The Comparative Amnestic Effects of Midazolam, Propofol, Thiopental, and Fentanyl at Equisedative Concentrations

Background: The authors evaluated the effects of midazolam, propofol, thiopental, and fentanyl on volunteer participants' memory for words and pictures at equisedative concentrations.

Methods: Sixty-seven healthy volunteers were randomized to receive intravenous infusions of midazolam (n = 11), propofol (n = 11), thiopental (n = 10), fentanyl with ondansetron pretreatment (n = 11), ondansetron alone (n = 8), or placebo (n = 16) in a double-blind design. Three increasing and then two decreasing sedative concentrations were achieved by computer-controlled infusion in each volunteer. Measures of sedation, memory, and drug concentration were obtained at each target concentration. Drug concentrations were normalized to equisedative effects using both Emax and logistic regression methods of pharmacodynamic modeling. The serum concentrations at 50% memory effect (Cp50s) were determined using four different memory end points. The relative potencies compared with midazolam for memory impairment were determined.

Results: Equisedative concentrations were midazolam, 64.5 +/- 9.4 ng/ml; propofol, 0.7 +/- 0.2 micro gram/ml; thiopental, 2.9 +/- 1.0 micro gram/ml; and fentanyl, 0.9 +/- 0.2 ng/ml. The Cp50s for 50% loss of memory for words were midazolam, 56 +/- 4 ng/ml; propofol, 0.62 +/- 0.04 micro gram/ml; thiopental, 4.5 +/- 0.3 micro gram/ml; and fentanyl, 3.2 +/- 0.4 ng/ml. Compared with midazolam, relative potencies (with 95% confidence intervals) were propofol, 0.96 (0.44-1.78); thiopental, 0.76 (0.52-0.94); and fentanyl, 0.34 (0.05-0.76). Large effects on memory were only produced by propofol and midazolam.     

Quantitation of Depth of Thiopental Anesthesia in the Rat

Background: In contrast to that of inhalational anesthetics, quantitation of anesthetic depth for intravenous agents has not been well defined. In this study, using rodents, the relationship between the constant plasma thiopental concentrations and the clinical response to multiple nociceptive stimuli were investigated characterizing the anesthetic state from light sedation to deep anesthesia and correlated to the degree of electroencephalogram (EEG) drug effect.

Methods: Thirty rats were instrumented with chronically implanted EEG electrodes, arterial and venous catheters. A computer-driven infusion pump was used to rapidly attain and then maintain constant, target plasma thiopental concentrations ranging from 7 to 100 micro gram/ml. Three different target plasma thiopental concentrations were achieved in each rat. Electroencephalographic effects were monitored with aperiodic waveform analysis. The following nociceptive stimuli were applied: (1) unprovoked righting reflex, (2) provoked righting reflex, (3) noise stimulus, (4) tail clamping with an alligator clip, (5) constant tail pressure with an analgesia-meter, (6) corneal reflex, and (7) tracheal intubation. For tail clamping, tail pressure, and intubation, either purposeful extremity movement or abdominal muscle contraction response was noted to be present or absent. The clinical responses (present or absent) were modeled using logistic regression to estimate the Cp50, the plasma thiopental concentration with a 50% probability of no response.

Results: The following mean Cp50 values (95% confidence interval) were obtained: unprovoked righting reflex, 15.9 (15.1-16.6) micro gram/ml; provoked righting reflex, 21.4 (20.2-22.7) micro gram/ml; noise stimuli, 31.3 (29.7-33.0) micro gram/ml; tail clamp and limb movement, 38.3 (36.1-40.4) micro gram/ml, tail pressure and limb movement, 39.2 (37.1-41.3) micro gram/ml; tail pressure and abdominal muscle contraction, 52.5 (50.0-55) micro gram/ml; tail clamping and abdominal muscle contraction, 56.1 (50.0-56.2) micro gram/ml; corneal reflex, 60.0 (56.6-63.4) micro gram/ml; and limb movement or muscle abdominal contraction response to intubation, 67.7 (59.2-76.1) micro gram/ml. At an EEG-effect of 9.1 and 2.2 waves/s, there was a 50% chance of limb movement response to tail clamping and tracheal intubation, respectively. There was a poor relationship between the plasma thiopental concentration and the percent increase of either heart rate or mean arterial blood pressure after applying either tail pressure or tail clamp stimuli.     

