Probability to tolerate laryngoscopy and noxious stimulation response index as general indicators of the anaesthetic potency of sevoflurane, propofol, and remifentanil.

BACKGROUND: The probability to tolerate laryngoscopy (PTOL) and its derivative, the noxious stimulation response index (NSRI), have been proposed as measures of potency of a propofol-remifentanil drug combination. This study aims at developing a triple drug interaction model to estimate the combined potency of sevoflurane, propofol, and remifentanil in terms of PTOL. We compare the predictive performance of PTOL and the NSRI with various anaesthetic depth monitors. METHODS: Data from three previous studies (n=120) were pooled and reanalysed. Movement response after laryngoscopy was observed with different combinations of propofol-remifentanil, sevoflurane-propofol, and sevoflurane-remifentanil. A triple interaction model to estimate PTOL was developed. The NSRI was derived from PTOL. The ability of PTOL and the NSRI to predict observed tolerance of laryngoscopy (TOL) was compared with the following other measures: (i) effect-site concentrations of sevoflurane, propofol, and remifentanil (CeSEVO, CePROP, and CeREMI); (ii) bispectral index; (iii) two measures of spectral entropy; (iv) composite variability index; and (v) surgical pleth index. RESULTS: Sevoflurane and propofol interact additively, whereas remifentanil interacts in a strongly synergistic manner. The effect-site concentrations of sevoflurane and propofol at a PTOL of 50% (Ce50; se) were 2.59 (0.13) vol % and 7.58 (0.49) µg ml(-1). A CeREMI of 1.36 (0.15) ng ml(-1) reduced the Ce50 of sevoflurane and propofol by 50%. The common slope factor was 5.22 (0.52). The PTOL and NSRI predict the movement response to laryngoscopy best. CONCLUSIONS: The triple interaction model estimates the potency of any combination of sevoflurane, propofol, and remifentanil expressed as either PTOL or NSRI.

Pharmacokinetic parameter sets of alfentanil revisited: optimal parameters for use in target controlled infusion and anaesthesia display systems.

BACKGROUND: In open TCI and anaesthesia display systems, the choice of pharmacokinetic (PK) parameter sets of opioids is clinically relevant. Accuracy and bias of the PK models may be affected by administration mode and the co-administered hypnotic drug. We retrospectively evaluated the performance of eight PK parameter sets for alfentanil in two data sets (infusion and bolus application). METHODS: With the dosing history from two studies in orthopaedic patients anaesthetized with propofol or inhalation anaesthetics the alfentanil plasma concentration over time was calculated with eight PK parameter sets. Median absolute performance error (MDAPE), log accuracy, median performance error (MDPE), log bias, Wobble, and Divergence were computed. Mann-Whitney rank test with Bonferroni correction was used for comparison between bolus and infusion data, repeated measures analysis of variance on ranks was used for comparison among parameter sets. RESULTS: The parameters by Scott (original and weight adjusted) and Fragen had a MDAPE ≤30% and a median log accuracy <0.15 independent of the administration mode, while MDPE was within ±20% and log bias nearly within ±0.1, respectively. The sets by Maitre and Lemmens were within these limits only in the bolus data. All other parameter sets were outside these limits. CONCLUSIONS: In healthy orthopaedic patients, the PK parameters by Scott and by Maitre were equally valid when alfentanil was given as repeated boluses. When given as infusion, the Maitre parameters were less accurate and subject to a significant bias. We cannot exclude that the difference between bolus and infusion is partially because of the different hypnotics used.

Different Learning Curves for Axillary Brachial Plexus Block: Ultrasound Guidance versus Nerve Stimulation.

Little is known about the learning of the skills needed to perform ultrasound- or nerve stimulator-guided peripheral nerve blocks. The aim of this study was to compare the learning curves of residents trained in ultrasound guidance versus residents trained in nerve stimulation for axillary brachial plexus block. Ten residents with no previous experience with using ultrasound received ultrasound training and another ten residents with no previous experience with using nerve stimulation received nerve stimulation training. The novices' learning curves were generated by retrospective data analysis out of our electronic anaesthesia database. Individual success rates were pooled, and the institutional learning curve was calculated using a bootstrapping technique in combination with a Monte Carlo simulation procedure. The skills required to perform successful ultrasound-guided axillary brachial plexus block can be learnt faster and lead to a higher final success rate compared to nerve stimulator-guided axillary brachial plexus block.

Heart rate variability does not discriminate between different levels of haemodynamic responsiveness during surgical anaesthesia.

