Mass spectrometers in anaesthesia.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to B Kay.
Explore the source record for details and available documents.
The respiratory effects of R 39209, a new short-acting analgesic, were studied and compared with those of fentanyl, in the rabbit. Minute volume, respiratory frequency and pH, PCO2 and standard bicarbonate of arterialized venous blood were measured. R 39209 had an earlier peak effect and shorter duration of action then fentanyl, but otherwise the respiratory effects of the two-drugs were similar. Fentanyl was between 2 and 3.5 times more potent than R 39209. Repeated doses of R 39209 produced reproducible peak effects even when only 10 min was allowed between administrations.
Buprenorphine 0.3 mg or fentanyl 0.125 mg i.v. were used to supplement nitrous oxide anaesthesia in a double-blind investigation of 40 patients undergoing major abdominal surgery. Initially both narcotics appeared to suppress tachycardia and increased arterial pressure in response to surgery, but 80% of the patients who received fentanyl eventually required a further supplement of halothane 0.5%, whereas no patient who received buprenorphine required halothane. Recovery from anaesthesia was similar in both groups, but the duration of analgesia after operation was significantly greater after buprenorphine than after fentanyl.
Alfentanyl is a new narcotic analgesic with a rapid onset and very short duration of effect, and a potency about one third of that of fentanyl. The respiratory effects of 1.6, 3.2 and 6.4 micrograms/kg Alfentanyl were studied in a randomised controlled trial in five volunteers. Alfentanyl 6.4 micrograms/kg induced a significant increase in respiration at 1 minute, then significant depression of mean minute volume 3 and 4 minutes after slow intravenous injection, compared with saline control, and pre-injection values. Mean end-expired carbon dioxide concentration was increased after Alfentanyl 6.4 micrograms/kg, significantly from 2 to 9 min after injection, and highly significantly at 3, 4 and 5 minutes. Examination of the effect on expired CO2 concentration at 4 minutes reveals a highly significant dose-response relationship with the three doses of Alfentanyl. The transient effect of ALfentanyl was confirmed by the fact that no change in mean ventilatory response to carbon dioxide was demonstrable 30 or 50 minutes after any dose. When Alfentanyl was given 1 minute before testing the ventilatory response to carbon dioxide the response curves showed a highly significant dose-related shift to the right. There were no significant changes in heart rate or blood pressure after Alfentanyl, but the drug produces the typical subjective effects of the opiates.
ICI 35868 (Diprivan), 1-2 mg/kg was used to induce anaesthesia in 20 patients, and the results compared with induction of anaesthesia by Althesin 0.5 ml/kg given to a similar group of 20 patients. ICI 35868 was effective in inducing anaesthesia, but produced more respiratory depression, and cardiovascular effects which were significantly different from those produced by Althesin. ICI 35868 gave a smoother induction. It is concluded that ICI 35868 is a promising new induction agent which may also find application for the maintenance of anaesthesia.
R39209 (Alfentanyl), a new narcotic analgesic with a uniquely short duration of effect, was used to supplement nitrous oxide and oxygen for the maintenance of anaesthesia. Twenty-two patients undergoing minor surgery were studied. Clinical anaesthesia was excellent or good in most (16) of the patients, and recovery was excellent or good in 18 patients, waking time being less than one minute in 15 patients. However the incidence of complications and side-effects, mainly movement, apnoea, difficulty in assisting ventilation, nausea and vomiting was high. Intravenous administration of R39209 during anaesthesia induced significant depression of respiratory rate and minute volume during the second, third and fourth minutes after injection. There was an unexplained significant rise in respiratory rate and minute volume in the first 30 seconds after the first injection. The first administration of R39209 also caused an unexplained, significant reduction in cardiac rate. An insignificant rise in mean systolic blood pressure followed injection of the drug. The transient effect of R39209 was confirmed in clinical practice, and the drug exhibited the features of a typical narcotic analgesic. It is concluded that R39209 will have a useful place in anaesthetic practice, and that better clinical results will be obtained with more experience of the drug, and better selection of indications for its use.
The use of mass spectrometers for total gas monitoring during anesthesia presents a number of problems which stem from the Cracking Pattern of the gases present, inlet design, viscosity variations, water vapour and machine deterioration. Some of these have been adequately solved, by making mechanical modifications to the inlet system, and by using more complex electronic circuitry to process the signals obtained. Remaining problems, however, still limit accuracy and ease of operation. CO2 measurements are particularly prone to error, especially when sampling halothane-containing gas which leads to significant internal production CO2. A study of the principal sources of error remaining in the machine suggests that the only definitive solution is to develop a microprocessor system which could cope with complex Cracking Patterns and non-linearities, and which would allow complete automation of the calibration procedure.
Explore the source record for details and available documents.
