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The acute and subchronic effects of low doses nocturnally administered amitriptyline were compared to placebo in a double-blind crossover randomized study on driving ability and driving-related skills involving seven chronic neuropathic pain patients. Performance testing occurred at the first and last day of each 15-day drug administration period, which was preceded by a 6-day washout phase. A standardized method of measuring driving ability, the on-the-road driving test, was performed on all visits. Patients were instructed to drive with a steady lateral position while maintaining a constant speed of 95 km/h. The primary outcome of the driving test is the Standard Deviation of Lateral Position (SDLP, cm), which is an index of weaving of the car. At the first treatment day, driving performance was significantly impaired in patients after nocturnal administration of 25 mg amitriptyline compared to placebo. The increase in SDLP of 3 cm was higher than the increment generally observed with a blood alcohol concentration of 0.5 mg/ml or higher, the legal limit for driving in many countries. Also, reaction times on a memory test were significantly increased, indicating worse performance after acute treatment of amitriptyline compared to placebo. In contrast, after 2 weeks of treatment, no significant differences were found between amitriptyline and placebo, suggesting that tolerance had developed to the impairing effects of amitriptyline.

Sudden movements from over-sedation during ophthalmic surgery can be detrimental to the eye. Bispectral index (BIS) and middle-latency auditory-evoked potentials (Alaris AEP index, AAI) were reported to be accurate indicators for the level of sedation and loss of consciousness. We assessed these monitors during sedation with special emphasis on preventing over-sedation. One-hundred patients scheduled for elective eye surgery were sedated with target-controlled propofol infusion and randomly allocated to BIS-guided, AAI-guided, BIS/AAI-guided, or clinically guided groups (n = 25 each). The initial target concentration was 0.5 microg x mL(-1) in patients >70 yr and 1.0 microg x mL(-1) in all other patients. The concentration was increased every 3 min by 0.1 or 0.2 microg x mL(-1), respectively until the patient had reached a BIS value of 75 (range 70-90) or an AAI of 40 (range 35-60). The surgeon who was blinded to group allocation assessed treatment quality after the procedure. Sedation was converted into general anesthesia in four patients because of excessive head movements. BIS was out of range 7% of the time vs 58% for AAI. No significant differences in treatment quality were observed among the four groups. We conclude that propofol sedation, guided by BIS or AAI monitoring, did not enhance ophthalmic surgical operating conditions over sedation guided by clinical observation only.

Background: Intrathecal clonidine prolongs spinal anaesthesia. We investigated the effect of the addition of clonidine (75 microg) to hyperbaric bupivacaine on postoperative morphine consumption after Caesarean section in a randomized controlled double-blind trial., Methods: A group of 106 women received spinal anaesthesia using either bupivacaine 0.5% (2.2 ml) heavy with 0.5 ml normal saline 0.9% (B) or bupivacaine 0.5% (2.2 ml) heavy with clonidine (75 microg) in 0.5 ml normal saline 0.9% (BC). The primary outcome was the total morphine consumption in the first 24 h after surgery. Secondary outcomes were the duration of postoperative analgesia, postoperative pain scores, the need for alfentanil during surgery, block regression, clonidine side-effects and morphine side-effects., Results: Total morphine consumption was similar in both study groups. The mean time to the first analgesic request in the BC group was 129 (SD 13.8) min, compared with 55 (14.2) min in the B group [mean difference (95% CI) -75 (-106 to -44) min]. In the BC group 22 (42%) patients had a complete motor block 1 h after surgery compared with 4 (8%) patients in the B group [RR (95% CI) 0.18 (0.07-0.49)]. Side-effects of intrathecal clonidine were not detected., Conclusions: The addition of clonidine (75 microg) to hyperbaric bupivacaine prolongs spinal anaesthesia after Caesarean section and improves early analgesia, but does not reduce the postoperative morphine consumption during the first 24 h. No clinically relevant maternal or neonatal side-effects were detected.

Neurologic and neurocognitive complications after cardiac surgery with cardiopulmonary bypass (CPB) have been reported repeatedly. To better understand its etiology and design protective strategies, an appropriate animal model may prove useful. Although impaired short-term neurocognitive function has been recently demonstrated after CPB in rats, the demonstration of persistent long-term neurocognitive changes would be more relevant from a clinical perspective. We hypothesized that CPB results in long-term impairment of neurocognitive performance in rats. Male rats were exposed to either 60 min of normothermic non-pulsatile CPB, using a roller-pump and a neonatal membrane oxygenator, or to cannulation only (sham animals). Long-term neurocognitive function was assessed at 4 to 7 weeks after CPB (Can test), and again after 12 weeks (Morris water maze) in both operated groups and in a non-operated control group, followed by histologic evaluation of the hippocampus. In separate groups of CPB and sham animals, we also measured TNF-alpha and IL-6 in plasma. There were no significant differences in long-term neurocognitive performance or histological outcome between the three groups. Cytokine patterns were also similar in both operated groups. We conclude that CPB did not appear to cause long-term neurocognitive dysfunction in this model of CPB in young healthy rats. The lack of long-term deficits may be due to the absence of clinically important etiologic factors such as atheromatous and gaseous embolization in this model. Similar cytokine patterns in both operated groups suggest that surgical trauma rather than exposure of blood to extra-corporeal circuit was probably responsible for the inflammatory response.

In the Octopus Study, 281 coronary artery bypass surgery patients were randomized to surgery with or without cardiopulmonary bypass. The primary objective was to compare cognitive outcome between off-pump and on-pump coronary artery bypass surgery. Before and after surgery, psychologists administered a battery of 10 neuropsychological tests to the patients. Cognitive decline was defined as a decrease in an individual's performance of at least 20% from baseline, in at least 20% of the main variables. According to this definition, cognitive decline was present in 21% in the off-pump group and 29% in the on-pump group, 3 months after the procedure (P = .15). At 12 months, cognitive decline was present in 31% in the off-pump group and 34% in the on-pump group (P = .69). These results indicated that patients undergoing coronary artery bypass surgery without cardiopulmonary bypass had improved cognitive outcomes 3 months after the procedure, but the effects were limited and became negligible at 12 months. The same definition of cognitive decline was also applied to 112 volunteers not undergoing surgery. The definition labeled 28% of the control subjects as suffering from cognitive decline, 3 months after their first assessment. This suggests that the natural fluctuations in performance during repeated neuropsychological testing should be included in the statistical analysis of cognitive decline. Using an alternative definition of cognitive decline that takes these natural fluctuations in performance into account, the proportions of coronary artery bypass surgery patients displaying cognitive decline were substantially lower. This indicates that the incidence of cognitive decline after coronary artery bypass surgery has been overestimated.

Most pain patients are treated in an outpatient setting and are engaged in daily activities including driving. Since several studies showed that cognitive functioning may be impaired in chronic nonmalignant pain, the question arises whether or not chronic nonmalignant pain affects driving performance. Therefore, the objective of the present study was to determine the effects of chronic nonmalignant pain on actual highway driving performance during normal traffic. Fourteen patients with chronic nonmalignant pain and 14 healthy controls, matched on age, educational level, and driving experience, participated in the study. Participants performed a standardized on-the-road driving test during normal traffic, on a primary highway. The primary parameter of the driving test is the Standard Deviation of Lateral Position (SDLP). In addition, driving-related skills (tracking, divided attention, and memory) were examined in the laboratory. Subjective assessments, such as pain intensity, and subjective driving quality, were rated on visual analogue scales. The results demonstrated that a subset of chronic nonmalignant pain patients had SDLPs that were higher than the matched healthy controls, indicating worse highway driving performance. Overall, there was a statistically significant difference in highway driving performance between the groups. Further, chronic nonmalignant pain patients rated their subjective driving quality to be normal, although their ratings were significantly lower than those of the healthy controls. No significant effects were found on the laboratory tests.

