VENTILATORY RESPONSES TO REBREATHING AND CARBON DIOXIDE INHALATION DURING ANAESTHESIA IN CHILDREN

In 12 spontaneously breathing intubated children (9.3–25kg), ventilatory responses to rebreathing and to the inhalationof carbon dioxide (CO₂) were investigated during halothane anaesthesiafor minor surgical procedures. A T-piece (Mapleson F system)was used, modified by the insertion of a pneumotachograph anda paediatric airway adaptor of an in-line capnograph in thepatient limb. Exhaled gas was collected for determination ofexpired CO₂ content. Measurements were made when the fresh gasflow (FGF) was at the borderline for rebreathing (FGF^r) andduring 10 min with a mean FGF 44% lower, producing a maximalinspired CO₂ (I_{CO2 max}) (%) of 1.45±0.38% (mean±1 SD). Measurements were repeated 5 min after returning to aflow exceeding FGF^r and then during CO₂ inhalation for 10 minafter the addition of 1.24±0.32 % CO₂ (mean±1SD) to this flow. During both rebreathing and CO₂ inhalationend-tidal CO₂ (E_CO2) was unchanged and did not increase significantly (18%), but duringCO₂ inhalation alveolar ventilation increased (P < 0.05),indicating an adequate and intact response to this level ofCO₂ inhalation. Estimations of I_{CO2 max} could be made from theexpression: l_CO2 max(%) = –0.7 x FGF/ +2.5 and FGF to minute ventilation () ratios lower than 1 were found to produce l_CO2max of 1.8% or higher. Such low FGF are likely to result inrebreathing within the alveolar ventilation and are thus ofclinical importance. We believe that to increase the marginof safety in anaesthetized spontaneously breathing children,FGF of at least 1.5 to 2 times should be used. Present addresses:^*Department of Anaesthesia, University HospitalS–22185 Lund, Sweden Department of Anaesthesia, Manchester Royal Infirmary, OxfordRoad, Manchester M13 9WL.     

VENTILATORY RESPONSE TO CARBON DIOXIDE DURING EXTRADURAL ANAESTHESIA WITH LIGNOCAINE AND FENTANYL

Twenty-seven patients undergoing extracorporeal shock-wave lithotripsyor knee arthroscopy received extradural anaesthesia with 2%lignocaine plus adrenaline 1 in 200000. They were allocatedrandomly to three groups, one receiving no fentanyl (n = 6),the two others receiving fentanyl 50 µg either extradurally(n = 15) or i.v. (n = 6). Three tests of sensitivity to carbondioxide (Read's method) were performed successively on eachpatient: before operation and at 1 and 2 h after the extraduralinjection. Whereas lignocaine and adrenaline alone had no significanteffects on basal ventilation and the ventilatory response tocarbon dioxide, extradural fentanyl caused a slight reductionin resting ventilatory rate and ventilation at 1 and 2 h withno change in resting end-tidal carbon dioxide concentration.In addition, the slope of the ventilatory response to carbondioxide was reduced slightly at 1 h and ventilation at end-tidalnCO₂ of 7.3 kPa was reduced also at 1 and 2 h. Conversely, thesame dose of fentanyl i.v. had lesser and shorter effects onventilation at rest and during carbon dioxide rebreathing. Ourresults show that fentanyl 50 µg given extradurally causedslight ventilatory depression which is probably clinically unimportant.     

CEREBROVASCULAR CARBON DIOXIDE REACTIVITY DURING EXPOSURE TO EQUIPOTENT ISOFLURANE AND ISOFLURANE IN NITROUS OXIDE ANAESTHESIA