Thiopental Uncouples Hippocampal and Cortical Synchronized Electroencephalograpbic Activity

Background: Thiopental produces a concentration-dependent continuum of effects on the cortical electroencephalogram (EEG) that has been linked to behavioral measures of anesthetic depth. The complexity of the response, however, limits a clear insight into the neurophysiologic actions of thiopental. The current study investigated thiopental actions on cortical EEG and hippocampal electrical activity, to determine whether similar effects occur on both structures and to compare synchronized activity between these structures.

Methods: Thiopental was administered intravenously via an implanted catheter in freely moving rats. Arterial blood oxygen/carbon dioxide concentration, thiopental concentrations, and temperature were monitored and controlled. Neocortical EEG was recorded from implanted dural surface electrodes and hippocampal neuron electrical activity was recorded from stereotaxically placed microelectrodes. Pharmacokinetic models were used to determine effect site concentrations.

Results: Thiopental produced an increase in EEG frequency and amplitude at low concentrations (15-20 micro gram/ml total plasma, approximately 10 micro Meter unbound), which produced a loss of righting reflex. This was followed by a frequency decrease and burst suppression activity at higher concentrations (50-80 micro gram/ml, approximately 60 micro Meter), which produced a loss of tail pinch and corneal reflexes. Higher concentrations of thiopental (> 60 micro gram/ml) uncoupled synchronized burst discharges recorded in hippocampus and cortex. Isoelectric EEG activity was associated with concentrations of 70-90 micro gram/ml (approximately 80 micro Meter) and a deep level of anesthesia; motor reflexes were abolished, although cardiovascular reflexes remained. In all frequency bands, similar concentration-EEG effect relationships were observed for cortical and hippocampal signals, only differing in the magnitude of response. A reversed progression of effects was observed on recovery.     

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.     

Epidural and Intravenous Fentanyl Produce Equivalent Effects during Major Surgery

Background: The benefit of epidural versus intravenous fentanyl administration for postoperative analgesia is controversial. In the current study, the intraoperative effects of epidural versus intravenous fentanyl administration were compared during major surgery.

Methods: Twenty elective patients scheduled for thoracoabdominal esophagectomy under general anesthesia with propofol infusion were randomly allocated to receive either intravenous or epidural boluses of 50-100 micro gram fentanyl in a double-blind fashion to maintain hemodynamic stability. Plasma cortisol and fentanyl, as well as total urinary catecholamines, were obtained at the end of the operations.

Results: Hemodynamic variations were similar except that patients receiving epidural fentanyl had a lower incidence of heart rate reduction (> 20% reduction from baseline, P < 0.05). There were no differences in mean intraoperative fentanyl (1,115 + 430 and 1,010 + 377 micro gram, epidural and intravenous, respectively) or propofol (2,281 + 645 and 2,452 + 1,169 mg) doses, number of boluses of fentanyl (nine in both groups), plasma fentanyl concentration (1.13 plus/minus 0.4 and 1.02 plus/minus 0.46 ng/ml), or number of anesthesiologists correctly identifying the site of fentanyl administration. Similarly, there were no differences in plasma glucose (8.9 + 1.8 and 9.3 + 1.8 mM) and cortisol (696 + 446 and 846 + 257 mM), or urinary epinephrine (12 + 3.7 and 13.1 + 9.2, micro gram/sample) and norepinephrine (42.7 plus/minus 26.7 and 39.1 plus/minus 2.76, micro gram/sample).     

