Differential neurotoxic effects of propofol on dissociated cortical cells and organotypic hippocampal cultures

BACKGROUND: Propofol is a widely used anesthetic agent for adults and children. Although extensive clinical use has demonstrated its safety, neurologic dysfunctions have been described after the use of this agent. A recent study on a model of aggregating cell cultures reported that propofol might cause irreversible lesions of gamma-aminobutyric acid-mediated (GABAergic) neurons when administered at a critical phase of brain development. We investigated this issue by comparing the effects of long-term propofol treatment on two models of brain cultures: dissociated neonatal cortical cell cultures and organotypic slice cultures. METHODS: Survival of GABAergic neurons in dissociated cultures of newborn rat cortex (postnatal age, 1 day) treated for 3 days with different concentrations of propofol was assessed using histologic and cytochemical methods. For hippocampal organotypic slice cultures (postnatal age, 1 and 7 days), cell survival was assessed by measuring functional and morphologic parameters: extracellular and intracellular electrophysiology, propidium staining of dying cells, and light and electron microscopy. RESULTS: In dissociated neonatal cell cultures, propofol induced dose-dependent lesions of GABAergic neurons and of glial cells. In contrast, no evidence for neurotoxic effects of propofol were found after long-term treatment of organotypic slice cultures. Excitatory transmission was not affected by propofol, and inhibitory transmission was still functional. Histologic preparations showed no evidence for cell degeneration or death. CONCLUSION: Although long-term applications of propofol to dissociated cortical cell cultures produced degeneration and death of GABAergic neurons and glial cells, no such lesions were found when using a model of postnatal organotypic slice cultures. This conclusion is based on both functional and morphologic tests.     

Mild hypothermia impairs left ventricular diastolic but not systolic function.

Hypothermia is a component of myocardial protection during cardiopulmonary bypass (CPB) and cardioplegic arrest (CA). Patients in the early post CPB period often show mild hypothermia and cardiac dysfunction. We sought to investigate the impact of hypothermia on left ventricular (LV) function. Anesthetized dogs (n = 12) were instrumented with myocardial ultrasonic crystals and LV micromanometer. Systolic function was measured by preload recruitable stroke work (PRSW). Diastolic function was measured by -dP/dt(max) and tau. In six dogs (Norm group), body temperature was maintained at baseline levels. In another six dogs (Hypo group), body temperature dropped gradually over the time course of the experiment. The body temperature in the Hypo group decreased from 37.0 +/- 0.3 degrees C to 35.2 +/- 1.0 degrees C. -dP/dt(max) decreased and tau increased significantly with hypothermia but were stable in the Norm group. Both tau and -dP/dt(max) showed a linear relationship to the body temperature (r =.91 and r = .93, respectively). PRSW did not change and cardiac output decreased with hypothermia. Thus, even mild hypothermia impairs LV diastolic but not systolic function. Cardiac output is temperature sensitive and therefore rewarming of patients post-CPB has priority.     

Anoxic depolarization of rat hippocampal slices is prevented by thiopental but not by propofol or isoflurane

Background. There is strong evidence to suggest that anoxicdepolarization (AD) is an important factor in hypoxia/ischaemia-inducedneural damage. Treatments that prevent the occurrence of ADmay be useful in providing neuronal protection against hypoxia.The current study was designed to determine whether generalanaesthetics which have been suggested to ‘induce prophylaxis’against hypoxia can attenuate the incidence of AD. Methods. The effects of anoxia (3 min) on evoked extracellularlyrecorded field potentials of CA1 neurons in rat hippocampalslices were assessed in the absence and presence of the i.v.general anaesthetics thiopental and propofol and the volatileanaesthetic isoflurane. Results. In the absence of anaesthetics, AD occurred in 81%of the preparations tested. Thiopental (2x10^–4 M) significantlyreduced the incidence of AD (16%, P=0.0006). In comparison,propofol (2x10^–4 M) and isoflurane (1.5 vol%) were ineffective(69% and 60%, respectively). Furthermore, in the presence ofthiopental, the population spike amplitude recovered with andwithout AD (90% and 94% of pre-anoxic value, respectively) following3 min anoxia. Conclusion. The prophylactic effect of thiopental against hypoxiamight be induced, in part, by preventing the generation of AD.     

