Halothane-nitrous Oxide Anesthesia Research Articles

Use of Continuous Positive Airway Pressure in Anesthetized Infants

We thank Dr. Rothstein for his interesting comments regarding our article.1As he correctly points out, the effect of added elastic and/or resistive load on respiratory drive may differ in the awake and anesthetized states. In the awake state, an increase in elastic and/or resistive load is compensated by an increase in neuronal inspiratory drive. This compensatory neuronal drive may be absent or diminished during general anesthesia,2and this may be particularly so in infants who are highly susceptible to anesthesia-induced attenuation of neuronal input. Continuous positive airway pressure (CPAP) may itself reduce inspiratory drive through the Herring-Breuer inflation reflex.3The resulting hypercapnia will depend on the reduction in minute alveolar ventilation. In previous studies in anesthetized children, the impact of CPAP on minute ventilation has been clinically insignificant.4Keidan et al. studied the effect of CPAP (6 cm H2O) on work of breathing and respiratory indices in healthy spontaneously breathing children (median age, 1.0 yr) during halothane–nitrous oxide anesthesia.4Application of CPAP via a facemask significantly decreased the work of breathing but had no significant effect on inspiratory tidal volume, inspiratory minute volume, or end-tidal carbon dioxide tension. To the extent that CPAP relieves existing upper airway narrowing, CPAP can also improve gas exchange, resulting in a reduction of hypercapnia and improved oxygenation. It was the purpose of our study to determine the interaction of propofol anesthesia and CPAP on upper airway caliber and configuration in infants. We considered it neither relevant to the study hypothesis nor ethically justifiable to perform arterial puncture for blood gas analysis in our infant subjects. Given the relatively brief duration of CPAP application, any increase in arterial carbon dioxide tension was likely small; indeed, after removal of CPAP, we observed no outpouring of carbon dioxide as determined by end-tidal measurement.*The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. mark.crawford@sickkids.ca

Time-course of action of rocuronium 0.3 mg.kg-1 in children with and without endstage renal failure.

The time-course of the neuromuscular effects of rocuronium 0.3 mg.kg-1 during nitrous oxide-halothane anaesthesia in children with and without renal failure is unknown. This study compared the neuromuscular blocking effects in these groups. The study was approved by the Hospital Ethical Committee. In the control group, 14 healthy children without renal disease were scheduled for various elective surgical procedures. Sixteen children with endstage renal failure, 14 of whom were already on renal dialysis, were scheduled for (re)placement of dialysis catheters (n=14) or for renal transplantation (n=2). Anaesthesia was induced and maintained with halothane and nitrous oxide in oxygen. Acceleromyographic thumb adduction after supramaximal ulnar nerve stimulation was recorded using train-of-four stimulation every 15 s. The onset time, the time to recovery of the first twitch to 25% or 75% and to recovery of a train-of-four ratio of 0.7 after rocuronium 0.3 mg.kg-1 were measured. Statistical analysis was performed with Student's t-test. P < 0.05 was considered statistically significant. The onset time was longer in children with renal failure (139 s, SD=71) than in control children (87 s, SD=43) (P=0.02). There were no significant differences in the duration of action of rocuronium between children without renal failure and in 15 out of 16 children with renal failure. In children with renal failure, aged over 1 year, a single bolus dose of rocuronium 0.3 mg.kg-1 does not cause a prolonged block, but has a slower onset than in healthy children.

Increased baroreceptor response in mice deficient in monoamine oxidase A and B.

The recent development of mice doubly deficient for monoamine oxidase A and B (MAO-A/B, respectively) has raised questions about the impact of these mutations on cardiovascular function, in so far as these animals demonstrate increased tissue levels of the vasoactive amines serotonin, norepinephrine, dopamine, and phenylethylamine. We recorded femoral arterial pressures and electrocardiograms in adult MAO-A/B-deficient mice during halothane-nitrous oxide anesthesia as well as 30 min postoperatively. During both anesthesia and recovery, systolic, diastolic, and mean arterial pressures were 10-15 mmHg lower in MAO-A/B-deficient mice compared with normal controls (P < 0.01). Mutants also showed a greater baroreceptor-mediated reduction in heart rate in response to hypertension after intravenous pulses of phenylephrine or angiotensin II. Tachycardia elicited in response to hypotension after nitroprusside was greater in mutants than in controls. Heart rate responsiveness to changes in arterial pressure was abolished after administration of glycopyrrolate, with no differences in this phenomenon noted between genotypes. These data suggest that prevention of hypertension may occur in chronic states of catecholaminergic/indoleaminergic excess by increased gain of the baroreflex.

