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Thiopental and ether anaesthesia decrease the prostaglandin receptor density of the rat liver.

Male Sprague-Dawley rats were killed either by decapitation or during anaesthesia with thiopental or diethylether by aortectomy. Livers were removed and liver plasma membranes were prepared using standard techniques. Direct binding experiments with 3H-PGE1 and 3H-iloprost revealed heterogeneity of the binding sites (high and low affinity binding sites), whereas 3H-PGE2 demonstrated only high affinity binding to the liver. The highest binding capacity for all radioligands was found for livers after decapitation. Livers obtained during anaesthesia showed a significantly (p less than 0.05 to p less than 0.001) lower binding capacity and binding affinity for 3H-PGE1, 3H-PGE2 and 3H-iloprost. The reduction in binding activity was more pronounced in livers obtained during inhalation than thiopental anaesthesia. Specific binding amounted to 82.1 +/- 7% for 3H-PGE2, 75.3 +/- 9% for 3H-PGE1 and 78.9 +/- 8% for iloprost in livers obtained after decapitation. In livers obtained during anaesthesia specific prostaglandin binding was significantly (p less than 0.01) decreased, again being more pronounced during inhalation than thiopental anaesthesia. These results suggest that some anaesthetics interfere with prostaglandin receptors of the liver.

Alprostadil↗

Population pharmacokinetics of high-dose thiopental in patients with cerebral injuries.

Thiopental monitoring was performed in 95 critically ill patients hospitalized for neurologic damage, High-dose thiopental was infused during long-term treatment. Total dose of 333 +/- 144 mg/kg (449 +/- 185 mg/kg for females and 302 +/- 113 mg/kg for men) were given in 125 +/- 43 hours. Plasma concentration-time data were analyzed according to a population pharmacokinetic approach with an initial group of 65 patients. Clearance (CL) and central volume of distribution (Vc) were modeled alone and under the influence of demographic covariates, assuming a two-compartment open model with first-order elimination. The final population models were as follows: CL (L/hr) = 11.7.weight (kg).age (yr)/(2136 + age2) and Vc = 1.52.weight (kg) + 44.8. Mean CL and Vc mean population estimates were 8.01 L/hr (133 ml/min or 2.02 ml/min/kg) and 145 L (2.19 L/kg). The predictive performance of the population modeling and parameters was evaluated with a bayesian fitting procedure in an independent validation set of 30 patients with similar physical and clinical characteristics. There was no statistically significant bias or imprecision between measured and predicted thiopental plasma concentrations in this validation group. Moreover, there was a good adequation (r = 0.939) between individual CL values predicted from the population formula and estimated with the bayesian approach.

Adolescent↗

Calcium and thiopental-induced spontaneous activity in rabbit papillary muscle.

Isolated rabbit papillary muscles exposed to 20 to 30 mg/l of thiopental developed spontaneous contractile activity. The spontaneous activity often appeared following the cessation of high frequency stimulation. The maximum rate of spontaneous beating decreased in parallel with the force of contraction when the extracellular Ca2+ concentration was lowered or when ryanodine, an inhibitor of sarcoplasmic reticular function, was added. Stretching of the muscles increased the incidence of thiopental-induced spontaneous activity. These results suggest that intracellular Ca2+ influences thiopental-induced spontaneous activity, analogous to arrhythmias associated with afterdepolarization.

Animals↗

The effects of anesthesia with thiopental on T lymphocyte responses to antigen and mitogens in vivo and in vitro.

In this study we show that antigen-specific lymphocyte proliferation and interleukin (IL)-2 production by peripheral blood lymphocytes from patients under thiopental anesthesia are significantly depressed. In contrast, mitogen-induced lymphocyte proliferation and IL-2 secretion are not depressed. We have also shown that tetanus toxoid (TT) specific CD4+ T cell clones, with a known cytokine production profile, were sensitive to the inhibitory effects of thiopental and exhibited decreased proliferation to TT as well as decreased secretion of IL-2. We observed no difference regarding IL-4 production by these clones. The data suggest that the immunosuppressive effect of thiopental is confined to antigen-specific responses. In addition, we have shown that whereas IL-2 and interferon-gamma production is dramatically impaired by the drug, IL-4 production is not significantly altered. This last finding has important implications regarding the type of immune response that is most affected by this anesthetic agent. In spite of the transient decrease in antigen-driven IL-2 synthesis, no clinical evidence of infection was noted in any healthy patient.

