The use of a ketamine-propofol combination during monitored anesthesia care.

UNLABELLED: Supplemental analgesics are commonly used to enhance analgesia and improve patient comfort during procedures performed under local anesthesia and sedation. Because the use of ketamine as an analgesic adjunct to propofol sedation has not been well established, we evaluated its impact on analgesia, sedation, and recovery after ambulatory surgery. One hundred female outpatients undergoing breast biopsy procedures under local anesthesia participated in this randomized, double-blinded, placebo-controlled study. After premedication with midazolam, 2 mg IV, patients received an infusion of a solution containing propofol (9.4 mg/mL) in combination with either placebo (saline) (Group 1) or ketamine, 0.94 mg/mL (Group 2), 1.88 mg/mL (Group 3), or 2.83 mg/mL (Group 4). The sedative infusion rate was varied to maintain a deep level of sedation (Observer Assessment of Alertness/Sedation score 4) and normal respiratory and hemodynamic functions. Sufentanil, 2.5 microg IV, "rescue" boluses were used as needed to treat patients' responses (if any) to local anesthetic infiltration or surgical stimulation. Ketamine produced a dose-dependent reduction in the "rescue" opioid requirements. However, there was an increase in postoperative nausea and vomiting, psychomimetic side effects, and delay in discharge times with the largest ketamine dosage (Group 4). The adjunctive use of ketamine during propofol sedation provides significant analgesia and minimizes the need for supplemental opioids. The combination of propofol (9.4 mg/mL)/ketamine (0.94-1.88 mg/mL) provides effective sedation/analgesia during monitored anesthesia care. IMPLICATIONS: Ketamine, when used in subhypnotic dosages, may be an useful adjuvant to propofol sedation.

The effect of fresh gas flow and anesthetic technique on the ability to control acute hemodynamic responses during surgery.

UNLABELLED: We evaluated the effect of the fresh gas flow (FGF) rate and the anesthetic technique on the ability to control the acute hyperdynamic response to a specific surgical stimulus during surgery in 90 consenting ASA physical status I-III patients undergoing lower abdominal procedures. After the administration of midazolam 2 mg IV, anesthesia was induced in all patients with propofol 1.5 mg/kg IV and fentanyl 1 microg/kg IV and was initially maintained with desflurane or isoflurane, 0.7 minimum alveolar anesthetic concentration, at total FGF rates of either 1 or 3 L/min. In response to the surgical stimulation of skin incision and retropubic dissection, an increase in mean arterial pressure (MAP) >20% above the preincision baseline MAP value provoked a stepwise increase in the inspired concentration of the volatile anesthetic or the IV administration of a variable-rate infusion of esmolol. At both FGF rates, the acute hemodynamic response to surgical stimulation was more efficiently treated by increasing the inspired concentration of desflurane than isoflurane. At 1 L/min, the average time to control the increase in MAP was significantly shorter with desflurane (17+/-12 min) compared with isoflurane (29+/-16 min), with 60% of the patients in the isoflurane group requiring rescue therapy. When an esmolol infusion was used to control the increase in MAP, supplementation with fentanyl was required in 40% and 53% of patients anesthetized with desflurane and isoflurane, respectively. In conclusion, desflurane provided more rapid and reliable control of acute hemodynamic responses to surgical stimulation than isoflurane or esmolol when the volatile anesthetics were administered at low FGF rates. IMPLICATIONS: At low fresh gas flow rates (1 L/min), desflurane more successfully and rapidly controlled the acute hemodynamic responses to painful surgical stimuli than isoflurane.

Effects of nicardipine and labetalol on the acute hemodynamic response to electroconvulsive therapy.

