Education and training in anaesthesia--revised guidelines by the European Board of Anaesthesiology, Reanimation and Intensive Care.

The expansion of the European Union during the last 2 yr has resulted in the need for a revision of existing guidelines to further harmonize education and training in the specialty of anaesthesiology throughout the European Union. Although each individual country is responsible for its own training and certification, these guidelines are intended to reflect minimum criteria for specialist training. It is the opinion of the Section and Board of Anaesthesia that specialist training will need to be for a minimum of 5 yr.

Cimetidine and ranitidine increase midazolam bioavailability.

Cimetidine has been shown to inhibit the oxidative metabolism of a variety of low- and high-extraction drugs. Despite the findings of initial investigators, there is evidence that ranitidine may exert similar effects. Eight healthy volunteer subjects took part in a within-subject crossover study. They received midazolam, 15 mg, by mouth after pretreatment with cimetidine, ranitidine, or nothing and midazolam, 10 mg, intravenously on separate occasions. Mean absolute bioavailability of midazolam was increased by more than 30% after cimetidine (P less than 0.01) and 26% after ranitidine (P less than 0.05). The data, which agree with a concurrent clinical study indicating greater hypnotic action of midazolam after ranitidine, indicate that this is not a result of enhanced midazolam absorption and that reduced hepatic clearance is the most likely explanation.

Comparative tolerability profiles of the inhaled anaesthetics.

Improved understanding of the structure/activity relationship of inhaled anaesthetics has resulted in the synthesis of fluorinated compounds which are more potent and less toxic than their unfluorinated antecedents. The toxic effects of inhaled anaesthetics on the liver and kidney are complex but, in general, are related to the extent to which individual inhaled agents are metabolised. Halothane hepatotoxicity is a rare, idiosyncratic reaction which typically occurs in obese women having more than one exposure to the drug within a short time interval. All currently available volatile anaesthetic drugs have depressant effects on the cardiovascular and respiratory systems; arrhythmias are more likely with halothane than with the fluorinated ethers. Cerebral blood flow tends to increase during inhalation anaesthesia, especially with halothane and in the presence of hypercarbia; isoflurane may be given sparingly during neurosurgical procedures whilst monitoring its end-tidal concentration. Although the volatile agents tend to cause uterine relaxation they may be given safely in low concentration to avoid awareness during Caesarean section. In general, young children require rather higher concentrations of volatile agents than adults and seem to be less susceptible to organ toxicity. Two relatively new volatile agents, sevoflurane and desflurane, offer some advantages over isoflurane but neither is an "ideal drug'. Sevoflurane interacts with soda-lime to produce a series of degradation products, the most important of which is compound A. Production is greatest during low-flow, closed circuit anaesthesia using high inspired concentrations of the drug. Compound A has nephrotoxic potential in rats but the clinical significance of the interaction between sevoflurane and soda-lime is unclear. Nitrous oxide when given for prolonged periods may cause irreversible bone marrow depression.

Frequency of atopy, allergy, and previous general anaesthesia in surgical specialties.

This paper reports part of a large survey of atopy, allergy, and previous anaesthesia in 10 000 preanaesthetic patients. The occurrence of these risk factors in the various surgical specialties has been assessed. Obstetric patients have a significantly higher frequency of atopy and allergy than the total female population studied. Among males cardiothoracic patients are the only group to have a significantly higher frequency of atopy and allergy than the overall figure for their sex.

Psychomotor and clinical assessment of flumazenil as an antagonist of midazolam.

The benzodiazepine antagonist flumazenil (0.01 mg/kg) has been compared with doxapram (1 mg/kg) and saline for the reversal of anaesthesia with intravenous midazolam, alfentanil, nitrous oxide in oxygen and isoflurane. The completeness of reversal was assessed by means of a four-choice reaction time test, 1 and 3 h following the antagonist. In addition, the level of sedation was graded using a five-point scale. Psychomotor testing showed that 60 min after administration of the antagonist, there were marked increases in reaction times (P less than 0.05) both in the control and doxapram groups, but not in those receiving flumazenil. At 180 min, however, reaction times in all groups had returned to baseline values. In contrast, there was a significant difference in the sedation scores between the saline and flumazenil groups throughout the study period (P less than 0.05). During the 4 h following midazolam, there was no evidence of re-sedation in any of the groups despite the relatively high midazolam dosage.