BACKGROUND: Hypnotic depth but not haemodynamic responsiveness is measured with EEG-based monitors. In this study we compared heart rate variability (HRV) in unstimulated patients and stimulation-induced HRV at different levels of anaesthesia. METHODS: A total of 95 ASA I or II patients were randomly assigned to five groups (Group 1: BIS 45(5), remifentanil 1 ng ml(-1); Group 2: BIS 45(5), remifentanil 2 ng ml(-1); Group 3: BIS 45(5), remifentanil 4 ng ml(-1); Group 4: BIS 30(5), remifentanil 2 ng ml(-1); Group 5: BIS 60(5), remifentanil 2 ng ml(-1)). A time- and frequency-domain analysis of the RR interval (RRI) from the electrocardiogram was performed. HRV before induction, before and after a 5 s tetanic stimulus of the ulnar nerve, and before and after tracheal intubation was compared between groups, between stimuli, and between responders to intubation [systolic arterial pressure (SAP) increase >20 mm Hg, a maximal heart rate (HR) after intubation >90 min(-1) or both] and non-responders (anova). RESULTS: Induction of anaesthesia significantly lowered HR and HRV. Mean RRI before stimulation was higher in G3 than in G1, G2, and G4 (P < 0.001), whereas the other HRV parameters were similar. Intubation induced a greater HRV response than tetanic stimulation. The mean RRI after intubation was lower in G3 compared with the other groups and the sd of the RRI after tetanic stimulation was lower in G3 compared with G5. Otherwise, unstimulated HRV and stimulation-induced HRV were similar in responders and non-responders. CONCLUSION: HRV parameters discriminate between awake and general anaesthesia, are different after tracheal intubation and a 5 s ulnar nerve stimulation, but do not discriminate between different levels of haemodynamic responsiveness during surgical anaesthesia.

Stimulation induced variability of pulse plethysmography does not discriminate responsiveness to intubation.

BACKGROUND: Hypnotic depth but not haemodynamic response to painful stimulation can be measured with various EEG-based anaesthesia monitors. We evaluated the variation of pulse plethysmography amplitude induced by an electrical tetanic stimulus (PPG variation) as a potential measure for analgesia and predictor of haemodynamic responsiveness during general anaesthesia. METHODS: Ninety-five patients, ASA I or II, were randomly assigned to five groups [Group 1: bispectral index (BIS) (range) 40-50, effect site remifentanil concentration 1 ng ml(-1);Group 2: BIS 40-50, remifentanil 2 ng ml(-1); Group 3: BIS 40-50, remifentanil 4 ng ml(-1); Group 4: BIS 25-35, remifentanil 2 ng ml(-1); Group 5: BIS 55-65, remifentanil 2 ng ml(-1)]. A 60 mA tetanic stimulus was applied for 5 s on the ulnar nerve. From the digitized pulse oximeter wave recorded on a laptop computer, linear and non-linear parameters of PPG variation during the 60 s period after stimulation were computed. The haemodynamic response to subsequent orotracheal intubation was recorded. The PPG variation was compared between groups and between responders and non-responders to intubation (anova). Variables independently predicting the response were determined by logistic regression. RESULTS: The probability of a response to tracheal intubation was 0.77, 0.47, 0.05, 0.18 and 0.52 in Groups 1-5, respectively (P<0.03). The PPG variability was significantly higher in responders than in non-responders but it did not improve the prediction of the response to tracheal intubation based on BIS level and effect site remifentanil concentration. CONCLUSION: Tetanic stimulation induced PPG variation does not reflect the analgesic state in a wide clinical range of surgical anaesthesia.

Interventional neuroradiology. Recent developments and anaesthesiologic aspects.

AIM: To summarise recent developments in interventional neuroradiology (INR) and to discuss related anaesthesiologic considerations. SUMMARY: Important Procedures: embolisation of cerebral aneurysms with Guglielmi detachable coils (GDC) as well as intra-arterial thrombolysis and angioplasty for acute ischaemic stroke and chronic atherosclerotic stenosis of cerebral arteries have been recently introduced into clinical practice. Their role in the management of aneurysms and cerebral ischaemia still remains to be defined. Embolisation of strongly vascularised neoplasms, arteriovenous malformations or fistulas and percutaneous transluminal angioplasty of refractory vasospasms after subarachnoid haemorrhage are standard procedures with established indications. The balloon occlusion test of the carotid artery and the WADA test are also frequently performed interventions in INR. ANAESTHETIC CONSIDERATIONS: The role of the anaesthetist in INR consists in providing patient comfort by analgesia and sedation, adequate monitoring, maintenance of vital functions and (if required) the management of systemic heparinisation. The patient's underlying condition, the duration and the kind of intervention have to be considered to decide on the anaesthetic management. Most of the procedures can safely be performed under light sedation, which allows continuous neurological evaluation of the patient. Knowledge of the risks and hazards of the different procedures and close collaboration with the neuroradiologist form the basis for appropriate management in case of a potentially fatal ischaemic or haemorrhagic complication that may occur in 1 to 8% of interventions. For prompt control of airway, respiration and blood pressure in these emergencies experienced anaesthesia staff is required.