Adolescent↗

Detection of thiopental and pentobarbital in head and pubic hair in a case of drug-facilitated sexual assault.

The quali-quantitative determination of two barbiturates, thiopental and its metabolite pentobarbital, in head and pubic hair samples of a woman who had been sexually assaulted during hospitalisation, is reported. Hair was analysed by means of solid-phase microextraction (SPME) and gas chromatography-multiple mass spectrometry (GC-MS-MS), in chemical ionisation conditions. Thiopental and pentobarbital were found in three proximal head hair segments (sample 1A: 0.30 and 0.40 ng/mg; sample 1B: 0.20 and 0.20 ng/mg; sample 3: 0.15 and 0.20 ng/mg) and pubic hair sample. Two distal head hair segments were negative for both barbiturates. Despite the lack of collection and toxicological analysis of blood or urine samples within the hospital setting, analytical findings from hair revealed the use of the anaesthetic agent thiopental to sedate the victim quickly and deeply and commit sexual assault.

Female↗

The effects of thiopental and generic and nongeneric propofol on respiratory resistance during anesthetic induction in patients with reactive airways.

STUDY OBJECTIVE: To demonstrate a favorable effect of propofol on respiratory system resistance during anesthetic induction, and to determine if generic propofol causes adverse effects on respiratory resistance. DESIGN: Randomized pilot study. SETTING: Anesthetic induction for elective surgery. PATIENTS: 27 consenting ASA physical status II and III patients with reactive airways (positive smoking history or chronic obstructive pulmonary disease), but not receiving bronchodilator therapy. INTERVENTIONS: Patients were randomized equally to one of three anesthetic induction (and maintenance) drugs: sodium thiopental, 5 mg/kg (25 microg/kg/min), generic or nongeneric propofol, 1.25 mg/kg (50 microg/kg/min). They received preinduction midazolam and fentanyl (2 mg and 150 microg) and intravenous lidocaine (0.5 mg/kg). After anesthetic induction, tracheal intubation was established, and predetermined settings for mechanical ventilation were initiated. MEASUREMENTS: Immediately after intubation, a sensor was placed on the 8-mm endotracheal tube to detect baseline airway pressure and flow. During maintenance, repeat measurements of pressure and flow were obtained at 2.5-minute intervals for 10 minutes. Respiratory system resistance was derived off-line using the isovolumetric technique. MAIN RESULTS: Patients were similar across groups. The respiratory resistance measured after anesthetic induction did not differ among groups. During the maintenance infusion of thiopental or propofol, respiratory resistance increased gradually across all groups. There was no difference in the response of respiratory resistance either at induction or during the 10-minute maintenance between the generic and the nongeneric propofol groups. CONCLUSIONS: In contrast to earlier reports, this pilot study was unable to document a difference in the respiratory resistance in patients induced with thiopental or propofol. In addition, we were unable to demonstrate any different respiratory responses between generic propofol, containing sodium metabisulfite preservative, and nongeneric propofol.

Airway Resistance↗

Etomidate and thiopental-based anesthetic induction: comparisons between different titrated levels of electrophysiologic cortical depression and response to laryngoscopy.

STUDY OBJECTIVE: To determine whether etomidate-based induction can provide better hemodynamics than a standard thiopental sodium-based anesthetic induction. DESIGN: Prospective, single-blind clinical trial. SETTING: Multicenter university neurosurgical operating room. PATIENTS: 66 ASA physical status II and III inpatients undergoing neurosurgical procedures for intracranial tumor or other pathology. INTERVENTIONS: Patients were divided into two groups for anesthetic induction. The first group (control) was divided into two subgroups, with the first subgroup receiving "low-dose" etomidate (LET) 0.4 to 0.6 mg/kg titrated to an electroencephalographic (EEG) spectral edge frequency (SEF) of 10 to 12 Hz. The second subgroup received thiopental sodium (THIO) 3 to 6 mg/kg titrated to the same EEG endpoint. The study group was given high-dose etomidate (HET) 0.5 to 1.7 mg/kg titrated to an early burst suppression pattern. MEASUREMENTS AND MAIN RESULTS: Baseline (awake) measurements of mean arterial pressure (MAP) heart rate (HR), and SEF were obtained prior to anesthetic induction that was accomplished using a small bolus plus an infusion of the induction drug titrated to the EEG target. MAP, HR, and SEF were recorded just prior to laryngoscopy and intubation (T1), 30 seconds after laryngoscopy and intubation (T2), and 90 seconds after (T3) laryngoscopy and intubation. Times to reach EEG endpoint, along with total dose of anesthetic given, were also recorded. Compared with baseline values, the THIO group had the highest increase in both HR (22.9 +/- 4.4 bpm.) and MAP (16.8 +/- 4.2 mmHg) (P < 0.05) after laryngoscopy and intubation. The LET group also had significant increases compared with the HET group that demonstrated the least hemodynamic variability. No correlations could be made between age and dose of induction drug. CONCLUSIONS: Etomidate-based anesthetic induction, titrated to EEG burst suppression, produced stable hemodynamics during laryngoscopy and intubation as compared with lower dose, more "classic" inductions with etomidate or thiopental.

