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PubMed2004

Physicochemical properties of neuromuscular blocking agents and their impact on the pharmacokinetic-pharmacodynamic relationship.

BACKGROUND: Among the factors influencing the onset of action of neuromuscular blocking agents (NMBA), the potency (EC50) and the rate of equilibration between blood and the effect compartment (k(e0)) have been highlighted. Although these descriptors are intrinsically influenced by the physicochemical characteristics of the drug, the impact of lipid solubility, molecular weight and protein binding on pharmacokinetic-pharmacodynamic (PK-PD) descriptors has not been established for most NMBA. METHODS: The octanol/phosphate buffer distribution coefficients (logD) of various NMBA (vecuronium, rocuronium, mivacurium isomers (cis-cis, cis-trans and trans-trans), doxacurium, cisatracurium, atracurium, succinylcholine) were determined. The free fraction for each drug was measured using an ultrafiltration technique. PK-PD descriptors were obtained from selected clinical studies. Correlations between physicochemical parameters (including molecular weight) and PK-PD descriptors were assessed by linear or multiple linear regression. RESULTS: A wide range of log D (-4.15 for succinylcholine to 0.75 for vecuronium) and free fraction (from 31% for vecuronium to 80% for succinylcholine) is observed for NMBA. Molecular weight combined with either lipid solubility (r2=0.70; P=0.001) or free fraction (r2=0.84; P<0.001) were highly correlated with potency, while for k(e0) a greater degree of correlation was obtained when both lipid solubility and free fraction (r2=0.74; P=0.002) were included. CONCLUSIONS: The basic characteristics of NMBAs, namely, molecular weight, lipid solubility and protein binding, are strongly associated with the kinetics of the drug response.

Chemical Phenomena↗
PubMed2005

Influence of muscle relaxation on neuromonitoring of the recurrent laryngeal nerve during thyroid surgery.

BACKGROUND: The influence of muscle relaxation on the intra-operative neuromonitoring of the recurrent laryngeal nerve during thyroid surgery is unclear. METHODS: In a prospective study involving 200 patients undergoing elective thyroid surgery, the influence of muscle relaxation on neuromonitoring of the recurrent laryngeal nerve was investigated. The patients received balanced anaesthesia with oxygen-nitrous oxide-isoflurane, and rocuronium bromide was used as the non-depolarizing neuromuscular blocking agent. The degree of relaxation was monitored continuously by accelerometry [twitch (% TW)]. Summed action potentials (SAcP) obtained from the vocalis muscle were characterized by the area under the electromyographic curve expressed in millivolt seconds. RESULTS: Evoked potentials were obtainable in all patients and at all time points. With decreasing neuromuscular blockade a significant increase in the potentials evoked at the vocalis muscle was observed. At 0% TW SAcP was 1.27 (SD 1.02) mV s. An increase in TW to 10% was accompanied by an increase in SAcP to 2.68 (2.01) mV s (P<0.01). At a TW of 25%, mean SAcPs of 5.08 mV s were recorded. CONCLUSIONS: There was a significant difference in the degree of relaxation of the adductor pollicis muscle and the vocalis muscle. The laryngeal muscles exhibited a shorter response time than the adductor pollicis and recovered more quickly. These results confirm the feasibility of intra-operative neuromonitoring of the recurrent laryngeal nerve during neuromuscular blockade.

Action Potentials↗
PubMed2007

Influence of acute normovolaemic haemodilution on the dose-response relationship and time course of action of cisatracurium besylate.

