Sympathetic Ganglionic Blockade Masks Beneficial Effect of Isoflurane on Histologic Outcome from Near-complete Forebrain Ischemia in the Rat

Background: Isoflurane-anesthetized rats have better outcome from global cerebral ischemia than rats anesthetized with fentanyl and nitrous oxide. The authors wanted to determine whether circulating catecholamine concentrations depend on the anesthetic agent and whether sympathetic ganglionic blockade affects anesthetic-mediated differences in outcome from near-complete forebrain ischemia.

Methods: For two different experiments, normothermic Sprague-Dawley rats that had fasted were assigned to one of four groups and subjected to 10 min of 30 mmHg mean arterial pressure and bilateral carotid occlusion. Rats were anesthetized with 1.4% isoflurane or fentanyl (25 [micro sign]g [middle dot] kg-1 [middle dot] h-1) and 70% nitrous oxide, with or without preischemic trimethaphan (2.5 mg given intravenously). In experiment 1, arterial plasma catecholamine concentrations were measured before, at 2 and 8 min during, and after ischemia (n = 5-8). In experiment 2, animals (n = 15) underwent histologic analysis 5 days after ischemia.

Results: In experiment 1, intraischemic increases in plasma norepinephrine and epinephrine levels were 28 and 12 times greater in the fentanyl-nitrous oxide group than in the isoflurane group (P < 0.01). Trimethaphan blocked all changes in plasma catecholamine concentrations (P < 0.02). In experiment 2, isoflurane reduced the mean +/- SD percentage of dead hippocampal CA1 neurons compared with fentanyl-nitrous oxide (43 +/- 22% vs. 87 +/- 10%; P < 0.001). Trimethaphan abolished the beneficial effects of isoflurane (91 +/- 6%; P < 0.001). Similar observations were made in the cortex.     

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).     

Periischemic Cerebral Blood Flow (CBF) Does Not Explain Beneficial Effects of Isoflurane on Outcome from Near-complete Forebrain Ischemia in Rats

Background: Isoflurane improves outcome from near-complete forebrain ischemia in rats compared with fentanyl-nitrous oxide (N2O). Sympathetic ganglionic blockade with trimethaphan abolishes this beneficial effect. To evaluate whether anesthesia-related differences in cerebral blood flow (CBF) may explain these findings, this study compared regional CBF before, during, and after near-complete forebrain ischemia in rats anesthetized with either isoflurane (with and without trimethaphan) or fentanyl-nitrous oxide.

Methods: Fasted, normothermic isoflurane anesthetized Sprague-Dawley rats were prepared for near-complete forebrain ischemia (10 min of bilateral carotid occlusion and mean arterial pressure = 30 mmHg). After surgery, rats were anesthetized with either 1.4% isoflurane (with or without 2.5 mg of trimethaphan intravenously at onset of ischemia) or fentanyl-nitrous oxide (25[mu]g [middle dot] kg-1 [middle dot] h-1 [middle dot] 70% N2O-1). Regional CBF was determined (14C-iodoantipyrine autoradiography) before ischemia, 8 min after onset of ischemia, and 30 min after onset of reperfusion.

Results: Regional CBF did not differ significantly among groups at any measurement interval. Ischemia caused a marked flow reduction to 5% or less of baseline (P < 0.001) in selectively vulnerable regions, such as the cortex, caudoputamen and hippocampus, whereas flow in the brain stem and cerebellum was preserved. Reperfusion at 30 min was associated with partial restoration of flow to 35-50% of baseline values in ischemic structures.     

Effects of Mild Hypothermia on Blood-Brain Barrier Disruption during Isoflurane or Pentobarbital Anesthesia

Background: This study was performed to determine whether mild hypothermia (32[degrees]C) could attenuate the degree of blood-brain barrier (BBB) disruption caused by a hyperosmolar solution and whether the degree of disruption would vary depending on anesthetic agents.

Methods: Rats were assigned to one of four groups: normothermic isoflurane, normothermic pentobarbital, hypothermic isoflurane, and hypothermic pentobarbital. During isoflurane (1.4%; normothermic or hypothermic) or pentobarbital (50 mg/kg administered intraperitoneally; normothermic or hypothermic) anesthesia, the external carotid artery and the femoral artery and vein were catheterized. Body temperature was maintained at 37 and 32[degrees]C for the normothermic and hypothermic groups, respectively. To open the BBB, 25% mannitol was infused through the right carotid artery at the rate of 0.25 ml [middle dot] kg-1 [middle dot] s-1 for 30 s. The transfer coefficient of 14C-[alpha]-aminoisobutyric acid was determined.

