Summary

Background and objective: For total intravenous anaesthesia an opioid is often combined with a hypnotic. A supra-additive interaction has been reported for clinical signs such as loss of consciousness or loss of the eyelash reflex. This study investigated the type of interaction of alfentanil and propofol on the electroencephalogram.

Methods: Twenty patients scheduled for abdominal surgery were enrolled in the study. Anaesthesia was induced and maintained with alfentanil and propofol. Each patient received a target-controlled infusion of alfentanil. Three target concentrations of 150, 225 and 300 ng mL−1 were applied to each patient in random order. Propofol was added to the alfentanil infusion by a feedback system. The set point was the range of 1.5–2.5 Hz median frequency of the electroencephalogram. Four arterial blood samples were taken within the last 20 min of each period. The mean drug concentrations were used to determine the type of interaction and an isobole was estimated by fitting Bernstein spline functions to the data.

Results: In 17 patients, all three alfentanil target concentrations could be administered. The test for supra-additivity as well as the isobole construction resulted in an additive type of interaction. The line of additivity cA/cA0 + cP/cP0 = 1 was best fitted for the values (standard deviation) cA0 = 1240 (51) ng mL−1 and cP0 = 5.21 (0.36) μg mL−1.

Conclusions: The type of interaction between alfentanil and propofol on the electroencephalogram in the investigated dose range is additive. This gives the freedom and need to select the appropriate dosing ratio of alfentanil and propofol by other considerations.

Summary

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

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

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

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

Summary

Background: Combinations of analgesic drugs provide the opportunity for better efficacy with less overall morbidity than provided by single analgesic agents. This article discusses the rationale, efficacy and safety for a novel analgesic combination: tramadol and acetaminophen (paracetamol).

Methods: Data supporting the rationale of combining tramadol and acetaminophen to provide pain relief will be reviewed in addition to clinical data demonstrating the efficacy and safety of this combination in acute and chronic pain states.

Results: Tramadol and acetaminophen are a rational combination product in that their mechanisms of action do not overlap and that in preclinical studies this combination acts synergistically. Also, this combination would be expected to provide more rapid pain relief than tramadol alone, and more persistent pain relief than acetaminophen alone. Moreover, each compound is broken down along separate metabolic pathways. Acute dental pain studies showed that pain relief and improvements in pain intensity associated with tramadol 75 mg plus acetaminophen 650 mg are superior to placebo, or tramadol or acetaminophen alone. This combination provided a rapid onset of action, identical to that achieved with acetaminophen alone, but the pain relief was also sustained, as for tramadol alone. Tramadol/acetaminophen also had the same adverse event profile as tramadol monotherapy. A chronic low back/osteoarthritic pain study showed that the drug combination can also be used similarly to codeine/acetaminophen combinations in treating benign chronic pain. The safety profile of the tramadol/acetaminophen combination is at least as favourable as that of codeine/acetaminophen, and is well tolerated with long-term use.

Conclusions: Tramadol/acetaminophen combination is a new preparation that is effective in acute or chronic moderate-to-moderately severe pain. It benefits from the complementary actions of the constituent analgesics, having the rapid onset of acetaminophen and the sustained effect of tramadol. The analgesic efficacy of this combination is comparable to that of positive controls, and its adverse event profile is in line with that of its single components.

Summary

Background and objective: Morbidity from subarachnoid haemorrhage is common and results from complications including myocardial dysfunction and neurogenic pulmonary oedema causing hypotension and hypoxia – both major causes of secondary brain injury. Predicting patients at risk of developing these complications may facilitate early intervention.

Methods: Using QTc dispersion to assess repolarization inhomogeneity, patients who had suffered severe acute subarachnoid haemorrhage were studied in an intensive care unit. Electrocardiograms were recorded within 24 h of ictus. Subsequent development of myocardial dysfunction was defined as a requirement for inotropes, and neurogenic pulmonary oedema as a PaO2 (kPa)/FiO2 ratio <40. Together they constituted cardiorespiratory compromise.

