The effect of analgesic state on implicit learning during propofol anesthesia in volunteers.

Noxious stimulation may enhance implicit learning during general anesthesia. It is unknown, however, whether analgesic state can influence this memory processing. Twenty healthy adult volunteers were enrolled our prospective, double-blinded, controlled experiments. Anesthesia was induced with a propofol target controlled infusion (TCI), titrated in step-wise increments to loss of consciousness. In phase A, a 10-word list was played to the subjects while a noxious stimulus was applied (hand immersion in cold water at 2-4 degrees C). In phase B, a remifentanil TCI infusion was added to the steady-state propofol TCI anesthesia, and titrated to loss of hand movement on cold water immersion. A second 10-word list was then played while maintaining the hand in cold water. Memory testing, 2 hours post-recovery revealed no evidence of explicit memory in any subject during either phase of the study. During phase A, the word stem completion test revealed implicit learning for played words. In contrast, no implicit memory was detected during phase B. This study indicates that analgesia with remifentanil TCI (titrated to loss of movement on noxious stimulation), prevented implicit memory processing during stable propofol anesthesia in healthy adult volunteers.

Absence of implicit and explicit memory during propofol/remifentanil anaesthesia.

BACKGROUND AND OBJECTIVE: High doses of opioid associated with low doses of hypnotic is a popular anaesthetic technique since the use of remifentanil has become widespread. This type of anaesthesia could result in a higher incidence of implicit memory. METHODS: Ten patients were anaesthetised with a target-controlled infusion of remifentanil (target concentration of 8 ng mL(-1)) combined with a target-controlled infusion of propofol with progressive stepwise increases until loss of consciousness was reached. A tape containing 20 words was then played to the patients. Bispectral index (BIS, Aspect Medical Systems, Newton, MA, USA) was continuously monitored during the whole study period. Implicit and explicit memories were tested between 2 and 4 h after recovery. RESULTS: Loss of consciousness was obtained with a mean calculated propofol plasma concentration of 1.3 +/- 0.4 microg mL(-1). At this low hypnotic concentration no implicit or explicit memory was found in the three postoperative memory tests. Median (range) BIS value during word presentation was 93 (80-98). CONCLUSIONS: In our group of young American Society of Anesthesiologists (ASA) I/II patients, no explicit or implicit memory was found when the calculated concentration of propofol combined with a high concentration of remifentanil was maintained at the level associated with loss of consciousness with high BIS values.

Effect site concentrations of remifentanil and pupil response to noxious stimulation.

BACKGROUND: Opioid drugs block reflex pupillary dilatation in response to noxious stimulation. The relationship between the target effect site concentration (Ce(T)) of remifentanil and the pupil diameter and reactivity in response to a standard noxious stimulus were evaluated. METHODS: Anaesthesia was induced with propofol TCI to obtain loss of consciousness (LOC) in 12 ASA I/II patients. Thereafter, remifentanil Ce(T) was titrated by increments of 1 up to 5 ng ml(-1). In the awake state, at LOC and at each plateau level of remifentanil Ce(T), arterial pressure, heart rate, and BIS (A2000) were recorded. Pupil size and dilatation after a 100 Hz tetanic stimulation (T100) were measured at LOC and at each plateau level of remifentanil Ce(T). RESULTS: LOC was observed at a mean propofol Ce(T) of 3.53 (SD 0.43) microg ml(-1). Arterial pressure and heart rate decreased progressively from LOC to 5 ng ml(-1) remifentanil Ce(T) without any statistical difference between each incremental dose of remifentanil. Mean BIS values decreased from 96 (2) in the awake state, to 46 (12) at LOC (P<0.05) and then remained unchanged at all remifentanil Ce(T). Pupil dilatation in response to 100 Hz tetanic stimulation decreased progressively from 1.55 (0.72) to 0.01 (0.03) mm and was more sensitive than pupil diameter measured before and after 100 Hz tetanus. An inverse correlation between pupil dilatation in response to 100 Hz tetanus and an increase in remifentanil Ce(T) from 0 to 5 ng ml(-1) was found (R(2)=0.68). CONCLUSIONS: During propofol TCI in healthy patients, the decrease in pupil response to a painful stimulus is a better measurement of the progressive increase of remifentanil Ce(T) up to 5 ng ml(-1) than haemodynamic or BIS measurements.