Isoflurane-induced neuronal degeneration: an evaluation in organotypic hippocampal slice cultures

Prolonged exposure of postnatal day (PND) 7 rat pups to anesthetics, which act via N-methyl-D-aspartate antagonism and/or gamma-amino butyric acid enhancement, causes neurodegeneration and persistent behavioral deficits. We studied these findings in vitro and determined whether the age of rat pups used for study or duration of anesthetic exposure modulates resultant neurodegeneration. Organotypic hippocampal slices (OHSs) were prepared from rat pups on PNDs 4, 7, and 14 and cultured 7 or 14 days in vitro. The slices were exposed to 1.5% isoflurane or fresh gas for durations of 1, 3, or 5 h. Hippocampal CA1, CA3, and dentate gyrus neuronal survival was assessed 3 days later. Neuronal cell death was greatest in OHSs prepared from PND 7 rat pups (P < 0.001) and was most evident after 5 h exposure to isoflurane (P < 0.001). By eliminating variables such as hemodynamics, nutrition, oxygenation, and carbon dioxide elimination, this in vitro investigation supports both an age- and duration-dependent relationship between 1.5% isoflurane exposure and perinatal neuronal death.     

gamma-Aminobutyric acid-A receptors contribute to isoflurane neuroprotection in organotypic hippocampal cultures

The mechanisms by which anesthetics such as isoflurane reduce cell death in rodent models of cerebral ischemia remain incompletely defined. Reduction in glutamate excitotoxicity explains some but not all of isoflurane's neuroprotection. Because isoflurane potentiates gamma-aminobutyric acid (GABA) receptor-mediated ion fluxes and GABA(A) receptor agonists have neuroprotective effects, we hypothesized that GABA(A) receptors contribute to isoflurane neuroprotection. As a model of cerebral ischemia and recovery, we used rat hippocampal slice cultures. Survival of CA1, CA3, and dentate neurons was examined 2 and 3 days after 1-h combined oxygen-glucose deprivation (OGD) at 37 degrees C. To define the role of GABA(A) receptors in mediating protection, the effect of 1% isoflurane on cell survival was examined in the presence of the GABA(A) antagonist bicuculline during OGD. Cell death was measured with propidium iodide fluorescence. Isoflurane and the selective GABA(A) agonist muscimol (25 micro M) reduced cell death after OGD to values similar to slices not exposed to OGD, with the exception that muscimol did not reduce cell death in CA3 neurons 2 days after OGD. The GABA(A) antagonist bicuculline reduced the neuroprotective effects of isoflurane on hippocampal neurons 2 and 3 days after OGD. We conclude that GABA(A) receptors contribute to neuroprotection against OGD produced by isoflurane in the hippocampal slice model. Based on this and other studies, it is likely that neuroprotection produced by isoflurane is multifactorial and includes actions at both GABA(A) and glutamate receptors and possibly other mechanisms. IMPLICATIONS: Isoflurane is neuroprotective in rodent brain ischemia models, but the mechanisms for this effect remain incompletely defined. In organotypic cultures of rat hippocampus, we show that protection of CA1, CA3, and dentate neurons by 1% isoflurane from death caused by oxygen and glucose deprivation involves GABA(A) receptors.     

