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.

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.

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.

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.

The accuracy of trained nurses in pre-operative health assessment: results of the OPEN study.

We quantified the accuracy of trained nurses to correctly assess the pre-operative health status of surgical patients as compared to anaesthetists. The study included 4540 adult surgical patients. Patients' health status was first assessed by the nurse and subsequently by the anaesthetist. Both needed to answer the question: 'is this patient ready for surgery without additional work-up, Yes/No?' (primary outcome). The secondary outcome was the time required to complete the assessment. Anaesthetists and nurses were blinded for each other's results. The anaesthetists' result was the reference standard. In 87% of the patients, the classifications by nurses and anaesthetists were similar. The sensitivity of the nurses' assessment was 83% (95% CI: 79-87%) and the specificity 87% (95% CI: 86-88%). In 1.3% (95% CI: 1.0-1.6%) of patients, nurses classified patients as 'ready' whereas anaesthetists did not. Nurses required 1.85 (95% CI: 1.80-1.90) times longer than anaesthetists. By allowing nurses to serve as a diagnostic filter to identify the subgroup of patients who may safely undergo surgery without further diagnostic workup or optimisation, anaesthetists can focus on patients who require additional attention before surgery.

Role of history and physical examination in preoperative evaluation.

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.

Postoperative analgesia with intramuscular morphine at fixed rate versus epidural morphine or sufentanil and bupivacaine in patients undergoing major abdominal surgery.

UNLABELLED: We assessed the efficacy and side effects of postoperative analgesia with three different pain regimens in 90 patients undergoing major abdominal surgery. The patients were randomly assigned to one of three groups: epidural morphine (EM) or sufentanil (ES), both combined with bupivacaine, or IM morphine (IM) at fixed intervals. Before incision, patients in the epidural groups received sufentanil or morphine in bupivacaine via a thoracic catheter, followed by a continuous infusion 1 h later. General anesthesia consisted of N2O/O2 and isoflurane for all groups. Patients in all groups received IV sufentanil as part of their anesthetic management. Patients in the IM group received IV sufentanil 1 microg/kg before incision, and patients in all groups received sufentanil 10 microg for inadequate analgesia. Postoperatively, the epidural or IM treatment was continued for > or =5 days. Postoperative analgesia at rest and during coughing and movement was significantly better in the epidural groups than in the IM group during the 5 consecutive days. There were no significant differences between the epidural groups. The incidence of most side effects was similar in all groups. We conclude that epidural analgesia provided better pain relief than IM analgesia, even if the latter was optimized by fixed-dose administration at fixed intervals and included adjustments on demand. Epidural sufentanil and morphine, both combined with bupivacaine, seemed to be equally effective with similar side effects. IMPLICATIONS: Postoperative analgesia with epidural sufentanil or morphine and bupivacaine after major abdominal surgery seemed to be better than the conventional method of IM morphine treatment, despite optimal administration, i.e., fixed doses at fixed intervals with regular adjustments. Analgesic efficacy and side effects of epidural sufentanil and morphine were similar.

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.

[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.

The effect of midazolam at two plasma concentrations of hemodynamics and sufentanil requirement in coronary artery surgery.

OBJECTIVES: In this study, the hemodynamics and sufentanil requirement were compared at two midazolam target plasma concentrations in patients undergoing coronary artery bypass grafting (CABG). DESIGN: Prospective, randomized study. SETTING: University hospital, single institution. PARTICIPANTS: Patients undergoing CABG. INTERVENTIONS: Patients were randomly assigned to receive midazolam at a target plasma concentration of 150 ng/mL (group 1; n = 10) or 300 ng/mL (group 2; n = 10). Sufentanil infusion was titrated to maintain hemodynamic stability, defined as mean arterial pressure within 15% of baseline values. All patients received preoperative beta-blocking agents. Arterial blood samples of midazolam and sufentanil were analyzed by high-performance liquid chromatography and radioimmunoassay, respectively. MEASUREMENTS AND MAIN RESULTS: The mean dose of sufentanil (7.5 +/- 1.7 microgram/kg in group 1 v 7.2 +/- 2.5 micrograms/kg in group 2) did not differ. There were no significant differences in hemodynamics between the groups in the period before or after cardiopulmonary bypass (CPB). Before CPB, in two patients in each group, hypertension was controlled with sufentanil only. One patient in group 1 required a vasodilator in addition to sufentanil. No ischemic events occurred before CPB. After CPB, one patient in group 2 required a vasodilator to control hypertension. Two patients in group 2 required treatment with nitroglycerin for myocardial ischemia. Stable plasma concentrations of sufentanil and midazolam were obtained during and after CPB. The midazolam infusion was continued in both groups at a rate of 1.25 micrograms/kg/min during the first 4 postoperative hours. The time to awakening did not differ between the groups (100 +/- 58 minutes in group 1 v 173 +/- 147 minutes in group 2) nor did the plasma concentrations of midazolam (96 +/- 28 ng/mL v 108 +/- 42 ng/mL) at the time of awakening. Intraoperative awareness was not reported. CONCLUSION: In patients undergoing CABG, good hemodynamic control with a similar incidence of hemodynamic interventions was observed at midazolam target plasma concentrations of 150 and 300 ng/mL when coadministered with sufentanil. The sufentanil requirement was identical in both groups. This study suggests that a midazolam plasma concentration of 150 ng/mL is sufficient to provide satisfactory hemodynamic control and to avoid intraoperative awareness.

Inotropic effects of propofol, thiopental, midazolam, etomidate, and ketamine on isolated human atrial muscle.