STUDY OBJECTIVE: To examine the acute hemodynamic effects of intravenous (i.v.) nicardipine and its ability to attenuate the hyperdynamic response to electroconvulsive therapy (ECT), when used alone or in combination with labetalol. DESIGN: Prospective, randomized, double-blind, positive-control, clinical investigation. SETTING: University hospital. PATIENTS: 36 patients undergoing ECT. INTERVENTIONS: In a series of three studies, the hemodynamic effects of nicardipine were assessed prior to, during, and after ECT. After administration of glycopyrrolate 0.1 mg i.v., placebo (saline) or nicardipine was administered by rapid infusion (1, 2.5, 5, 10, and 15 mg) or bolus injection (1.25, 2.5, and 5 mg), either alone or in combination with labetalol 10 mg i.v. Unconsciousness was induced with methohexital 1 mg/kg i.v.; succinylcholine 1.2 to 1.5 mg/kg i.v. was administered for muscle relaxation. A bilateral electrical stimulus was delivered and the durations of motor and electroencephalographic (EEG) seizures were noted. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure (MAP) and heart rate (HR) values were recorded at 1- to 5-minute intervals throughout the study period. When administered as a rapid infusion, nicardipine 5 mg i.v. produced a significant decrease in MAP; however, nicardipine dosages of 10 to 15 mg i.v. did not produce a significantly greater decrease in MAP than 5 mg. Bolus administration of nicardipine 1.25 to 5 mg produced a rapid onset of its hemodynamic effects without exacerbating the cardiovascular depressant effects of methohexital. However, the decrease in MAP was accompanied by an increase in HR after administration of the 5 mg i.v. bolus dose. The acute hyperdynamic response to ECT was most effectively controlled by nicardipine 2.5 to 5 mg i.v. bolus, in combination with labetalol 10 mg i.v. Seizure duration was not significantly altered by the use of nicardipine as part of the anesthetic regimen for ECT. CONCLUSION: Nicardipine 2.5 mg i.v. bolus in combination with labetalol 10 mg i.v. was the most effective pretreatment regimen for preventing the acute hyperdynamic response to ECT. However, this combination produced a 20% decrease in MAP immediately prior to ECT and a lower MAP at the time of discharge.

Use of alfentanil and propofol for outpatient monitored anesthesia care: determining the optimal dosing regimen.

UNLABELLED: Propofol and alfentanil are both rapid and short-acting drugs that can be used for sedation and analgesia during monitored anesthesia care (MAC). This study was designed to determine the optimal infusion rates of propofol and alfentanil when administered during local anesthesia. In this randomized, double-blind study, we evaluated the effects of different propofol infusion rates on the alfentanil requirement, level of sedation, intraoperative recall, respiratory and cardiovascular variables, and recovery. Seventy-two consenting ASA physical status I or II female outpatients undergoing breast biopsy procedures with local anesthesia were randomly assigned to one of four treatment groups. All patients received midazolam, 2 mg intravenously (I.V.) for premedication. Propofol was infused at 0, 25, 50, or 75 microg x kg(-1) x min(-1) during the operation. Sedation was evaluated using the Observer's Assessment of Alertness/Sedation (OAA/S) scale at 5-min intervals by a blinded observer. Two minutes before the infiltration of the local anesthetic solution, a bolus of alfentanil, 2.5 microg/kg I.V., was administered, followed by a maintenance infusion of 0.5 microg x kg(-1) x min(-1). The alfentanil infusion rate was subsequently varied to maintain patient comfort and stable cardiovascular and respiratory function. Pictures were shown at the start of the propofol infusion, upon initiating the alfentanil infusion, and at 45 min after the skin incision to evaluate recall of intraoperative events. Propofol produced dose-dependent increases in the level of sedation (with median OAA/S scores of 2-4, P < 0.05). Higher infusion rates of propofol (50-75 microg x kg(-1) x min(-1)) produced significant amnesia, opioid-sparing effects (alfentanil 0.3 +/- 0.2 vs 0.6 +/- 0.2 microg x kg(-1) x min(-1)), and less postoperative nausea and vomiting (P < 0.05). However, episodes of transient hemoglobin oxygen desaturation were more common in the deeply sedated patients. Thus, in healthy outpatients premedicated with midazolam, 2 mg I.V., a propofol infusion of 25-50 microg x kg(-1) x min(-1) in combination with an alfentanil infusion of 0.2-0.4 microg x kg(-1) x min(-1) is recommended for sedation and analgesia during MAC in the ambulatory setting. IMPLICATIONS: Sedation is often given during local anesthesia. This study demonstrated that administration of an intravenous anesthetic, propofol, in combination with an opioid infusion (i.e., alfentanil) to provide sedation analgesia and amnesia with a low incidence of side effects, such as nausea and vomiting and respiratory depression in outpatients premedicated with midazolam.