Prolonged severe hemorrhagic shock and resuscitation in rats does not cause subtle brain damage.

Some patients who survived severe hemorrhagic shock (HS) seem to exhibit persistent subtle neurobehavioral deficits. This finding is of concern if limited hypotensive fluid resuscitation is applied in hypotensive victims with penetrating trauma. This study was designed to determine whether subtle brain damage would occur in rats after severe prolonged HS. We hypothesized that rats surviving HS with mean arterial pressure (MAP) controlled at 40 mm Hg for 60 minutes would recover with slight permanent brain damage in terms of cognitive function without morphologic loss of neurons and that rats surviving HS with MAP at 30 mm Hg for 45 minutes (60 minutes were not tolerated) would have grossly abnormal brain function and loss of neurons. Under light nitrous oxide-halothane anesthesia, spontaneously breathing rats underwent MAP-controlled HS (HS phase I), volume resuscitation to normotension and invasive monitoring to 60 minutes (resuscitation phase II), and observation to 10 days with detailed assessment of cognitive function (observation phase III). Five conscious rats served as normal controls. Three treatment groups were compared: group 1, shams (11 of 12 rats survived to 10 days); group 2, HS at MAP 40 mm Hg for 60 minutes (10 of 17 rats survived); group 3, HS at 30 mm Hg for 45 minutes (10 of 14 rats survived). On post-HS day 10, all normal controls and all survivors of all three groups were functionally normal with overall performance category = 1 (normal) (overall performance category 1 = normal, 5 = death) and neurologic deficit scores < or = 7% (neurologic deficit scores 0-10% = normal, 100% = brain death). Post-HS beam balance, beam walking, and Morris water maze test results in HS groups 2 and 3 showed latencies not significantly different from those in shams and normal controls. Light microscopic scoring of five selectively vulnerable brain regions and other regions in five coronal sections revealed no ischemic (pyknotic, shrunken, eosinophilic) neurons in any of the survivors to 10 days. There was no statistical difference between normal controls, sham animals, and both HS groups in the number of normal neurons counted in the hippocampal CA-1 region in the 10-day survivors. All nonsurvivors died with intestinal necrosis. HS at MAP 40 mm Hg for 60 minutes or MAP 30 mm Hg for 45 minutes does not cause subtle functional or histologic brain damage in surviving rats. Controlling MAP at 30 mm Hg carries a risk of sudden cardiac arrest. These data suggest that limited fluid resuscitation, to maintain MAP at about 40 mm Hg, as recommended for victims of penetrating trauma with uncontrolled HS, is safe for the brain.