We have studied the effects of hypocapnia on cerebrovascularchanges in two MAC-equivalent anaesthetic regimens, using thetranscranial Doppler technique as an index of cerebral bloodflow (CBF) in 24healthy ASA I patients undergoing spinal surgery.Eight of the patients were subjected to carbon dioxide reactivitychallenges in the awake state. Before surgery, the other 16patients received, in random order, either 1.15% isofluranein oxygen or 0.5% isoflurane with 70% nitrous oxide. Carbondioxide reactivity was calculated for each group as the increasein flow velocity per kPa change in PÉ_CO2 (cm s^–1kPa^–1). It was significantly greater for the isofluranegroup (14.09 (SD 2.44) cm s^–1 kPa^–1) and significantlyless for the isoflurane—nitrous oxide group (7.95 (1.32)cm s-^–1 kPa^–1) compared with the awake group (11.24(0.95) cm s^–1 kPa^–1). We conclude that cerebrovascularresponsiveness to changes in arterial carbon dioxide concentrationis influenced markedly by the anaesthetic procedure. Hyperventilationis more likely to affect CBF during isoflurane anaesthesia thanduring an MAC-equivalent isoflurane—nitrous oxide anaesthesia.     

PATTERN OF RESPIRATION AND RESPONSES TO CARBON DIOXIDE DURING TRICHLOROETHYLENE ANAESTHESIA IN THE CAT

Tidal volume (VT), minute ventilation (E), the duration of inspiration and expiration, andPa_co2, were measured via a tracheostomy in adult cats anaesthetizedwith 0.7%, 1% and 1.5% (inspired) trichloroethylene (TCE). Thetracheal cannula was occluded at intervals at the start of inspirationand the tracheal pressure was measured to assess the force ofcontraction of the respiratory muscles. Anaesthesia with TCE0.7% was associated with an increase in E, a reduction in VT, and a marked increase in respiratoryfrequency and mean inspiratory flow rate, but Pa_co2 values didnot differ significantly from those in conscious animals. Ventilationwas also greater than in conscious animals during anaesthesiawith TCE 1%. TCE 1.5% caused a significantly greater Pa_co2,than in conscious animals. All concentrations of TCE causeda reduction in the ventilatory response to carbon dioxide, measuredby the steady-state method. Cervical vagal section did not abolishthe tachypnoea caused by TCE. ^*Present addresses: Ente Ospedaliera Regionale, Ospedale Maggiore,Piazza Ospedale, 34100 Trieste, Italy. Present addresses: Department of Anaesthetics, Royal Infirmaryof Edinburgh, Edinburgh EH3 9YW.     

VENTILATION, VENTILATORY CARBON DIOXIDE AND HORMONAL RESPONSE DURING HALOTHANE ANAESTHESIA AND SURGERY IN CHILDREN AFTER MIDAZOLAM PREMEDICATION

In 14 intubated, spontaneously breathing children with bodyweight (bw) ranging from 8.3 to 25.6 kg, the influence of midazolam0.1 mg kg^–1 i.m. (group M_0.1', n = 7) and 0.2 mg kg^–1i.m. (group M_0.2' n = 7) as pre-medication, on sedation, ventilation,ventilatory response to carbon dioxide and hormonal stress responsewas studied in connection with minor surgical procedures duringhalothane anaesthesia. The concentrations of catecholamines,ACTH and cortisol were measured immediately after induction,during undisturbed anaesthesia, during surgery and 15 min afterthe end of the surgical procedure. Sedation was better and plasmacatecholamine concentrations during undisturbed anaesthesiawere less in children receiving the larger dose of midazolam.During surgery and in recovery there were no differences inhormone concentrations. In recovery, the concentrations of allhormones were significantly greater compared with during undisturbedanaesthesia. During surgery, VE and respiratory rate were somewhatlower in group M_0.2 while E'_CO2, was similar. A dose dependentdepression of the response to carbon dioxide was found. However,clinically, the response to carbon dioxide after surgery wasconsidered to be adequate in both groups. ^*Department of Anaesthesia, Manchester Royal Infirmary, OxfordRoad, Manchester Ml3 9WL. Department of Anaesthesia, University Hospital, S-221 85 Lund,Sweden Department of Clinical Chemistry, University Hospital, S-22185 Lund, Sweden Department of Anesthesiology, Vanderbilt University, Nashville,Tennessee 37232, U.S.A.     

