Plasma Concentration of Fentanyl with Xenon to Block Somatic and Hemodynamic Responses to Surgical Incision

Background: Although anesthesia with xenon has been supplemented with fentanyl, its requirement has not been established. This study was conducted to determine the plasma concentrations of fentanyl necessary to suppress somatic and hemodynamic responses to surgical incision in 50% patients in the presence of 0.7 minimum alveolar concentration (MAC) xenon.

Methods: Twenty-five patients were allocated randomly to predetermined fentanyl concentration between 0.5 and 4.0 ng/ml during 0.7 MAC xenon anesthesia. Fentanyl was administered using a pharmacokinetic model-driven computer-assisted continuous infusion device. At surgical incision each patient was monitored for somatic and hemodynamic responses. A somatic response was defined as any purposeful bodily movement. A positive hemodynamic response was defined as a more than 15% increase in heart rate or mean arterial pressure more than the preincision value. The concentrations of fentanyl to prevent somatic and hemodynamic responses in 50% of patients were calculated using logistic regression.

Results: The concentration of fentanyl to prevent a somatic response to skin incision in 50% of patients in the presence of 0.7 MAC xenon was 0.72 +/- 0.07 ng/ml and to prevent a hemodynamic response was 0.94 +/- 0.06 ng/ml.     

Effects of Xenon on Hemodynamic Responses to Skin Incision in Humans

Background: The authors evaluated the hemodynamic suppressive effects of xenon in combination with sevoflurane at skin incision in patients undergoing surgery.

Methods: Forty patients were assigned randomly to receive one of the following four anesthetics: 1.3 minimum alveolar concentration (MAC) sevoflurane, 0.7 MAC xenon with 0.6 MAC sevoflurane, 1 MAC xenon with 0.3 MAC sevoflurane, or 0.7 MAC nitrous oxide with 0.6 MAC sevoflurane (n = 10 each group). Systolic blood pressure and heart rate were measured before anesthesia, before incision, and approximately 1 min after incision.

Results: The changes in hemodynamic variables in response to incision were less with sevoflurane in combination with xenon and nitrous oxide than with sevoflurane alone. Changes in heart rate (in beats/min) were 19 +/- 11 (+/- SD) for sevoflurane alone, 11 +/- 6 for 0.7 MAC xenon-sevoflurane, 4 +/- 4 for 1 MAC xenon-sevoflurane, and 8 +/- 7 for nitrous oxide-sevoflurane. Changes in systolic blood pressure were 35 +/- 18 mmHg for sevoflurane alone, 18 +/- 8 mmHg for 0.7 MAC xenon-sevoflurane, 16 +/- 7 mmHg for 1 MAC xenon-sevoflurane, and 14 +/- 10 mmHg for nitrous oxide-sevoflurane.     

The Pharmacodynamic Interaction between Propofol and Fentanyl with Respect to the Suppression of Somatic or Hemodynamic Responses to Skin Incision, Peritoneum Incision, and Abdominal Wall Retraction

Background: Sufficient propofol or fentanyl doses necessary to prevent the response to skin incision do not necessarily attenuate hemodynamic responses during surgery. The goal of this study was to characterize the pharmacodynamic interaction between propofol and fentanyl with respect to the suppression of somatic or hemodynamic responses after three stimuli: skin incision, peritoneum incision, and abdominal wall retraction.

Methods: Propofol and fentanyl were administered via computer-assisted continuous infusion to provide equilibration between plasma-blood and biophase concentrations. Patients were randomized to nine groups that received predetermined concentrations of fentanyl (from 0 to 9 ng/ml). Each patient was administered different target concentrations of propofol. Somatic and hemodynamic responses were measured before and after each of three different stimulations: skin incision (si), peritoneum incision (pi), and abdominal wall retraction (ret). The propofol plasma concentrations at which 50% of the patients did not respond to each type of stimulation (Cp50si, Cp50pi, and Cp50ret) were calculated by fitting the Loewe synergistic model.

