Cerebral Blood Flow and CO2 Reactivity Is Similar during Remifentanil/N2 O and Fentanyl/N2 O Anesthesia

Background: Remifentanil, a rapidly metabolized [micro sign]-opioid agonist, may offer advantages for neurosurgical procedures in which prolonged anesthetic effects can delay assessment of the patient. This study compared the effects of remifentanil-nitrous oxide on cerebral blood flow (CBF) and carbon dioxide reactivity with those of fentanyl-nitrous oxide anesthesia during craniotomy.

Methods: After institutional approval and informed patient consent were obtained, 23 patients scheduled to undergo supratentorial tumor surgery were randomly assigned to remifentanil or fentanyl infusion groups in a double-blinded manner. Midazolam, thiopental, and pancuronium induction was followed by equipotent narcotic loading infusions of remifentanil (1 [micro sign]g [middle dot] kg-1 [middle dot] min-1) or fentanyl (2 [micro sign]g [middle dot] kg-1 [middle dot] min-1) for 5-10 min. Patients were ventilated with 2:1 nitrous oxide-oxygen, and opioid rates were reduced and then titrated to a stable hemodynamic effect. After dural exposure, CBF was measured by the intravenous133 xenon technique at normocapnia and hypocapnia. Reactivity of CBF to carbon dioxide was calculated as the absolute increase in CBF per millimeters of mercury increase in the partial pressure of carbon dioxide (PaCO2). Data were analyzed by repeated-measures analysis of variance, unpaired Student's t tests, or contingency analysis.

Results: In the remifentanil group (n = 10), CBF decreased from 36 +/- 11 to 27 +/- 8 ml [middle dot] 100 g-1 [middle dot] min-1 as PaCO2 decreased from 33 +/- 5 to 25 +/- 2 mmHg. In the fentanyl group (n = 8), CBF decreased from 37 +/- 11 to 25 +/- 6 ml [middle dot] 100 g-1 [middle dot] min-1 as PaCO2 decreased from 34 +/- 3 to 25 +/- 3 mmHg. Absolute carbon dioxide reactivity was preserved with both agents: 1 +/- 1.2 ml [middle dot] 100 g-1 [middle dot] min-1 [middle dot] mmHg-1 for remifentanil and 1.5 +/- 0.5 ml [middle dot] 100 g-1 [middle dot] min-1 [middle dot] mmHg-1 for fentanyl (P = 0.318).     

Critical oxygen delivery in conscious humans is less than 7.3 ml O2 x kg(-1) x min(-1)

BACKGROUND: The "critical" level of oxygen delivery (DO2) is the value below which DO2 fails to satisfy the metabolic need for oxygen. No prospective data in healthy, conscious humans define this value. The authors reduced DO2 in healthy volunteers in an attempt to determine the critical DO2. METHODS: With Institutional Review Board approval and informed consent, the authors studied eight healthy, conscious volunteers, aged 19-25 yr. Hemodynamic measurements were obtained at steady state before and after profound acute isovolemic hemodilution with 5% albumin and autologous plasma, and again at the reduced hemoglobin concentration after additional reduction of DO2 by an infusion of a beta-adrenergic antagonist, esmolol. RESULTS: Reduction of hemoglobin from 12.5+/-0.8 g/dl to 4.8+/-0.2 g/dl (mean +/- SD) increased heart rate, stroke volume index, and cardiac index, and reduced DO2 (14.0+/-2.9 to 9.9+/-20 ml O2 x kg(-1) x min(-1); all P<0.001). Oxygen consumption (VO2; 3.0+/-0.5 to 3.4+/-0.6 ml O2 x kg(-1) x min(-1); P<0.05) and plasma lactate concentration (0.50+/-0.10 to 0.62+/-0.16 mM; P<0.05; n = 7) increased slightly. Esmolol decreased heart rate, stroke volume index, and cardiac index, and further decreased DO2 (to 7.3+/-1.4 ml O2 x kg(-1) x min(-1); all P<0.01 vs. before esmolol). VO2 (3.2+/-0.6 ml O2 x kg(-1) x min(-1); P>0.05) and plasma lactate (0.66+/-0.14 mM; P>0.05) did not change further. No value of plasma lactate exceeded the normal range. CONCLUSIONS: A decrease in DO2 to 7.3+/-1.4 ml O2 x kg(-1) min(-1) in resting, healthy, conscious humans does not produce evidence of inadequate systemic oxygenation. The critical DO2 in healthy, resting, conscious humans appears to be less than this value.     

Intravenous Magnesium Sulfate Administration Reduces Propofol Infusion Requirements during Maintenance of Propofol-N2O Anesthesia: Part I: Comparing Propofol Requirements According to Hemodynamic Responses: Part II: Comparing Bispectral Index in Control and Magnesium Groups

Background: The authors investigated whether an intravenous administration of magnesium sulfate reduces propofol infusion requirements during maintenance of propofol-N2O anesthesia.