CARBON DIOXIDE PRODUCTION IN CYANOTIC CHILDREN DURING ANAESTHESIA WITH CONTROLLED VENTILATION

Carbon dioxide production and ventilatory efficiency were measuredduring undisturbed anaesthesia with intermittent positive pressureventilation in 34 children about to undergo closed or open cardiacsurgery. Anaesthesia was provided with fentanyl or halothaneand nitrous oxide. There were 15 cyanotic and 19 acyanotic children.Children with cyanotic heart disease produced approximately20% less carbon dioxide per unit body weight than acyanoticchildren, but ventilation was approximately 20% less efficient.Adequate ventilation should therefore be obtained when "normal"ventilation in relation to body weight is used in cyanotic children. Previously presented at the Anaesthetic Research Society [1].     

CHANGES IN VENTILATORY PATTERNS DURING HALOTHANE ANAESTHESIA IN CHILDREN

Changes in ventialtory variables (VE, VE, f, T₁/T^tot. VT/T₁.PE'_co2) were studied in 12 unpremeicated children, weighingbetween 10 and 20 kg, during halothane anaesthesia. at an inspiredconcentration of 0.5% halothane, respiratory rate increased,VT decreased, and VE did not change markedly. When the inspired.;halothane concentration increased further, there was a significantdecrease in VE, mainly as a result of a marked decrease inVT.PE'_CO2 increased significantly and inspiratory duty cycle decreasedat high inspired halothane concentrations. On return to baseline(0.5% halothane), there was a significant decrease in inspiratorytiming and a significant increase in PE'_CO2- The relations betweenthese changes and the effect of halothane on inspiratory musclesare discussed.     

EFFECT OF PROPRANOLOL ON CATECHOLAMINE-INDUCED ARRHYTHMIAS DURING NITROUS OXIDE-HALOTHANE ANAESTHESIA IN THE DOG

In dogs under nitrous oxide-halothane anaesthesia, ventriculararrhythmias were produced by intravenous injection of adrenalineand noradrenaline 2–3 µg/kg or isoprenaline 1µg/kg,and completely prevented by propranolol 0.3 mg/kg. Adrenalineor noradrenaline (20–30 µg/kg) produced slow rateventricular extrasystoles and ventricular bigeminy, withoutincrease in the rate of sinus rhythm. Doses of 100 to 150 µg/kgproduced ventricular tachycardia in all and ventricular fibrillationin some experiments. Increase in sinus rate always precededventricular tachycardia. Isoprenaline 10 µ/kg producedventricular tachycardia preceded by an increase in sinus rate.Very large doses (50 µg/kg) produced a greater increasein sinus rate, and later ventricular tachycardia and even ventricularfibrillation resulted in all the experiments. Dosages of catecholamineswhich did not produce any increase in the rate of sinus rhythmnever produced ventricular tachycardia or fibrillation.     

THE RESPIRATORY RESPONSE TO CARBON DIOXIDE DURING INNOVAR-NITROUS OXIDE ANAESTHESIA IN MAN

In seven patients anaesthesia was induced by injection of asingle dose of Innovar and maintained with nitrous oxide andoxygen. Marked respiratory depression persisted for longer thanone hour. Tidal volume, respiratory rate and minute volume measurementswere inadequate indicators of this effect which is well shownby measurement of end-tidal carbon dioxide tension. The bestquantitation is the slope of the ventilatory response to elevatedcarbon dioxide tension, determined in l./min/mm Hg. Displacementof the response curve was very variable after loss of consciousness.The data indicate that spontaneous respiration with this anaesthetictechnique, as with the majority of other general anaesthetics,is accompanied by respiratory acidosis.     

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.     