Chronic pain may impair performance on attentional processing capacity tasks. In the present study, event-related potentials were recorded to examine whether pain patients show performance decrements on attentional processing capacity tasks due to shared resources by pain and attention or, alternatively, due to deficits in allocating attentional resources during pain. Fourteen chronic pain patients and thirty age and education matched healthy controls were investigated. An attentional capacity probe task was used in which the difficulty level was manipulated, resulting in an easy and a difficult condition, while task-irrelevant visual probes were presented. These probe-elicited P3 amplitudes were assumed to provide the most pure estimate of processing capacity since they are relatively free from target-related processes. Event-related potentials were recorded from the midline electrodes Fz, Cz, Pz, and Oz. For the behavioral measures, it was found that pain patients maintained a different speed-accuracy tradeoff. Pain patients showed faster reaction time responses and higher error rates compared to controls. No significant differences were found between pain patients and controls on the primary task. Pain patients differed from controls with respect to amplitudes elicited by task-irrelevant probe stimuli. For healthy controls, the expected decreased amplitude was found for probe stimuli in the difficult compared to the easy task. In contrast, the pain patients did not show decreased probe amplitudes with increasing task load. The data may imply that allocation of attentional resources is deficient in pain patients, instead of attentional capacity.

We prospectively estimated the prevalence of heart murmurs in 2522 consecutive adult non-cardiac surgery patients during pre-operative evaluation. Factors that contribute to the detection of a heart murmur were identified, and echocardiography was used to evaluate to what extent a murmur reflected presence of valvular heart disease. A cardiac murmur was detected in 106 patients (prevalence 4.2%, 95% CI: 3.5-5.1%). Multivariable logistic regression analyses showed that age and general physical impression were independently associated with detecting a murmur (p-values < 0.01). In 83 (79%) of the patients with a murmur, an echocardiographic diagnosis was available: 39% had aortic valve abnormalities, 24% had mitral valve regurgitation, 7% had other valvular heart disease and 30% did not have any abnormality. Thus, 58 of the 83 patients had valvular heart disease (positive predictive value using routine cardiac auscultation for diagnosing VHD: 70%, 95% CI: 59-79%). Murmurs in patients younger than 40 years never reflected valvular heart disease. Pre-operative cardiac auscultation seems only reasonable in patients aged 40 years or older. Subsequent echocardiography in these selected patients is necessary.

Background: The occurrence of metabolic acidosis, rhabdomyolysis, hyperkalemia, and sudden cardiac death after long-term, high-dose propofol infusion has been referred to as propofol infusion syndrome (PRIS)., Objectives: The purpose of this study was to explore the ECG abnormalities observed in a patient with PRIS in order to identify possible pathophysiologic mechanisms of the syndrome., Methods: ECG changes in the index case were characterized by down-sloping ST-segment elevation in precordial leads V1 to V3 (Brugada-like ECG pattern). We subsequently assessed the relationship between this ECG pattern and the propofol infusion rate, the development of arrhythmias, and the occurrence of sudden death in a previously described cohort of 67 head-injured patients, seven of whom had been identified as having PRIS., Results: Six of the PRIS patients developed the ECG pattern of ST-segment elevation in leads V1 to V3 and died within hours of irrecoverable electrical storm. This ECG pattern was the first aberration recorded hours before the death of these patients. ECGs that were available for 30 of 60 unaffected patients exhibited a normal pattern. None of the 60 patients developed ventricular arrhythmias., Conclusion: Our findings indicate that development of an acquired Brugada-like ECG pattern in severely head-injured patients is a sign of cardiac electrical instability that predicts imminent cardiac death. Future studies will determine whether such an ECG pattern also predicts imminent cardiac arrhythmia in other patient populations.

Rationale: Little is known about the effects of low doses of amitriptyline, prescribed in the treatment of neuropathic pain, on attentional processing capacity., Objectives: Changes due to amitriptyline treatment on attentional processing capacity were investigated on behavioral measures and event-related brain potentials (ERPs) in six patients with neuropathic pain., Materials and Methods: Patients were treated for 15 consecutive days with 25 mg nocturnally administered amitriptyline or placebo in a double-blind crossover randomized design. Measurements were carried out on day 1 and day 15 of each treatment period. An attentional capacity probe task was used in which the difficulty level was manipulated, resulting in an easy and a hard condition, while task-irrelevant visual probes were presented. During task performance, ERPs were measured from the midline electrodes Fz, Cz, Pz, and Oz., Results: Amitriptyline increased reaction times (RTs) after acute but not after subchronic administration. ERP analyses showed that P3 amplitudes to the task stimuli were not affected by amitriptyline in either treatment phase. Moreover, P3 amplitudes to the probes were increased in the easy compared to the hard task condition after subchronic amitriptyline treatment, indicating beneficial effects of repeated amitriptyline administration. In contrast, acute amitriptyline administration did reduce an earlier visual evoked potential, N1, preceding the P3 component., Conclusions: The results suggest that amitriptyline, even at low dosages of 25 mg, affects performance after acute administration in chronic neuropathic pain patients. After 2 weeks of treatment, performance appears to be unaffected. No deficits in processing capacity due to amitriptyline treatment were found.

Background: The main complications of herpes zoster (HZ) are postherpetic neuralgia and, in case of HZ ophthalmicus, eye disorders. Antiviral treatment may modify the course of disease and reduce the risk of complications., Objective: To assess which doctors' and patients' characteristics were related to prescription of antiviral therapy for HZ., Methods: Ninety general practices (358 008 patients) in The Netherlands registered all patient contacts in a database for one year as part of the Second Dutch National Survey of General Practice. The present study used ICPC code S70 to search that database for patients with a new diagnosis of HZ. The full-text medical records of the selected patients were then reviewed and the potential determinants for the prescription of antiviral drugs (including characteristics of patients, GPs, and practices) analysed using multilevel logistic regression modelling., Results: Of the 1129 patients diagnosed with HZ (incidence 3.2/1000 patients/year), 22.5% received antiviral drugs. Independent determinants for prescription of antiviral therapy were age [45-54 years: adjusted odds ratio (OR) 2.9 (95% CI 1.6-5.0); 55-64 years: OR 4.2 (95% CI 2.4-7.6); 65-74 years: OR 5.1 (95% CI 2.7-9.6); > or =75 years: OR 8.1 (95% CI 4.4-15.1)], ophthalmic localisation of the shingles (OR 3.2, 95% CI 1.6-6.7), and the presence of asthma/COPD (OR 1.6, 95% CI 1.0-2.6). GPs who reported to strongly adhere to professional guidelines prescribe more frequently antiviral drugs (OR 1.9, 95% CI 1.2-3.1)., Conclusions: A minority of HZ patients were prescribed antiviral treatment. Increasing age, ophthalmic localisation, presence of asthma/COPD, and adherence to professional guidelines were factors favouring prescription. More information on the determinants of GPs' treatment decisions is necessary for successful implementation of HZ guidelines.

Background: After coronary artery bypass grafting (CABG), 20-30% of patients are reported to suffer from cognitive decline. Studies reporting these high incidences, however, have not included an appropriate control group., Methods: We repeatedly administered a series of neuropsychological tests to 112 healthy middle-aged volunteers not undergoing surgery, and applied two widely used definitions of cognitive decline to their test results. In addition, we re-analysed the neuropsychological test data of 281 CABG patients with a definition of cognitive decline that takes into account the natural variability of test performance that was found in the volunteers., Results: Three months after their first assessment, 14-28% of the volunteers suffered from cognitive decline according to the definitions of cognitive decline after CABG. Using the controlled definition of cognitive decline that takes the natural variability in test performance into account, we found that only 7.7% of the CABG patients suffered from cognitive decline at 3 months after their operation., Conclusion: These data suggest that the incidence of cognitive dysfunction after CABG has previously been greatly overestimated.

