Facilitated self-reported anaesthetic medication errors before and after implementation of a safety bundle and barcode-based safety system.

BACKGROUND: Anaesthetic medication administration errors are a significant threat to patient safety. In 2002, we began collecting data about the rate and nature of anaesthetic medication errors and implemented a variety of measures to reduce errors. METHODS: Facilitated self-reporting of errors was carried out in 2002-2003. Subsequently, a medication safety bundle including 'smart' infusion pumps were implemented. During 2014 facilitated self-reporting commenced again. A barcode-based medication safety system was then implemented and the facilitated self-reporting was continued through 2015. RESULTS: During 2002-2003, a total of 11 709 paper forms were returned. There were 73 reports of errors (0.62% of anaesthetics) and 27 reports of intercepted errors (0.23%). During 2014, 14 572 computerised forms were completed. There were 57 reports of errors (0.39%) and 11 reports of intercepted errors (0.075%). Errors associated with medication infusions were reduced in comparison with those recorded in 2002-2003 (P<0.001). The rate of syringe swap error was also reduced (P=0.001). The reduction in error rate between 2002-2003 and 2014 was statistically significant (P=0.0076 and P=0.001 for errors and intercepted errors, respectively). From December 2014 through December 2015, 24 264 computerised forms were completed after implementation of a barcode-based medication safety system. There were 56 reports of errors (0.23%) and six reports of intercepted errors (0.025%). Vial swap errors in 2014-2015 were significantly reduced compared with those in 2014 (P=0.004). The reduction in error rate after implementation of the barcode-based medication safety system was statistically significant (P=0.0045 and P=0.021 for errors and intercepted errors, respectively). CONCLUSIONS: Reforms intended to reduce medication errors were associated with substantial improvement.

Stress (Takotsubo) Cardiomyopathy During Liver Transplantation: Case Study and Literature Review.

A case of stress (takotsubo) cardiomyopathy (TC) that occurred intraoperatively during liver transplantation surgery was identified by transesophageal echocardiography. Only a few cases of TC occurring during liver transplantation have been reported to date. Unlike other cases reported, TC occurred during the anhepatic stage of the liver transplantation, with subsequent complete recovery. Notwithstanding the large number of cases of TC in the perioperative settings reported worldwide, the exact reasons of this syndrome occurring intraoperatively as well as precipitating factors and conditions remain mostly unknown.

Combined use of high-frequency jet ventilation and abdominal lift for laparoscopic cholecystectomy in a patient with glottic impairment.

Effective airway management during laparoscopic anesthesia is important to minimize the adverse consequences of the carbon dioxide (CO2) pneumoperitoneum (PP). During PP, reduced respiratory excursion and tidal volumes with increased CO2 absorption may lead to hypoxia, hypercapnia, and respiratory acidosis. Although these problems can usually be avoided by use of positive pressure ventilation and an endotracheal tube, patients with a restricted airway who cannot be intubated pose a unique challenge. High-frequency jet ventilation (HFJV) has been described as an alternative to endotracheal intubation in other settings. The use of the small-diameter jet tube allows relatively unobstructed access to the larynx during laryngeal surgery. In patients with glottic impairment related to vocal fold immobility, jet ventilation allows positive pressure ventilation without the use of an endotracheal tube or tracheostomy in cases where lung and diaphragmatic compliance permit adequate excursion for ventilation and glottal diameter permits an adequate outflow of air. In this report, we describe the successful use of HFJV combined with an abdominal lifting technique and low-pressure PP for laparoscopic surgery in a patient with glottic compromise related to vocal fold immobility. Using these techniques, a laparoscopic cholecystectomy was performed successfully without endotracheal intubation or the need for a tracheostomy.

The effect of bispectral index monitoring on end-tidal gas concentration and recovery duration after outpatient anesthesia.