In-vitro-Effekte von Anästhetika auf die Blut-Hirn-Schranke

BACKGROUND: The blood-brain barrier (BBB) forms a selective barrier between blood and brain and regulates the passage of most molecules. Pathological conditions such as ischemia lead to breakdown of the BBB. Vascular endothelial growth factor (VEGF) has been shown to be responsible for hypoxia-induced hyperpermeability of the BBB in vivo as well as in vitro. To eliminate factors which alter the permeability of the BBB in vivo, an in vitro model was used to test the effects of intravenous and volatile anesthetics on the permeability and on VEGF expression during normoxia and hypoxia. METHODS: The in vitro model of the BBB consisted of primary cultures of porcine brain microvascular endothelial cells (BMEC). The permeability was measured by the paracellular passage of [3H]inulin across the BMEC monolayer and the expression of VEGF was determined by northern blot analysis. RESULTS: All intravenous and volatile anesthetics tested (etomidate, ketamine, fentanyl, propofol, midazolam, sodium-gamma-hydroxybutyrate as well as halothane, enflurane, isoflurane, sevoflurane, desflurane) did not alter the permeability of the BBB or the expression of VEGF in vitro. Hypoxia (2 vol%) increased the permeability and the VEGF expression significantly which was not altered in the presence of the anesthetics. CONCLUSION: The in vitro model represents a suitable model of the BBB to investigate direct effects of anesthetics on functions of the BBB independent of hemodynamic factors.     

Dose Comparison of Remifentanil and Alfentanil for Loss of Consciousness

Background: This study evaluated the efficacy and safety of remifentanil, a potent mu agonist opioid with a rapid onset and offset of effect, as a sole induction agent for loss of consciousness (LOC) and compared it with alfentanil.

Methods: Remifentanil and alfentanil were administered intravenously over 2 min in ascending doses (remifentanil 2, 3, 4, 5, 6, 8, 10, 15, 20 micro gram/kg; alfentanil 40, 60, 80, 100, 120, 160, 200 micro gram/kg) to unpremedicated healthy patients. Patients were observed for rigidity and LOC for 30 s after the end of infusion. If patients had not lost consciousness, 2 mg [center dot] kg sup -1 [center dot] min sup -1 thiopental was administered until LOC was achieved. Arterial blood samples, obtained at specified time intervals, were analyzed for remifentanil and alfentanil whole-blood concentration. Blood pressure and heart rate were also recorded at preset time intervals.

Results: Neither drug could reliably produce LOC. With both drugs, there was a dose-dependent decrease in thiopental requirements and a dose-dependent increase in the incidence and severity of rigidity (P <0.05). The median effective dose (ED50) for LOC with remifentanil was 12 micro gram/kg, and for alfentanil it was 176 micro gram/kg. The median effective concentration (EC50; whole-blood concentration) of remifentanil was 53.8 ng/ml and for alfentanil it was 1,012 ng/ml. Minimal hemodynamic changes were observed after either drug was given.     

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.     

The Effect of Isoflurane, Halothane, Sevoflurane, and Thiopental/Nitrous Oxide on Respiratory System Resistance after Tracheal Intubation

Background: After tracheal intubation, lung resistance and therefore respiratory system resistance (Rrs) routinely increase, sometimes to the point of clinical bronchospasm. Volatile anesthetics generally have been considered to be effective bronchodilators, although there are few human data comparing the efficacy of available agents. This study compared the bronchodilating efficacy of four anesthetic maintenance regimens: 1.1 minimum alveolar concentration (MAC) end-tidal sevoflurane, isoflurane or halothane, and thiopental/nitrous oxide.

Methods: Sixty-six patients underwent tracheal intubation after administration of 2 micro gram/kg fentanyl, 5 mg/kg thiopental, and 1 mg/kg succinylcholine. Vecuronium or pancuronium (0.1 mg/kg) was then given to ensure paralysis during the rest of the study. Postintubation R sub rs was measured using the isovolume technique. Maintenance anesthesia was then randomized to thiopental 0.25 mg [center dot] kg sup -1 [center dot] min sup -1 plus 50% nitrous oxide, or 1.1 MAC end-tidal isoflurane, halothane, or sevoflurane. The Rrs was measured after 5 and 10 min of maintenance anesthesia. Data were expressed as means +/- SD.

Results: Maintenance with thiopental/nitrous oxide failed to decrease Rrs, whereas all three volatile anesthetics significantly decreased Rrs at 5 min with little further improvement at 10 min. Sevoflurane decreased Rrs more than either halothane or isoflurane (P < 0.05; 58 +/- 14% of the postintubation Rrs vs. 69 +/- 20% and 75 +/- 13%, respectively).     