Results: For propofol alone, Cp50si, Cp50pi, and Cp50ret were 12.9, 17.1 and 19.4 [micro sign]g/ml, respectively. Increasing the fentanyl concentration markedly reduced propofol Cp50si, Cp50pi, and Cp50ret for somatic response, indicating the potential synergistic interaction of both drugs. During the prestimulation period, fentanyl did not decrease systolic blood pressure; however, propofol specifically decreased systolic blood pressure. Both drugs had a synergistic drug interaction on the systolic blood pressure increase after various surgical stimulations. Fentanyl and propofol concentrations that suppressed both the 50% probability of somatic response and the 50% probability of moderate hemodynamic change defined by the 15% systolic blood pressure increase over the prestimulation value were 3.6 ng/ml and 2.5 [micro sign]g/ml for skin incision, 8.4 ng/ml and 1.6 [micro sign]g/ml for peritoneum incision, and 5.9 ng/ml and 5.1 [micro sign]g/ml for wall retraction, respectively.     

The Effect of Fentanyl on Sevoflurane Requirements for Somatic and Sympathetic Responses to Surgical Incision

Background: Fentanyl produces a reduction in the minimum alveolar concentration (MAC) of isoflurane and desflurane needed to blockade adrenergic response (BAR) to surgical incision in 50% of patients (MAC-BAR). MAC-BAR of sevoflurane and the reduction in MAC-BAR of sevoflurane by fentanyl have not been described previously. The purpose of this study was to determine the MAC and MAC-BAR reduction of sevoflurane by fentanyl with and without nitrous oxide (N2 O).

Methods: Two hundred twenty-six patients were randomly assigned to one of two groups: a sevoflurane group and a sevoflurane/N2 O group. Patients in each group were randomly assigned to one of five different fentanyl concentration subgroups. Patients were anesthetized with sevoflurane and fentanyl in the sevoflurane group and with sevoflurane, fentanyl, and N (2) O (66 vol%) in the sevoflurane/N2 O group. Somatic and sympathetic responses to surgical incision were observed for MAC and MAC-BAR assessment at predetermined concentrations of sevoflurane.

Results: Fentanyl produced an initial steep reduction in the MAC and MAC-BAR of sevoflurane, with 3 ng/ml resulting in a 61% reduction in MAC and an 83% reduction in MAC-BAR. A ceiling effect was observed for MAC and MAC-BAR, with 6 ng/ml fentanyl providing only an additional 13% and 9% reduction in MAC and MAC-BAR, respectively. In the presence of 66 vol% N2 O, MAC and MAC-BAR of sevoflurane were reduced with increasing concentrations of fentanyl. A ceiling effect was not observed for reduction in MAC and MAC-BAR in the presence of N2 O.     

The Effects of Fentanyl on Sevoflurane Requirements for Loss of Consciousness and Skin Incision

Background: Fentanyl produces a minimal reduction in the minimum alveolar concentration of sevoflurane to prevent response to a verbal command in 50% of patients (MACawake) at low but analgesic plasma concentrations. The reduction in MACawake, however, is still unknown at higher fentanyl concentrations. The reduction in the MAC of sevoflurane by fentanyl has not been described accurately. The purpose of this study was to determine the MACawake and MAC reduction of sevoflurane by fentanyl.

Methods: Ninety-two patients were randomly allocated to seven fentanyl concentration groups (target plasma concentrations of 0, 1, 1.5, 3, 6, 10, and 14 ng/ml). Responses to verbal command were observed for MACawake assessment at predetermined sevoflurane concentrations. Thereafter, in patients whose target fentanyl concentration was 0 to 10 ng/ml, responses to skin incision were observed for MAC assessment at new steady-state sevoflurane concentrations. The reduction in the MACawake and MAC of sevoflurane by the measured fentanyl concentration was calculated.

Results: There was an initial steep reduction in the MAC of sevoflurane by fentanyl, with 3 ng/ml resulting in a 59% MAC reduction. A ceiling effect was observed, with 10 ng/ml providing only a further 17% reduction in MAC. The initial reduction in MACawake was not as steep as that in MAC. Fentanyl reduced MACawake by approximately 24% at a plasma concentration of 3 ng/ml. Although the reduction curve of MACawake was parabolic, no manifest ceiling effect was observed at concentrations administered in the present study.     

Reduction by Fentanyl of the Cp sub 50 Values of Propofol and Hemodynamic Responses to Various Noxious Stimuli

Background: Propofol and fentanyl infusion rates should be varied according to the patient's responsiveness to stimulation to maintain satisfactory anesthetic and operative conditions. However, somatic and autonomic responses to various noxious stimuli have not been investigated systematically for intravenous propofol and fentanyl anesthesia.