Absence of explicit and implicit memory in unconscious patients using a TCI of propofol.

BACKGROUND: Episodes of implicit memory have been described during propofol anaesthesia. It remains unclear whether implicit memory is caused by short periods of awareness or occurs in an unconscious subject. METHODS: Sixty patients were randomized in an experimental group (EG), a control group (CG) and a reference group (RG). Loss of consciousness (LOC) was obtained by progressive stepwise increases of propofol using a target-controlled infusion device (Diprifusor, Alaris Medical Systems, San Diego, CA). A tape containing 20 words was played to the patients in the CG before the start of anaesthesia and to the patients in the EG at a constant calculated concentration of propofol associated with LOC. The tape was not played to the patients in the RG. Three memory tests were performed postoperatively. RESULTS: Explicit and implicit memories were evidenced in the CG but not in the EG. CONCLUSION: In our group of young ASA I/II patients, in the absence of any noxious stimulus, no implicit or explicit memory was found when the calculated concentration of propofol using a Diprifusor was maintained at the level associated with LOC.

Target-controlled infusion of propofol induction with or without plasma concentration constraint in high-risk adult patients undergoing cardiac surgery.

BACKGROUND: Calculated plasma (Cp) and calculated effect site concentrations (Ce) of propofol associated with loss of consciousness (LOC) have been studied in young healthy patients. The aim of the study was to evaluate the calculated propofol concentrations required to induce LOC in ASA III adult patients undergoing cardiac surgery using a smooth target controlled infusion of propofol. METHODS: After informed consent, 44 patients were premedicated with 0.5 mg alprazolam orally. Propofol TCI using the pharmacokinetic set of Marsh et al. incorporated in the Diprifusor (ThalfKeo of 2.6 min) was used. Propofol Ce was progressively increased by 0.5 micro g/ml until LOC was obtained. The constraint on the maximum gradient between Cp and Ce was either 1 micro g/ml in group 1 or not limited in group 2. Hemodynamic variations were assessed. RESULTS: Mean preoperative left ventricular ejection fractions were 44 +/- 15.4% and 56 +/- 11.4% in groups 1 and 2, respectively (P < 0.01). At LOC, mean Cp was 1.9 micro g/ml in both groups but mean Ce was 1.08 +/- 0.31 and 1.43 +/- 0.42 micro g/ml in groups 1 and 2, respectively (P < 0.01). The mean induction time was 12.8 +/- 7.1 min in group 1 and 8.5 +/- 2.7 min in group 2 (P < 0.05). No episode of hypotension has been observed in either group. CONCLUSION: In ASA III patients undergoing cardiac surgery, smooth propofol TCI induction, using the pharmacokinetic set of Marsh et al. incorporated in the Diprifusor, is associated with LOC at a low mean calculated plasma concentration of 1.9 micro g/ml and good hemodynamic stability.

Acute renal failure in the ICU: risk factors and outcome evaluated by the SOFA score.

OBJECTIVES: To describe risk factors for the development of acute renal failure (ARF) in a population of intensive care unit (ICU) patients, and the association of ARF with multiple organ failure (MOF) and outcome using the sequential organ failure assessment (SOFA) score. DESIGN: Prospective, multicenter, observational cohort analysis. SETTING: Forty ICUs in 16 countries. PATIENTS: All patients admitted to one of the participating ICUs in May 1995, except those who stayed in the ICU for less than 48 h after uncomplicated surgery, were included. After the exclusion of 38 patients with a history of chronic renal failure requiring renal replacement therapy, a total of 1411 patients were studied. MEASUREMENTS AND RESULTS: Of the patients, 348 (24.7%) developed ARF, as diagnosed by a serum creatinine of 300 micromol/l (3.5 mg/dl) or more and/or a urine output of less than 500 ml/day. The most important risk factors for the development of ARF present on admission were acute circulatory or respiratory failure; age more than 65 years, presence of infection, past history of chronic heart failure (CHF), lymphoma or leukemia, or cirrhosis. ARF patients developed MOF earlier than non-ARF patients (median 24 vs 48 h after ICU admission, p < 0.05). ARF patients older than 65 years with a past history of CHF or with any organ failure on admission were most likely to develop MOF. ICU mortality was 3 times higher in ARF than in other patients (42.8% vs 14.0%, p < 0.01). Oliguric ARF was an independent risk factor for overall mortality as determined by a multivariate regression analysis (OR = 1.59 [CI 95%: 1.23-2.06], p < 0.01). Infection increased the risk of death associated with all factors. Factors that increased the ICU mortality of ARF patients were a past history of hematologic malignancy, age more than 65 years, the number of failing organs on admission and the presence of acute cardiovascular failure. CONCLUSION: In ICU patients, the most important risk factors for ARF or mortality from ARF are often present on admission. During the ICU stay, other organ failures (especially cardiovascular) are important risk factors. Oliguric ARF was an independent risk factor for ICU mortality, and infection increased the contribution to mortality by other factors. The severity of circulatory shock was the most important factor influencing outcome in ARF patients.

