[Agitation on induction with sevoflurane in children. Some elements in the response to clinical questions about sevoflurane].
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Recovery from anaesthesia is associated with large changes in cardiovascular autonomic activity, which are poorly documented in children. This study was undertaken to investigate the cardiovascular autonomic activity in anaesthetized and recovering children, using a noninvasive approach based on spectral analysis of heart rate (HR) and blood pressure (BP) variability. Ten children (aged 5-13 years) undergoing major surgery were studied. Continuous HR and BP were recorded using a noninvasive device during deep anaesthesia and recovery. Spectral analysis was used to determine the main oscillatory components of HR and BP signals. For each power spectrum, the frequency components were identified as follows (i): the low frequency (LF) component (0.04-0.14 Hz) both parasympathetically and sympathetically mediated for HR and corresponding to vasomotor sympathetic modulation for BP; and (ii) the high frequency (HF) component (0.2-0.6 Hz) parasympathetically mediated for HR, and reflecting mechanical influence of ventilation on cardiac output for BP. In addition, the LF : HF ratio for HR, reflecting the cardiac sympathovagal balance, was calculated. Under deep anaesthesia, HR variability and BP variability were very low and mainly due to mechanical influence of intermittent positive pressure ventilation. Conversely, the recovery period was associated with a marked increase of HR and BP overall variability. Compared to anaesthesia, spectral analysis of HR and BP revealed that the LF component of BP and HR spectra increased 40-fold during recovery; the LF : HF ratio of HR was also increased during recovery (0.1 +/- 0.1 versus 1.3 +/- 1.2, P=0.008). The results of this study demonstrate that the recovery period is associated with an increase of cardiovascular sympathetic drive in children after major surgery.
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BACKGROUND: This study was design to assess clinical agitation, electroencephalogram (EEG) and autonomic cardiovascular activity changes in children during induction of anesthesia with sevoflurane compared with halothane using noninvasive recording of EEG, heart rate, and finger blood pressure. METHODS: Children aged 2-12 yr premedicated with midazolam were randomly assigned to one of three induction techniques: 7% sevoflurane in 100% O2 (group SevoRAPID); 2%, 4%, 6%, and 7% sevoflurane in 100% O2 (group SevoINCR); or 1%, 2%, 3%, and 3.5% halothane in 50% N2O-50% O2 (group HaloN2O). An additional group of children who received 7% sevoflurane in 50% N2O-50% O2 (group SevoN2O) was enrolled after completion of the study. Induction was videotaped. EEG, heart rate, and finger blood pressure were continuously recorded during induction until 5 min after tracheal intubation and analyzed in frequency domain using spectral analysis. RESULTS: Agitation was more frequent when anesthesia was induced with 100% O2 compared to the mixture of oxygen and nitrous oxide. No seizures were recorded in any group. In the four groups, induction of anesthesia was associated with an increase in EEG total spectral power and a shift toward the low-frequency bands. Sharp slow waves were present on EEG tracings of the three sevoflurane groups, whereas slow waves and fast rhythms (spindles) were observed in the halothane group. Sevoflurane induced a greater withdrawal of parasympathetic activity than halothane and a transient relative increase in sympathetic vascular tone at loss of eyelash reflex. CONCLUSIONS: Agitation observed during sevoflurane induction was not associated with seizures. Sevoflurane induction induced a marked inhibition of parasympathetic control of heart rate.
Prolonged exposure to elevated FFA levels has been shown to induce peripheral insulin resistance and to alter the beta-cell secretory response to glucose. To investigate the effects of FFAs on preproinsulin gene expression, we measured insulin release, cell content, and messenger RNA (mRNA) levels in rat islets after a 24-h exposure to 1 mM palmitate. Insulin release increased at all glucose concentrations studied; in contrast, preproinsulin mRNA levels were specifically reduced by palmitate at high glucose with a decrease in insulin stores, suggesting that palmitate inhibits the glucose-stimulated increase in preproinsulin gene expression. The mechanisms by which palmitate affects preproinsulin gene expression implicate both preproinsulin mRNA stability and transcription, as suggested by an actinomycin D decay assay, quantification of primary preproinsulin transcripts, and transient transfection experiments in Min6 cells. Metabolism of palmitate is not required to obtain these effects, inasmuch as they can be reproduced by 2-bromopalmitate. However, oleate and linoleate did not significantly influence preproinsulin mRNA levels. We conclude that insulin release and preproinsulin gene expression are not coordinately regulated by palmitate and that chronically elevated FFA levels may interfere with beta-cell function and be implicated in the development of noninsulin-dependent diabetes.