BACKGROUND: Acute normovolaemic haemodilution (ANH) is an efficacious blood conservation strategy aiming at avoiding allogeneic blood transfusion. ANH was shown to increase the potency of vecuronium, atracurium, and rocuronium. The aim of our study was to investigate whether cisatracurium potency is altered with ANH. METHODS: Using the Relaxometer mechanomyograph, we compared cisatracurium dose-response relationship and time course of action in 60 patients randomly allocated to the ANH or control groups. Patients in each group were randomly allocated to receive one of three cisatracurium doses (30, 40, 50 microg kg(-1)) followed by a second supplemental dose to reach a total of 100 microg kg(-1). RESULTS: ANH did not result in a significant shift in cisatracurium log dose-probit dose-response curve. There was no significant difference in mean (95% confidence intervals) ED(50), ED(90), and ED(95) (effective doses required for 50, 90, and 95% first twitch depression) between the ANH group [29.5 (27-32), 50.4 (47.4-53.4), 58.7 (55.3-62) microg kg(-1)] and the control group [28.2 (25.3-31), 47.6 (44.9-50.3), 55.3 (52.5-58.1) microg kg(-1)], whereas there was no difference in mean (SD) Dur(25) and Dur(0.8) (time until 25% first twitch and 0.8 train-of-four ratio recoveries) between the ANH group [40.8 (5.9), 64.7 (8.4) min] and the control group [42.2 (7.6), 66.5 (10.7) min]. CONCLUSIONS: Our results demonstrated that unlike other previously reported neuromuscular blocking drugs, ANH did not alter cisatracurium potency. Thus, cisatracurium would be the neuromuscular blocking drug of choice in patients who undergo surgery with ANH, as no dose adjustments are required.

Adult↗
PubMed2000

Comparison of different doses of remifentanil on the cardiovascular response to laryngoscopy and tracheal intubation.

We have compared three bolus and infusion regimens of remifentanil on the cardiovascular response to laryngoscopy and orotracheal intubation in three groups of 20 ASA I-II female patients, in a randomized, double-blind study. Patients in group 1 received glycopyrolate 200 micrograms i.v. followed by a bolus dose of remifentanil 1 microgram kg-1 over 30 s and an infusion of remifentanil at a rate of 0.5 microgram kg-1 min-1. The other patients received remifentanil 0.5 microgram kg-1 over 30 s and an infusion of 0.25 microgram kg-1 min-1 with (group 2) or without (group 3) pretreatment with glycopyrrolate 200 micrograms. All patients then received a sleep dose of propofol, rocuronium 0.6 mg kg-1 and 1% isoflurane with 67% nitrous oxide in oxygen. Laryngoscopy and tracheal intubation were performed 3 min later. Heart rate and arterial pressure were recorded at 1-min intervals from before induction of anaesthesia until 5 min after intubation. Baseline heart rate was similar in all groups, but decreased in group 3 (no glycopyrrolate) after induction and remained significantly lower after intubation compared with the other groups (P < 0.05). Heart rate and arterial pressure increased slightly after intubation in each group but there were no significant differences in mean arterial pressure between groups at any time. The incidence of bradycardia (one patient in group 2) and hypotension (two patients in groups 1 and 2 and three patients in group 3) was low.

Adult↗
PubMed1999

The costs of intense neuromuscular block for anesthesia during endolaryngeal procedures due to waiting time.

UNLABELLED: The goal of this double-blinded, prospective study was to compare the costs incurred by waiting time of intense neuromuscular block while posttetanic count (PTC) was maintained at 0-2 during jet ventilation. Fifty patients were randomized into five groups to receive atracurium (ATR), mivacurium (MIV), rocuronium (ROC), vecuronium (VEC), and succinylcholine (SUCC). PTC < or =2 was maintained until completion of laryngomicroscopy by administering additional doses of relaxants or by adjusting the speed of the infusion of SUCC. We compared waiting time, i.e., onset time and recovery time, and costs of intense neuromuscular block. The expenses due to waiting time were calculated based on the average costs in the otorhinolaryngological operating room in Tampere University Hospital: FIM 40 (approximately $8) per minute in 1997. MIV and SUCC differ favorably from ATR, ROC, and VEC when waiting time and costs are concerned. The recovery times with MIV and SUCC were considerably shorter than those with ATR, ROC, and VEC (P < 0.001 in all pairwise comparisons). Using the muscle relaxant with the longest waiting time instead of that with the shortest waiting time (difference 21.8 min) cost more than FIM 800 (approximately $160) extra per patient. IMPLICATIONS: In this randomized, double-blinded, prospective study, we evaluated the costs of intense neuromuscular block due to waiting time. Succinylcholine and mivacurium are the most economical muscle relaxants to use when intense neuromuscular block is mandatory. Using intermediate-acting muscle relaxants results in unduly prolonged recovery time and extra costs.