Results: Twenty-seven patients were recruited. QTc dispersion was greater in patients (74.1 ms, SD ± 26.1) than in controls (48.3 ms, 12.0) P < 0.0001, 95% CI 14.6, 37.0. Thirteen patients developed cardiorespiratory compromise and had greater QTc dispersion (84.5 ms, 26.2) than patients who did not develop cardiorespiratory compromise (64.5 ms, 22.7) P = 0.046, 95% CI 0.3, 39.6. There was no difference in QTc dispersion between patients who did and those who did not develop myocardial dysfunction alone. Similarly, there was no difference in QTc dispersion between patients who did and those who did not develop neurogenic pulmonary oedema alone.

Conclusions: Increased QTc dispersion is associated with the later development of cardiorespiratory compromise in poor-grade subarachnoid haemorrhage patients. QTc dispersion may be used as a marker to predict impending clinical deterioration, providing an opportunity for early intervention.

Summary

Background and objective: The implication of intrathecal lidocaine in neurological toxicity has made intrathecal bupivacaine the commonly used drug for local anaesthesia in ambulatory surgery. However, in high doses intrathecal bupivacaine may produce a high level of sensory and motor block, and arterial hypotension; discharge from hospital may be delayed. Intrathecal opioids added to low-dose local anaesthetics produce a synergistic effect without increasing the sympathetic block or delaying discharge. The aim of our study was to identify the minimum effective dose of intrathecal fentanyl that in combination with low-dose intrathecal bupivacaine would provide adequate surgical conditions without prolonging recovery.

Methods: A prospective, single, blind, randomized study was conducted in 45 adult males scheduled for minor urological procedures using intrathecal anaesthesia on a day care basis. Patients were randomly assigned to one of three groups (n = 15 each). They received bupivacaine 0.17% 5 mg – with either fentanyl 7.5 μg (fenta-7.5), 10 μg (fenta-10) or 12.5 μg (fenta-12.5) intrathecally in a total volume of 3 mL. The quality of anaesthesia, haemodynamic stability, time to two-segment and S2 regression, time to micturition, and time to discharge were assessed.

Results: The time to two-segment regression and S2 regression with fenta-12.5 was significantly longer than with fenta-7.5 and fenta-10 (P < 0.01). Fenta-7.5 had a significantly higher number of failed blocks (four patients) compared with fenta-12.5 (P < 0.05). The time out of bed, time to micturition and time to discharge were significantly longer with fenta-10 and fenta-12.5 compared with fenta-7.5, and also with fenta-12.5 compared with fenta-10 (P < 0.01). Haemodynamic stability did not differ for all the drug combinations.

Conclusions: Fentanyl 12.5 μg added to low-dose bupivacaine (5 mg) intrathecally provides better surgical anaesthesia and increased reliability of block than intrathecal fentanyl 7.5 or 10 μg. Haemodynamic stability was the same for all dose combinations used.

Summary

Background and objective: Monitoring the depth of anaesthesia by the bispectral index facilitates the titration of anaesthetic drugs during operation as well as assisting in early recovery. We planned to use this index to control the administration of anaesthetic agents in order to stabilize haemodynamics and promote recovery from anaesthesia in patients undergoing cardiac surgery with cardiopulmonary bypass.

Methods: Thirty adult patients undergoing valve replacement or coronary artery grafting under cardiopulmonary bypass were studied in a prospective, randomized, controlled study. Bispectral index monitoring was used in all patients. Patients received isoflurane anaesthesia and boluses of morphine: in the study group, anaesthetic depth was controlled using the bispectral index and clinical variables. In the control group, the bispectral index monitor could not be viewed by the anaesthesiologist. Bispectral index, mean arterial pressure and heart rate were noted every 5 min, and the incidence of hypotension, hypertension, tachycardia and bradycardia also noted. The time to recovery, when patients started obeying commands, was also recorded.

Results: Patients in the study group had significantly less hypertension and tachycardia (P < 0.05) than those in the control group. The time to recovery of consciousness was less in the study group than in the control group (n.s., P > 0.05). The bispectral index rose significantly in the control group at the time of institution and termination of cardiopulmonary bypass (P < 0.05).