Pharmacokinetic model-driven infusion of sufentanil and midazolam during cardiac surgery: assessment of the prospective predictive accuracy and the quality of anesthesia.

OBJECTIVE: To evaluate the prospective predictive accuracy and the quality of anesthesia of pharmacokinetic model-driven infusion of sufentanil and midazolam designed to establish and maintain a plasma level of drug during cardiac surgery. DESIGN: Prospective analysis. SETTING: Operating room at a university hospital. PARTICIPANTS: Twenty adult patients younger than 75 years old scheduled for valvular or coronary artery bypass graft surgery. INTERVENTIONS: Patients were anesthetized using a variable predicted concentration of sufentanil (1 to 10 ng/mL) combined with a stable predicted concentration of midazolam (100 ng/mL). MEASUREMENTS AND MAIN RESULTS: For each patient, arterial samples were taken before (6 samples), during (2 samples), and after (2 samples) cardiopulmonary bypass (CPB). Plasma sufentanil and midazolam concentrations were measured by specific radioimmunoassay and high-performance liquid chromatography techniques. Predicted sufentanil and midazolam concentrations were derived using the data sets of Gepts et al and Maitre et al. The predictive performance, the percentage prediction error (PE), and the absolute percentage error were calculated for each sample. The bias, inaccuracy, and dispersion were assessed by determining the median of the individual medians of the prediction errors (MDPE), the median of the individual median of the absolute prediction errors (MDAPE), and the 10th and 90th percentiles of PE. For midazolam, the inaccuracy was low (MDAPE < 21%), but CPB was associated with a dilution of the measured concentration associated with a negative bias. For sufentanil, the inaccuracy was also low before CPB (MDAPE = 18%) but increased during and after CPB (MDAPE > 40%). During the whole procedure, the hemodynamic control necessitated only a few interventions. CONCLUSIONS: Pharmacokinetic model-driven infusion of sufentanil and midazolam using the pharmacokinetic sets of Gepts et al and Maitre et al is a safe and accurate anesthetic technique before CPB in adult patients undergoing cardiac surgery when high sufentanil (1 to 10 ng/mL) and low midazolam (100 ng/mL) predicted plasma concentrations are targeted.

Predictive accuracy of target-controlled propofol and sufentanil coinfusion in long-lasting surgery.

BACKGROUND: The predictive accuracy of target concentration infusions of propofol has been documented only for less than 4 h, and no prospective study of sufentanil target controlled infusion is available. The authors investigated the predictive accuracy of pharmacokinetic models for propofol and sufentanil coadministered during long-lasting surgery. METHODS: Ten patients, American Society of Anesthesiologists physical status I and II, were studied during extended cervicofacial surgery. Target controlled infusion of propofol and sufentanil was administered during surgery using decisional algorithms, taking into consideration pain assessment, hemodynamic changes, and peroperative blood losses. Intrasubject data analysis included calculation of performance error, median performance error, median absolute performance error, divergence, and wobble. RESULTS: The range of plasma target concentrations was 2-5 microgram/ml for propofol and 0.2-1 ng/ml for sufentanil. Median performance error was -12.1% for propofol and -10% for sufentanil. The wobble values were 11.6% and 22.3% for propofol and sufentanil, respectively. The pharmacokinetic sets used slightly overpredicted the concentrations, with negative values of divergence of 2.92% and 0.22% units/h for propofol and sufentanil, for a mean infusion period of 762 min. CONCLUSIONS: This prospective study demonstrates the predictive accuracy of the pharmacokinetic model for sufentanil infusion and confirms that for propofol during long-lasting surgery using standardized rules for the management of target controlled infusion and blood loss replacement.