Ketamine, but not propofol, anaesthesia is regulated by metabotropic glutamate 5 receptors

Background. Group I metabotropic glutamate receptors (mGluRs)have been reported to regulate N-methyl-D-aspartate (NMDA) receptorfunction in various brain regions. The selective mGluR5 antagonist2-methyl-6-(phenylethynyl)-pyridine (MPEP) can potentiate NMDAantagonists such as PCP and MK-801-induced behavioural responses.In the present study, the role of group I mGluRs on ketamine-and propofol-induced general anaesthesia was examined. Methods. Mice were pretreated with various doses of the groupI mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG), selectivemGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG),mGluR1 antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylateethyl ester (CPCCOEt) and mGluR5 antagonist MPEP followed byadministration of ketamine (120 mg kg^–1) or propofol (140mg kg^–1) to induce anaesthesia. The duration of loss ofrighting reflex was recorded. Results. DHPG and CHPG antagonized and MPEP potentiated ketamine-inducedanaesthesia in a dose-dependent manner. CPCCOEt was ineffective.However, propofol-induced anaesthesia was not affected aftermanipulating mGluR1 and mGluR5 receptors. Conclusions. mGluR5 receptors play an important role in modulationof anaesthesia induced by ketamine, but not propofol.     

Sevoflurane, but not propofol, significantly prolongs the Q-T interval

Prolongation of the Q-T interval may be associated with polymorphic ventricular tachycardia known as torsade de pointes, syncope and sudden death. Existing data show that isoflurane prolongs the Q-T interval, whereas halothane shortens it. The aim of this study was to determine whether sevoflurane or propofol affects the Q-T interval. Thirty female patients undergoing gynecologic surgery were randomly assigned to two groups, one receiving inhaled induction with sevoflurane and the other receiving total IV anesthesia with propofol. Before and 20 min after the induction, a six-lead electrocardiogram was recorded, and blood pressure was measured. The Q-T interval and heart rate adjusted Q-T interval (Q-Tc interval) were significantly prolonged during the administration of anesthesia with sevoflurane, while the Q-T interval was significantly shortened, and the Q-Tc interval was statistically unaffected during propofol anesthesia administration. We conclude that, in otherwise healthy female patients, sevoflurane prolongs the Q-Tc. IMPLICATIONS: In this study, we evaluated the effect of sevoflurane induction and anesthesia versus propofol induction and anesthesia on the Q-T interval. Sevoflurane significantly prolonged the Q-T interval and the heart rate adjusted Q-T interval, whereas propofol shortened the Q-T interval but not the heart rate adjusted Q-T interval.     

Systemic hypothermia,but not regional gut hypothermia,improves survival from prolonged hemorrhagic shock in rats

BACKGROUND: Extracorporeal blood perfusion of the gut or enterectomy can improve survival during hemorrhagic shock (HS), suggesting that the gut may be of primary importance in resuscitation. We hypothesized that cooling the gut alone could improve survival in a rat HS model and avoid potential deleterious effects of systemic hypothermia. METHODS: Thirty-two Sprague-Dawley rats were anesthetized with halothane. The gut (small intestine, cecum, and colon) was exteriorized. The right atrial (T ), rectal, and gut (T ) intraluminal temperatures were monitored. HS was induced by withdrawal of 2 mL of blood per 100 g body weight over 10 minutes. Mean arterial pressure was then maintained at 35 to 40 mm Hg to HS 90 min. From HS 20 min to resuscitation time 1 h, rats were randomized into four groups (n = 8 each): normothermia (T and T approximately 38.0 degrees C), gut-25 degrees C (T approximately 38 degrees C, T approximately 25 degrees C, induced by rinsing the gut with cooled saline), gut-33 degrees C (T approximately 38 degrees C, T approximately 33 degrees C), and systemic hypothermia (T approximately 33 degrees C, T approximately 25 degrees C). At HS 90 min, shed blood and Ringer's solution were infused to restore normotension. Survival, metabolism, and tissue damage were observed to 72 hours. RESULTS: Blood pressure was not different between groups. Compared with the normothermia group, the systemic hypothermia group had lower base deficit and lactate, and needed less fluid during resuscitation for normotension (p < 0.05), but these values were not different in the gut hypothermia groups. In addition, there were no significant improvements in tissue protection induced by regional gut hypothermia, whereas the systemic hypothermia group had lower plasma potassium, lower ornithine carbamoyltransferase (marker of liver injury), and higher glucose levels after HS (all p < 0.05). All rats in the systemic hypothermia group survived to 72 hours, whereas there was only one survivor in the normothermia group, two in the gut-33 degrees C group, and none in the gut-25 degrees C group (all p < 0.05 vs. systemic hypothermia). CONCLUSION: Cooling the gut alone does not improve acute survival from HS, suggesting that early deaths are not secondary to gut ischemia. Mild systemic hypothermia allowed 100% survival from prolonged HS.     

