann-Whitney U test). CONCLUSION:Simulation training with force feedback significantly improved the performance of cricoid pressure in the clinical setting. Simulation training should be used more frequently to train and maintain resuscitation skills.

Cricoid pressure has been used for over 200 years. During that time, training in the technique has not changed greatly, despite the well-documented potential for complications if performed improperly. Typically, training relies on quantitative or qualitative descriptions such as “firm” pressure, a number of Newtons of force or equivalent force to that causing pain while pressing on the nose. This study tests the value of these descriptive methods in training to apply cricoid pressure. Fifty subjects were asked to apply cricoid pressure after receiving a description of the force required and again after having tested how much finger pressure on the bridge of their nose was required to cause discomfort. Initial force, force at 45 seconds, minimum force, and maximum force was recorded. The results were analysed using the Wilcoxon signed ranks test, which showed no significant difference in performance between the two types of training. One subject maintained pressure in the range of 25 to 35 Newtons for the entire 45 seconds of the first attempt but no subject performed this well on the second attempt. The use of qualitative and quantitative descriptors of the appropriate pressure does not appear useful in the training of the technique of cricoid pressure. Training incorporating force feedback is recommended.

BACKGROUND:All medical practitioners should be able to manage the airway of an unconscious patient. Endotracheal intubation is the most effective method of securing the airway but is a complex skill requiring much practice. Traditionally, endotracheal intubation has been taught on patients, but this is not ideal.METHODS:We have developed a short course on endotracheal intubation taught in a clinical simulation unit (CSU). This unit has a large range of airway trainers and patient simulators, some of which can be manipulated to make intubation more difficult. Endotracheal intubation is taught in a series of steps in order to avoid cognitive overload. Each step is taught on an airway trainer that has no difficult features. Once this is mastered, more difficult situations are presented which require application of new techniques and/or equipment. In this way, students learn useful schemas to apply clinically.RESULTS:In 1 year, over 100 students and trainees were taught endotracheal intubation in the CSU. The ideal group size was found to be two students and one trainer. It took 75 to 90 minutes for most students to reach a standard where they could be expected to safely perform the technique on a patient. All comments on learning endotracheal intubation in this setting were positive. Many students felt more comfortable learning on a model than on a patient.CONCLUSION:Learning clinical procedures on simulators is becoming an essential part of medical education. More than one airway trainer may be needed to give students the expertise to perform endotracheal intubation on patients.

Objective: To assess the extent of the variability in insulin delivery over time, under conditions used in Australian neonatal units, studying the following variables: diluent, preconditioning, flushing, sequential preconditioning and flushing, insulin concentration, flow rate, catheter type, and addition of albumin.Methodology: A range of simulated insulin infusions was studied. Infusions were run over 22 h, with aliquots of infusate collected at baseline and after 15 min, 30 min, 1 h, 2 h, 6 h and 22 h. Insulin concentration was assayed using a radioimmunoassay.Results: An infusion of 50 mU insulin/mL at 1 mL/h gave negligible insulin delivery until 22 h. However, after preconditioning and flushing the tubing, consistent insulin delivery was attained by 6 h. An infusion of 200 mU insulin/mL at 1 mL/h did not provide consistent delivery until 6 h. At this concentration and rate, consistent insulin delivery was attained within 30 min of the start of the infusion either by preconditioning and flushing the tubing, or by addition of albumin to the infusate.Conclusion: Clinically significant variation in intravenous insulin delivery will occur in the neonatal setting unless counter-measures are taken, such as sequential preconditioning and flushing of the delivery system or the addition of albumin to the infusate.

We aimed to determine the optimum timing of midazolam administration prior to propofol to achieve the maximal reduction in the dose of propofol required to induce anaesthesia. Female (ASA 1–2) patients, aged 18 to 45 years, weighing 40 to 75 kg and scheduled for gynaecological surgery were eligible for the study. Consenting patients were randomly assigned to six groups. Group 1 received saline and Groups 2 to 6 received midazolam 3 mg at 1, 2, 4, 6 or 10 minutes respectively prior to propofol (n=20 to 22 per group) in a blinded manner. Propofol was administered IV over 10 seconds and flushed in with saline 5 ml. Two minutes later, the patient's response to pressure applied to the finger was determined as an index of loss of consciousness. The ED50 of propofol in each group was determined by the up-and-down method. Propofol ED50 was reduced to 34 to 67% (P<0.001) in the midazolam treated groups. There was no significant (P=0.14) difference in propofol ED50 among the five groups which received midazolam. Patients who received midazolam had less recollection of events surrounding induction (P<0.001) and recalled the induction experience as being more pleasant (P=0.03) than those who did not receive midazolam. These results indicate that midazolam may be given up to 10 minutes prior to propofol and still achieve a substantial dose reduction.