Effects of Cisatracurium in Children During Halothane-Nitrous Oxide Anesthesia

Study Objective: To determine the neuromuscular blocking effect and recovery profile of cisatracurium besylate in children after administration of a bolus dose that was twice the estimated dose required to produce 95% of the maximum effect (2 × ED 95; 0.08 mg/kg) followed by an infusion during halothane-nitrous oxide anesthesia. Study Design: Open-label study. Setting: Teaching hospital. Patients: 30 male and female (ASA physical status I and II) patients, 2 to 10 years of age, scheduled for elective surgery of low to moderate risk. Interventions: After induction of general anesthesia, patients received cisatracurium 0.08 mg/kg administered over 5 to 10 seconds. For surgical procedures requiring neuromuscular block for at least 60 minutes, a second bolus dose of cisatracurium 0.02 mg/kg was administered after the first response to a train-of-four stimuli (T 1) recovered to 25% of baseline. When T 1 was 5% of baseline after the second dose, a 3 μg/kg/min infusion of cisatracurium was initiated and titrated to maintain 89% to 99% block for the duration of the surgery. For procedures requiring neuromuscular block of less than 60 minutes, one or more maintenance doses of 0.02 mg/kg cisatracurium were administered when T 1 was 25% of baseline after the preceding dose. In 10 patients, recovery was facilitated with edrophonium 1.0 mg/kg administered when T 1 was 26% to 48% of the final baseline. Measurements and Main Results: Evoked muscular response at the adductor pollicis was measured by electromyography. With 0.08 mg/kg, onset time (mean ± SEM) was 4.1 ± 0.4 minutes, and clinically effective duration was 27.3 ± 0.9 minutes. Mean 5% to 95% and 25% to 75% recovery indices were 28.4 ± 2.7 minutes and 11.2 ± 0.8 minutes, respectively. The mean infusion rate necessary to maintain 89% to 99% T 1 suppression for 17 to 145 minutes was 1.7 μg/kg/min. After termination of infusion, the mean 5% to 95% and 25% to 75% recovery indices were similar to those after a single bolus dose, and time to 95% recovery was 30.4 ± 3.0 minutes. After administration of edrophonium, full recovery (T 4:T 1 ≥ 70%) occurred in 1.5 ± 0.4 minutes. No clinically significant changes in heart rate or blood pressure were noted during the first 5 minutes after administration of cisatracurium 0.08 mg/kg. Conclusions: Cisatracurium provided maximal neuromuscular block, cardiovascular stability, and predictable recovery at the doses tested. In view of this finding, cisatracurium should be a useful intermediate-duration neuromuscular blocking drug for children during general anesthesia.

Neuromuscular effects of rocuronium in children during halothane anaesthesia.

Rocuronium bromide, a nondepolarizing muscle relaxant has been shown to have a short onset and intermediate duration of action in adults and young children. We evaluated onset time, intubating conditions, as well as duration of action of rocuronium in children ages four to 12 years during nitrous oxide-halothane anaesthesia. Following a stable recording of train-of-four (TOF) impulses at the ulnar nerve, patients were given rocuronium 600 micrograms.kg-1 intravenously. We found that the time to 90% and 100% neuromuscular (N-M) block of the (TOF) was 51 +/- 18 s and 66 +/- 32 s respectively. Intubation was achieved at 94 +/- 31 s and rated as good or excellent in all cases. Time to recovery of N-M transmission to 25%, 75% and 90% of control was 29 +/- 8 min, 42 +/- 14 min and 46 +/- 16 min respectively. Heart rate increased approximately 12 BPM after drug injection, while the blood pressure remained unchanged. From our data we conclude that, as in other age groups, rocuronium has a rapid onset, intermediate duration of action in children 4-12 years of age, and appears devoid of significant side effects.

Effects of intravenous mepivacaine on renal sympathetic nerve activity in the cat during nitrous oxide and nitrous oxide-halothane anesthesia.

Because hemodynamic responses to systemic mepivacaine may be influenced by sympathetic change and concurrent general anesthesia, the authors directly measured renal sympathetic nerve activity (RSNA) during intravenous administration of mepivacaine in subseizure through seizure doses under N2O-O2 and N2O-O2-halothane anesthesia. Thirty-four cats were randomly assigned to five groups. Groups I-A, I-B, and I-C received incremental subseizure doses of intravenous mepivacaine (2 mg/kg, 5 mg/kg, and 10 mg/kg). Groups II-A and II-B received intravenous infusion of mepivacaine (4 mg/kg/min). Anesthesia was maintained with N2O(70%)-O2 in groups I-A, I-C, and II-A, and with N2O(70%)-O2-halothane (1%) in groups I-B and II-B. Cats in group I-C had undergone total baroreceptor denervation. Heart rate (HR), mean arterial pressure (MAP), and RSNA were measured. In group I-A, MAP did not significantly change with intravenous mepivacaine, though RSNA and HR significantly decreased (P < .05) respectively with 5 mg/kg i.v. and 10 mg/kg i.v. mepivacaine. In group I-C, HR, MAP, and RSNA did not change significantly. In group I-B, HR and MAP decreased with bolus intravenous doses of mepivacaine in a dose-dependent fashion, but RSNA did not change significantly. All cats in group II-A developed seizure by mepivacaine infusion at mean total dose of 28.9 +/- 4.2 mg/kg without significant changes in HR, MAP, or RSNA. In group II-B, mepivacaine infusion resulted in circulatory collapse at mean total dose of 34.3 +/- 4.6 mg/kg without seizure or significant RSNA change. The authors conclude that intravenous mepivacaine induces occasional depression in HR and RSNA during N2O-O2 anesthesia, but in addition induces dose-related circulatory depression during N2O-O2-halothane anesthesia via nonsympathetic mechanism(s).