Results: Blood pressure was similar among the four groups of animals. The degree of the BBB disruption by hyperosmolar mannitol was less with isoflurane than pentobarbital anesthesia in the normothermic groups (transfer coefficient: 29.9 +/- 17.1 and 50.4 +/- 17.5 [mu]l [middle dot] g-1 [middle dot] min-1 for normothermic isoflurane and pentobarbital, respectively;P < 0.05). Mild hypothermia decreased the BBB disruption during anesthesia with both anesthetic agents (hypothermic isoflurane: 9.8 +/- 8.3 [mu]l [middle dot] g-1 [middle dot] min-1, P < 0.05 vs. normothermic isoflurane; hypothermic pentobarbital: 30.2 +/- 13.9 [mu]l [middle dot] g-1 [middle dot] min-1, P < 0.05 vs. normothermic pentobarbital), but the disruption was less during isoflurane anesthesia (hypothermic isoflurane vs. hypothermic pentobarbital, P < 0.005). In the contralateral cortex, there were no significant differences among these four experimental groups.     

Effects of isoflurane, ketamine, and fentanyl/N2O on concentrations of brain and plasma catecholamines during near-complete cerebral ischemia in the rat

We postulated that adrenergic responses to global cerebral ischemia are anesthetic-dependent and similar in both brain and arterial blood. Rats were anesthetized with isoflurane (1.4%), ketamine (1 mg x kg(-1) x min(-1)), or fentanyl (25 microg x kg(-1) x h(-1))/70% N2O. The carotid arteries were occluded for either 20 min with mean arterial pressure (MAP) 50 mm Hg (incomplete ischemia) or 10 min with MAP 30 mm Hg (near-complete ischemia). Norepinephrine was measured in hippocampal microdialysate. Norepinephrine and epinephrine were measured in arterial plasma. In both hippocampus and plasma, basal norepinephrine was similar among anesthetics. During incomplete ischemia, hippocampal norepinephrine was twofold greater with fentanyl/N2O than with isoflurane (P = 0.037), but plasma norepinephrine and epinephrine were similar and unchanged among all three anesthetics. During near-complete ischemia, hippocampal norepinephrine was threefold greater with ketamine than fentanyl/N2O (P = 0.005), whereas plasma norepinephrine and epinephrine were markedly greater with fentanyl/N2O than with ketamine (P < 0.0005) or isoflurane (P = 0.05). There was no correlation between norepinephrine concentrations in hippocampus and plasma for either incomplete or near-complete ischemia. This study demonstrates that adrenergic responses to global ischemia are anesthetic-dependent, particularly during more severe insults. The absence of a correlation between plasma and brain catecholamine concentrations indicates that adrenergic responses to ischemia are independent in brain and blood. Implications: It has been proposed that anesthetics modulate cerebral ischemic outcome by influencing peripheral adrenergic responses to ischemia. This experiment demonstrates that anesthetics differentially modulate adrenergic responses to ischemia but that effects in plasma and brain are independent. This suggests that events detected in the peripheral circulation do not implicate direct mechanisms of action of catecholamines at the neuronal/glial level.     

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).     

Effect of Low Isoflurane Concentrations on the Ventilation-Perfusion Distribution in Injured Canine Lungs

Background: Rapid recovery and weaning from ventilatory support and cardiovascular stability are suggested advantages of isoflurane inhalation, in concentrations ranging from 0.1 to 0.6 vol%, for long-term sedation in mechanical ventilated patients. This study was designed to determine whether isoflurane in low concentrations impairs pulmonary gas exchange by increasing ventilation and perfusion ([latin capital V with dot above]A/[Latin capital letter Q with dot above]) mismatch during lung injury.

Methods: Fourteen anesthetized dogs received in random order 0, 0.25, or 0.5 vol% end-tidal isoflurane before and after induction of lung injury with oleic acid. Gas exchange was assessed by blood gas analysis and by estimating the [latin capital V with dot above]A/[Latin capital letter Q with dot above] distributions using the multiple inert gas elimination technique.

