High-affinity blockade of voltage-operated skeletal muscle and neuronal sodium channels by halogenated propofol analogues.

BACKGROUND AND PURPOSE: Voltage-operated sodium channels constitute major target sites for local anaesthetic-like action. The clinical use of local anaesthetics is still limited by severe side effects, in particular, arrhythmias and convulsions. These side effects render the search for new local anaesthetics a matter of high interest. EXPERIMENTAL APPROACH: We have investigated the effects of three halogenated structural analogues of propofol on voltage-operated human skeletal muscle sodium channels (Na(V)1.4) and the effect of one compound (4-chloropropofol) on neuronal sodium channels (Na(V)1.2) heterologously expressed in human embryonic kidney cell line 293. KEY RESULTS: 4-Iodo-, 4-bromo- and 4-chloropropofol reversibly suppressed depolarization-induced whole-cell sodium inward currents with high potency. The IC(50) for block of resting channels at -150 mV was 2.3, 3.9 and 11.3 microM in Na(V)1.4, respectively, and 29.2 microM for 4-chloropropofol in Na(V)1.2. Membrane depolarization inducing inactivation strongly increased the blocking potency of all compounds. Estimated affinities for the fast-inactivated channel state were 81 nM, 312 nM and 227 nM for 4-iodopropofol, 4-bromopropofol and 4-chloropropofol in Na(V)1.4, and 450 nM for 4-chloropropofol in Na(V)1.2. Recovery from fast inactivation was prolonged in the presence of drug leading to an accumulation of block during repetitive stimulation at high frequencies (100 Hz). CONCLUSIONS AND IMPLICATIONS: Halogenated propofol analogues constitute a novel class of sodium channel-blocking drugs possessing almost 100-fold higher potency compared with the local anaesthetic and anti-arrhythmic drug lidocaine. Preferential drug binding to inactivated channel states suggests that halogenated propofol analogues might be especially effective in suppressing ectopic discharges in a variety of pathological conditions.

Pre-operative and anaesthesia-related risk factors for mortality in equine colic cases.

Mortality rates for horses that have undergone emergency abdominal surgery are higher than for other procedures. Here, multivariable modelling of data from 774 surgical colic cases is used to identify pre-operative and anaesthesia-related variables associated with intra- and post-operative mortality. Intra-operative mortality was significantly (P<0.05), and positively associated with heart rate and packed cell volume (PCV) at admission, and negatively associated with the severity of pain. Post-operative mortality increased with increasing age and PCV at admission. Draught horses, Thoroughbreds and Thoroughbred-cross horses carried a significantly worse prognosis. We detected a small but significant variability in the risk of intra-operative death amongst referring veterinary surgeons. Different anaesthetic induction agents, inhalation maintenance agents and the use, or not, of intermittent positive pressure ventilation had no significant effect on risk of death. We conclude that cardiovascular compromise, level of pain, age, and breed are all associated with the risk of mortality in equine surgical colic cases.

Effect of magnetic resonance imaging on human respiratory burst of neutrophils.

It is known that low intensity magnetic fields increase superoxide anion production during the respiratory burst of rat peritoneal neutrophils in vitro. We investigated whether the high intensity magnetic fields (1.5 T) during magnetic resonance imaging can influence the human neutrophil function under in vivo conditions. Blood samples were obtained from 12 patients immediately before and after magnetic resonance imaging (mean time 27.6(+/-11.4 min)). The induced respiratory burst was investigated by the intracellular oxidative transformation of dihydrorhodamine 123 to the fluorescent dye rhodamine 123 via flow cytometry. The respiratory burst was induced either with phorbol 12-myristate 13-acetate, Escherichia coli, N-formyl-methionyl-leucylphenylalanine or priming with tumor necrosis factor followed by FMLP stimulation. There was no significant difference between the respiratory burst before and after magnetic resonance imaging, irrespective of the stimulating agent. Short time exposure to a high intensity magnetic field during magnetic resonance imaging seems not to influence the production of radical species in living neutrophils.

Voltage-dependent block of normal and mutant muscle sodium channels by 4-Chloro-m-Cresol.