Ionic Mechanisms Mediating the Differential Effects of Methohexital and Thiopental on Action Potential Duration in Guinea Pig and Rabbit Isolated Ventricular Myocytes

Background: Commonly used barbiturate anesthetics may significantly influence cardiac electrophysiologic characteristics. The authors evaluated thiopental (a thiobarbiturate) and methohexital (an oxybarbiturate), two compounds with similar physicochemical properties but different structures, to determine whether they have distinct effects on the major ionic currents that determine action potential duration (APD) in ventricular myocytes.

Methods: The effects of thiopental and methohexital (50 [micro sign]M) on APD at 50% (APD50) and 90% (APD90) repolarization were studied in guinea pig and rabbit single ventricular myocytes using the patch-clamp technique in a whole-cell configuration. The ionic mechanisms underlying the APD changes were evaluated by measuring the anesthetics' effects on the L-type calcium inward current, the inward rectifier potassium current, and the delayed rectifier potassium current in guinea pig cells and on the transient outward potassium current in rabbit cells.

Results: Thiopental and methohexital caused opposite effects on APD. Whereas thiopental prolonged APD50 and APD90 in guinea pig and rabbit ventricular myocytes, methohexital shortened them. Thiopental markedly depressed both the inward and outward components of the inward rectifier potassium current, whereas methohexital caused minimal inhibition of the inward component and no change in the outward component. The delayed rectifier potassium current was inhibited by thiopental but significantly potentiated by methohexital. Neither thiopental nor methohexital significantly affected the transient outward potassium current or the L-type calcium inward current.     

Role of the Endocardial Endothelium in the Negative Inotropic Effects of Thiopental

Background: Myocardial function is regulated by endocardial endothelium (EE). Several studies have demonstrated the involvement of vascular endothelium in regulating the vasoactive effects of anesthetic agents. Because vascular endothelium and EE form a contiguous layer, it was postulated that EE might also be involved in regulating the inotropic effects of anesthetics. The effects of thiopental on isolated feline papillary muscle with and without EE were examined.

Methods: The study was performed on isolated cat papillary muscles (n = 48). The effects of increasing doses of thiopental (1.5, 3, 6, 9, 12, and 24 micro gram/ml) on isometric and isotonic muscle contraction parameters were evaluated in three protocols under different experimental conditions. In the first protocol, the effects of thiopental were studied in the muscles with an intact EE (group A, n = 8) and muscles in which the EE was selectively damaged by a 1-s immersion in 0.5% Triton X-100 (group B, n = 8). In the second protocol, cumulative concentration responses for thiopental were obtained in muscles with (group C, n = 8) and without (group D, n = 8) EE, pretreated with 10 sup -3 M of the blocking NG -nitro-L-arginine methyl ester (L-NAME). In the third protocol, the same cumulative concentration responses were obtained for thiopental in muscles with (group E, n = 8) and without (group F, n = 8) EE after pretreatment with 5 x 10 sup -4 M L-arginine.

Results: In the presence of an intact EE, thiopental induced a dose-dependent decrease in myocardial function. With the EE removed, low doses of thiopental (1.5 to 6 micro gram/ml) no longer altered myocardial function. Pretreatment of the muscles with L-NAME inhibited the negative inotropic effects of low doses of thiopental and mimicked the response obtained after EE was removed. Pretreatment with L-arginine slightly accentuated the negative inotropic effects of low doses of thiopental.     

Awakening Propofol Concentration with and without Blood-Effect Site Equilibration after Short-term and Long-term Administration of Propofol and Fentanyl Anesthesia

Background: The propofol awakening concentration can vary. However, the effect site awakening propofol concentration will be a fixed value. The purpose of this study was to determine the awakening propofol concentrations obtained from infusion Schede using abrupt discontinuation of propofol (half-maximal effective concentration [EC sub 50]) or a descending decrease in concentration to allow blood-effect site equilibration (EC50 eq).

Methods: Patients undergoing short-term (group 1) and long-term (group 2) elective surgery were anesthetized with computer-assisted continuous infusion of propofol and fentanyl, with both groups receiving the same propofol (3 micro gram/ml) and fentanyl (1 ng/ml) concentrations 20-30 min before the end of surgery until the end. Then both groups were further divided into two subgroups: subgroup A abrupt discontinuation, and subgroup B descending concentrations of propofol (15-min duration per concentration). In the A subgroups, the response to verbal command was evaluated every 30 s. In the B subgroups, the blood propofol concentrations just permitting and just preventing response to command were averaged individually. The EC50 and EC50 eq values were determined by probit analysis.