Results: Administration of oleic acid produced a lung injury with severe [latin capital V with dot above]A/[Latin capital letter Q with dot above] mismatch and 38 +/- 4% intrapulmonary shunting of blood. During lung injury, isoflurane accounted for a dose-related increase in blood flow to shunt units from 38 +/- 4 to 42 +/- 3 (0.25 vol%) and 48 +/- 4% (0.5 vol%) (P < 0.05), dispersion pulmonary blood flow distribution from 0.94 +/- 0.07 to 1.01 +/- 0.09 (0.25 vol%) and 1.11 +/- 0.11% (0.5 vol%) (P < 0.05), and a decrease in perfusion of normal [latin capital V with dot above]A/[Latin capital letter Q with dot above] units from 58 +/- 5 to 55 +/- 4 (0.25 vol%) and 50 +/- 4% (0.5 vol%) (P < 0.05) (mean +/- SE). Isoflurane decreased arterial oxygen partial pressure from 72 +/- 4 to 62 +/- 4 mmHg (0.25 vol%) and 56 +/- 4 mmHg (0.5 vol%) (P < 0.05) and oxygen delivery from 573 +/- 21 to 529 +/- 19 ml [middle dot] kg-1 [middle dot] min-1 (0.25 vol%) and 505 +/- 22 ml [middle dot] kg-1 [middle dot] min-1 (0.5 vol%) (P < 0.05). Gas exchange, perfusion of shunt and normal [latin capital V with dot above]A/[Latin capital letter Q with dot above] units, and pulmonary blood flow distribution was similar in absence of lung injury with and without isoflurane. Isoflurane 0.5 vol% lowered cardiac output during all conditions (P < 0.05).     

Comparison of Adenosine and Remifentanil Infusions as Adjuvants to Desflurane Anesthesia

Background: Because adenosine has been alleged to produce both anesthetic and analgesic sparing effects, a randomized, double-blinded study was designed to compare the perioperative effects of adenosine and remifentanil when administered as intravenous adjuvants during general anesthesia for major gynecologic procedures.

Methods: Thirty-two women were assigned randomly to one of two drug treatment groups. After premedication with 0.04 mg/kg intravenous midazolam, anesthesia was induced with 2 [micro sign]g/kg intravenous fentanyl, 1.5 mg/kg intravenous propofol, and 0.6 mg/kg intravenous rocuronium, and maintained with desflurane, 2%, and nitrous oxide, 65%, in oxygen. Before skin incision, an infusion of either remifentanil (0.02 [micro sign]g [middle dot] kg-1 [middle dot] min-1) or adenosine (25 [micro sign]g [middle dot] kg-1 [middle dot] min-1) was started and subsequently titrated to maintain systolic blood pressure, heart rate, or both within 10-15% of the preincision values.

Results: Adenosine and remifentanil infusions were effective anesthetic adjuvants during lower abdominal surgery. Use of adenosine (mean +/- SEM, 166 +/- 17 [micro sign]g [middle dot] kg-1 [middle dot] min-1) was associated with a significantly greater decrease in systolic blood pressure and higher heart rate values compared with remifentanil (mean +/- SEM, 0.2 +/- 0.03 [micro sign]g [middle dot] kg-1 [middle dot] min-1). Total postoperative opioid analgesic use was 45% and 27% lower in the adenosine group at 0-2 h and 2-24 h after surgery, respectively.     

A comparison of desflurane and isoflurane in patients undergoing coronary artery surgery

