A randomised controlled trial of perineural vs intravenous dexamethasone for foot surgery.

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.

Spinal anaesthesia for ambulatory arthroscopic surgery of the knee: a comparison of low-dose prilocaine and fentanyl with bupivacaine and fentanyl.

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.

Learning on a simulator does transfer to clinical practice.

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 training: how useful are descriptions of force?

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.

Predictors of preoperative anxiety in children.

This study aimed to identify factors contributing to anxiety at induction of anaesthesia in children. One hundred and twenty children aged five to twelve years and scheduled for surgery requiring general anaesthesia were included. Children were interviewed and assessed prior to surgery. Parents completed anxiety measures prior to surgery and were interviewed after the induction of anaesthesia. The level of children's anxiety was determined at the time of induction of anaesthesia by the modified Yale Preoperative Anxiety Scale. Factors associated with increased levels of anxiety in the children included increased number of people in the room at induction of anaesthesia; longer waiting time between admission at the hospital and induction of anaesthesia; negative memories of previous hospital experiences; and having a mother who does not practise a religion. Suggestions for implementation of the findings and for future research are provided.

Learning endotracheal intubation in a clinical skills learning center: a quantitative study.

This study aimed to develop statistical models describing the learning of endotracheal intubation (ETI). We collected data from 100 subjects undergoing ETI training with intubatable medical models and manikins (airway trainers). Trainees initially viewed a video about ETI and an instructor demonstrated the technique. Subjects then made up to 17 supervised trials. Each trial was scored as a success or failure; this score was the primary outcome used in analyses. Random effects and population-averaged logit models, and a learning model intended to quantify the relative contributions of failed and successful trials to the learning process, were fitted to the data. The logit models provided evidence of differences in difficulty between different airway trainers and differences in success rate related to previous ETI experience. Trainees became familiar with an airway trainer after multiple trials, as demonstrated by a 50% decrease in the odds of successful ETI when starting on a new trainer. The learning model indicated that a trainee learns about as much from 1 successful ETI as from 12 (95% confidence interval, 2-23) failed trials. The results demonstrate the feasibility of statistical modeling of the learning of ETI and provide insight into the learning process.

Direct cardiac effects of intracoronary bupivacaine, levobupivacaine and ropivacaine in the sheep.

1. The racemic local anaesthetic agent bupivacaine is widely used clinically for its long duration of action. Levobupivacaine and ropivacaine are bupivacaine enantiopure congeners, developed to improve upon the clinical safety of bupivacaine, especially the risk of fatal arrhythmogenesis. 2. In previous preclinical studies of the safety of these drugs with intravenous administration in conscious ewes over a wide dose range, we found that central nervous system (CNS) excito-toxicity reversed the cardiac depressant effects when doses approached the convulsant threshold and thus precluded accurate comparison of their cardiovascular system (CVS) effects. 3. To study CVS effects over a wide range of doses with minimal CNS and other influences, brief (3 min) infusions of bupivacaine, levobupivacaine or ropivacaine were administered into the left main coronary arteries of previously instrumented conscious ewes (approximately 50 Kg body weight). After dose-ranging studies, the drugs were compared in a randomized, blinded, parallel group design. Equimolar doses were increased from 8 micromol (approximately 2.5 mg) in 8 micromol increments, to either a fatal outcome or a 40 micromol (approximately 12.5 mg) maximum. 4. All three drugs produced tachycardia, decreased myocardial contractility and stroke volume and widening of electrocardiographic QRS complexes. Thirteen of 19 animals died of ventricular fibrillation: four of six with bupivacaine (mean+/-s.e.mean actual fatal dose: 21.8+/-6.4 micromol), five of seven with levobupivacaine (22.9+/-3.5 micromol), four of six with ropivacaine (22.9+/-5.9 micromol). No significant differences in survival or in fatal doses between these drugs were found. 5. The findings suggest that ropivacaine, levobupivacaine and bupivacaine have similar intrinsic ability to cause direct fatal cardiac toxicity when administered by left intracoronary arterial infusion in conscious sheep and do not explain the differences between the drugs found with intravenous dosage.