1 The effects of 4-Chloro-m-Cresol (4-CmC) were examined on heterologously expressed wild type (WT), Paramyotonia Congenita (R1448H) and Hyperkalemic Periodic Paralysis (M1360V) mutant alpha-subunits of human muscle sodium channels. 2 Block of rested sodium channels caused by 4-CmC was concentration-dependent with an ECR50 of 0.40 mM in WT, 0.45 mM in R1448H and 0.49 mM in M1360V. 3 Inactivation significantly promoted 4-CmC-induced sodium channel block in all clones indicated by 4-CmC-induced shifts of steady-state availability curves, reflecting a higher proportion of channel block at depolarized membrane potentials. Channel block was almost complete (>90%) at concentrations close to the ECR50 (0.5 mM) on application of an inactivating prepulse before the test pulse. 4 4-CmC accelerated the current decay following depolarization and prolonged recovery from inactivation in all clones. Of these, R1448H, the mutant which displayed severely impaired inactivation in the controls, responded to 4-CmC with the most pronounced acceleration of inactivation. Control experiments revealed enhanced recovery from inactivation in the mutants, which was restored to normal in 0.1 mM 4-CmC. 5 4-CmC induced no additional frequency-dependent block. 6 Our results clearly demonstrate that 4-CmC is as effective as lidocaine (Fan et al., 1996) in blocking muscle sodium channels. Low concentrations of the compound (

Structural requirements for voltage-dependent block of muscle sodium channels by phenol derivatives.

We have studied the effects of four different phenol derivatives, with methyl and halogen substituents, on heterologously expressed human skeletal muscle sodium channels, in order to find structural determinants of blocking potency. All compounds blocked skeletal muscle sodium channels in a concentration-dependent manner. The methylated phenol 3-methylphenol and the halogenated phenol 4-chlorophenol blocked sodium currents on depolarization from -100 mV to 0 mV with IC(50) values of 2161 and 666 microM respectively. Methylation of the halogenated compound further increased potency, reducing the IC(50) to 268 microM in 2-methyl-4-chlorophenol and to 150 microM in 3,5-dimethyl-4-chlorophenol. Membrane depolarization before the test depolarization increased sodium channel blockade. When depolarizations were started from -70 mV or when a 2.5 s prepulse was introduced before the test pulse inducing slow inactivation, the IC(50) was reduced more than 3 fold in all compounds. The values of K(D) for the fast-inactivated state derived from drug-induced shifts in steady-state availability curves were 14 microM for 3,5-dimethyl-4-chlorophenol, 19 microM for 2-methyl-4-chlorophenol, 26 microM for 4-chlorophenol and 115 microM for 3-methylphenol. All compounds accelerated the current decay during depolarization and slowed recovery from fast inactivation. No relevant frequency-dependent block after depolarizing pulses applied at 10, 50 and 100 Hz was detected for any of the compounds. All the phenol derivatives that we examined are effective blockers of skeletal muscle sodium channels, especially in conditions that are associated with membrane depolarization. Blocking potency is increased by halogenation and by methylation with increasing numbers of methyl groups.

Voltage-dependent blockade of normal and mutant muscle sodium channels by benzylalcohol.

1. We studied the effects of benzylalcohol on heterologously expressed wild type (WT), paramyotonia congenita (R1448H) and hyperkalaemic periodic paralysis (M1360V) mutant alpha-subunits of human skeletal muscle sodium channels. 2. Benzylalcohol blocked rested channels at -150 mV membrane potential, with an ECR(50) of 5.3 mM in wild type, 5.1 mM in R1448H, and 6.2 mM in M1360V. When blockade was assessed at -100 mV, the ECR(50) was reduced in R1448H (2 mM) compared with both wild type (4.3 mM; P<0.01) and M1360V (4.3 mM). 3. Membrane depolarization before the test depolarization significantly promoted benzylalcohol-induced sodium channel blockade. The values of K(D) for the fast-inactivated state derived from benzylalcohol-induced shifts in steady-state availability curves were 0.66 mM in wild type and 0.58 mM in R1448H. In the presence of slow inactivation induced by 2.5 s depolarizing prepulses, the ECI(50) for benzylalcohol-induced current inhibition was 0.59 mM in wild type and 0.53 mM in R1448H. 4. Recovery from fast inactivation was prolonged in the presence of drug in all clones. 5. Benzylalcohol induced significant frequency-dependent block at stimulating frequencies of 10, 50, and 100 Hz in all clones. 6. Our results clearly show that benzylalcohol is an effective blocker of muscle sodium channels in conditions that are associated with membrane depolarization. Mutants that enter voltage-dependent inactivation at more hyperpolarized membrane potentials compared with wild type are more sensitive to inhibitory effects at the normal resting potential.