Animal studies indicate that desflurane and isoflurane have similar hemodynamic effects when administered in equipotent anesthetic concentrations. The authors compared desflurane and isoflurane, used as primary anesthetics for patients undergoing elective coronary artery bypass surgery whose left ventricular ejection fractions were greater than 0.34. After induction of anesthesia with thiopental (dose 180 +/- 45 mg [mean +/- standard deviation]) and fentanyl, 10 micrograms.kg-1, either desflurane or isoflurane was administered to maintain systolic blood pressure within 70-120% of, and heart rates less than 120% of, the patients' average preoperative values. If adjusting the end-tidal anesthetic concentration within the range of 0-2.0 MAC could not maintain these predefined hemodynamic limits, additional fentanyl or vasoactive drugs were used. Induction and maintenance of anesthesia was accompanied by a significant decrease in mean arterial pressure in both groups (desflurane 97 +/- 12 mmHg at control, decreasing to 71 +/- 5 mmHg during skin preparation; isoflurane 95 +/- 9 mmHg at control, 74 +/- 9 mmHg during skin preparation). One minute after sternotomy, mean arterial pressure in the isoflurane group had returned to control, 97 +/- 9 mmHg, which was significantly greater than in the desflurane group, 87 +/- 12 mmHg. Systolic arterial pressure was also significantly greater in the isoflurane group 1 min after intubation, during skin preparation, and 1 min after sternotomy. Otherwise, the hemodynamic effects of these volatile agents were similar. There were no differences between groups in the incidence of ECG changes indicative of myocardial ischemia prior to cardiopulmonary bypass, perioperative myocardial infarction, or perioperative mortality.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of the α2-Agonist Dexmedetomidine on Cerebral Neurotransmitter Concentrations during Cerebral Ischemia in Rats

Background: This study investigates whether neuroprotection seen with dexmedetomidine is associated with suppression of peripheral or central sympathetic tone.

Methods: Thirty fasted male Sprague-Dawley rats were intubated and ventilated with isoflurane and N2O/O2 (fraction of inspired oxygen = 0.33). Catheters were inserted into the right femoral artery and vein and into the right jugular vein. Cerebral blood flow was measured using laser Doppler flowmetry. Bilateral microdialysis probes were placed into the cortex and the dorsal hippocampus. At the end of preparation, the administration of isoflurane was replaced by fentanyl (bolus: 10 [mu]g/kg; infusion: 25 [mu]g [middle dot] kg-1 [middle dot] h-1). Animals were randomly assigned to one of the following groups: group 1 (n = 10): control animals; group 2 (n = 10): 100 [mu]g/kg dexmedetomidine administered intraperitoneally 30 min before ischemia; group 3 (n = 10): sham-operated rats. Ischemia (30 min) was produced by unilateral carotid artery occlusion plus hemorrhagic hypotension to a mean arterial blood pressure of 30-35 mmHg to reduce ipsilateral cerebral blood flow by 70%. Pericranial temperature, arterial blood gases, and p H were maintained constant. Cerebral catecholamine and glutamate concentrations and plasma catecholamine concentrations were analyzed using high-performance liquid chromatography.

Results: During ischemia, dexmedetomidine suppressed circulating norepinephrine concentrations by 95% compared with control animals. In contrast, brain norepinephrine and glutamate concentrations were increased irrespective of dexmedetomidine infusion before ischemia.     

The Anabolic Effect of Epidural Blockade Requires Energy and Substrate Supply

Background: The authors examined the hypothesis that continuous thoracic epidural blockade with local anesthetic and opioid, in contrast to patient-controlled intravenous analgesia with morphine, stimulates postoperative whole body protein synthesis during combined provision of energy (4 mg [middle dot] kg-1 [middle dot] min-1 glucose) and amino acids (0.02 ml [middle dot] kg-1 [middle dot] min-1 Travasol(TM) 10%, equivalent to approximately 2.9 g [middle dot] kg-1 [middle dot] day-1).

Methods: Sixteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding) on the second day after colorectal surgery performed with or without perioperative epidural blockade. Protein synthesis, breakdown and oxidation, glucose production, and clearance were measured by l-[1-13C]leucine and [6,6-2H2]glucose.

Results: Epidural blockade did not affect protein and glucose metabolism in the fasted state. Parenteral alimentation decreased endogenous protein breakdown and glucose production to the same extent in both groups. Administration of glucose and amino acids was associated with an increase in whole body protein synthesis that was modified by the type of analgesia, i.e., protein synthesis increased by 13% in the epidural group (from 93.3 +/- 16.6 to 104.5 +/- 11.1 [mu]mol [middle dot] kg-1 [middle dot] h-1) and by 4% in the patient-controlled analgesia group (from 90.0 +/- 27.1 to 92.9 +/- 14.8 [mu]mol [middle dot] kg-1 [middle dot] h-1;P = 0.054).     