Results: The EC50 of group 1A was 1 micro gram/ml, which was significantly less than the 1.6 micro gram/ml of group 2A (P < 0.05). The awakening time of group 1A was 5.2 +/- 1.8 min, which was significantly shorter than the 9.3 +/- 3.5 min of group 2A (means +/- SD). The EC50 eq of both groups 1B and 2B was 2.2 micro gram/ml.     

Mood during Epidural Patient-controlled Analgesia with Morphine or Fentanyl

Background: Mood states during epidural opioids are not known. The authors studied the change in mood during the 48-h period of epidural morphine and epidural fentanyl in 47 patients after elective hip or knee joint arthroplasty.

Methods: An epidural catheter was inserted at the L2-L3 or L3-L4 interspace. Anesthesia was induced with thiopenthal and maintained with isoflurane and nitrous oxide. One hour before the conclusion of the operation, patients received an epidural bolus injection of 2 mg morphine (n = 23) or 100 micro gram fentanyl (n = 24), followed by the same opiate (125 micro gram/ml morphine or 25 micro gram/ml fentanyl) epidurally delivered by a patient-controlled analgesia (PCA) pump in the postoperative period for 48 h. Mood was assessed using the bipolar form of the Profile of Mood States before operation and 24 h, 48 h, and 72 h after operation.

Results: There was no significant difference in pain intensity between the groups during epidural PCA. Mood states became more positive over time in the patients who received morphine (P < 0.01 at 48 h) and negative in those who were given fentanyl (P < 0.01 at 24 and 48 h, respectively) compared with those before the operation, and they were more positive in the morphine than in the fentanyl group at 24 h, 48 h (P < 0.05), and 72 h (P < 0.01). Patients in the morphine group were more composed, agreeable, elated, confident, energetic, and clearheaded than were those in the fentanyl group (P < 0.05). There was no correlation between mood scores and pain scores in either group. There was an inverse correlation at 48 h between mood scores and plasma fentanyl concentrations (r = -0.58, P < 0.05).     

Wheezing during Induction of General Anesthesia in Patients with and without Asthma: A Randomized, Blinded Trial

Background: Patients with asthma who require general anesthesia and tracheal intubation are at increased risk for the development of bronchospasm during induction. The incidence of wheezing during induction with different intravenously administered agents is unknown. A randomized, double-blinded prospective study was undertaken to evaluate the incidence of wheezing in asymptomatic asthmatic and nonasthmatic patients receiving three commonly used intravenous anesthetic agents for induction of anesthesia.

Methods: Fifty-nine asymptomatic asthmatic and 96 nonasthmatic patients of ASA physical status 1 and 2 were studied. All patients received 1.5 micro gram/kg fentanyl, oxygen, followed by either 5 mg/kg thiopental or thiamylal, 1.75 mg/kg methohexital or 2.5 mg/kg propofol, 1.5 mg/kg succinylcholine, tracheal intubation, and inhalational anesthesia. Wheezing was assessed by an independent blinded observer auscultating the lungs at 2 and 5 min postintubation. Data were analyzed by Pearson's chi-squared, Fisher's exact test, and multiple logistic regression with significance set at P < 0.05.

Results: Both asthmatic and nonasthmatic patients who received a thiobarbiturate for induction had a greater incidence of wheezing than did patients receiving propofol. In asthmatic patients, 45% (23, 67) (mean and 95% confidence interval) who received a thiobarbiturate, 26% (8, 44) who received an oxybarbiturate, and none (0, 17) who received propofol wheezed after intubation. In nonasthmatic patients, 16% (3, 28) who received thiobarbiturate and 3% (0, 9) who received propofol wheezed.     

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).     