Methods: Propofol and fentanyl were administered via computer-assisted continuous infusion to provide stable concentrations and to allow equilibration between plasma-blood and effect-site concentrations. The propofol concentrations needed to suppress eye opening to verbal command and motor responses after 50-Hz electric tetanic stimulation, laryngoscopy, tracheal intubation, and skin incision in 50% or 95% of patients (Cp50 and Cp95) were determined at fentanyl concentrations of 0.0, 1.0, 2.0, 3.0, and 4.0 ng/ml in 133 patients undergoing lower abdominal surgery. The ability of propofol with fentanyl to suppress hemodynamic reactions in response to various noxious stimuli also was evaluated by measuring arterial blood pressure and heart rate before and after stimulation.

Results: The various Cp50 values for propofol alone (no fentanyl) for the various stimuli increased in the following order: Cp sub 50loss of consciousness, 4.4 micro gram/ml (range, 3.8-5.0); Cp50tetanus, 9.3 micro gram/ml (range, 8.3-10.4); Cp50laryngoscopy, 9.8 micro gram/ml (range, 8.9-10.8); Cp50skin incision, 10.0 micro gram/ml (range, 8.1-12.2); and Cp50intubation, 17.4 micro gram/ml (range, 15.1-20.1; 95% confidence interval). The reduction of Cp50loss of consciousness, with fentanyl was minimal; 11% at 1 ng/ml of fentanyl and 17% at 3 ng/ml of fentanyl. A plasma fentanyl concentration of 1 ng/ml (3 ng/ml) resulted in a 31-34% (50-55%) reduction of the propofol Cp50 s for tetanus, laryngoscopy, intubation, and skin incision. Propofol alone depresses prestimulation blood pressure but had no influence on the magnitude blood pressure or heart rate increase to stimulation. Propofol used with fentanyl attenuated the systolic blood pressure increases to various noxious stimuli in a dose-dependent fashion.     

Anesthetic doses of sevoflurane to block cardiovascular responses to incision when administered with xenon or nitrous oxide.

BACKGROUND: The authors' previous study demonstrated that xenon (Xe) and nitrous oxide (N2O) in combination with sevoflurane can attenuate cardiovascular responses to skin incision. To quantitatively evaluate their suppressive effects on cardiovascular responses, the authors compared the MAC-BAR (minimum alveolar concentration that blocks adrenergic or cardiovascular response to incision) values of sevoflurane when administered with Xe or N2O. METHODS: Forty-three patients received sevoflurane with one of three anesthetics; 1 MAC Xe, 0.7 MAC Xe and 0.7 MAC N2O. The MAC-BAR of sevoflurane was determined in each anesthetic using the "up and down" method. The response was considered positive if the heart rate or mean arterial pressure increased 15% or more. The end-tidal sevoflurane concentration given to the next patient was increased or decreased by 0.3 MAC if the response was positive or negative in the previous patient, respectively. The MAC-BAR was calculated as the mean of four independent cross-over responses. RESULTS: The MAC-BAR of sevoflurane, including the contribution of Xe or N2O, was 2.1+/-0.2 MAC and 2.7+/-0.2 MAC when administered with 1 MAC and 0.7 MAC Xe, respectively, and 2.6+/-0.4 MAC when administered with 0.7 MAC N2O (mean +/- SD). CONCLUSIONS: Although 1 MAC Xe has a more potent suppressive effect on cardiovascular responses to incision than 0.7 MAC Xe or N2O, Xe and N2O have a similar suppressive effect at 0.7 MAC.     

Xenon suppresses the hypnotic arousal in response to surgical stimulation.

