Biomedical subjects
Publications and source records attributed to W S Wren.
This paper reviews the approach to pain during surgery in the newborn under five general headings: (1) current attitudes to pain in the newborn during anaesthesia and intensive care; (2) current evidence on the response of the newborn to pain; (3) current approaches to the management of pain in the newborn; (4) the complications of these approaches; (5) the resultant principles of the management of anaesthesia in the newborn.
A method for preparing standard gas mixtures of the volatile anaesthetics halothane, enflurane and isoflurane is described. Static mixtures of gases of known concentration can be prepared manometrically by measuring the required pressure of anaesthetic gas into a bulb and diluting to atmospheric pressure with air. Standard gas mixtures in the concentration range 0-4% V/V can be prepared with an accuracy of +/- 0.01% V/V, and the relative standard error of measurements of a single standard concentration is less than 0.8%. Significant adsorptive losses in the gas sampling valve were observed for gas standards prepared in the absence of any diluent gas. These losses were not detected for measurements of standards made up to atmospheric pressure in air. A comparison with calibration procedures currently in practice is presented.
A method is described for the direct determination of the volatile anaesthetics halothane and isoflurane in blood by gas chromatography with flame-ionisation detection. The method is accurate and precise and allows rapid measurements of blood levels of anaesthetic agents. Headspace concentrations of anaesthetic agents in the concentration range 0-3% V/V are determined with an accuracy of +/- 0.01% V/V. The relative standard deviation of these results is less than 4.0%. A relatively small volume of blood is required for each determination, a factor of great significance in the treatment of children. The need for separate blood calibration graphs for each patient is discussed, further emphasising the need for a rapid calibration procedure. The results from the clinical application of this method show conclusively its suitability for the management of anaesthetised subjects.
The performance of the Ohio 5400 electronic anemometer and the Ohmeda SE302 heated platinum filament respirometer were assessed in a series of bench tests in which they were incorporated into the patient circuit of a Siemens-Elema Servo 900C ventilator. The reference instrument was a Fleisch pneumotachograph. The Ohio 5400 was accurate to within 10% when measuring air flows between 23 and 44 l/min, provided the cycling frequency did not exceed 30 b.p.m. and the flow wave form was not accelerating. The Ohmeda SE302 was accurate to within 10% when measuring air flows between 8 and 48 l/min, regardless of cycling frequency or shape of respiratory wave form. Both instruments displayed marked inaccuracies (of the order of 20-30%) when measuring 100% oxygen or 66% nitrous oxide/oxygen mixtures. The performance of the flow transducer of the Servo 900C was also assessed. This was significantly superior, and its output was virtually identical to the uncorrected output of the pneumotachograph.
The ventilatory effects of halothane in eight children were compared with those of isoflurane in eight children and enflurane in six children. All studies were completed before surgery commenced, and the children received no preoperative medication. The depression of ventilation produced by the three agents increased in a dose-related fashion as the alveolar concentrations were increased, and the depression of ventilation that they produced in oxygen was greater than that produced by equipotent concentrations in nitrous oxide. While the increase in ventilatory frequency and the decrease in TE associated with increasing concentrations of halothane were statistically significant (P less than 0.05), the increase in frequency associated with isoflurane was not, although it was sufficient to maintain the end-tidal and arterialized venous PCO2 in the isoflurane group at a value which did not differ significantly from that in the halothane group. Profound depression of ventilation was produced in the children by enflurane, clearly because no increase in ventilatory frequency was associated with its use. It was evident that the ventilatory effects of the three volatile agents in unstimulated children are very similar to those described elsewhere in the adult. There was no difference of any clinical significance between the degree of depression of ventilation produced by halothane and isoflurane in children.
The anaesthetic management of 350 consecutive patients with congenital hypertrophic pyloric stenosis over an 8-year period is reviewed. The anaesthetic technique is discussed and the complications encountered reviewed. The morbidity rate was 15.9%. The anaesthetic related morbidity rate was 3.7%. One patient in the series died (0.27%) 8 weeks after pyloromyotomy, as a result of an underlying myopathy.