To investigate the differences between heart rate (HR) variability and pulse rate (PR) variability, short-term variability of finger pulse wave and ECG signals were studied in 10 children with a fixed ventricular pacemaker rhythm (80 beats/min). Ten healthy children in sinus rhythm served as a reference population. Distal PR and HR were measured continuously using a Finapres device and an ECG respectively. Power spectra for HR and PR were calculated in both the supine and orthostatic positions. In paced subjects, PR spectra exhibited the characteristic respiratory peak, although the HR spectra were flat. Similarly, in healthy children the respiratory fluctuations were more pronounced when calculated from the finger pulse wave signal compared with the ECG signal. The overestimation of HR respiratory fluctuation resulting from distal PR measurement was more pronounced in the standing position; however, this postural effect was demonstrated only in healthy subjects. We observed mechanical respiratory modulation of distal PR independent of classical HR modulations. Our results suggest a mechanical respiratory influence via cardiac output and aortic transmural pressure changes on pulse wave velocity. We conclude that respiratory PR variability does not precisely reflect respiratory HR variability in standing healthy subjects and in patients with low HR variability. Consequently, HR modulation should be studied using the ECG signal rather than the distal pulse wave signal. However, when ECG recording is not available, the distal pulse wave is an acceptable alternative.
This study was designed to evaluate the clinical characteristics of three induction techniques using sevoflurane in children scheduled for tonsillectomy: incremental induction with sevoflurane(2,4,6,7%) in 100% O2 (group IC-O2; n=23); induction with high concentration of sevoflurane in 100% O2 (group HC-O2; n=22); and induction with high concentration of sevoflurane in a mixture of O2:N2O(50:50) (group HC-N2O; n=20). Induction was well accepted and well tolerated in most children. The addition of nitrous oxide resulted in faster loss of consciousness (P< 0.001) compared to the other induction techniques and in a tendency for reduced excitement compared with the same rapid technique without nitrous oxide (P=0.053). Time to tracheal intubation was identical in the three groups and intubation conditions were scored as good in most children. During the early induction phase, an increase in SAP and HR was observed in the three groups. Changes were maximal at two min after the beginning of induction in the three groups. SAP and HR values were back to baseline values at the time of tracheal intubation. In conclusion, the addition of nitrous oxide to a high sevoflurane concentration decreases the time to loss of eyelash reflex, tends to reduce the incidence of excitement and is not associated with an increased incidence of respiratory complications even in patients with obstructive airway.
The insulin and glucagon genes are expressed in the beta and alpha cells of the islets of Langerhans, respectively. The factors controlling their cell- and islet-specific expression are poorly known. Insulin-enhancer factor-1 (IEF1) has previously been shown to interact with the E boxes of the rat insulin I and II genes and was proposed to play a critical role in beta cell-specific expression. BETA2, a recently identified basic helix-loop-helix (bHLH) protein, binds with high affinity and transactivates the rat insulin II gene upon dimerization with the ubiquitous bHLH protein E47. We show here that the heterodimer E47/BETA2 also binds and transactivates the rat insulin I and glucagon genes and exhibits the same characteristics as IEF1. In transfection experiments, the E boxes of the insulin I and glucagon genes confer transcriptional activity in both insulin- and glucagon-producing cells, which is increased by overexpression of E47 and BETA2. However, overexpression of E47 inhibits only E box-mediated glucagon gene expression, whereas it activates insulin gene transcription, indicating that the E boxes of the insulin and glucagon genes display gene-specific characteristics. We conclude that the heterodimer E47/BETA2 represents an islet-specific factor that controls both insulin and glucagon gene transcription and that the E47/BETA2 ratio may be important for regulated gene expression.