Comparative hemodynamic study of anesthesia induction with propofol (Diprivan), thiopental, methohexital, etomidate and midazolam in patients with coronary disease

In patients undergoing cardiac surgery, the induction of anesthesia is not without risk because of specific cardiovascular effects of the anesthetic and the preoperative state of the patient. The hemodynamic effects of etomidate, midazolam, thiopental, and methohexital are well known: etomidate is an anesthetic that induces only minor cardiovascular changes; its influence on the endocrine system, however, has reduced its clinical indication. Barbiturates such as thiopental and methohexital produce negative inotropic effects in combination with an increase in heart rate and myocardial oxygen consumption; midazolam reduces pre- and afterload in patients with poor left ventricular function. Propofol, a new short-acting induction agent with good anesthetic properties, is said to diminish arterial pressure as well as myocardial oxygen consumption. METHODS: In a randomized study we investigated the hemodynamic effects of intravenous induction with propofol (2 mg/kg body wt.), thiopental (5 mg/kg), methohexital (1 mg/kg), etomidate (0.3 mg/kg), and midazolam (0.15 mg/kg) in 50 patients undergoing coronary artery bypass grafting. All patients were premedicated with flunitrazepam (0.03 mg/kg up to 2 mg) and morphine hydrochloride (0.2 mg/kg up to 15 mg) 100 min before the investigation. After 0.003 mg/kg fentanyl the patients received the induction agent in the above-mentioned dosage within 40 s followed by 0.1 mg/kg pancuronium bromide. Hemodynamic measurements were performed 1, 3, and 5 min after the end of the injection as well as 1 and 5 min after intubation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Barbiturates on Hydroxyl Radicals, Lipid Peroxidation, and Hypoxic Cell Death in Human NT2-N Neurons

Background: Barbiturates have been shown to be neuroprotective in several animal models, but the underlying mechanisms are unknown. In this study, the authors investigated the effect of barbiturates on free radical scavenging and attempted to correlate this with their neuroprotective effects in a model of hypoxic cell death in human NT2-N neurons.

Methods: Hydroxyl radicals were generated by ascorbic acid and iron and were measured by conversion of salicylate to 2,3-dihydroxybenzoic acid. The effect of barbiturates on lipid peroxidation measured as malondialdehyde and 4-hydroxynon-2-enal was also investigated. Hypoxia studies were then performed on human NT2-N neurons. The cells were exposed to 10 h of hypoxia or combined oxygen and glucose deprivation for 3 or 5 h in the presence of thiopental (50-600 [mu]M), methohexital (50-400 [mu]M), phenobarbital (10-400 [mu]M), or pentobarbital (10-400 [mu]M), and cell death was evaluated after 24 h by lactate dehydrogenase release.

Results: Pentobarbital, phenobarbital, methohexital, and thiopental dose-dependently inhibited formation of 2,3-dihydroxybenzoic acid and iron-stimulated lipid peroxidation. There were significant but moderate differences in antioxidant action between the barbiturates. While phenobarbital (10-400 [mu]M) and pentobarbital (10-50 [mu]M) increased lactate dehydrogenase release after combined oxygen and glucose deprivation, thiopental and methohexital protected the neurons at all tested concentrations. At a higher concentration (400 [mu]M), pentobarbital also significantly protected the neurons. At both 50 and 400 [mu]M, thiopental and methohexital protected the NT2-N neurons significantly better than phenobarbital and pentobarbital.     

The Response of Patients with Duchenne's Muscular Dystrophy to Neuromuscular Blockade with Vecuronium

Background: The authors hypothesized that patients with Duchenne's muscular dystrophy (DMD) are more sensitive to nondepolarizing muscle relaxants.

Methods: Eight children with DMD and eight healthy children having orthopedic procedures were studied. Anesthesia consisted of thiopental, 60% nitrous oxide in 40% oxygen, and intravenous fentanyl and midazolam. Using electromyography, the ulnar nerve was stimulated and the electromyographic train-of-four ratio (TOFr) of the first dorsal interosseous muscle was recorded every 60 s. After baseline TOFr recording, all patients received 50 micro gram/kg vecuronium and the TOFr at 3 min was compared. Vecuronium (10 micro gram/kg) was then administered every minute until TOFr was or= to 0.01. Then 10 micro gram/kg of vecuronium were administered to maintain TOFr Results: The initial dose of vecuronium resulted in greater TOFr depression in patients with DMD than in controls (0.14 vs. 0.86). Less vecuronium was needed to produce TOFr or= to 0.1 after the initial dose was longer in the patients with DMD than in the controls (28 vs. 20 min; P = 0.03), and the maintenance dose of vecuronium was less in patients with DMD (0.6 vs. 1.3 micro gram [center dot] kg sup -1 [center dot] min sup -1; P < 0.01). The time for TOFr recovery from 0.1 to 0.25 was 36 min in the patients with DMD and 6 min in the controls (P <0.01). After neostigmine, the TOFr was 1.0 in the controls and 0.91 (P = 0.03) in the patients with DMD.     