BACKGROUND: Cardiovascular instability after intravenous induction of anesthesia may be explained partly by direct negative inotropic effects. The direct inotropic influence of etomidate, ketamine, midazolam, propofol, and thiopental on the contractility of isolated human atrial tissue was determined. Effective concentrations were compared with those reported clinically. METHODS: Atrial tissue was obtained from 16 patients undergoing coronary bypass surgery. Each fragment was divided into three strips, and one anesthetic was tested per strip in increasing concentrations (10(-6) to 10(-2) M). Strips were stimulated at 0.5 Hz, and maximum isometric force was measured. Induction agents were studied in two groups, group 1 (n = 7) containing thiopental, midazolam, and propofol, and group 2 (n = 9) consisting of etomidate, ketamine, and propofol. RESULTS: The tested anesthetics caused a concentration-dependent depression of contractility resulting in complete cessation of contractions at the highest concentrations. The IC50s (mean +/- SEM; microM) for inhibition of the contractility were: thiopental 43 +/- 7.6, propofol 235 +/- 48 (group 1), and 246 +/- 42 (group 2), midazolam 145 +/- 54, etomidate 133 +/- 13, and ketamine 303 +/- 54. CONCLUSIONS: This is the first study demonstrating a concentration-dependent negative inotropic effect of intravenous anesthetics in isolated human atrial muscle. No inhibition of myocardial contractility was found in the clinical concentration ranges of propofol, midazolam, and etomidate. In contrast, thiopental showed strong and ketamine showed slight negative inotropic properties. Thus, negative inotropic effects may explain in part the cardiovascular depression on induction of anesthesia with thiopental but not with propofol, midazolam, and etomidate. Improvement of hemodynamics after induction of anesthesia with ketamine cannot be explained by intrinsic cardiac stimulation.

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).

Effects of hypothermic cardiopulmonary bypass on the pharmacodynamics and pharmacokinetics of rocuronium.

OBJECTIVE: To study the influence of hypothermic cardiopulmonary bypass (CPB) on the pharmacodynamics and pharmacokinetics of rocuronium. DESIGN: Prospective, descriptive study. SETTING: Operating room at a university hospital. PARTICIPANTS: Ten ASA class III and IV patients, ranging in age from 35 to 75 years, scheduled for elective coronary artery bypass grafting. INTERVENTIONS: Neuromuscular transmission was monitored mechanomyographically. The time course of action of maintenance doses and plasma concentration-response relationships were determined before, during, and after CPB. The plasma concentration decay and renal elimination were studied simultaneously. Plasma and urine concentration of rocuronium were determined by high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: Hypothermic CPB prolonged the duration of action of maintenance doses and coincided with a lower plasma concentration at a twitch response of 5% of control. The duration of action of maintenance doses returned to prehypothermic CPB level after rewarming to a nasopharyngeal temperature of 37 degrees C. The plasma concentration-response relationship did not return to precooling control value, probably owing to persisting peripheral hypothermia. Both the renal elimination of rocuronium and the plasma concentration decay after the last maintenance dose under normothermic conditions resembled values obtained in patients not undergoing hypothermic CPB. CONCLUSIONS: Hypothermic CPB prolongs the duration of action of maintenance doses and alters the plasma concentration-response relationship of rocuronium. These changes may be the result of, on the one hand, an increased sensitivity of the neuromuscular transmission and/or decreased muscle contractility and, on the other hand, the result of a reduced plasma clearance during hypothermia.

Hypothermic cardiopulmonary bypass influences the concentration-response relationship and the biodisposition of rocuronium.

In 10 patients scheduled for elective coronary artery bypass grafting under midazolam-sufentanil anaesthesia, the influence of hypothermia on the plasma concentration-response and biodisposition of rocuronium were investigated. Neuromuscular function was monitored mechanomyographically. Plasma and urine concentrations of rocuronium were determined by high performance liquid chromatography. Hypothermic cardiopulmonary bypass prolonged the duration of action of maintenance doses and altered the plasma concentration-response relationship. The elimination and distribution half-lives, following the last maintenance dose after rewarming, and the urinary excretion of rocuronium were similar to values obtained during normothermia. A diminished hepatic uptake and storage in the liver of rocuronium during hypothermia may explain the more pronounced prolongation of the duration compared to that of other steroidal neuromuscular blocking agents.

Neuromuscular and cardiovascular effects of neostigmine and methyl-atropine administered at different degrees of rocuronium-induced neuromuscular block.

The neuromuscular and cardiovascular effects of neostigmine, 40 micrograms kg-1, and methyl-atropine, 7 micrograms kg-1, administered at different degrees of rocuronium-induced (600 micrograms kg-1) neuromuscular block were evaluated. In one group of patients spontaneous recovery was awaited (Group A; n = 20). Neostigmine and methyl-atropine were administered 2 minutes after rocuronium (Group B; n = 20) or at 25% twitch recovery (Group C; n = 20). Neuromuscular transmission was monitored mechanomyographically. Data are presented as mean (SD) [95%-CI]. The initial rate of recovery (time until a TOF ratio of 0.2) in group B, i.e. 14.2 (4.5) [12.1-16.3] min, was significantly faster than in group C, i.e. 28.7 (5.3) [26.3-31.1] min. However, the time until clinically sufficient recovery (time until a TOF ratio of 0.7) was similar for groups B, i.e. 29.3 (9.5) [24.9-33.7] min and group C, i.e. 31.8 (5.6) [29.2-34.4] min, both significantly different from that of group A, i.e. 53.2 (14.5) [46.5-59.9] min. The increase in heart rate following neostigmine/methyl-atropine was more pronounced in the group reversed at 2 min after rocuronium (P < 0.01).