Bone mineral density in high-level endurance runners: Part B-genotype-dependent characteristics.

PURPOSE: Inter-individual variability in bone mineral density (BMD) exists within and between endurance runners and non-athletes, probably in part due to differing genetic profiles. Certainty is lacking, however, regarding which genetic variants may contribute to BMD in endurance runners and if specific genotypes are sensitive to environmental factors, such as mechanical loading via training. METHOD: Ten single-nucleotide polymorphisms (SNPs) were identified from previous genome-wide and/or candidate gene association studies that have a functional effect on bone physiology. The aims of this study were to investigate (1) associations between genotype at those 10 SNPs and bone phenotypes in high-level endurance runners, and (2) interactions between genotype and athlete status on bone phenotypes. RESULTS: Female runners with P2RX7 rs3751143 AA genotype had 4% higher total-body BMD and 5% higher leg BMD than AC + CC genotypes. Male runners with WNT16 rs3801387 AA genotype had 14% lower lumbar spine BMD than AA genotype non-athletes, whilst AG + GG genotype runners also had 5% higher leg BMD than AG + GG genotype non-athletes. CONCLUSION: We report novel associations between P2RX7 rs3751143 genotype and BMD in female runners, whilst differences in BMD between male runners and non-athletes with the same WNT16 rs3801387 genotype existed, highlighting a potential genetic interaction with factors common in endurance runners, such as high levels of mechanical loading. These findings contribute to our knowledge of the genetic associations with BMD and improve our understanding of why some runners have lower BMD than others.

Bone mineral density in high-level endurance runners: part A-site-specific characteristics.

PURPOSE: Physical activity, particularly mechanical loading that results in high-peak force and is multi-directional in nature, increases bone mineral density (BMD). In athletes such as endurance runners, this association is more complex due to other factors such as low energy availability and menstrual dysfunction. Moreover, many studies of athletes have used small sample sizes and/or athletes of varying abilities, making it difficult to compare BMD phenotypes between studies. METHOD: The primary aim of this study was to compare dual-energy X-ray absorptiometry (DXA) derived bone phenotypes of high-level endurance runners (58 women and 45 men) to non-athletes (60 women and 52 men). Our secondary aim was to examine the influence of menstrual irregularities and sporting activity completed during childhood on these bone phenotypes. RESULTS: Female runners had higher leg (4%) but not total body or lumbar spine BMD than female non-athletes. Male runners had lower lumbar spine (9%) but similar total and leg BMD compared to male non-athletes, suggesting that high levels of site-specific mechanical loading was advantageous for BMD in females only and a potential presence of reduced energy availability in males. Menstrual status in females and the number of sports completed in childhood in males and females had no influence on bone phenotypes within the runners. CONCLUSION: Given the large variability in BMD in runners and non-athletes, other factors such as variation in genetic make-up alongside mechanical loading probably influence BMD across the adult lifespan.

The anion study: effect of different crystalloid solutions on acid base balance, physiology, and survival in a rodent model of acute isovolaemic haemodilution.

BACKGROUND: Commercially available crystalloid solutions used for volume replacement do not exactly match the balance of electrolytes found in plasma. Large volume administration may lead to electrolyte imbalance and potential harm. We hypothesised that haemodilution using solutions containing different anions would result in diverse biochemical effects, particularly on acid-base status, and different outcomes. METHODS: Anaesthetised, fluid-resuscitated, male Wistar rats underwent isovolaemic haemodilution by removal of 10% blood volume every 15 min, followed by replacement with one of three crystalloid solutions based on acetate, lactate, or chloride. Fluids were administered in a protocolised manner to achieve euvolaemia based on echocardiography-derived left ventrical volumetric measures. Removed blood was sampled for plasma ions, acid-base status, haemoglobin, and glucose. This cycle was repeated at 15-min intervals until death. The primary endpoint was change in plasma bicarbonate within each fluid group. Secondary endpoints included time to death and cardiac function. RESULTS: During haemodilution, chloride-treated rats showed significantly greater decreases in plasma bicarbonate and strong ion difference levels compared with acetate- and lactate-treated rats. Time to death, total volume of fluid administered: chloride group 56 (3) ml, lactate group 62 (3) ml, and acetate group 65 (3) ml; haemodynamic and tissue oxygenation changes were, however, similar between groups. CONCLUSIONS: With progressive haemodilution, resuscitation with a chloride-based solution induced more acidosis compared with lactate- and acetate-based solutions, but outcomes were similar. No short-term impact was seen from hyperchloraemia in this model.

