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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since cardiovascular depression at induction is among the most common complications of anesthesia this comparative study was undertaken. Unpremedicated dogs (n = 16) were induced with 3 mg/kg piritramide i.v. and normoventilated (N2O/O2 = 2/1). In 8 animals 0.8 and 1.6 mg/kg Etomidate and 5.0 and 10.0 mg/kg thiopentone and in 8 further dogs 5.0 and 10.0 mg/kg Propanidid were tested. Equipotent doses of Thiopentone and Propanidid caused a marked myocardial depression, which was seen in a decrease in stroke volume and max dp/dt and in an increase of leftventricular end-diastolic pressure and pulmonary arterial pressure. The increased myocardial O2- cosumption mainly due to the rise in heart rate was covered after Thiopentone by an increase of coronary bloodflow (measured with a pitot-catheter) and an increase of arterio-coronaryvenous difference in oxygen. As the latter decreased after Propanidid, it appeared that Propanidid has coronary dilatory properties. The results demonstrated the uneconomic work of the heart under the influence of Thiopentone and Propanidid. In contrast to this the cardiovascular system after Etomidate remained nearly unaffected. The data of this study suggest the use of Etomidate rather than Thiopentone and Propanidid in cases of shock syndrome, heart and/or coronary insufficiency.
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PMID:Comparison of the immediate effects of etomidate, propanidid and thiopentone on haemodynamics, coronary bloodflow and myocardial oxygen consumption. 122 40

Etomidate 0.2 mg/kg i.v. was used to induce sleep in 198 children. It produced sleep rapidly and safely, with negligible effect on the cardiovascular system and little respiratory depression. Clinical acceptability was reduced by a 27% incidence of pain after injection, a 10% incidence of myoclonia and inadequate dosage in 19%. Etomidate has little analgesic activity and these problems can be reduced by the use of an analgesic as premedication or with induction of anaesthesia, by increasing the induction dose of etomidate to 0.3-0.4 mg/kg, or by changing the formulation of the solution.
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PMID:A clinical assessment of the use of etomidate in children. 125 86

This review deals with the adverse reactions associated with general anaesthetic agents in current use. These reactions fall into 2 categories; those which are more common, predictable and often closely related, and those which are rare, unpredictable and carry a high mortality. Both inhalational and intravenous anaesthetic agents affect the central nervous and cardio-respiratory systems in a dose-related manner. Neuronal inhibition results in decreasing levels of consciousness and depression of the medullary vital centres which can lead to cardiorespiratory failure. Both groups of agents have some depressant effect on the myocardium and vascular smooth muscle leading to a fall in cardiac output and hypotension. Centrally-mediated respiratory depression is common to both groups and the inhalational agents have a direct effect on lung physiology. The most important idiosyncratic reactions to the volatile agents are malignant hyperpyrexia and 'halothane hepatitis'. Malignant hyperpyrexia has an incidence of 1:12,000 with a mortality of about 24%. It is triggered most often by halothane together with suxamethonium. Post halothane hepatic necrosis is rare. Evidence points to 2 distinct syndromes; direct toxicity from the products of reductive metabolism, and a more serious illness, immunologically mediated via haptens formed by liver proteins and the products of oxidative metabolism. Prolonged nitrous oxide exposure can cause bone marrow depression and life-threatening pressure effects by expansion of air-filled spaces within the body. The idiosyncratic reactions to the intravenous agents include anaphylactoid reactions (which are rare) and triggering of acute porphyria. Etomidate is immunologically 'clean', but it inhibits cortisol synthesis.
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PMID:Adverse effects of general anaesthetics. 141 99

The effects of propofol, etomidate, midazolam, and fentanyl on motor evoked responses to transcranial stimulation (tc-MERs) were studied in five healthy human volunteers. Each subject, in four separate sessions, received intravenous bolus doses of propofol 2 mg.kg-1, etomidate 0.3 mg.kg-1, midazolam 0.05 mg.kg-1, and fentanyl 3 micrograms.kg-1. Electrical tc-MERs (tce-MERs) were elicited with anodal stimuli of 500-700 V. Magnetic tc-MERs (tcmag-MERs) were elicited using a Cadwell MES-10 magnetic stimulator at maximum output. Compound muscle action potentials were recorded from the tibialis anterior muscle. Duplicate tce-MERs and tcmag-MERs were recorded before and up to 30 min after drug injection. Reproducible baseline tce-MERs (amplitude 4.7 +/- 0.43 (SEM) mV, latency 29.4 +/- 0.35 ms) and tcmag-MERs (amplitude 3.7 +/- 0.43 mV, latency 31.1 +/- 0.39 ms) were obtained in all subjects. Pronounced depression of tce-MER amplitude to 2% of baseline values (P less than 0.01) was observed 2 min after injection of propofol. Thirty minutes after injection of propofol, amplitude depression to 44% of baseline (P less than 0.05) was still present, despite an apparent lack of sedation. Midazolam caused significant (P less than 0.01) amplitude depression, e.g., tcmag-MER to 16% of baseline values 5 min after injection. Significant depression persisted throughout the 30-min study period. Fentanyl did not cause any statistically significant amplitude changes in this small population. Etomidate caused significant but transient depression of tc-MER amplitude. However, there was considerable intersubject variability. Latency did not change significantly after any drug.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of propofol, etomidate, midazolam, and fentanyl on motor evoked responses to transcranial electrical or magnetic stimulation in humans. 155 Feb 74