Since 1985 midwives have been responsible for choice of drug and timing of epidural top-up doses for women in labour at Flinders Medical Centre. The midwife may choose from one of three different prescribed preparations, namely: bupivacaine 12.5 mg plus pethidine 25 mg, bupivacaine 25 mg, and bupivacaine 50 mg - each made up in a volume of 10 ml. This prospective study examined the incidence of adverse effects and level of patient satisfaction with midwife-managed epidural analgesia. Between 1987 and 1992, 6935 women received midwife-managed epidural analgesia. The pethidine/bupivacaine mixture was generally used for the first dose (75% of women) with a shift towards bupivacaine 25 mg or 50 mg for subsequent top-ups. Sixty-one per cent of women had normal vaginal deliveries, 25% instrumental and 14% caesarean deliveries. The most common side-effects were shivering, hypotension and itch. Shivering occurred following 11% of bupivacaine, and 2% of bupivacaine/pethidine top-ups. Itching was more common after bupivacaine/pethidine (3%) than after bupivacaine (1%). Women reported a high level of satisfaction with the overall experience of childbirth, though this was lower for instrumental and caesarean deliveries than for vaginal deliveries. On the other hand, satisfaction with pain relief provided by the epidural was greater in women who had caesarean or instrumental deliveries. The most commonly cited benefits of epidurals were good pain relief (83%), ability to cope (74%), feeling relaxed (67%), and being aware (60%), while feeling numb (23%) and experiencing severe pain at delivery (17%) were the most common causes of dissatisfaction.

Extracorporeal circuits can cause haemolysis resulting in an increase in plasma-free haemoglobin (PFHb). High pressures and clots within the circuit have been identified as factors increasing the likelihood of haemolysis. Continuous venovenous haemodiafiltration (CVVHD) is associated with high circuit pressures as the pump-driven circuit clots over a period of time. PFHb was measured during CVVHD to determine if circuit life, maximum circuit pressure or the clotting of the haemofilter was associated with evidence of haemolysis. Circuit life up to 50 hours, circuit pressures or haemofilter clotting had no significant effect on PFHb. There was a small rise in PFHb in the circuits lasting beyond 50 hours. CVVHD circuits can be run up to 50 hours without concern for haemolysis.

Combinations of drugs are frequently used in the treatment of pain. This article reviews experimental designs and statistical techniques for studies aimed at determining whether the effects of drug combinations are additive, supra-additive (synergistic), or subadditive (antagonistic). The choice of design will depend on how the investigator chooses to define 'additive' drug effects, whether the drug effect is graded or dichotomous, and whether log(dose)-response curves are linear. The use of isobolograms, which allow the graphical representation of results for some study designs, is discussed. Methods for the statistical analysis of the most common designs are given, with examples.

With increasing interest in the application of dextromethorphan in pain control, it is probable that patients will receive this drug in combination with analgesics such as opioids, giving rise to the potential for previously unobserved drug interactions. The interaction between dextromethorphan, and its pharmacologically active metabolite dextrorphan, and norpethidine, a toxic metabolite of pethidine, was examined in rats. Rats were assigned to receive dextromethorphan (0, 20 or 40 mg/kg) or dextrorphan (0, 15 or 30 mg/kg) combined with norpethidine (0, 28 or 42 mg/kg). The occurrence of seizures, myoclonic jerks and shivering was recorded for 60 min after drug administration. Norpethidine produced dose-related increases in the incidence of seizures, myoclonic jerks and shivering. Dextromethorphan, but not dextrorphan, increased the incidence of these behaviours. It is recommended that extreme caution be exercised if dextromethorphan and pethidine are to be used together.