Occlusion pressure (Po max) was used to indicate the depression of respiratory drive following rapid administration of methohexitone 0.5 mg/kg and etomidate 0.067 mg/kg to fourteen patients under stable light anaesthesia. Methohexitone produced considerably more respiratory depression than etomidate, the difference probably being clinically significant. Po max is the maximum sub-atmospheric pressure generated in the trachea when inspiration is prevented by occlusion of the airway, at functional residual capacity. The factors concerning the use of this simple, non-invasive technique during anaesthesia are discussed, and suggestions made for producing consistent, useful, measurements.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The I.V. administration in dogs of high and massive doses of narcotics produced an acute rise in CO2 consumption, a rise of plasma catecholamines and other slight biochemical and metabolic perturbances. A general trend towards metabolic acidosis and hypermetabolism was noticed but important differences appeared according the drugs and doses chosen. The safety margin for metabolic toxicity (ratio between IV doses producing severe metabolic side-effects and doses necessary for deep surgical analgesia) were calculated for each narcotic and found as follows: 1 for pethidine, 3.3 for piritramide, 13 for morphine and phenoperidine, 12.5 for R 39 209, 60 for fentanyl, 800 for sufentanil and 4 000 for R 34 995. Drug associations may decrease or increase the metabolic safety margin of the narcotics. Beneficial associations with morphinomimetics are found with droperidol, etomidate and flunitrazepam.
Explore the source record for details and available documents.
The experimental design, described in part I, was again used here. The electrocortical activity was registered with an EEG amplifier using a bipolar derivation of needle electrodes fixed in the scalp of a dog in the fronto-occipital position. In this situation the convlusion threshold for the 8 substances is as follows: pethidine 20 mg.kg-1 I.V., piritramide 30, morphine 180, phenoperidine 4, R 39 209 5, fentanyl 4, sufentanil 4 and R 34 995 10 mg.kg-1 I.V. Comparing the I.V. doses producing severe convulsions with the doses necessary for deep surgical analgesia a safety margin of neurological toxicity was calculated. This was for pethidine 2.2, for piritramide 6.6, for phenoperidine 16, for R 39 209 62.5, for morphine 72, for fentanyl 160, for sufentanil 1 000 and for R 34 995 10 000. It is concluded that for pure narcotics there exists an inverse relationship between analgesic potency and neurological toxicity which is always accompanied by a hyperactivity of the automatic nervous system. Factors modifying the convulsive level of the narcotics are still under investigation. In the meanwhile it can be stated that the association of a strong narcotic with flunitrazepam, droperidol or etomidate will increase the convulsion threshold of the morphinomimetics.
A double-blind, between-patient comparison has been made of the effects of morphine 10 mg i.v. and buprenorphine 0.3 mg i.v. on the prevention of pain after operation. The drugs were given by the anaesthetist at the end of the operation, and the onset and severity of pain were assessed by a trained nurse. Both drugs caused a significant delay in the appearance of severe pain when compared with the control group, but with buprenorphine the mean delay of 10.5 h was more than twice that of morphine. The only side-effect to occur more frequently after administration of the analgesics was drowsiness, the incidence being greater after buprenorphine than after morphine.
In patients under anesthesia, ventilation is often monitored less adequately than circulation. A simple method, neglected in adults, is the use of a precordial or oesophageal stethoscope. Respiratory volumes may be measured directly, or inferred from flowrates or pressure changes. A rough measurement of inspired volumes may be made using a nonrebreathing valve, and controlling fresh gas input to maintain a constant underfilled reservoir bag. Spirometry of expired volumes is difficult and requires sophisticated apparatus. Respiratory volumes are easily inferred from flowrates using the Wright or Dräger respirometers. Flowrates may also be inferred from pressure changes, which are easy to record, as in the pneumotachorgraph. Accurate measurements require attention to many details, such as linearity of the transducer response over the flowrates measured. Calibration should be with the anesthetic gases used, at controlled temperature and humidity. Positive pressure ventilation peaks give a high flow artefact, and electronic drift requires regular recalibration. Electrical impedance changes may also be used to infer and record respiratory volumes, with reasonable accuracy if individual calibration is carried out. Anesthesia offers excellent opportunities to measure compliance and resistance, but itself changes these values, so that relation to normal values or changes due to pathology is difficult. Occlusion pressure is also readily measured during anesthesia, as an indication of respiratory drive, but rigid control of all other factors affecting respiratory muscle tensions is necessary.
Explore the source record for details and available documents.
In a double-blind trial, in a total of 45 patients, sulfentanil was compared with fentanyl and morphine in equipotent doses, as a narcotic supplement to anesthesia. Initially, morphine was shown to have a significantly longer duration of effect than fentanyl and sulfentanil, which for the first 3 doses had similar durations of action to each other. Later doses of fentanyl, however, had an extended effect, presumably because of cumulation. This was not seen with sulfentanil.