Prospective study of liver function following repeat halothane and enflurane.

In a prospective study of liver function following repeat anaesthesia, patients who received repeat halothane had a higher frequency of abnormal liver enzyme results than a similar group who received repeat enflurane. Obesity and short intervals between administrations increased the likelihood of abnormal liver enzyme activity in the halothane group. Enflurane would seem to be the volatile agent of choice for repeat anaesthesia in such circumstances.

The provision of adult intensive care in Northern Ireland with reference to the role of high dependency care.

In 1991 an audit of Intensive Care Services was carried out by the Northern Ireland Intensive Care Group. In conjunction with this regional overview, all patients in the Regional Intensive Care Unit, (RICU) in the Royal Victoria Hospital were assessed daily, over a 10 month period in 1990-91 and classified as conforming to either intensive care or high dependency status. These data were then used to compare adult intensive care service in Northern Ireland with recent national and international recommendations on intensive care. Ten units in Northern Ireland were surveyed. In regard to national or international guidelines, all ten were deficient to some degree. Four units had significant deficiencies; small patient numbers, lack of 'dedicated' 24 hr medical cover and or deficiencies in the provision of appropriate monitoring and or equipment. There was a large diversity in casemix among the ten units surveyed which suggested differing admission criteria. The bed occupancy of RICU was 100%. Refused admissions constituted a further 13% of unresourced workload. The lack of physically separate, dedicated high dependency unit facilities meant that 26% of bed days were devoted to HDU care (usually for "improved" intensive care unit patients not yet ready for discharge to a general ward. Achieving nationally recommended intensive care standards (on a regional basis) is probably only possible if a number of the smaller intensive care units are redesignated as high dependency units, and patients requiring intensive care are concentrated in a smaller number of larger ICUs. This will increase the frequency of interhospital transfer of critically ill patients.

The effect of high altitude commercial air travel on oxygen saturation.

Air travel has increased steadily over the last decade, and its effect on the health of passengers has been the subject of much debate. There is a paucity of evidence on the effects of air travel on oxygen saturation in general populations. The peripheral oxygen saturation and pulse rate of 84 passengers, aged 1-78 years, were measured by pulse oximetry at round level and altitude during air travel. There was a statistically significant reduction in oxygen saturation in all passengers travelling long haul and short haul flights (p < 0.05). The mean [range] (SD) SpO(2) for all flights at ground level was 97% [93-100] (1.33) and at cruising altitude 93% [85-98] (2.33). Fifty-four per cent of passengers had SpO(2) values of 94% or less at cruising altitude. This is a value which may prompt physicians to administer supplemental oxygen in hospital patients.

Patient controlled analgesia for labour: a comparison of remifentanil with pethidine.

We compared the analgesic efficacy and safety of remifentanil and pethidine via patient controlled analgesia for women in established uncomplicated labour. Women received either remifentanil 40 microg with a 2-min lockout (n = 20) or pethidine 15 mg with a 10-min lockout (n = 19). Visual analogue scores for pain during the study and for overall pain were similar for both groups (mean (SD) 6.4 (1.5) cm for remifentanil and 6.9 (1.7) cm for pethidine). The area under the curve for visual analogue scores of satisfaction with analgesia was higher for remifentanil than for pethidine (p = 0.001). Maternal arterial oxygen saturation was similar in both groups. Neurologic and Adaptive Capacity Scores at 30 min were higher for remifentanil than for pethidine (median (interquartile range [range]) 36 (34.5-37 [32-39]) vs 34 (33-35 [30-35]), respectively; p = 0.003).

Endothelial function, insulin action and cardiovascular risk factors in young healthy adult offspring of parents with Type 2 diabetes: effect of vitamin E in a randomized double-blind, controlled clinical trial.