Background: The recurrent failure of apparently promising neuroprotective drugs to improve outcome in trials of patients with acute ischaemic stroke may partially be explained by over-optimistic conclusions about efficacy as a result of methodological shortcomings in preclinical studies. We assessed the methodological quality of animal studies of five different neuroprotective agents that have been tested in 21 clinical trials including a total of more than 12,000 patients with acute ischaemic stroke., Methods: We performed a literature search restricted to full publications on the effects of clomethiazole, gavestinel, lubeluzole, selfotel, or tirilazad mesylate on infarct volume or functional outcome in animal models of acute focal cerebral ischaemia. We used a rating scale to assess the methodological quality of the included studies. One point was attributed to each of 10 items. A score of 4 to 6 points was considered "medium" and a score above 7 "high.", Results: A total of 45 articles were included. The median score on the methodological quality index was 3; 18 studies had a medium score and one a high score. Randomised treatment allocation was mentioned in 19 studies (42 %), blinded administration of study medication in 10 (22 %), and blinded outcome assessment in 18 (40 %). The study drug was administered at a median of 10 min (range, -60 to 360 min) after the onset of ischaemia., Conclusion: The evidence for neuroprotective efficacy that formed the basis for initiating the 21 trials was obtained in animal studies with a methodological quality that would, in retrospect, not justify such a decision. More rigorous preclinical study methodology may lead to more reliable and reproducible results.

Background: Conventional coronary artery bypass surgery has been associated with cerebral injury attributed to cardiopulmonary bypass (CPB) and surgical manipulation of the ascending aorta. Off-pump coronary artery surgery avoids these factors and could prevent cerebral injury. However, moving the heart from its natural position affects the circulation and could compromise cerebral oxygenation and perfusion. We set out to compare episodes of poor global cerebral oxygenation, defined as a jugular bulb saturation less than 50%, between patients randomized to off-pump or (conventional) on-pump coronary artery surgery., Methods: One hundred and eighty-seven patients were assigned randomly to off-pump or on-pump coronary artery surgery. Oxygen saturation in the jugular bulb (SjO2) was measured during revascularization of the three main coronary vessels in the off-pump group, and at the start of CPB, before rewarming, and after rewarming in the on-pump group. We compared samples with jugular bulb with desaturation (SjO2) < or = 50%) between treatment groups., Results: One hundred and seventy-five patients (81 in the off-pump group [93%] and 94 in the on-pump group [94%]) had complete jugular oxygen saturation data. Thirty-nine patients in the off-pump group (48%) and 25 patients in the on-pump group (27%) had one or more samples with desaturation during revascularization or CPB (odds ratio after adjustment for other factors, 0.39; 95% confidence interval, 0.21-0.73, P<0.01)., Conclusion: Jugular bulb desaturation occurs more frequently during off-pump coronary artery surgery than during conventional coronary artery surgery.

Preoperative anxiety has been suggested as a predictor of postoperative nausea and vomiting (PONV), but supporting data are lacking. We quantified the added predictive value of preoperative anxiety to established predictors of PONV in 1389 surgical inpatients undergoing various procedures, by using multivariate logistic regression analysis. Investigated predictors were a history of PONV or motion sickness, smoking, sex, age, ethnicity, body mass index, ASA physical status, surgery type, duration of anesthesia, anesthetic technique, and postoperative opioid analgesia. Anxiety was measured by the Spielberger State-Trait Anxiety Inventory and the Amsterdam Preoperative Anxiety and Information Scale. The outcome was the occurrence of PONV in the first 24 h after surgery. The area under the receiver operating characteristic curve of a multivariate (logistic regression) model including sex, age, smoking, history of PONV or motion sickness, surgery type, and anesthetic technique was 0.72 (95% confidence interval, 0.70-0.74). There was a weak but significant association of anxiety with PONV, but the addition of anxiety to the model did not further increase the area under the receiver operating characteristic curve. Therefore, routine preoperative measurement of anxiety does not seem warranted, provided that the other predictors are already considered.

Background: Activation of the complement system after coronary artery bypass graft surgery involves C-reactive protein (CRP). This inflammatory response is related to baseline CRP levels and associated with postoperative arrhythmia, in particular atrial fibrillation (AF). We investigated whether baseline CRP levels are a risk indicator for the occurrence of AF and whether this phenomenon is cardiopulmonary bypass dependent., Methods: C-reactive protein was measured in perioperative blood samples of patients of the Octopus Study (coronary artery bypass graft surgery with [n = 73] or without cardiopulmonary bypass [n = 79]). Baseline CRP was dichotomized into a low and a high baseline group, using a cutoff value of 3.0 mg/L., Results: After coronary artery bypass graft surgery with cardiopulmonary bypass 11 of 53 patients (21%) with low preoperative CRP levels had AF versus 11 of 20 patients (55%) with high baseline CRP levels (p = 0.01). In the off-pump group AF occurred in 4 of 52 patients (8%) who had low baseline CRP levels, versus 8 of 27 patients (30%) with high preoperative CRP levels (p = 0.002). After adjusting for age, the odds ratio (95% confidence interval) was 4.6 (1.4 to 15.3) with cardiopulmonary bypass, 3.7 (0.93 to 14.7) in the off-pump group, and 3.3 (1.4 to 7.6) for both groups together. Continuous baseline CRP was an independent predictor for AF in a multivariate logistic regression model (p = 0.02)., Conclusions: Patients with high baseline CRP levels are at higher risk of having postoperative AF in both on-pump and off-pump surgery.

We have validated two scoring systems for predicting postoperative nausea and vomiting, derived by Apfel et al. and Koivuranta et al. from 1388 adult inpatients undergoing a wide range of surgical procedures. The predictive accuracy of the scoring systems was evaluated in terms of the ability to discriminate between patients with and without postoperative nausea and vomiting (discrimination) and agreement between observed and predicted outcomes (calibration). Discrimination and calibration were less than expected based on previous reports, with both scoring systems providing risk predictions that were too extreme. The area under the ROC curve was 0.63 for Apfel et al.'s scoring system and 0.66 for Koivuranta et al.'s scoring system. Neither of the scoring systems provided a risk threshold for administering anti-emetic prophylaxis that yielded satisfying results in terms of predictive values, sensitivity and specificity. Hence, in their original forms, the scoring systems do not guarantee accurate prediction of the risk of postoperative nausea and vomiting in other patient populations. Koivuranta et al.'s scoring system appears to be more robust across different populations.

Background: Perioperative assessment of spinal cord oxygenation might guide measures to prevent neurologic deficits secondary to ischemic or traumatic damage of the spinal cord. Although cerebrospinal fluid (CSF) partial pressure of oxygen (Po2) measurement has been used to detect spinal cord ischemia (SCI), the diagnostic value and the temporal resolution of CSF Po2 measurement compared with functional assessment of the spinal cord is unknown. This study compared CSF Po2 with transcranial motor evoked potentials (tcMEPs) for detection of experimental SCI., Methods: The aorta and segmental arteries were exposed in 10 sufentanil-ketamine-anesthetized pigs (weight, 40-50 kg). Myogenic tcMEPs were recorded from the upper and lower limbs, and continuous assessment of CSF Po2 was provided by two Clark-type microcatheters inserted in the lumbar and thoracic intrathecal space. Graded lumbar SCI was produced by sequential clamping of segmental arteries. The relation between CSF Po2 and tcMEP during graded SCI was determined using linear regression. Diagnostic characteristics of CSF Po2 values for clinical SCI were determined using different cutoff points of CSF Po2., Results: Lumbar CSF Po2 (baseline, 44 [interquartile range, 38-54] mmHg) decreased below 50% in all animals and was linearly related to loss of tcMEP amplitude in all animals. The median lumbar CSF Po2 during reduction of tcMEP to less than 25% of baseline was 11 (4-29) mmHg, whereas thoracic CSF Po2 remained constant (40 [28-50] mmHg). During absence of the tcMEP signal, lumbar CSF Po2 was less than 20 mmHg in 80% of the animals. Optimal sensitivity and predictive values of CSF Po2 measurement for SCI were in the range of 40-60% of baseline., Conclusions: The data indicate that intrathecal Po2 measurement is a sensitive monitoring technique to track real-time changes in local spinal cord oxygenation. Continuous monitoring of CSF Po2 might be applied for evaluation of patients who are at risk for direct or secondary SCI.