Preoperative exercise capacity in adult inflammatory bowel disease sufferers, determined by cardiopulmonary exercise testing.

BACKGROUND AND AIMS: Aerobic exercise capacity appears impaired in children with inflammatory bowel disease (IBD). Whether this holds true in adults with IBD is not known. Using cardiopulmonary exercise testing (CPET), we assessed anaerobic threshold (AT) in such patients comparing data with reference values and other elective surgical patients. We also sought to confirm whether the presence of a fistula further reduced AT. METHODS: CPET was performed between November 2007 and December 2010 on patients awaiting abdominopelvic surgery. Gender-specific normal reference values were used for comparison. Unadjusted comparison between two groups was made using Mann-Whitney U test and by unpaired t test. Data were adjusted by analysis of covariance, using age and sex as covariates. Differences between patients' observed values and reference values were tested using paired t tests. RESULTS: Four hundred and fourteen patients (234 male) were studied (mean ± SD age, 56.6 ± 16.4 years; weight, 74.2 ± 15.6 kg). Adjusted AT values in Crohn's disease (CD) were lower than colorectal cancer (11.4 ± 3.4 vs 13.2 ± 3.5 ml.kg(-1).min(-1), p = 0.03) and for all other colorectal disease groups combined (12.6 ± 3.5 ml.kg(-1).min(-1), p = 0.03). AT of Ulcerative colitis (UC) and CD patients together were reduced compared to population reference values (p < 0.05). CONCLUSION: After adjusting for age and sex, CD patients had a reduced AT compared to patients with colorectal cancer and other colorectal disease groups combined. The pathogenesis of this low AT remains to be defined and warrants further investigation.

Cardiopulmonary exercise testing predicts postoperative outcome in patients undergoing gastric bypass surgery.

BACKGROUND: For several types of non-cardiac surgery, the cardiopulmonary exercise testing (CPET)-derived variables anaerobic threshold (AT), peak oxygen consumption (VO2 peak), and ventilatory equivalent for CO(2) (VE/VCO2 ) are predictive of increased postoperative risk: less physically fit patients having a greater risk of adverse outcome. We investigated this relationship in patients undergoing gastric bypass surgery. METHODS: All patients (<190 kg) who were referred for CPET and underwent elective gastric bypass surgery at the Whittington Hospital NHS Trust between September 1, 2009, and February 25, 2011, were included in the study (n=121). Fifteen patients did not complete CPET. CPET variables (VO2 peak, AT, and VE/VCO2 ) were derived for 106 patients. The primary outcome variables were day 5 morbidity and hospital length of stay (LOS). The independent t-test and Fisher's exact test were used to test for differences between surgical outcome groups. The predictive capacity of CPET markers was determined using receiver operating characteristic (ROC) curves. RESULTS: The AT was lower in patients with postoperative complications than in those without [9.9 (1.5) vs 11.1 (1.7) ml kg(-1) min(-1), P=0.049] and in patients with a LOS>3 days compared with LOS ≤ 3 days [10.4 (1.4) vs 11.3 (1.8) ml kg(-1) min(-1), P=0.023]. ROC curve analysis identified AT as a significant predictor of LOS>3 days (AUC 0.640, P=0.030). The VO2 peak and VE/VCO2 were not associated with postoperative outcome. CONCLUSIONS: AT, determined using CPET, predicts LOS after gastric bypass surgery.

HIF1A P582S gene association with endurance training responses in young women.

Sequence variations in the gene encoding the hypoxia-inducible factor-1alpha, HIF1A, have been associated with physiologic function and could be associated with exercise responses. In the HIF1A P582S gene polymorphism (C1772T; rs 11549465 C/T), a single nucleotide transition from C → T alters the codon sequence from the usual amino acid; proline (C-allele), to serine (T-allele). This polymorphism was examined for association with endurance training responses in 58 untrained young women who completed a 6-week laboratory-based endurance training programme. Participant groups were defined as CC homozygotes versus carriers of a T-allele (CC vs. CT genotypes). Adaptations were examined at the systemic-level, by measuring [Formula: see text] and the molecular-level by measuring enzymes determined from vastus lateralis (n = 20): 3-hydroacyl-CoA-dehydrogenase (HAD), which regulates mitochondrial fatty acid oxidation; cytochrome C oxidase (COX-1), a marker of mitochondrial density; and phosphofructokinase (PFK), a marker of glycolytic capacity. CT genotypes showed 45% higher training-induced gains in [Formula: see text] compared with CC genotypes (P < 0.05). At the molecular level, CT increased the ratios PFK/HAD and PFK/COX-1 (47 and 3%, respectively), while in the CC genotypes these ratios were decreased (-26 and -54%, respectively). In conclusion, the T-allele of HIF1A P582S was associated with greater gains in [Formula: see text] following endurance training in young women. In a sub-group we also provide preliminary evidence of differential muscle metabolic adaptations between genotypes.