Methods: Part I study: 54 patients undergoing total abdominal hysterectomy were randomly divided into two groups (n = 27 per group). The patients in the control group received 0.9% sodium chloride solution, whereas the patients in the magnesium group received magnesium (50 mg/kg as a bolus, then 8 mg [middle dot] kg-1 [middle dot] h-1). To maintain mean arterial blood pressure (MAP) and heart rate (HR) at baseline value, the propofol infusion rate was changed when the MAP or the HR changed. The amount of propofol infused excluding the bolus dosage was divided by patient's body weight and total infusion time. Part II study: Another 20 patients were randomly divided into two groups (n = 10 per group). When the MAP and HR had been maintained at baseline value and the propofol infusion rate had been maintained at 80 [mu]g [middle dot] kg-1 [middle dot] min-1 (magnesium group) and 160 [mu]g [middle dot] kg-1 [middle dot] min-1 (control group), bispectral index (BIS) values were measured.

Results: Part I: The mean propofol infusion rate in the magnesium group (81.81 +/- 13.09 [mu]g [middle dot] kg-1 [middle dot] min-1) was significantly less than in the control group (167.57 +/- 47.27). Part II: BIS values in the control group (40.70 +/- 3.89) were significantly less than those in the magnesium group (57.80 +/- 7.32).     

Acute Pain Induces Insulin Resistance in Humans

Background: Painful trauma results in a disturbed metabolic state with impaired insulin sensitivity, which is related to the magnitude of the trauma. The authors explored whether pain per se influences hepatic and extrahepatic actions of insulin.

Methods: Ten healthy male volunteers underwent two randomly sequenced hyperinsulinemic-euglycemic (insulin infusion rate, 0.6 mU [middle dot] kg-1 [middle dot] min-1 for 180 min) clamp studies 4 weeks apart. Self-controlled painful electrical stimulation was applied to the abdominal skin for 30 min, to a pain intensity of 8 on a visual analog scale of 0-10, just before the clamp procedure (study P). In the other study, no pain was inflicted (study C).

Results: Pain reduced whole-body insulin-stimulated glucose uptake from 6.37 +/- 1.87 mg [middle dot] kg-1 [middle dot] min-1 (mean +/- SD) in study C to 4.97 +/- 1.38 mg [middle dot] kg-1 [middle dot] min-1 in study P (P < 0.01) because of a decrease in nonoxidative glucose disposal, as determined by indirect calorimetry (2.47 +/- 0.88 mg [middle dot] kg-1 [middle dot] min-1 in study P vs. 3.41 +/- 1.03 mg [middle dot] kg-1 [middle dot] min-1 in study C;P < 0.05). Differences in glucose oxidation rates were not statistically significant. The suppression of isotopically determined endogenous glucose output during hyperinsulinemia tended to be decreased after pain (1.67 +/- 0.48 mg [middle dot] kg-1 [middle dot] min-1 in study P vs. 2.04 +/- 0.45 mg [middle dot] kg-1 [middle dot] min-1 in study C;P = 0.06). Pain elicited a twofold to threefold increase in serum cortisol (P < 0.01), plasma epinephrine (P < 0.05), and serum free fatty acids (P < 0.05). Similarly, circulating concentrations of glucagon and growth hormone tended to increase during pain.     

Mild Hypothermia Has Minimal Effects on the Tolerance to Severe Progressive Normovolemic Anemia in Swine

Background: The benefits of hypothermia during acute severe anemia are not entirely settled. The authors hypothesized that cooling would improve tolerance to anemia.

Methods: Eight normothermic (38.0 +/- 0.5[degrees]C) and eight hypothermic (32.0 +/- 0.5[degrees]C) pigs anesthetized with midazolam-fentanyl-vecuronium-isoflurane (0.5% inspired concentration) were subjected to stepwise normovolemic hemodilution (hematocrit, 15%, 10%, 7%, 5%, 3%). Critical hemoglobin concentration (HgbCRIT) and critical oxygen delivery (DO2CRIT), i.e., the hemoglobin concentration (Hgb) and oxygen delivery (DO2) at which oxygen consumption (VO2, independently measured by indirect calorimetry) was no longer sustained, and Hgb at the moment of death, defined prospectively as the point when VO2 decreased below 40 ml/min, were used to assess the tolerance of the two groups to progressive isovolemic anemia.