OXYGEN CONSUMPTION AND CARBON DIOXIDE ELIMINATION IN INFANTS AND CHILDREN DURING ANAESTHESIA AND SURGERY

Oxygen consumption (VO₂, ml min^–1) and carbon dioxideelimination (VCO₂, ml min^–1), minute ventilation (VE),tidal volume (VT), rate of ventilation (f) and end-tidal carbondioxide concentration (E' _co2 %) were measured in 38 infantsand children (body weights 3.6–25 kg). Four children (bodyweight < 5 kg) had congenital heart malformations and werestudied during controlled mechanical ventilation, where-as theremainder (n = 34) who were healthy, breathed spontaneously.Anaesthesia was maintained with oxygen in air (Fl_O2 0.45) andhalothane through a non-rebreathing circuit. Minute ventilationwas measured by pneumo-tachography, E'_CO2 with an in-line infra-redcarbon dioxide meter and gas concentrations with a mass spectrometer.There were no differences in VO₂ and VCO₂ between children withand without heart disease. VO₂ was related to body weight bythe equation: VO₂ = 5.0xkg+19.8 (r = 0.94) and VCO₂ to bodyweight by the equation: VCO₂ = 4.8xkg+6.4 (r = 0.94). Therewere no differences between VO₂ or VCO₂ before and after thestart of surgery. In 11 of 21 patients weighing less than 10kg, a reduced VCO₂ was noted, giving respiratory quotients ofless than 0.7. It is speculated that this age-dependent variationof VCO₂ may result from partial inhibition of lipolysis in brownadipose tissue produced by halothane.     

RESPIRATORY EFFECTS OF NITROUS OXIDE DURING ISOFLURANE ANAESTHESIA IN CHILDREN

Respiratory effects of nitrous oxide and isoflurane were studiedin 13 children (mean age 45.6± 19.3 months, mean weight14.9±4.8kg) during surgery under continuous extraduralanaesthesia. Three different anaesthetic states were studied:(1) isoflurane 0.5 MAC in oxygen (27 study periods), (2) isoflurane0.5 MAC with 50% nitrous oxide (32), (3) isoflurane 1 MAC inoxygen (25). End-tidal carbon dioxide (PE¹_CO2) and isoflurane,respiratory indices (tidal volume, VT; minute ventilation, VE;mean inspiratory flow, VI; respiratory frequency f, effectiveinspiratory timing T1/T^tot were measured. The addition of nitrousoxide (comparison of respiratory variables obtained in 25 successiveperiods at(1) and (2)) produced a significant increase in PE'_CO2significant decreases in VT, VE and VI, a significant increasein f. The increase in alveolar concentration of isoflurane ((1)compared with (3) in 25 successive periods) was associated witha significant increase in PE'_CO2 significant decreases in VT,VE, VI and a significant increase in f. The equipotent anaestheticstates (2) and (3) were compared in 21 successive periods. Inchildren, the net result of substituting nitrous oxide for anequal MA C fraction of isoflurane was to produce a smaller decreasein Vr responsible for a smaller decrease in VE without significantchange in respiratory rate.     

CARBON DIOXIDE ELIMINATION DURING INSUFFLATION ANAESTHESIA

Carbon dioxide elimination during apnoea was measured in sixtypatients undergoing diagnostic bronchoscopy. Paralysis was maintainedusing suxamethonium after thiopentone induction of anaesthesia.In forty patients a 50 per cent mixture of nitrous oxide andoxygen was insufflated by nylon catheter in the trachea at arate of 10 l./min. The mean quantity of carbon dioxide eliminatedwas approximately 20 ml/min (range 0–0.8 per cent). Intwenty patients without insufflation the corresponding ratewas approximately 6 ml/min (range 0–0.25 per cent). Therelationship of this finding to the known effect of the heartbeatin producing a small amount of alveolar ventilation is discussed.     