We performed this study to determine whether instituting monitoring of bispectral index (BIS) throughout an entire operating room would affect end-tidal gas concentration (as a surrogate for anesthetic use) or speed of recovery after outpatient surgery. Primary caregivers (n = 69) were randomly assigned to a BIS or non-BIS Control group with cross-over at 1-mo intervals for 7 mo. Data were obtained in all outpatients except for those having head-and-neck surgery. Mean end-tidal gas concentration and total recovery duration were compared by unpaired t-test. Overall, 469 patients (80%) received propofol for induction and sevoflurane for maintenance. This homogeneous group was selected for statistical analysis. Mean end-tidal sevoflurane concentration was 13% less in the BIS group (BIS, 1.23%; Control, 1.41%; P < 0.0001); differences were most evident when anesthesia was administered by first-year trainees. Mean BIS values were 47 in the BIS-Monitored group. Total recovery was 19 min less with BIS monitoring in men (BIS group, 147 min; Controls, 166 min; P = 0.035), but not different in women. We conclude that routine application of BIS monitoring is associated with a modest reduction in end-tidal sevoflurane concentration. In men, this may correlate with a similar reduction (11%) in recovery duration.

A randomized double-blinded multicenter comparison of remifentanil versus fentanyl when combined with isoflurane/propofol for early extubation in coronary artery bypass graft surgery.

UNLABELLED: We compared a fentanyl/isoflurane/propofol regimen with a remifentanil/isoflurane/propofol regimen for fast-track cardiac anesthesia in a prospective, randomized, double-blinded study on patients undergoing elective coronary artery bypass graft surgery. Anesthesia was induced with a 1-min infusion of 0.5 mg/kg propofol followed by 10-mg boluses of propofol every 30 s until loss of consciousness. After 0.2 mg/kg cisatracurium, a blinded continuous infusion of remifentanil at 1 microg. kg(-1). min(-1) or the equivalent volume rate of normal saline was then started. In addition, a blinded bolus syringe of 1 microg/kg remifentanil or 10 microg/kg fentanyl, respectively, was given over 3 min. Blinded remifentanil, 1 microg. kg(-1). min(-1) (or the equivalent volume rate of normal saline), together with 0.5% isoflurane, were used to maintain anesthesia. Significantly more patients (P < 0.01) in the fentanyl regimen experienced hypertension during skin incision and maximum sternal spread compared with patients in the remifentanil regimen. There were no differences between the groups in time until extubation, discharge from the surgical intensive care unit, ST segment and other electrocardiogram changes, catecholamine levels, or cardiac enzymes. The remifentanil-based anesthetic (consisting of a bolus followed by a continuous infusion) resulted in significantly less response to surgical stimulation and less need for anesthetic interventions compared with the fentanyl regimen (consisting of an initial bolus, and followed by subsequent boluses only to treat hemodynamic responses) with both drug regimens allowing early extubation. IMPLICATIONS: Both fentanyl and the newer opioid remifentanil, when each is combined with isoflurane and propofol, allowed for fast-track cardiac anesthesia. The remifentanil regimen used in this study resulted in significantly less hemodynamic response to surgical stimulation.

The efficacy and resource utilization of remifentanil and fentanyl in fast-track coronary artery bypass graft surgery: a prospective randomized, double-blinded controlled, multi-center trial.