Application of a new verification technique allowing craniospinal irradiation in supine position.

To minimize anaesthesia related risks during craniospinal irradiation in children, treatment in supine position would be preferable. Verification especially of the cervical three-field junction causes problems, because direct visual control is not possible. We present clinical experiences with a new verification technique with all three fields exposed on one single film.

GM-CSF increases in vitro the respiratory burst of human neutrophils after liver transplantation.

OBJECTIVE: Superoxide production by polymorphonuclear neutrophils (PMNs) under cyclosporin A (CsA) therapy following kidney transplantation is impaired. We investigated if the respiratory burst of PMNs is similarly depressed in patients undergoing CsA treatment following orthotopic liver transplantation (OLTx). Additionally, the in vitro influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the superoxide anion production was examined during the respiratory burst. PATIENTS: 10 patients after OLTx and 10 healthy blood donors (control group). MEASUREMENTS AND RESULTS: PMNs were stimulated with bacteria (Escherichia coli) or a combination of tumour necrosis factor alpha (TNFalpha) and N-formyl-methionyl-leucyl-phenylalanine (FMLP). The respiratory burst was measured by oxidation of non-fluorescent dihydrorhodamine to the fluorescent rhodamine by means of flow cytometry. No differences in respiratory bursts from OLTx patients compared to those from healthy blood donors could be seen. Under TNFalpha/FMLP stimulation, the respiratory burst was significantly increased after in vitro incubation with GM-CSF (500 U ml(-1)) in patients following OLTx (from 58.2 to 74.5 %) as well as in the control group (from 47.4 to 61.9%). CONCLUSIONS: Our results demonstrate that superoxide production is not impaired under CsA treatment following OLTx. The respiratory burst of these patients' PMNs can even be augmented by GM-CSF in vitro.

Predictors of respiratory function deterioration after transfer of critically ill patients.

OBJECTIVES: Critically ill patients are often transferred due to the growing number of diagnostic procedures required to be performed outside the intensive care unit. These transfers have proved to be very critical. The aim of this study was to evaluate predictors for the deterioration of respiratory function in critically ill patients after transfer. DESIGN: Prospective, clinical, observational study. SETTING: 1800-bed university teaching hospital. SUBJECTS: 98 mechanically ventilated patients were investigated during transfer. MEASUREMENT AND MAIN RESULTS: Before transfer, all patients were classified according to the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Therapeutic Intervention Scoring System (TISS). Haemodynamics and arterial blood gases were measured at 11 different times. Arterial oxygen tension (PaO2), fractional inspired oxygen (FIO2), PaO2/FIO2 ratio, lowest PaO2/FIO2 ratio, minimal PaO2 and maximal FIO2, APACHE II score, TISS before transfer, age and duration of transfer were analysed as potential predictors for deterioration of respiratory function after transfer. Variables were analysed using Classification and Regression Trees and Clustering by Response. In 54 transports (55%) there was a decrease in the PaO2/FIO2 ratio, and a decrease of more than 20% from baseline was noted in 23 of the transferred patients (24%). Age > 43 years and FIO2 > 0.5 were identified as predictors for respiratory deterioration. CONCLUSIONS: Our predictors were able to indicate deterioration after transfer correctly in 20 of 22 patients (91%), combined with a false-positive rate in 17 of 49 (35%).

Standard calculation of ethanol elimination rate is not sufficient to provide ethanol substitution therapy in the postoperative course of alcohol-dependent patients.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a severe complication during postoperative treatment of alcohol-dependent patients. Besides the use of clomethiazole, clonidine, and benzodiazepines, there is another possible way to prevent AWS by deliberate administration of ethanol. The appropriate dosage of ethanol has not been known up to now and it could be defined according to the average ethanol elimination rate (EER) which, from forensic analysis, is known to be 15 mg/dl per h in a normal population. However, it is questionable whether these data are suitable for the calculation of the correct dosage in alcohol-dependent patients. DESIGN: Preliminary retrospective descriptive study. SETTING: Intensive care unit of a university teaching hospital. PATIENTS: 11 alcohol-dependent patients (9 males, 2 females, mean age 50.8 years, range 33 to 60 years). INTERVENTIONS: Ethanol substitution (ES) by parenteral application. MEASUREMENTS AND RESULTS: Ethanol kinetics were evaluated by repeated measurement of the blood ethanol concentration (BEC) over a period of at least 6 h parallel to the administration of ethanol. The average EER was found to be 28 mg/dl per h with a standard deviation of 11 mg/ dl per h. The minimum value was 18 mg/dl per h and the maximum 50 mg/dl per h. These EERs were significantly higher than the EERs known from forensic analysis. AWS was prevented in all 11 patients. CONCLUSIONS: Close control of BEC and precise adjustment of ethanol administration are necessary prerequisites for ES. The standard EER is not sufficient to define the appropriate ethanol dosage due to enormous variations in the ethanol metabolism of alcohol-dependent patients.