Salivary biomass assessed by bioluminescence ATP assay related to (bacterial and somatic) cell counts.

The present work aimed (1) to evaluate ATP content in saliva by the bioluminescent luciferin-luciferase method, (2) to evaluate the relationships between ATP content, bacterial count and epithelial cell numbers in saliva, (3) to study the effect of two different antiseptics (peroxidase system producing hypothiocyanite and chlorhexidine) on the salivary biomass. In 45 young adults, the salivary ATP content ranged from 8 to 1515 nM. Salivary ATP content was significantly and directly correlated to bacterial count and epithelial cell numbers (Spearman-Rank correlation, P< or =0.001). Regression analysis allowed the inference of a mean epithelial cell and bacterial ATP content of 152.7 fg and 8.3 fg per cell, respectively. The salivary ATP content decreased significantly to 38. 8+/-12.3 per cent (mean+/-SEM, N=6) of its initial value after a 30-min incubation in the presence of a peroxidase system producing hypothiocyanite (OSCN(-)). Chlorhexidine (CHX) reduced salivary ATP content to 52.0+/-16.7 per cent. OSCN(-) did not affect the transformed logarithm of bacterial count but CHX reduced it from 7. 02+/-0.26 to 0.52+/-0.33. No effect of OSCN(-) was seen on the ratio of epithelial cell viability while CHX reduced it from 46.7+/-5.1 to 3.9+/-1.1 per cent. It is concluded that the combination of the evaluations of the ATP content and cell numbers in saliva can provide reliable data about the effects of oral antiseptics on salivary biomass.

The first object oriented monitor for intravenous anesthesia.

OBJECTIVE: To describe the design and implementation of "INFUSION TOOLBOX," a software tool to control and monitor multiple intravenous drug infusions simultaneously using pharmacokinetic and pharmacodynamic principles. METHODS: INFUSION TOOLBOX has been designed to present a graphical interface. Object Oriented design was used and the software was implemented using Smalltalk, to run on a PC. Basic tools are available to manage patient, drugs, pumps and reports. These tools are the PatientPanel, the DrugPanel, the PumpPanel and the HistoryPanel. The screen is built dynamically. The panels may be collapsed or closed to avoid a crowded display. We also built control panels such as the Target ControlPanel which calculates the best infusion sequence to bring the drug concentration in the plasma compartment to a preset value. Before drug delivery, the user enters the patient's data, selects a drug, enters its dilution factor and chooses a pharmacokinetic model. The calculated plasma concentration is continually displayed and updated. The anesthetist may ask for the history of the delivery to obtain a graphic report or to add events to the logbook. A panel targeting the effect is used when a pharmacodynamic model is known. Data files for drugs, pumps and surgery are upgradable. DISCUSSION: By creating a resizeable ControlPanel we enable the anesthetist to display the information he wishes, when he wishes it. The available panels are diverse enough to meet the anesthetist needs; they may be adapted to the drug used, pumps used and surgery. It is the anesthetist who builds dynamically its different control screens. CONCLUSION: By adopting an evolutionary solution model we have achieved considerable success in building our drug delivery monitor. In addition we have gained valuable insight into the anesthesia information domain that will allow us to further enhance and expand the system.

The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis related Problems of the ESICM.