Influence of intestinal flora on the development of fibrosis and cirrhosis in a rat model.

BACKGROUND AND AIMS: The gut flora play a significant role in the disposition of many foreign substances, as well as producing nutrients and toxins that may be absorbed and reach the liver. This study examines the influence of antibiotic-induced alterations in gut flora on the development of hepatic fibrosis in a rat model. METHODS: Thirty-six male Porton rats were fed alcohol (3.9 g/kg per day) in the drinking water and exposed to carbon tetrachloride (CCl4) vapor (80 p.p.m.) for 6 h each night, five nights per week. Half were also given neomycin (330 mg/kg per day) and polymyxin B (105 mg/kg per day) in the drinking water. Fecal cultures were carried out at 0, 3, 8 and 13 weeks; rats were killed at 14 weeks. Coded liver section were assessed for fibrosis using a graded scale (0, no abnormal fibrosis to 4, early or established cirrhosis). RESULTS: Rats that received antibiotics had significantly higher fibrosis scores than those that did not (mean score 2.4 vs 1.4, P < 0.01, ordinal logistic regression). Three rats, all of which were in the antibiotic group, were cirrhotic. Rats that had received antibiotics fell into three groups. Four had overgrowth of Proteus mirabilis; in these the fibrosis scores (mean 1.5) were similar to those in the rats that did not receive antibiotic. In six, no organisms could be cultured; fibrosis scores of these (mean 2.3) were slightly elevated (P = 0.03), but this was mainly because of a single rat in this subgroup being cirrhotic. The remaining eight had overgrowth of Morganella morganii; these had significantly (P < 0.001) elevated fibrosis scores. Furthermore, in this subgroup, fibrosis scores were significantly correlated (Spearman's r = 0.82, P = 0.01) with the number of weeks of Morganella colonization. CONCLUSIONS: Antibiotic treatment exacerbated fibrosis in the alcohol/CCl4 rat model; this effect appeared to be related to the type of gut flora and may be endotoxin-mediated.

Timing of midazolam and propofol administration for co-induction of anaesthesia.

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 i.v. 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.

Haemolysis associated with continuous venovenous renal replacement circuits.

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.

Influence of premedication with diazepam or morphine on the induction dose of eltanolone.

BACKGROUND: This study examined the influence of premedication with morphine or diazepam on the dose of eltanolone, a steroidal intravenous anaesthetic agent, required to induce anaesthesia. METHODS: Two hundred and sixteen patients, aged 18 to 65 years, were randomly assigned to receive premedication with diazepam 10 mg orally, morphine 10 mg intramuscularly, or placebo. The double-dummy technique was used to maintain blinding. Eltanolone 0.16-0.75 mg x kg(-1) was given intravenously over 20 s. At the commencement of injection patients were instructed to begin counting; if the patient ceased counting within 120 s and failed to respond to commands to continue, anaesthesia was considered to have been induced. The dose required to anaesthetise 50% of patients (ED50) was determined by logistic regression. RESULTS: The ED50 (95% confidence interval) of eltanolone in patients who received placebo premedication was 0.31 (0.27-0.34) mg x kg(-1). It was reduced slightly and nonsignificantly by premedication with diazepam, to 0.27 (0.24-0.30) mg x kg(-1), or morphine, to 0.26 (0.23-0.29) mg x kg(-1). Involuntary movement occurred in 65% of placebo premedicated patients. Its incidence was not significantly reduced by diazepam (57%), but was significantly (P<0.001) reduced by morphine (37%). Morphine premedication was, however, associated with a significant (P<0.01) increase in the incidence of apnoea (21%) compared to placebo premedicated patients (4%). CONCLUSION: Premedication with diazepam or morphine had little influence on the dose of eltanolone required to induce anaesthesia.

Epidural analgesia in labour using intermittent doses determined by midwives.

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.

A technique for obtaining repeated liver biopsies from rats.

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.

Morphine patient-controlled analgesia is superior to meperidine patient-controlled analgesia for postoperative pain.

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.