Intravenous lidocaine and ephedrine, but not propofol, suppress fentanyl-induced cough

PURPOSE: The aim of this study was to evaluate the effectiveness of lidocaine, propofol and ephedrine in suppressing fentanyl-induced cough. METHODS: One hundred and eighteen patients were randomly assigned into four groups and the following medications were given intravenously: patients in Group I (n = 31) received normal saline 2 mL, Group II (n = 29) received lidocaine 2 mg.kg(-1), Group III (n = 30) received propofol 0.6 mg.kg(-1) and Group IV (n = 28) received ephedrine 5 mg. At one minute after the study medication, fentanyl 2.5 microg.kg(-1) was given intravenously within two seconds. The occurrence of cough and vital sign profiles were recorded within two minutes after fentanyl bolus by an anesthesiologist blinded to study design. RESULTS: Sixty-five percent of patients in the placebo group had cough, whereas the frequency was significantly decreased in Groups II (14%) and IV (21%). Although a numerically lower frequency of cough was noted in Group III (37%), it was not statistically different from that of the placebo group. SpO(2) decreased significantly in patients of Group III compared to placebo; one patient experienced hypoxemia necessitating mask ventilation. Patients in Group III showed a decrease in heart rate and systolic blood pressure (2 beats.min(-1) and 8 mmHg vs baseline). Patients in Group IV showed an increase in both measurements (5 beats.min(-1) and 8 mmHg vs baseline). No truncal rigidity was observed throughout the study. CONCLUSIONS: Intravenous lidocaine 2 mg.kg(-1) or ephedrine 5 mg, but not propofol 0.6 mg.kg(-1), was effective in preventing fentanyl-induced cough. The results provide a convenient method to decrease fentanyl-induced cough.     

Midazolam/propofol but not propofol alone reversibly depress the swallowing reflex

General anaesthetics depress swallowing and this is a reason to delay oral intake after general anaesthesia. The swallowing reflex was studied 2 h after general anaesthesia for patients undergoing colonoscopy. Forty–one patients were anaesthetized with midazolam 75 μgkg^-1 followed by a continuous infusion of propofol and 39 patients with propofol 1.5 mgkg^-1 bolus followed by an infusion. Swallowing reflex was measured by electromyography 2 h after induction of anaesthesia, before and 5 min after the administration of flumazenil (0.2 mg) or placebo. Two h after anaesthesia, the state of consciousness was almost normal in all patients and did not change after flumazenil. At two hours, the latency times for the swallowing reflex in patients treated with propofol alone were of 1.4 ± 0.4 s and were significantly shorter ( P < 0.05) than the value of 1.9 ± 0.8 s observed in patients who received midazolam with propofol. In the latter group the latency time of the swallowing reflex was significantly reduced following the administration of flumazenil but not placebo. In patients who received propofol without midazolam, the administration of flumazenil or placebo was not associated with significant changes in the latency times. There were also no significant differences in the latency times in the subgroup that received midazolam followed by flumazenil and the propofol alone groups that did or did not receive flumazenil. These results suggest that midazolam still exerts a depressive effect on the swallowing reflex 2 h after its administration despite the recovery of normal consciousness.     