Adult↗
PubMed2000

Nondepolarizing neuromuscular blockers inhibit the serotonin-type 3A receptor expressed in Xenopus oocytes.

UNLABELLED: Molecular cloning and sequence comparison indicates a high degree of structural homology between muscle nicotinic acetylcholine (nACh) and serotonin-type 3 (5-HT(3A)) receptors, both members of the direct ligand-gated family of ion channels. Because of the structural similarities and common evolutionary origin of these receptors, neuromuscular blockers (competitive nACh antagonists) may demonstrate pharmacologic cross talk and exhibit attributes of 5-HT(3A) receptor antagonists. We examined six clinically-used neuromuscular blockers for their ability to antagonize currents flowing through the 5-HT(3A) receptors in voltage clamped Xenopus oocytes. The neuromuscular blockers reversibly inhibited the 5-HT(3A) receptor-gated current in the rank order potency of (IC50 mean +/- SEM): d-tubocurarine (0.046 +/- 0.003 microM), atracurium (0.40 +/- 0.03 microM), mivacurium (15.1 +/- 2.93 microM), vecuronium (16.3 +/- 2.24 microM), and rocuronium (19.5 +/- 2.31 microM). Gallamine was essentially inactive as a 5-HT(3A) receptor antagonist with an extrapolated IC50 of 1170 microM. We demonstrate that drugs classically known as competitive nACh receptor antagonists also block 5-HT(3A) receptors. It is likely that certain neuromuscular blockers share pharmacological properties with 5-HT(3A) receptor antagonists, such as a reduction in postoperative nausea and vomiting. With careful drug selection, pharmacological cross talk could potentially be used to minimize polypharmacy and optimize patient management. IMPLICATIONS: Muscle nicotinic acetylcholine and serotonin-type 3A (5-HT(3A)) receptors are similar. Therefore neuromuscular relaxants may block 5-HT(3A) receptors. Our pharmacological study demonstrates that neuromuscular relaxants, as with ondansetron, are 5-HT(3A) receptor antagonists. It is likely that certain neuromuscular relaxants exhibit ondansetron-like clinical properties, such as reduction in postoperative nausea and vomiting.

Animals↗
PubMed2000

Can succinylcholine be abandoned?

The elective use of succinylcholine in anesthesia has largely been abandoned because of unwanted side effects. Alternatives now exist for short, intermediate, or long elective surgical procedures. NMBDs are frequently used only to facilitate tracheal intubation; rapacuronium fills an important niche particularly for a short elective case (e.g., same-day surgery). However, an equally critical issue is whether there is a reliable replacement for succinylcholine for the treatment of laryngospasm or for rapid sequence induction in patients with "full stomachs." Succinylcholine produces more intense block in a shorter time at the laryngeal muscles, compared with the adductor pollicis, compared with vecuronium, rocuronium, mivacurium, and rapacuronium (30). Although most intubations can be facilitated with 80%-90% neuromuscular block, the ideal relaxant for a rapid sequence induction should produce uniformly complete neuromuscular blockade in 1 min. Variability in the degree of neuromuscular blockade and onset time can be compared for various relaxants by using the standard deviation (Table 1), the coefficient of variation (Table 2), or a plot of the degree of maximum neuromuscular block and the time to maximum block. Figure 1 shows such a plot for mivacurium (13). There is less variability in the maximum block at the larger dose of rapacuronium but still variability in onset time. Further studies will be important in defining the role of rapacuronium for rapid sequence induction in various clinical settings.

Anesthesia↗
PubMed2000

Postoperative recovery after desflurane, propofol, or isoflurane anesthesia among morbidly obese patients: a prospective, randomized study.