Hydroxyethyl starch and modified fluid gelatin maintain plasma volume in a porcine model of septic shock with capillary leakage.

OBJECTIVE: To compare the effects of different volume replacement therapies on maintenance of plasma volume in septic shock and capillary leakage syndrome. DESIGN AND SETTING: Prospective randomized, controlled animal laboratory study in a university animal laboratory. MEASUREMENTS AND RESULTS: Twenty-five fasted, anaesthetized, mechanically ventilated and multi-catheterized pigs (20.8+/-1.8 kg) received 1 g/kg body weight faeces into abdominal cavity to induce sepsis and were observed over 8 h. Five animals each received volume replacement therapy with modified fluid gelatin 4% or 8% (MFG4%, MFG8%), 6% HES 200/0.5, or Ringer's solution and were compared to controls receiving 6% HES 200/0.5. Infusion rate was titrated to maintain a central venous pressure of 12 mmHg. Plasma volume was determined using (51)Cr-labelled erythrocytes and standard formulae. Albumin escape rate was calculated using technetium (99m)Tc-labelled albumin. Colloid osmotic pressure, systemic haemodynamics and oxygenation were obtained before and 4 and 8 h after induction of sepsis. Plasma volume was reduced in the Ringer's solution group (-46%) but was maintained in HES (+/-0%), MFG4% (+4%), MFG8% (+23%) groups. Albumin escape rate increased in HES (+52%), MFG4% (+47%), MFG8% (+54%) and the Ringer's solution group (+41%) compared to controls. CONCLUSION: In this porcine septic shock model with concomitant capillary leakage syndrome, confirmed by an increased albumin escape rate, the artificial colloids HES, MFG4%, and MFG8% maintained plasma volume and colloid osmotic pressure. These results suggest the intravascular persistency of artificial colloids in the presence of albumin leakage. An editorial regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-002-1283-9)

Evaluation of noninvasive determinants for capillary leakage syndrome in septic shock patients.

OBJECTIVE: Capillary leakage syndrome (CLS) is a frequent complication in sepsis, characterized by loss of intravasal fluids leading to generalized edema and hemodynamic instability despite massive fluid therapy. In spite of its importance no standardized diagnostic criteria are available for CLS. DESIGN: Prospective clinical study. SETTING: 1,800-bed university hospital PATIENTS: Six septic shock patients with CLS were compared to six control patients. MEASUREMENTS AND RESULTS: CLS was clinically determined by generalized edema, positive fluid balance, and weight gain. Plasma volume was measured by indocyanine green, red blood cell volume by chromium-51 labeled erythrocytes, and colloid osmotic pressure before and 90 min after the administration of 300 ml 20% albumin. Extracellular water (ECW) was measured using the inulin distribution volume and bioelectrical impedance analysis. Red blood cells averaged 20.2 +/- 1.0 ml/ kg body weight in CLS patients and 23.3 +/- 4.1 in controls. ECW was higher in CLS patients than in controls (40.0 +/- 6.9 vs. 21.7 +/- 3.71; p< 0.05). ECW of inulin was correlated with that measured by bioelectrical impedance analysis (r = 0.74, p< 0.01). The increase in colloid osmotic pressure over the 90 min was less in CLS patients than in controls (1.1 +/- 0.3 vs. 2.8 +/- 1.3 mmHg;p< 0.05). CONCLUSION: These results suggest that measurements of an increased ECW using bioelectrical impedance analysis combined with a different response of colloid osmotic pressure to administration of albumin can discriminate noninvasively between patients with and those without CLS.

Septic shock after liver transplantation for Caroli's disease: clinical improvement after treatment with C1-esterase inhibitor.