Mild hypothermia does not increase blood loss during total hip arthroplasty

BACKGROUND: The effects of mild hypothermia on blood loss are little known. METHODS: Patients, undergoing primary prosthetic hip surgery under spinal anaesthesia, were randomised to the operative procedure, with (n=25) or without (n=25) forced air warming. Core temperature was repeatedly measured from the tympanic membrane. The blood loss was calculated by three different methods; the intraoperative loss was estimated visually. The loss during and after the operation was obtained by determination of lost haemoglobin (the Hb-method). The blood loss during hospital stay was also calculated from the haemoglobin balance. RESULTS: Among controls, core temperature decreased by 1.3+/-0.6 degrees C (mean+/-SD) and in the warmed patients 0.5+/-0.4 degrees C (P<0.0001). Preoperative variables and the number of allogeneic units transfused did not differ between the groups. In controls, the blood loss during operation was, with the visual method, 698+/-314 ml, compared with 665+/-292 ml in warmed patients. With the Hb-method, the loss was 662+/-319 and 657+/-348 ml, respectively. With this method, the external loss during the entire hospital stay was, in controls, 1066+/-441 ml and in the warmed group, 1047+/-413 ml. The balance method yielded 1674+/-646 ml and 1507+/-652 ml, respectively. Indices of blood loss did not differ significantly between groups and there was no covariation between those variables and the decrease in core temperature. CONCLUSIONS: Forced air warming did not decrease the blood loss. Methods for determination of blood loss yielded widely differing results.     

Mild hypothermia does not increase bacterial proliferation on implanted vascular grafts

BACKGROUND: Mild hypothermia may offer protection against spinal cord ischemia during aortic surgery. However, hypothermia also promotes postoperative infection via two mechanisms: peripheral vasoconstriction and impairment of various immune functions. If mild hypothermia aggravates graft infections, immune function impairment would presumably be the most important factor because thermoregulatory vasoconstriction does not appreciably reduce aortic blood flow. We therefore tested the hypothesis that resistance to vascular graft infection is not reduced by mild perioperative hypothermia in dogs. METHODS: After colonization with a solution of Staphylococcus epidermidis, prostheses were used to replace the infrarenal aorta in 20 dogs. During surgery, the dogs were randomly assigned to maintain of normothermia or passive cooling. Seven days later, grafts were recovered for bacteriologic study. RESULTS: Colony counts for the grafts removed from the normothermic and hypothermic dogs did not differ significantly. CONCLUSIONS: Mild perioperative hypothermia does not increase proliferation of S epidermidis on aortic vascular grafts.     

Pentobarbitone, but not propofol, produces pre-emptive analgesia in the rat formalin model

Injection of formalin into the hindpaw of a rat induces a biphasicresponse in pain-related behaviours, such that C-fibre activationduring phase 1 triggers a state of central sensitization characterizedby a longer lasting phase 2. As the inhibitory neurotransmittergamma-aminobutyric acid (GABA) may participate in processingof nociceptive inputs, we hypothesized that pentobarbitone andpropofol, i.v. anaesthetics with known GABA_A agonist properties,would inten'ere with development of central sensitization andthereby modify the phase 2 hyperalgesic response. Pentobarbitoneadministered i. v. before injection of formalin produced dose-dependentsuppression of phase 2, even though animals had recovered fromanaesthesia, whereas it had substantially less effect when givenafter phase 1 had resolved. Picrotoxin, a GABA_A antagonist,reversed the effect of pentobarbitone on phase 2 pain behaviourbut was itself a mild analgesic. In contrast, propofol had noeffect on phase 2 formalin-induced pain behaviour. Thus we concludethat pentobarbitone, but not propofol, produced pre-emptiveanalgesia in this model, presumably by suppressing noxious stimulation-inducedcentral sensitization via activation of GABA_A receptors. ^*Present address: Department of Anesthesia, Teikyo University,Ichihara Hospital, 3426-3 Anesaki, Ichihara, Chiba 299-01, Japan     