Conclusions: Anaesthesia controlled by bispectral index monitoring decreases the incidence of haemodynamic disturbances and facilitates titration of anaesthetic agents during cardiopulmonary bypass and thus may assist recovery from anaesthesia.

Summary

Background and objective: Endogenous catecholamines are released in brain-dead organ donors following painful stimulation during retrieval surgery, and might be harmful to harvested organs. Our hypothesis was that inhibition of pain by fentanyl would inhibit such catecholamine release.

Methods: We tested 17 brain-dead organ donors in a randomized, placebo-controlled, double-blinded study. Blood samples for determination of epinephrine and norepinephrine concentrations were obtained before and 10 min after in take of either fentanyl 7 μg kg−1 or an equivalent volume of placebo. Further points of measurement were taken after skin incision and sternotomy. Mean arterial pressure and heart rate at these points were recorded.

Results: Catecholamine concentrations rose following painful stimuli. No differences in haemodynamics, between the fentanyl and the placebo group were detectable. Epinephrine concentrations, but not those of norepinephrine, were higher in the fentanyl group, reaching significance following sternotomy.

Conclusion: We conclude that the use of fentanyl (7 μg kg−1) was not effective in suppressing the catecholamine release, following painful surgical stimulation in brain-dead organ donors.

Summary

Background and objective: It has recently been suggested that recruitment proceeds far above the lower inflection point of the elastic pressure–volume (Pel/V) curve of the respiratory system. Accordingly, the value of the lower inflection point as a guide to set the positive end-expiratory pressure (PEEP) has been challenged. Our aim was to evaluate the derecruitment induced by stepwise decreasing PEEP levels.

Methods: Seven consecutive sedated and paralysed patients with acute respiratory distress syndrome were studied. Multiple Pel/V curves of the respiratory system were recorded at PEEP levels progressively decreasing in steps of 3.75 cmH2O from +15 to zero according to the principles of the low flow inflation method.

Results: Multiple Pel/V curves shifted towards lower volumes at decreasing PEEP. Dynamic compliance was higher for Pel/V curves recorded from lower PEEP levels. A high correlation (r = 0.99) was found between dynamic compliance and PEEP. The lower inflection point was on average 9.2 cmH2O. However, the transition between the lower segment and the linear part of the Pel/V curve was in general smooth to the eye. The upper inflection point was on average 23.8 cmH2O. A high correlation (r = 0.98) between the upper inflection point and PEEP was found.

Conclusions: The lower inflection point is a poor indicator of alveolar closure. The evaluation of derecruitment induced by a stepwise reduction in PEEP seems to be more useful than individual titration of PEEP and tidal volume in patients with adult respiratory distress syndrome.

Summary

Background and objective: Knowledge of the pharmacodynamic interaction between remifentanil and propofol is important to permit optimal dosage strategies. We studied this pharmacodynamic interaction using the median power frequency of the processed electroencephalogram as a control parameter for feedback-controlled dosing of propofol.

Methods: Twenty-one patients were given total intravenous anaesthesia with remifentanil and propofol. During three target-controlled infusion regimens, the target concentrations of remifentanil (5, 10, 15 ng mL−1) and propofol dosing were automatically adjusted to keep the median power frequency in the range 2 ± 0.5 Hz. In each patient and during each remifentanil target concentration, four arterial propofol/remifentanil concentration pairs were measured. The type of interaction was tested using the relative distance from the line of additivity and the isobole was modelled using Bernstein splines.

Results: The results from 13 patients were used for data analysis. The measured remifentanil concentrations during the three targets were (mean ± SD): 3.6 ± 0.9, 8.1 ± 2.5 and 12.4 ± 2.8 ng mL−1. The corresponding propofol concentrations were 2.64 ± 0.86, 2.13 ± 0.58 and 2.09 ± 0.58 μg mL−1. The data were best described with an additive type of interaction and the isobole was estimated using:

Conclusions: Within the studied concentration range, remifentanil and propofol showed an additive type of pharmacodynamic interaction on the electroencephalogram.