OBJECTIVE: To evaluate the performance of total maximum sequential organ failure assessment (SOFA) score and a derived measure, delta SOFA (total maximum SOFA score minus admission total SOFA) as a descriptor of multiple organ dysfunction/failure in intensive care. DESIGN: Prospective, multicentre and multinational study. SETTING: Forty intensive care units (ICUs) from Australia, Europe, North and South America. PATIENTS: Data on 1,449 patients, evaluated at admission and then consecutively every 24 h until ICU discharge (11,417 records) during May 1995. Excluded from data collection were all patients with a length of stay in the ICU less than 2 days following uncomplicated scheduled surgery. MAIN OUTCOME MEASURE: Survival status at ICU discharge. INTERVENTIONS: The collection of raw data necessary for the computation of a SOFA score on admission and then every 24 h, and basic demographic and clinical statistics. MEASUREMENTS AND MAIN RESULTS: Mean total maximum SOFA score presented a very good correlation to ICU outcome, with mortality rates ranging from 3.2% in patients without organ failure to 91.3% in patients with failure of all the six organs analysed. A maximum score was reached 1.1 +/- 0.2 days after admission for all the organ systems analysed. The total maximum SOFA score presented an area under the ROC curve of 0.847 (SE 0.012), which was significantly higher than any of its individual components. The cardiovascular score (odds ratio 1.68) was associated with the highest relative contribution to outcome. No independent contribution could be demonstrated for the hepatic score. No significant interactions were found. Principal components analysis demonstrated the existence of a two-factor structure that became clearer when analysis was limited to the presence or absence of organ failure (SOFA score > or = 3 points) during the ICU stay. The first factor comprises respiratory, cardiovascular and neurological systems and the second coagulation, hepatic and renal systems. Delta SOFA also presented a good correlation to outcome. The area under the receiver operating characteristic (ROC) curve was 0.742 (SE 0.017) for delta SOFA, lower than the total maximum SOFA score or admission total SOFA score. The impact of delta SOFA on prognosis remained significant after correction for admission total SOFA. CONCLUSIONS: The results show that total maximum SOFA score and delta SOFA can be used to quantify the degree of dysfunction/failure already present on ICU admission, the degree of dysfunction/failure that appears during the ICU stay and the cumulative insult suffered by the patient. These properties make it a good instrument to be used in the evaluation of organ dysfunction/failure.

Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine.

OBJECTIVE: To evaluate the use of the Sequential Organ Failure Assessment (SOFA) score in assessing the incidence and severity of organ dysfunction in critically ill patients. DESIGN: Prospective, multicenter study. SETTING: Forty intensive care units (ICUs) in 16 countries. PATIENTS: Patients admitted to the ICU in May 1995 (n = 1,449), excluding patients who underwent uncomplicated elective surgery with an ICU length of stay <48 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome measures included incidence of dysfunction/failure of different organs and the relationship of this dysfunction with outcome. In this cohort of patients, the median length of ICU stay was 5 days, and the ICU mortality rate was 22%. Multiple organ dysfunction and high SOFA scores for any individual organ were associated with increased mortality. The presence of infection on admission (28.7% of patients) was associated with higher SOFA scores for each organ. The evaluation of a subgroup of 544 patients who stayed in the ICU for at least 1 wk showed that survivors and nonsurvivors followed a different course. This subgroup had greater respiratory, cardiovascular, and neurologic scores than the other patients. In this subgroup, the total SOFA score increased in 44% of the nonsurvivors but in only 20% of the survivors (p < .001). Conversely, the total SOFA score decreased in 33% of the survivors compared with 21% of the nonsurvivors (p < .001). CONCLUSIONS: The SOFA score is a simple, but effective method to describe organ dysfunction/failure in critically ill patients. Regular, repeated scoring enables patient condition and disease development to be monitored and better understood. The SOFA score may enable comparison between patients that would benefit clinical trials.

Integration of a blood pressure controller and an infusion toolbox system using client-server technology.

This paper shortly describes an Infusion Toolbox and a blood pressure (BP) control application. It explains how we applied an agent model and client-server technology to integrate them. We show that by using this framework and object oriented technologies the necessary changes to the existing applications are reduced. Many elements of the tested original systems could be re-used, which enhances safe development.

Visual evaluation of residual curarization in anesthetized patients using one hundred-hertz, five-second tetanic stimulation at the adductor pollicis muscle.

UNLABELLED: We were looking for a clinical test to indicate a train-of-four (TOF) ratio of approximately 0.9. We compared the adductor pollicis muscle (AP) visually evaluated response to ulnar nerve 100-Hz, 5-s tetanus (RF100 Hz) with the measured AP TOF ratio in 30 ASA physical status I or II adult anesthetized (propofol, sufentanil, N2O/O2) patients. After the induction of anesthesia, the left ulnar nerve was stimulated at the wrist (single twitch and TOF) and the resultant isometric force was measured. When TOF was assessed, the independent investigators, unaware of the left AP-measured TOF ratios, visually evaluated the presence or absence of AP fading elicited by right ulnar nerve 100-Hz, 5-s tetanus. The 30 patients were randomly allocated to receive either 0.5 mg/kg atracurium (n = 15) or 0.1 mg/kg vecuronium (n = 15). The neuromuscular blockade was allowed to resolve spontaneously. A multiple logistic regression analysis was performed by computing the 771 visual observations. The probabilities of success of 100-Hz, 5-s tetanus to detect TOF ratios of 0.8, 0.85, and 0.9 were 99%, 96%, and 67%, respectively. The sensitivity and specificity of 100-Hz, 5-s tetanus as an indicator of TOF ratios of 0.85 and 0.9 are 100% and 75%, 54% and 67%, respectively. We conclude that RF100 Hz visual assessment seems to be highly sensitive in evaluating residual paralysis, as the absence of RF100 Hz visual fading at the AP is compatible with a TOF ratio > 0.85. IMPLICATIONS: After the administration of muscle relaxants, the absence of visual fading at the adductor pollicis, elicited in anesthetized patients by 100-Hz, 5-s tetanus, is compatible with a train-of four ratio > 0.85. Therefore, clinical observation of fading after 100-Hz, 5-s tetanus seems to be a highly sensitive test in evaluating residual paralysis.