BACKGROUND AND AIMS: Endothelial dysfunction, insulin resistance and oxidative stress are believed to be central and associated mechanisms in atherogenesis. We aimed to determine the effect of the antioxidant vitamin E on endothelial function, insulin action and cardiovascular risk markers in young healthy adult offspring of parents with Type 2 diabetes. METHODS: Healthy, glucose-tolerant adults (18-38 years), 14 (12 male/2 female) with at least one parent with Type 2 diabetes, and 14 (12 male/2 female) subjects with no family history of diabetes (controls) were studied. Insulin action was assessed by euglycaemic hyperinsulinaemic clamp (1 mU/kg/min). Endothelial function was assessed by forearm blood flow (FBF) responses to intra-brachial artery infusions of acetylcholine (ACh) (endothelium-dependent vasodilation), sodium nitroprusside (SNP) (endothelium-independent vasodilation) and N(G)-monomethyl L-arginine (LNMMA) (nitric oxide synthase inhibition). Thirteen offspring (18-38 years, 11 male/2 female, BMI < 30 kg/m2) completed a randomized, double-blind, crossover trial (12 weeks vitamin E 800 IU/day or placebo, 6-week washout). RESULTS: Exogenous glucose infusion rates to maintain euglycaemia were positively associated with response to acetylcholine in offspring (r = 0.61, P < 0.05), and were linked with triglycerides. Vitamin E had no effect on endothelial function, insulin action or cardiovascular risk markers in healthy adult offspring of parents with Type 2 diabetes. CONCLUSIONS: Our results support a positive association between insulin action and endothelial-dependent vasodilation in young healthy adult offspring of parents with Type 2 diabetes, but indicate no effect of vitamin E on these parameters.

Pain on injection of propofol: comparison of lignocaine with metoclopramide.

We have conducted a randomized, double-blind study in 255 ASA I and II patients to compare the efficacy of lignocaine and metoclopramide in minimizing the pain of injection of i.v. propofol. When administered immediately before propofol into a dorsal hand vein, compared with placebo both drugs significantly reduced the incidence of pain on subsequent injection of propofol (P < 0.001). Twenty patients who had received metoclopramide (n = 85) experienced pain, compared with 18 who had received lignocaine (n = 85) and 42 who had been pretreated with saline (n = 85).

Inhalational anaesthesia.

Sevoflurane and desflurane have important advantages over isoflurane and halothane. Disadvantages, which the clinician should keep in mind, include the degradation of both agents by soda lime under certain circumstances during closed circuit anaesthesia. As a result compound A and carbon monoxide (CO) may be generated in soda lime canisters and may be inhaled by patients. The extent to which this constitutes a significant problem during routine anaesthesia in humans is not clear. Recent developments in absorbent technology have the potential to reduce any hazard to negligible proportions. Other undesirable properties of the newer inhalation agents include agitation with sevoflurane in children and cardiovascular and airway effects with desflurane.

Ineffective analgesia after extradural tramadol hydrochloride in patients undergoing total knee replacement.

Postoperative analgesia after two extradural tramadol regimens was compared with that obtained using a standard extradural morphine regimen in patients undergoing total knee replacement. Extradural anaesthesia with light general anaesthesia was used. Patients received extradurally either: tramadol 50 mg by bolus injection followed by infusion (5 mg.h-1 for 12 h and 2.5 mg.h-1 for a further 12 h) (group T50), tramadol 100 mg by bolus injection followed by infusion (10 mg.h-1 for 12 h and 5 mg.h-1 for a further 12 h) (group T100) or morphine sulphate 2 mg by bolus injection followed by infusion (0.2 mg.h-1 for 12 h and at 0.1 mg.h-1 for further 12 h) (group M). Analgesia was allocated according to a controlled double-blind design. Visual analogue pain scores were markedly poorer (p < 0.05) and patient-controlled analgesic consumption was significantly greater (p < 0.01) in the two tramadol groups when compared with the morphine group. The study was discontinued after recruitment of 12 patients, as analgesia was deemed inadequate in those receiving tramadol extradurally. However, further study of this drug may be warranted to examine its effectiveness where postoperative pain is expected to be less severe, and to assess the effect of larger extradural doses and of co-administration of tramadol and morphine by this route.

Anaesthesia and adverse effects after intrathecal pethidine hydrochloride for urological surgery.