EFFECT OF NALBUPHINE HYDROCHLORIDE ON THE VENTILATORY AND OCCLUSION PRESSURE RESPONSES TO CARBON DIOXIDE IN VOLUNTEERS

We studied the effect of nalbuphine on the ventilatory and occlusionpressure reponses to carbon dioxide rebreathing in six healthymale volunteers (mean age 25.5 yr) in a single-blind laboratorystudy. On four separate days volunteers were assigned randomlyto receive either placebo (0.9% sodium chloride) or three i.v.doses of nalbuphine (15, 30 and 60 mg 70 kg^–1), followed90 min later by naloxone 0.4 mg 70 kg^–1. Duplicate rebreathingtests were performed and the mean intercept at PE'_co2 7 kPaand the slopes of the linear relationship between inspiratoryminute ventilation (Vl) or occlusion pressure (P_0.1) with PE'_co2were measured. Nalbuphine significantly decreased the mean interceptof the Vl (P < 0.01) and P_0.1 (P < 0.05) responses, butcaused no changes in the slopes. No significant difference betweenthe doses was noted, suggesting that an Effect maximum (E'max)for respiratory depression was reached with a dose of approximately15 mg 70 kg^–1. Naloxone was less effective in antagonizingthe depression in Vl at the higher dose of nalbuphine. SimilarP_0.1 values were associated with the same inspiratory flow rate(1 litre s^–1) before and after drug treatment, suggestingthat nalbuphine acts centrally to depress ventilation. Sedationincreased significantly following each dose of nalbuphine (P< 0.001). No demonstrable difference between the doses wasshown, suggesting an Effect maximum (E'max) for sedation wasreached at about 15 mg 70 kg^–1. Administration of nalbuphinewas associated with pain at the injection site, dizziness, dreaming,nausea and vomiting. Cardiovascular stability was maintainedin all subjects.     

VENTILATORY RESPONSE TO CARBON DIOXIDE IN PATIENTS WITH HOMOZYGOUS SICKLE-CELL DISEASE

The ventilatory response to carbon dioxide was measured by arebreathing technique in 21 Nigerians who had homozygous sickle-celldisease. The slope of the carbon dioxide response curve wasobtained by plotting the ventilation at successive half-minuteintervals against the corresponding mean end-tidal Pco2. Ourresults showed that sickle-cell patients are as sensitive tocarbon dioxide as are normal subjects.     

CARBON DIOXIDE TENSIONS IN NON-ARTERIALISED CAPILLARY AND ARTERIAL BLOOD DURING ANAESTHESIA

In der vorliegenden Untersuchung werden die Werte der Wasserstoffionenkonzentration und der Kohlensäurespannung von 31 Kapillarblutproben aus den Ohrläppchen und 21 Proben aus den Fingerkuppen mit den Werten verglichen, die aus arteriellen Blutproben bei den gleichen Patienten stammten. Alle Proben wurden während der Narkose von chirurgischen Patienten abgenommen. Die Messungen wurden in der Hauptsache nach der Methode von P. A strup (1959)¹ und O. S iggaard A ndersen et al. (1960)^4,5 vorgenommen.
Es konnte festgestellt werden, dass die pH- und PCO₂-Werte aus den Ohrläppchenproben für praktische Zwecke ausreichend mit denen übereinstimmten, die in gleichzeitig abgenommenem arteriellem Blut gefunden wurden. Dies war auch dann der Fall, wenn eine ausgesprochene respiratorische Alkalose vorlag und auch wenn keine Massnahmen getroffen wurden, das Kapillarblut des Ohrläppchens vor der Abnahme zu arterialisieren.
Zwischen dem arteriellen Blut und dem nicht-arterialisierten Kapillarblut, das aus der Fingerbeere entnommen wurde, fand sich eine geringere Übereinstimmung.     

CARBON DIOXIDE OUTPUT IN SPONTANEOUSLY BREATHING INFANTS DURING ANAESTHESIA AND SURGERY

Twenty-eight infants were anaesthetized with halothane, nitrousoxide and oxygen and allowed to breathe spontaneously througha non-rebreathing system during minor paediatric surgery. Carbondioxide output was correlated negatively with body weight forinfants greater than 10 kg, but not for children less than 10kg. Carbon dioxide output was unchanged compared with beforesurgery.     