Intrathecal low-dose hyperbaric bupivacaine-clonidine combination in outpatient knee arthroscopy: a randomized controlled trial.

BACKGROUND: Spinal anesthesia for knee arthroscopy can be produced with a low dose of bupivacaine, but additional intrathecal drugs are often required to lower the risk of failed blocks. We investigated the effect of the addition of clonidine (0, 15 or 30 microg) to 5 mg hyperbaric bupivacaine on the duration of the motor block, analgesic quality and ability to void after the surgery in a randomized controlled trial. METHODS: Seventy-five patients received spinal anesthesia using either 5 mg hyperbaric bupivacaine (B5C0), 5 mg hyperbaric bupivacaine with 15 microg clonidine (B5C15) or 5 mg hyperbaric bupivacaine with 30 microg clonidine (B5C30). The primary outcome was the duration of the motor block. Secondary outcomes included the time until spontaneous voiding, and the need for additional analgesia or general anesthesia. RESULTS: The mean time to complete regression of motor block was 70 (+/-43) min in group B5C0. Adding 15 and 30 microg of clonidine increased the motor block duration by 25 [95% confidence interval (CI): 2-48] and 34 (95% CI: 11-57) min, respectively, but resulted in better analgesic quality. The mean time until spontaneous voiding was 177 min in the B5C0 group. This time increased with 18 (95% CI -13 to 49) and 44 (95% CI 15-74) min in group B5C15 and group B5C30, respectively. CONCLUSION: The addition of 15 microg clonidine to 5 mg of intrathecal hyperbaric bupivacaine prolongs the duration of motor block and improves the quality of the block.

Influence of age on the pharmacokinetics of alfentanil. Gender dependence.

Studies on the effects of age on the pharmacokinetics of alfentanil are inconclusive. A possible factor in explaining the differences between various studies could be the effect of gender. The authors studied the effects of age on the pharmacokinetics of alfentanil in female (n = 21) and male (n = 15) patients undergoing lower abdominal surgery under nitrous oxide alfentanil anaesthesia. There was a significant negative correlation (r = -0.79, p less than 0.001) between plasma alfentanil clearance (CL) and age in women (less than 50y, median CL 24.84 L/h; greater than 50y, median CL 14.52 L/h), but not in men (less than 50y, median CL 19.44 L/h; greater than 50y, median CL 16.2 L/h). The conclusion is drawn that the effects of age on the pharmacokinetics of alfentanil are gender-dependent.

Quantification of the EEG effect of midazolam by aperiodic analysis in volunteers. Pharmacokinetic/pharmacodynamic modelling.

The effects of midazolam on the EEG were related to plasma midazolam concentrations in 8 healthy male volunteers in order to develop a pharmacokinetic-pharmacodynamic model. The EEG parameters were derived by aperiodic analysis. The EEG was recorded between Fp1-M1 and Fp2-M2. Following a 15-minute baseline EEG registration, midazolam 15 mg was given intravenously over 5 minutes. Venous blood samples were taken until 8 hours after the start of the infusion. Within 2 to 4 minutes of starting the infusion all subjects became asleep, with loss of eyelid reflex. The most obvious EEG changes, in the beta frequency range (12 to 30 Hz), were observed within 2 minutes of the start of drug administration. Seven subjects awoke 60 to 70 minutes after the start of the infusion and 1 awoke after 45 minutes. The EEG parameter that best characterised the effect of midazolam was the total number of waves per second in the frequency range 12 to 30 Hz (TNW12-30). This was used as the effect parameter in the pharmacokinetic-pharmacodynamic modelling. The plasma concentration-time data were characterised by a triexponential function for all subjects. To allow for a possible delay between plasma midazolam concentration and EEG effect, a hypothetical effect compartment was included in the pharmacokinetic-pharmacodynamic model. A sigmoid maximum effect (Emax) model was used to characterise the effect compartment midazolam concentration-TNW12-30 data. The plasma drug concentration corresponding to half the maximum increase in TNW12-30 (EC50) was 290 +/- 98 micrograms/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics and EEG effects of flumazenil in volunteers.