Anaesthesia, postoperative analgesia and the incidence of adverse effects after intrathecal pethidine hydrochloride 0.50 mg.kg-1 and 0.75 mg.kg-1 were assessed and compared with a conventional technique using isobaric bupivacaine 13.75 mg in patients undergoing transurethral resection of the prostate gland. Sensory and motor block were significantly shorter with both pethidine regimens than with bupivacaine (p < 0.001). Although sensory and motor block were shorter after pethidine 0.50 mg.kg-1 than after pethidine 0.75 mg.kg-1 the difference in duration was clinically insignificant. The incidence of incomplete motor block was significantly greater with pethidine 0.50 mg.kg-1 than with bupivacaine 13.75 mg.kg-1 (p < 0.01). Visual analogue pain scores recorded after the operation were low and were similar in the pethidine groups to those obtained with bupivacaine alone. Mean arterial blood pressure was significantly lower in both pethidine groups compared with the bupivacaine group between 30 and 240 min after intrathecal injection (p < 0.001). However, the within-group reductions in blood pressure were within clinically acceptable limits. The incidences of nausea and emesis were low and emesis occurred in patients in the bupivacaine group only (p < 0.03). Pruritus was seen only in patients receiving pethidine. Intra-operative sedation occurred more often in patients receiving both pethidine 0.50 mg.kg-1 and 0.75 mg.kg-1 compared with patients receiving bupivacaine (p < 0.04). Both pethidine regimens provided acceptable anaesthesia and there were no significant differences between the two regimens in quality of intra-operative anaesthesia, incidence of adverse events or postoperative analgesia.

A comparison of intrathecal morphine-6-glucuronide and intrathecal morphine sulfate as analgesics for total hip replacement.

Postoperative analgesia was assessed after intrathecal administration of morphine-6-glucuronide (M6G) 100 micrograms and 125 micrograms in 75 patients undergoing total hip replacement. Analgesia was excellent and was similar to that obtained after intrathecal administration of morphine sulfate 500 micrograms. Visual analog pain scores recorded postoperatively were low (median = 0) and were similar in all three groups. However, at 6 and 10 h after operation significantly more patients in the M6G 125 group recorded pain as 0 compared with patients in the morphine group (P < 0.04, P < 0.01) and significantly more patients in the M6G 100 group recorded pain as 0 at 24 h after operation compared with patients in the morphine group (P < 0.04). Postoperative meperidine consumption using a patient-controlled system was also similar in each of the three treatment groups. Nausea and emesis occurred frequently in all groups; morphine (nausea 88%, vomiting 76%), M6G 100 micrograms (nausea 76%, vomiting 64%), and M6G 125 micrograms (nausea 88%, vomiting 60%). Respiratory depression occurred in two and three patients, respectively, in the M6G 100-microgram and 125-microgram groups but did not occur in any patient who received morphine sulfate. The lack of statistical significance in the difference in incidence of respiratory depression between the groups may represent a type II error. However, the risk of late respiratory depression developing after administration of any intrathecal opioid necessitates careful postoperative observation of patients. As M6G is a potent intrathecal analgesic further investigation of this drug using small doses may be useful.

Cardiovascular effects of 50% nitrous oxide in older adult patients anaesthetized with isoflurane or halothane.

We have studied the cardiovascular effects of equipotent concentrations of halothane or isoflurane, with or without 50% nitrous oxide in oxygen, in 80 patients, aged 60 yr or more, during 20 min of stable equipotent anaesthesia. Non-invasive measurement techniques were used, with suprasternal Doppler ultrasonography for estimating cardiac output. Both isoflurane and halothane reduced heart rate and systemic arterial pressure. With isoflurane, mean rate decreased from 72 (SD 9.7) to 67 (10.4) beat min-1 and with halothane from 76 (10.1) to 65 (9.1) beat min-1 (P < 0.05). Mean diastolic arterial pressure decreased from 81 (11.3) to 58 (17.0) mm Hg with isoflurane and from 86 (14.7) to 70 (13.3) mm Hg with halothane (P < 0.05). Cardiac index decreased from 3.1 (1.03) to 2.7 (0.71) litre min-1 m-2 with isoflurane and from 3.1 (0.98) to 2.5 (0.57) litre min-1 m-2 with halothane (P < 0.05). Systemic vascular resistance decreased significantly in all groups except those receiving halothane with nitrous oxide. Nitrous oxide resulted in significantly less depression of cardiac index when given with isoflurane than when given with halothane. The mean percentage change in cardiac index during isoflurane anaesthesia without nitrous oxide was 16.7%; with nitrous oxide there was a 0.5% increase. Halothane, in combination with nitrous oxide, resulted in greater depression of cardiac index than isoflurane with nitrous oxide. The mean percentage change with halothane was 20.4% (22.2%); with isoflurane there was a 0.5% (27.1%) increase (P < 0.05). Hypotension was more pronounced in patients anaesthetized with isoflurane (n = 40) than those anaesthetized with halothane (n = 40), irrespective of the presence of nitrous oxide. The mean percentage decrease with isoflurane was 29.7% (21.10%) compared with 16.8% (16.78%) with halothane (P < 0.05).