Summary

Background and objective: Neutrophils are important both for the immunological defence system and for the inflammatory tissue autoinjury mechanism. However, many local anaesthetics impair certain neutrophil functions. The aim was to assess the effects of ropivacaine, bupivacaine and lidocaine on human neutrophils from adult volunteers.

Methods: Chemotaxis, phagocytosis, reactive oxygen species production, intracellular calcium ion ([Ca2+]i) concentrations and protein kinase C activity were measured in the absence and presence of ropivacaine, bupivacaine or lidocaine. The lowest concentrations of the local anaesthetics were similar to those clinically observed in the plasma.

Results: Bupivacaine did not affect any neutrophil function (P > 0.05). Ropivacaine failed to change chemotaxis or phagocytosis, while lidocaine suppressed both these neutrophil functions. Ropivacaine (15, 150 μg mL−1) and lidocaine (20, 200 μg mL−1) impaired neutrophil production of O2−, H2O2 and OH− (P < 0.05) at similar rates (by 7–10%). These same concentrations of ropivacaine and lidocaine suppressed [Ca2+]i elevation. Finally, neither ropivacaine nor bupivacaine inhibited protein kinase C activity, while lidocaine did.

Conclusions: Suppression of the [Ca2+]i response in neutrophils by ropivacaine may represent one of the mechanisms responsible for the impairment of neutrophil functions. It should be emphasized that the inhibitory effects of ropivacaine are minor and are attained only at high concentrations, which may minimize the clinical implication of ropivacaine-associated impairment of reactive oxygen species production. Further studies using in vivo systems are required to identify the inhibitory effects of ropivacaine on reactive oxygen species production in clinical settings.

Summary

Background and objective: Since reports have shown that outpatient preoperative evaluation increases the quality of care and cost-effectiveness, an increasing number of patients are being evaluated purely on an outpatient basis. To improve cost-effectiveness, it would be appealing if those patients who are healthy and ready for surgery without additional testing could be easily distinguished from those who require more extensive evaluation. This paper examines whether published studies provide sufficient data to determine how detailed preoperative history taking and physical examination need to be in order to assess the health of surgical patients and to meet the objective of easy and early distinction.

Methods: A MEDLINE search was conducted from 1991 to 2000 with respect to preoperative patient history and physical examination. Altogether, 213 articles were found, of which 29 were selected. Additionally, 38 cross-references, 7 articles on additional testing and 4 recently published papers were used.

Results: It is questionable to what extent an extensive history is relevant for anaesthesia and long-term prognosis. With respect to physical examination, it seems unreasonable to diagnose valvular heart disease based on cardiac auscultation only, and it is unclear which method should be used to predict the difficulty of endotracheal intubation. The benefits of routine testing for all surgical patients before operation are extremely limited and are not advocated.

Conclusions: The amount of detail of preoperative patient history and the value of physical examination to obtain a reasonable estimate of perioperative risk remains unclear. Although not evidence based, a thorough history taking and physical examination of all patients before surgery seems important until more evidence-based guidelines become available. Diagnostic and prognostic prediction studies may provide this necessary evidence.

Summary

Background and objective: The effects of the volatile anaesthetic desflurane on platelet activation in vitro were studied and compared to those of halothane.

Methods: Platelet-rich plasma was exposed to 2 MAC of desflurane or halothane, or air only and stimulated by platelet agonists ADP (2.5, 5 and 10 μmol L−1) and collagen (10 μg mL−1). Platelet response was measured by Born aggregometry (maximum aggregation response, area under the curve) and flow cytometry (mean channel fluorescence, percentage of CD62P-positive cells, index of platelet activation for positive platelets).

Results: Aggregation response was significantly reduced in platelets exposed to desflurane or halothane; the inhibitory effect was more pronounced when the areas under the curve were analysed: values ranged from 37.5% to 73.3% of control samples for ADP stimulation and 77.1% to 79.8% for collagen stimulation. CD62P expression before and after stimulation with receptor agonists was not statistically different in platelets exposed to desflurane, halothane or air.