UNLABELLED: Recovery from anesthesia might be compromised in obese patients. Because of its pharmacological properties, desflurane might allow rapid postoperative recovery for these patients. We compared postoperative recovery for 36 obese patients randomized to receive either desflurane, propofol, or isoflurane to maintain anesthesia during laparoscopic gastroplasties. Anesthesia was induced with propofol and succinylcholine IV and was maintained with rocuronium, alfentanil, inhaled nitrous oxide, and the study drug. Immediate recovery (i.e., times from the discontinuation of anesthesia to tracheal extubation, eye opening, and the ability to state one's name) was measured. At the time of postanesthesia care unit (PACU) admission, arterial saturation and the ability of patients to move were recorded. In the PACU, intermediate recovery was measured by using sedation and psychometric evaluations, 30, 60, and 120 min postoperatively. Data were compared between groups by using the Kruskal-Wallis and chi(2) tests. Results were reported as means +/- SD. P: < 0.05, compared with desflurane, was considered significant. Immediate recovery occurred faster, and was more consistent, after desflurane than after propofol or isoflurane (times to extubation were 6 +/- 1 min, 13 +/- 8 min [P: < 0.05, compared with desflurane], and 12 +/- 6 min [P: < 0.05, compared with desflurane], respectively). At PACU admission, SpO(2) values were significantly higher and patient mobility was significantly better after desflurane than after isoflurane or propofol. Sedation was significantly less pronounced with desflurane at 30 and 120 min postoperatively. In morbidly obese patients, postoperative immediate and intermediate recoveries are more rapid after desflurane than after propofol or isoflurane anesthesia. This advantage of desflurane persists at least for 2 h after surgery and is associated with both an improvement in patient mobility and a reduced incidence of postoperative desaturation. IMPLICATIONS: In morbidly obese patients, postoperative immediate and intermediate recoveries are more rapid and consistent after desflurane than after propofol or isoflurane anesthesia.

Adult↗
PubMed2001

Oxygenation during one-lung ventilation: the effects of inhaled nitric oxide and increasing levels of inspired fraction of oxygen.

UNLABELLED: We studied whether inhaled nitric oxide (NO) would improve arterial oxygen tension (PaO(2)) and reduce the occurrence of oxygen saturation of hemoglobin (O(2)Hb) < 90% during one-lung ventilation (OLV). One-hundred-fifty-two patients were ventilated either with or without NO (20 ppm) with an inspired fraction of oxygen (FIO(2)) of either 0.3, 0.5, or 1.0 during OLV. Anesthesia was induced and maintained with propofol, remifentanil, and rocuronium IV, and lung separation was achieved with a double-lumen tube. During OLV, we set positive end-expiratory pressure at 5 cm H(2)O, peak pressure at 30 cm H(2)O, and end-tidal CO(2) at 30 mm Hg. The nonventilated lung was opened to room air and collapsed. During OLV, three consecutive measurements were performed every 10 min. The operated lung was temporarily ventilated if pulse oximetric saturation (SpO(2)) decreased to < 91%. SpO(2) <9 1% occurred in 2 of the 152 patients. SpO(2) overestimated O(2)Hb by 2.9% +/- 0.1%. NO failed to improve oxygenation or alter occurrence of O(2)Hb < 90% during OLV across all time points and all levels of FIO(2). Increasing FIO(2) increased oxygenation and decreased occurrence of O(2)Hb < 90% (P: < 0.001). At FIO(2) = 1, PaO(2) was higher (P < 0.01) and O(2)Hb < 90% rate tended to be lower (P = 0.1) during right versus left lung ventilation. PaO(2) was higher in patients undergoing pneumonectomy and lobectomy than in those undergoing metastasectomy or video-assisted operations (P < 0.05). IMPLICATIONS: Inhaled nitric oxide failed to improve oxygenation during one-lung ventilation. Oxygenation during one-lung ventilation was improved with increasing levels of FIO(2) during ventilation of the right versus the left lung and with increasing pathology of the nonventilated lung.

Adult↗
PubMed2001

The pharmacoeconomics of neuromuscular blocking drugs: a perioperative cost-minimization strategy in children.