Adult↗

Bolus administration of eltanolone, thiopental, or etomidate does not affect systemic vascular resistance during cardiopulmonary bypass.

OBJECTIVE: To discover possible effects on systemic vascular resistance of the anesthetic induction agent eltanolone in comparison with thiopental and etomidate. The measurements were performed during cardiopulmonary bypass to maintain a constant cardiac output (approximately pump flow). DESIGN: The patients were prospectively randomized in three groups to receive either eltanolone, thiopental, or etomidate. SETTING: University hospital as a single center. PARTICIPANTS: Seventy-five patients scheduled for elective coronary artery bypass grafting. INTERVENTIONS: The anesthetic induction agents were repeated at the same dosage when cardiopulmonary bypass was instituted. The respective mean dosages were eltanolone, 0.41 +/- 0.1 mg/kg; thiopental, 2.88 +/- 0.62 mg/kg; etomidate, 0.26 +/- 0.06 mg/kg. MEASUREMENTS AND MAIN RESULTS: Systemic vascular resistance was calculated from the mean of a triple measurement (normal pump flow and +/- 20%). Points of measurement were before, and 2 and 5 minutes after injection of the hypnotic agent. None of the injected drugs made a significant change in the systemic vascular resistance. A small (not significant) decrease from 1,295 +/- 296 dyne/s/cm-5 to 1,196 +/- 323 dyne/s/cm-5 (mean +/- SD) was seen in the eltanolone group, whereas the other patients did not show any change during the study period. CONCLUSIONS: The reason for the significant reduction of the arterial pressure attributed to anesthetic induction by eltanolone may be more a cardiodepressive effect than a direct vasodilation.

Anesthetics, Intravenous↗

The excitability of human corticospinal neurons is depressed by thiopental.

BACKGROUND: We tested the effect of thiopental on the excitability of the corticospinal-motoneuron axis in normal human subjects. METHODS: Magnetic stimulation was used to excite the neurons in the motor cortex which give rise to the fast conducting corticospinal pathway. The characteristics of the composite excitatory post-synaptic potentials (EPSPs) produced in individual spinal motoneurons by cortical stimulation were derived from changes in the firing probability of voluntarily activated motor units of the first dorsal interosseous muscle. RESULTS: In 5 normal subjects, we found that thiopental, in incremental doses sufficient to sustain drowsiness (total dose 75 to 175 mg), significantly reduced the amplitude of these composite EPSPs. CONCLUSIONS: Thiopental reduced the facilitation of motoneurons from the cortex most likely by depressing cortical neurons.

Adult↗

Molecular understanding of Abeta peptide interaction with isoflurane, propofol, and thiopental: NMR spectroscopic study.

Abeta peptide is the major component of senile plaques (SP), which accumulate in the brain of a patient with Alzheimer's disease (AD). A recent report indicated that isoflurane enhanced Abeta oligomerization (micro-aggregation) and subsequent cytotoxicity of the Abeta peptide. A separate study showed that a clinically relevant concentration of isoflurane induces apoptosis and increases Abeta production in a human neuroglioma cell line. In vitro studies have indicated that halothane interacts specifically with Abeta peptide to induce oligomerization and that Abeta42 oligomerizes faster than Abeta40. The specific interactions of isoflurane, propofol, and thiopental with uniformly 15N labeled Abeta40 and Abeta42 peptide were investigated using multidimensional nuclear magnetic resonance (NMR) experiments. We found that isoflurane and propofol (at higher concentration) interact with Abeta40 peptides and induce Abeta oligomerization. Thiopental does not interact with specific residues (G29, A30, and I31) of Abeta40; hence, the peptide remains in the monomeric form. On the basis of our NMR study, thiopental does not oligomerize Abeta40 even at higher concentrations.