Effects of isoflurane-nitrous oxide and halothane-nitrous oxide anaesthesia on myocardial contractility assessed by transoesophageal echocardiography

In order to evaluate the direct effect of isoflurane-nitrous oxide and halothane-nitrous oxide anaesthesia on cardiac contractility in 20 adults, we have used a method based on left ventricular end-systolic wall stress (LVESWS) vs velocity of circumferential fibre shortening with corrected heart rate (Vcfc), obtained by transoesophageal echocardiography. We found that LVESWS (index of afterload) decreased significantly with isoflurane-nitrous oxide (n = 10) in concentrations of 1.5-1.95 MAC, but there were no significant changes in LVESWS with halothane-nitrous oxide (n = 10). Vcfc decreased significantly with halothane-nitrous oxide in concentrations of 1.5-1.95 MAC, but this index did not change significantly with isoflurane-nitrous oxide. However, there was no significant difference between the two groups in LVESWS or Vcfc. In the analysis of the LVESWS-Vcfc relationship, myocardial contractility associated with isoflurane-nitrous oxide anaesthesia did not differ significantly from that associated with halothane-nitrous oxide anaesthesia at equiMAC concentrations. The results suggest that halothane-nitrous oxide anaesthesia, at 1.5-1.95 MAC, maintained myocardial contractility in similar anaesthetic concentrations to isoflurane-nitrous oxide.

Clinical Pharmacology of Mivacurium in Pediatric Patients Less Than Two Years Old During Nitrous Oxide-Halothane Anesthesia

We determined the dose-response relationship of mivacurium in infants 2-6 and 7-11 mo of age during nitrous oxide-halothane anesthesia. The neuromuscular and cardiovascular effects of a bolus dose of mivacurium larger than the ED95 in infants and young children from 2-23 mo of age were observed. The infusion rate of mivacurium required to maintain approximately 95% neuromuscular block was determined. There was no significant difference between the estimated dose-response relationship in infants 2-6 mo and that in infants 7-11 mo. The ED50 and ED95 were 44 micrograms/kg and 85 micrograms/kg for infants 2-11 mo (n = 70), r = 0.53. A bolus dose of 150 micrograms/kg mivacurium in infants (2-6 mo) produced 100% depression of the initial twitch height (T1) in 8 out of 9 infants and 85% depression in 1 infant. The time to onset of maximum block was 1.6 +/- 0.3 (0.7-2.7) (mean, SEM [range]) min, and time to recovery to 25% of T1 (T25) was 7.5 +/- 0.7 (5.5-11) min after 150 micrograms/kg in these patients. A bolus dose of 200 micrograms/kg mivacurium in infants and young children (7-23 mo) produced 100% depression of T1 in 14 of 17 patients, 97% depression in 2, and 90% depression in 1. The time to onset of maximum block was 1.5 +/- 0.1 (0.8-3) min and T25 was 10.3 +/- 1.5 (4.8-30.5) min after 200 micrograms/kg in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Pancuronium dose-response revisited