Conclusions: By impairing platelet aggregation while not affecting α-degranulation desflurane has a differential effect on various aspects of platelet activation similar to halothane. Our results are compatible with the hypothesis of an impairment of platelet thromboxane receptor signalling by halothane. We suggest a similar mechanism for desflurane.

Summary

Background and objective: Ropivacaine used for axillary plexus block provides effective motor and sensory blockade. Varying clinical dosage recommendations exist. Increasing the dosage by increasing the concentration showed no improvement in onset. We compared the behaviour of a constant dose of ropivacaine 150 mg diluted in a 30, 40 or 60 mL injection volume for axillary (brachial) plexus block.

Methods: A prospective, randomized, observer-blinded study on patients undergoing elective hand surgery was conducted in a community hospital. Three groups of patients with a constant dose of ropivacaine 150 mg, diluted in 30, 40 or 60 mL NaCl 0.9%, for axillary plexus blockade were compared for onset times of motor and sensory block onset by assessing muscle strength, two-point discrimination and constant-touch sensation.

Results: Increasing the injection volume of ropivacaine 150 mg to 60 mL led to a faster onset of motor block, but not of sensory block, in axillary plexus block, compared with 30 or 40 mL volumes of injection.

Conclusions: The data show that the onset of motor, but not of sensory block, is accelerated by increasing the injection volume to 60 mL using ropivacaine 150 mg for axillary plexus block. This may be useful for a more rapid determination of whether the brachial plexus block is effective. However, when performing surgery in the area of the block, sensory block onset seems more important.

Summary

Background and objective: We set out to compare the efficacy of clevidipine and sodium nitroprusside infusions in the control of blood pressure and the haemodynamic changes they produce in hypertensive patients after operation for elective coronary bypass grafting.

Methods: Thirty patients were randomly allocated to receive either clevidipine or sodium nitroprusside after their mean arterial pressure (MAP) had reached >90 mmHg for at least 10 min in the postoperative period. The MAP was continuously measured and related to time. Thus, the efficacy of the drugs in controlling arterial pressure could be inversely related to the total area under the MAP–time curve outside a target MAP range of 70–80 mmHg normalized per hour (AUCMAP mmHg min h−1). Haemodynamic variables and the number of dose-rate adjustments required to maintain MAP were also studied.

Results: There was no statistically significant difference in the efficacy (AUCMAP mmHg min h−1) of clevidipine (106 ± 25 mmHg min h−1) compared with sodium nitroprusside (101 ± 28 mmHg min h−1). Nor was any significant difference found in the total number of dose adjustments required to control MAP within the target range. The heart rate in patients receiving clevidipine increased less than in those given sodium nitroprusside. Stroke volume, central venous pressure and pulmonary artery pressure were significantly reduced upon administration of sodium nitroprusside but not of clevidipine.

Conclusions: There was no significant difference between clevidipine and sodium nitroprusside in their efficacy in controlling MAP. The haemodynamic changes, including tachycardia, were less pronounced with clevidipine than with sodium nitroprusside.

Summary

Background and objective: Sevoflurane has been used for the induction and maintenance of anaesthesia during cardiac surgery owing to its favourable haemodynamic effects. It has been suggested that it offers protection against myocardial ischaemia–reperfusion injury.

Methods: We investigated the effect of sevoflurane on plasma concentrations of tumour necrosis factor-α (TNF-α) after ex vivo stimulation of whole-blood leukocytes by lipopolysaccharide from 20 patients undergoing coronary artery bypass surgery. The patients were randomized to two groups. Group 1 patients were induced and maintained with sevoflurane; those in Group 2 were anaesthetized with moderate doses of midazolam–sufentanil. Blood samples were drawn from the patients on seven occasions from before induction of anaesthesia until 24 h after skin closure.

Results: Plasma concentrations of TNF-α were lower in Group 1 than in Group 2 after cessation of cardiopulmonary bypass (median (interquartiles): 25 (21–30) versus 37 (28–79) pg mL−1; P < 0.05) and 24 h after skin closure (196 (100–355) versus 382 (233–718) pg mL−1; P < 0.05). Postoperatively, two cases of myocardial infarction were recorded, one in each group. Six patients in Group 2 needed continued inotropic support after the first morning to maintain haemodynamic stability versus one patient in Group 1 (P < 0.05). The length of stay in the intensive care unit was significantly lower in Group 1 than in Group 2 (mean ± SD: 25 ± 16 versus 54 ± 30 h; P < 0.05).