The effect of intravenous flumazenil 10 mg on the electroencephalogram (EEG) was investigated in 7 volunteers in a placebo-controlled, randomised, double-blind, crossover study. The EEG was recorded between Fp1-M1 and Fp2-M2 and analysed using an aperiodic analysis technique. Two volunteers were excluded from the study because of significant asymmetry between baseline EEG recordings of the left and right hemisphere, in the remainder there were no changes in the beta-frequency range (12 to 30 Hz) or in other ranges of the EEG during or after flumazenil or placebo administration, with regard to the parameters total number of waves per second or total amplitude per second. There were no changes in heart rate, respiratory rate or blood pressure after administration of flumazenil or placebo. Three volunteers reported feelings of 'pressure to move' during the initial 2 min of the flumazenil infusion. The pharmacokinetics of flumazenil were investigated in the same volunteers. Flumazenil 10 mg was administered intravenously over 10 min; the data from 1 volunteer were excluded from this analysis because of blood sampling problems. The plasma concentration-time data of the remaining 6 volunteers were characterised by a biexponential function. The pharmacokinetic parameters were (mean +/- SD): initial volume of distribution, 16 +/- 5.7L; volume of distribution at steady-state, 64.8 +/- 12.5L; total body clearance, 53.8 +/- 1.2 L/h; distribution half-life, 4.1 +/- 1.3 min; and elimination half-life, 70.2 +/- 9.9 min. The authors conclude that flumazenil has no significant EEG effects. The rapid distribution and elimination of flumazenil may explain its previously reported short duration of action after intravenous anaesthesia with high doses of midazolam.

Pharmacokinetic-pharmacodynamic modelling of the interaction between flumazenil and midazolam in volunteers by aperiodic EEG analysis.

The CNS effects resulting from the combined administration of midazolam and flumazenil were studied in 8 healthy volunteers to develop a model of the pharmacokinetic-pharmacodynamic interaction. Electroencephalograms (EEG) were recorded between Fp1-M1 and Fp2-M2. The EEG parameter total number of waves between 12 and 30 Hz (TNW12-30) derived by aperiodic analysis was used to quantify the effect. Following a 15 min baseline EEG recording, infusion of placebo or flumazenil was started. Infusion regimens for flumazenil were designed so that 'steady-state' concentrations of 10 and 20 micrograms/L were obtained. Doses of midazolam 15, 30 and 60 mg over 5 min were given 30 min after the start of placebo infusion (session A) or flumazenil infusion to 10 micrograms/L (session B) or 20 micrograms/L (session C), respectively. Venous blood samples were taken until 8 h after the start of the flumazenil or placebo infusion. A sigmoid maximum effect (Emax) model was used to characterise the relationship between the plasma concentration of midazolam which is in equilibrium with the effect compartment concentration (Cem) [Cem/Kp] and TNW12-30. Within 2 to 5 min of starting the midazolam infusion all subjects fell asleep, with loss of eyelid reflex. They awoke between 25 and 82 min later in all 3 sessions. The mean (+/- SD) plasma drug concentrations of midazolam corresponding to half the maximum increase in TNW12-30 (EC50) were 276 +/- 64, 624 +/- 187 and 1086 +/- 379 micrograms/L in sessions A, B and C, respectively. The half-lives reflecting equilibration between plasma concentration and effect (t1/2ke0), estimated by a nonparametric method, were 2.2 +/- 1.2, 3.3 +/- 3.3 and 2.9 +/- 1.2 min for the 3 different sessions. Emax and N were not affected by flumazenil. In each subject the plot of the average measured steady-state plasma flumazenil concentration versus the EC50 of midazolam showed a linear relationship. The plasma concentration of flumazenil that doubled the EC50 of midazolam (Cf,2) was 6.5 +/- 1.0 micrograms/L. The observed interaction is consistent with the competitive nature of the antagonism of midazolam by flumazenil.

Growth of an aorta-coronary anastomosis. An experimental study in pigs.

The influence of growth of an aorta-coronary anastomosis, comparable to the coronary translocation anastomosis during the arterial switch operation, was studied in pigs. The anastomosis between the right coronary artery and the aorta did not grow, and this lack of growth may result in stenosis. With another technique, by which the coronary artery was excised with a cuff of aortic wall, the effects caused by absence of growth were circumvented and a normal-sized coronary ostium was present after growth. However, when no cuff was used, stenosis occurred at the suture line and caused growth retardation of the animal as well as histologic damage to the right ventricle.