Summary We were interested in determining the cumulative dose-response relationship of pancuronium in infants and children during nitrous oxide–halothane anaesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10 s intervals. Forty patients were divided into four equal groups according to age: 3–6 months, 7–12 months, 13–47 months and 48–83 months. The effective dose, ED50 (mean ± SEM), of pancuronium in these age groups was 24 ± 2, 30 ± 2, 34 ± 3, 29 ± 2 μgμkg-1, respectively; the ED95 (mean ± SEM) was 45 ± 2, 52 ± 3, 62 ± 6, 62 ± 4 μgμkg-1, respectively. The ED95 of pancuronium was significantly less (P < 0.05) for infants from 3 to 6 months of age than for children from 13 to 83 months of age. Infants thus appear to be more sensitive than children to the neuromuscular blocking effects of pancuronium during halothane anaesthesia.

Transcranial doppler for detection of cerebral ischaemia during carotid endarterectomy

We evaluated transcranial Doppler sonography (TCD) for the detection of cerebral ischaemia during carotid endarterectomy in 30 male and 14 female patients with ipsilateral focal cerebro-vascular symptoms. Surgery was performed during halothane-nitrous oxide anaesthesia with moderate hypocapnia. Eight patients had a temporary shunt owing to contralateral occlusion or a stump pressure below 40 mmHg, and/or EEG flattening. Transcranial Doppler sonography was followed intra-operatively together with electro-encephalography (EEG), internal carotid artery (ICA) pressures and cerebral blood flow (CBF). Middle cerebral artery mean flow velocity (Vmean) was 38 (22-96) cm s-1 (median and range) and decreased during cross-clamping to 28 (10-60) cm s-1 (p less than 0.0001). After removal of the clamp it increased to 42 (20-102) cm s-1 (p less than 0.0001). AVmean clamp of less than 30 cm s-1 together with a Vmean clamp: Vmean pre-clamp ratio of less than 0.6 showed an accuracy with respect to CBF below 20 ml 100 g-1 min-1 of 89%. AVmeanclamp:Vmean pre-clamp ratio below 0.4 detected all all patients with EEG flattening (n = 3) (accuracy 97%). The corresponding level of accuracy obtained with stump pressure was 80%. The results indicate that middle cerebral flow velocity enables an increase in the accuracy of detecting cerebral ischaemia during carotid endarterectomy.

Okuläre Kreislaufveränderungen bei Halothan-Lachgas-Intubationsnarkose unter besonderer Berücksichtigung des arteriellen CO2-Partialdrucks - Teil 1: Phänomenologie der Veränderungen

In 20 patients (5 with cataract, 15 with strabismus), general anesthesia was performed using halothane (inspiratory concentration: 0.5 vol.%) and nitrous oxide (65 vol.%); thiopental was employed for induction of anesthesia, vecuronium and succinylcholine were used for neuromuscular blockade prior to intubation. In series 1, the patients were slightly hyperventilated (PCO2 33 mmHg, on average). In series 2, the arterial PCO2 was changed in a range between 20 and 45 mmHg. By means of oculo-oscillo-dynamography, we determined the systolic retinal and ciliary perfusion pressures (PPs,ret and PPs,cil) as well as the respective ocular blood pressures (Ps,ret and Ps,cil), the ocular pulsation volume (PVoc) and the pulsatile ocular blood flow (Fp,oc = PVoc x heart rate). The intraocular pressure (Pio) was measured with the Draeger hand-applanation tonometer. Results of series 1: Measured 5 and 15 min after intubation, PPs,ret was reduced by averages of 12.5 and 20.2 mmHg, respectively, corresponding to decreases of 13.1 and 21.2% compared to the initial values. Ps,ret was decreased by 15.4 mmHg (14.2%) 5 min after intubation and by 27.1 mmHg (25.0%) 15 min after intubation. The ciliary pressures (PPs,cil and Ps,cil) were changed by similar amounts. PVoc was reduced by 0.3 microliters (50.8%) during both time periods after intubation. Fp,oc was lowered by 19.5 microliters/min (41.0%) and by 26.4 microliters/min (55.5%), measured 5 and 15 min after intubation, respectively. Pio was decreased by 1.6 mmHg (11.3%) and by 7.6 mmHg (53.5%), respectively. The systolic brachial artery pressure was reduced by 12.6 mmHg (9.5%) 5 min after intubation and by 29.1 mmHg (21.9%) 15 min after intubation. The diastolic branchial artery pressure showed a slight initial increase, followed by a small decrease. All changes were highly significant (P less than 0.001; 1-factor analysis of variance plus Scheffé test). Results of series 2: In a PCO2 range between 40 and 45 mmHg (normo-until slight hypoventilation; determined 5 min after intubation), PVoc and Fp,oc averaged 0.43 microliter and 42.9 microliters/min, respectively. In a PCO2 range between 30 and 35 mmHg (slight hyperventilation), PVoc and Fp,oc averaged 0.38 microliters and 36.1 microliters/min, respectively; and in a PCO2 range between 20 and 25 mmHg (forced hyperventilation), they averaged 0.21 microliter and 22.8 microliters/min, respectively. All other variables were not dependent on the PCO2 level. The lowering of PVoc and Fp,oc, observed during halothane-nitrous oxide anesthesia--especially with forced hyperventilation-, may be interpreted as reduced pulsatile choroidal blood flow.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of Sufentanil and Fentanyl to Supplement N2O-Halothane Anesthesia for Total Hip Arthroplasty in Elderly Patients