Cardiovascular support during combined extradural and general anaesthesia.

We have examined the effect of prophylactic treatment with i.v. fluid 1000 ml, ephedrine 24 mg or methoxamine 4 mg on cardiovascular responses to both extradural and combined extradural and general isoflurane anaesthesia in 45 adult patients undergoing knee arthroplasty. Heart rate (HR) and systemic arterial pressure (AP) were measured using automated oscillotonometry and cardiac output was measured using continuous wave suprasternal Doppler ultrasonography. After lumbar extradural anaesthesia (LEA) there were no significant differences in arterial pressure between treatments, although cardiac index was significantly greater after fluid preloading (mean 4.3 (95% confidence interval 3.7-4.9) litre min-1 m-2) than after ephedrine (3.1 (2.6-3.6) litre min-1 m-2) or methoxamine (2.6 (2.0-3.2) litre min-1 m-2). During combined LEA and general anaesthesia, systolic AP was significantly greater after ephedrine (114 (103-125) mm Hg) than after either preloading (98 (88-107) mm Hg) or methoxamine (97 (89-105) mm Hg). The reduction in AP after induction of general anaesthesia was associated with a decrease in cardiac index after fluid preloading and a decrease in vascular resistance after methoxamine.

Double-blind comparison of extradural block with three bupivacaine-ketamine mixtures in knee arthroplasty.

We have compared 0.5% bupivacaine 75 mg (group A; n = 15) with three 0.5% bupivacaine 75 mg-ketamine mixtures for extradural block in 59 ASA I-III patients undergoing total knee replacement in a randomized, double-blind study. The following doses of preservative-free 1% ketamine were used: 0.3 mg kg-1 (group B: n = 14); 0.5 mg kg-1 (group C: n = 5); and 0.67 mg kg-1 (group D: n = 15). Level of sensory block, degree of motor weakness and sedation scores were recorded before and after operation. Duration of postoperative analgesia was also noted. There was no difference between groups in median maximum level of sensory block (group A: T4 (range T10-T2); group B: T4 (T10-T2); group C: T4 (T8-T2); and group D: T3 (T8-C3)) or in the degree of motor block. Thirty-three of the 44 patients who received ketamine showed signs of systemic absorption (blurred vision, sedation) within 10 min of injection. There was no significant difference between groups in median duration of analgesia (group A: 240 (range 115-340) min; group B: 198 (97-460) min; group C: 150 (122-448) min; and group D: 210 (130-390) min). No patient suffered any adverse psychomimetic effects. We conclude that at the doses used, addition of ketamine to extradural bupivacaine did not improve extradural block in adult patients undergoing total knee replacement.

Intrathecal ropivacaine or bupivacaine with fentanyl for labour.

Combined spinal-epidural (CSE) is widely used to provide pain relief in labour while minimizing motor blockade. Aiming to further reduce associated motor weakness, we compared ropivacaine 2.5 mg in the intrathecal injection with a standard bupivacaine CSE in a double-blind study. Forty women were randomized to receive either bupivacaine 2.5 mg or ropivacaine 2.5 mg intrathecally, both with fentanyl 0.025 mg. There were no significant differences between the groups regarding the onset, duration or quality of analgesia or the level of sensory block attained. Forty per cent of the women (8/20) receiving bupivacaine developed detectable motor block compared with only 5% (1/20) in the ropivacaine group (P<0.05). Vibration sense was impaired in one woman in each group. Adverse effects did not differ between groups. We conclude that intrathecal ropivacaine 2.5 mg in combination with fentanyl 0.025 mg as part of a CSE technique provides rapid and safe analgesia for labour as effective as that achieved with bupivacaine 2.5 mg and with significantly less motor block.