Caudal anaesthesia is indicated for surgical procedures lasting less than 90 min. Fentanyl and clonidine are known to prolong postoperative caudal analgesia, but there are no data on their effect on duration of surgical analgesia. We evaluated if the addition of clonidine or fentanyl to local anaesthetics prolonged the duration of surgical analgesia after single shot caudal block in children in a randomized, double-blind study. We studied 64 children, aged 6-108 months, undergoing bilateral correction of vesicoureteral reflux which was expected to last more than 90 min. Patients were allocated to one of four groups: group O received 1 ml kg-1 of a mixture of 0.25% bupivacaine with epinephrine and 1% lidocaine in equal parts; group F received the same mixture of local anaesthetics in addition to fentanyl 1 microgram kg-1; group C received the same mixture of local anaesthetics in addition to clonidine 1.5 micrograms kg-1; and group C + F received the same mixture of local anaesthetics in addition to fentanyl 0.5 microgram kg-1 and clonidine 0.75 microgram kg-1. Single shot caudal block was sufficient in only 57% of children in group O compared with 93% in groups C and F and 86% in group C + F (P = 0.035). Global assessment of anaesthesia, defined as the time from caudal injection to the first administration of analgesic (either during or after surgery), was significantly longer in the three groups of children who received additives compared with local anaesthetics alone (P = 0.035), but there were no differences between the three additive groups. Vomiting was observed only in children who received fentanyl. Addition of clonidine or fentanyl to local anaesthetics prolonged the duration of surgical analgesia of caudal block, allowing single shot caudal anaesthesia to be recommended for surgery lasting 90-150 minutes. Clonidine had some advantages over fentanyl as it did not produce clinically significant side effects.
We studied prospectively the effects of the technique of tracheal extubation on arterial haemoglobin oxygen saturation (SpO2) in 120 ASA I-III children, mean age 5.3 (range 0.25-16.9) yr. At completion of surgery, tracheal extubation was performed when spontaneous ventilation had resumed, children were fully awake and SpO2 was 99-100%. Children were allocated randomly to receive a single lung inflation manoeuvre with 100% oxygen before tracheal extubation (group I; n = 59) or to have the tracheal tube removed while applying suction through the tube (group S; n = 61). SpO2 was monitored during the first 5 min after tracheal extubation in the operating room. Supplementary oxygen was given if SpO2 decreased to less than 92%. The time between tracheal extubation and decrease in SpO2 to 92% (T92) was recorded. Children in group S required oxygen administration more frequently after tracheal extubation than those in group I (65.6% vs 45.8%; P = 0.04), and had a three-fold shortening of T92 (mean 25 (SD 19) s vs 85 (63) s; P = 0.0001). These effects were more pronounced in children less than 4 yr of age compared with older children. We conclude that tracheal extubation greatly impaired oxygenation and therefore administration of oxygen was appropriate. This impairment was more marked when suction was used, and in young children. Lung inflation with 100% oxygen before removal of the tracheal tube is advised before routine tracheal extubation in children.
1. To investigate the influence of heart rate variability on blood pressure variability, short-term variability in heart rate and blood pressure was studied in 10 children with fixed ventricular pacemaker rhythm (80 beats/min). Ten healthy children, in sinus rhythm, served as a reference population. 2. Arterial blood pressure and heart rate were measured continuously using a finger arterial device and an ECG respectively. Power spectra for heart rate and blood pressure (systolic and diastolic) were calculated in both supine and orthostatic positions. In addition, acute changes in blood pressure and heart rate during active standing were studied. 3. Healthy children exhibited considerable heart rate variability, which was slightly more pronounced in the supine position, while children with a fixed ventricular rate had no heart rate variability in either position. 4. Despite the differences in heart rate variability, mean systolic blood pressure and its variability profiles were poorly affected by the suppression of heart rate variability. The lack of autonomic control on the sinus node was associated with a reduction in magnitude of the changes in systolic blood pressure variability induced by orthostatic posture. 5. The suppression of heart rate fluctuations induced a noticeable decrease in diastolic blood pressure fluctuations, which was most conspicuous in the children with fixed cardiac rhythm when in the supine position. This may be explained by the lack of diastolic blood pressure fluctuations, physiologically due to heart rate fluctuations through the run-off effect: the longer the cardiac cycle, the greater the diastolic pressure decay. These results may challenge the classical theory of baroreflex-mediated diastolic blood pressure control described in adult patients. 6. During active standing, the early drop in systolic blood pressure was greater in subjects with fixed ventricular rhythm. A rise in heart rate of 36 beats/min was observed in the healthy subjects in response to active standing. 7. We conclude that in normal children, heart rate fluctuations increase the blood pressure variability rather than buffering it. However, during acute orthostatic stress, the abrupt baroreflex-mediated heart rate rise may partly compensate for the reduction in blood pressure.