Sufentanil was compared with fentanyl as a supplement to nitrous oxide-halothane anesthesia in a double-blind study of 30 elderly patients undergoing total hip arthroplasty. Comparisons were made with respect to (a) hemodynamic (heart rate and blood pressure) and adrenergic (plasma norepinephrine and epinephrine levels) responses during surgery and recovery; (b) time to extubation after the end of surgery; and (c) postoperative analgesia. No difference was observed between the two groups with respect to demographic data, blood gas tensions, or hemodynamic and adrenergic responses to surgery and recovery. Total doses of opioids used were 0.7 +/- 0.3 micrograms/kg of sufentanil and 6 +/- 2.6 micrograms/kg of fentanyl. Times between end of surgery and extubation were not different (60 +/- 54 min in the fentanyl group and 58 +/- 52 min in the sufentanil group). The number of patients needing postoperative analgesia did not differ between the two groups, but use of analgesia was significantly delayed in the sufentanil group (168 +/- 25 vs 127 +/- 29, P less than 0.05). This study suggests that in elderly patients sufentanil confers a greater residual analgesia than fentanyl in the immediate postoperative period.

Oral nociceptive activity in the rat superior colliculus

Single units were recorded using extracellular glass microelectrodes in all laminae of the superior colliculus of the rat under halothane nitrous oxide anaesthesia. Fifty-one units were encountered which responded to a low intensity mechanical stimulus applied to a contralateral or bilateral field located in the oral sphere (intraoral 11, perioral 16), on the face (29) or on the rest of the body (21). Sixteen units responded to a jaw movement. Sixty-one cells were recorded which were preferentially (10) or only (51) activated (30) or inhibited (21) by noxious stimuli. Contralateral or bilateral mechanoreceptive fields located in intraoral (34) and perioral (35) areas were frequent. There is therefore a high incidence of the nociceptive representation of the mouth in the superior colliculus. The other functional properties of the nociceptive units were similar to those reported in other studies. From the subsequent histological localization of the recorded units, it appeared that the nociceptive projections from the intraoral and perioral regions to the superior colliculus reach the lateral part of the intermediate and deep layers of the superior colliculus.

Responses of trigeminal subnucleus oralis nociceptive neurones to subcutaneous formalin in the rat

Extracellular recordings of 33 single nociceptive neurones of the trigeminal subnucleus oralis (SNO) were made in rats under halothane nitrous oxide anaesthesia. These neurones were tested for their responses to a s.c. injection of formalin in their receptive field. Such a chemical noxious stimulation is known to induce a biphasic response of nociceptive dorsal horn neurones, the second period of which would be due to inflammation. Twenty-three neurones were characterized as nociceptive non-specific (NnS) and 10 as nociceptive specific neurones (NS). Formalin activated both SNO NS and NnS neurones, but, when they responded, NS neurones ( n = 5) showed only the first phase of activity while NnS neurones showed either one ( n = 13) or two phases ( n = 6). Biphasic responses were most often observed for NnS neurones with Aδ- and C-fibre inputs. These results indicate that the time-course similarity between the behavioural and the neuronal responses to formalin exists only for some SNO convergent neurones and that therefore the SNO does not seem to be very involved in the inflammatory component of the pain caused by formalin.