Etomidate (ET) is a known hypnotic agent in neuroanesthesia. This study was designed to examine the reliability of motor evoked potentials (MEPs) after transcranial magnetic stimulation in monkeys anesthetized intravenously with ET. The ET regimen was as follows: an initial dose (0.5 mg/kg) followed by 13 doses (0.2 mg/kg every 6-12 min; mean, 8.0 +/- 1.3 min). The total dose administered was 3.1 mg/kg. The magnetic coil was placed over the MEP scalp stimulation region. Evoked electromyographic responses were recorded from the contralateral abductor pollicis brevis (APB) and abductor hallucis (AH) muscles of the fore- and hindlimbs, respectively. Reproducible MEP responses were consistently recorded while the animal was under total ET anesthesia. The coil demography was altered and the MEP scalp topography was moderately reduced by ET injections. Significant threshold elevation was noted after a total dose of 1.7 mg/kg for APB responses and 0.5 mg/kg for AH responses (P less than 0.05). Marked prolongation of latency was observed after a dose of 0.5 mg/kg for APB MEPs and 2.5 mg/kg for AH MEPs (P less than 0.05). MEP amplitude responses showed marked variability. Repeated doses of ET produced a mean threshold rise of 14 to 28% for the APB and 19 to 29% for the AH. The mean latency delay was 5 to 11% for the APB and 0.5 to 8% for the AH, while the mean amplitude depression was 24 to 59% for the APB and 15 to 50% for the AH. Apparent seizure activity or abnormalities in behavior and feeding were not noted over a 1-year period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of etomidate on motor evoked potentials induced by transcranial magnetic stimulation in the monkey. 192 26

The influence of etomidate on regional cerebral function as reflected by regional cerebral glucose utilization (rCMRGlc) was studied. Three experiments were performed. In the first, rats had both left femoral vessels cannulated and were placed in restraining cages. Etomidate was infused intravenously (12 mg/kg) at a rate of 6 mg X kg-1 X min-1. This large dose had a modest effect on blood pressure and heart rate, which could be explained by the elimination of stress in restrained rats, and no effect on body temperature, Pao2, PaCo2, or pH. A second group of rats were used to determine the effect of etomidate on the ratio of brain glucose to plasma glucose, which is necessary for calculating rCMRGlc. In the third experiment rCMRGlc was measured in unstressed rats. The rats were anesthetized with an intravenous dose of 1, 2, 6, or 12 mg/kg etomidate infused at a rate of 6 mg X kg-1 X min-1. Etomidate had a marked effect on glucose consumption in many, but not all, cerebral structures. The forebrain (telencephalon and diencephalon) was most affected (-25% to -35%) while the hindbrain was minimally affected. There was no demonstrable dose dependency; 1 mg/kg depressed rCMRGlc as much as 12 mg/kg. The pattern of rCMRGlc depression is in accord with the minimal effects observed on physiologic variables and similar to that caused by the steroid anesthetic Althesin, although the depression seen was not as severe. The pattern of metabolic depression produced by etomidate differs markedly from that produced by barbiturates, which affect all brain regions to a similar degree.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional brain glucose utilization in rats during etomidate anesthesia. 371 38

To determine the effect of aging on the pharmacokinetics and pharmacodynamics of etomidate, we administered etomidate (5 to 10 mg/min) by intravenous infusion to 21 healthy surgical patients, age 22 to 82 yr. Etomidate produced progressive slowing of the EEG to an easily recognized pattern (stage 3) that determined the dosage endpoint. Subsequent power-spectrum analysis of the EEG gave the median frequency. Median frequency values and simultaneous measurements of blood etomidate concentration were incorporated into a sigmoid Emax pharmacodynamic model that permitted an estimate of IC50, the blood etomidate concentration which produced a 50% reduction in the median frequency. The dose of etomidate required to reach the uniform EEG endpoint decreased significantly with increasing age (r2 = .68) as did the dose needed to produce maximal median frequency depression (r2 = .69). None of the parameters of the pharmacodynamic effect model, including IC50, correlated with age, suggesting that increased brain sensitivity in the elderly does not cause the age-related change in dose requirement. The initial distribution volume for etomidate decreased significantly with increasing age (r = .56), implying that a higher initial blood concentration in the elderly following any given dose of etomidate is part of the cause of the lower dose requirement in the elderly patient. A contracted initial distribution volume in the elderly may result from well described physiologic changes of age. Etomidate clearance also decreased with age. Age-dependent changes in etomidate pharmacokinetics rather than altered brain responsiveness may be the basis for the decreased etomidate dose requirement in the elderly.
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PMID:Increased sensitivity to etomidate in the elderly: initial distribution versus altered brain response. 372 56