UNLABELLED: The purpose of this investigation was to compare the costs of intermediate-acting neuromuscular blocking drugs in children during routine ambulatory surgery. We studied 200 healthy, 2-10-yr-old children undergoing elective dental restorative surgery. During Part 1 of the study, children received an inhaled anesthetic with halothane and nitrous oxide, whereas in Part 2, the anesthetic was IV propofol with nitrous oxide. The study drugs were atracurium, cisatracurium, mivacurium, rocuronium, and vecuronium. Patients were initially administered 2x the effective dose for 95% of the study drug. After recovery to 10% of baseline neuromuscular function, the neuromuscular blockade was rigidly maintained with an infusion of the study drug at about 10% of baseline function. Neuromuscular drug costs were approximated as drug usage x cost/unit. The initial drug costs were not substantially different for both Parts 1 and 2, but over time, mivacurium became the most expensive drug and cisatracurium the least expensive. In conclusion, based on current costs, cisatracurium is the least expensive intermediate-acting neuromuscular drug. IMPLICATIONS: For children undergoing minor ambulatory procedures of 1-2 h, and continuous intraoperative neuromuscular blockade is indicated, cisatracurium currently is the least expensive drug.

Anesthesia↗
PubMed2002

The Laryngeal Mask Airway ProSeal(TM) as a temporary ventilatory device in grossly and morbidly obese patients before laryngoscope-guided tracheal intubation.

UNLABELLED: We determined the efficacy of the laryngeal mask airway ProSeal(TM) (PLMA) as a temporary ventilatory device in morbidly obese patients before laryngoscope-guided tracheal intubation. Sixty patients (body mass index 35--60 kg/m(2)) scheduled for elective surgery, who preferred airway management under general anesthesia, were studied. The induction of anesthesia was with midazolam/fentanyl/propofol and maintenance was with sevoflurane 1%--3% in oxygen 100%. The PLMA was inserted and an effective airway established. Rocuronium was given IV for paralysis. Oropharyngeal leak pressure, ease of gastric tube placement, residual gastric volume, fiberoptic position of the airway/drainage tube, and ease of ventilation at a tidal volume of 8 mL/kg was determined. The PLMA was then removed and laryngoscope-guided tracheal intubation attempted. The number of insertion/intubation attempts (maximum two each) and time taken to establish an effective airway with each device were recorded. An effective airway was obtained at the first insertion attempt in 90% of patients (54/60) and at the second attempt in 10% (6/60). The time taken to provide an effective airway was 15 plus minus 7 s (7--42 s). Oropharyngeal leak pressure was 32 plus minus 8 cm H(2)O (12--40 cm H(2)O). The residual gastric volume was 36 plus minus 46 mL (0--240 mL). Positive pressure ventilation without air leaks was possible in 95% of patients (57/60). The vocal cords were seen from the airway tube in 75% of patients (45/60), but the esophagus was not seen. The fiberoptic view from the drainage tube revealed mucosa in 93% of patients (56/60) and an open upper esophageal sphincter in 7% (4/60). Tracheal intubation was successful at the first attempt in 90% of patients (54/60), at the second attempt in 7% (4/60), and failed in 3% (2/60). In these latter two patients, the PLMA was reinserted and surgery performed uneventfully with the PLMA. The time taken to tracheally intubate the patient was 13 plus minus 10 s (8--51 s). There were no episodes of hypoxia (SpO(2) <90%) or other adverse events. There were no differences in insertion success rate, or the time to successful insertion between the PLMA and laryngoscope-guided intubation. We conclude that the PLMA is an effective temporary ventilatory device in grossly or morbidly obese patients before laryngoscope-guided tracheal intubation. IMPLICATIONS: The laryngeal mask airway ProSeal(TM) is an effective temporary ventilatory device in grossly and morbidly obese patients before laryngoscope-guided tracheal intubation.

Adult↗
PubMed2002

The hemodynamic effects of rapacuronium in patients with coronary artery disease: succinylcholine and vecuronium compared.