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The mathematical relationship between peak ventilator breathing system pressure displayed on the digital meter of the Siemens SV900C ventilator, and peak intratracheal pressure measured at the distal end of the tracheal tube, was defined and incorporated into a computer program. The mean difference between peak airway pressure calculated by the computer and directly measured peak intratracheal pressure was 0.02 kPa (SD 0.10) in 18 infants and children. The mean difference between ventilator breathing system pressure and intratracheal pressure in the same group was 0.82 kPa (SD 0.91). Bench tests established that the decrease in peak pressure displayed by the ventilator (from 1.36 to 0.38 kPa) while inspiratory time was increased from 20 to 80% of the respiratory period, concealed an increase (from 0.2 to 0.38 kPa) in intratracheal pressure which occurs during this process; and that the large increase in pressure displayed by the ventilator (from 0.3 to 6 kPa) while respiratory frequency was increased from 20 to 120 breaths/minute, concealed a small increase in peak intratracheal pressure (0.2-0.3 kPa) which occurs during this process. These changes were accurately predicted by the computer program. The increase in intratracheal pressure associated with prolonged inspiratory times explains the high incidence of barotrauma which has recently been associated with this procedure in infants.
An increase in ventilation in spontaneously breathing children, when nitrous oxide was withdrawn from the nitrous oxide-halothane inspired mixture, was previously suggested to be a direct effect of decreased alveolar nitrous oxide concentration. To test whether a "gas effect" of oxygen inflow had caused a false increase in tidal volume signal, in the present study nitrous oxide was withdrawn in two stages, with equilibrium at each stage; there was a 7% increase in VT, to 3.88 ml kg-1. During that nitrous oxide withdrawal, despite a constant vaporizer setting for halothane, the alveolar concentration of halothane decreased (from 1.06% to 0.9%). When the alveolar halothane concentration was subsequently deliberately decreased from 1.06% to 0.9% with nitrous oxide maintained constant at 65%, there was a 14% increase in VT, again to 3.88 ml kg-1. It is concluded that nitrous oxide did not produce significant depression of ventilation in children, and that the observed increases in tidal volume were the result of decreases in end-tidal halothane concentration, produced by a decrease in its inspired concentration.
The effect of changing the composition of the carrier gas from 66% nitrous oxide in oxygen to 100% oxygen was examined in three halothane vaporizers (Fluotec Mk 3, Drager Vapor 19 and Abingdon halothane vaporizer). All showed a transient increase in output following the discontinuation of the nitrous oxide. The effect was minor (2-8% of indicated output) and short-lived (1-4 min) at the fresh gas flows used. The steady-state output of the vaporizers, once the transient response was over, was found to be lower with 100% oxygen as carrier gas than it had been with 66% nitrous oxide in oxygen. The difference was minor in the case of the Drager Vapor 19 (1% of indicated output) and Fluotec Mk 3 (5% of indicated output), but greater in the case of the Abingdon (15% of indicated output).
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The characteristics of induction with and recovery from isoflurane anaesthesia were studied in 248 children. The mean time to loss of consciousness was 1.5 min (SD 0.5). Tracheal intubation, without interruption of spontaneous ventilation, was accomplished in a mean time of 4.2 min (SD 54 seconds). Movement and excitement, of 20-30 seconds duration, occurred in 23.9% children and 22 patients coughed during induction; 15 (12.6%) during the first 124 inductions; 7 (5.6%) subsequently. The mean half-times of reduction of alveolar isoflurane concentrations in 28 children whose lungs were ventilated with isoflurane and in 13 children who breathed isoflurane spontaneously during anaesthesia were: 45 sec after exposure for one hour, 70 sec after exposure of 2-3 hours and 110 seconds following exposures of 4-8 hours. The mean recovery times of the three groups were 6.5, 9.5 and 11.5 min respectively. In two further groups of nine children the mean half times of elimination of halothane and isoflurane were 220 seconds and 54 seconds respectively; recovery from isoflurane was markedly faster. Isoflurane is well accepted by children; induction is more rapid than with halothane, and the marked flexibility in the control of its effects are due to its relative insolubility. It has wide application in paediatric anaesthesia.