Results: At hematocrits of 15% and 10% (Hgb, 47 and 31 g/l), VO2 was maintained in both groups by an increase (P < 0.001) in cardiac output (CO) and extraction ratio (ER;P < 0.001) with unchanged mean arterial lactate concentration (Lart). At hematocrit of 7% (Hgb, 22 g/l), all normothermic but no hypothermic animals had DO2-dependent VO2. No normothermic and three hypothermic animals survived to 5% hematocrit (Hgb, 15 g/l), and none survived to 3%. HgbCRIT was 23 +/- 2 g/l and 19 +/- 6 g/l (mean +/- SD) in normothermic and hypothermic animals, respectively (P = 0.053). Hgb at death was 19 +/- 3 g/l versus 14 +/- 4 g/l (P = 0.015), and DO2CRIT was 8.7 +/- 1.7 versus 4.6 +/- 0.8 ml [middle dot] kg-1 [middle dot] min-1 (P < 0.001).     

Effect of Dobutamine on Splanchnic Carbohydrate Metabolism and Amino Acid Balance after Cardiac Surgery

Background: As a predominant [beta]-adrenergic agonist, dobutamine may modify blood flow distribution and increase metabolic demands. The authors investigated the effect of a dobutamine-induced increase in cardiac output on splanchnic and femoral blood flow and metabolism in patients after cardiac surgery.

Methods: Seventeen stable patients were randomized to receive dobutamine or placebo (n = 8 per group, one dropout). After baseline measurement for systemic, splanchnic, and femoral blood flow (by dye dilution); oxygen consumption; gastric mucosal pressure of carbon dioxide (PCO2); total and splanchnic glucose production (by stable isotope tracer dilution); and regional lactate and amino acid balance, patients received either dobutamine, at a dosage (6 [mu]g [middle dot] kg-1min-1) sufficient to increase cardiac index by at least 25%, or placebo. A second set of measurements was performed 60 min after the start of dobutamine or placebo infusion.

Results: Dobutamine increased cardiac index (3.0 +/- 0.6 to 4.4 +/- 1.0 l [middle dot] min-1m-2, mean +/- SD;P< 0.05), splanchnic blood flow (from 0.8 +/- 0.2 to 1.0 +/- 0.2 l [middle dot] min-1m-2;P< 0.05), femoral blood flow (from 0.2 +/- 0.1 to 0.3 +/- 0.1 l [middle dot] min-1m-2;P< 0.05), and the arterial-gastric mucosal PCO2 gap (from 11.4 +/- 9.5 to 11.9 +/- 8.0 mmHg;P< 0.05). Dobutamine increased systemic oxygen consumption (from 132 +/- 14 to 146 +/- 13 ml [middle dot] min-1 [middle dot] m-2;P< 0.05) but not splanchnic or femoral oxygen consumption. Splanchnic glucose production and lactate and amino acid balance did not change.     

Remifentanil versus Morphine Analgesia and Sedation for Mechanically Ventilated Critically Ill Patients: A Randomized Double Blind Study

Background: The rapid onset and offset of action of remifentanil could make it quickly adjustable to the required level of sedation in critically ill patients. The authors hypothesized that the efficacy of a remifentanil-based regimen was greater than that of a morphine-based regimen.

Methods: Forty intent-to-treat patients were randomly allocated to receive a blinded infusion of either remifentanil 0.15 [mu]g[middle dot]kg-1[middle dot]min-1 or morphine 0.75 [mu]g[middle dot]kg-1[middle dot]min-1. The opioid infusion was titrated, in the first intent, to achieve optimal sedation defined as Sedation Agitation scale of 4. A midazolam open-label infusion was started if additional sedation was required.

Results: The mean percentage hours of optimal sedation was significantly longer in the remifentanil group (78.3 +/- 6.2) than in the morphine group (66.5 +/- 8.5). This was achieved with less frequent infusion rate adjustments (0.34 +/- 0.25 changes/h) than in the morphine group (0.42 +/- 0.22 changes/h). The mean duration of mechanical ventilation and extubation time were significantly longer in the morphine group (18.1 +/- 3.4 h, 73 +/- 7 min) than in the remifentanil group (14.1 +/- 2.8 h, 17 +/- 6 min), respectively. Remifentanil mean infusion rate was 0.13 +/- 0.03 [mu]g[middle dot]kg-1[middle dot]min-1, whereas morphine mean infusion rate was 0.68 +/- 0.28 [mu]g[middle dot]kg-1[middle dot]min-1. More subjects in the morphine group (9 of 20) than in the remifentanil group (6 of 20) required midazolam. The incidence of adverse events was low and comparable across the two treatment groups.     

Epidural Blockade Modifies Perioperative Glucose Production without Affecting Protein Catabolism

Background: Epidural blockade with local anesthetic has been shown to blunt the increase in plasma glucose concentration during and after abdominal surgery. The aim of the study was to test the hypothesis that epidural blockade inhibits this hyperglycemic response by attenuating endogenous glucose production. The authors further examined if the modification of glucose production by epidural blockade has an impact on perioperative protein catabolism.