STUDY OBJECTIVE: To evaluate the suppressive effects of xenon (Xe) on hypnotic arousal at skin incision. DESIGN: Prospective, randomized study. SETTING: Operating rooms at a university hospital. PATIENTS: 35 ASA physical status I and II patients presenting for elective lower abdominal surgery. INTERVENTIONS: Patients were randomly assigned to receive one of the following regimens: 1.3 minimum alveolar concentration (MAC) isoflurane, 1.3 MAC sevoflurane, 0.7 MAC Xe with 0.6 MAC sevoflurane, 1 MAC Xe with 0.3 MAC sevoflurane, or 0.7 MAC nitrous oxide (N2O) with 0.6 MAC sevoflurane (n = 7 each group). MEASUREMENTS AND MAIN RESULTS: The bispectral index (BIS) was measured at baseline, during anesthesia, and after skin incision. BIS increased significantly at skin incision from the values noted during anesthesia in the sevoflurane and N2O groups, whereas it remained stable at incision in the other three groups (mean change in BIS: 0 +/- 9 for isoflurane, 15 +/- 8 for sevoflurane, 5 +/- 6 for 0.7 MAC Xe, 4 +/- 11 for 1 MAC Xe, and 9 +/- 5 for N2O). CONCLUSIONS: Unlike N2O, Xe was able to suppress hypnotic arousal in response to surgical stimulation when administered with sevoflurane.     

Fentanyl Augments the Blockade of the Sympathetic Response to Incision (MAC-BAR) Produced by Desflurane and Isoflurane: Desflurane and Isoflurane MAC-BAR without and with Fentanyl

Background: Heart rate (HR) or mean arterial blood pressure (MAP) may increase in response to incision despite the absence of a motor response. The authors hypothesized that the MAC-BAR (minimum alveolar concentration of an anesthetic that blocks adrenergic response to incision) for isoflurane would exceed that for desflurane, and that fentanyl would decrease the MAC-BAR for each anesthetic in a dose-dependent manner.

Methods: Seventy-one patients were randomly allocated to one of six groups: desflurane or isoflurane without fentanyl or with 1.5 or 3 micro gram/kg fentanyl given intravenously 5 min before surgical incision. Anesthesia was induced with 2 mg/kg propofol given intravenously, and tracheal intubation facilitated with 0.1 mg/kg given intravenously. The first patient in each group received 1 MAC (end-tidal) of the inhaled anesthetic in 60% nitrous oxide (0.55 MAC), balance oxygen, maintained for at least 10 min before incision. The response was considered positive if the HR or MAP increased 15% or more. If the response was positive, the end-tidal concentration given to the next patient was 0.3 MAC greater; if the response was negative, the end-tidal concentration was 0.3 MAC less. The MAC-BAR level was calculated as the mean of four independent cross-over responses in each group.

Results: Desflurane and isoflurane anesthesia with 60% nitrous oxide did not change HR (P > 0.05) and decreased MAP (P < 0.05) before incision. Plasma epinephrine and norepinephrine concentrations after anesthesia and before incision were normal in all groups. The MAC-BAR level, without fentanyl, did not differ (P > 0.05) between desflurane (1.30 +/- 0.34 MAC [mean +/- SD]) and isoflurane (1.30 +/- 0.18 MAC). Fentanyl given at 1.5 micro gram/kg intravenously equivalently (P > 0.05) reduced the MAC-BAR for desflurane (to 0.40 +/- 0.18 MAC; P <0.05) and isoflurane (to 0.55 +/- 0.00 MAC; P < 0.05), but a further increase in fentanyl to 3 micro gram/kg caused no greater decrease in the MAC-BAR for desflurane (0.48 +/- 0.16 MAC) and isoflurane (0.40 +/- 0.30 MAC).     

Anesthetic Doses of Sevoflurane To Block Cardiovascular Responses to Incision when Administered with Xenon or Nitrous Oxide

Background: The authors' previous study demonstrated that xenon (Xe) and nitrous oxide (N2 O) in combination with sevoflurane can attenuate cardiovascular responses to skin incision. To quantitatively evaluate their suppressive effects on cardiovascular responses, the authors compared the MAC-BAR (minimum alveolar concentration that blocks adrenergic or cardiovascular response to incision) values of sevoflurane when administered with Xe or N2 O.

Methods: Forty-three patients received sevoflurane with one of three anesthetics; 1 MAC Xe, 0.7 MAC Xe and 0.7 MAC N2 O. The MAC-BAR of sevoflurane was determined in each anesthetic using the "up and down" method. The response was considered positive if the heart rate or mean arterial pressure increased 15% or more. The end-tidal sevoflurane concentration given to the next patient was increased or decreased by 0.3 MAC if the response was positive or negative in the previous patient, respectively. The MAC-BAR was calculated as the mean of four independent cross-over responses.