UNLABELLED: Rapacuronium is a nondepolarizing muscle relaxant similar in structure to pancuronium, rocuronium, and vecuronium. Rapacuronium has a mild to moderate effect on heart rate and arterial blood pressure in ASA physical status I and II patients. However, rapacuronium was often administered after, e.g., thiopental, an inhaled anesthetic, and fentanyl, thus modifying or masking the hemodynamic effects of rapacuronium. In this study, we investigated the hemodynamic effects of rapacuronium and compared its effects with those of vecuronium and succinylcholine. Sixty patients scheduled to undergo routine coronary artery bypass grafting were selected to receive rapacuronium 1.5 mg/kg, vecuronium 0.1 mg/kg, or succinylcholine 1 mg/kg. Heart rate, blood pressure, pulmonary artery pressures, and cardiac index were measured at 30- and 60-s intervals during the 2 min after the induction of anesthesia with diazepam and for a 3-min period after study drug administration. The Rapacuronium group exhibited significantly larger decreases in blood pressure and systemic vascular resistance than the Vecuronium or Succinylcholine groups. One patient in the Rapacuronium group experienced cutaneous flushing associated with a 33% decrease in blood pressure. IMPLICATIONS: Rapacuronium is associated with a significantly larger decrease in blood pressure than succinylcholine or vecuronium, and this decrease should be considered when using rapacuronium in patients who cannot tolerate this decrease.

Adult↗
PubMed2002

The neuropathologic effects in rats and neurometabolic effects in humans of large-dose remifentanil.

UNLABELLED: Given in clinically relevant large doses to rats, mu-opioids produce limbic system hypermetabolism and histopathology. This investigation extends these observations, in both rats and humans, for the short-acting drug remifentanil, which allows more precise control and assessment of the effects of duration of opioid exposure. We performed two series of experiments: one in rats for neuropathologic effects and the second in humans for neurometabolic effects. Fifty mechanically ventilated rats received saline solution or remifentanil 20-160 microg x kg(-1) x min(-1) for 3 h, followed by neuropathologic evaluation 7 days later. Four volunteers underwent induction of anesthesia and endotracheal intubation with propofol and rocuronium administration followed by remifentanil infusion at 1-3 microg x kg(-1) x min(-1) with positron emission tomography evaluation of cerebral metabolic rate for glucose. In rats, dose-related electroencephalogram activation was evident and 19 of 40 remifentanil-treated rats showed brain damage, primarily in the limbic system (P < 0.01). In humans, cerebral metabolic rate for glucose in the temporal lobe increased from 6.29 +/- 0.32 to 7.68 +/- 1.05 mg x 100 g(-1) x min(-1) (P < 0.05). These data indicate that prolonged large-dose remifentanil infusion is neurotoxic in rats with congruent metabolic effects with brief infusion in humans and suggest that some adverse effects reported in rats may be clinically relevant. IMPLICATIONS: This study demonstrates dose-related remifentanil neurotoxicity in physiologically controlled rats with congruent brain metabolic effects in four humans undergoing positron emission tomography evaluation during brief large-dose remifentanil anesthesia. These data suggest that some adverse effects reported in rats may be clinically relevant.

Analgesics, Opioid↗
PubMed2002

Mild core hypothermia and anesthetic requirement for loss of responsiveness during propofol anesthesia for craniotomy.

UNLABELLED: Mild hypothermia may be induced during neurosurgery for brain protection. However, its effect on propofol requirement has not been defined. Accordingly, we tested the hypothesis that 3 degrees C of core hypothermia decreases the propofol blood concentration at which patients respond to command (CP50-awake) in neurosurgical patients. Forty patients were anesthetized with alfentanil 50 microg/kg i.v., nitrous oxide, propofol target-controlled infusion, and rocuronium. The bispectral index (version 3.12) was monitored continuously. Patients were randomized to a core temperature of 34 degrees C or 37 degrees C. At the end of surgery, neuromuscular blockade was reversed, nitrous oxide was ceased, and propofol was infused to achieve a blood target determined by the previous patient's response. Responsiveness to command was assessed 15 min later. Results were analyzed with logistic regression models; P < 0.05 was considered statistically significant. The CP50-awake of propofol was 3.05 microg/mL (95% confidence interval, 2.34-3.66). Propofol concentration, but not core temperature, predicted loss of response to command (odds ratio, 11.76; 95% confidence interval, 2.40-57.63; P < 0.01). Core temperature did not alter the relationship between bispectral index and response to command. Propofol infusion regimens may not require adjustment during mild hypothermia. IMPLICATIONS: Neurosurgical patients may be allowed to become mildly hypothermic during anesthesia in an effort to provide brain protection. Propofol maintenance infusion doses may not require adjustment in these patients.