UNLABELLED: We compared (a) the perioperative complications; (b) times to eligibility for, and actual time of the following: extubation, less intense monitoring, intensive care unit (ICU), and hospital discharge; and (c) resource utilization of nursing ratio for patients receiving either a typical fentanyl/isoflurane/propofol regimen or a remifentanil/isoflurane/propofol regimen for fast-track cardiac anesthesia in 304 adults by using a prospective randomized, double-blinded, double-dummy trial. There were no differences in demographic data, or perioperative mortality and morbidity between the two study groups. The mini-mental status examination at postoperative Days 1 to 3 were similar between the two groups. The eligible and actual times for extubation, less intense monitoring, ICU discharge, and hospital discharge were not significantly different. Further analyses revealed no differences in times for extubation and resource utilization after stratification by preoperative risk scores, age, and country. The nurse/patient ratio was similar between the remifentanil/isoflurane/propofol and fentanyl/isoflu-rane/propofol groups during the initial ICU phase and less intense monitoring phase. Increasing preoperative risk scores and older age (>70 yr) were associated with longer times until extubation (eligible), ICU discharge (eligible and actual), and hospital discharge (eligible and actual). Times until extubation (eligible and actual) and less intense monitoring (eligible) were significantly shorter in Canadian patients than United States' patients. However, there was no difference in hospital length of stay in Canadian and United States' patients. We conclude that both anesthesia techniques permit early and similar times until tracheal extubation, less intense monitoring, ICU and hospital discharge, and reduced resource utilization after coronary artery bypass graft surgery. IMPLICATIONS: An ultra-short opioid technique was compared with a standard fast-track small-dose opioid technique in coronary artery bypass graft patients in a prospective randomized, double-blinded controlled study. The postoperative recovery and resource utilization, including stratification of preoperative risk score, age, and country, were analyzed.

Intraindividual variability in male hepatic CYP3A4 activity assessed by alfentanil and midazolam clearance.

Clinical investigations using isoform-selective probes to phenotype cytochrome P450 activity and interaction studies using isoform-selective inhibitors to determine P450 involvement in drug metabolism assume minimal interday variability in P450 activity. CYP3A4 is the most abundant human P450 isoform and metabolizes approximately half of all therapeutic agents. This investigation evaluated interday variability in hepatic CYP3A4 activity in males, using the clearances of midazolam and alfentanil as metabolic probes. Midazolam (1 mg) followed 1 hour later by alfentanil (20 micrograms/kg) were administered by intravenous bolus to 9 nonsmoking male volunteers (ages 30 +/- 8 years). Drug administration was repeated 12 and 20 days later. Venous plasma midazolam and alfentanil concentrations were determined by gas chromatography/mass spectrometery. Drug clearances were determined by noncompartmental and multiexponential analysis. There were no significant interday differences in plasma drug concentrations or clearances (3.9 +/- 1.4, 3.9 +/- 1.7, and 4.2 +/- 1.7 ml/kg/min for alfentanil, respectively, and 6.6 +/- 2.0, 7.9 +/- 2.4, and 7.9 +/- 2.5 ml/kg/min for midazolam, respectively, on days 1, 13, and 21 [mean +/- SD]). Interday variability in clearance was 13% +/- 6% and 19% +/- 12% for alfentanil and midazolam, respectively. Interday variability in the clearance of these probes, and presumably hepatic CYP3A4 activity, was small compared with interindividual variability. Consideration of interday variability in the hepatic metabolism of CYP3A4 substrates does not appear significant in the design of clinical trials.

Does ketamine-mediated N-methyl-D-aspartate receptor antagonism cause schizophrenia-like oculomotor abnormalities?

Evidence from histological and pharmacological challenge studies indicates that N-methyl-D-aspartate (NMDA) receptor hypofunction may play an important role in the pathophysiology of schizophrenia. Our goal was to characterize effects of NMDA hypofunction further, as related to schizophrenia-associated neuropsychological impairment. We administered progressively higher doses of ketamine (target plasma concentrations of 50, 100, 150, and 200 ng/ml) to 10 psychiatrically healthy young men in a randomized, single-blind, placebo-controlled design and assessed oculomotor, cognitive, and symptomatic changes. Mean ketamine plasma concentrations approximated target plasma concentrations at each infusion step. Verbal recall, recognition memory, verbal fluency, pursuit tracking, visually guided saccades, and fixation all deteriorated significantly during ketamine infusion; lateral gaze nystagmus explained some, but not all, of the smooth pursuit abnormalities. We concluded that ketamine induces changes in recall and recognition memory and verbal fluency reminiscent of schizophreniform psychosis. During smooth pursuit eye tracking, ketamine induces nystagmus as well as abnormalities characteristic of schizophrenia. These findings help delineate the similarities and differences between schizophreniform and NMDA-blockade-induced cognitive and oculomotor abnormalities.