Methods: Sixteen patients undergoing colorectal surgery received either general anesthesia and epidural blockade with local anesthetic (n = 8) or general anesthesia alone (control, n = 8). Glucose and protein kinetics were assessed by stable isotope tracer technique ([6,6-2H2]glucose, L-[1-13C]leucine) during and 2 h after surgery. Plasma concentrations of glucose, lactate, free fatty acids (FFA), cortisol, glucagon, and insulin were also determined.

Results: Epidural blockade blunted the perioperative increase in the plasma concentration of glucose, cortisol, and glucagon when compared with the control group (P < 0.05). Plasma concentrations of lactate, FFA, and insulin did not change. Intra- and postoperative glucose production was lower in patients with epidural blockade than in control subjects (intraoperative, epidural blockade 8.2 +/- 1.9 vs. control 10.7 +/- 1.4 [mu]mol[middle dot]kg-1[middle dot]min-1, P < 0.05; postoperative, epidural blockade 8.5 +/- 1.8 vs. control 10.5 +/- 1.2 [mu]mol[middle dot]kg-1[middle dot]min-1, P < 0.05), whereas glucose clearance decreased to a comparable extent in both groups (P < 0.05). Protein breakdown (P < 0.05), protein synthesis (P < 0.05), and amino acid oxidation (P > 0.05) decreased with both anesthetic techniques.     

Remifentanil Requirements during Sevoflurane Administration to Block Somatic and Cardiovascular Responses to Skin Incision in Children and Adults

Background: The authors found no studies comparing intraoperative requirements of opioids between children and adults, so they determined the infusion rate of remifentanil to block somatic (IR50) and autonomic response (IRBAR50) to skin incision in children and adults.

Methods: Forty-one adults (aged 20-60 yr) and 24 children (aged 2-10 yr) undergoing lower abdominal surgery were studied. In adults, anesthesia induction was with sevoflurane during remifentanil infusion, whereas in children remifentanil administration was started after induction with sevoflurane. After intubation, sevoflurane was administered in 100% O2 and was adjusted to an ET% of 1 MAC-awake corrected for age at least 15 min before surgery. Patients were randomized to receive remifentanil at a rate ranging from 0.05 to 0.35 [mu]g [middle dot] kg-1 [middle dot] min-1 for at least 20 min before surgery. At the beginning of surgery, only the skin incision was performed, and the somatic and autonomic responses were observed. The somatic response was defined as positive with any gross movement of extremity, and the autonomic response was deemed positive with any increase in heart rate or mean arterial pressure equal to or more than 10% of preincision values. Using logistic regression, the IR50 and IRBAR50 were determined in both groups of patients and compared with unpaired Student t test. A P value less than 0.05 was considered significant.

Results: The IR50 +/- SD was 0.10 +/- 0.02 [mu]g [middle dot] kg-1 [middle dot] min-1 in adults and 0.22 +/- 0.03 [mu]g [middle dot] kg-1 [middle dot] min-1 in children (P < 0.001). The IRBAR50 +/- SD was 0.11 +/- 0.02 [mu]g [middle dot] kg-1 [middle dot] min-1 in adults and 0.27 +/- 0.06 [mu]g [middle dot] kg-1 [middle dot] min-1 in children (P < 0.001).     

Technique for Using Video Microscopy and Indicator Dilution for Repeated Measurements of Cardiac Output in Small Animals

Background: The authors developed an indicator dilution technique for small animals to repeatedly determine cardiac output and blood volume without cardiac instrumentation or blood sampling.

Methods: Observations were made in the hamster (N = 32, 70 mg/kg pentobarbital) cremaster using in vivo fluorescence videomicroscopy. Fluorescein isothiocyanate-conjugated bovine serum albumin (10 mg/ml) was injected as a bolus dose (right jugular) while video recording the light intensity in a 20-[mu]m arteriole (intensified charge-coupled device [CCD] camera at fixed gain). The intensity signal was analyzed over time (background subtracted) and calibrated to the dye concentration. The ex vivo calibration was performed using a constant optical path length (20 [mu]m) and a range of dye and hematocrit concentrations. In vivo tube hematocrit was determined using standard methods with fluorescently labeled erythrocytes. Thus, quenching of the fluorescence signal by hemoglobin was corrected for the calibration, and the plasma space in the arteriole was determined. The steady state dye concentration measured by the light intensity at 2 min was not different from the dye concentration found by direct spectrophotometric analysis of the plasma.

