Peri-operative changes in plasma C3a and C5a concentrations in infants

It is well known that complement activation plays a key role in the development of pulmonary insufficiency; it is also well known that cortisol suppresses complement activation. By measuring the plasma concentrations of C3a and C5a, we investigated peri-operative changes in the activation of the complement system in 18 infants undergoing elective abdominal surgery. We also measured plasma cortisol concentrations to assess the peri-operative relationship between complement activation and the stress produced by multiple peri-operative factors following two anaesthetic techniques. Eighteen infants ranging in age from 1 to 11 months were randomly divided into two groups according to the anaesthetic technique used: Group 1 consisted of nine infants in whom general anaesthesia was maintained with halothane and nitrous oxide (N₂O) in oxygen, while Group 2 consisted of nine infants in whom general anaesthesia was maintained with fentanyl and N₂O in oxygen. Plasma C3a and C5a concentrations were higher in the fentanyl group than in the halothane group during the peri-operative period. Plasma cortisol concentration, in contrast, was lower in the fentanyl group both during and after surgery. The post-operative clinical course showed no significant intergroup differences between the two groups throughout the study. These observations suggest that the difference in peri-operative complement activation between the halothane and the fentanyl groups may have been due, in part, to different peri-operative stress responses. However, further studies are required to elucidate the precise causative mechanisms and the clinical implications of complement activation in infants.     

Perioperative complement activation in neonates under halothane or fentanyl anaesthesia

We investigated perioperative changes in complement activation in 18 neonates undergoing elective abdominal surgery with or without thoracotomy by measuring plasma concentrations of C3a and C5a, and leucocyte counts in peripheral blood. The 18 neonates, ranging in age from 1 to 17 days, were randomly divided into two groups according to type of anaesthetic procedures; the "halothane group" consisted of nine neonates in whom general anaesthesia was maintained with halothane and nitrous oxide (N2O) in oxygen, while the "fentanyl group" consisted of nine neonates in whom general anaesthesia was maintained with fentanyl and N2O in oxygen. Plasma C3a and C5a concentrations were higher in the fentanyl group than in the halothane group during the perioperative period. We have demonstrated that abdominal surgical trauma caused complement activation even in neonates undergoing the fentanyl rather than the halothane anaesthesia. Further studies are required to elucidate the precise mechanisms and the clinical implication of perioperative complement activation in neonates.     

Haemodynamic depression by halothane is age-related in paediatric patients

The hypothesis that young infants are more sensitive to the haemodynamic depressant effects of halothane compared with older children was tested. One hundred and sixty unpremedicated, ASA physical status I or II paediatric patients without cardiac or pulmonary disease were divided into five age groups: term neonates, 1-6 months, 6-24 months, 2-6 years and 6-12 years. Anaesthetic induction was achieved with halothane in oxygen and air via mask. Vecuronium 0.1 mg.kg-1 was administered intravenously. During normocapnic manual ventilation by mask, endtidal halothane concentration was maintained at either 2xage-specific MAC (Method I) or 1.7% (Method II) in 20 patients in each age group for 10 min. In both Method I and Method II, systolic and mean blood pressure of term neonates and infants aged 1-6 months decreased significantly (P < 0.01) compared with other age groups. The results of this study demonstrate that neonates and young infants are more susceptible to haemodynamic depression during halothane anaesthesia than are older children, confirming clinical experience.     

PLASMA HYDROCORTISONE CONCENTRATIONS IN RELATION TO ANAESTHESIA AND SURGERY

Pre-anaesthetic, pre-surgical and post-surgical concentrationsof unconjugated plasma hydrocortisone were determined in eighteenpatients by quantitative paper chromatography. The mean pre-anaestheticlevel was slightly, but not significantly, higher than the meanconcentration in the control series. Small, but statisticallyinsignificant, mean rises of plasma hydrocortisone concentrationswere found after anaesthesia maintained with nitrous oxide andoxygen or halothane. Rises in individual patients occurred onlyafter 30 minutes of anaesthesia, the magnitude of these increasesbeing proportional to the duration of anaesthesia. Increasesin mean concentrations after surgical stimulation were insignificantwhen anaesthesia was maintained with nitrous oxide, oxygen andd-tubocurarine and possibly significant when halothane was used.A significant rise of mean post-surgical concentrations abovemean pre-anaesthetic concentrations was measured during bothtypes of anaesthesia. Possible causes of observed changes havebeen discussed.     

Respiratory effects of 'lissive" anaesthesia using gallamine.