Adverse effects of opioid agonists and agonist-antagonists in anaesthesia.

The traditional view of opioids held that the individual opioid agonists shared the same mechanism of action, differing only in their potency and pharmacokinetic properties. However, recent advances in opioid receptor pharmacology have made this view obsolete. Distinguishing features of the synthetic opioid agonists are related, at least in part, to variation in affinity and intrinsic efficacy at multiple opioid receptors. Respiratory depression is the opioid adverse effect most feared by anaesthesiologists. Specific kappa-receptor agonists produce analgesia with little or no respiratory depression. There are a number of commercially available kappa-receptor partial agonist drugs, the so-called agonist-antagonist or nalorphine-like opioids, which appear to have a limited effect on breathing. Within the series of fentanyl analogues there are differences in behaviour towards particular opioid receptors and there is evidence for subtle differences in respiratory depressant effects. Pethidine (meperidine) causes histamine release and myocardial depression, while the fentanyl analogues do not. Pethidine has atropine-like effects on heart rate, while fentanyl analogues reduce heart rate by a vagomimetic action. Severe bradycardia or even asystole is possible with fentanyl analogues, especially in conjunction with the vagal stimulating effects of laryngoscopy. Fentanyl analogues often produce minor reductions in blood pressure, and occasionally severe hypotension by centrally mediated reduction in systemic vascular resistance. Muscle rigidity and myoclonic movement occurs frequently during induction of anaesthesia with larger doses of opioids. Fentanyl and alfentanil have been reported to produce localised temporal lobe electrical seizure activity in patients with complex partial epilepsy. There are probably fewer biliary effects with agonist-antagonist opioids than the agonist opioids. The mechanism of adverse effects after spinal administration is distinctly different for morphine, which is very water soluble, compared with more lipid-soluble opioids. The systemic absorption of morphine after intrathecal or epidural administration is very slow, resulting in long duration of analgesia and low plasma concentrations, while lipid-soluble opioids are rapidly absorbed into the circulation and redistributed to the brain. The serotonin syndrome may result from coadministration of pethidine, dextromethorphan, pentazocine or tramadol with monoamine oxidase inhibitors (MAOIs) or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). There are clinically important interactions between opioids and hypnosedatives, resulting in synergistic effects on sedation, breathing and blood pressure.

Psychedelic effects of ketamine in healthy volunteers: relationship to steady-state plasma concentrations.

BACKGROUND: Ketamine has been associated with a unique spectrum of subjective "psychedelic" effects in patients emerging from anesthesia. This study quantified these effects of ketamine and related them to steady-state plasma concentrations. METHODS: Ketamine or saline was administered in a single-blinded crossover protocol to 10 psychiatrically healthy volunteers using computer-assisted continuous infusion. A stepwise series of target plasma concentrations, 0, 50, 100, 150, and 200 ng/ml were maintained for 30 min each. After 20 min at each step, the volunteers completed a visual analog (VAS) rating of 13 symptom scales. Peripheral venous plasma ketamine concentrations were determined after 28 min at each step. One hour after discontinuation of the infusion, a psychological inventory, the hallucinogen rating scale, was completed. RESULTS: The relation of mean ketamine plasma concentrations to the target concentrations was highly linear, with a correlation coefficient of R = 0.997 (P = 0.0027). Ketamine produced dose-related psychedelic effects. The relation between steady-state ketamine plasma concentration and VAS scores was highly linear for all VAS items, with linear regression coefficients ranging from R = 0.93 to 0.99 (P < 0.024 to P < 0.0005). Hallucinogen rating scale scores were similar to those found in a previous study with psychedelic doses of N,N-dimethyltryptamine, an illicit LSD-25-like drug. CONCLUSIONS: Subanesthetic doses of ketamine produce psychedelic effects in healthy volunteers. The relation between steady-state venous plasma ketamine concentrations and effects is highly linear between 50 and 200 ng/ml.