The use of intraoperative fentanyl in spontaneously breathing dogs undergoing orthopaedic surgery

Nineteen dogs were assigned randomly to one of three groups. Animals in Group 1 were pre-medicated with acepromazine, 50 μg/kg bodyweight (bwt) intramuscularly (im) and received 10 ml of 0.9 per cent saline intravenously (iv) at the time of skin incision. Dogs in Group 2 were pre-medicated with acepromazine, 50 μg/kg bwt im, and received fentanyl 2 μg/kg bwt iv at skin incision. Dogs in Group 3 were pre-medicated with acepromazine, 50 μg/kg bwt and atropine, 30 to 40 μg/kg bwt, im and received fentanyl, 2 μg/kg bwt iv at skin incision. Pulse rate, mean arterial blood pressure, respiratory rate and end tidal carbon dioxide were measured before and after fentanyl or saline injection. Fentanyl caused a short-lived fall in arterial blood pressure that was significant in dogs premedicated with acepromazine, but not in dogs pre-medicated with acepromazine and atropine. A significant bradycardia was evident for 5 mins in both fentanyl treated groups. The effect on respiratory rate was most pronounced in Group 3, in which four of seven dogs required intermittent positive pressure ventilation (IPPV) for up to 14 mins. Two of six dogs in Group 2 required IPPV, whereas respiratory rate remained unaltered in the saline controls. The quality of anaesthesia was excellent in the fentanyl treated groups; however, caution is urged with the use of even low doses of fentanyl in spontaneously breathing dogs under halothane-nitrous oxide anaesthesia.

Serum gastrin and blood glucose levels during halothanenitrous oxide anaesthesia and strabismus surgery in children

The purpose of this study was to determine whether serum gastrin levels are increased by reflexogenic stimuli applied to the extrinsic muscles of the eye. Serum gastrin and blood glucose concentrations were measured in ten normal children aged between 5 and 12 yr during general anaesthesia with halothane and nitrous oxide and during strabismus surgery. Fasting basal concentrations of gastrin (33.6 +/- 14.8 pg.ml-1) and of glucose (4.43 +/- 0.72 mmol.L-1) were in the normal range of values for children. Intravenous atropine (0.01 mg.kg-1), general anaesthesia with halothane in nitrous oxide and oxygen by mask for three minutes, tracheal intubation, extraocular muscle stimulation and surgical stress did not cause any variation in the mean serum gastrin concentration. On the contrary, tracheal intubation and surgical stress increased blood glucose concentrations (P less than 0.05). There was no difference in the serum gastrin levels after extraocular muscle stimulation between children with positive or negative oculocardiac reflexes (44.5 +/- 16.7 pg.ml-1 vs 38 +/- 14.7 pg.ml-1, respectively). The incidence of vomiting predischarge was 60 per cent. Serum gastrin levels did not differ between children who vomited and children who did not (44.3 +/- 18.5 pg.ml-1 vs 47.1 +/- 16.9 pg.ml-1, respectively). Vomiting after strabismus surgery cannot be attributed to high gastrin serum levels. Consequently, it is unlikely that vomiting after strabismus surgery is linked to an "oculogastric reflex" with the vagus nerve as the efferent pathway.