An integrated model for the interaction of muscle relaxants with their antagonists.

An integrated model describing the interaction of nondepolarizing neuromuscular blocking agents with reversible anticholinesterase agents is derived and compared with a naive model using experimental data obtained from four anesthetized dogs. Three consecutive but separate steady-state d-tubocurarine blocks (approximately 50, 70, and 90%) were induced in each of the four dogs and reversed by short edrophonium infusions. Edrophonium arterial concentrations and twitch tension of the anterior tibialis muscle were measured. Both the integrated and the naive model were fit to the twitch tension data using a model with a hypothetical "effect" compartment. The integrated model consistently fit the twitch tension data better than the naive model; the sum of squared deviations was lower by 46, 45, 87, and 69%, respectively, with the integrated model than with the naive model. Also, in contrast to the naive model, the integrated model is capable of describing the interaction of the anticholinesterase agent and the neuromuscular blocking agent when the concentration of either varies with time.

Clinical pharmacology of rocuronium (Org 9426): study of the time course of action, dose requirement, reversibility, and pharmacokinetics.

STUDY OBJECTIVE: To evaluate the time course of action, dose requirement, reversibility, and pharmacokinetics of rocuronium (Org 9426) under 3 anesthetic techniques (nitrous oxide-fentanyl supplemented with propofol, halothane, or isoflurane). DESIGN: Prospective, randomized study. SETTING: Operating suite at a university hospital. PATIENTS: 36 ASA physical status I-III patients aged 18 to 65 years who were scheduled for elective surgery. INTERVENTIONS: The time course of action of an intubation dose of rocuronium 600 micrograms/kg was investigated in 36 patients. In 18 of these patients, the maintenance dose requirement of rocuronium and reversibility by neostigmine were evaluated. In the remaining 18 patients, the pharmacokinetics of rocuronium after the intubating dose were studied. Neuromuscular transmission was monitored by mechanomyography. Venous blood samples and urine were analyzed by high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: With the exception of a longer clinical duration of rocuronium-induced neuromuscular block in the isoflurane group compared with the propofol group (p = 0.03), time course of action variables were similar in the 3 groups. In patients receiving maintenance doses of rocuronium, the dose requirement until reversal was 636 +/- 191 micrograms/kg/hr, 496 +/- 107 micrograms/kg/hr, and 384 +/- 127 micrograms/kg/hr for the propofol, halothane, and isoflurane groups, respectively (p = 0.02 for the isoflurane group vs. the propofol group). With respect to the reversal of a rocuronium-induced neuromuscular block, there were no differences in the percentage recovery or rate of recovery among the 3 groups. Pharmacokinetic analysis showed no significant differences for rocuronium during the 3 anesthetic techniques. CONCLUSION: Isoflurane potentiates the rocuronium-induced neuromuscular block, resulting in a longer clinical duration and lower maintenance dose requirement. This difference is not explained by differences in pharmacokinetics but is probably due to increased sensitivity of the neuromuscular junction to rocuronium during isoflurane anesthesia.

[Better postoperative pain management in children by introduction of guidelines; a prospective study]. / Verbetering van de postoperatieve pijnzorg bij kinderen door invoering van richtlijnen; een prospectief onderzoek.

OBJECTIVE: To investigate the influence of recommendations on the quality of postoperative pain management in children. DESIGN: Prospective. SETTING: University Hospital Groningen, the Netherlands. METHOD: After interdisciplinary recommendations on postoperative pain were developed, the quality of postoperative pain management was investigated before implementation (phase I; n = 50 children aged 0-14 who underwent elective surgery), three months after the implementation (phase II; n = 51), and nine months later (phase III; n = 50). Quality was defined by a pain score (for ages 0 to 4 with the 'Children's Hospital of Eastern Ontario pain scale' (CHEOPS) and for ages 4-14 with the Oucher scale) and the prescription of analgetics: kind, dose, frequency, prescription by anaesthetist and doctor on the ward. Pain was scored every 2 hours during the first 24 hours after surgery. A CHEOPS score < or = 6 an Oucher score < or = 50 was defined as adequate; higher scores were defined as inadequate. RESULTS: Pain measurement showed a statistically significant improvement of pain scores in time (phase II and III compared with phase I: odds ratio: 2.5; 95% confidence interval: 1.03-6.00; p < 0.01). Searching for factors that could be responsible for this improvement, like medication, we found no statistically significant differences in everyday practice in phase II and III compared with phase I. However, children who could score their pain by self-report (Oucher) showed the best results in all 3 phases of the study. The youngest children, i.e. less than 6 months old, showed inadequate results during the whole study. The greatest improvement in time during the first 12 hours was seen in the group of children older than 6 months. The recommendations were followed more strictly in younger children, and when continuous morphine was given. CONCLUSION: Pain scores in children improved after the introduction of recommendations on postoperative pain. However, the improvement could not be attributed to factors like medication. Factors like a change in attitude towards pain could be responsible for this change.