Low Doses of Fentanyl Block Central Sensitization in the Rat Spinal Cord In Vivo

Background: [mu]-Opioid receptor agonists are strong analgesics. However, their usefulness for preemptive analgesia is controversial. The authors tested antinociceptive and preemptive properties of fentanyl as a [mu]-opioid receptor agonist in a model of spinal nociception in vivo.

Methods: C fiber-evoked potentials were recorded in the superficial laminae I-II of the rat lumbar spinal cord with glass microelectrodes in response to electrical stimulation of the sciatic nerve. High-frequency stimulation was applied on the sciatic nerve to induce long-term potentiation of C fiber-evoked field potentials, a form of central sensitization. To test the effect of fentanyl on acute nociception, fentanyl was infused intravenously at increasing doses (6-192 [mu]g [middle dot] kg-1 [middle dot] h-1). One hour after start of infusion, high-frequency stimulation was applied to evaluate effects of fentanyl on the induction of long-term potentiation.

Results: In the absence of fentanyl, high-frequency stimulation potentiated C fiber-evoked field potentials to 149 +/- 12% of controls (mean +/- SEM; n = 6) for at least 1 h. Increasing doses of fentanyl led to a significant reduction of C fiber-evoked potentials in a dose-dependent manner. The induction of long-term potentiation was blocked by low doses of fentanyl (infusion 12-48 [mu]g [middle dot] kg-1 [middle dot] h-1). At high doses, fentanyl did not block the induction of long-term potentiation (infusion 96-192 [mu]g [middle dot] kg-1 [middle dot] h-1).     

A Comparison of Left Ventricular Performance Indices Measured by Transesophageal Echocardiography with Automated Border Detection

Background: Automated border detection (ABD) allows semiautomated measurement of left ventricular (LV) areas. They can be combined with left ventricular pressure signals to generate pressure-area loops and pressure-dimension indices of contractility. This study compared conventional indices of ventricular performance (fractional area change [FAC] and circumferential fiber shortening [Vcfc]) with pressure-dimension indices of contractility. A secondary aim was to compare the effects of volatile anesthetics on the indices.

Methods: Using transesophageal echocardiography with automated border detection, FAC and Vcfc were obtained in 23 patients after cardiopulmonary bypass. Left ventricular pressures were obtained with a left ventricular catheter. Preload reduction by inferior vena caval occlusion was used to obtain end-systolic elastance (Ees), preload recruitable stroke force (PRSF), and dP/dtmax [middle dot] EDA-1 (EDA = end-diastolic area). In 11 patients, the measurements were repeated at 1 end-tidal minimum alveolar concentration of halothane or isoflurane. The results are expressed as mean +/- SD.

Results: After cardiopulmonary bypass, FAC was 31.1 +/- 7.9%, Vcfc was 0.6 +/- 0.2 circ [middle dot] s-1, Ees was 25.8 +/- 11.6 mmHg [middle dot] cm-2, PRSF was 60.8 +/- 26.6 mmHg, and dP/dtmax [middle dot] -EDA-1 was 245 +/- 123.4 mmHg [middle dot] s-1 [middle dot] cm-2. At 1 minimum alveolar concentration of a volatile anesthetic agent, FAC, Vcfc, and dP/dtmax [middle dot] EDA-1 remained unchanged. Significant decreases in Ees (19%) and PRSF (28%) were observed.     

Comparison of Remifentanil and Fentanyl in Patients Undergoing Craniotomy for Supratentorial Space-occupying Lesions

Background: Remifentanil hydrochloride is an ultra-short-acting, esterase-metabolized micro-opioid receptor agonist. This study compared the use of remifentanil or fentanyl during elective supratentorial craniotomy for space-occupying lesions.

Methods: Sixty-three adults gave written informed consent for this prospective, randomized, double-blind, multiple-center trial. Anesthesia was induced with thiopental, pancuronium, nitrous oxide/oxygen, and fentanyl (n = 32; 2 micro gram [center dot] kg [center dot] sup -1 min sup -1) or remifentanil (n = 31; 1 micro [center dot] kg sup -1 [center dot] min sup -1). After tracheal intubation, infusion rates were reduced to 0.03 micro gram [center dot] kg sup -1 [center dot] min sup -1 (fentanyl) or 0.2 micro gram [center dot] kg sup -1 [center dot] min sup -1 (remifentanil) and then adjusted to maintain anesthesia and stable hemodynamics. Isoflurane was given only after specified infusion rate increases had occurred. At the time of the first burr hole, intracranial pressure was measured in a subset of patients. At bone flap replacement either saline (fentanyl group) or remifentanil ([nearly equal] 0.2 micro gram [center dot] kg sup -1 [center dot] min sup -1) were infused until dressing completion. Hemodynamics and time to recovery were monitored for 60 min. Analgesic requirements and nausea and vomiting were observed for 24 h. Neurological examinations were performed before operation and on postoperative days 1 and 7.