Effect of Subarachnoid Bupivacaine Block on Anesthetic Requirements for Thiopental in Rats

Background: Subarachnoid bupivacaine blockade has been reported to reduce thiopental and midazolam hypnotic requirements in patients. The purpose of this study was to examine if local anesthetically induced lumbar intrathecal blockade would reduce thiopental requirements for blockade of motor responses to noxious and nonnoxious stimuli in rats.

Methods: After intrathecal and external jugular catheter placement, rats were assigned randomly to two groups in a crossover design study, with each rat to receive either 10 micro liter of 0.75% bupivacaine or 10 micro liter of normal saline intrathecally. The doses of intravenously administered thiopental required to ablate the eyelid reflex, to block the withdrawal reflex of a front limb digit, and to block the corneal reflex were compared. In two separate groups of animals, hemodynamic parameters and concentrations of thiopental in the brain were compared between intrathecally administered bupivacaine and saline.

Results: The thiopental dose required to block the described responses was decreased with intrathecally administered bupivacaine versus intrathecally administered saline from (mean +/- SD) 40 +/- 5 to 24 +/- 4 mg/kg (P < 0.001) for the eyelid reflex, from 51 +/- 6 to 29 +/- 6 mg/kg (P < 0.005) for front limb withdrawal, and from 67 +/- 8 to 46 +/- 8 mg/kg (P < 0.01) for the corneal reflex. The concentration of thiopental in the brain at the time of corneal reflex blockade for the group given bupivacaine was significantly lower than in the group given saline (24.1 vs. 35.8 micro gram/g, P = 0.02).     

Prophylactic Use of Epidural Mepivacaine/Morphine, Systemic Diclofenac, and Metamizole Reduces Postoperative Morphine Consumption after Major Abdominal Surgery

Background: Surgical trauma induces nociceptive sensitization leading to amplification and prolongation of postoperative pain. While preemptive analgesic treatment with numerous agents has been successful in experimental animals, results of human studies remain conflicting. The authors used a multimodal approach for preemptive analgesia before abdominal surgery: diclofenac and metamizole inhibit prostaglandin synthesis, thus influencing peripheral sensitization; epidural local anesthetics induce conduction block, epidural opioids inhibit nociceptive synaptic transmission, and metamizole induces descending inhibition. The interaction of these drugs might suppress spinal nociceptive sensitization and postoperative analgesic demand.

Methods: One hundred forty-two patients scheduled for major abdominal surgery were randomly assigned to one of three groups and studied prospectively. Epidural catheters in groups 1 and 2 were placed at interspaces T8-T10, the position of the catheter was confirmed by epidurography, and sensory testing after administration of 5 ml mepivacaine 1%. Group 1 received 75 mg intramuscular diclofenac, 1000 mg intravenous metamizole, 5.3+/-1 mg epidural morphine, and 15-20 ml mepivacaine 1% 85+/-41 min before skin incision. Epidural analgesia was maintained by injections of 0.1 ml *symbol* kg sup -1 *symbol* h sup -1 mepivacaine 1%. Group 2 patients received the balanced analgesia regimen before wound closure (221+/-86 min after skin incision). Group 3 patients did not receive any study substances. General anesthesia was induced with 5 mg/kg thiopental and 2 micro gram/kg fentanyl and maintained with enflurane and nitrous oxide. Postoperative analgesia consisted of patient-controlled intravenous morphine over 5 days.

Results: Median visual analog scale pain intensities were < 3 cm and did not differ among the groups. Morphine consumption per hour on postoperative day 2 was 0.8+/-0.1 mg/h (group 1) < 1.2+/- 0.1 mg/h (group 2) = 1.1+/-0.1 mg/h (group 3) and cumulative morphine consumption (in mg) on the morning of day 5 was 95+/-9 (group 1) < 111+/-11 (group 2) < 137+/-10 (group 3).