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Biomedical subjects

I Murat

Publications and source records attributed to I Murat.

At least 91 records · Page 5Linked to original sources

[Hormonal changes induced by etomidate in children during the first 24 postoperative hours].

The hormonal effects of an etomidate infusion were assessed postoperatively in children undergoing hypospadias or clubfoot repair. The study was carried out in 12 children, aged between 9 and 70 months, randomly assigned to two equal groups. The anaesthetic protocol was identical for all the children, consisting in a light general anaesthesia (halothane induction, intubation after 60 to 80 micrograms.kg-1 vecuronium) combined with lumbar epidural anaesthesia (initial dose of 0.75 ml.kg-1 bupivacaine with adrenaline, with repeat injections of half the previous dose when there was a change in the haemodynamic parameters suggesting inadequate analgesia). Anaesthetic maintenance was different in both groups: 1 to 1.5 vol% enflurane in a nitrous oxide-oxygen mixture (1/1 v/v) in the control group, and 16.8 +/- 3.0 mg.kg-1.min-1 etomidate infusion in the etomidate group. Venous blood samples were collected after induction of anesthesia (before starting the epidural anaesthesia and the etomidate infusion), at the end of surgery (H0), at the 3rd (H3), 6th (H6), 12th (H12) and 24th h (H24) following surgery. The following hormonal blood concentrations were measured: cortisol, 11 beta-desoxycortisol, aldosterone, 11 beta-desoxycorticosterone, dehydroepiandrosterone (DHA) and DHA sulphate (DHA-S). In the control group, cortisol and DHA-S concentrations decreased significantly at H0, aldosterone levels also being significantly lower at H24. In the etomidate group, cortisol concentrations remained significantly lower at H0, H3 and H6; aldosterone concentrations were also significantly lower than control values throughout the study period. There was an important prolonged rise in the concentrations of their precursors. DHA and DHA-S concentrations did not change in the etomidate group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

Isoflurane attenuates baroreflex control of heart rate in human neonates.

Clinical studies have suggested that baroreflex regulation of heart rate may be more affected by inhalational anesthetics in human neonates or young animals than in adults. To test this hypothesis, baroreceptor reflex control of heart rate was studied in eight neonates during administration of 1 MAC isoflurane. The neonates were hemodynamically stable and their lungs were mechanically ventilated. No other anesthetic was used. Mean (+/- SD) corrected gestational age was 39.4 +/- 2.0 weeks and mean weight was 2,710 +/- 430 g. The pressor response was tested with the use of phenylephrine and the depressor response with nitroglycerin. Changes in heart rate (R-R interval) were plotted against the changes in systolic arterial pressure, and the slope of the linear portion of this relationship was used to define the baroreflex response. Both baroresponses measured in awake neonates varied widely between patients. With administration of approximately 1 MAC isoflurane, the pretest mean systolic arterial pressure decreased by about 30% (P less than 0.001), whereas mean heart rate values remained unchanged compared with control awake values. During isoflurane administration, the mean (+/- SD) pressor response decreased to 23% of control awake values (11.2 +/- 7.7 ms/mmHg vs. 2.6 +/- 3.7 ms/mmHg; P less than 0.01) and the depressor response to 28% of control (4.3 +/- 3.2 ms/mmHg vs. 1.2 +/- 0.8 ms/mmHg; P less than 0.05). These changes can be attributed to a significant resetting of heart rate itself (calculated as the change in R-R interval at a constant pressure).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Effect of lumbar epidural anaesthesia on plasma cortisol levels in children.

The cortisol response to surgery was studied in two groups of children one to eight years old during the first 24 hours after lower abdominal or peripheral surgery. The children were randomly allocated to a control (C) group (n = 6) or an epidural (E) group (n = 7). In Group C, surgery was performed under general anaesthesia and postoperative pain relief was achieved by using non-narcotic analgesics only. In Group E, lumbar epidural anaesthesia was combined with light general anaesthesia and postoperative pain relief was achieved by intermittent doses of bupivacaine administered through an epidural catheter. Cortisol levels were assessed before surgery (C), at the end of surgery (H0), at the 3rd, 6th, 12th and 24th postoperative hours (H3, H6, H12, H24). In Group C, cortisol levels increased significantly at H0, H3 and H6, whereas in Group E, a significant decrease was observed at H0 and a significant increase at H12. Mean cortisol values at H0 and H24 were significantly lower in Group E, when compared with those measured in Group C. In Group E, all postoperative cortisol values remained within the normal range, despite the low level of sensory blockade achieved. This suggests that minimal doses of epidural bupivacaine are effective in decreasing the endocrine stress response to surgery in children. This could be of clinical relevance in high-risk children with poor nutritional status. In Group C, the cortisol response remained altered for a longer period of time.