The management of cerebral perfusion pressure (CPP) remains a controversial issue in the critical care of severely head-injured patients. Recently, it has been proposed that the state of cerebrovascular autoregulation should determine individual CPP targets. To find optimal perfusion pressure, we pharmacologically manipulated CPP in a range of 51 mm Hg (median; 25th-75th percentile, 48-53 mm Hg) to 108 mm Hg (102-112 mm Hg) on Days 0, 1, and 2 after severe head injury in 13 patients and studied the effects on intracranial pressure (ICP), autoregulation capacity, and brain tissue partial pressure of oxygen. Autoregulation was expressed as a static rate of regulation for 5-mm Hg CPP intervals based on middle cerebral artery flow velocity. When ICP was normal (26 occasions), there were no major changes in the measured variables when CPP was altered from a baseline level of 78 mm Hg (74-83 mm Hg), indicating that the brain was within autoregulation limits. Conversely, when intracranial hypertension was present (11 occasions), CPP reduction to less than 77 mm Hg (73-82 mm Hg) further increased ICP, decreased the static rate of regulation, and decreased brain tissue partial pressure of oxygen, whereas a CPP increase improved these variables, indicating that the brain was operating at the lower limit of autoregulation. We conclude that daily trial manipulation of arterial blood pressure over a wide range can provide information that may be used to optimize CPP management.

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.

Activation of coagulation, fibrinolysis, and the vascular endothelium occurs after heart surgery with cardiopulmonary bypass (CPB), but the effects of eliminating CPB in patients undergoing coronary artery bypass grafting (CABG) are unknown. Therefore, we compared the hemostatic profiles of off-pump and on-pump CABG patients. Two groups of consecutive patients participating in a larger trial (the Octopus Trial) were randomly allocated to undergo CABG with (n = 20) or without (n = 20) CPB. Platelet numbers and plasma concentrations of P-selectin, prothrombin fragment 1.2 (F1.2), soluble fibrin, d-dimers, and von Willebrand factor (as a marker of endothelial cell activation) were measured and corrected for hemodilution. Compared with the on-pump CABG group, F1.2 and d-dimer levels were significantly lower (P = 0.004 and P = 0.03, respectively) in patients having CABG surgery performed off-pump. In the CPB group, F1.2 (median [interquartile range], 450% of baseline [233%-847%]) and d-dimer (538% [318%-1192%]) peaked in the immediate postoperative period and remained increased until Day 4, whereas in the off-pump group, F1.2 and d-dimer levels increased more gradually and peaked on Day 4 (342% [248%-515%] and 555% [387%-882%], respectively). In both groups, von Willebrand factor concentrations were increased until Day 4 (CPB, 308% [228%-405%]; off-pump, 288% [167%-334%]). Despite heparinization, CABG surgery with CPB was associated with excessive thrombin generation and fibrinolytic activity immediately after surgery. The off-pump group demonstrated a delayed postoperative response that became equal in magnitude to the CPB in the later (20-96 h) postoperative period.

Background: Intrathecal administration of opioids may cause lower urinary tract dysfunction. In this study, the authors compared the effects of morphine and sufentanil administered intrathecally in a randomized double-blind fashion (two doses each) on lower urinary tract function in healthy male volunteers., Methods: Urodynamic evaluation was performed before and every hour after drug administration up to complete recovery of lower urinary tract function using pressure and flow measurements recorded from catheters in the bladder and rectum. Sense of urge and urinary flow rates were assessed every hour by filling the bladder with its cystometric capacity and asking the patient to void. Full recovery was defined as a residual volume of less than 10% of bladder capacity and a maximum flow rate within 10% of the initial value., Results: Intrathecal administration of both opioids caused dose-dependent suppression of detrusor contractility and decreased sensation of urge. Mean times to recovery of normal lower urinary tract function were 5 and 8 h after 10 or 30 microg sufentanil and 14 and 20 h after 0.1 or 0.3 mg morphine, respectively. This recovery profile can be explained by the spinal pharmacokinetics of both opioids., Conclusions: Intrathecal opioids decrease bladder function by causing dose-dependent suppression of detrusor contractility and decreased sensation of urge. Recovery of normal lower urinary tract function is significantly faster after intrathecal sufentanil than after morphine, and the recovery time is clearly dose dependent.

Objective: To describe the association between cognitive outcome in the first postoperative week and that at three months after both off-pump and on-pump coronary bypass surgery, and to make a direct comparison of early cognitive outcome after off-pump versus on-pump surgery., Design: Randomised trial with an additional prediction study within the two randomised groups., Setting: Three centres for heart surgery in the Netherlands., Patients: 281 patients, mean age 61 years., Interventions: Participants were randomly assigned to off-pump or on-pump coronary bypass surgery., Main Outcome Measures: Cognitive outcome, assessed by psychologists who administered neuropsychological tests one day before and four days and three months after surgery. A logistic regression model was used to study the predictive association between early cognitive outcome, together with eight clinical variables, and cognitive outcome after three months., Results: Cognitive outcome in the first week after surgery was determined for 219 patients and was a predictor of cognitive decline after three months. This association was stronger in on-pump patients (odds ratio (OR) 5.24, p < 0.01) than in off-pump patients (OR 1.80, p = 0.23). Early decline was present in 54 patients (49%) after off-pump surgery and 61 patients (57%) after on-pump surgery (OR 0.73, p = 0.25)., Conclusions: In patients undergoing first time coronary bypass surgery, early cognitive decline predicts cognitive outcome after three months. Early cognitive decline is not significantly influenced by the use of cardiopulmonary bypass.

BACKGROUND: Postherpetic neuralgia (PHN) is by far the most common complication of herpes zoster (HZ) and one of the most intractable pain disorders. Since PHN is seen most often in the elderly, the number of patients with this disorder is expected to increase in our ageing society. PHN may last for months to years and has a high impact on the quality of life. The results of PHN treatment are rather disappointing. Epidural injection of local anaesthetics and steroids in the acute phase of HZ is a promising therapy for the prevention of PHN. Since randomised trials on the effectiveness of this intervention are lacking, the PINE (Prevention by epidural Injection of postherpetic Neuralgia in the Elderly) study was set up. The PINE study compares the effectiveness and cost-effectiveness of a single epidural injection of local anaesthetics and steroids during the acute phase of HZ with that of care-as-usual (i.e. antivirals and analgesics) in preventing PHN in elderly patients. METHODS / DESIGN: The PINE study is an open, multicenter clinical trial in which 550 elderly (age >/= 50 yr.) patients who consult their general practitioner in the acute phase of HZ (rash < 7 days) are randomised to one of the treatment groups. The primary clinical endpoint is the presence of HZ-related pain one month after the onset of the rash. Secondary endpoints include duration and severity of pain, re-interventions aiming to treat the existing pain, side effects, quality of life, and cost-effectiveness. CONCLUSION: The PINE study is aimed to quantify the (cost-) effectiveness of a single epidural injection during the acute phase of HZ on the prevention of PHN.