Adult↗
PubMed1997

Using an anesthesia information management system as a cost containment tool. Description and validation.

BACKGROUND: Medical informatics provide a new way to evaluate the practice of medicine. Anesthesia automated record keepers have introduced anesthesiologists to computerized medical records. To derive useful information from the stored data requires programming that is not currently commercially available. The authors describe how they custom-programmed an automated record keeper's database to perform cost calculations, how they validated the programming, and how they used the data in a successful pharmaceutical cost-containment program. METHODS: The Arkive (San Diego, CA) automated record keeper database was programmed at Duke University Medical Center as an independent noncommercial project to calculate costs according to standard formulae and to follow adherence to Duke University Department of Anesthesiology's prescribing guidelines for anesthetic drugs. Validation of that programming (including analysis of discarded drugs) was accomplished by comparing database calculated costs with actual pharmacy distribution of drugs during a 1-month period. RESULTS: Validation data demonstrated a 99% accuracy rate for total costs of the drugs studied (atracurium, vecuronium, rocuronium, propofol, midazolam, fentanyl, and isoflurane). The study drugs represented approximately 67% of all drug costs for the period studied. CONCLUSIONS: Programming of an anesthesia automated record keeper's database yields essential information for management of an anesthetic practice. Accurate economic evaluation of anesthetic drug use is now possible. In the future, as definitive identification of best anesthetic practices that yield optimal patient outcomes and higher measures of patient satisfaction is pursued, large numbers of patients should be studied. This is only possible through database analysis and complete computerization of the perioperative medical record.

Anesthesiology↗
PubMed1999

Comparison of adenosine and remifentanil infusions as adjuvants to desflurane anesthesia.

BACKGROUND: Because adenosine has been alleged to produce both anesthetic and analgesic sparing effects, a randomized, double-blinded study was designed to compare the perioperative effects of adenosine and remifentanil when administered as intravenous adjuvants during general anesthesia for major gynecologic procedures. METHODS: Thirty-two women were assigned randomly to one of two drug treatment groups. After premedication with 0.04 mg/kg intravenous midazolam, anesthesia was induced with 2 micro/kg intravenous fentanyl, 1.5 mg/kg intravenous propofol, and 0.6 mg/kg intravenous rocuronium, and maintained with desflurane, 2%, and nitrous oxide, 65%, in oxygen. Before skin incision, an infusion of either remifentanil (0.02 microg x kg(-1) x min(-1)) or adenosine (25 microg x kg(-1) x min(-1)) was started and subsequently titrated to maintain systolic blood pressure, heart rate, or both within 10-15% of the preincision values. RESULTS: Adenosine and remifentanil infusions were effective anesthetic adjuvants during lower abdominal surgery. Use of adenosine (mean +/- SEM, 166+/-17 microg x kg(-1) x min(-1)) was associated with a significantly greater decrease in systolic blood pressure and higher heart rate values compared with remifentanil (mean +/- SEM, 0.2+/-0.03 microg kg(-1) x min(-1)). Total postoperative opioid analgesic use was 45% and 27% lower in the adenosine group at 0-2 h and 2-24 h after surgery, respectively. CONCLUSIONS: Adjunctive use of a variable-rate infusion of adenosine during desflurane-nitrous oxide anesthesia was associated with acceptable hemodynamic stability during the intraoperative period. Compared with remifentanil, intraoperative use of adenosine was associated with a decreased requirement for opioid analgesics during the first 24 h after operation.