This case-control study was designed to evaluate the potential advantages and disadvantages of video-assisted thoracoscopic surgery for right middle lobectomy in children. Ten children (6.1 +/- 3.0 yr, mean +/- SD) who underwent right middle lobectomy under videoscopy were compared with 10 controls matched for age (6.8 +/- 3.5 yr) and operated by thoracotomy (muscle-sparing technique) during the same period by the same surgeon. Operating time was significantly longer in the videoscopy group than in the thoracotomy group (146 +/- 28 mn vs 100 +/- 27 mn, P < 0.001). Minimum oxygen saturation values were significantly higher in the videoscopy group whereas oxygen requirements did not differ between groups. Incidence of postoperative respiratory complications (mainly atelectasis) was similar in the two groups. No difference in postoperative analgesic requirements in the postoperative period was demonstrated. No real benefit or disadvantage of videoscopy over standard thoracotomy could be observed in this retrospective case-control study.
Glucagon gene transcription in the endocrine pancreas is regulated by at least four cis-acting DNA control elements. We showed previously that G1 is critical for alpha cell-specific expression. G1 contains three AT-rich sequences important for promoter function, which represent candidate binding sites for homeodomain transcription factors. Performing reverse transcription-polymerase chain reaction amplifications with degenerate oligonucleotide primers homologous to the Antennapedia homeobox, cDNA clones corresponding to the caudal-related gene cdx-2/3 were predominantly obtained from glucagon-producing cells and primary non-beta cells. From RNase protection and polymerase chain reaction analyses, cdx-2/3 turned out to be the only caudal-related gene that is expressed at significant levels in cells of the endocrine pancreas. Cdx-2/3 binds with high affinity to an AT-rich motif of G1, which matches the consensus binding site of caudal-related proteins. In the glucagon-producing hamster cell line InR1G9, Cdx-2/3 is a subunit of complex B3 formed on G1. Alternative splicing generates two cdx-2/3 transcripts in islet cells, coding for a full-length protein and an amino-terminally truncated isoform. Although both isoforms bind G1 with similar affinity, only the full-length Cdx-2/3 A protein activates glucagon gene transcription in non-glucagon-producing cells, transcriptional activation being dose-dependent. We therefore conclude that the caudal-related gene cdx-2/3 is implicated in the transcriptional control of glucagon gene expression in the alpha cells of the islets of Langerhans.