This study compared pain relief and adverse events from sustained-release ibuprofen and paracetamol administered for a week after laparoscopic cholecystectomy. Patients were randomly assigned to receive sustained-release ibuprofen (2x800mg once daily) or paracetamol (2x500mg PRN up to 4 hourly). Oxycodone tablets (5 mg) were available for rescue analgesia. Patients kept a pain diary for 1 week and were assessed by the investigators 24 h after surgery and at the surgical follow-up clinic. Patients receiving ibuprofen (n=46) reported lower pain scores (scale 0-4, where 0=no pain and 4=unbearable pain) than those receiving paracetamol (n=44) (mean 1.07 vs 1.35) and consumed less oxycodone (mean 0.83 vs 1.67 tablets). Although these differences were not statistically significant (P=0.057 and P=0.12 respectively), the 95% confidence interval for the difference in mean pain scores was -0.01 to +0.55 indicating that sustained-release ibuprofen was equivalent or superior to paracetamol. Nineteen patients who received ibuprofen reported a total of 33 adverse events compared to 13 patients receiving paracetamol who reported 13 adverse events (P=0.24). Sustained-release ibuprofen is as good as or better than paracetamol for the control of pain after laparoscopic surgery.

The choice between morphine and meperidine for postoperative pain is usually based on the preference of the prescriber, as few objective comparative data are available.This blind, randomized study compared the efficacy and side effects of morphine and meperidine administered by patient-controlled analgesia (PCA) for postoperative pain. One hundred two consenting patients scheduled for major abdominal surgery were randomly assigned to receive PCA with morphine (0.75, 1.0, or 1.5 mg bolus dose size) or meperidine (9, 12, or 18 mg) for pain control. Postoperative assessments included pain at rest and on sitting, nausea, unusual dreams, the Multiple Affect Adjective Check List (a measure of mood), and the trailmaking tests A and B (measures of ability to concentrate). Pain on sitting (P = 0.037) but not pain at rest (P = 0.8) was significantly less in patients receiving morphine. Meperidine use was associated with poorer performance in the trailmaking tests and a greater incidence of dryness of the mouth. Severity of nausea, mood, and incidence of unusual dreams did not differ significantly between drugs. We conclude that meperidine should be reserved for those patients in whom morphine is judged inappropriate. (Anesth Analg 1997;84:794-9)

Many morphological, pharmacological and toxicological studies of hepatotoxicity require frequent sampling of liver over time. In the past this has been achieved by including large numbers of animals in the study and killing subgroups at different times. In this paper we describe a technique for repeated liver biopsy that procures sufficient liver tissue for histopathological assessment and for additional studies, for example measurement of hepatic iron concentration or vitamin A measurement. The advantages and disadvantages of this technique are discussed.

We examined the effect on the quality of analgesia and side effects of increasing the patient control component of morphine patient-controlled analgesia (PCA) by offering the patient a choice of bolus dose sizes. Using a three-button hand piece, patient could choose between 0.5-, 1.0-, and 1.5-mg boluses of morphine (variable-dose PCA, VDPCA). Successful demands were delivered by a modified Graseby 3400 Anaesthesia Pump controlled by a Toshiba T1900 computer. This system was compared with conventional fixed-dose PCA (FDPCA) (1.0 mg of morphine) delivered by a Graseby 3300 PCA Pump. Both treatment groups had a 5-min lockout interval. Sixty patients were randomly assigned to receive either VDPCA or FDPCA after major abdominal gynecological surgery or hip or knee arthroplasty. Treatment groups did not differ in their duration of PCA therapy, total morphine consumption, or time spent with mild or severe oxyhemoglobin desaturation. There were no differences in their ease of controlling pain, satisfaction with pain control, experience of pain on movement, quality of sleep, severity of nausea, or incidence of vomiting. Although the more complex VDPCA technique provides adequate postoperative analgesia, it does not offer any advantage over conventional FDPCA. (Anesth Analg 1996;83:1060-4)