Effects of target-controlled anesthesia with propofol and sufentanil on the hemodynamic response to Mayfield head holder application.

The effects of target-controlled anesthesia with propofol and sufentanil on the hemodynamic response to Mayfield head holder (MH) application were evaluated in 18 ASA I and II patients undergoing scheduled intracranial surgery. Premedication consisted of hydroxyzine, alprazolam and atropine given orally 1 h before surgery. Anesthesia was provided with propofol and sufentanil using a target-controlled infusion device; constant calculated plasma concentrations of 4 micrograms ml-1 propofol and 0.5 ng ml-1 sufentanil were maintained throughout the study. Muscle relaxation was obtained with atracurium and ventilation was controlled with air/oxygen. The MH was fixed 45 +/- 12 min (mean +/- SD) after induction of anesthesia. Heart rate and systolic, diastolic, and mean non invasive arterial pressure were monitored and recorded 5 min before induction of anesthesia (control), 1 min before MH application (MH-1), at MH application, and 1 and 2 min after MH application. Systolic, diastolic, mean arterial pressure, and heart rate increased significantly during and after MH application when compared with MH-1 values, but remained constantly lower than control. Hemodynamic parameters measured 1 min before MH application were significantly lower than control. The results of the study indicate that target-controlled anesthesia maintained with constant calculated plasma concentrations of 4 micrograms ml-1 propofol and 0.5 ng ml-1 sufentanil prevents the increase in arterial pressure and heart rate beyond control values following MH application but may induce some degree of arterial hypotension in the absence of nociceptive stimulation.

Emergence from target-controlled anesthesia with propofol and sufentanil in patients undergoing intracranial surgery.

The study was designed to characterise the emergence from target-controlled anesthesia assessed by the recovery of spontaneous breathing, eye opening to command, and extubation in 18 adult patients undergoing intracranial surgery. Total intravenous anesthesia was induced and maintained with propofol and sufentanil. Target plasma concentration of propofol ranged between 3.0 and 5.5 micrograms.ml-1 and infusion was stopped after head dressing. The initial target plasma sufentanil concentration of 0.50 ng.ml-1 was decreased to 0.15 ng.ml-1 after craniotomy; sufentanil infusion was discontinued at the dura closure. The time from the end of surgery (head dressing) to recovery of spontaneous breathing was 8.3 +/- 6.5 min, and the time to eye opening and extubation was 14.7 +/- 10.0 min. At the end of surgery, the calculated plasma propofol concentration was 3.42 +/- 0.26 micrograms.ml-1. It significantly decreased to 2.11 +/- 0.51 micrograms.ml-1 at recovery of spontaneous breathing and to 1.81 +/- 0.41 micrograms.ml-1 at eye opening and extubation. The calculated plasma sufentanil concentration was 0.108 +/- 0.019 ng.ml-1 at the end of surgery but did not change significantly between recovery of spontaneous breathing (0.089 +/- 0.013 ng.ml-1), eye opening and extubation (0.087 +/- 0.013 ng.ml-1). The calculated plasma propofol concentrations recorded at emergence were not correlated with patient age, total dose of propofol, and duration of infusion; corresponding calculated sufentanil concentrations were not correlated with age and total dose of sufentanil. An inverse relationship (p < 0.05) was found between the duration of sufentanil infusion and the calculated sufentanil concentrations at emergence. No correlation was observed between calculated concentrations of propofol and sufentanil at emergence.

Clinical evaluation of an automatic blood pressure controller during cardiac surgery.