Cost-effective reduction of neuromuscular-blocking drug expenditures.

BACKGROUND: Anesthetic drug expenditures have been a focus of cost-containment efforts. The aim of this study was to determine whether expenditures for neuromuscular-blocking agents could be reduced without compromising outcome, and to determine whether such a cost-effective pattern of neuromuscular blocker use could be sustained. METHODS: Education, practice guidelines, and paperwork barriers were used to persuade anesthesiologists to substitute low-cost neuromuscular-blocking drugs (pancuronium or a metocurine-pancuronium combination) for a more costly neuromuscular-blocking drug (vecuronium). Neuromuscular-blocking drug use in all patients during a historical control period (6 months; n = 4,804) was compared with that during two consecutive 1-yr periods of intervention (n = 9,761/n = 10,695). Expenditures for vecuronium and for all neuromuscular-blocking drugs were compared for the control and intervention periods. The rate of complications related to neuromuscular-blocking drugs was determined by an ongoing continuous quality improvement program. RESULTS: Vecuronium use decreased by 76% during the first and second yr of intervention, compared with the historical period (P < 0.01). The cost of neuromuscular-blocking drugs decreased by 31% (P < 0.01) and 47% (P < 0.01) for the first and second yr, respectively. The complication rate related to neuromuscular-blocking drugs was 0.081% in the historical period and 0.11% and 0.093% during the intervention periods (P = 0.29 and 0.41). CONCLUSION: Practice guidelines, education, and paperwork barriers used together substantially reduced the expenditures for neuromuscular-blocking drugs for 2 yr without adversely affecting clinical outcome.

Assessment of cytochrome P450 3A4 activity during the menstrual cycle using alfentanil as a noninvasive probe.

BACKGROUND: Gender-dependent differences in cytochrome P450 activity, drug metabolism, drug elimination, and their clinical consequences are increasingly apparent. P450 3A4 is the most abundant P450 isoform in the human liver and is responsible for metabolizing a vast and diverse assortment of therapeutic agents, including opioids, benzodiazepines, and local anesthetics. P450, 3A4 activity is higher in women, influenced by steroid hormone levels, and is speculated to vary during the menstrual cycle. This investigation tested the hypothesis that P450 3A4 activity varies during the menstrual cycle. Alfentanil clearance was used as a metabolic probe for P450 3A4 activity. METHODS: Alfentanil (20 micrograms/kg bolus) was administered to nine nonsmoking, nonpregnant female volunteers (age, 26 +/- 5 yr) with normal menstrual cycles on three separate occasions during the same menstrual cycle: days 2 (menstrual phase), 13 (estrogen peak), and 21 (progesterone peak). Venous plasma alfentanil concentrations were determined by gas chromatography-mass spectrometry. Alfentanil clearance was determined by noncompartmental methods and by a three-compartment model with both pooled population and two-stage analysis. RESULTS: There was no significant difference in any measure of alfentanil clearance. Noncompartmental clearances (mean +/- SD) were 3.62 +/- 0.76, 3.81 +/- 0.96, and 3.60 +/- 0.84 ml/kg/ min, respectively, on days 2, 13, and 21 of the menstrual cycle. CONCLUSIONS: Alfentanil clearances were not different on menstrual cycle days 2, 13, and 21, strongly suggesting no change in P450 3A4 activity. Menstrual cycle differences in alfentanil clearances do not contribute to interindividual variability in alfentanil disposition in women. If other P450 3A4 substrates are comparable, then menstrual cycle variability in their metabolism may not be a consideration in dosing or in the design of pharmacokinetic investigations.

Transition to post-operative epidural or patient-controlled intravenous analgesia following total intravenous anaesthesia with remifentanil and propofol for abdominal surgery.