Results: Cardiac index was calculated as milliliters of blood per minute per kilogram body weight. The calculated cardiac index was 359 +/- 18 ml [middle dot] min-1 [middle dot] kg-1, which is not different from the reported values for hamsters. Cardiac output was increased twofold when enough intravenous nitroprusside or nitroglycerine was injected to decrease mean arterial pressure from 90 to 70 mmHg. Cardiac output was elevated during dobutamine infusion (16 [mu]g [middle dot] kg-1 [middle dot] min-1) and decreased during esmolol infusion (50, 75 [middle dot] kg-1 [middle dot] min-1). Blood volume determined from the steady state dye concentrations was 6.2 +/- 0.5 ml/100 g body weight, within the normal range for hamsters.     

Isoflurane Preconditions Myocardium against Infarction via Release of Free Radicals

Background: Isoflurane exerts cardioprotective effects that mimic the ischemic preconditioning phenomenon. Generation of free radicals is implicated in ischemic preconditioning. The authors investigated whether isoflurane-induced preconditioning may involve release of free radicals.

Methods: Sixty-one [alpha]-chloralose-anesthetized rabbits were instrumented for measurement of left ventricular (LV) pressure (tip-manometer), cardiac output (ultrasonic flowprobe), and myocardial infarct size (triphenyltetrazolium staining). All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Rabbits of all six groups underwent a treatment period consisting of either no intervention for 35 min (control group, n = 11) or 15 min of isoflurane inhalation (1 minimum alveolar concentration end-tidal concentration) followed by a 10-min washout period (isoflurane group, n = 12). Four additional groups received the radical scavenger N-(2-mercaptoproprionyl)glycine (MPG; 1 mg [middle dot] kg-1 [middle dot] min-1) or Mn(III)tetrakis(4-benzoic acid)porphyrine chloride (MnTBAP; 100 [mu]g [middle dot] kg-1 [middle dot] min-1) during the treatment period with (isoflurane + MPG; n = 11; isoflurane + MnTBAP, n = 9) or without isoflurane inhalation (MPG, n = 11; MnTBAP, n = 7).

Results: Hemodynamic baseline values were not significantly different between groups (LV pressure, 97 +/- 17 mmHg [mean +/- SD]; cardiac output, 228 +/- 61 ml/min). During coronary artery occlusion, LV pressure was reduced to 91 +/- 17% of baseline and cardiac output to 94 +/- 21%. After 2 h of reperfusion, recovery of LV pressure and cardiac output was not significantly different between groups (LV pressure, 83 +/- 20%; cardiac output, 86 +/- 23% of baseline). Infarct size was reduced from 49 +/- 17% of the area at risk in controls to 29 +/- 19% in the isoflurane group (P = 0.04). MPG and MnTBAP themselves had no effect on infarct size (MPG, 50 +/- 14%; MnTBAP, 56 +/- 15%), but both abolished the preconditioning effect of isoflurane (isoflurane + MPG, 50 +/- 24%, P = 0.02; isoflurane + MnTBAP, 55 +/- 10%, P = 0.001).     

Anaphylactic Shock: A Form of Distributive Shock without Inhibition of Oxygen Consumption

Background: The pathophysiology of anaphylactic shock during anesthesia is incompletely characterized. It is described as distributive by analogy with septic shock (anaerobic metabolism, high tissue oxygen pressure [Ptio2] values). The Ptio2 profile and its metabolic consequences during anaphylaxis are not known.

Methods: Ovalbumin-sensitized anaphylactic shock rats (n = 11) were compared to nicardipine-induced hypotension rats (n = 12) for systemic hemodynamics, Ptio2, sympathetic nervous system activation, skeletal muscle blood flow, and interstitial lactate and pyruvate concentrations using combined microdialysis and polarographic Clark-type oxygen probes.

Results: In both groups, the time course and the magnitude of arterial hypotension were similar. The ovalbumin group but not the nicardipine group displayed decreased skeletal muscle blood flow (from 45 +/- 6.2 ml [middle dot] 100 g-1[middle dot]min-1 to 24.3 +/- 5 ml[middle dot]100 g-1[middle dot]min-1; P < 0.0001) and Ptio2 values (from 42 +/- 5 to 5 +/- 2; P < 0.0001). The ovalbumin group had more intense sympathetic nervous system activation with higher plasma epinephrine and interstitial norepinephrine concentrations. For the ovalbumin group, there was skeletal muscle anaerobic metabolism (lactate concentration increased from 0.446 +/- 0.105 to 1.741 +/- 0.459 mm; P < 0.05) and substrate depletion (pyruvate concentration decreased from 0.034 +/- 0.01 mm to 0.006 +/- 0.002 mm; P < 0.05) leading to increased interstitial lactate/pyruvate ratios (from 17 +/- 6 to 311 +/- 115; P < 0.05).     