Results: Induction hemodynamics were similar. Systolic blood pressure was greater in the patients receiving fentanyl after tracheal intubation (fentanyl = 127 +/- 18 mmHg; remifentanil = 113 +/- 18 mmHg; P = 0.004). Intracranial pressure (fentanyl = 14 +/- 13 mmHg; remifentanil = 13 +/- 10 mmHg) and cerebral perfusion pressure (fentanyl = 76 +/- 19 mmHg; remifentanil = 78 +/- 14 mmHg) were similar. Isoflurane use was greater in the patients who received fentanyl. Median time to tracheal extubation was similar (fentanyl = 4 min: range = -1 to 40 min; remifentanil = 5 min: range = 1 to 15 min). Seven patients receiving fentanyl and none receiving remifentanil required naloxone. Postoperative systolic blood pressure was greater (fentanyl = 134 +/- 16 mmHg; remifentanil = 147 +/- 15 mmHg; P = 0.001) and analgesics were required earlier in patients receiving remifentanil. Incidences of nausea and vomiting were similar.     

Racemic Ketamine Decreases Muscle Sympathetic Activity but Maintains the Neural Response to Hypotensive Challenges in Humans

Background: Cardiovascular stimulation and increased catecholamine plasma concentrations during ketamine anesthesia have been attributed to increased central sympathetic activity as well as catecholamine reuptake inhibition in various experimental models. However, direct recordings of efferent sympathetic nerve activity have not been performed in humans. The authors tested the hypothesis that racemic ketamine increases efferent muscle sympathetic activity (MSA) and maintains the muscle sympathetic response to hypotensive challenges.

Methods: Muscle sympathetic activity was recorded by microneurography in the peroneal nerve of six healthy subjects before and during anesthesia with racemic ketamine (2 mg/kg intravenously plus 30 [mu]g [middle dot] kg-1 [middle dot] min-1). Catecholamine plasma concentrations, heart rate, and blood pressure were also determined. Muscle sympathetic neural responses to a hypotensive challenge were assessed by injection of sodium nitroprusside (2-10 [mu]g/kg) before and during ketamine anesthesia. In the final step, increased arterial pressure observed during ketamine anesthesia was adjusted to preanesthetic baseline by sodium nitroprusside infusion (1-6 [mu]g [middle dot] kg-1 [middle dot] min-1).

Results: Ketamine significantly decreased MSA burst frequency (mean +/- SD, 18 +/- 9 bursts/min to 9 +/- 8 bursts/min) and burst incidence (26 +/- 11 bursts/100 heart beats to 9 +/- 6 bursts/100 heart beats). However, when increased mean arterial pressure (85 +/- 8 mmHg to 121 +/- 20 mmHg) was normalized to the awake baseline by sodium nitroprusside, MSA recovered (25 +/- 18 bursts/min; 23 +/- 14 bursts/100 heart beats). During ketamine anesthesia, both epinephrine (15 +/- 10 pg/ml to 256 +/- 193 pg/ml) and norepinephrine (250 +/- 105 pg/ml to 570 +/- 270 pg/ml) plasma concentrations significantly increased, as did heart rate (67 +/- 13 beats/min to 113 +/- 15 beats/min). Hypotensive challenges similarly increased MSA both in the awake state and during ketamine anesthesia.     