Amyloid beta-Peptides↗

Efficacy and safety of rectal thiopental: sedation for children undergoing computed tomography and magnetic resonance imaging.

PURPOSE: We evaluated the clinical safety, effectiveness, efficiency and potential side effects of rectally administered thiopental in 30 children undergoing computed tomography (CT) and magnetic resonance imaging (MRI). METHODS: The doses of thiopental used were 50 mg/kg for infants under 6 months of age, 35 mg/kg for infants between 6 and 12 months of age and 25 mg/kg for older children. After administration of the sedative, oxygen saturation was continuously monitored and vital signs were recorded every 20 min during the imaging procedure and then every 20 min until discharge. RESULTS: Successful sedation and adequate imaging were obtained in 29 of 30 (96.7%) patients. Respiratory depression was not observed in any patient. However, oxygen saturation dropped below 90% transiently (to 88%) in three patients (10.0%) and this was immediately corrected by repositioning the child's neck to open the upper airway. All successfully sedated patients were asleep within 15 min (mean +/- SD 7.3 +/- 2.7 min) and sedation was sufficient for at least 30 min. Prolonged sedation was observed in two patients. CONCLUSIONS: We believe that rectal thiopental is a safe, effective and efficient form of sedation for pediatric imaging.

Administration, Rectal↗

Efficacy and safety of rectal thiopental sedation in outpatient echocardiographic examination of children.

UNLABELLED: The efficacy and safety of rectal thiopental administration in sedation for paediatric echocardiographic examination were prospectively investigated in infants with known or suspected congenital heart disease in an outpatient manner. A total of 1150 patients (546F, 604M) were studied; 264 were 7 d to 6 mo old (group I), 572 were 6 mo to 2-y-old (group II), and 314 were 2 to 6-y-old (group III). Thiopental sodium dissolved in 10 ml of water in a syringe to which a 6-F feeding catheter was attached was administered prior to echocardiographic examination to patients in groups I, II and III with doses of 50, 35 and 25 mg/kg, respectively in an emergency care environment. Length of time to achieve sedation (induction time), duration of sedation, length of time to return to normal activity (recovery time), whether sedation was successful and side effects were recorded. In the overall study population, sedation was successful in 1094 (95.1%) of the patients, the induction time was 16.34 +/- 3.69 min, the duration of sedation was 35.07 +/- 7.04 min, the recovery time was 63.25 +/- 10.17 min and the overall side-effect prevalence was 2%. Sedation was significantly more successful, the induction time was significantly shorter, the recovery time was significantly longer and side effects significantly more prominent in groups I and II compared to group III. CONCLUSION: Rectally administered thiopental is a safe and efficacious agent for sedation of infants and young children with known or suspected congenital heart disease who are undergoing echocardiography in an outpatient cardiology clinic, provided that it is used in an emergency care setting considering the risk of respiratory depression even though the prevalence of this side effect is significantly low.

Administration, Rectal↗

Differential effects of propofol, ketamine, and thiopental anaesthesia on the skeletal muscle microcirculation of normotensive and hypertensive rats in vivo.

BACKGROUND: This study utilized the dorsal microcirculatory chamber (DMC) model to determine differential effects of i.v. propofol, ketamine, and thiopental anaesthesia on the skeletal muscle microcirculation (10-180 micro m) of normotensive (Male Wistar Kyoto, WKY) and hypertensive (spontaneously hypertensive Harlan, SHR) rats, importantly, comparing responses to a conscious baseline. METHODS: Three weeks following implantation of the DMC in WKY (n=8) and SHR (n=6) (130 g) 0.25 ml 100 g(-1) FITC-BSA (i.v.) was administered and the microcirculation viewed using fluorescent in vivo microscopy for a 30 min baseline (t=0-30 min). This was followed by either propofol, thiopental, ketamine, or saline (i.v. bolus induction over 5 min (t=30-35 min)), then maintenance step-up infusion for 60 min (t=45-105 min), so that animals received all four agents 1 week apart (56 experiments). RESULTS: Dilation of A3 arterioles (15-30 micro m) and V3 venules (20-40 microm) with propofol was greater in SHR (t=95 min, A3 36.7 (12)%, V3 15.5 (2.3)%) than WKY (t=95 min, A3 19.4 (7.4)%, V3 8.0 (2.3)%) (P<0.05). Constriction of A3 with ketamine was greater in SHR (t=95 min, A3 -29.1 (6.4)%) than WKY (A3 -17.5 (8.8)%) (P<0.05). This was accompanied by hypotension with propofol in SHR (-32% decrease in systolic arterial pressure), but not WKY (-6%) and hypertension with ketamine in WKY (-15%) and SHR (-24%) (P<0.05). During thiopental anaesthesia there was dilation of A1 (80-180 microm), A3, and V3 in WKY (P<0.05). Conversely, in SHR dilation of venules (29.2 (8.7)%) was accompanied by constriction of A1 and A3 (t=95 min, A1 -25.1 (5.9)%, A3-45.2 (3.1)%) (P<0.05). CONCLUSION: Within the skeletal muscle microcirculation of hypertensive rats there is enhanced dilation with propofol and constriction with ketamine, associated with exaggerated changes in arterial pressure. Thus, dysfunctional control mechanisms at the level of the microcirculation alter responses to anaesthesia during hypertension.