Background: Previous studies suggest that auditory evoked potentials (AEP) may be used to monitor anaesthetic depth. However, during surgery and anaesthesia, the quality of AEP recordings may be reduced by artefacts. This can affect the interpretation of the data and complicate the use of the method. We assessed differences in expert ratings of the signal quality of perioperatively recorded AEPs., Methods: Signal quality of 180 randomly selected AEP, recorded perioperatively during a European multicentre study, was rated independently by five experts as 'invalid' (0), 'poor' (1), or 'good' (2). Average (n=5) quality rating was calculated for each signal. Differences between quality ratings of the five experts were calculated for each AEP: inter-rater variability (IRV) was calculated as the difference between the worst and best classification of a signal., Results: Average signal quality of 57% of the AEPs was rated as 'invalid', 39% as 'poor', and only 4% as 'good'. IRV was 0 in only 6%, 1 in 62%, and 2 in 32% of the AEP, that is in 32% one expert said signal quality was good, whereas a different expert thought the identical signal was invalid., Conclusions: There is poor agreement between experts regarding the signal quality of perioperatively recorded AEPs and, as a consequence, results obtained by one expert may not easily be reproduced by a different expert. This limits the use of visual AEP analysis to indicate anaesthetic depth and may affect the comparability of AEP studies, where waveforms were analysed by different experts. An objective automated method for AEP analysis could solve this problem.

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.

Background: The authors recently demonstrated that administration of the melanocortin-4 receptor antagonist SHU9119 decreased neuropathic pain symptoms in rats with a sciatic chronic constriction injury. The authors hypothesised that there is a balance between tonic pronociceptive effects of the spinal melanocortin system and tonic antinociceptive effects of the spinal opioid system. Therefore, they investigated a possible interaction between these two systems and tested whether opioid effectiveness could be increased through modulation of the spinal melanocortin system activity., Methods: In chronic constriction injury rats, melanocortin and opioid receptor ligands were administered through a lumbar spinal catheter, and their effects on mechanical allodynia were assessed by von Frey probing., Results: Naloxone (10-100 microg) dose-dependently increased allodynia (percent of maximum possible effect of -67 +/- 9%), which is in agreement with a tonic antinociceptive effect of the opioid system. SHU9119 decreased allodynia (percent of maximum possible effect of 60 +/- 13%), and this effect could be blocked by a low dose of naloxone (0.1 microg), which by itself had no effect on withdrawal thresholds. Morphine (1-10 microg) dose-dependently decreased allodynia (percent of maximum possible effect of 73 +/- 14% with the highest dose tested). When 0.5 microg SHU9119 (percent of maximum possible effect of 47 +/- 14%) was given 15 min before morphine, there was an additive antiallodynic effect of both compounds., Conclusions: Together, these data confirm that there is an interaction between the spinal melanocortin and opioid systems and that combined treatment with melanocortin-4 receptor antagonists and opioids might possibly contribute to the treatment of neuropathic pain.

Background: Coronary artery bypass grafting (CABG) is associated with significant cerebral morbidity. This is usually manifested as cognitive decline and may be caused by cardiopulmonary bypass. The primary objective of this study was to explore whether patients report more cognitive failures 1 year after CABG than preoperatively. Secondary objectives were to evaluate whether there is a difference in reported cognitive failures between patients undergoing on-pump and off-pump CABG and whether a difference between CABG patients and healthy control subjects exists. Finally the relation between objective and subjective cognitive functioning was quantified., Methods: In this prospective study, the Cognitive Failures Questionnaire (CFQ) was assigned preoperatively and 1 year postoperatively to 81 patients who were randomly assigned to undergo off-pump (n = 45) or on-pump (n = 36) CABG. A control sample of 112 age-matched healthy subjects was included who were administered the CFQ once., Results: No difference was found in the total CFQ score (p = 0.222) and CFQ worry score (p = 0.207) between 1 year after CABG and before CABG. There was no difference between on-pump and off-pump CABG (total score, p = 0.458; worry score, p = 0.563). A significant difference was found in CFQ total score between CABG patients and control subjects (p < 0.001), with control subjects reporting more cognitive failures than CABG patients. Finally, patients who showed cognitive decline in the Octopus trial did not have a higher CFQ total score (p = 0.671) and CFQ worry score (p = 0.772) than patients without cognitive decline 1 year after CABG., Conclusions: The present findings suggest that CABG does not result in a substantial proportion of patients with subjectively experienced cognitive decline 1 year after the procedure, irrespective of the type of surgical technique (on-pump versus off-pump).

Zero-balanced ultrafiltration (ZBUF) might reduce the systemic inflammatory response (SIRS) during cardiopulmonary bypass (CPB) by removing inflammatory mediators. The objective of this study was to determine the effect of ZBUF on postoperative serum S100b levels, a marker of neuronal injury. In addition, the possible effects of ZBUF on postoperative neurocognitive function were assessed. Sixty patients undergoing elective coronary bypass grafting were randomly assigned either to a control group or to a protocol group in which ZBUF was performed. Serum S100b levels were measured five minutes after intubation, at the end of bypass and eight and 20 hours after arrival at the intensive care unit (ICU). Cognitive function was assessed with neuropsychological tests on the day before the operation and the sixth day after surgery. The S100b level at 20 hours after arrival at the ICU was 0.27 g/L (SD 0.16) in the control and 0.25 g/L (SD 0.12) in the group with ZBUF. There were no statistical differences at any time between the two groups. S100b was not detectable in the ultrafiltrate, indicating that these results were not obscured by washout of S100b. Thirteen patients (52%) in the control group and 14 patients (56%) in the ZBUF group showed a cognitive deficit. In conclusion, ZBUF during CPB does not decrease the release of S100b. This result is not affected by washout. ZBUF did not reduce the incidence of early neurocognitive deficits. The role of SIRS in the development of cognitive dysfunction following CPB remains to be resolved.

Background: Both mechanical and pharmacological effects may contribute to the haemodynamic consequences of carbon dioxide (CO2) pneumoperitoneum. The aim of the present study was to evaluate the haemodynamic effects of low-pressure pneumoperitoneum [intra-abdominal pressure (IAP) 5 mmHg] in young children (< 3 years)., Methods: Thirteen children, aged 6-36 months, ASA physical status I-III, who were scheduled for laparoscopic fundoplication for gastro-oesophageal reflux were investigated in the head-up position (10 degrees ). Noninvasive thoracic electrical bioimpedance cardiac index (CI), stroke volume index (SVI), heart rate (HR), mean arterial pressure (MAP) and peak inspiratory pressure (PIP) were recorded, together with PetCO2 and PaCO2 at five time points: before insufflation, 20, 35 and 70 min after start of CO2 insufflation and 12 min after desufflation. During insufflation, minute ventilation was not adjusted and the IAP was maintained at 5 mmHg., Results: During insufflation, PetCO2 increased from 29 +/- 4 to 37 +/- 5 mmHg (P < 0.001) and PaCO2 increased from 31 +/- 4 to 39 +/- 5 mmHg (P < 0.01). CI increased from 2.39 +/- 0.86 to 2.92 +/- 0.94 l x min-1 x m2 (P < 0.01), HR increased from 108 +/- 10 to 126 +/- 22 b x min-1 (P < 0.01), MAP increased from 52 +/- 10 to 63 +/- 9 (P < 0.05) and PIP increased from 16 +/- 3 to 18 +/- 3 cm H2O (P < 0.001). There were no changes in SVI and arterial oxygen saturation., Conclusions: We conclude that low-pressure CO2 pneumoperitoneum (with IAPs not exceeding 5 mmHg) for laparoscopic fundoplication in infants and children does not decrease their cardiac index.