The extent of complement and contact activation is related to outcome in sepsis. A low functional index of their main blocker C1-esterase inhibitor (C1-INH) is considered as a relative deficiency of C1-INH and might contribute to the development of fatal complications in the intensive care unit. The first results of therapeutic intervention with C1-INH concentrate in septic shock are promising. We report on our experience of C1-INH concentrate administration in a young woman with Caroli's disease as ultimate rescue therapy for septic shock with capillary leakage syndrome after combined liver and kidney transplantation. No focus of infection was detectable and thus surgical intervention was not indicated. Antibiotic therapy at that time included vancomycin, tobramycin, meropenem and fluconazol. Hemodynamic stabilization occurred within hours after administration of C1-INH concentrate. Simultaneously a reduction in vasopressor medication was possible and negative fluid balance was achieved.

Effects of C1 inhibitor and r-SP-C surfactant on oxygenation and histology in rats with lavage-induced acute lung injury.

OBJECTIVE: To assess the effects of C1 inhibitor (INH) administration and r-SP-C surfactant application on oxygenation and lung histology in an acute respiratory distress syndrome model. DESIGN AND SETTING: Randomized, controlled experimental study in an animal research laboratory. MATERIAL: 36 adult male Sprague-Dawley rats. INTERVENTIONS: Animals were subjected to repetitive lung lavage. Four experimental groups and two control groups were studied: groups 1 and 2 served as controls. Animals of groups 3-6 received 200 U/kg body weight C1-INH (group 3), 25 mg/kg r-SP-C surfactant (group 4) or both (group 5) at 60 min postlavage (pl). Animals of group 6 were treated with 200 U/kg C1-INH1 at 10 min pl. Animals of group 1 were killed 60 min (min) pl, animals of groups 2-6 were killed at 210 min pl. Thereafter the lungs were excised for histological examination. MEASUREMENTS AND RESULTS: Hyaline membrane formation, intra-alveolar neutrophil (PMN) accumulation and intra-alveolar/perivascular haemorrhage were graded semiquantitatively (0-4). Blood gases were determined 120, 150, 180 and 210 min pl. At 210 min pl pO(2) in group 4 (456+/-74 mmHg) and group 5 (387+/-155 mmHg) was significantly higher than in controls (72+/-29 mmHg) or after C1-INH monotherapy (group 3: 120+/-103, group 6: 63+/-12 mmHg). PMN infiltration after C1-INH monotherapy was significantly less severe than in controls. The combination of r-SP-C surfactant and C1-INH led to significantly lower PMN infiltration than surfactant monotherapy. CONCLUSION: In this lavage-induced acute respiratory distress syndrome model the administration of C1-INH might be followed by a higher clinical efficacy of exogenously supplied recombinant SP-C surfactant.

Phenol derivatives accelerate inactivation kinetics in one inactivation-deficient mutant human skeletal muscle Na(+) channel.

Altered inactivation kinetics in skeletal muscle Na(+) channels due to mutations in the encoding gene are causal for the alterations in muscle excitability in nondystrophic myotonia. Na(+) channel blockers like lidocaine and mexiletine, suggested for therapy of myotonia, do not reconstitute inactivation in channels with defective inactivation in vitro. We examined the effects of four methylated and/or halogenated phenol derivatives on one heterologously expressed inactivation-deficient Paramyotonia congenita-mutant (R1448H) muscle Na(+) channel in vitro. All these compounds accelerated delayed inactivation of R1448H-whole-cell currents during a depolarization and delayed accelerated recovery from inactivation. The potency of these effects paralleled the potency of the drugs to block the peak current amplitude. We conclude that the investigated phenol derivatives affect inactivation-deficient Na(+) channels more specifically than lidocaine and mexiletine. However, for all compounds, the effect on inactivation was accompanied by a substantial block of the peak current amplitude.

Structural requirements of phenol derivatives for direct activation of chloride currents via GABA(A) receptors.

Propofol directly activates gamma-aminobutyric acid (GABA(A)) receptors in the absence of the natural agonist. This mechanism is supposed to contribute to its sedative-hypnotic actions. We studied the effects of seven structurally related phenol derivatives on chloride inward currents via rat alpha1beta2gamma2 GABA(A) receptors, heterologously expressed in HEK 293 cells in order to find structural determinants for this direct agonistic action. Only compounds with the phenolic hydroxyl attached directly to the benzene ring and with aliphatic substituents in ortho position to the phenolic hydroxyl activated chloride currents in the absence of GABA. Concentrations required for half-maximum effect were 980 microM for 2-methylphenol, 230 microM for 2,6-dimethylphenol, 200 microM for thymol, and 23 microM for propofol. Drug-induced chloride currents showed no desensitisation during the 2-s application. These results show that the position of the aliphatic substituents with respect to the phenolic hydroxyl group is the crucial structural feature for direct GABA(A) activation by phenol derivatives.