Results: The MAC-BAR of sevoflurane, including the contribution of Xe or N2 O, was 2.1 +/- 0.2 MAC and 2.7 +/- 0.2 MAC when administered with 1 MAC Xe, respectively, and 2.6 +/- 0.4 MAC when administered with 0.7 MAC N (2) O (mean +/- SD).     

Effect of xenon on catecholamine and hemodynamic responses to surgical noxious stimulation in humans

STUDY OBJECTIVE: To determine the effect of xenon in combination anesthesia with sevoflurane on the catecholamine and hemodynamic responses to surgical noxious stimulation in humans. DESIGN: Randomized study. SETTING: A university hospital. PATIENTS: This study involved 32 female ASA physical status I and II patients, age 20-58 years, scheduled for abdominal hysterectomy. INTERVENTIONS: Patients were randomly divided into 4 groups: group X50-S1.5, 50% xenon and 1.5% sevoflurane; group X70-S1.5, 70% xenon and 1.5% sevoflurane; group G70-S1.5, 70% nitrous oxide and 1.5% sevoflurane; and group S2.8, 2.8% sevoflurane. No premedication was administered to the patients, and anesthesia was induced by administration of sevoflurane in oxygen and 0.10 to 0.15 mg/kg of vecuronium. After tracheal intubation, the combination of anesthetics was started, and skin incision was performed after equilibration for more than 15 minutes. MEASUREMENTS: Systolic blood pressure and heart rate (HR) were recorded, and the plasma concentrations of norepinephrine, epinephrine (E), and dopamine were measured 0, 2.5, 5, 7.5, 10, 12.5, and 15 minutes after skin incision. MAIN RESULTS: The maximal increase in the E concentration and the values of the area under the curve for E were significantly smaller in the X50-S1.5 and X70-S1.5 groups compared with that in the S2.8 group (P<0.05). At 1 minute after incision, the HR in X50-S1.5 was significantly lower than those in G70-S1.5 and S2.8 groups and the HR in X70-S1.5 was lower than that in S2.8 group (P<0.01). The systolic blood pressure in S2.8 group at 1 minute was significantly higher than those of other groups (P<0.01). CONCLUSION: Combination anesthesia using xenon and sevoflurane suppresses the plasma E concentration and hemodynamic response after skin incision more effectively than sevoflurane anesthesia alone.     

Fentanyl augments block of sympathetic responses to skin incision during sevoflurane anaesthesia in children

We studied 61 healthy ASA 1 patients (aged 2-6 yr) to determine if fentanyl affects the minimum alveolar concentration which blocks adrenergic responses to skin incision (MAC-BAR) in 50% of children in the presence of 60% nitrous oxide. Patients were allocated randomly to one of three fentanyl groups to receive 0, 2 or 4 micrograms kg-1. Patients also received sevoflurane at a preselected end-tidal concentration according to an 'up-and-down' design. After a steady- state sevoflurane concentration had been maintained for at least 15 min, fentanyl was given i.v. Skin incision was performed 5 min after administration of fentanyl. The response was considered positive if heart rate (HR) or mean arterial pressure (MAP) increased by 15% or more. The MAC-BAR of sevoflurane was 1.45 MAC (95% confidence intervals 1.25-1.65 MAC), and this was reduced markedly to 0.63 MAC and 0.38 MAC by addition of fentanyl 2 and 4 micrograms kg-1, respectively. A ceiling effect was not observed and there was a significant difference between the 2 and 4 micrograms kg-1 groups.      

Effects of two target-controlled concentrations (1 and 3 ng/ml) of remifentanil on MAC(BAR) of sevoflurane