Different benefit of bispectal index (BIS) in desflurane and propofol anesthesia.

BACKGROUND: Bispectal index (BIS) monitoring may reduce drug usage and hasten recovery in propofol and inhalation anesthesia. The faster emergence profile of desflurane may reduce the effect of BIS monitoring on recovery from desflurane compared with propofol. This study compared hypnotic drug usage, recovery, patient satisfaction and incidence of inadequate sedation in BIS monitored and nonmonitored women anesthetized with desflurane or propofol. METHODS: One hundred and sixty patients scheduled for elective gynecological surgery were randomly assigned to desflurane or propofol anesthesia with and without BIS monitoring. Fentanyl, vecuronium and remifentanil were administered according to clinical criteria. The BIS monitor was used in all patients, but the monitor screen was covered in the controls. A BIS level between 45 and 55 was targeted in the BIS monitored patients whereas depth of anesthesia was assessed by clinical criteria in the controls. RESULTS: The mean (SD) desflurane MAC-hours administered with and without BIS were 0.70 (0.15) and 0.76 (0.12), respectively, resulting in extubation times of 6.5 (4.1) and 8.3 (6.1) min. (NS). Bispectal index monitoring was associated with improved patient satisfaction, reduced postoperative nausea and antiemetic drug requirement, and fewer episodes with sustained BIS levels > 60. The mean (SD) propofol infusion rates were 6.0 (1.4) and 6.6 (0.9) mg kg(-1)h(-1) with and without the BIS monitor (P = 0.023), resulting in mean (SD) extubation times of 6.8 (4.6) and 10.5 min (5.9), respectively (P < 0.05). CONCLUSION: Bispectal index monitoring reduced propofol usage and hastened recovery after propofol anesthesia, whereas in desflurane anesthesia it was associated with improved patient satisfaction, probably because of decreased postoperative nausea and fewer episodes of inadequate hypnosis.

Prediction of the haemodynamic response to tracheal intubation: comparison of laser-Doppler skin vasomotor reflex and pulse wave reflex.

BACKGROUND: The laser-Doppler skin vasomotor reflex (SVmR) caused by tetanic stimulation of the ulnar nerve may be a test that can predict the haemodynamic response to tracheal intubation. A decrease in pulse wave amplitude (pulse wave reflex, PWR) may be an alternative index of this response. We compared the abilities of PWR and SVmR to predict the haemodynamic response to tracheal intubation and studied how alfentanil, muscle relaxation, stimulation site and stimulation pattern affected the two reflexes. METHODS: Anaesthesia was induced and maintained with 2% sevoflurane and 50% nitrous oxide in two groups of 10 ASA status 1 patients. Tetanic stimuli were applied to the flexor muscles of the forearm and the ulnar nerve before and after administration of vecuronium. The change in skin blood flow (laser-Doppler) and pulse wave amplitude (pulse oximetry) after a 5 and 10 s stimulation was measured on the opposite hand. If skin blood flow (laser-Doppler) decreased by more than 10%, a computer-controlled infusion of alfentanil was started and the target plasma concentration was increased in steps until this response was suppressed (< 10%). The trachea was intubated and arterial pressure and heart rate responses were recorded. Plasma alfentanil concentration was measured. RESULTS: When PWR and SVmR were suppressed, the haemodynamic response to tracheal intubation was reduced in 100 and 53% of patients respectively. PWR and SVmR responses decreased with increasing plasma alfentanil concentration. The SVmR response to muscle stimulation was reduced by muscle relaxants. The pulse wave response to both muscle and neural stimulation was reduced by relaxants. The responses to 5 and 10 s stimulations were similar. CONCLUSION: An absent SVmR does not predict a blunted arterial pressure or heart rate response to tracheal intubation. The PWR may be a better predictor.

Coronary artery spasm and non-Q-wave myocardial infarction following intravenous ephedrine in two healthy women under spinal anaesthesia.