Neurocognitive decline following cardiac surgery is an increasing problem, particularly affecting older patients. The use of cardiopulmonary bypass is a suspected cause. Research into pathophysiology and possible preventive measures requires the use of an animal model. Commercial oxygenators are too large and expensive for use in small animals. We describe a fiber oxygenator scaled for use in the rat. In vitro and in vivo testing show that it is able to support full gas exchange in this size of animal, and causes no allergic or toxic reactions.

Background: We have developed a prediction rule for the occurrence of perioperative red blood cell transfusion to help to reduce the number of unnecessary preoperative type and screen procedures. We evaluated the robustness of this prediction rule in patients from another hospital., Methods: The rule was retrospectively applied to 1282 consecutive patients ('validation set') who underwent similar surgical procedures to the patients in the derivation study. The outcome was similarly defined as any allogeneic transfusion on the day of surgery or during the first postoperative day. The predictive value of the rule was assessed using a Receiver Operating Characteristic curve (ROC) and compared with the results of the derivation study. Subsequently, the number of correctly predicted transfusions was compared., Results: The patient characteristics did not differ between the two sets, except for the incidence of transfusion (derivation study: 18%; present study: 8%). In the validation set, the ROC area of the prediction rule was 0.78 (95% confidence intervals [CI]: 0.73-0.82), which was within the CI of the ROC area found in the derivation study (0.75; 95% CI: 0.72-0.79). In total, 35% of the type and screen procedures could be omitted (derivation study: 50%), with 13% missed transfused patients (derivation study: 20%)., Conclusions: After comparing the results of this validation study with that of the derivation study, the prediction rule was robust and may work in other clinics as well.

Background: Monitoring of myogenic motor evoked potentials to transcranial stimulation (tcMEPs) is clinically used to assess motor pathway function during aortic and spinal procedures that carry a risk of spinal cord ischemia (SCI). Although tcMEPs presumably detect SCI before irreversible neuronal deficit occurs, and prolonged reduction of tcMEP signals is thought to be associated with impending spinal cord damage, experimental evidence to support this concept has not been provided. In this study, histopathologic and neurologic outcome was examined in a porcine model of SCI after different durations of intraoperative loss of tcMEP signals., Methods: In 15 ketamine-sufentanil-anesthetized pigs (weight, 35-45 kg) the spinal cord feeding lumbar arteries were exposed. tcMEP were recorded from the upper and lower limbs. Under normothermic conditions, animals were randomly allocated to undergo short-term tcMEP reduction (group A, < 10 min, n = 5) or prolonged tcMEP reduction (group B, 60 min, n = 10), resulting from temporary or permanent clamping of lumbar segmental arteries. Neurologic function was evaluated every 24 h, and infarction volume and the number of eosinophilic neurons and viable motoneurons in the lumbosacral spinal cord was evaluated 72 h after induction of SCI., Results: In all animals except one, segmental artery clamping reduced tcMEP to below 25% of baseline. All but one animal in group A had reduced tcMEP for less than 10 min and had normal motor function and no infarction at 72 h after the initial tcMEP reduction. Seven animals in group B (70%) had reduced tcMEP signals for more than 60 min and were paraplegic with massive spinal cord infarction at 72 h. Two animals (one in both groups) had tcMEP loss for 40 min, with moderate infarction and normal function. In general, histopathologic damage and neurologic dysfunction did not occur when tcMEP amplitude recovered within 10 and 40 min after the initial decline, respectively., Conclusion: Prolonged reduction of intraoperative tcMEP amplitude is predictive for postoperative neurologic dysfunction, while recovery of the tcMEP signal within 10 min after the initial decline corresponds with normal histopathology and motor function in this experimental model. This finding confirms that intraoperative tcMEPs have a good prognostic value for neurologic outcome during procedures in which the spinal cord is at risk for ischemia.

Context: Coronary artery bypass graft (CABG) surgery is associated with a decline in cognitive function, which has largely been attributed to the use of cardiopulmonary bypass (on-pump procedures). Cardiac stabilizers facilitate CABG surgery without use of cardiopulmonary bypass (off-pump procedures) and should reduce the cognitive decline associated with on-pump procedures., Objective: To compare the effect of CABG surgery with (on-pump) and without (off-pump) cardiopulmonary bypass on cognitive outcome., Design and Setting: Randomized controlled trial conducted in the Netherlands of CABG surgery patients enrolled from March 1998 through August 2000, with 3- and 12-month follow-up., Participants and Intervention: Patients scheduled for their first CABG surgery (mean age, 61 years; n = 281) were randomly assigned to off-pump surgery (n = 142) or on-pump surgery (n = 139)., Main Outcome Measures: Cognitive outcome at 3 and 12 months, which was determined by psychologists (blinded for randomization) who administered 10 neuropsychological tests before and after surgery. Quality of life, stroke rate, and all-cause mortality at 3 and 12 months were secondary outcome measures., Results: Cognitive outcome could be determined at 3 months in 248 patients. Cognitive decline occurred in 21% in the off-pump group and 29% in the on-pump group (relative risk [RR], 0.65; 95% confidence interval [CI], 0.36-1.16; P =.15). The overall standardized change score (ie, improvement of cognitive performance) was 0.19 in the off-pump vs 0.13 in the on-pump group (P =.03). At 12 months, cognitive decline occurred in 30.8% in the off-pump group and 33.6% in the on-pump group (RR, 0.88; 95% CI, 0.52-1.49; P =.69). The overall standardized change score was 0.19 in the off-pump vs 0.12 in the on-pump group (P =.09). No statistically significant differences were observed between the on-pump and off-pump groups in quality of life, stroke rate, or all-cause mortality at 3 and 12 months., Conclusion: Patients who received their first CABG surgery without cardiopulmonary bypass had improved cognitive outcomes 3 months after the procedure, but the effects were limited and became negligible at 12 months.

Unlabelled: We examined the effects of low-pressure carbon dioxide pneumoperitoneum on regional cerebral oxygen saturation (ScO(2)) and cerebral blood volume (CBV) in children. Fifteen children, ASA I--III, scheduled for laparoscopic fundoplication, were investigated in the head-up position (10) and ventilated to a baseline end-tidal CO(2) (PETCO(2)) between 25 and 33 mm Hg. Ventilatory settings remained unchanged during the operation. ScO(2) and CBV were assessed with near-infrared spectroscopy and recorded together with end-tidal and arterial carbon dioxide (PaCO(2)) at 5 time points: before insufflation, 30, 60, and 90 min after the start of CO(2) insufflation, and 10 min after desufflation. The intraabdominal pressure was kept between 5 and 8 mm Hg. During insufflation, PETCO(2) increased from 30.0 plus minus 2.8 to 38.3 plus minus 5.1 mm Hg (P < 0.001) and PaCO(2) increased from 32.0 plus minus 4.7 to 40.4 plus minus 5.9 mm Hg (P < 0.001). ScO(2) increased by 15.7% plus minus 8.8% (from 61 plus minus 9 to 70 plus minus 9 arbitrary units ) (P < 0.001). CBV increased by 4.6% plus minus 8.8% (from 123 plus minus 66 to 128 plus minus 66 arbitrary units [P = 0.048]). After desufflation, PETCO(2) and PaCO(2) decreased, but did not return to preinsufflation values. ScO(2) and CBV also decreased after desufflation. In conclusion, hyperventilation and the head-up position before CO(2) insufflation are not sufficient to prevent the CO(2)-mediated cerebral hemodynamic effects of low-pressure pneumoperitoneum (5--8 mm Hg) in children., Implications: Peritoneal CO(2) absorption during laparoscopic surgery causes hypercapnia and CO(2)-mediated cerebral hemodynamic effects. Hyperventilation and the head-up position before CO(2) insufflation is not sufficient to counteract these effects of low-pressure pneumoperitoneum (5--8 mm Hg) in children.