Sustained release morphine formulations are now generally accepted as the formulations of choice in the treatment of severe cancer pain. Kapanol™/Kadian™ (Glaxo/Faulding), a new sustained release formulation consisting of polymer coated pellets in a capsule, has recently been shown to have a superior morphine release profile compared to the standard tablet, MS Contin. If fact, the release characteristics of morphine from Kapanol suggested the possibility that one oral dose of Kapanol per 24 hours could effectively treat severe cancer pain. Twenty four patients completed a randomised, double-blind, two period, crossover study comparing 24-hourly Kapanol to 12-hourly MS Contin. The morphine dose per 24 hours was identical for the two formulations and morphine pharmacokinetics were determined over 24 hours at steady state for each formulation (i.e. after 7 days). The Cmax, Cmin, AUC and fluctuations in plasma morphine concentrations were not significantly different between the two formulations (P > 0.05, repeated measures ANOVA). Kapanol had significantly longer Tmax values (P < 0.001) than MS Contin. These results indicate that one Kapanol dog per 24 hours should at least be as efficacious as 12 hourly MS Contin in die treatment of severe cancer pain from the pharmacokinetic perspective. Sustained release morphine formulations are now generally accepted as the formulations of choice in the treatment of severe cancer pain. Kapanol™/Kadian™ (Glaxo/Faulding), a new sustained release formulation consisting of polymer coated pellets in a capsule, has recently been shown to have a superior morphine release profile compared to the standard tablet, MS Contin. If fact, the release characteristics of morphine from Kapanol suggested the possibility that one oral dose of Kapanol per 24 hours could effectively treat severe cancer pain. Twenty four patients completed a randomised, double-blind, two period, crossover study comparing 24-hourly Kapanol to 12-hourly MS Contin. The morphine dose per 24 hours was identical for the two formulations and morphine pharmacokinetics were determined over 24 hours at steady state for each formulation (i.e. after 7 days). The Cmax, Cmin, AUC and fluctuations in plasma morphine concentrations were not significantly different between the two formulations (P > 0.05, repeated measures ANOVA). Kapanol had significantly longer Tmax values (P < 0.001) than MS Contin. These results indicate that one Kapanol dog per 24 hours should at least be as efficacious as 12 hourly MS Contin in die treatment of severe cancer pain from the pharmacokinetic perspective.

Twenty-six patients with severe pain associated with cancer were entered into a study where they were required to take morphine mixture for 7 days. Prior to this, their morphine dose had been optimised to provide the most favourable balance between pain relief and side effects. After 6 days of taking their optimised morphine dose at 4-hourly intervals, the patients were admitted to the Pain Management Unit such that the doses from 18:00 h on day 6 were taken under direct nursing supervision. Frequent blood samples were collected after the 10:00 h (dose 1), 14:00 h (dose 2) and 18:00 h (dose 3) on day 7. There was a significant difference between the 3 doses with respect to Cmax values for morphine with dose 3 > dose 1 > dose 2. Further, there was considerable variability in the percentage change of either dose 1 or dose 3 Cmax. values relative to dose 2. The Cnmax values of the active metabolite morphine-6-glucuronide (M6G), measured in 6 of the patients, for the 3 dosing intervals followed a similar trend to the parent drug; but only doses 1 and 2 differed significantly. Similar but less pronounced changes were observed in the area-under-curve parameter calculated for both morphine and M6G during the 3 dosing intervals. There were no significant differences in the Cmin or Tmax parameters for either morphine or M6G between the 3 dosing intervals. These results suggest intra-individual variation in the absorption of morphine or changes in the volume of distribution during the day. The clinical significance of these data concerns the possible mismatch between the chronopharmacokinetic variability in plasma morphine concentrations demonstrated in this communication and literature reports of circadian variability in patients' reports of pain.

This study investigated the feasibility of using patient-controlled analgesia (PCA) effectively in a small 70 bed isolated rural hospital. The first 50 patients to use a Bard PCA 1, in the Port Lincoln Hospital, South Australia, were studied. The patients consumed morphine at a mean rate of 1.24 mg/h and used PCA for a mean of 48 h. Thirty-eight per cent of patients required treatment for nausea and other complications which is similar to the rate of those in other published series. Visual analogue pain scores showed excellent pain control, generally without evidence of oversedation; however, there was one episode of respiratory depression. Seventy-eight per cent of patients reported that their pain was relieved most or all of the time. The study demonstrated that a PCA service provided by nursing staff, the GP anaesthetist and rural surgeons is feasible in an isolated rural hospital.

This study investigated behavioural effects of the toxic pethidine metabolite, norpethidine, in rats and its interactions with reserpine, apomorphine and physostigmine. Following intraperitoneal administration, brain concentrations of norpethidine reached a plateau after 20-40 min and remained elevated for 2 h. In the dose range 0.06-0.18 mmol/kg, norpethidine induced myoclonic jerks, a characteristic splayed posture, and episodes of exaggerated shivering. Forward locomotion, grooming, yawning and rearing were suppressed. Seizures and reverse locomotion occurred occasionally. Administration of reserpine 1 h prior to norpethidine, or of apomorphine or physostigmine 15 min after norpethidine, did not alter the norpethidine-induced behaviours; neither did norpethidine block the effects of apomorphine or physostigmine. The characteristic profile of behaviours induced by norpethidine make this toxicant readily amenable to animal studies. Our results indicate that its mechanism of action is unlikely to involve dopaminergic or cholinergic pathways.