Vasovagal episodes occur frequently in young healthy patients undergoing venous cannulation and loco-regional anaesthesia. We report two cases of severe coronary vasospasm and non-Q-wave infarction in healthy young women after administration of ephedrine for vasovagal symptoms at the onset of spinal anaesthesia. In the light of unopposed vagal predominance pre-disposing patients to coronary vasospasm, even in young healthy patients, atrophine and not ephedrine should be the first line treatment for bradycardia with or without hypotension under spinal anaesthesia.

Comparison of five experimental pain tests to measure analgesic effects of alfentanil.

BACKGROUND: Several experimental pain models have been used to measure opioid effects in humans. The aim of the current study was to compare the qualities of five frequently used experimental pain tests to measure opioid effects. METHODS: The increase of electrical, heat, and pressure pain tolerance and the decrease of ice-water and ischemic pain perception was determined at baseline and at four different plasma concentrations of alfentanil (n = 7) administered as target controlled infusion or placebo (n = 7). A linear mixed-effects modeling (NONMEM) was performed to detect drug, placebo, and time effect as well as interindividual and intraindividual variation of effect. RESULTS: Only the electrical, ice-water, and pressure pain tests are sensitive to assess a concentration-response curve of alfentanil. At a plasma alfentanil concentration of 100 ng/ml, the increase in pain tolerance compared with baseline was 42.0% for electrical pain, 22.2% for pressure pain, and 21.7% for ice-water pain. The slope of the linear concentration-response curve had an interindividual coefficient of variation of 58.3% in electrical pain, 35.6% in pressure pain, and 60.0% in ice-water pain. The residual error including intraindividual variation at an alfentanil concentration of 100 ng/ml was 19.4% for electrical pain, 6.1% for pressure pain, and 13.0% for ice-water pain. Electrical pain was affected by a significant placebo effect, and pressure pain was affected by a significant time effect. CONCLUSION: Electrical, pressure, and ice-water pain, but not ischemic and heat pain, provide significant concentration-response curves in the clinically relevant range of 200 ng/ml alfentanil or lower. The power to detect a clinically relevant shift of the curve is similar in the three tests. The appropriate test(s) for pharmacodynamic studies should be chosen according to the investigated drug(s) and the study design.

Comparison of the analgesic potency of xenon and nitrous oxide in humans evaluated by experimental pain.

We have compared the analgesic potency of MAC-equivalent concentrations of xenon (10, 20, 30 and 40%) and nitrous oxide (15, 30, 45 and 60%) in humans using a multimodal experimental pain testing and assessment technique. We tested 12 healthy volunteers in a randomized, single-blind, crossover study. The following experimental pain tests were used: nociceptive reflex to repeated stimuli; pain tolerance to maximal effort tourniquet ischaemia; electrical stimulation; mechanical pressure; and cold. Reaction time was also measured. Xenon and nitrous oxide produced analgesia to ischaemic, electrical and mechanical stimulation, but not to cold pain. There was no difference in MAC-equivalent concentrations of xenon and nitrous oxide. Both increased reaction time in a similar manner. Xenon and nitrous oxide evoked nausea and vomiting in a large number of volunteers.

Adding sodium bicarbonate to lidocaine enhances the depth of epidural blockade.

UNLABELLED: It is controversial whether adding CO2 or sodium bicarbonate to local anesthetics enhances the depth of epidural blockade. Repeated electrical stimulation is a reliable test for assessing epidural analgesia and evokes temporal summation. We used this test to investigate the analgesic effect of lidocaine, with or without CO2 or bicarbonate. Twenty-four patients undergoing epidural blockade with 20 mL lidocaine 2% at L2-3 were randomly divided into three groups: lidocaine hydrochloride, lidocaine CO2, and lidocaine plus 2 mL sodium bicarbonate 8.4%. Pain threshold after repeated electrical stimulation (five impulses at 2 Hz), pinprick, and cold test were performed at S1 and L4. Motor block was assessed. The addition of bicarbonate resulted in higher pain thresholds (P < 0.0001), faster onset of action (P = 0.009), and higher degree of motor block (P = 0.004) compared with lidocaine hydrochloride. We found no significant differences between lidocaine CO2 and hydrochloride. Most of these results were not confirmed by pinprick and cold tests. We conclude that the addition of sodium bicarbonate to lidocaine enhances the depth of epidural blockade, increases inhibition of temporal summation, and hastens the onset of block. Pinprick and cold are inadequate tests for comparing drugs for epidural anesthesia. IMPLICATIONS: We measured pain perception during epidural anesthesia by delivering electrical stimuli to the knee and foot. We found that the addition of sodium bicarbonate to the local anesthetic lidocaine enhances analgesia. We observed no effect of adding carbon dioxide to lidocaine.