Remifentanil is an ultrashort acting mu opioid, well suited to total intravenous (i.v.) anaesthesia. Pain immediately following emergence from anaesthesia is a potential problem because of the rapid offset. This study investigated the transition from remifentanil/propofol total intravenous anaesthesia to post-operative analgesia with epidural or patient controlled analgesia morphine in 22 patients undergoing major abdominal surgery. A remifentanil post-operative infusion initiated during emergence was titrated in the recovery room for 30 min, at which time 14% of patients had a pain score of 2 and 86% had pain scores of 0 or 1 (0 = no pain; 1 = mild pain; 2 = moderate pain; 3 = severe pain), at a mean infusion rate of 0.086 microgram kg-1 min-1. A smooth transition was then made to either epidural analgesia or patient controlled analgesia with morphine; pain scores were not significantly changed during the transition. Nausea occurred in 16 of the 22 patients, but only following administration of morphine. Epidural analgesia produced significantly lower pain scores on the surgical ward compared with patient controlled analgesia.

Assessment of low-flow sevoflurane and isoflurane effects on renal function using sensitive markers of tubular toxicity.

BACKGROUND: Carbon dioxide absorbents degrade sevoflurane, particularly at low gas flow rates, to fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A). Compound A causes renal proximal tubular injury in rats but has had no effect on blood urea nitrogen (BUN) or creatinine concentrations in patients. This investigation compared the effects of low-flow sevoflurane and isoflurane on renal tubular function in surgical patients using conventional (BUN and creatinine) and finer indices of renal injury, specifically those biomarkers sensitive for compound A toxicity in rats (glucosuria, proteinuria, and enzymuria [N-acetyl-beta-D-glucosaminidase (NAG) and alpha-glutathione-S-transferase (alpha GST)]). METHODS: Consenting patients with normal preoperative renal function at two institutions were randomized to receive sevoflurane (n = 36) or isoflurane (n = 37) in oxygen and air. Total gas flow was 1 l/min, opioid doses were minimized, and barium hydroxide lime was used to maximize anesthetic degradation. Inspiratory and expiratory compound A concentrations were quantified every 30-60 min. Blood and urine were obtained before and 24-72 h after anesthesia for laboratory evaluation. RESULTS: Sevoflurane and isoflurane groups were similar with respect to age, weight, sex, American Society of Anesthesiologists status, anesthetic duration (3.7 or 3.9 h), and anesthetic exposure (3.6 or 3 minimum alveolar concentration [MAC]-hour). Maximum inspired compound A concentration (mean +/- standard deviation) was 27 +/- 13 ppm (range, 10-67 ppm). Areas under the inspired and expired compound A concentration versus time curves (AUC) were 79 +/- 54-ppm-h (range, 10-223 ppm-h) and 53 +/- 40 ppm-h (range, 6-159 ppm-h), respectively. There was no significant difference between anesthetic groups in postoperative serum creatinine or BUN, or urinary excretion of protein, glucose, NAG, proximal tubular alpha GST, or distal tubular pi GST. There was no significant correlation between compound A exposure (AUC) and protein, glucose, NAG, alpha GST, or pi GST excretion. Postoperative alanine and aspartate aminotransferase concentrations were not different between the anesthetic groups, and there were no significant correlations between compound A exposure and alanine or aspartate aminotransferase concentrations. CONCLUSIONS: The renal tubular and hepatic effects of low-flow sevoflurane and isoflurane were similar as assessed using both conventional measures of hepatic and renal function and more sensitive biochemical markers of renal tubular cell necrosis. Moderate duration low-flow sevoflurane anesthesia, during which compound A formation occurs, appears to be as safe as low-flow isoflurane anesthesia.

A multicenter evaluation of remifentanil for early postoperative analgesia.