'Lissive anaesthesia', the administration of a small dose of a non-depolarising muscle relaxant to a patient breathing nitrous oxide, oxygen and an anaesthetic vapour, is a technique popularly employed for minor procedures. In this study, the effects of intravenous gallamine triethiodide (40 mg) on the blood-gas status of 20 patients under general anaesthesia with oxygen, nitrous oxide and halothane after pethidine and atropine premedication, were assessed. The results are compared with those obtained from a control group of 10 patients anaesthetised in an identical manner, but omitting the muscle relaxant drug. All patients in both the relaxant and control groups in this study developed respiratory acidaemia. The rise in mean arterial carbon dioxide tension was, however, greater after injection of gallamine. Significant hypoxia or metabolic acidaemia was not encountered, except in one grossly obese patient in the gallamine group. The implications of these findings are discussed.     

Halothane-Relaxant Anaesthesia in Elderly Patients

Twenty-three elderly patients, scheduled for elective cholecystectomy, were studied during halothane-relaxant anaesthesia. Anaesthesia was induced with thiopentone and maintained with halothane in 12 patients, six of whom had also received premedication. Eleven patients were anaesthetized with halothane, without thiopentone induction and with no premedication. Measurements of central haemodynamics were performed awake and during anaesthesia at end-tidal halothane concentrations of 0.5 and 1.0%; at the lower concentration, measurements were also made after addition of nitrous oxide. Premedication and thiopentone had no influence on the subsequent halothane anaesthesia. Halothane caused reductions of cardiac index, mean arterial blood pressure and oxygen uptake. However, neither right atrial nor pulmonary capillary venous pressure increased and the arterio-venous oxygen content difference decreased. These findings differ from those made by others in younger subjects and are probably attributable to a dose-dependent reduction in systemic vascular resistance. The addition of nitrous oxide had only minor effects on central circulation. The results suggest that the age of the patients influences their reaction to halothane anaesthesia.     

Carbon dioxide tensions in infants during mask anaesthesia with spontaneous ventilation

Carbon dioxide tensions (PCO2) in arterialized capillary blood samples were measured in 39 infants anaesthetized for minor paediatric surgery. Anaesthesia was induced and maintained with oxygen, nitrous oxide and halothane, using a Mapleson-D system with spontaneous ventilation and a Rendell-Baker face mask. The duration of anaesthesia was between 15 and 95 min. Two capillary blood samples were obtained during stable anaesthesia before and after surgery. The PCO2 values varied between 3.7 and 8.0 kPa. The highest values were found in infants aged 15-30 days, 6.6 +/- 0.7 kPa (mean +/- s.d.), compared to 5.9 +/- 0.7 in infants aged 31-60 days, 5.6 +/- 0.8 in infants aged 61-180 days and 5.5 +/- 0.7 in infants aged 181-300 days. Comparison between measurements before and after surgery did not in any group indicate a progressive hypoventilation or a correlation between the length of the anaesthesia and the PCO2. It is concluded that anaesthesia with oxygen, nitrous oxide and halothane with spontaneous mask ventilation is a satisfactory method for minor procedures in infants over 1 month of age, while in younger infants controlled ventilation with intubation may be a safer choice of method.     

The effect of halothane on mivacurium infusion requirements in adult surgical patients

Background: The extent of interaction between volatile anaesthetics and neuromuscular blocking agents depends both on the inhalational anaesthetic and the muscle relaxant. Halothane has the weakest potentiating effect on neuromuscular blocking drugs and previous studies of the interaction between halothane and mivacurium have been contradictory. We were interested in determining the effect of different levels of halothane-nitrous oxide anaesthesia on infusion requirements of mivacurium. Methods: Sixty adult surgical patients were studied. Anaesthesia was induced with thiopentone and fentanyl and intubation facilitated with mivacurium 0.15 mg kg^-1. The patients were randomly assigned to one of four study groups. The control group received nitrous oxide in oxygen (2: 1) supplemented with fentanyl, while in the other groups halothane was administered at different end-tidal concentrations: 0.19% (Group 2), 0.37% (Group 3), 0.74% (Group 4), corresponding to 0.25, 0.5 and 1.0 MAC of halothane. Neuromuscular block was kept at 95% with a closed-loop feedback infusion of mivacurium and monitored with electromyography. Plasma cholinesterase concentrations and dibucaine numbers were determined. Results: Mivacurium infusion requirements (mean±SD) were 7.5±3.1 μg kg^-1 min^-1 with nitrous oxide-fentanyl anaesthesia. In the groups receiving 0.25, 0.5 or 1.0 MAC of halothane the steady-state infusion rates of mivacurium were reduced to 6.3±2.8, 5.6±1.4 and 5.7±2.5 μg-kg^-1min^-1 (P < 0.05), respectively. There was a linear relationship between mivacurium infusion requirements and plasma cholinesterase activity. Conclusion: Halothane anaesthesia reduces mivacurium infusion requirements by 15–25% compared to nitrous oxide-fentanyl anaesthesia. Interindividual differences in the extent of this interaction are great.     