Clinical Pharmacology of Pipecuronium in Infants and Children During Halothane Anesthesia

We determined the cumulative dose-response relations of pipecuronium in infants and children during nitrous oxidehalothane anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Patients were stratified into four groups according to age: 3 mo or older but not yet 6 mo (n = 10), 6 mo or older but not yet 12 mo (n = 10), 1 yr or older but not yet 3 yr (n = 10), and 3 yr or older but not yet 6 yr (n = 9). The mean ED50 of pipecuronium in these age groups was 18, 20, 21, and 24 micrograms/kg, respectively; the mean ED95 was 33, 38, 47, and 49 micrograms/kg, respectively. The ED95 of pipecuronium was statistically significantly less for the 3-6-mo-old patients than for children between 1 and 6 yr of age. Similarly, pipecuronium dosage requirements calculated on the basis of body surface area were significantly less in infants 3-12 mo of age than in children 1-6 yr of age. Thus, compared with children, infants appear to be more sensitive to the neuromuscular blocking effects of pipecuronium. Duration (T25) of action after cumulative dosing with pipecuronium was approximately 20 min in infants and 30 min in children. Spontaneous recovery indices were not prolonged in the younger patients. The average T25-75 recovery index was 27.1 +/- 9.6 min. There were no changes in cardiac rhythm, heart rate, or blood pressure attributable to pipecuronium during this study.

Mivacurium Infusion Requirements in Pediatric Surgical Patients During Nitrous Oxide-Halothane and During Nitrous Oxide-Narcotic Anesthesia

We were interested in determining the infusion rate of mivacurium required to maintain approximately 95% neuromuscular blockade during nitrous oxide-halothane (0.8% end-tidal) or nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity (Datex NMT) of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Mivacurium steady-state infusion requirements averaged 315 +/- 26 micrograms.m-2.min-1 during nitrous oxide-halothane anesthesia and 375 +/- 19 micrograms.m-2.min-1 (mean +/- SEM) during nitrous oxide-narcotic anesthesia. Higher levels of pseudocholinesterase activity were generally associated with a higher mivacurium infusion requirement. During both anesthetics, younger age was associated with a higher infusion requirement when the infusion requirement was calculated in terms of micrograms.kg-1.min-1. This difference was not present when the infusion rate was calculated in terms of micrograms.m-2.m-1. There was no evidence of cumulation during prolonged mivacurium infusion. There was no difference in the rates of spontaneous or reversal-mediated recovery between anesthetic groups. After the termination of the infusion, spontaneous recovery to T4/T1 greater than or equal to 0.75 occurred in 9.8 +/- 0.4 min, with a recovery index, T25-75, of 4.0 +/- 0.2 min (mean +/- SEM). In summary, pseudocholinesterase activity is the major factor influencing mivacurium infusion rate in children during nitrous oxide-narcotic or nitrous oxide-halothane (0.8% end-tidal) anesthesia.

Renin and angiotensin converting enzyme concentrations in the fetal and neonatal guinea‐pig.

1. Plasma renin concentration (PRC) and plasma and pulmonary angiotensin converting enzyme (ACE) concentration were measured in fetal and neonatal guinea-pigs from 45 days gestational age (GA) until 21 days post-partum. 2. Fetal PRC increased towards term to reach values greater than those measured in normal adult males. Pentobarbitone anaesthesia of the mother resulted in significant elevation of fetal PRC after 66 days GA but not before this time. 3. PRC were very high in the newborn guinea-pig, decreased rapidly during the first 24 h after birth and then more gradually, to reach approximately adult values by day 21. 4. Fetal plasma ACE concentration increased towards term to reach values greater than those measured in adult males and decreased subsequently. 5. Pulmonary ACE concentrations were very low throughout gestation but increased considerably between days 3 and 14 post-partum. Low concentrations of ACE were measured in other fetal tissues but placental concentrations were relatively high. 6. Propranolol (0.1 mg I.P.) or saline was administered (under halothane-nitrous oxide anaesthesia) to fetuses of litters of various GA from 55 days to term. Fetal PRC were measured 3 h later. Propranolol treatment resulted in significantly lower fetal PRC than saline treatment in litters aged 63 days to term but not in younger litters. 7. These data indicate that the renin-angiotensin system is functional in the fetal guinea-pig during the last third of gestation. Fetal plasma renin concentrations near term are greater than those measured in normal adult males. This may, in part, reflect an increased influence of the fetal sympathetic nervous system.