A comparison of propofol and remifentanil during monitored anesthesia care.

STUDY OBJECTIVE: To compare remifentanil, an esterase-metabolized opioid, to a standard propofol-based sedation technique for monitored anesthesia care (MAC). DESIGN: Non-randomized, open label. SETTING: University hospital. PATIENTS: 44 healthy female outpatients undergoing breast biopsy procedures under local anesthesia. INTERVENTIONS: All patients received intravenous (IV) midazolam 2 mg, followed by a continuous infusion of either propofol 75 micrograms/kg/min, or remifentanil 0.1 microgram/kg/min, which was subsequently titrated to maintain optimal patient comfort without respiratory depression. Surgical-related pain was treated by injecting additional local anesthetic solution and "rescue" boluses of fentanyl 25 micrograms IV. MEASUREMENTS AND MAIN RESULTS: Sedation, pain, and discomfort were monitored using standardized rating scales at 1 to 5 minute intervals. Recovery times were measured from the end of the study drug infusions. Propofol resulted in significantly higher median sedation scores compared with remifentanil, with 73% of patients requiring a decrease in the propofol infusion rate because of "excessive" sedation. Local anesthetic requirements, pain, and discomfort scores during surgery were similar in both groups. Remifentanil resulted in greater respiratory depression compared with propofol, with decreases in the remifentanil infusion rate required by 41% of patients because of a slow respiratory rate (< 8 bpm) and/or oxygen desaturation measured by pulse oximetry (SpO2 < 90%). Median times to ambulation and to being judged "fit for discharge" were significantly shorter following propofol (40 and 47 minutes, respectively) compared with remifentanil (52 and 58 minutes, respectively). CONCLUSION: Remifentanil provided comparable intraoperative conditions and patient comfort at a lower sedation level compared with propofol. However, remifentanil was associated with greater respiratory depression and a longer time to home readiness.

Interactions between midazolam and remifentanil during monitored anesthesia care.

BACKGROUND: Remifentanil, an ultra-short-acting opioid analgesic, may be useful as an intravenous adjuvant to local anesthesia for treating patient discomfort and pain during monitored anesthesia care (MAC). However, the remifentanil dose requirements, interactions with other commonly used sedative drugs (such as midazolam), and recovery characteristics after ambulatory procedures have not been determined. Therefore, this study was designed to evaluate the safety and efficacy of remifentanil alone and in combination with different doses of midazolam during MAC. METHODS: Eighty-one healthy consenting women scheduled for elective breast biopsy procedures were randomly assigned to one of four treatment groups according to an institutional review board-approved, double-blind, placebo-controlled protocol. The study medication (containing either saline or 2 mg, 4 mg, or 8 mg of midazolam) was administered intravenously 5 min before starting an infusion of remifentanil at 0.1 microgram.kg-1.min-1. The remifentanil infusion was subsequently adjusted in 0.025- and 0.05-microgram.kg-1.min-1 increments to maintain patient comfort and adequate ventilation during the operation. The level of sedation was assessed at 1- to 10-min intervals during the procedure using the inverted observer's assessment of alertness/sedation (OAA/S) scale, with a score of 1 = awake, alert to 5 = asleep, unarousable. Discomfort and pain were assessed using numerical rating scales. Hemoglobin oxygen saturation, respiratory rate, blood pressure (systolic, diastolic, mean), and heart rate were monitored at 1- to 5-min intervals. Intraoperative amnesia was assessed by asking patients to recall a picture shown 5 min after the study medication was administered. Recovery was evaluated using the Aldrete score and the times to "home readiness" and actual discharge. Side effects and patient satisfaction were assessed in a follow-up telephone interview on the first postoperative day. RESULTS: Midazolam produced dose-dependent increases in the median level of sedation. Remifentanil produced a greater reduction in respiratory rate in the 4-mg and 8-mg midazolam groups. However, there were no significant differences in the hemodynamic variables or discharge times. Patients with OAA/S scores of 1 to 3 ("light" sedation) 5 min after the study medication experienced a greater incidence of intraoperative pruritus and postoperative nausea and vomiting (PONV) compared with those with OAA/S scores of 4 to 5 ("deep" sedation). Discharge times were prolonged for patients in the light sedation group in whom PONV developed. CONCLUSIONS: Use of remifentanil alone for MAC did not provide optimal sedation during local anesthesia. However, 0.05 to 0.1 microgram.kg-1.min-1 remifentanil in combination with 2 mg midazolam given intravenously, provided effective sedation and analgesia during MAC in healthy patients classified as American Society of Anesthesiologists status 1 to 2. Midazolam also produced dose-dependent potentiation of remifentanil's depressant effect on respiratory rate. In outpatients receiving a combination of midazolam and remifentanil during local anesthesia, the level of sedation appears to influence the incidence of both intraoperative pruritus and PONV.