Continuous infusion of alfentanil in infants undergoing inguinal herniorraphy

We evaluated the safety and efficacy of continuous alfentanil infusions in 37 full-term infants aged 4 to 52 weeks undergoing inguinal herniorraphy as outpatients. The infants were randomly assigned to one of two groups. In all patients anaesthesia was induced with halothane, nitrous oxide and oxygen by mask, then atropine and atracurium were administered intravenously. In the alfentanil group, anaesthesia was maintained with nitrous oxide, oxygen and alfentanil (100 μg·kg^-1) followed by a 2.0 μg·kg^-1·min^-1 continuous infusion whereas in the control group anaesthesia was maintained with nitrous oxide, oxygen, and halothane (1.5%). There were no differences between the groups with respect to intra-operative values of blood pressure and heart rate, post-operative values of oxygen saturation as measured by pulse oximetry and respiratory rate, or post-operative incidence of vomiting and use of pain medication. Sedation lasted longer post-operatively in the alfentanil group, delaying oral intake but not prolonging hospitalization time. This study affirms that intravenous anaesthesia with alfentanil is safe and effective in infants.     

Safety and efficacy of alfentanil and halothane in paediatric surgical patients

Alfentanil, a congener of the opioid fentanyl, possesses properties that make it an attractive choice for use during short operative procedures. Since the phannacodynamic aspects of alfentanil have not been well documented in children, this study was undertaken to evaluate the safety, efficacy, and dose requirements of alfentanil when used with nitrous oxide or halothane in paediatric patients. Eighty unpremedicated patients, ASA physical status I or II and aged 2–12 yr were studied. Patients were randomly assigned to one of four groups. After induction of anaesthesia with nitrous oxide, oxygen, and halothane, the groups were treated as follows. In Group I (n = 19), after halothane was discontinued, alfentanil 50 μg · kg^?1 was infused over 30 sec. In Group 2 (n = 20), the end-tidal halothane was maintained at 0.5% and alfentanil 25 μg · kg^?1 was infused. In Group 3 (n = 20), the end-tidal halothane concentration was maintained at 1% and alfentanil 12.5 μg · kg^?1 was infused. In Group4(n = 21), the end-tidal halothane concentration was maintained at 1.5% and no alfentanil was administered. Patients in Groups 1, 2, and 3 received bolus doses of alfentanil 12.5 μg · kg^?1 as needed to maintain haemodynamic stability. After alfentanil administration, there were transient decreases in systolic blood pressure in Groups 1 and 2, and in heart rate in Group 2. With surgical stimulation, haemodynamic stability was well maintained except in patients in Group 1, who had an increase in systolic blood pressure. Children Group 1 were alert sooner and their tracheas were extubated earlier than those in Groups 2, 3, and 4. The four groups were similar in postoperative narcotic analgesic administration and incidence of vomiting. In summary, alfentanil (12.5–50.0 μg · kg^?1) was a safe anaesthetic, whether combined with nitrous oxide alone or with nitrous oxide and halothane.     

Plasma levels of vitamin E and lipoperoxide during paediatric anaesthesia

We measured plasma levels of vitamin E (total tocopherol) and lipoperoxide in seventeen neonates (less than 10 days), twenty infants (1-12 months) and ten children (1-5 years) during anaesthesia. The seventeen neonates were randomly divided into two groups; seven who received 30 mg X kg-1 of alpha-tocopheryl acetate intramuscularly before anaesthesia and ten who did not. The 20 infants were divided into three groups: Group 1: eight infants who did not receive vitamin E; Group 2: six who received 30 mg X kg-1 of alpha-tocopheryl acetate orally for three days before anaesthesia; Group 3: six who received 30 mg X kg-1 of alpha-tocopheryl acetate intramuscularly three hours before anaesthesia. In the neonates who did not receive alpha-tocopheryl acetate, plasma vitamin E and lipoperoxide levels were unchanged following surgery. In Group 1 infants, plasma vitamin E levels decreased (p less than 0.05) and plasma lipoperoxide levels increased (p less than 0.05). In both neonates who received vitamin E and Group 3 infants the mean plasma vitamin E levels increased significantly (p less than 0.05) following surgery. In Group 2 infants, the levels of plasma vitamin E before surgery were high, as compared to the other groups: however, plasma vitamin E levels decreased following surgery. In the children, the plasma vitamin E levels were unchanged, while the plasma lipoperoxide levels decreased significantly (p less than 0.05) during anaesthesia. It is suggested from our studies that plasma vitamin E levels decrease and plasma lipoperoxide levels increase during anaesthesia and surgery in infants; however, those levels are unchanged in neonates.     