BACKGROUND: The aim of this prospective, randomized, double-blind study was to determine the effects of two different target-controlled concentrations of remifentanil (1 and 3 ng/ml) on the sevoflurane requirement for blunting sympathetic responses after surgical incision (MACBAR). METHODS: Seventy-four patients aged 20-50 yr, with American Society of Anesthesiologists physical status I, were anesthetized with propofol, cisatracurium, and sevoflurane with a mixture of 60% nitrous oxide in oxygen. Then, patients were randomly allocated to receive no remifentanil infusion (n = 27) or a target-controlled plasma concentration of 1 ng/ml (n = 27) or 3 ng/ml remifentanil (n = 20). Sympathetic responses to surgical incision (presence or absence of an increase in either heart rate or mean arterial blood pressure of 15% or more above the mean of the values measured during the 2 min before skin incision) were determined after a 20-min period of stable end-tidal sevoflurane and target-controlled remifentanil concentrations. Predetermined end-tidal sevoflurane concentrations and the MACBAR for each group were determined using an up-and-down sequential-allocation technique. RESULTS: The MACBAR of sevoflurane was higher in the group receiving no remifentanil (2.8% [95% confidence interval: 2.5-3.0%]) as compared with patients of the groups receiving 1 ng/ml (1.1% [0.9-1.3%]; P = 0.012) and 3 ng/ml remifentanil (0.2% [0.1-0.3%]; P = 0.006). When considering a minimum anesthetic concentration (MAC) value in this age population and the contribution of 60% nitrous oxide (0.55 MAC), the combined MACBAR values, expressed as multiples of the MAC, were 1.95 MAC, 1.1 MAC, and 0.68 MAC, in the three groups, respectively. CONCLUSION: A target-controlled concentration of 1 ng/ml remifentanil results in a 60% decrease in the MACBAR of sevoflurane combined with 60% nitrous oxide. Increasing the target concentration of remifentanil to 3 ng/ml produces a further 30% decrease in the MACBAR values of sevoflurane.     

Effects of Two Target-controlled Concentrations (1 and 3 ng/ml) of Remifentanil on MACBAR of Sevoflurane

Background: The aim of this prospective, randomized, double-blind study was to determine the effects of two different target-controlled concentrations of remifentanil (1 and 3 ng/ml) on the sevoflurane requirement for blunting sympathetic responses after surgical incision (MACBAR).

Methods: Seventy-four patients aged 20-50 yr, with American Society of Anesthesiologists physical status I, were anesthetized with propofol, cisatracurium, and sevoflurane with a mixture of 60% nitrous oxide in oxygen. Then, patients were randomly allocated to receive no remifentanil infusion (n = 27) or a target-controlled plasma concentration of 1 ng/ml (n = 27) or 3 ng/ml remifentanil (n = 20). Sympathetic responses to surgical incision (presence or absence of an increase in either heart rate or mean arterial blood pressure of 15% or more above the mean of the values measured during the 2 min before skin incision) were determined after a 20-min period of stable end-tidal sevoflurane and target-controlled remifentanil concentrations. Predetermined end-tidal sevoflurane concentrations and the MACBAR for each group were determined using an up-and-down sequential-allocation technique.

Results: The MACBAR of sevoflurane was higher in the group receiving no remifentanil (2.8% [95% confidence interval: 2.5-3.0%]) as compared with patients of the groups receiving 1 ng/ml (1.1% [0.9-1.3%]; P = 0.012) and 3 ng/ml remifentanil (0.2% [0.1-0.3%]; P = 0.006). When considering a minimum anesthetic concentration (MAC) value in this age population and the contribution of 60% nitrous oxide (0.55 MAC), the combined MACBAR values, expressed as multiples of the MAC, were 1.95 MAC, 1.1 MAC, and 0.68 MAC, in the three groups, respectively.     

Narcotic requirements for intravenous anesthesia

MAC BAR, the minimum end-tidal alveolar anesthetic concentration that inhibits adrenergic response to a noxious stimulus in 50% of subjects, is a quantifiable physiological parameter that can be used to determine potency and therapeutic indices of volatile anesthetics. We wished to determine whether there is a minimal intraarterial plasma concentration (MIC BAR) of an opiate such as fentanyl that will prevent a hypertensive response to noxious stimuli in 50% of patients undergoing aortocoronary bypass surgery (ACBP). Forty-three patients with good left ventricular function were studied. All patients were premedicated with diazepam, morphine, and scopolamine. Five groups of patients were anesthetized with different fentanyl anesthesia protocols, each designed to produce different plasma fentanyl concentrations (PFC). A 20% increase in systolic blood pressure compared to control was considered an adrenergic response that related to the plasma fentanyl concentration inferred from each patient's PFC time-concentration curve. Only four patients became hypertensive with a PFC greater than 20 ng/ml. One patient became hypertensive at intubation with a PFC of 12.3 ng/ml. There was no statistically significant difference in the mean PFC in patients who became hypertensive at each event. During aortic dissection, when significantly more patients became hypertensive, there was no difference in the incidence of hypertension in patients with a PFC above or below 20 ng/ml. Two patients became hypertensive at skin incision with a PFC over 30 ng/ml. A MIC BAR could not be identified because of the great variability in the PFC of patients who became hypertensive.(ABSTRACT TRUNCATED AT 250 WORDS)     