OBJECTIVE: During surgery, computers can be of great use to support the anesthesiologist in providing task automation. In this paper we describe a closed loop blood pressure controller and show the results of its clinical evaluation. METHODS: The controller is based on a simple and robust Proportional-Integral controller and a supervising, rule based, expert system. Adaptive control is necessary because the sensitivity of the patients to sodium nitroprusside varies over a wide range. Thirty-three clinical tests during cardiac surgery, including the cardiopulmonary bypass phase, were performed. RESULTS: On average the controller was in automatic mode for 90.6 +/- 9.6% of the time. The performance during automatic control showed the mean arterial pressure to be within 10 mmHg of the setpoint for 71.4 +/- 15.5% of the time. The average absolute distance to the setpoint was 8.1 +/- 7.2 mmHg. CONCLUSIONS: The overall performance of the controller was noted as very satisfactory by the anesthesiologists.

Radiocarpal articular pressures during the reduction of distal radius fractures.

OBJECTIVES: To measure in vivo radiocarpal articular pressures during closed reduction and external fixation of distal radius fractures. DESIGN: Intraoperative measurements using a sterile pressure sensitive sensor specially constructed for this application. SETTING AND PATIENTS: Ten patients with a closed distal radius fracture stabilized by radiometacarpal external fixation. Radiocarpal pressures measured during transarticular distraction, wrist palmar flexion, wrist ulnar inclination, and fracture reduction. MAIN OUTCOME MEASUREMENTS AND RESULTS: Transarticular distraction resulted in a substantial decrease of the articular pressure, averaging -158.1 mmHg. Palmar flexion resulted in a mean pressure increase of 91.8 mmHg. The reduction of the fracture using a combination of distraction, palmar flexion and ulnar deviation resulted in either an increase or decrease of articular pressure, but always with a tendency toward progressive normalization of the pressure, with a mean slope of 3.2 mmHg/min. CONCLUSIONS AND CLINICAL RELEVANCE: The phenomena leading to the reduction of distal radius fractures could be related in part to a decrease of the intraarticular pressure, which may be responsible for a suction effect on the intraarticular bone fragments.

Predictive accuracy of continuous propofol infusions in neurosurgical patients: comparison of pharmacokinetic models.

The performance of 10 pharmacokinetic models in predicting blood propofol concentrations was evaluated in patients during neurosurgical anesthesia. Eight patients-ASA category I or II, aged 49 +/- 18-years, weighing 71 +/- 20 kg, and scheduled for routine neurosurgery-were anesthetized with propofol and sufentanil using Ohmeda pumps controlled with a personal computer. Sufentanil was administered as a bolus of 0.3 microgram.kg-1, 5 min before induction of anesthesia, and infused at a constant rate of 0.5 microgram.kg-1.h-1 throughout the study. At induction, propofol was administered as a bolus of 1.5 mg.kg-1 followed by a continuous infusion of 6 mg.kg-1.h-1. During surgery, the propofol infusion rate was deliberately increased by 2 mg.kg-1.h-1 every 15 min up to 12 mg.kg-1.h-1. Arterial blood samples were drawn at the end of each infusion step for measurement of propofol concentrations by high-performance liquid chromatography. Measured propofol concentrations were compared with theoretical concentrations derived from 10 published pharmacokinetic models designed in different clinical settings. Each model has been assessed by calculating the median of the performance error, the median of the absolute performance error, and their 10th and 90th percentiles. Models designed for certain categories, such as children, young, or elderly patients who received propofol as a bolus injection, showed a bad predictive accuracy. The models of Gepts et al. (Anesth Analg 1987; 66:1256-1263, Anaesthesia 1988; 43(suppl):8-13), Tackley et al. (Br J Anaesth 1989;62:46-53), and Cockshott (Postgrad Med J 1985;61:55), derived from healthy patients receiving continuous propofol infusions, provided the best agreement between expected and measured propofol concentrations; they showed bias and inaccuracy lower than 17%. In conclusion, the accurate prediction of blood propofol concentrations from different continuous infusion rates in ASA I or II patients requires the selection of appropriate pharmacokinetic models derived from similar categories of patients and using a similar technique of propofol administration. However, in clinical practice, the selection of a specific set among the appropriate models is balanced by the interindividual variability in blood propofol concentrations adjusted to clinical effects.