Anesthesia, Epidural↗

Effects of fentanyl on baroreceptor reflex control of heart rate in newborn infants.

Baroreceptor reflex control of heart rate was studied in ten neonates and young infants before and after intravenous fentanyl (10 micrograms/kg). All infants were in stable condition while being mechanically ventilated. Mean (+/- SD) corrected gestational age was 40.1 +/- 3.7 weeks, mean weight 3120 +/- 700 g. The pressor response was tested using phenylephrine and the depressor response using nitroglycerin. Changes in heart rate (R-R interval) were plotted against changes in systolic arterial pressure, and the slope of the linear portion of this relationship expresses the baroreflex sensitivity. No significant changes in systolic arterial pressure, heart rate, and blood gas values were observed after fentanyl injection when compared to control values. Mean (+/- SEM) control phenylephrine slope was 8.44 +/- 2.05 msec/mmHg, and mean nitroglycerin slope was 2.54 +/- 0.37 msec/mmHg. Both slopes decreased significantly by 48% and 42%, respectively, after fentanyl injection (P less than 0.02). Mean plasma fentanyl concentrations measured at the end of each test were not statistically different (5.11 +/- 0.65 ng/ml and 4.28 +/- 0.58 ng/ml, respectively). This suggests that the baroreflex control of heart rate is present in term neonates and markedly depressed during fentanyl anesthesia. Changes in blood pressure occurring during fentanyl anesthesia have to be carefully considered, because cardiac output is principally rate-dependent in newborns.

Fentanyl↗

Minimum alveolar concentrations (MAC) of halothane, enflurane, and isoflurane in ferrets.

The minimum alveolar concentrations (MAC) of isoflurane, enflurane, and halothane were determined in adult male ferrets during controlled ventilation at normothermia (37 degrees C). Mean (+/- SD) MAC values for isoflurane (n = 8), enflurane (n = 8), and halothane (n = 8) at 37 degrees C were 1.52 +/- 0.10%, 1.99 +/- 0.18%, and 1.01 +/- 0.10%, respectively. Halothane MAC was reduced by 26% in the presence of 70% N2O. At 29.9 +/- 0.2 degrees C, the mean MAC value of halothane (0.85 +/- 0.11%) was 16% less than MAC at 37 degrees C. The relative potencies of the halogenated anesthetics are of the same order as those reported for large animals and for humans.

Animals↗

Comparative effects of halothane, enflurane, and isoflurane at equipotent anesthetic concentrations on isolated ventricular myocardium of the ferret. I. Contractility.

The effects of halothane, enflurane, and isoflurane on myocardial contractility were compared in papillary muscles of the right ventricle of adult male ferrets at 30 degrees C. Isotonic and isometric variables of contractility were measured before, during, and after exposure to incremental concentrations of halothane (n = 9 muscles), enflurane (n = 9 muscles), and isoflurane (n = 9 muscles), in steps of 0.25 MAC up to 1.5 MAC of halothane and of enflurane, and up to 2.0 MAC of isoflurane. Each of the three anesthetics caused a dose-dependent reversible decrease in contractility. The onset of maximal myofibrillar activation was delayed in a dose-dependent manner, and time to peak shortening of the isotonic preloaded twitch was unchanged, except for a slight decrease at greater than 1 MAC of enflurane. Isoflurane's negative inotropic effects were clearly less than those of either halothane or enflurane. Comparison of the time course of contraction and relaxation in both isometric and isotonic twitches suggests that, in addition to effects on intracellular calcium availability, these anesthetics decrease the myofibrillar responsiveness to calcium and/or the calcium sensitivity of the contractile proteins.

Anesthesiology↗

Comparative effects of halothane, enflurane, and isoflurane at equipotent anesthetic concentrations on isolated ventricular myocardium of the ferret. II. Relaxation.