We evaluated the use of an infusion of remifentanil to provide postoperative analgesia during recovery from total intravenous anesthesia (TIVA) with remifentanil and propofol. One hundred fifty-seven patients from seven medical centers underwent abdominal, spine, joint replacement, or thoracic surgery. Remifentanil was titrated in an effort to limit pain to 0 or 1 on a 0-3 scale. At the end of the 30-min titration period, 78% of infusion rates were in the range of 0.05 to < or = 0.15 microgram.kg-1.min-1, 5% were < 0.05 microgram.kg-1.min-1, and 17% were > 0.15 microgram.kg-1.min-1. Pain scores were 0 or 1 in 64% of patients. Nausea occurred in 35% and emesis in 8% of patients; the peak incidence of nausea followed discontinuation of the remifentanil infusion at the time of administering morphine. Respiratory adverse events (oxygen saturation by pulse oximetry [Spo2] < 90% or respiratory rate < 12) affected 29% of patients. Apnea occurred in 11 patients (7.0%). There was a large variation in the incidence of respiratory depression between the centers, ranging from 0 to 75%. The explanation for the large variability in respiratory outcome was not evident.

A multicenter evaluation of total intravenous anesthesia with remifentanil and propofol for elective inpatient surgery.

Remifentanil is a mu-opioid receptor agonist with a context sensitive half-time of 3 min and an elimination half-life < or = 10 min. This study sought to evaluate the efficacy of remifentanil and propofol total intravenous anesthesia (TIVA) in 161 patients undergoing inpatient surgery. Remifentanil 1 microgram/kg was given intravenously (i.v.) followed by one of two randomized infusion rates: small dose (0.5 micrograms.kg-1.min-1) or large dose (1 microgram.kg-1.min-1). Propofol (0.5-1.0 mg/kg i.v. bolus and 75 micrograms.kg-1.min-1 infusion) and vecuronium were also given. Remifentanil infusions were decreased by 50% after tracheal intubation. End points included responses (hypertension, tachycardia, and somatic responses) to tracheal intubation and surgery. More patients in the small-dose than in the large-dose group responded to tracheal intubation with hypertension and/or tachycardia (25% vs 6%; P = 0.003) but there were no other differences between groups in intraoperative responses. Recovery from anesthesia was within 3-7 min in both groups. The most frequent adverse events were hypotension (systolic blood pressure [BP] < 80 mm Hg or mean BP < 60 mm Hg) during anesthesia induction (10% small-dose versus 15% large-dose group; P = not significant [NS]) and hypotension (27% small-dose versus 30% large-dose group; P = NS), and bradycardia (7% small-dose versus 19% large-dose group; P = NS) during maintenance. In conclusion, when combined with propofol 75 micrograms.kg-1.min-1, remifentanil 1 microgram/kg i.v. as a bolus followed by an infusion of 1.0 microgram.kg-1.min-1 effectively controls responses to tracheal intubation. After tracheal intubation, remifentanil 0.25-4.0 micrograms.kg-1.min-1 effectively controlled intraoperative responses while allowing for rapid emergence from anesthesia.

Syringe pumps for infusion of vasoactive drugs: mechanical idiosyncrasies and recommended operating procedures.

Syringe pumps for vasoactive infusions have the advantages of small size and weight, portability, and low cost of the disposable components. However, limited syringe capacity necessitates the use of high drug concentrations, and the accidental delivery of even a small volume of infusate could seriously alter the patient's hemodynamics. To determine the circumstances under which drug delivery might be delayed, or inadvertent boluses could be delivered into the manifold, two brands of commercially available clinical syringe pumps were connected to a stopcock manifold via small-bore tubing and a series of tests were performed. When the syringe pumps were operated at 3 mL/h against a closed stopcock, the pumps' occlusion alarms did not sound for 18-22 min, and when the stopcock subsequently was opened, 0.6-0.9 mL of infusate was delivered as a bolus. Elevating the syringe pump by 120 cm resulted in the delivery of up to 0.5 mL of infusate with the pump turned off. When a syringe pump operating at 6 mL/h was turned off, typically an additional 0.05 mL was delivered during the ensuing 2-3 min. Depending upon the method used to flush the tubing prior to use, delays in drug delivery of 2-3 min occurred at an infusion rate of 3 mL/h. These observations emphasize the need for careful equipment setup and proper use of the manifold stopcocks to avoid unintended drug administration or delay in drug administration.