Objective: Clinical monitoring of myogenic motor evoked potentials to transcranial stimulation provides rapid evaluation of motor-pathway function during surgical procedures in which spinal cord ischemia can occur. However, a severe reduction of spinal cord blood flow that remains confined to the thoracic spinal cord might render ischemic only the descending axons of the corticospinal pathway. In this situation lower-limb motor evoked potentials could respond relatively late compared with a similar spinal cord blood flow reduction of the lumbar spinal cord that renders predominantly motoneurons ischemic., Methods: Selective thoracic and lumbar spinal cord ischemia was induced by sequential clamping of segmental arteries during continuous assessment of laser-Doppler spinal cord blood flow at the thoracic and lumbar spinal cord. Myogenic motor evoked potentials were recorded from the upper and lower limbs. The time to loss of motor evoked potentials was compared (n = 11) during reduction of laser-Doppler spinal cord blood flow below 25% of baseline (ischemic segment), and flow was maintained at greater than 75% of baseline in the nonischemic segment, both during thoracic and lumbar spinal cord ischemia., Results: Average laser-Doppler spinal cord blood flow in the ischemic segment was similar during thoracic (26% +/- 15% [+/- SD]) and lumbar (26% +/- 16%) ischemia, whereas normal flow was maintained in the nonischemic segment. The time to motor evoked potentials loss was considerably longer after thoracic spinal cord ischemia (15 +/- 11 minutes) than after lumbar spinal cord ischemia (3 +/- 2 minutes, P <.005)., Conclusion: In this experimental model of selective spinal cord ischemia, a severe reduction of lumbar spinal cord blood flow results in rapid loss of myogenic motor evoked potentials, whereas a similar blood flow reduction in the thoracic spinal cord results in relatively slow loss of motor evoked potentials. The effectiveness of motor evoked potentials to rapidly assess spinal cord integrity might be limited when spinal cord ischemia is confined to the thoracic segments.

Unlabelled: To evaluate the possible effects of outpatient preoperative evaluation (OPE) for new surgical patients who will be inpatients, we conducted an observational study at a university hospital in The Netherlands. Various outcomes before and after the introduction of an OPE clinic were compared. The study population comprised all 21,553 elective adult inpatients operated on between January 1, 1997 and December 31, 1999. Cardiac surgery, obstetric and pediatric patients, and patients operated on in same-day surgery were excluded. The main outcome measures were surgical cases canceled for medical reasons, rate of same-day admissions (who were expected to increase), and length of hospital stay. After introduction of OPE, the rate of cancellations for medical reasons decreased from 2.0% to 0.9% (adjusted odds ratio 0.7, 95% CI, 0.5--0.9). The rate of same-day admissions increased from 5.3% before to 7.7% after OPE introduction (adjusted odds ratio 1.2, 95% CI, 1.01--1.39), and the total hospital length of stay (in days) significantly decreased by a factor of 0.92 (0.90--0.94), which was partly the result of a reduction in preoperative admission time. We concluded that, although smaller than anticipated, the use of OPE for potential inpatients leads to a significant reduction of cancelled cases and of length of admission. Further increase of these benefits from OPE requires changes in institutional policy, such as forcing surgical departments to increase their number of same-day admissions., Implications: An observational study was conducted to compare various outcomes before and after the introduction of outpatient preoperative evaluation (OPE). Although smaller than anticipated, OPE for potential inpatients leads to a significant reduction of canceled cases and of length of admission.

Background: The disposition of inhalation anaesthetics is governed by the factors described in the Fick principle., Methods: We have recalibrated a previously validated physiological model for enflurane closed-circuit inhalation anaesthesia, using individual continuous cardiac output measurements as well as age-related enflurane solubility coefficients as inputs to the model. Two model versions using 'calculated' (Brody's formula) or 'measured' (thoracic electrical bioimpedance) cardiac output values, and two versions with 'standard' (fixed) or 'age-related' solubility coefficients were formulated., Results: Data from 62 ophthalmic surgical patients were used to validate the predictive performance of the four model versions. The root mean squared errors (total error) and scatters (error variation) were similar with the extended model versions, but the group biases (systematic error component) were significantly less with the model versions that included age-related solubility compared with the versions using standard solubility coefficients (bias -0.76/-0.78% vs -3.44/-3.60%)., Conclusion: The inclusion of age-related solubility coefficients but not of continuous cardiac output measurements improves the predictive performance of the physiological model for closed-circuit inhalation anaesthetic conditions in routine clinical practice.

Objective: In patients with thoracoabdominal aortic aneurysms (TAAAs), the blood supply to the spinal cord is highly variable and unpredictable because of obstructed intercostal and lumbar arteries. This study was performed for the prospective documentation of patent segmental arteries during TAAA repair and the assessment of their functional contribution to the spinal cord blood supply., Methods: TAAA repair was performed in 184 consecutive patients (68 with type I aneurysm, 91 with type II, and 25 with type III) according to a protocol that included left heart bypass grafting, cerebrospinal fluid drainage, and the monitoring of motor-evoked potentials (MEPs). Patent intercostal and lumbar arteries were documented, and all reattached, selectively grafted, and oversewn segmental arteries were noted. MEP amplitude that decreased to less than 25% of baseline was considered an indication of critical spinal cord ischemia and prompted spinal cord revascularization., Results: Adequate MEP levels were encountered in 183 of 184 patients. One patient had early paraplegia (absent MEPs), two patients had delayed paraplegia develop, and two patients had temporary paraparesis, which accounted for an overall neurologic deficit of 2.7%. The median total number of patent intercostal and lumbar arteries in type I, II, and III aneurysms was three, five, and five, respectively. In eight of 68 type I cases, no segmental arteries were seen between the fifth thoracic vertebrae (T5) and the first lumbar vertebrae (L1) and MEP levels remained adequate because of distal aortic perfusion. In 18 of 91 type II cases, the aortic segment T5 to L1 did not contain patent arteries, and in six of these patients, the segment L1 to L5 did not have lumbar arteries either. In the latter patients, MEP levels depended on the pelvic circulation provided with the left heart bypass graft. In the other 12 of 91 type II cases, the only patent arteries were the lumbar arteries between L3 and L5. The loss of MEPs could be corrected with the reattachment of these arteries. In seven of 25 type III cases, the MEP levels also depended on lumbar arteries L3 to L5 and in three of 25 cases, no segmental arteries were available and MEP levels recovered after the reperfusion of the pelvic circulation. With the combination of the findings of type II and III cases, spinal cord perfusion was directed by lower lumbar arteries in 16% of the cases (19 of 116) and pelvic circulation in 8% of the cases (nine of 116)., Conclusion: In patients with TAAA, most intercostal and lumbar arteries are occluded and spinal cord perfusion depends on an eminent collateral network, which includes lumbar arteries and pelvic circulation. The monitoring of MEPs is a sensitive technique for the assessment of spinal cord ischemia and the identification of segmental arteries that critically contribute to spinal cord perfusion. Surgical strategies on the basis of this technique reduced the incidence rate of neurologic deficit to less than 3%.