NEUROMUSCULAR AND CARDIOVASCULAR EFFECTS OF MIVACURIUM CHLORIDE (BWB1090U) DURING NITROUS OXIDE-FENTANYL-THIOPENTONE AND NITROUS OXIDE-HALOTHANE ANAESTHESIA

Seventy-two adult surgical patients were studied to compareneuromuscular and cardiovascular effects of mivacurium chlorideduring nitrous oxide-fentanyl-thiopentone (BAL group) or nitrousoxide-halothane (HAL group) anaesthesia. Eighteen patients inthe BAL group received an initial bolus of mivacurium, eitherthe ED₂₅ (n = 9) or the ED50 (n = 9) (0.03 and 0.05 mg kg^–1).These doses were based on the assumption that the slope of thedose-response curve during nitrous oxide-opioid anaesthesiawould be approximately the same as the slope of the neuromuscularresponse from the first human studies with mivacurium. Twenty-sevenadditional patients were allocated to subgroups of nine patientsto receive mivacurium 0.04. 0.08 or 0.15 mg kg^–1. Twenty-sevenpatients in the HAL group were allocated also to subgroups ofnine patients to receive mivacurium 0.03, 0.04 or 0.15 mg kg^–1.During stable anaesthesia, mean endtidal halothane concentrationswere maintained at 0.49±0.01%. The estimated ED₅₀, ED₇₅and ED₉₅ for BAL and HAL groups were 0.039, 0.05 and 0.073 mgkg^–1 and 0.040, 0.053 and 0.081 mg kg^–1, respectively.Halothane did not potentiate maximum block or time to maximumblock. Halothane did affect spontaneous recovery. With the 0.15-mgkg^–1 dose, time to 95% recovery was prolonged significantlyin the HAL group (30.0 (SEM 1.4) min) compared with the BALgroup (24.1 (1.5) min). Recovery index from 25% to 75% recoverywas also prolonged significantly in the HAL group (7.0 (0.4)min) compared with the BAL group (5.4 (0.4) min). There wereno significant haemodynamic changes in groups given mivacuriumdoses up to and including 2 x ED₉₅ by bolus i.v. administration ^*Department of Anesthesia, University of Iowa Hospitals andClinics, Iowa City, Iowa 52242, U.S.A.     

INSPIRATORY TO END-TIDAL OXYGEN DIFFERENCE DURING NITROUS OXIDE ANAESTHESIA

In order to evaluate the value of the inspiratory to end-tidaloxygen concentration difference (I_O2–É_O2) as amonitor during general anaesthesia. we studied 40 orthopaedicpatients allocated randomly to four groups: anaesthesia withenflurane or isoflurane in nitrous oxide with either spontaneousor controlled ventilation. (I_O2–É_O2) followed anasymptotically increasing curve because of decreasing uptakeof nitrous oxide. At 1 h, (I_O2–É_O2) approachedthe end-tidal carbon dioxide concentration (É_CO2 Duringspontaneous ventilation, (I_O2–É_O2) correlated bestwith É_CO2. During controlled ventilation, there was anegative correlation between (I_O2–É_O2) and nitrousoxide uptake rate. Changes in oxygen uptake rate were reflectedin (I_O2–É_O2) provided that the total ventilationvolume was constant and the nitrous oxide uptake rate approachedsteady state conditions.     

EFFECT OF PROPIOMAZINE, PERPHENAZINE, PROMETHAZINE AND PROMAZINE ON ADRENALINE-INDUCED VENTRICULAR ARRHYTHMIAS DURING NITROUS OXIDE-HALOTHANE ANAESTHESIA IN THE DOG

Ventricular tachycardia was produced in the dog by intravenousinjection of 2–3 µg/kg of adrenaline during nitrousoxide-halothane anaesthesia. On a weight basis, propiomazinewas found to be as effective as perphenazine in preventing thearrhythmias. Promethazine and promazine showed similar effectsin much higher doses. The protection provided by all these drugscould be surmounted by doses of adrenaline of 4–6 µg/kg.Propiomazine did not produce any action on blood pressure whereasthe other drugs tested produced a prolonged fall in pressurein all the experiments. Since the clinical dose of propiomazineis 2–4 times that of perphenazine, it is possible thatthe former may prove superior to the latter in clinical trials.