S (+)-Ketamine Increases Muscle Sympathetic Activity and Maintains the Neural Response to Hypotensive Challenges in Humans

Background: S (+)-Ketamine is reported to exert twofold greater analgesic and hypnotic effects but a shorter recovery time in comparison with racemic ketamine, indicating possible differential effects of stereoisomers. However, cardiovascular regulation during S (+)-ketamine anesthesia has not been studied. Muscle sympathetic activity (MSA) may be an indicator of the underlying alterations of sympathetic outflow. Whether S (+)-ketamine decreases MSA in a similar manner as the racemate is not known. Thus, the authors tested the hypothesis that S (+)-ketamine changes MSA and the muscle sympathetic response to a hypotensive challenge.

Methods: Muscle sympathetic activity was recorded by microneurography in the peroneal nerve of six healthy participants before and during anesthesia with S (+)-ketamine (670 [mu]g/kg intravenously followed by 15 [mu]g [middle dot] kg-1 [middle dot] min-1). Catecholamine and ketamine plasma concentrations, heart rate, and arterial blood pressure were also determined. MSA responses to a hypotensive challenge were assessed by injection of sodium nitroprusside (2-10 [mu]g/kg) before and during S (+)-ketamine anesthesia. In the final step, increased arterial pressure observed during anesthesia with S (+)-ketamine was adjusted to preanesthetic values by sodium nitroprusside infusion (1-6 [mu]g [middle dot] kg-1 [middle dot] min-1).

Results: Anesthesia with S (+)-ketamine (ketamine plasma concentration 713 +/- 295 [mu]g/l) significantly increased MSA burst frequency (mean +/- SD; 18 +/- 6 to 35 +/- 11 bursts/min) and burst incidence (32 +/- 10 to 48 +/- 15 bursts/100 heartbeats) and was associated with a doubling of norepinephrine plasma concentration (from 159 +/- 52 to 373 +/- 136 pg/ml) parallel to the increase in MSA. Heart rate and arterial blood pressure also significantly increased. When increased arterial pressure during S (+)-ketamine was decreased to awake values with sodium nitroprusside, MSA increased further (to 53 +/- 24 bursts/min and 60 +/- 20 bursts/100 heartbeats, respectively). The MSA increase in response to the hypotensive challenge was fully maintained during anesthesia with S (+)-ketamine.     

Citrate Storage Affects Thrombelastograph® Analysis

Background: Thrombelastograph(R) analysis (TEG(R)) is used to evaluate blood coagulation. Ideally, whole blood is immediately processed. If impossible, blood may be citrated and assessed after recalcification. No data describe the effect of such treatment and storage on TEG(R) parameters.

Methods: Three studies were performed in 90 surgical patients. In 30 patients, blood was citrated (1:10, 0.129 M) and recalcified (20 [mu]l 2 M CaCl2 to 340 [mu]l citrated blood), and TEG(R) was performed with native blood and after recalcification after 0, 15, and 30 min of citrate storage. In another 30 patients, TEG(R) was performed with citrated blood recalcified immediately and after 1-72 h storage. In a third study, thrombin-antithrombin complex, prothrombin fragment 1+2, and [beta]-thromboglobulin were measured (using enzyme-linked immunoabsorbant assay tests) at corresponding time points. Data were compared using repeated-measures analysis of variance and post hoc paired t tests.

Results: TEG(R) parameters were different in recalcified citrated blood compared with native blood (P < 0.05) and changed significantly during 30-min (P < 0.025) and 72-h (P < 0.001) citrate storage. TEG(R) parameters measured between 1 and 8 h of citrate storage were stable. Thrombin-antithrombin complex and prothrombin fragment 1+2 values were not elevated in native blood. After 30 min of citrate storage a gradual thrombin activation was observed, as evidenced by increasing thrombin-antithrombin complex and prothrombin fragment 1+2 values (P < 0.05). [beta]-Thromboglobulin level was increased after 2 and 8 h of citrate storage (P < 0.01).     

Effects of a Dobutamine-induced Increase in Splanchnic Blood Flow on Hepatic Metabolic Activity in Patients with Septic Shock

Background: Septic shock leads to increased splanchnic blood flow (Qspl) and oxygen consumption (VO2 spl). The increased Qspl, however, may not match the splanchnic oxygen demand, resulting in hepatic dysfunction. This concept of ongoing tissue hypoxia that can be relieved by increasing splanchnic oxygen delivery (DO2 spl), however, was challenged because most of the elevated VO2 spl was attributed to increased hepatic glucose production (HGP) resulting from increased substrate delivery. Therefore the authors tested the hypothesis that a dobutamine-induced increase in Qspl and DO2 spl leads to increased VO sub 2 spl associated with accelerated HGP in patients with septic shock.