Inhibition of neurotoxic events that lead to delayed cellular damage may prevent motor function loss after transient spinal cord ischemia. An important effect of the neuroprotective substance aminoguanidine (AG) is the inhibition of inducible nitric oxide synthase (iNOS), a perpetrator of focal ischemic damage. The authors studied the protective effects of AG on hind limb motor function and histopathologic outcome in an experimental model for spinal cord ischemia, and related these findings to the protein content of iNOS in the spinal cord. Temporary spinal cord ischemia was induced by 28 minutes of infrarenal balloon occlusion of the aorta in 40 anesthetized New Zealand White rabbits. Animals were assigned randomly to two treatments: saline (n = 20) or AG (n = 20; 100 mg/kg intravenously before occlusion). Postoperatively, treatment was continued with subcutaneous injections twice daily (saline or 100 mg/kg AG). Normothermia (38 degrees C) was maintained during ischemia, and rectal temperature was assessed before and after subcutaneous injections. Animals were observed for 96 hours for neurologic evaluation (Tarlov score), and the lumbosacral spinal cord was examined for ischemic damage after perfusion and fixation. Lastly, iNOS protein content was determined using Western blot analysis 48 hours after ischemia in five animals from each group. Neurologic outcome at 96 hours after reperfusion was the same in both groups. The incidence of paraplegia was 67% in the saline-treated group versus 53% in the AG-treated group. No differences in infarction volume, total number of viable motoneurons, or total number of eosinophilic neurons were present between the groups. At 48 hours after reperfusion, iNOS protein content in the spinal cord was increased in one animal in the AG-treated group and in three animals in the control group. The data indicate that peri-ischemic treatment with high-dose AG in rabbits offers no protection against a period of normothermic spinal cord ischemia. There was no conclusive evidence of spinal cord iNOS inhibition after treatment with AG.

Monitoring myogenic motor EPs after transcranial electrical stimulation is effective in detecting spinal cord ischemia. During thoracoabdominal aortic aneurysm surgery, this technique is sufficiently rapid to allow timely interventions aimed at correcting ischemic conditions and preserving spinal cord blood flow. If strategies are applied to protect the spinal cord during thoracoabdominal aortic aneurysm repair (e.g., distal bypass, cerebrospinal fluid drainage, reattachment of segmental arteries), motor EP monitoring should be included in this protocol to improve neurologic outcome further. Although SSEPs provide information regarding the adequacy of spinal cord blood flow, monitoring SSEPs during thoracoabdominal aortic aneurysm repair has serious limitations. The response time is too slow to be of practical use. SSEPs also do not provide information regarding anterior horn motor function and supply, whereas the motor neurons in the anterior horn are most likely to sustain ischemic injury.

Background: Middle latency auditory evoked responses (MLAER) as a measure of depth of sedation are critically dependent on data quality and the analysis technique used. Manual peak labeling is subject to observer bias. This study investigated whether a user-independent index based on wavelet transform can be derived to discriminate between awake and unresponsive states during propofol sedation., Methods: After obtaining ethics committee approval and written informed consent, 13 volunteers and 40 patients were studied. In all subjects, propofol was titrated to loss of response to verbal command. The volunteers were allowed to recover, then propofol was titrated again to the same end point, and subjects were finally allowed to recover. From three MLAER waveforms at each stage, latencies and amplitudes of peaks Pa and Nb were measured manually. In addition, wavelet transform for analysis of MLAER was applied. Wavelet transform gives both frequency and time information by calculation of coefficients related to different frequency contents of the signal. Three coefficients of the so-called wavelet detail level 4 were transformed into a single index (Db3d4) using logistic regression analysis, which was also used for calculation of indices for Pa, Nb, and Pa/Nb latencies. Prediction probabilities for discrimination between awake and unresponsive states were calculated for all MLAER indices., Results: During propofol infusion, subjects were unresponsive, and MLAER components were significantly depressed when compared with the awake states (P < 0.001). The wavelet index Db3d4 was positive for awake and negative for unresponsive subjects with a prediction probability of 0.92., Conclusion: These data show that automated wavelet analysis may be used to differentiate between awake and unresponsive states. The threshold value for the wavelet index allows easy recognition of awake versus unresponsive subjects. In addition, it is independent of subjective peak identification and offers the advantage of easy implementation into monitoring devices.

In humans, damage to the nervous system can lead to a pain state referred to as neuropathic pain. Here, we give a short overview of the clinical picture and classification of neuropathic pain and highlight some of the currently known pathophysiological mechanisms involved, with special emphasis on neuropeptide plasticity. In this context, we discuss a specific group of neuropeptides, the melanocortins. These peptides have been demonstrated to play a role in nociception and to functionally interact with the opiate system. Recently, we demonstrated that spinal melanocortin receptors are upregulated in a rat model of neuropathic pain and that blockade of the melanocortin MC(4) receptor has anti-allodynic effects in this condition, suggesting that the melanocortin system plays a role in neuropathic pain. A natural agonist of melanocortin receptors is alpha-melanocyte-stimulating hormone (alpha-MSH), derived from the precursor molecule pro-opiomelanocortin (POMC). Cleavage of this precursor also yields beta-endorphin, which is co-released with alpha-MSH in nociception-associated areas of the spinal cord. We hypothesise that melanocortin receptor blockade attenuates a tonic influence of alpha-MSH on nociception, thus allowing the analgesic effects of beta-endorphin to develop, resulting in the alleviation of allodynia. In this way, treatment with melanocortin receptor antagonists might enhance opioid efficacy in neuropathic pain, which would be of great benefit in clinical practice.

Background: Pharmacokinetic-pharmacodynamic (PKPD) modeling can be used to characterize the concentration-effect relation of drugs. If the concentration-effect relation of a hypnotic drug is stable over time, an effect parameter derived from the processed electroencephalographic signal may be used to control the infusion for hypnosis. Therefore, the stability of the propofol concentration-electroencephalographic effect relation over time was investigated under non-steady state conditions., Methods: Three propofol infusions (25 mg x kg(-1) x h(-1) for 10 min, 22 mg x kg(-1) x h(-1) for 10 min, and 12.5 mg x kg(-1) x h(-1) for 20 min) were administered to 10 patients during extradural analgesia. Each successive infusion was started immediately after the patient had regained responsiveness after termination of the preceding infusion. Electroencephalography was recorded from bilateral prefrontal to mastoid leads. Electroencephalographic amplitude in the 11- to 15-Hz band and the Bispectral Index were used as electroencephalographic effect variables. PKPD parameters were calculated with use of parametric and nonparametric models based on electroencephalographic data and arterial propofol concentrations derived during the initial infusion, and these were used to predict electroencephalographic effect during the subsequent infusions. The predictability of the electroencephalographic effects was determined by the coefficient of determination (R2) and of the -2 log likelihood of the sequential infusions., Results: The direction of electroencephalographic changes in response to the infusions was reproducible. Although PKPD parameters could be estimated well during the initial infusion (median [range] parametric R2 = 0.74 [0.56-0.95] for electroencephalographic amplitude and 0.90 [0.27-0.99] for Bispectral Index), none of the modeling techniques could predict accurately the electroencephalographic effect during subsequent infusions (R2 = 0.00 [-0.31-0.46] for electroencephalographic amplitude and 0.15 [-.46-0.57] for Bispectral Index; P < 0.01)., Conclusions: The relation between blood propofol concentrations and the electroencephalographic effect under non-steady state conditions is not stable over time and is too complex to be modeled by any of the applied PKPD models.

The time course of four EEG effect variables, amplitude in the 2-5 Hz and in the 11-15 Hz band, spectral edge frequency 95% (SEF95), and bispectral index (BIS), in response to increasing concentrations of thiopental, propofol, etomidate, midazolam, or sevoflurane during a 10 min induction of anaesthesia was studied in 25 patients to determine the existence of a biphasic effect and to study the relationship of the EEG effect to the moment of loss of consciousness. A biphasic effect, that is, an initial increase of the effect variable followed by a decrease at higher concentrations, during the transition from consciousness to unconsciousness was found in EEG amplitude (both frequency bands) and in SEF95 for all anaesthetics except midazolam. There was a concentration-related decrease in BIS for all anaesthetics. There was no consistent relationship between the time of occurrence of the peak EEG effect, or the value of the EEG variable and the moment of loss of consciousness. With rapidly changing drug concentrations during the induction of anaesthesia, none of these EEG effect variables could be correlated to the moment of loss of consciousness.