The objective of the present study was to investigate whether increased beta-human chorionic gonadotrophin (beta HCG) plasma concentrations in an unselected population of nulliparas could predict the occurrence of complicated pregnancy-induced hypertension (PIH). The design was that of a prospective population study. It was conducted at the obstetric departments of Amiens University Hospital and Creil General Hospital on 434 consecutive nulliparas with singleton pregnancies after natural fertilization who accepted the systematic offer of trisomy 21 screening but for whom this disorder was finally estimated. Measurement of plasma concentration of beta HCG (ELISA method) was carried out between 14 and 20 weeks (mean: 17 weeks) of amenorrhea, and measurement of blood pressure and proteinuria (> 300 mg/24 h or Albustix +2) during the first, second and third term and 2-3 months after the delivery, as well as measurement of birth weight for determination of small for gestational age (SGA) babies, 37 women developed PIH, 10 without other complication, 16 with proteinuria (5 of which with SGA babies) and 11 with SGA babies. Furthermore 2 patients presented abruptio placentae without PIH. 395 women did not develop PIH including 389 normotensive women and 6 chronic hypertensive patients without superimposed toxemia. Only 1 was diabetic. None had chronic renal disease. Mean (+/- SD) levels of beta HCG were higher in PIH than in controls: 46,805 +/- 19,068 versus 23,479 +/- 13,463 IU. A pathologic threshold was chosen as the mean for the whole population + 1 SD: 25,613 + 15,479 = 41,082 IU. Elevated levels (above this value) were significantly associated with isolated PIH or PIH complicated with proteinuria and/or with SGA babies. The positive predictive value of this criterion was respectively 11, 15 and 12% for each of these complications. The relative risk (and 95% confidence limit) of women with elevated beta HCG for each of these complications was 20 (6-79), 11 (4-43) and 22 (7-93). Elevated plasma beta HCG found around 17 weeks of amenorrhea predicts PIH complicated with either proteinuria or SGA babies with a positive predictive value comparable to that of the best and earliest test proposed up to now to select nulliparas at high risk of preeclampsia, namely the abnormalities of the Doppler waveforms of the uterine arteries. Since this test is simpler to perform, it represents the most convenient method to screen a population of nulliparas for evaluation of the benefits of low-dose aspirin.
1. The aim of the study was to examine the short-term variability in blood pressure and heart rate in 19 children who had received heart transplants and in eight normal control children. 2. Blood pressure was determined by a finger arterial pressure device. We examined the power spectra for heart rate and systolic blood pressure in the supine and tilted positions. In addition, we studied the acute changes in blood pressure and heart rate during active standing. 3. In the transplanted children we could distinguish two groups (groups A and B) in whom heart rate variability differed, although in both it was greatly reduced compared with controls (group C). In group A there were no significant fluctuations in the mid-frequency range for heart rate. The gain of the relationship between systolic blood pressure and heart rate was very low and there were virtually no heart rate changes associated with passive tilting. 4. By contrast, in group B transplant patients the heart rate variability, as assessed by standard deviation, was about half that of normal controls. The power spectra attenuation was greater in the high-frequency than in the mid-frequency bands. On passive tilting the latter became enhanced, but not the high-frequency variability. On active standing the tachycardic response was about half that of controls. The findings suggest some reinnervation involving cardiac sympathetic fibres to a greater degree than the fast-responding vagal fibres. 5. In both groups A and B the drop in systolic blood pressure observed early in active standing was about 4-6 times as great as in controls.(ABSTRACT TRUNCATED AT 250 WORDS)
This paper describes another case of severe anaphylactic reaction due to allergy to natural rubber during anaesthesia in a child without known risk factors. The day after surgery the child reported that he experienced a few months ago an impressive skin reaction of both face and lips after inflating a latex balloon. It is suggested to try to detect latex allergy during the preoperative visit in all patients by including questions about latex sensitivity such as previous skin reactions or respiratory symptoms after wearing latex gloves or after inflating toy balloons. Patients in whom latex sensitivity is suspected should be tested appropriately in order to perform the planned surgery in a latex-free environment.
The aim was to examine the short-term variability of blood pressure (BP) and heart rate (HR) in 19 children who had received heart transplants and in 8 normal control children. BP was determined by a finger arterial pressure device. We examined the power spectra for HR and systolic blood pressure (SBP) in the supine and standing posture. In the transplanted children we could distinguish two groups (groups A and B) in whom HR variability differed, though in both it was greatly reduced compared to controls (group C). In group A there were no significant fluctuations in the mid frequency (MF) range for HF. Gain of the relationship between SBP and HR was very low and there were virtually no HR changes associated with passive tilting. By contrast, in group B transplant patients the HR variability, as assessed by standard deviation was about half that of normal controls. The power spectra attenuation was greater in the high frequency (HF) than in the MF bands. On standing the latter became enhanced, but not the HF variability. The findings suggest some reinnervation involving cardiac sympathetic fibres to a greater degree than the fast-responding vagal fibres. Time since operation was a critical factor for reinnervation since all subjects from group B were transplanted more than 44 months prior to the recording. We conclude that in a proportion of children who have received heart transplantation there is a delayed reinnervation of the heart, which probably involves sympathetic effectors rather than the vagus.