LOW VENTILATORY RESPONSE TO CARBON DIOXIDE NOT ASSOCIATED WITH INCREASED DEPRESSION BY MORPHINE

Ventilation (E), end-tidal (P')_co2 mixed venous Pco₂ (P_co2andthe ventilatory response to carbon dioxide (E/Pco₂) were measured before and within 90 min asgtermorphine 0.15 mg kg^–1 i.m. given to 17 adult patientsundergoing elective surgery under general anaesthesia. The hypothesisthat pastients with a low ventilastory response to carbon dioxideare more susceptible to the ventilatory depressant effecstsof morphine was tested. Morephine induced increases in PE'_co2andP_co2 were not correlasted witheither the slope or the position of the preinjection responseto carbon dioxide. Mean E/Pco₂was depressed after morphine (P <0.05), but individual responsesvaried widely. Seven pastients whose control E/Pco₂ was 9.9 litre min^–1kPa^–1 or lessdecreased E/Pco₂ after morphine.In four patients, E/Pco₂ increasedafter morphine; however, in each case, PE'co₂ and Pco₂ increased also. Morphine disphine displaced thecarbon dioxide response to the right (P < 0.001) but no correlationwas found between either the magnitude of the displacement orchange in slope and control E/Pco₂.The results suggest that patients with a low value for E/Pco₂ are not more susceptible tothe ventilatory depressant action of morphine.     

CONTROL OF BREATHING AFTER FENTANYL AND INNOVAR ANAESTHESIA

Ventilation (VI), end-tidal (Pco₂), mixed venous (PVco₂) andthe ventilatory response to carbon dioxide were measured beforesurgery, and during the first 4h of recovery in 18 adult patientswho underwent elective limb surgery under fentanyl or Innovaranaesthesia. End-tidal and mixed venous PCO₂ were increasedsignificantly in the first 150 min after the last dose of drug(P<0.001, P<0.01). but had returned to control valuesby 4 h. Ventilation and ventilatory response to carbon dioxidewere significantly depressed in all patients (P < 0.001),but returned to near control values at 4 h. Fentanyl and Innovaranaesthesia displaced the carbon dioxide response to the right,but no correlation was found between either the magnitude ofthe displacement of the response curve or the alteration inslope and the control values. This suggests that patients witha low value of VI/Pco₂ are not more susceptible to the ventilatorydepressant action of narcotic anaesthetics. Recovery of ventilatoryresponsiveness towards normal during the 4 h after anaesthesia,occurred in a graded and progressive manner; there was no evidenceof a biphasic pattern of recovery. ^*Present address: Centre for Advanced Studies in Health Sciences,Western Australian Institute of Technology, Bentley, WesternAustralia. Presented to the annual meeting of the Canadian AnaesthetistsSociety, Ottawa, Ontario, June 1978.     

A METHOD FOR ACHIEVING RAPIDLY STEADY-STATE BLOOD CONCENTRATIONS OF I.V. DRUGS

The theoretical basis of a pharmacokinetic method to obtainrapidly and maintain a steady plasma concentration of an i.v.drug is described. Computer simulations of morphine dispositionin man, using pharmacokinetic constants obtained from the literature,are provided as examples of steady-state dose regimens. Theusefulness and potential limitations of the method are discussed. ^*Presented in part at the 1978 meeting of the Canadian Anaesthetists'Society; the V European Congress of Anesthesiology, Paris 1978,and the 1979 meetings of the American Society for Clinical Pharmacologyand Therapeutics, Kansas City, and the Australian Society ofAnaesthetists, Adelaide, Australia.     

VENTILATORY EFFECTS AND PLASMA CONCENTRATION OF MORPHINE IN MAN

The relationship between the plasma concentration of morphineand morphine-induced changes in ventilation and the ventilatoryresponse to carbon dioxide was studied in 17 healthy adultsundergoing elective surgery under general anaesthesia. Eachsubject was given morphine sulphate 0.15 mg kg^–1 i.m.;ventilation (E), end-tidal Pco₂(PE'_CO2), mixed venous PV_CO2(P_CO2)and ventilatory response to carbon dioxide (E/P_CO2) were measured before and within 90 min afterinjection. Mixed venous P_CO2 and E/P_CO2were measured by standard rebreathing methods; plasma morphineconcentration was measured by radioimmunoassay. Maximum plasmamorphine ranged from 30 to 120 ng ml^–1, between 4 and60 min after injection. There was a significant increase inmixed venous PE'_CO2 (P<0.001), and PE'_CO2 (P<0.01) aftermorphine while E decreased insignificantly. Morphine displaced the carbon dioxide responsecurve to the right (P<0.01) and E/P_CO2decreased from 12.3 to 10.0 litre min^–1 kPa^–1 (P<0.05).The magnitude of changes in E and E/P_CO2 were not relatedto the peak plasma concentration of morphine or to the meanconcentration immediately before and after the carbon dioxideresponse measurement. Plasma concentrations of morphine, underthe conditions of the present study, are not an objective indicatorof pharmacological activity between one patient and another. Presented in part at the VI World Congress of Anaesthesiology,MexicoCity, Mexico, April 1976     

THE VENTILATORY RESPONSE TO CARBON DIOXIDE DURING PARTIAL PARALYSIS WITH TUBOCURARINE

The ventilatory response to carbon dioxide of five normal subjectswas measured at two levels of partial paralysis of the respiratoryand peripheral muscles with tubocurarine. During mild paralysisthe mean reduction of vital capacity was 14 per cent, maximumpleural pressure 19 per cent and grip strength 55 per cent ofmeasurements before curarization. With moderate paralysis, meanreduction of vital capacity was 34 per cent, maximum pleuralpressure 28 per cent and grip strength 94 per cent of controlmeasurements. There was no change in the ventilatory responseto carbon dioxide during mild or moderate paralysis.     

CONTROLLED HYPOTENSION FOR CEREBRAL ANEURYSM SURGERY IN THE PRESENCE OF SEVERE AORTIC COARCTATION

A patient is described with a bicuspid aortic valve and an undiagnosedaortic coarctation. presenting with a subarachnoid haemorrhage.A cerebral aneurysm was clipped under controlled hypotension.In view of the risk of inducing severe hypotension in the distalaorta in this patient, femoral arterial pressure was monitored.A marked reduction in the radial–femoral arterial pressuregradient during controlled hypotension was noted.     

USE OF SODIUM NITROPRUSSIDE FOR DELIBERATE HYPOTENSION DURING PREGNANCY

Deliberate hypotension with sodium nitroprusside was used tofacilitate surgery for cerebral aneurysm in two pregnant patients,with no apparent adverse effects on the fetus. The evidencethat nitroprusside is harmful to the fetus appears to arisefrom one animal experiment in which insufficient detail of dosagewas given.