Methods: Twelve patients with hyperdynamic septic shock in whom blood pressure had been stabilized (mean arterial pressure greater or equal to 70 mmHg) with volume resuscitation and norepinephrine received dobutamine to obtain a 20% increase in cardiac index (CI). Qspl, DO2 spl, and VO sub 2 spl were assessed using the steady-state indocyanine green clearance technique with correction for hepatic dye extraction, and HGP was determined from the plasma appearance rate of stable, non-radioactive-labeled glucose using a primed-constant infusion approach.

Results: Although the increase in CI resulted in a similar increase in Qspl (from 0.91 +/- 0.21 to 1.21 +/- 0.34 l [center dot] min sup -1 [center dot] m2; P < 0.001) producing a parallel increase of DO2 spl (from 141 +/- 33 to 182 +/- 44 ml [center dot] min sup -1 [center dot] m2; P < 0.001), there was no effect on VO2 spl (73 +/- 16 and 82 +/- 21 ml [center dot] min sup -1 [center dot] m2, respectively). Hepatic glucose production decreased from 5.1 +/- 1.6 to 3.6 +/- 0.9 mg [center dot] kg sup -1 [center dot] min sup -1 (P < 0.001).     

Treatment of Pulmonary Hypertension and Hypoxia Due to Oleic Acid Induced Lung Injury with Intratracheal Prostaglandin E1 during Partial Liquid Ventilation

Background: Partial liquid ventilation using perfluorocarbon liquids may be of therapeutic benefit in patients with acute respiratory failure. This study investigated the effects of prostaglandin E1 (PGE1) delivered intratracheally during partial liquid ventilation on lung function and pulmonary circulation in rabbits with acute respiratory distress syndrome.

Methods: Lung injury was induced by intravenous oleic acid in adult Japanese white rabbits, 1 h after which they were divided into four groups of 10 animals. Group 1 received mechanical ventilation alone, group 2 received aerosolized PGE1 (5 [micro sign]g followed by 0.1 [micro sign]g [middle dot] kg-1 [middle dot] min-1) under mechanical ventilation combined with 5 cm H2 O positive end-expiratory pressure, and groups 3 and 4 received partial liquid ventilation with 15 ml/kg perflubron. Group 4 received a 5-[micro sign]g bolus followed by 0.1 [micro sign]g [middle dot] kg-1 [middle dot] min-1 PGE1 instilled intratracheally (not by aerosol) in combination with partial liquid ventilation. Measurements were performed at 30-min intervals for 120 min after lung injury.

Results: After lung injury, hypoxemia, hypercapnia, acidosis, and pulmonary hypertension developed in all animals and were sustained in groups 1 and 2 throughout the experiment. The partial pressure of oxygen in arterial blood of animals in group 3 improved with initiation of treatment, with statistical significance achieved at the 30 and 60 min time points as compared with controls. Group 4 animals had immediate and sustained increases in the partial pressure of oxygen in arterial blood that were significant compared with all other groups during the experiment. Statistically significant reductions in mean pulmonary artery pressure were seen only in group 4 animals compared with all other groups.     

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 [mu]g/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 [mu]g [middle dot] kg-1 [middle dot] 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 (MACBIS50). Plasma lidocaine concentrations were measured.

Results: The MACBIS50 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 [mu]g/ml) were similar to those in the epidural lidocaine group (2.0 [mu]g/ml).     

Cerebral Blood Volume (CBV) in Humans during Normo- and Hypocapnia: Influence of Nitrous Oxide (N2O)

Background : It is generally argued that variations in cerebral blood flow create concomitant changes in the cerebral blood volume (CBV). Because nitrous oxide (N2O) inhalation both increases cerebral blood flow and may increase intracranial pressure, it is reasonable to assume that N2O acts as a general vasodilatator in cerebral vessels both on the arterial and on the venous side. The aim of the current study was to evaluate the effect of N2O on three-dimensional regional and global CBV in humans during normocapnia and hypocapnia.

Methods : Nine volunteers were studied under each of four conditions: normocapnia, hypocapnia, normocapnia + 40-50% N2O, and hypocapnia + 40-50% N2O. CBV was measured after 99mTc-labeling of blood with radioactive quantitative registration via single photon emission computer-aided tomography scanning.