Conclusions: Sevoflurane reduces production of TNF-α more than total intravenous anaesthesia with midazolam–sufentanil during cardiac surgery. This may reduce cardiac morbidity and the length of stay in the intensive care unit.

Summary

Background and objective: Trials in acute postoperative pain are usually small. Pooling homogenous data from a number of trials in a meta-analysis enables a truer estimate of efficacy. The aims of the present meta-analysis were to assess the analgesic efficacy and adverse effects of single-dose oral tramadol plus acetaminophen (paracetamol) in acute postoperative pain, and to demonstrate the efficacy of the combination formulation compared with its components.

Methods: Individual data from >1400 adult dental or gynaecologic/orthopaedic patients with moderate-to-severe pain were taken from seven randomised, double-blind, placebo controlled trials of tramadol (75 mg or 112.5 mg) plus acetaminophen (650 mg or 975 mg) with identical methods. The primary outcome measure was the number of patients needed to be treated (NNT) for one patient to obtain at least 50% pain relief. Information on adverse effects was also collected and the number needed to harm (NNH) was estimated.

Results: The tramadol/acetaminophen combination was more effective than either of its two components administered alone. For dental patients, who formed the bulk of the population, the combination formulation also had a significantly lower (better) NNT (≈3) than the components alone (≈8–12), comparable to ibuprofen 400 mg. The adverse effects associated with tramadol/acetaminophen were similar to those associated with the components alone. The commonest were dizziness, drowsiness, nausea, vomiting and headache.

Conclusions: Meta-analysis confirmed the analgesic superiority of the combination treatment over its components, without additional toxicity. Combination analgesic formulations are an important and effective means of pain relief, and should prove useful in treating elderly and other groups of patients who often cannot tolerate non-steroidal anti-inflammatory drugs, including the newer COX-2 inhibitors.

Summary

Background and objective: To compare, using prilocaine, the effects of continuous spinal anaesthesia (CSA) and continuous epidural anaesthesia (CEA) on haemodynamic stability as well as the quality of anaesthesia and recovery in patients undergoing transurethral resection of the prostate gland.

Methods: Thirty patients (>60 yr) were randomized into two groups. Prilocaine, 2% 40 mg, was given to patients in the CSA group, and prilocaine 1% 150 mg was given to patients in the CEA group. Incremental doses were given if the level of sensory block was lower than T10 or if needed during surgery.

Results: There was a significant decrease in mean arterial pressure in Group CEA compared with Group CSA (P < 0.01). The decrease in heart rate in Group CSA occurred 10 min after the first local anaesthetic administration and continued through the operation (P < 0.05). The level of sensory anaesthesia was similar in both groups. The times to reach the level of T10 and the upper level of sensory blockade (Tmax) were 18.0 ± 4.7 and 25.3 ± 7.0 min in Groups CSA and CEA, respectively, and were significantly longer in Group CEA. The duration of anaesthesia was 76.8 ± 4 min and was shorter in Group CSA (P < 0.01).

Conclusions: Spinal or epidural anaesthesia administered continuously was reliable in elderly patients undergoing transurethral resection of the prostate. Continuous spinal anaesthesia had a more rapid onset of action, produced more effective sensory and motor blockade and had a shorter recovery period. Prilocaine appeared to be a safe local anaesthetic for use with either continuous spinal anaesthesia or continuous epidural anaesthesia.

Summary

Background and objective: The aim was to study the rapid changes in cardiac output and systemic vascular resistance produced by intravenous epinephrine (5 μg) on a beat-by-beat basis.

Methods: Ten patients were studied during cardiac surgery. Radial or brachial arterial pressure was recorded continuously during intravenous administration of epinephrine (5 μg). Cardiac output and systemic vascular resistance were derived for each beat using arterial pulse contour analysis calibrated by lithium indicator dilution. In each patient a further dose of epinephrine (5 μg) was administered during cardiopulmonary bypass with the blood flow kept constant so that changes in arterial pressure corresponded to changes in systemic vascular resistance.