The effects of halothane, enflurane, and isoflurane on myocardial relaxation were compared in papillary muscles of the right ventricle of adult male ferrets at 30 degrees C. The sensitivity of cardiac relaxation to the loading conditions was determined by examining the time course of relaxation before, during, and after exposure to incremental concentrations of halothane (n = 9 muscles), enflurane (n = 9 muscles), and isoflurane (n = 9 muscles) in steps of 0.25 MAC up to 1.5 MAC of halothane and of enflurane and up to 2.0 MAC of isoflurane. Load sensitivity of relaxation was quantified by comparing force and time coordinates at the onset of the isometric relaxation phase in several afterloaded isotonic twitch contractions with relaxation of the isometric twitch. Load sensitivity of relaxation, which is of particular benefit during early rapid filling of the heart, was decreased in a dose-dependent reversible fashion by halothane, enflurane, and, to a lesser extent, by isoflurane. These anesthetics abbreviated isometric relaxation, yet prolonged the time course of muscle lengthening which is suggestive of an impairment of calcium uptake by the sarcoplasmic reticulum and of a decrease in calcium sensitivity of the contractile proteins.

Anesthetics↗

Halothane, enflurane, and isoflurane decrease calcium sensitivity and maximal force in detergent-treated rat cardiac fibers.

This study was designed to test the hypothesis that the volatile anesthetics directly affect cardiac contractile proteins. For this purpose, the effects of various anesthetic doses of halothane, enflurane, and isoflurane on myocardial calcium sensitivity and maximal calcium-activated force were examined in rat cardiac fibers skinned with Triton X-100. In this preparation, all membranes are chemically destroyed, and the sarcoplasmic reticulum is not functional. The three anesthetics shifted the pCa/tension curves (pCa = -log10[Ca2+]) toward higher calcium concentrations and decreased pCa for half-maximum activation (pCa50) in a dose-dependent and reversible fashion without changing the slope of this relationship (Hill coefficient). No differences between agents were observed at equipotent anesthetic concentrations. In addition, the three anesthetics decreased both maximal activated tension and tension at half-maximal activation in a dose-dependent fashion. Both the decrease in calcium sensitivity and the decrease in maximum activated tension may contribute to the negative inotropic effects of these agents. The relative importance of such effects compared with the other mechanisms of action remains to be determined, however.

Animals↗

Respiratory effects of nitrous oxide during halothane or enflurane anaesthesia in children.

The respiratory effects of nitrous oxide (N2O) were studied during halothane and enflurane anaesthesia in 12 children (mean age 46.4 +/- 29.3 months, mean weight 15.3 +/- 4.2 kg) during surgery under continuous extradural anaesthesia. Four equipotent anaesthetic states were studied in random order: 1) halothane 1 MAC in oxygen, 2) halothane 0.5 MAC + 50% N2O, 3) enflurane 1 MAC in oxygen, 4) enflurane 0.5 MAC +50% N2O. End-tidal fractions of CO2 (PetCO2) and halothane and enflurane were measured using infrared analysers. The respiratory variables (tidal volume VT, minute ventilation VE, respiratory frequency F, inspiratory time Ti, mean inspiratory flow VI, effective inspiratory time Ti/Ttot) were measured using a pneumotachograph. Significant changes were observed between the four states for VE, VI, F and PetCO2, whereas the values of VT, Ti and Ti/Tot did not differ significantly. The respiratory depressant effect of 1 MAC of either halothane alone or of the mixture of halothane and N2O was very similar. During enflurane anaesthesia, PetCO2 was less increased when N2O was substituted for enflurane, owing to a significant increase in respiratory frequency. A marked decrease in VE together with an increase in PetCO2 was observed during enflurane anaesthesia (states 3 and 4) when compared to the corresponding states during halothane anaesthesia (states 1 and 2). The respiratory depressant effect of enflurane is greater than that of halothane in unpremedicated children, even when substituting N2O for an equal MAC fraction of enflurane.2+ The effect of N2O on respiratory patterns seems to depend on the inhalational agent used and/or on the vesting respiratory frequency.

Anesthesia, Inhalation↗

Bupivacaine pharmacokinetics during epidural anaesthesia in children.