Postoperative analgesia with continuous epidural sufentanil and bupivacaine: a prospective study in 614 patients.

To assess the efficacy and safety of postoperative analgesia with continuous epidural sufentanil and bupivacaine, we performed a prospective study in 614 patients undergoing major surgery. Before surgical incision, all patients received an initial dose of 50 micrograms sufentanil in 6-10 mL bupivacaine 0.125% via a lumbar or thoracic catheter. After 1 h, a continuous infusion was started with 50 micrograms sufentanil in 50 mL bupivacaine 0.125% at a rate of 6-10 mL/h. The infusion was continued postoperatively for 1-5 days or longer, depending on the type of operation and the patient's analgesic need. In the majority of patients, adequate pain relief was obtained at rest and during movement. Late respiratory depression was observed in three patients; in most patients only minor side effects were seen. Technical complications during epidural puncture or insertion of the catheter were 4% and 3%, respectively. We conclude that continuous epidural sufentanil and bupivacaine is safe and effective.

Does epidural sufentanil provide effective analgesia per- and postoperatively for abdominal aortic surgery?

To assess the efficacy of epidural sufentanil in providing per- and postoperative analgesia, 40 patients undergoing elective abdominal aortic surgery received either 50 mu g sufentanil in 10 ml normal saline solution (n = 20, ES group) or 10 ml normal saline (n = 20, control group) via a thoracic epidural catheter. The study solution was given (double-blind and at random) after the patients had been anaesthetized with i.v. midazolam, sufentanil and vecuronium. Anaesthesia was maintained with 60% nitrous oxide in oxygen and halothane at a 1% inspiratory concentration. When patients showed signs of inadequate analgesia, supplementary doses of 25 mu g sufentanil were given i.v. The number of patients requiring additional i.v. sufentanil differed significantly between the two groups: 5 out of 20 patients in the ES group vs 13 out of 20 patients in the control group required additional sufentanil (P<0.05). The mean dose administered i.v. did not differ significantly between the two groups: 105 +/- 109.5 mu g vs 138.5 +/- 126.9 mu g (mean +/- SD) in 5 and 13 patients, respectively. No cardiovascular changes were observed after the epidural bolus dose. Postoperative analgesia, consisting of a continuous epidural infusion of 50 mu g sufentanil in 50 ml bupivacaine 0.125% at a rate of 6-10 ml/h after a bolus dose of 10 ml of this solution, was adequate in the majority of patients, as determined by VAS-scores assessed during the epidural treatment (4.3 +/- 1.5 days).

A case of malignant hyperthermia?

An acute episode of a malignant hyperthermia-like syndrome is described which occurred after suxamethonium and isoflurane anaesthesia in a 41-year-old healthy male patient undergoing a minor elective hand operation. Dantrolene therapy rapidly reversed the life-threatening signs. Laboratory results appeared to confirm the suspicion of malignant hyperthermia. However, the in vitro contracture test, which was carried out according to the standards of the European Malignant Hyperthermia Group, was equivocal.

Quantitative electroencephalographic analysis of the biphasic concentration-effect relationship of propofol in surgical patients during extradural analgesia.

We studied effects on the EEG of propofol infused at a rate of 0.5 mg kg-1 min-1 for 10 min in 10 healthy male surgical patients under extradural analgesia. The EEG amplitude in six frequency bands was related to arterial blood propofol concentrations and responsiveness to verbal commands. The EEG amplitude showed a characteristic biphasic response to increasing blood propofol concentrations in all frequency bands. During the infusion, patients lost responsiveness when EEG amplitudes in the high frequency bands were decreasing after having reached a maximum. EEG changes were different during infusion and emergence. Pharmacodynamic modelling, using two effect compartments with dissimilar equilibration constants, resulted in satisfactory fits. We conclude that propofol exerts a biphasic effect on the EEG amplitude in all frequency bands. The dissimilarity of EEG changes during infusion and during emergence suggests that two effect compartments with different equilibration constants exert opposing effects on the EEG.