The interaction of nitrous oxide and isoflurane with incomplete cerebral ischemia in the rat

In rats with incomplete cerebral ischemia the effects of 70% N2O alone, isoflurane alone (0.5 and 1 MAC), and the combination of N2O + isoflurane on neurologic outcome, neurohistopathology, and EEG were compared. Moderate and severe ischemia were produced by right carotid artery occlusion combined with hemorrhagic hypotension (moderate ischemia, MAP = 30 mmHg, FIO2 = 0.30; severe ischemia, MAP = 25 mmHg, FIO2 = 0.20). Neurologic outcome was evaluated using a graded deficit score from 0 to 5 (0 = normal, 5 = death associated with stroke), and neurohistopathology was evaluated using a 40-point scale from 0 = normal to 40 = total hemisphere infarct at the level of the caudate nucleus in coronal section. Compared with N2O alone, isoflurane (0.5 and 1 MAC) improved neurologic outcome following moderate ischemia (P less than 0.05). Isoflurane also decreased histopathologic damage following moderate ischemia (N2O control = 33 +/- 1 vs. 0.5 MAC isoflurane = 11 +/- 4 and 1 MAC isoflurane = 12 +/- 3, P less than 0.05), whereas only 0.5 MAC isoflurane decreased histopathologic damage following severe ischemia (N2O control = 38 +/- 1 vs. 0.5 MAC isoflurane = 25 +/- 5; P less than 0.05) Adding N2O to 0.5 MAC isoflurane attenuated the neurologic protective effect of isoflurane alone and increased histopathologic damage following both moderate and severe ischemia (moderate = 23 +/- 5, severe = 37 +/- 2; both P greater than 0.05 compared with N2O controls). The effect of adding 70% N2O to isoflurane on cerebral blood flow (CBF) and cerebral oxygen consumption(CMRO2) was also evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)     

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).     

Local Cerebral Blood Flow, Local Cerebral Glucose Utilization, and Flow-Metabolism Coupling during Sevoflurane versus Isoflurane Anesthesia in Rats

Background: Compared to isoflurane, knowledge of local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) during sevoflurane anesthesia is limited.

Methods: LCGU, LCBF, and their overall means were measured in Sprague-Dawley rats (8 groups, n = 6 each) during sevoflurane and isoflurane anesthesia, 1 and 2 MAC, and in conscious control animals (2 groups, n = 6 each) using the autoradiographic 2-[(14) C]deoxy-D-glucose and 4-iodo-N-methyl-[(14) C]antipyrine methods.

Results: During anesthesia, mean cerebral glucose utilization was decreased: control, 56 +/- 5 [micro sign]mol [middle dot] 100 g-1 [middle dot]-1; 1 MAC isoflurane, 32 +/- 4 [micro sign]mol [middle dot] 100 g-1 [middle dot] min-1 (-43%); 1 MAC sevoflurane, 37 +/- 5 [micro sign]mol [middle dot] 100 g-1 [middle dot] min-1 (-34%); 2 MAC isoflurane, 23 +/- 3 [micro sign]mol [middle dot] 100 g-1 [middle dot] min-1 (-58%); 2 MAC sevoflurane, 23 +/- 5 [micro sign]mol [middle dot] 100 g-1 [middle dot] min-1 (-59%). Local analysis showed a reduction in LCGU in the majority of the 40 brain regions analyzed. Mean cerebral blood flow was increased as follows: control, 93 +/- 8 ml [middle dot] 100 g-1 [middle dot] min-1; 1 MAC isoflurane, 119 +/- 19 ml [middle dot] 100 g-1 [middle dot] min-1 (+28%); 1 MAC sevoflurane, 104 +/- 15 ml [middle dot] 100 g-1 [middle dot] min-1 (+12%); 2 MAC isoflurane, 149 +/- 17 ml [middle dot] 100 g-1 [middle dot] min-1 (+60%); 2 MAC sevoflurane, 118 +/- 21 ml [middle dot] 100 g-1 [middle dot] min-1 (+27%). LCBF was increased in most brain structures investigated. Correlation coefficients obtained for the relationship between LCGU and LCBF were as follows: control, 0.93; 1 MAC isoflurane, 0.89; 2 MAC isoflurane, 0.71; 1 MAC sevoflurane, 0.83; 2 MAC sevoflurane, 0.59).     

Intracarotid Infusion of the Nitric Oxide Synthase Inhibitor, l-NMMA, Modestly Decreases Cerebral Blood Flow in Human Subjects

Background: The authors hypothesized that if nitric oxide (NO) was a determinant of background cerebrovascular tone, intracarotid infusion of NG-monomethyl-l-arginine (l-NMMA), a NO synthase (NOS) inhibitor, would decrease cerebral blood flow (CBF) and intracarotid l-arginine would reverse its effect.