Blood concentrations and pharmacokinetic parameters of bupivacaine were measured after epidural injection in children aged from 1 to 7 years. The children were allocated to two groups. In Group 1 (five children), pharmacokinetic parameters were measured after a single bolus injection of bupivacaine 0.25% with adrenaline 1:200,000. In Group 2 (eight children), pharmacokinetic parameters were measured after the initial injection and the second injection. The same local anaesthetic was used. The volume of the second injection was half of the initial volume. In children of Group 1, maximum mean concentration (CPmax) was 0.64 +/- 0.05 microgram ml-1, time to maximum concentration (Tmax) 19.2 +/- 3.9 min, vascular absorption (T1/2 abs) 4.3 +/- 1.5 min, terminal half-life (T1/2 beta) 227 +/- 37.7 min, volume of distribution (Vd) 3.4 +/- 0.51 kg-1, and total body clearance (Clt) 11.0 +/- 2.0 ml min-1 kg-1. When compared to an adult's pharmacokinetic parameters, both Vd and Clt were increased, so that T1/2 beta remained essentially unchanged. In children of Group 2, the first repeat injection was performed at 110 +/- 6.9 min. Mean CPmax increased significantly (20% after the second injection), whereas the values of the pharmacokinetic parameters measured did not differ significantly from those measured in children in Group 1. The results obtained in the present study demonstrate that the pharmacokinetic parameters of bupivacaine in children do not differ markedly from those reported in adults and that in the recommended dosage, the mean maximum concentrations, even after the second injection, are less than the presumed toxic levels.

Anesthesia, Epidural↗

Continuous extradural anaesthesia in children. Clinical and haemodynamic implications.

This study reports the experience of a department of paediatric anaesthesia with 234 continuous extradural anaesthetics performed in 229 children over a 15-month period. Fifty-nine of the children were aged 0-2 yr, 71 were aged 2-8 yr and 104 were older than 8 yr. The surgical procedures lasted more than 60 min (mean 150 +/- 10.6 min); all were carried out under light general anaesthesia. Technical procedure and difficulties are reported. The only local anaesthetic agent used was bupivacaine with or without adrenaline. Mean initial dosage was 0.75 ml kg-1 for children weighing less than 20 kg and 1 ml/10 cm of height for children taller than 100 cm. Using 0.25% bupivacaine mean times until a further injection were 92.0 +/- 2.0 min for bupivacaine with adrenaline and 71.0 +/- 2.5 min for bupivacaine without adrenaline (P less than 0.001). A much longer duration of analgesia was found for younger children using the solution with adrenaline. A haemodynamic study was performed in 74 unpremedicated children (ASA I; aged 0-2 yr (n = 15), 2-8 yr (n = 26) and older than 8 yr (n = 35). Before induction of anaesthesia, heart rate (HR) was significantly increased in the youngest children, but no significant change was found for systolic arterial pressure (SAP). After extradural anaesthesia with 0.25% bupivacaine with adrenaline 1:200000, minimal changes in HR or SAP occurred in children younger than 8 yr; in those older than 8 yr a significant decrease in both HR and SAP was observed. Changes in SAP were at their maximum 25 min after the extradural block and changes in HR were not statistically significant before the 25th min following injection of local anaesthetic. The catheter remained in place in 155 children for postoperative analgesia, mainly for the first 48 h.

Adolescent↗

The respiratory effects of isoflurane, enflurane and halothane in spontaneously breathing children.

The respiratory effects of halothane, isoflurane and enflurane were assessed during nitrous oxide anaesthesia (N2O 50%) in three groups of unstimulated, spontaneously breathing children who weighed 10-20 kg and were aged 1-6 years. Respiratory variables were measured or calculated from capnographic and pneumotachographic recordings at three multiples of minimal alveolar concentration (MAC). The slope of the carbon dioxide response was measured. Similar increases in end tidal carbon dioxide were found for the three agents at each MAC multiple, and similar decreases in tidal volume and in the slope of the ventilatory response to carbon dioxide. A dose-related tachypnoea occurred with halothane and a significant decrease in the duration of inspiration and the duration of each breath at the deepest level of anaesthesia. A significant increase in both these times occurred with enflurane, and a decrease in respiratory rate. No change in respiratory rate occurred with isoflurane at increasing alveolar concentrations whereas at each level of anaesthesia inspiratory time was significantly reduced.

Anesthesia, Inhalation↗