Isoflurane, but not mild hypothermia, depresses the human pupillary light reflex

The pupillary light reflex is often evaluated in the perioperative period as a measure of cranial nerve and midbrain integrity. Although surgical concentrations of some anesthetic agents and severe hypothermia qualitatively alter the light reflex, confounding factors frequently present during postanesthetic recovery have not been specifically quantified. We therefore studied 12 volunteers to determine the effects of residual isoflurane concentrations and typical (mild) hypothermia on the human pupillary light reflex. Young, healthy volunteers were assigned to one of three treatments: 1) normothermic isoflurane-oxygen anesthesia; 2) isoflurane-oxygen anesthesia with 2.2 +/- 0.5 degree C central hypothermia; and 3) central hypothermia (1.6 +/- 0.3 degree C) without anesthesia, induced by internal jugular infusion of iced lactated Ringer's solution. In normothermic anesthetized volunteers, the amplitude of the light reflex was depressed 80-90% at end-tidal concentrations greater than 0.5% isoflurane: reflex (percent of control) = 14 - 67.log (percent isoflurane); r = -0.92. In the mildly hypothermic anesthetized volunteers, pupillary responses were not statistically different from those in anesthetized normothermic volunteers: reflex (percent of control) = 16 - 62.log (percent isoflurane); r = -0.97. Hypothermia alone did not alter the magnitude of the light reflex. Our data suggest that mild hypothermia does not depress the light reflex but that isoflurane reversibly depresses the light reflex in a dose-related manner.     

Cerebral blood flow velocity increases when propofol is changed to desflurane, but not when isoflurane is changed to desflurane in children

BACKGROUND: Children may exhibit delayed emergence following maintenance of anesthesia with propofol or isoflurane. Desflurane is often used towards the end of procedures to facilitate emergence. This study evaluated the effect on middle cerebral artery blood flow velocity (Vmca) in anesthetized children when propofol or isoflurane was substituted with desflurane. METHODS: Forty-two healthy children aged 1-6 years were enrolled. A standardized anesthetic induction was used. Anesthesia was maintained with remifentanil (0.5 microg.kg(-1) bolus followed by an infusion of 0.2 microg.kg(-1).min(-1)) and a randomly selected sequence of propofol/desflurane/propofol, desflurane/propofol/desflurane, isoflurane/desflurane/isoflurane or desflurane/isoflurane/desflurane. Propofol was administered to maintain a steady-state serum concentration of 3 microg.ml(-1). Desflurane and isoflurane were administered at age-corrected 1 MAC. Hemodynamic stability was maintained. Transcranial Doppler sonography was used to measure Vmca. Hemodynamic variables as well as Vmca were measured 30 min after skin incision and repeated 30 min after each change in anesthetic maintenance agent. RESULTS: The mean age and weight was 2.3 +/- 1.3 years and 13.0 +/- 3.7 kg, respectively. The Vmca (mean) increased by 35% from 37.7 +/- 10.5 cm s(-1) to 57.8 +/- 14.6 cm s(-1) (P < 0.0001) when propofol was changed to desflurane but was unaffected when desflurane replaced isoflurane. CONCLUSION: When propofol is changed to desflurane, cerebral blood flow velocity increases significantly in normal children. This cerebral vasodilatory effect may have important implications in the neurosurgical setting.     