Methods: In angiographically normal cerebral hemispheres, after the initial dose-escalation studies (protocol 1), the authors determined the effect of intracarotid l-NMMA (50 mg/min for 5 min) on CBF and mean arterial pressure (MAP) over time (protocol 2). Changes in CBF and MAP were then determined at baseline, during l-NMMA infusion, and after l-NMMA during l-arginine infusion (protocol 3). To investigate effects of higher arterial blood concentrations of l-NMMA, changes in CBF and MAP were assessed at baseline and after a bolus dose of l-NMMA (250 mg/1 min), and vascular reactivity was tested by intracarotid verapamil (1 mg/min, protocol 4). CBF changes were also assessed during induced hypertension with intravenous phenylephrine (protocol 5).

Results: Infusion of l-NMMA (50 mg/min for 5 min, n = 7, protocol 2) increased MAP by 17% (86 +/- 8 to 100 +/- 11 mmHg;P < 0.0001) and decreased CBF by 20% (45 +/- 8 to 36 +/- 6 ml [middle dot] 100 g-1 [middle dot] min-1;P < 0.005) for 10 min. Intracarotid l-arginine infusion after l-NMMA (protocol 3) reversed the effect of l-NMMA. Bolus l-NMMA (protocol 4) increased MAP by 20% (80 +/- 11 to 96+/-13 mmHg;P < 0.005), but there was no significant decrease in CBF. Intracarotid verapamil increased CBF by 41% (44+/- 8 to 62 +/- 9 ml [middle dot] 100 g-1 [middle dot] min-1;P < 0.005). Phenylephrine-induced hypertension increased MAP by 20% (79 +/- 9 to 95 +/- 6 mmHg;P = 0.001) but did not affect CBF.     

A comparison of the cerebral protective effects of isoflurane and barbiturates during temporary focal ischemia in primates

Isoflurane has protective properties during experimental global brain ischemia or hypoxia. However, this has not been evaluated in the more common case of focal ischemia, e.g., as caused by middle cerebral artery occlusion (MCAO). The authors therefore compared the effects of isoflurane, thiopental, and N2O/fentanyl anesthesia on neurologic and neuropathologic outcome in baboons subjected to 6 h of transorbital left MCAO. Prior to MCAO, animals were assigned to one of three groups: Group 1 (n = 7) received isoflurane (in O2/air) in concentrations sufficient to maintain deep burst suppression on the EEG (2.0% +/- 0.5% inspired, mean +/- SD); group 2 (n = 6) received thiopental (O2/air) in doses adequate to maintain similar EEG suppression (3.6 +/- 0.7 g total); and group 3 (n = 6) received 60% N2O/40% O2 and fentanyl (25 micrograms/kg load, 3 micrograms X kg-1 X h-1 infusion). Efforts were made to keep mean arterial pressure (MABP) between approximately 80 and 100 mmHg, using nitroprusside/hydralazine or phenylephrine/metaraminol, with PaCO2 at approximately 30 mmHg. The selected anesthetic was established 45 min before MCAO, was maintained until 1 h after clip removal, and in decreasing concentrations for 5 h. Neurologic status was scored for 7 days and formalin-fixed brains were later sectioned for determination of infarction volume. Six of seven group 1 (isoflurane) animals were hemiplegic, and 7/7 had verified infarctions. By contrast, 4 of 6 group 2 (thiopental) animals were normal, with 2/6 having infarctions. Outcome in group 3 (N2O/fentanyl) was intermediate between groups 1 and 2 (3/6 hemiplegic, 4/6 with infarctions). Differences in the infarction rates between groups 1 and 2 was significant (P less than 0.05), while a similar comparison of neurologic outcome scores achieved a P value of 0.055. Infarctions in group 1 were more hemorrhagic in character than in group 3 (groups 1 and 2 could not be meaningfully compared). These results must be considered in light of differences in MABP during the occlusion period; MABP in group 1 was approximately 80 mm Hg in spite of vasopressor use, while that in group 2 was approximately 100 mmHg (in spite of vasodilators). Nevertheless, they fail to demonstrate any protective value of isoflurane anesthesia, at least when compared with thiopental.