Rectal premedication in children

Two hundred and eight healthy children who were to undergo minor elective surgery during halothane, nitrous oxide, oxygen anaesthesia were studied in a double blind investigation to evaluate the sedative and anticholinergic effects of two rectal premedications. Group I received diazepam 0.75 mg/kg rectally; Group II received a mixture of diazepam 0.5 mg/kg, morphine 0.15 mg/kg and hyoscine 0.01 mg/kg rectally. No significant difference was found between the two groups in sedative or anticholinergic effects during induction of anaesthesia or in the postoperative period. No adverse effects were seen.     

The reduction of amnesic wakefulness during Caesarean section

Wakefulness during general anaesthesia was assessed by the isolated forearm technique in two groups of patients for Caesarean section. The anaesthetic was based on the use of oxygen 66%, nitrous oxide 33% and halothane 0.4% during the induction delivery interval. There was a highly significant reduction in wakefulness in the Group who received nitrous oxide at 66% for the first 3 min only. The wakefulness was amnesic in all cases.     

Nitrous oxide and postoperative vomiting in children undergoing myringotomy as a day case

The effect of avoiding nitrous oxide during anaesthesia for myringotomy as an outpatient procedure in children aged 18 months to 10 yr was investigated. One hundred and four children were allocated randomly to receive either nitrous oxide, oxygen and halothane or oxygen and halothane for maintenance of anaesthesia. Ten of 47 (21%) children receiving nitrous oxide experienced postoperative vomiting, compared with two of 48 (4%) of those that did not receive nitrous oxide (P < 0.05). The possible mechanisms are discussed.     

Exposure of operating room personnel to nitrous oxide during paediatric anaesthesia

This study was undertaken to quantify the exposure of operating room staff to nitrous oxide during routine paediatric otolaryngeal surgery and to determine the influence of the method of induction of anaesthesia on this exposure. The nitrous oxide exposure of the anaesthetist, the surgeon and the circulating nurse were measured, using body-worn passive atmospheric samplers, during twelve routine paediatric otolaryngeal surgical lists. During six of the lists an inhalational technique, with nitrous oxide, oxygen and halothane, was used for the induction of anaesthesia. During the other six lists anaesthesia was induced using intravenous thiopentone. In all cases, anaesthesia was maintained using nitrous oxide, oxygen and halothane. Regardless of the induction technique used, the mean nitrous oxide exposures of the anaesthetist, the surgeon and the nurse all exceeded the maximum level of 25 ppm.hr-1 recommended by the United States National Institute for Occupational Safety and Health (NIOSH). The use of an intravenous technique for the induction of anaesthesia reduced the nitrous oxide exposure of the anaesthetist and the circulating nurse. This suggests that, although the use of an intravenous induction may reduce exposure to nitrous oxide, the NIOSH recommendations for maximum exposure of operating room personnel to nitrous oxide are currently unattainable in practice.     

VARIABILITY OF HAEMOGLOBIN CONCENTRATION DURING ANAESTHESIA: A Statistical Investigation of three Anaesthetic Methods

Changes in haemoglobin concentration and systolic blood pressurewere measured for fifty-six patients receiving three differentmethods of anaesthesia. One group received anaesthesia comprisinga relaxant with nitrous oxide and oxygen and controlled respiration:no significant changes occurred. A second group received halothaneinhaled spontaneously with oxygen: significant decreases inmean (integral) operative blood pressure and Hb concentrationwere observed. A third group had lumbar epidural block, spontaneousrespiration and halothane inhalation. There was a statisticallysignificant fall in blood pressure and Hb concentration. Thefall in Hb concentration correlated significantly with the bloodpressure decrease occurring some 5 minutes before. The possiblesources of an increase in plasma volume during anaesthesia accompaniedby peripheral vasodilatation are discussed.     

The absence of antagonism by naloxone during halothane/nitrous oxide anaesthesia in man

Sixteen patients were studied to determine if naloxone could be shown to affect general anaesthesia with halothane and oxygen or nitrous oxide and oxygen with halothane. Changes in blood pressure, pulse rate, electroencephalogram and evidence of physical response were observed. The end-tidal halothane and carbon dioxide were controlled. The temperature and blood gases were held constant, as was the degree of neuromuscular blockade. Naloxone 1.2 mg was administered during general anaesthesia with either halothane in oxygen or halothane with nitrous oxide to 16 patients who were premedicated without a narcotic. No significant responses were recorded.     