Mild hypothermia fails to protect late hippocampal neuronal loss following forebrain cerebral ischaemia in rats

Summary Anaesthetized male rats (n=86) from both Long-Evans strain (LES) (n=43) and Wistar strain (WS) (n=43) were utilized for the experiments. While three animals from each strain were used as control, 40 rats from each strain underwent up to 10 minutes forebrain ischaemia by bilateral common carotid artery (CCA) occlusion combined with systemic hypotension [Mean Arterial Blood Pressure (MABP)=50 mm/Hg]. The animals from each strain were divided into four (n=10) groups. In both strains, groups (n=10) 1 and 2, temporalis muscle (TM) and body temperatures of the animals were kept at 36–37 °C during the experiments. The groups 1 and 2 were killed in 3 and 7 days after the ischaemic insult, respectively. The groups 3 and 4 were also killed 3 and 7 days after the ischaemic insult, but the forebrain ischaemia was carried out under mild cerebral hypothermia (TM temperature = 33 °C). Pyramidal neurons of the hippocampal CA1 region from each group was evaluated semiquantitatively. In WS, groups 1 and 2 showed moderate and severe neuronal loss in the CA1 region, respectively. However, in LES while the group 1 (3 days survival) did not show any neuronal loss, group 2 showed moderate neuronal loss of the CA1 region. While in group 3 (3 days survival, hypothermia) WS and LES, hypothermia protected the CA1 region, group 4 of LES showed mild neuronal loss. However WS, group 4 (7 days survival, hypothermia) showed severe neuronal loss of the CA1 region.It was concluded that mild hypothermia during ischaemic insults did not prevent the delayed postischaemic neuronal damage of the hippocampal CA1 region of both strains, and following 10 minutes forebrain ischaemia, male LES rats were found more resistant than male WS rats to neuronal loss of the CA1 region.     

Sevoflurane and isoflurane, but not propofol, decrease mivacurium requirements over time

PURPOSE: Volatile anesthetic agents potentiate neuromuscular blockade, but the magnitude of potentiation appears to be time dependent. The time course of this interaction was studied by measuring mivacurium infusion rates during sevoflurane, isoflurane and propofol anesthesia. METHODS: After informed consent, anesthesia was induced in 48 ASA physical status I-II adults with propofol, fentanyl and mivacurium 0.25 mg.kg(-1) and maintained with N(2)O (60%) and one of the three agents chosen at random: sevoflurane 1.9%; isoflurane 1.2%; or propofol 100-150 microgram.kg(-1).min(-1). Train-of-four stimulation was applied every 15 sec to the ulnar nerve. Neuromuscular blockade was monitored with accelerometry. At 5% recovery of the first twitch (T1), a mivacurium infusion was started and adjusted every five minutes to maintain 90-95% T1 depression. RESULTS: The time to 5% T1 recovery after the initial dose was similar in all groups (13-15 min). Fifteen minutes after the start of the infusion mivacurium requirements were greater (P < 0.05) in the propofol group (7.5 +/- 1.7 microgram.kg(-1).min(-1); mean +/- SD) than in either isoflurane (4.7 +/- 1.6 microgram.kg(-1).min(-1)) or sevoflurane (4.5 +/- 1.5 microgram.kg(-1).min(-1)) group. Then, the rate remained stable for propofol (6.2 +/- 1.4 microgram.kg(-1).min(-1) after 90 min of infusion) while it decreased with isoflurane to 2.9 +/- 1.6 microgram.kg(-1).min(-1) at 90 min (P < 0.05 vs propofol) and to 1.4 +/- 1.0 microgram.kg(-1).min(-1) in the sevoflurane group (P < 0.05 vs propofol and isoflurane). CONCLUSION: Sevoflurane and isoflurane do not prolong the effect of a bolus dose of mivacurium, but potentiation increases with time from 30-105 min of exposure. This interaction is greater with sevoflurane than isoflurane.     