The effects of the withdrawal of nitrous oxide from the inspired gas mixture were studied in 10 spontaneously breathing children during nitrous oxide-halothane anaesthesia, before and during surgery, using a computerized system for the measurement, recording and analysis of data. Before surgery the decline in the alveolar nitrous oxide concentration was associated with an increase in minute ventilation (32.7%, P less than 0.05), and a decrease in alveolar carbon dioxide concentration (8.4%, P less than 0.05). These effects were produced solely by an increase in tidal volume (42.7%, P less than 0.001), as no significant change in respiratory rate was observed. The hypoventilation produced by an alveolar mixture of 60% nitrous oxide and 0.9% halothane, a reduction of VE by 50%, exceeded the hypoventilation caused by 0.9% halothane alone, which reduced VE by 36.6%; and the hypoventilation produced by nitrous oxide and halothane was rapidly reversed by the withdrawal of nitrous oxide from the inspired gas mixture. During surgery all indices of ventilation were stimulated, and there was greater variability of response, but the pattern and degree of change in response to nitrous elimination, VE increased by 33.3%, VT by 33.8%, closely resembled the changes before surgery. Five children had received papaveretum as premedication, and five thiopentone per rectum; the depression of carbon dioxide responsiveness was more severe in the group who received papaveretum, and their responses to nitrous oxide elimination were less than, and occurred later than the responses in the group given thiopentone.
A 4.2-kg full-term male infant underwent treatment of acute respiratory distress as a result of gross bilateral pneumothoraces, pneumomediastinum and interstitial emphysema. When a trial of continuous positive airway pressure failed conventional intermittent positive pressure ventilation was instituted, but this also failed to achieve satisfactory ventilation at a respiratory frequency of 60 b.p.m. while producing peak airway pressures of 30 cmH2O. High frequency positive pressure ventilation was instituted with a Siemens 900C ventilator delivering a minute volume of 3 litre min-1 at a respiratory frequency of 72 b.p.m., while registering peak airway pressures in the range of 20-23 cm H2O. During the first 30 min of this regimen the patient's condition improved such that FIO2 was decreased to 0.6. Six hours later FIO2 was decreased to 0.55 and the inspired minute volume to 2.8 litre min-1 with a further decrease in peak airway pressure. The infant was maintained on high frequency positive pressure ventilation for a total of 42 h, and following weaning made an uneventful recovery. In another newborn infant, weight 1.9 kg, the measurement of airway pressure at the distal end of the tracheal tube and gas flow in the inspiratory limb of the respiratory circuit established that the tracheal peak airway pressure was 10 cm H2O less that the pressure registered on the ventilator. The 900C ventilator produced a pattern of high frequency low pressure ventilation, with sustained PEEP, which closely resembles the defined pattern of HFPPV.
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Two Bordetella bronchiseptica isolates, S-55 and D-2, were evaluated in dogs for inducement of (i) infection, (ii) clinical bordetellosis, and (iii) histopathologic changes on tracheal and bronchiole tissues. Further, each isolate was characterized for variance in (i) toxicity for mice and (ii) intracellular proteins. Both S-55 and D-2 were detectable in test dog groups during the 26-day test period, although 545 times more D-2 was recovered than was S-55. In dogs inoculated with D-2, clinical infectious tracheobronchitis appeared in 4 days and continued for 22 days. Bordetellosis was not observed in dogs given S-55 or in noninoculated dogs. Tracheal and bronchiole tissues from dogs inoculated with the S-55 and D-2 isolates were microscopically examined for lesions. Dogs inoculated with S-55 did not have tracheal or bronchiole lesions. Lesions were not observed in noninoculated dogs. Dogs inoculated with D-2 had marked lesions in the tracheal and bronchiole tissues. The D-2 whole cells were an average 4.8 times as lethal as S-55 whole cells in mice (given intraperitoneal inoculation), whereas cell-free culture supernatants from S-55 and D-2 isolates were nontoxic. Cell-free sonicated extracts of S-55 and D-2 proved toxic to mice (intraperitoneal inoculation), but after the extracts were heated at 56 C for 30 minutes, both were nontoxic. Intracellular proteins of approximately 116,000 and 44,000 daltons were found in higher concentration in D-2 cells than in S-55 cells.
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