Minimum alveolar concentration (MAC) of xenon with sevoflurane in humans

BACKGROUND: Although more than 30 yr ago the minimum alveolar concentration (MAC) of xenon was determined to be 71%, that previous study had technological limitations, and no other studies have confirmed the MAC value of xenon since. The current study was designed to confirm the MAC value of xenon in adult surgical patients using more modern techniques. METHODS: Sixty patients were anesthetized with sevoflurane with or without xenon. They were randomly allocated to one of four groups; patients in group 1 received no xenon, whereas those in groups 2, 3, and 4 received end-tidal concentrations of 20, 40, and 60%, respectively (n = 15 each group). Target end-tidal sevoflurane concentrations were chosen using the "up-and-down" method in each group. After steady state sevoflurane and xenon concentrations were maintained for at least 15 min, each patient was monitored for a somatic response at surgical incision. Somatic response was defined as any purposeful bodily movement. The MAC of sevoflurane and its reduction by xenon was evaluated using the multiple independent variable logistic regression model. RESULTS: The interaction coefficient of the multiple variable logistic regression was not significantly different from zero (P = 0.143). The MAC of xenon calculated as xenon concentration that would reduce MAC of sevoflurane to 0% was 63.1%. CONCLUSIONS: The authors could not determine whether interaction in blocking somatic responses in 50% of patients is additive. The MAC of xenon is in the range of the values that were predicted in a previous study.     

Xenon does not reduce opioid requirement for orthopedic surgery

PURPOSE: Is to test the hypothesis that 70% xenon has a relevant opioid sparing effect compared to a minimum alveolar concentration (MAC)-equivalent combination of N(2)O and desflurane. METHODS: In this randomized, controlled study of 30 patients undergoing major orthopedic surgery, we determined the plasma alfentanil concentration required to suppress response to skin incision in 50% of patients (Cp(50)) anesthetized with xenon (70%) or a combination of N(2)O (70%) and desflurane (2%). A response was defined as movement, pressor response > 15 mmHg, heart rate > 90 beats x min(-1), autonomic reactions or a combination of these. At skin incision, alfentanil was administered at a randomly selected target plasma concentration thereafter the concentration was increased or decreased according to the patient's response. After skin incision, desflurane was adjusted to maintain the bispectral index below 60 and prevent responsiveness in both groups. RESULTS: The Cp(50) (+/- standard error) of alfentanil was 83 +/- 48ng x mL(-1) with xenon and 49 +/- 26 ng x mL(-1) with N(2)O/desflurane (P =0.451). During surgery five xenon and 15 N(2)O/desflurane patients were given desflurane at 1.0 +/- 0.5 volume % and 2.5 +/- 0.7 volume %. The total age adjusted MAC was 0.97 +/- 0.07 and 0.94 +/- 0.07 respectively (P = 0.217). The intraoperative plasma alfentanil concentrations were 95 +/- 80 and 93 +/- 60 ng x mL(-1) respectively (mean +/- SD; P = 0.451). Patients given xenon were slightly more bradycardic, whereas blood pressure was similar. CONCLUSION: Xenon compared to a MAC-equivalent combination of N(2)O and desflurane does not substantially reduce opioid requirement for orthopedic surgery. A small but clinically irrelevant difference cannot be excluded, however.     

Reduction of the MAC of desflurane with fentanyl.