Anesthetics, Dissociative↗

Enhanced visual memory effect for negative versus positive emotional content is potentiated at sub-anaesthetic concentrations of thiopental.

BACKGROUND: Emotional information has the ability to alter the formation and strength of a memory ('memory modulation'). Memory modulation by negative emotion is mediated by the amygdala. It is not known how gamma aminobutyric acid (GABA)ergic drugs affect the processes involved in memory modulation. This study investigates whether memory for negative emotional stimuli is more refractory to the effects of GABAergic drugs. METHODS: Eighty-three healthy volunteers were shown a randomized sequence of 60 visual stimuli consisting of negative, positive and neutral emotive pictures, while receiving a controlled infusion of thiopental (n=31), propofol (n=31), dexmedetomidine (n=10) or placebo (n=11). After a 5 h retention interval, when drug concentration was negligible, subjects performed a recognition task with 'old' pictures randomly mixed with 'new' pictures. Drug effect was calculated as the proportionate reduction in recognition for images of each emotional valence. RESULTS: Forty-eight subjects were included in a within-subject logistic dose-response model analysis. In the thiopental group there was a smaller drug effect seen for negative vs positive images (proportional memory reduction from baseline 0.27 (SD 0.20) vs 0.56 (0.25), P<0.001, n=20 included in analysis). A similar trend was seen in the propofol group (0.25 (0.28) vs 0.54 (0.30), n=10), but this did not attain statistical significance. No trend was seen in the dexmedetomidine group (0.33 (0.26) vs 0.24 (0.22), n=7). CONCLUSIONS: Over a specific dose range of thiopental (target serum concentration 2-7 micro g ml(-1)), impairment of explicit memory for images with negative emotional valence is less than that for images with positive emotional valence. There is a strong possibility that propofol (target serum concentration 0.3-2.4 micro g ml(-1)) causes a similar effect. Modulation of visual memory by negative emotional content continues at sub-anaesthetic concentrations of GABAergic drugs associated with explicit memory impairment.

Adult↗

Comparative effects of thiopental and propofol on atrial vulnerability: electrophysiological study in a porcine model including acute alcoholic intoxication.

BACKGROUND: Atrial tachyarrhythmias (AT) frequently complicate the perioperative period. Alcohol intoxication is a recognized causative factor for dysrrhythmias. We studied the effects of propofol and thiopental on atrial electrophysiology and vulnerability to AT in a closed-chest porcine model in which AT are facilitated by ethanol. METHODS: Thirty-eight pigs were randomly assigned to thiopental (T-group, n=19) or propofol (P-group n=19). All animals were assigned to undergo a right atrial electrical stimulation protocol (RASP) at baseline. Thirty pigs were assigned to undergo additional RASP during ethanol infusion, while the remaining eight were assigned to undergo additional RASP during saline infusion (control group). We analysed effective refractory period (ERP), and intra-atrial conduction interval (ICI) (between atrial sites 4 cm apart), at several cycle lengths (CL). RESULTS: There were no significant differences at baseline. During ethanol infusion, propofol produced a greater rate-dependent decrease in excitability, manifested by a longer minimum paced CL with 1:1 atrial capture: 145 (11) vs 164 (27) ms in the T- and P-group, respectively (P=0.01). Propofol was associated with a greater rate-related slowing in conduction: difference between ICI at CL of 300 ms and ICI at minimum CL: 30 ms in P-group and 22 ms in T-group (P<0.03). In the P-group we observed a longer duration of induced arrhythmias (145 (131) vs 74 (91) s, P<0.03) and a higher proportion with atrial flutter (AFl) (76 vs 19%, P<0.001). CONCLUSIONS: Propofol in this model was more arrhythmogenic than thiopental, as manifested by a longer duration of induced arrhythmias, particularly AFI.