Effects of rectal thiopentone and methohexitone on carbon dioxide tension in infant anaesthesia with spontaneous ventilation

The influence of rectal administration of barbiturates on PCO2 during mask anaesthesia with spontaneous ventilation was studied in 72 infants. The age of the patients ranged between 6 and 24 months and they were all subjected to minor paediatric surgery. The patients were divided into four equally large groups: a control group receiving no premedication, a group receiving rectal thiopentone 30 mg X kg-1 and two groups receiving methohexitone either 20 or 30 mg X kg-1. In all patients PCO2 was measured in an arterialized capillary blood sample obtained during stable anaesthesia with oxygen, nitrous oxide and halothane before and after surgery. After rectal induction with barbiturates, the mean PCO2 was significantly higher in the different barbiturate groups than in the control group (P less than 0.05). The mean PCO2 value +/- s.d. in kPa for the control group was 5.6 +/- 0.7, for the group receiving thiopentone 30 mg X kg-1 6.5 +/- 1.6, for the groups receiving methohexitone 20 or 30 mg X kg-1 6.1 +/- 1.2 and 6.3 +/- 1.1, respectively. It is concluded that the combination of rectal induction with barbiturates and mask anaesthesia with oxygen, nitrous oxide and halothane carries an increased risk of hypoventilation in infants under 2 years of age.     

USE OF AN EMULSION OF ICI 35868 (PROPOFOL) FOR THE INDUCTION AND MAINTENANCE OF ANAESTHESIA

2,6-Diisopropyl phenol in a fat emulsion formulation (propofol)has been used to supplement 67% nitrous oxide in oxygen anaesthesiain 20 patients premedicated with morphine 0.15 mg kg^-1and atropine0.6 mg, and undergoing body surface surgery. Following an inductiondose of propofol 2.5 mg kg^-1, the mean maintenance dose was73.4µg kg^-1min^-1. When compared with 10 patients receivingAlthesin to supplement nitrous oxide in oxygen in a similarmanner, recovery was considerably faster following propofol.The only major side-effect associated with the use of propofolwas pain on injection in nine out of 20 patients. When the patientsreceiving propofol were compared with a second control group(n = 11) in whom anaesthesia was induced with thiopentone 4mg kg^-1and maintained with 1 % halothane and nitrous oxide inoxygen, the former group showed a significant (P<0.01) decreasein the plasma cortisol concentration 30 min after the inductionof anaesthesia. However, by 3 h after induction, the cortisolconcentration in both groups was not significantly differentfrom the baseline (pre-induction) value. The mechanism of thisdecrease is not known. In vestigation of the influence of thefat emulsion on blood coagulation andfibrinolysis revealed nodifferences when compared with patients receiving Althesin.     

The efficacy of clonidine for reducing perioperative haemodynamic changes and volatile anaesthetic requirements in children

Background: Oral clonidine given as a premedicant in adults has been shown to reduce intraoperative inhalation anaesthetic requirements and provide perioperative haemodynamic stability. We conducted the current study to ascertain whether or not these beneficial effects of clonidine can be reproduced in children. Methods: In a prospective, randomized, double-blind, controlled clinical trial, 60 children (ASA I) aged 5–11 yr, received placebo (control), 2 μg kg^-1 clonidine, or 4 μg kg^-1 clonidine orally 105 min before induction of anaesthesia. Anaesthesia was induced with halothane, nitrous oxide in oxygen via mask and maintained with halothane and 60% nitrous oxide in oxygen. The halothane concentration was titrated to the concentration required to maintain haemodynamic stability (defined as 20% of blood pressure (BP) and heart rate (HR)) for maintenance of anaesthesia. The end-tidal concentration of halothane was monitored throughout anaesthesia. On completion of surgery, nitrous oxide and halothane were discontinued. Following confirmation of recovery from anaesthesia and muscle relaxation, the endotracheal tube was removed. Results: Higher inspired concentrations of halothane (%) were required in the control and 2 μg kg^-1 clonidine-treated groups (mean SD: 1.1 ±0.2 and 1.0±0.2, respectively) than in the 4 μg kg^-1 clonidine-treated group (0.6±0.1) for haemodynamic stability (P<0.05). Clonidine, 4 μg kg^-1, significantly reuced the intraoperative lability (coefficient of variation) of systolic and diastolic BP and HR compared with the other two regimens. Conclusion: Oral clonidine premedication at a dose of 4 μg kg^-1 provided intraoperative haemodynamic stability and reduced anaesthetic requirements in children. However, we are unable to extrapolate these observations to younger children and infants.