Adenosine↗
PubMed1999

Effects of prophylactic nalmefene on the incidence of morphine-related side effects in patients receiving intravenous patient-controlled analgesia.

BACKGROUND: Opioid-related side effects associated with intravenous patient-controlled analgesia can be reduced by a low-dose naloxone infusion. The influence of nalmefene, a pure opioid antagonist with a longer duration of action, on opioid-related side effects has not been evaluated. This study was designed to determine the dose-response relation for nalmefene for the prevention of morphine-related side effects in patients receiving intravenous patient-controlled analgesia. METHODS: One hundred twenty women undergoing lower abdominal surgery were enrolled in the study. General anesthesia was induced using thiopental and rocuronium and maintained with desflurane, nitrous oxide, and fentanyl or sufentanil. All patients received neostigmine and glycopyrrolate to reverse residual neuromuscular blockade. No prophylactic antiemetics were administered. At the end of surgery, patients were randomized to receive saline, 15 microg nalmefene, or 25 microg nalmefene intravenously. The need for antiemetic and antipruritic drugs and the total consumption of morphine during the 24-h study were recorded. The incidences of postoperative nausea, vomiting, pruritus, and pain were recorded 30 min after patients were admitted to the postanesthesia care unit. In addition, patient remembrance of these side effects was noted at 24 h after operation. RESULTS: The need for antiemetic and antipruritic medications during the 24-h study period was significantly lower in the patients receiving nahmefene compared with those receiving placebo. However, the need to treat side effects was similar in the two nahmefene groups. Prophylactic administration of nalmefene reduced the patients remembrance of nausea and itching as assessed 24 h after operation. Although the total consumption of morphine during the 24-h study period was similar in the three groups, retrospectively patients who received nalmefene characterized their pain as less severe in the previous 24 h. CONCLUSION: Compared with placebo, prophylactic administration of nalmefene significantly decreased the need for antiemetics and antipruritic medications in patients receiving intravenous patient-controlled analgesia with morphine.

Adult↗
PubMed2001

Epidural lidocaine decreases sevoflurane requirement for adequate depth of anesthesia as measured by the Bispectral Index monitor.

BACKGROUND: Epidural anesthesia potentiates sedative drug effects and decreases minimum alveolar concentration (MAC). The authors hypothesized that epidural anesthesia also decreases the general anesthetic requirements for adequate depth of anesthesia as measured by Bispectral Index (BIS). METHODS: After premedication with 0.02 mg/kg midazolam and 1 microg/kg fentanyl, 30 patients aged 20-65 yr were randomized in a double-blinded fashion to receive general anesthesia with either intravenous saline placebo or intravenous lidocaine control (1-mg/kg bolus dose; 25 microg x kg(-1) x min(-1)). A matched group was prospectively assigned to receive epidural lidocaine (15 ml; 2%) with intravenous saline placebo. All patients received 4 mg/kg thiopental and 1 mg/kg rocuronium for tracheal intubation. After 10 min of a predetermined end-tidal sevoflurane concentration, BIS was measured. The ED50 of sevoflurane for each group was determined by up-down methodology based on BIS less than 50 (MAC(BIS50)). Plasma lidocaine concentrations were measured. RESULTS: The MAC(BIS50) of sevoflurane (0.59% end tidal) was significantly decreased with lidocaine epidural anesthesia compared with general anesthesia alone (0.92%) or with intravenous lidocaine (1%; P < 0.0001). Plasma lidocaine concentrations in the intravenous lidocaine group (1.9 microg/ml) were similar to those in the epidural lidocaine group (2.0 microg/ml). CONCLUSIONS: Epidural anesthesia reduced by 34% the sevoflurane required for adequate depth of anesthesia. This effect was not a result of systemic lidocaine absorbtion, but may have been caused by deafferentation by epidural anesthesia or direct rostral spread of local anesthetic within the cerebrospinal fluid. Lower-than-expected concentrations of volatile agents may be sufficient during combined epidural-general anesthesia.

Adult↗