Even though the anesthetic agents thiopental, ketamine, propanidid and etomidate all belong to very different chemical families they are all characterized by a very large degree of liposolubility. This explains their rapid penetration into the brain. The pharmacokinetic model of thiopental is a three compartment model. There is strong protein binding and only the free fraction is active. The very short action of the product after a single injection is due to the rapid redistribution of the agent into the muscle mass because its hepatic metabolization is very slow. However, when given over prolonged time the adipose compartment plays an important role in the mixture of the product, explaining the prolonged sleep produced. The central depressant actions of thiopental and consequently its action on CMRO2 depend on the initial dose and the route of administration. A single and massive injection produces a small and temporary reduction in the CMRO2 even though the plasmic concentration is high. In contrast prolonged intravenous infusion produces more severe and longer lasting depression of the CMRO2. The pharmacokinetic model of ketamine is tri-compartmental. There is weak protein binding. After IV injection ketamine rapidly enters the brain and the maximum concentration is reached one minute later. After that the cerebral concentration rapidly falls as does the plasma level. Signs of waking are seen at a concentration of 130 micrograms per gram of tissue. An increase in the dose of ketamine does not much influence the duration of analgesia but increase the waking time. This suggests that its indication in ambulatory anesthesia should be looked at with care. It is metabolized by the liver with the formation of several metabolites of which some are active. The kinetics of propanidid can be explained on the basis of a monocompartmental model. The speed of the fall in plasma level of the product is related to the speed of injection. High plasma concentrations mobilize a larger quantity of plasma pseudo-cholinesterases, increasing thus the speed of degradation. The product is rapidly hydrolized (plasma and liver cholinesterases). The duration of action is longer when used at low doses or when it is administered at a constant dose. Propanidid does not have any accumulative effect. The kinetics of etomidate follow a tri-compartmental model. It is very rapidly and largely distributed in the organism, the peak cerebral concentration being reached in less than one minute. There is strong protein binding. Repeated administration of the drug produces an increase in anesthetic sleep but also a delay in recovery. Etomidate is hydrolized by hepatic esterases.
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PMID:[Pharmacokinetics of intravenous non-steroidal anesthetics]. 611

Currently available anesthetic induction agents provide adequate hypnosis but are not ideal, particularly in the high risk patient (ASA class III-V), because most cause myocardial and/or respiratory depression and some have other important side effects. Etomidate was recently marketed as an intravenous anesthetic induction agent. It is a non-barbiturate hypnotic without analgesic properties that has less cardiovascular and respiratory depressant actions than sodium thiopental, even in patients with minimal cardiovascular reserve. Laboratory studies indicate that etomidate is approximately 25 times more potent and has a therapeutic index six times greater than sodium thiopental. In contrast to most other induction agents, etomidate does not cause histamine release. Furthermore, tolerance does not occur with repeated administration. Etomidate's rapid distribution half life (t 1/2 alpha = 2.81 +/- 1.64 min), short elimination half life 1/2 beta = 3.88 +/- 1.11 hr) and rapid clearance (954 +/- 178 ml/min) explain its rapid onset and short duration of action. The compound produces electroencephalographic changes and effects on cerebral blood flow, metabolism and intracranial pressure that are similar to sodium thiopental, suggesting that it may have a place in neurosurgery and as a "brain protective" agent in patients at risk of a brain hypoxic insult. Etomidate did not affect hepatorenal and hematologic function after repeated injections in animal toxicology studies, but few investigations addressing its effects on hepatic, renal, and neuromuscular function in man have been accomplished. The most noticeable side effects of etomidate include myoclonia, pain on injection and postoperative nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Etomidate: a new intravenous anesthetic induction agent. 635 80

In spontaneously breathing rats, continuous infusion of etomidate with and without fentanyl caused a slight decrease in blood pressure and heart rate. Coadministration of fentanyl and etomidate in order to obtain full anaesthesia and analgesia resulted in respiratory depression. In artificially ventilated rats both etomidate as well as the anaesthetic combination caused a strong reduction in aortic flow and an increase in total peripheral resistance. A single infusion of etomidate did not change blood pressure. Etomidate combined with fentanyl reduced blood pressure. Under adjusted ventilation blood pressure, aortic flow, max(dF/dt) and heart rate were progressively reduced during a 4 h period. In contrast, urethane anaesthesia reduced aortic flow to a minor extent. Total peripheral resistance and max(dF/dt) were hardly affected. The slightly reduced blood pressure and blood gas variables remained stable during the experiment. From pharmacokinetic studies it was established that effective etomidate plasma levels were maintained constant during the experimental period. Pharmacokinetic interaction between etomidate and fentanyl did not occur. It is concluded that for anaesthesia of longer duration during cardiovascular experiments in rats, urethane is preferable to etomidate/fentanyl because it does not cause serious changes in basal haemodynamic variables.
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PMID:Etomidate-anaesthesia, with and without fentanyl, compared with urethane-anaesthesia in the rat. 665 37


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