Electroencephalogram, cerebral metabolic, and vascular responses to propofol anesthesia in dogs.

Previous studies on the cerebral effects of propofol report conflicting results regarding the cerebral metabolic rate for oxygen (CMRO2), cerebral blood flow (CBF), autoregulation of CBF, intracranial pressure, and cerebral perfusion pressure (CPP). The present studies were designed to examine these issues as well as propofol effects on the CBF responses to hypocapnia and on the electroencephalogram (EEG) in a well-known canine model that permits continuous determination of EEG activity, CMRO2, CBF, and cerebrospinal fluid (CSF) pressure. Dogs were studied at normocapnia (n = 6) and at hypocapnia (n = 6) during three doses of propofol (12, 24, and 48 mg kg(-1) h(-1)) and during a combination of propofol and elevated (20-25 mm Hg) CSF pressure. In both groups propofol caused dose-related decreases of EEG power and number of waveforms, CMRO2 (by 25-30%), and CBF (by 73-76%). The cerebral vasoconstrictor response to hypocapnia was preserved at all three doses of propofol. Autoregulation of CBF was preserved at the low and moderate doses of propofol but was impaired at the high dose of propofol (where CPP decreased significantly to approximately 41 +/- 13 mm Hg) and at the high dose of propofol combined with elevated CSF pressure (where CPP decreased significantly to approximately 32 +/- 12 mm Hg). Cerebrospinal fluid pressure decreased (by 33-42%) when the continuous infusion of propofol was begun, but returned to prepropofol values as infusion of propofol continued. The authors conclude that low and moderate doses of propofol decrease EEG activity and CMRO2, causing an associated decrease of CBF and CSF pressure. Autoregulation of CBF and cerebral vascular CO2 reactivity are preserved at these propofol doses. In contrast, high dose propofol significantly decreases CPP, resulting in impaired autoregulation of CBF.

Effect of serum protein binding on the entry of lidocaine into brain and cerebrospinal fluid in dogs.

To test the hypothesis that lidocaine passage into the central nervous system is a function of free rather than total lidocaine concentration, we examined the effect of serum protein binding on the distribution of lidocaine into brain and cerebrospinal fluid (CSF) in dogs. Six of the 13 dogs studied were pretreated with rifampin to induce a 4-fold increase (P = 0.019) in serum concentration of alpha 1-acid glycoprotein, which is a major binding protein for lidocaine. The dogs were anesthetized and prepared surgically to obtain samples of cortical brain tissue or CSF from the cisterna magna. Lidocaine at a dose of 3 mg/kg was infused intravenously over 15 s. Arterial blood and brain cortex or CSF were sampled serially during a 60-min interval and analyzed for lidocaine content. Unbound or free fraction of lidocaine in serum was measured by equilibrium dialysis. Rifampin pretreatment led to a significant decrease in average serum free fraction of lidocaine, from 0.24 +/- 0.08 to 0.080 +/- 0.030 (P less than 0.001). Total lidocaine concentration in serum was higher, but free lidocaine concentration was lower in the rifampin group. Equilibration of lidocaine between serum and brain or CSF was reached by 10 min after lidocaine administration. Rifampin-pretreated dogs had consistently lower partition ratios of lidocaine between brain and serum or between CSF and serum. A strong and positive correlation between time-averaged brain to serum or CSF to serum ratios and serum free fractions were observed (r = 0.92, P less than 0.001 for brain; r = 0.90, P less than 0.01 for CSF).(ABSTRACT TRUNCATED AT 250 WORDS)