Mild core hypothermia and anesthetic requirement for loss of responsiveness during propofol anesthesia for craniotomy

Mild hypothermia may be induced during neurosurgery for brain protection. However, its effect on propofol requirement has not been defined. Accordingly, we tested the hypothesis that 3 degrees C of core hypothermia decreases the propofol blood concentration at which patients respond to command (CP50-awake) in neurosurgical patients. Forty patients were anesthetized with alfentanil 50 microg/kg i.v., nitrous oxide, propofol target-controlled infusion, and rocuronium. The bispectral index (version 3.12) was monitored continuously. Patients were randomized to a core temperature of 34 degrees C or 37 degrees C. At the end of surgery, neuromuscular blockade was reversed, nitrous oxide was ceased, and propofol was infused to achieve a blood target determined by the previous patient's response. Responsiveness to command was assessed 15 min later. Results were analyzed with logistic regression models; P < 0.05 was considered statistically significant. The CP50-awake of propofol was 3.05 microg/mL (95% confidence interval, 2.34-3.66). Propofol concentration, but not core temperature, predicted loss of response to command (odds ratio, 11.76; 95% confidence interval, 2.40-57.63; P < 0.01). Core temperature did not alter the relationship between bispectral index and response to command. Propofol infusion regimens may not require adjustment during mild hypothermia. IMPLICATIONS: Neurosurgical patients may be allowed to become mildly hypothermic during anesthesia in an effort to provide brain protection. Propofol maintenance infusion doses may not require adjustment in these patients.     

Intubating conditions provided by propofol and alfentanil - acceptable, but not ideal

Background: The use of muscle relaxants to facilitate intubation is associated with several side effects regardless of whether depolarizing or non-depolarizing drugs are used. In the present study we compared the intubating conditions, haemodynamic responses and changes in oxygen saturation following induction with alfentanil and propofol or alfentanil, thiopental and suxamethonium.
Methods: Eighty patients (ASA I or II) were in a double-blind manner assigned to receive either of the two induction methods. Intubating conditions were assessed on the basis of jaw relaxation, ease of insertion of the endotracheal tube and coughing on intubation. Heart rate, systolic arterial pressure and oxygen saturation were monitored throughout the procedure.
Results: The use of alfentanil and propofol resulted in significantly lower scored intubation points. Systolic arterial pressure decreased and heart rate increased significantly in the alfentanil-thiopental-suxamethonium group as compared to the alfentanil-propofol group. There were no significant changes in oxygen saturation.
Conclusion: The results show that propofol and alfentanil in combination provides haemodynamic stability and unaltered oxygen saturation but less optimal intubating conditions.     

Sevoflurane but not propofol preserves myocardial function in coronary surgery patients

BACKGROUND: Sevoflurane has been shown to protect against myocardial ischemia and reperfusion injury in animals. The present study investigated whether these effects were clinically relevant and would protect left ventricular (LV) function during coronary surgery. METHODS: Twenty coronary surgery patients were randomly assigned to receive either target-controlled infusion of propofol or inhalational anesthesia with sevoflurane. Except for this, anesthetic and surgical management was the same in all patients. A high-fidelity pressure catheter was positioned in the left ventricle and the left atrium. LV response to increased cardiac load, obtained by leg elevation, was assessed before and after cardiopulmonary bypass (CPB). Effects on contraction were evaluated by analysis of changes in dP/dt(max). Effects on relaxation were assessed by analysis of the load dependence of myocardial relaxation (R = slope of the relation between time constant tau of isovolumic relaxation and end-systolic pressure). Postoperative concentrations of cardiac troponin I were followed during 36 h. RESULTS: Before CPB, leg elevation slightly increased dP/dt(max) in the sevoflurane group (5 +/- 3%), whereas it remained unchanged in the propofol group (1 +/- 6%). After CPB, leg elevation resulted in a decrease in dP/dt(max) in the propofol group (-5 +/- 4%), whereas the response in the sevoflurane group was comparable to the response before CPB (5 +/- 4%). Load dependence of LV pressure fall (R) was similar in both groups before CPB. After CPB, R was increased in the propofol group but not in the sevoflurane group. Troponin I concentrations were significantly lower in the sevoflurane than in the propofol group. CONCLUSIONS: Sevoflurane preserved LV function after CPB with less evidence of myocardial damage in the first 36 h postoperatively. These data suggest a cardioprotective effect of sevoflurane during coronary artery surgery.