Identification of movement artefact by the Nellcor N-200 and N-3000 pulse oximeters.

OBJECTIVES: The Nellcor N-3000 pulse oximeter is designed to be able to identify signal artefact related to movement of the body part to which the probe is attached. It may therefore provide a reliable means of monitoring arterial oxyhemoglobin saturation (SpO2) in awake, moving patients. This study compared the Nellcor N-3000 and N-200 pulse oximeters in terms of their ability to identify readings associated with movement, in a group of volunteers making standardized movements. METHODS: Thirty-six volunteers were studied. Volunteers breathed room air throughout the study. SpO2 of each volunteer was monitored by both a Nellcor N-200 and a Nellcor N-3000 simultaneously on both hands. Volunteers made a series of five standardized movements, each lasting one minute, with each hand during the monitoring session, while SpO2 and oximeter status were recorded from all four oximeters. The mean SpO2 reading was calculated during each movement. SpO2 readings which the oximeter identified as being associated with movement, pulse search not locked, sensor not attached, or break in communications were excluded from analysis. RESULTS: The N-3000 rejected from 17 to 78% of readings taken during movement, compared to 0 to 2% with the N-200. Although the remaining readings of both types of oximeters were subject to some movement artefact, which led to spuriously low SpO2, this was significantly less with the N-3000. CONCLUSIONS: The Nellcor N-3000 pulse oximeter is able, to some extent, to identify movement artefact. It should offer an advantage over the N-200 when monitoring moving patients.

Use of artificial sweeteners to promote alcohol consumption by rats.

Cirrhosis may be reliably produced in rats by exposing them intermittently to low levels of carbon tetrachloride vapour while feeding alcohol in the Lieber-DeCarli liquid diet. Providing the alcohol in drinking water that has been sweetened with sucrose is a cheaper and more convenient method but it does not yield reliable results. This study aimed to determine whether alcohol in drinking water sweetened with artificial sweeteners would give adequate alcohol intake to achieve the desired hepatic effects. Rats were fed alcohol (8% v/v) in drinking water sweetened with sucrose (5% w/v) (n = 12), or with one of the artificial sweeteners aspartame (0.025%), saccharin (0.025%) or cyclamate (0.05%) (n = 8 per agent). During the alcohol treatment the animals were exposed to carbon tetrachloride vapour, 40 ppm, six hours per night for five nights per week, over a period of 14 weeks. All groups achieved good alcohol intakes of 5-6 g/kg/day. Only one rat, in the aspartame group, became cirrhotic; all the others had varying degrees of fibrosis which did not differ significantly among the treatments. Although it was not effective in reliably achieving cirrhosis, sweetening the alcohol solution with artificial sweeteners led to reasonable alcohol intakes with resultant hepatic fibrosis, and without the high carbohydrate intake which occurs when sucrose is used.

Interaction between dextromethorphan and norpethidine in rats.

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.

Dose-related effects of dietary iron supplementation in producing hepatic iron overload in rats.

The influence of varying the level of supplemental dietary iron on the development of hepatic iron overload was examined in rats. Two days after giving birth, Porton rats were fed a diet supplemented with 0, 0.5, 1 or 2% carbonyl iron, to institute dietary iron supplementation to the young via breast milk. After weaning, the offspring continued to receive the assigned diet until 32 weeks of age. Liver biopsies were taken from some rats at 8, 16 and 24 weeks of age and from all rats at 32 weeks of age, for assessment of iron overload. For both male and female rats, hepatic iron content was increased in a dose-related manner by feeding supplemented diet. Hepatic iron content of male rats tended to reach a plateau after 8, 16 weeks of supplementation, while that of female rats continued to rise throughout the experimental period, such that the hepatic iron content of female rats was 2.8-fold that of similarly treated males at 32 weeks of age. Iron supplementation was associated with only moderate retardation of growth. By choosing an appropriate level of iron supplementation, good (grade III-IV) hepatic iron loading can be achieved with minimal adverse effects on the animals' overall health.

A comparison of variable-dose patient-controlled analgesia with fixed-dose patient-controlled analgesia.

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, patients 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.