Methods for monitoring the level of sedation.

Sedative drugs commonly are titrated to effect in critically ill patients. Subjective clinical assessment tools are used to determine the patient's level of sedation, and there clearly is a need for improved quantitative methods of monitoring sedation. This article describes the current methods for assessing the level of sedation in critically ill patients and discusses the potential role of neurophysiologic monitoring using processed electroencephalograms and evoked potentials.

The comparative effects of methohexital, propofol, and etomidate for electroconvulsive therapy.

The intravenous anesthetics which are commonly used for electroconvulsive therapy (ECT) possess dose-dependent anticonvulsant properties. Since the clinical efficacy of ECT depends on the induction of a seizure of adequate duration, it is important to determine the optimal dose of the hypnotic for use during ECT. We compared the duration of seizure activity and cognitive recovery profiles after different doses of methohexital, propofol, and etomidate administered to induce hypnosis prior to ECT. Ten outpatients with major depressive disorders receiving maintenance ECT participated in this prospective, randomized, cross-over study. Patients were premedicated with glycopyrrolate, 0.2 mg intravenously (i.v.), and labetalol, 20-30 mg i.v., and hypnosis was induced with an i.v. bolus injection of methohexital or propofol (0.75, 1.0, and 1.5 mg/kg), or etomidate (0.15, 0.2, and 0.3 mg/kg), administered over 10-15 s. Adequate muscle paralysis was achieved with succinylcholine, 1.0-1.4 mg/kg i.v. Each patient's seizure threshold was determined prior to enrollment in the study and the electrical stimulus variables were kept constant throughout the study period. After delivery of a bilateral electrical stimulus, the duration of the resulting electroencephalographic (EEG) and motor seizures were recorded. A total of 90 ECT treatments were evaluated. The durations of EEG and motor seizures were longest after etomidate and shortest after propofol. There were no significant dose-related differences in motor and EEG seizure durations (means +/- SD) after the low, intermediate, and high doses of etomidate of 44 +/- 11 and 77 +/- 19, 43 +/- 10 and 76 +/- 34, 42 +/- 16 and 78 +/- 56 s, respectively. Conversely, both methohexital and propofol, 0.75, 1.0, and 1.5 mg/kg, produced dose-dependent decreases in motor and EEG seizure durations (i.e., 37 +/- 10 and 58 +/- 12, 36 +/- 8 and 62 +/- 24, and 29 +/- 13 and 48 +/- 20 for methohexital; 34 +/- 15 and 56 +/- 29, 31 +/- 8 and 50 +/- 17, and 20 +/- 6 and 33 +/- 12 for propofol, respectively). The awakening times were similar, regardless of the hypnotic or dose administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Lignocaine-induced convulsion does not induce c-fos protein (c-Fos) in rat hippocampus.