Results : Global CBV during normocapnia and inhalation of 50% O2 was 4.25 +/- 0.57% of the brain volume (4.17 +/- 0.56 ml/100 g, mean +/- SD) with no change during inhalation of 40-50% N2O in O2. Decreasing carbon dioxide (CO2) by 1.5 kPa (11 mmHg) without N2O inhalation and by 1.4 kPa (11 mmHg) with N2O inhalation reduced CBV significantly (F = 57, P < 0.0001), by 0.27 +/- 0.10% of the brain volume per kilopascal (0.26 +/- 0.10 ml [middle dot] 100 g-1 [middle dot] kPa-1) without N2O inhalation and by 0.35 +/- 0.22% of the brain volume per kilopascal (0.34 +/- 0.22 ml [middle dot] 100 g-1 [middle dot] kPa-1) during N2O inhalation (no significant difference). The amount of carbon dioxide significantly altered the regional distribution of CBV (F = 47, P < 0.0001), corresponding to a regional difference in [DELTA]CBV when CO2 is changed. N2O inhalation did not significantly change the distribution of regional CBV (F = 2.4, P = 0.051) or [DELTA]CBV/[DELTA]CO2 in these nine subjects.     

High-dose Remifentanil Does Not Impair Cerebrovascular Carbon Dioxide Reactivity in Healthy Male Volunteers

Background: Cerebrovascular carbon dioxide reactivity during high-dose remifentanil infusion was investigated in volunteers by measurement of regional cerebral blood flow (rCBF) and mean CBF velocity (CBFv).

Methods: Ten healthy male volunteers with a laryngeal mask for artificial ventilation received remifentanil at an infusion rate of 2 and 4 [mu]g [middle dot] kg-1 [middle dot] min-1 under normocapnia, hypocapnia, and hypercapnia. Stable xenon-enhanced computed tomography and transcranial Doppler ultrasonography of the left middle cerebral artery were used to assess rCBF and mean CBFv, respectively. If required, blood pressure was maintained within baseline values with intravenous phenylephrine to avoid confounding effects of altered hemodynamics.

Results: Hemodynamic parameters were maintained constant over time. Remifentanil infusion at 2 and 4 [mu]g [middle dot] kg-1 [middle dot] min-1 significantly decreased rCBF and mean CBFv. Both rCBF and mean CBFv increased as the arterial carbon dioxide tension increased from hypocapnia to hypercapnia, indicating that cerebrovascular reactivity remained intact. The average slopes of rCBF reactivity were 0.56 +/- 0.27 and 0.49 +/- 0.28 ml [middle dot] 100 g-1 [middle dot] min-1 [middle dot] mmHg-1 for 2 and 4 [mu]g[middle dot]kg-1[middle dot]min-1 remifentanil, respectively (relative change in percent/mmHg: 1.9 +/- 0.8 and 1.6 +/- 0.5, respectively). The average slopes for mean CBFv reactivity were 1.61 +/- 0.95 and 1.54 +/- 0.83 cm [middle dot] s-1 [middle dot] mmHg-1 for 2 and 4 [mu]g [middle dot] kg-1 [middle dot] min-1 remifentanil, respectively (relative change in percent/mmHg: 1.86 +/- 0.59 and 1.79 +/- 0.59, respectively). Preanesthesia and postanesthesia values of rCBF and mean CBFv did not differ.     

Potentiation of Mivacurium Blockade by Low Dose of Pancuronium: A Pharmacokinetic Study

Background: Mivacurium is potentiated by pancuronium to a much greater extent than other relaxants. In a previous investigation we suggested that this potentiation could be due to the ability of pancuronium to inhibit plasma cholinesterase activity, but we did not measure plasma concentrations of mivacurium. In the current study we performed a pharmacokinetic analysis by measuring the plasma concentration of mivacurium when preceded by administration of a low dose of pancuronium.

Methods: After induction of general anesthesia with propofol and fentanyl and orotracheal intubation, 10 patients (pancuronium-mivacurium group) received 15 [mu]g/kg pancuronium followed 3 min later by 0.1 mg/kg mivacurium, whereas 10 other patients (mivacurium group) received saline followed by 0.13 mg/kg mivacurium 3 min later. Plasma cholinesterase activity was measured before and 3 and 30 min after pancuronium dosing in the pancuronium-mivacurium group and was measured before and after administration of saline in the mivacurium group. Arterial plasma concentrations of mivacurium and its metabolites were measured at 0.5, 1, 1.5, 2, 4, 10, 20, and 30 min after injection. Neuromuscular blockade was assessed by mechanomyography.

Results: Plasma cholinesterase activity decreased by 26% in the pancuronium-mivacurium group 3 min after injection of pancuronium (P < 0.01) and returned to baseline values 30 min later; however, no significant variation was observed in the mivacurium group. The clearances of the two most active isomers (Cis-Trans and Trans-Trans) were lower in the pancuronium-mivacurium group (17.6 +/- 5.1, 14.7 +/- 5.3 ml [middle dot] min-1[middle dot] kg-1, respectively) than in the mivacurium group (32.4 +/- 20.2, 24.8 +/- 13.5 ml [middle dot] min-1[middle dot] kg-1;P < 0.05).