Opioids are known to affect the MAC of inhalational anesthetics. We have determined the interaction between fentanyl and desflurane, following a bolus injection of fentanyl at induction in 134 adult patients. Five groups of patients were studied. Four groups received desflurane or isoflurane in oxygen with either fentanyl 3 or 6 micrograms/kg and thiopental 2-5 mg/kg given as a bolus injection at the time of induction. An additional group received desflurane in oxygen alone. Groups were stratified by age. MAC determination, in response to the stimulus of skin incision, was made using the "up-down" method and logistic regression. The MAC desflurane in oxygen was 6.3% (5.3-7.6%, 95% confidence interval [CI]). Fentanyl 3 micrograms/kg produced a fentanyl plasma concentration of 0.78 +/- 0.53 ng/ml at skin incision and resulted in a MAC for desflurane of 2.6% (2.0-3.2%, 95% CI) %. Fentanyl 6 micrograms/kg produced a fentanyl plasma concentration of 1.72 +/- 0.76 ng/ml at skin incision and resulted in a MAC for desflurane of 2.1% (1.5-2.6%, 95% CI). To compare recovery times to eye-opening and response to commands, patients were grouped according to the plasma fentanyl concentrations at the time of awaking. Recovery was faster in patients who received desflurane than in those who received isoflurane. The authors conclude that the MAC of desflurane is significantly reduced 25 min following a single dose of 3 micrograms/kg of fentanyl and that increasing the fentanyl dose to 6 micrograms/kg produces little further decrease in MAC. Desflurane is also associated with faster recovery from anesthesia than is isoflurane.     

Low-dose enflurane as adjunct to high-dose fentanyl in patients undergoing coronary artery surgery: stable hemodynamics and maintained myocardial oxygen balance

The effects of enflurane (end-tidal concentration 0.7%) on central and coronary hemodynamics and myocardial oxygenation were studied during steady state, high-dose fentanyl anesthesia in ten patients undergoing coronary artery bypass grafting operations. Compared with the response in ten patients receiving the same fentanyl anesthesia (100 micrograms/kg) without enflurane supplementation, enflurane caused a moderate reduction in mean arterial pressure, systemic vascular resistance, and left ventricular stroke work index. No patient showed signs of myocardial ischemia, and mean coronary sinus flow and calculated coronary resistance remained unchanged. Surgical stimulation induced no central or coronary hemodynamic responses in the enflurane-fentanyl group. No coronary hemodynamic changes occurred in the fentanyl group, but a marked increase in arterial pressure and systemic vascular resistance was seen. Myocardial oxygen extraction decreased in the enflurane supplemented group although it increased in the fentanyl group after surgical stimulation. Three fentanyl group patients and one enflurane-fentanyl group patient had a low myocardial lactate extraction as a sign of myocardial ischemia during surgery. We conclude that a 0.7% enflurane supplementation of 100 micrograms/kg fentanyl anesthesia does not endanger myocardial oxygenation and effectively prevents central and coronary hemodynamic responses to skin incision and sternotomy in patients undergoing coronary artery surgery.     

The additive contribution of nitrous oxide to isoflurane MAC in infants and children

The purpose of this study was to determine the contribution of nitrous oxide to isoflurane MAC in pediatric patients. MAC was determined in 47 infants and small children (mean ages 16.6 +/- 6.7 months) during isoflurane and oxygen anesthesia (n = 11) and isoflurane and nitrous oxide anesthesia (25% nitrous oxide [n = 12], 50% nitrous oxide [n = 12], and 75% nitrous oxide [n = 12]). After assigning patients to one of four groups, anesthesia was induced with increasing inspired concentrations of isoflurane in oxygen. After anesthetic induction and tracheal intubation, ventilation was controlled (carbon dioxide partial pressure = 32 +/- 5 mmHg), and nitrous oxide was added to the inspired gas mixture to achieve end-expired nitrous oxide concentrations of 0, 25, 50, or 75%. Inspired and expired gas samples were obtained from a distal sampling port in the tracheal tube. The response to skin incision in each patient was assessed at a previously selected end-tidal concentration of isoflurane. The MAC of isoflurane was determined in each group using the up-and-down method described for evaluating quantal responses. The mean duration of constant end-tidal concentrations prior to skin incision was 14 +/- 7 min (range 6-46 min). The ratio of expired to inspired nitrous oxide and isoflurane concentrations during the period of constant end-tidal concentrations was 0.96 +/- 0.01 and 0.93 +/- 0.03 respectively. The MAC of isoflurane in oxygen was 1.69 +/- 0.13 vol% (mean +/- standard deviation).(ABSTRACT TRUNCATED AT 250 WORDS)