Recent studies have shown that proto-oncogene c-fos mRNA is induced in the central nervous system by a variety of stimuli including generalised convulsions. In this study, the expression of c-fos protein (c-Fos) following lignocaine-induced convulsions was examined and compared with that following convulsions induced by non-anesthetic convulsants, such as pentylenetetrazol, kainic acid and electroconvulsive shocks, in rat brain. Administration of 120 mg.kg-1 lignocaine by the intraperitoneal route induced generalised convulsions in all rats examined within 10 min. C-Fos was markedly induced in the piriform cortex and amygdala, and slightly induced in the neocortex and thalamus, while no c-Fos expression was observed in the hippocampus. In contrast, c-Fos expression following generalised convulsions induced by non-anaesthetic convulsants was very marked in the hippocampal region, piriform cortex and amygdala, and extended to the thalamus and neocortex. These results contradict those of previously reported local cerebral metabolic studies using 2-deoxyglucose as a metabolic marker, and suggest that lignocaine-induced convulsions, unlike those induced by non-anaesthetic convulsants, may not cause severe sequelae (plastic changes) in the hippocampus.

Electroencephalographic changes during vital capacity breath induction with halothane.

We investigated the EEG responses in 17 patients during induction of anaesthesia with vital capacity breaths of 4% halothane. The control alpha activity changed to a low voltage, 5-25 muV, fast, 20-28 Hz activity at the time of loss of consciousness at 78 (SD 27) s and typical spindle bursts (20-75 muV, 12-15 Hz) developed at 223 (51) s. All patients remained haemodynamically stable. This sequence of EEG changes was similar to that observed during induction with the conventional method of normal tidal volume breathing and a gradual increase of the inspired concentration of halothane.

Nitrous oxide antagonizes CNS stimulation by laudanosine in mice.

We have investigated whether nitrous oxide antagonizes or augments the CNS stimulant action of laudanosine in mice by comparing the mean convulsive doses (CD50 (SE] of a control group and those following pretreatment with 65% nitrous oxide in oxygen for 20 and 180 min. Nitrous oxide significantly increased CD50 from 46.8 (1.4) mg kg-1 of control to 57.3 (1.3) mg kg-1 at 20 min and 53.5 (1.7) mg kg-1 at 180 min. The attenuation of the effect of nitrous oxide at 180 min, suggestive of possible partial drug tolerance, was not statistically significant. These findings indicate that nitrous oxide antagonizes the CNS stimulating action of laudanosine.

Progressive changes in electroencephalographic responses to nitrous oxide in humans: a possible acute drug tolerance.

The possibility of acute tolerance to nitrous oxide was examined during halothane anesthesia in humans. Nitrous oxide was added to the inspired gas twice. The first admixture induced three successive stages of electroencephalogram (EEG): delta-waves lasting for 13 +/- 12 min, theta-waves lasting for 41 +/- 21 min, and, finally, spindle-type waves. The spindle-type EEG was similar to that of halothane anesthesia in configuration, but smaller in amplitude and faster in frequency than that seen during halothane anesthesia. The second admixture, given after a 20-30-min interval, induced a continuous delta-wave EEG in one patient, theta-waves followed by spindle EEG in eight patients, and spindle-type EEG in four patients. The successive changes of electroencephalographic response during the first admixture indicate that an alteration of central nervous system function occurred. The altered state was maintained in the absence of nitrous oxide: responses to a second admixture were characteristic of the later, altered, stages of responses seen after the first admixture. These findings support the view of acute tolerance to nitrous oxide.

Effects of different speeds of induction with sevoflurane on the EEG in man.

The effects of two kinds of induction speed of sevoflurane anesthesia on the EEG pattern were compared in the same individual using medical student volunteers: a first exposure of 4% was given, followed after full recovery, by incremental doses of 1, 2 and 4% successively, each being administered for 10 min. The arterial blood level of the anesthetic was measured using gaschromatograph. The changes of EEG pattern during fast induction with 4% were not represented by the abbreviation of those observed during the slow induction with the incremental doses. The administration of 4% induced a sudden appearance of high voltage, rhythmic slow waves of 2-3 Hz at 1-3 min when the arterial blood anesthetic level increased maximally, which was then followed by a pattern of faster activities of 10-14 Hz mixed with 5-8 Hz slow waves. In contrast, the administration of incremental doses induced an increase in frequency and amplitude of EEG activities in the light plane, followed by their decreases in deeper planes. The final EEG patterns were identical for both these methods of induction. These findings confirmed our previous hypothesis that not only the arterial blood level of anesthetics but the rate of its increase are important factors determining the EEG pattern of anesthesia