Alcoholic Intoxication↗

Influence of isoflurane, fentanyl, thiopental, and alpha-chloralose on formation of brain edema resulting from a focal cryogenic lesion.

The objective of this study was to analyze the effects of various anesthetics on the formation of brain edema resulting from a focal cryogenic lesion. Thirty rabbits (six per group) were anesthetized with isoflurane (1 minimum alveolar anesthetic concentration [MAC] 2.1 vol%), fentanyl (bolus 5 micrograms/kg; infusion rate 1.0-0.5 micrograms.kg-1.min-1), thiopental (32.5 mg.kg-1.h-1), or alpha-chloralose (50 mg/kg). Control animals (sham operation, no lesion) received alpha-chloralose (50 mg/kg). Regional cerebral blood flow (rCBF) in perifocal brain tissue was measured by H2-clearance. Animals anesthetized with isoflurane required support of arterial pressure by angiotensin II (0.15 micrograms.kg-1.min-1). Six hours after trauma the animals were killed. Formation of brain edema was studied by specific gravity of cortical gray matter, white matter, hippocampus, caudate nucleus, putamen, and thalamus. Brain tissue samples were collected at multiple sites close to and distant from the lesion. Mean arterial pressure, arterial PCO2 and PO2, hematocrit, body temperature, and blood glucose were not different between groups during the posttraumatic course (except for an increased arterial pressure with alpha-chloralose compared to thiopental 4-6 h after trauma). The specific gravity of cortical gray matter was significantly reduced up to a distance of 6 mm from the center of the lesion in animals anesthetized with isoflurane, thiopental, or alpha-chloralose and up to 9 mm in animals given fentanyl.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗

Hemodynamic effects of anesthetic induction with eltanolone-fentanyl versus thiopental-fentanyl in coronary artery bypass patients.

We evaluated the hemodynamic profile of eltanolone and fentanyl versus thiopental and fentanyl anesthetic induction in patients with documented coronary artery disease. Fifty patients scheduled for coronary artery bypass grafting were randomly assigned to two treatment groups (25 patients each). Anesthesia was induced by eltanolone (0.5 mg/kg) or by thiopental (3 mg/kg). Each patient also received 3 micrograms/kg fentanyl and 0.1 mg/kg vecuronium. Heart rate, arterial, pulmonary arterial, central venous, and pulmonary capillary wedge pressures, and cardiac output were determined in the awake state, 2 min after induction of anesthesia, and at 1 and 5 min after intubation, which was performed 3 min after induction. Between-group statistics showed significantly (P < 0.05) lower mean arterial pressure and systemic vascular resistance for eltanolone-treated patients at all measuring points. Pulmonary capillary wedge pressure was lower at 1 min after intubation; left ventricular stroke work index was lower at 1 and 5 min after intubation in the eltanolone group. We conclude that the lower mean arterial pressure with eltanolone as compared to thiopental is a result of greater peripheral vasodilation.

Adult↗

The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions.

UNLABELLED: We investigated the effect of thiopental, midazolam, and ketamine (at clinically relevant concentrations and at 0.1 and 10 times these concentrations) on several aspects of human neutrophil functions. The three intravenous (i.v.) anesthetics significantly decreased chemotaxis, phagocytosis, and reactive oxygen species (ROS) (O2-, H2O2, OH) production of neutrophils in a dose-dependent manner. At clinically relevant concentrations, thiopental and midazolam significantly depressed these neutrophil functions. However, ketamine at the clinical plasma concentration did not impair chemotaxis or ROS production, except phagocytosis. In contrast, the three anesthetics had no effect on the levels of ROS production by a cell-free ROS generating system. In addition, intracellular calcium concentrations in neutrophils stimulated by N-formyl-L-methionyl-L-leucil-L-phenylalanine were dose-dependently decreased in the presence of each of the three anesthetics. The suppression of an increase in intracellular calcium concentrations may be responsible for the inhibition of neutrophil functions by the i.v. anesthetics. IMPLICATIONS: Neutrophils play an important role in the antibacterial host defense system and autotissue injury. We found that thiopental and midazolam (but not ketamine), at clinically relevant concentrations, impaired the neutrophil functions.

Anesthetics↗