Results: When the patients were not on cardiopulmonary bypass, the epinephrine produced an initial increase in systemic vascular resistance to 129 ± 15% (mean ± SD) of control, followed by a more prolonged reduction to 57 ± 13% of control. Cardiac output showed a small initial reduction coincident with the increase in systemic vascular resistance, followed by an increase to 152 ± 24% of control. During cardiopulmonary bypass, the changes produced by epinephrine on systemic vascular resistance were qualitatively similar but smaller in amplitude, probably because of a greater volume of dilution in the bypass circuit.

Conclusions: Small bolus doses of epinephrine produce an initial increase in systemic vascular resistance followed by a much greater reduction that may cause hypotension.

Summary

Background and objective: Inflammation promotes hyperalgesia and increases opioid binding protein (α1-acid glycoprotein) inducing increased opioid requirement. To investigate the influence of an acute episode of inflammatory bowel disease in opioid requirement during major abdominal surgery, 17 patients with Crohn's disease, 12 patients with ulcerative colitis and seven patients without any inflammatory process (control group) were prospectively studied. Sufentanil requirements were assessed during surgery.

Methods: Sufentanil administration was adjusted when haemodynamic variables changed more than 20% of preoperative values. In a subgroup of 20 patients (Crohn's disease: 7, ulcerative colitis: 7, control group: 6), plasma concentrations of α1-acid glycoprotein and unbound sufentanil were measured. Total plasma clearance of sufentanil was also determined. Data presented as median (25–75‰) were analysed by non-parametric and ANOVA tests.

Results: Despite similar surgery duration, intraoperative sufentanil requirements were significantly larger in both the Crohn's disease group (0.9 (0.6–1.6) μg kg−1 h−1) and the ulcerative colitis group (1.1 (0.6–1.7) μg kg−1 h−1) than in the control group (0.5 (0.4–0.5) μg kg−1 h−1). Total plasma clearance of sufentanil was larger in patients with inflammatory bowel disease than in the control group. The plasma α1-acid glycoprotein concentration was increased in the inflammatory bowel disease group. However, the free fraction of sufentanil was similar in all three groups. The largest sufentanil consumption in patients with inflammatory bowel disease was observed during time of pain stimulation in the area of referred hyperalgesia from the affected viscus. In the control group, the sufentanil requirement was constant throughout surgery.

Conclusion: Inflammatory bowel disease increases opioid requirement during major abdominal surgery.

Summary

Background and objective: Isoflurane is commonly used for neurosurgery but the effects of sevoflurane on human cerebral blood flow and cerebral metabolic rate of oxygen have not been fully evaluated. We therefore assessed the effects of sevoflurane and isoflurane on global cerebral blood flow and cerebral metabolic rate of oxygen in patients without noxious stimuli or neurological disorders.

Methods: General anaesthesia was induced with midazolam (0.2 mg kg−1) and fentanyl (5 μg kg−1) in 20 ASA I patients undergoing knee joint endoscopic surgery. Epidural anaesthesia was also performed to avoid noxious stimuli during surgery. Cerebral blood flow and cerebral arteriovenous oxygen content difference was measured using the Kety–Schmidt method with 15% nitrous oxide as a tracer before and after administration of either sevoflurane or isoflurane (1.5 minimum alveolar concentration, 60 min) and cerebral metabolic rate of oxygen was then calculated.

Results: Sevoflurane and isoflurane both increased cerebral blood flow (17%, P < 0.05; 25%, P < 0.05, respectively) and decreased cerebral metabolic rate of oxygen (26%, P < 0.01; 38%, P < 0.01, respectively). There were no significant differences in cerebral blood flow and cerebral metabolic rate of oxygen between sevoflurane and isoflurane.

Conclusions: Sevoflurane and isoflurane similarly increased cerebral blood flow and decreased cerebral metabolic rate of oxygen in human beings anaesthetized with midazolam and fentanyl.