In vitro influence of parenteral lipid emulsions on the respiratory burst of neutrophils.

The in vitro effect of a fish oil-derived lipid emulsion (omega-3) on the superoxide anion production during the respiratory burst (RB) of human neutrophils was compared to a LCT lipid (Intralipid), and an LCT/MCT emulsion (Lipofundin MCT). The effects of two concentrations (60 and 600 micrograms/mL) were evaluated by rhodamine in a flow cytometer. The RB was induced either by stimulation with Escherichia coli (E. coli) or by priming with TNF-alpha and FMLP stimulation. The results (mean +/- SD%, P < 0.05) were compared to positive control responses (RB without lipids). omega-3 (60 micrograms/mL, -8.2 [9.3]%; 600 micrograms/mL, -9.6 [11.1]%) and LCT (600 micrograms/mL, -8.0 [9.3]%) significantly suppressed the RB after stimulation with E. coli. LCT/MCT increased the RB after E. coli (60 micrograms/mL, 15.7 [15.4]%; 600 micrograms/mL, 42.7 [21.4]%) as well as after TNF-alpha/FMLP stimulation (600 micrograms/mL, 27.4 [23.7]%). The in vitro influence of parenteral lipid emulsions on the superoxide anion production of human neutrophils is dependent on the length of the fatty acid molecule.

Inhibition of neutrophil respiratory burst and chemotaxis in vitro by thiopentone but not methohexitone.

Administration of high-dose barbiturates may be used as an appropriate adjunctive treatment for control of intracranial pressure. The thiobarbiturate, thiopentone, has been reported to increase the rate of nosocomial pulmonary infection. This may be a substance-related effect of thiobarbiturates and it may be clinically important in barbiturate-sedated patients with severe head injury. Thus, the effects of the dose-response relationship of two commonly used barbiturates (thiopentone and methohexitone) on two vital aspects of neutrophil function were tested. We studied the production of superoxide anion during the respiratory burst by means of a flow cytometric method, and we assessed N-formyl-methionyleucylphenylalanine-induced neutrophil chemotaxis using the results produced by specific migration. The concentrations of thiopentone and methohexitone tested in vitro were adjusted to conform to the plasma concentrations reported for anesthesia and also to 10-fold higher concentrations. Only thiopentone dose dependently decreased respiratory burst and N-formyl-methionyleucylphenylalanine-induced chemotaxis. Methohexitone produced minimal effects in both concentrations. It was demonstrated that thiopentone had a direct effect on the intracellular respiratory burst oxidase enzyme system. The postulated free radical scavenging capacity of thiopentone was ruled out.

General anesthesia for interventional neuroradiology: propofol versus isoflurane.

STUDY OBJECTIVE: To compare recovery of psychomotor and cognitive ability after isoflurane and propofol-based general anesthesia. DESIGN: Prospective, blinded interventional study. SETTING: University hospital. PATIENTS: 24 ASA physical status I and II patients undergoing embolization procedures for intracranial vascular lesions. INTERVENTIONS: Isoflurane anesthesia or propofol anesthesia was given to patients. MEASUREMENTS: Awakening time; early recovery (5 minutes, 15 minutes, 30 minutes) was assessed using orientation and Steward tests; medium recovery (30 minutes, 60 minutes, 120 minutes) was tested using Controlled World Association (COWAT) and Digit Span tests; late recovery (4 hours, 24 hours) was assessed using a Verbal Learning and Memory Test and three subtests of a computerized attention test battery. MAIN RESULTS: Awakening time and early recovery of motor and respiratory function did not differ between groups. The propofol group scored worse in COWAT and Digit Span tests up to 60 minutes after anesthesia. Both groups showed an impairment of higher cognitive functions up to 24 hours after anesthesia. CONCLUSIONS: Both isoflurane- and propofol-based anesthesia allow early extubation and recovery of basic psychomotor functions. More sophisticated tests show a decline of cognitive functions up to 24 hours after isoflurane- as well as propofol-based anesthesia. Because both anesthetics show similar recovery of psychomotor functions after long duration anesthesia, other factors such as subjective well-being and costs may be considered when deciding between these two anesthetics.