A NEW METHOD FOR MEASURING PCO2 DURING ANAESTHESIA

We have evaluated a new method for measuring the oxygenatedmixed venous () in patients undergoing general anaesthesia. Thelungs were inflated with a gas mixture containing 0% carbondioxide and then 12% carbon dioxide and the expired gas wasanalysed both before and after a brief period of breath-holding. was estimated from the differences in carbon dioxide concentration before and after the apnoeicperiod. Simultaneous measurements of were made in blood obtained from radial artery puncture. Therange of , studied was 3·2–6·13 kPa. The relationship between mixed venous and arterial was found to be = 0.87 –0.44 (r= 0·91). We conclude that this method for measuring can be used during anaesthesia allowing to be estimated with considerable accuracy.     

EFFECTS OF INCREASED CARDIAC OUTPUT ON PULMONARY BLOOD FLOW DISTRIBUTION DURING LOBAR VENTILATION HYPOXIA AND COLLAPSE

Electromagnetic flow probes were placed around the pulmonaryartery and left lower lobe artery in anaesthetized open-chestdogs in order to measure possible changes in the ratio of lobar-to-totalpulmonary blood flow (l/t) in response to changes in cardiacoutput produced by the opening of arterio-venous fistulae orfluid loading. Ventilation of the lobe with 7% oxygen or lobarcollapse reduced l/t by 35% and 42%, respectively, butthere were no significant changes in l/t in response to increases in t of 29–133%. It is concludedthat the changes in t, pulmonary vascular pressures and mixed venous PO₂ within the range studieddid not influence l/t.     

REVERSAL OF NITROUS OXIDE-INDUCED DEPRESSION OF HYPOXIC PULMONARY VASOCONSTRICTION BY LIGNOCAINE HYDROCHLORIDE DURING COLLAPSE AND VENTILATION HYPOXIA OF THE LEFT LOWER LOBE

The blood flow to the left lower lobe (L), and total (T) pulmonary blood flow, were measured in 10 open-chest dogs usingelectromagnetic flowmeters. Ventilation of the left lower lobewith 7% oxygen in nitrogen produced a greater reduction in L/T (41%) than lobar ventilation with 7% oxygen in nitrous oxide(33%). Lobar collapse reduced QL/QT by 65%, but there was nochange in L/T when 50% nitrous oxide was administered to theright lung. The i.v. infusion of lignocaine hydrochloride duringventilation of the lobe with 7% oxygen in nitrogen producedno change in L/T. However, lignocaine infusion during lobar ventilationwith 7% oxygen in nitrous oxide produced a further reductionin L/T to a value which was not significantly differentfrom that observed during ventilation with 7% oxygen in nitrogen.Lignocaine had no effect on L/T during lobar collapse whether theright lung was ventilated with 50% oxygen in nitrogen or 50%oxygen in nitrous oxide. It is concluded that lignocaine reversesthe depression of hypoxic pulmonary vasoconstriction producedby lobar ventilation with nitrous oxide.     

AN EVALUATION OF REBREATHING WITH THE BAIN SYSTEM DURING ANAESTHESIA WITH SPONTANEOUS VENTILATION

Data from 12 anaesthetized patients breathing spontaneouslyfrom the Bain system were used to calculate the degree of rebreathingoccurring when the fresh gas flowrate(F) was equal to 2,1 and 0.7 times the estimated normalminute ventilation (_tot)- Measurementsof the expired minute volume (E) and end-tidal carbon dioxide tension (PE'_CO2) were made to determinethe effects of this rebreathing. No rebreathing occurred whenF was equal to twice tot. When F was equal to tot rebreathing was usually small in amount and produced no changes in E or PE'_CO2. Changes attributable torebreathing occurred in only two patients when F was reduced to 0.7 _tot.These results are explained by the presence of anaesthesia-inducedventilatory depression and favourable changes occurring in therespiratory wave forms in the majority of patients studied.In some patients, greater values of E and rebreathing occurred in response to strong surgical stimulation.The net result of increased ventilation in these patients wasa decrease in PE'_CO2-,. It is concluded that during anaesthesia,when the Bain system is used with F equal to _tot, any increasein PE'_CO2 which may result from rebreathing is likely to besmall and seldom of clinical importance.     

FRESH GAS REQUIREMENTS OF AN ENCLOSED AFFERENT RESERVOIR BREATHING SYSTEM IN ANAESTHETIZED, SPONTANEOUSLY VENTILATING CHILDREN

We have determined the minimum fresh gas flow rate (F) for use with the Ohmeda enclosedafferent reservoir breathing system (EAR) in 10 anaesthetizedchildren breathing spontaneously. First, we determined the F required to prevent rebreathing asdetected by increased total ventilation (E) and end-tidal carbon dioxide partial pressure.Second, we used a mathematical model to calculate the degreeof rebreathing occurring at each F.A F equal to the predictedalveolar ventilation was sufficient to prevent clinically detectablerebreathing in all pateints. From the model, no rebreathingoccurred when F//E was 0.78 or more. We have shown previously thatthe EAR functions efficiently during controlled ventilationwith a F = 0.6x weight^0.5.As this F is slightly greaterthan the predicted alveolar ventilation, we suggest that theEAR may be used with a F =0.6 x weight ^0.5 regardless of the mode of ventilation.     

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.     

A SYSTEM FOR THE CONTINUOUS MEASUREMENT OF OXYGEN UPTAKE AND CARBON DIOXIDE OUTPUT IN ARTIFICIALLY VENTILATED PATIENTS

A continuous, non-invasive system is described for measuringoxygen uptake () and carbon dioxide output () in mechanically ventilated patients. Inspiratory and mixed expiratory gas sampleswere pumped through fine-bore tubing to a remote mass spectrometerfor analysis. The expiratory flow transducer of a Siemens Servo900B ventilator was used for expiratory flow measurement andinspiratory flow was calculated from this using the Haldanetransformation. A desk-top computer calculated , and respiratory quotient. The system has been validated against standard methodsof gas analysis and flow measurement ( mean difference –lOml min^–1: SD9.13; mean difference 8.12ml min^–1:SD4.66). Comparison with Douglas bag measurements in patientshas been made ( mean difference 10.7ml min^–1: SD9.8; mean difference –1.07ml min^–1: SD4.7).     

REBREATHING CHARACTERISTICS OF THE BAIN CIRCUIT An Experimental and Theoretical Study

The Bain circuit was studied in a model lung on the assumptionthat, in addition to the ratio of fresh gas flow to total ventilation(FG/E), different time fractions of the respiratory cycle might influencerebreathing. We found that the time fraction for active expiration(FE_t) governed rebreathing for each FG/E value. With FE_t, as an independentvariable, a theoretical formula was derived for rebreathing.Rearranging this formula made it possible to calculate the necessaryincrease in ventilation to keep end-tidal carbon dioxide constantfor each FG/E. Thus, at a fresh gas flow of 70 ml kg^-1 min^-1,I has to be increased 2.6 times. For spontaneously breathing patients inhalation anaestheticsthat do not depress carbon dioxide sensitivity seem to be bettersuited to use in the Bain circuit. The FE_CO2 can then kept constantthrough increased ventilation in spite of the concomitant increasein rebreathing     

PULMONARY BLOOD FLOW DURING CLOSED HEART SURGERY: Use of a Modified Formula Ratio to Assess Adequacy of Palliation of Systemic-Pulmonary Artery Shunts

The ability to assess changes in pulmonary blood flow, usinga modified ratio (), was evaluated in 12 infants withcongenital heart disease and complete intracardiac mixing whounderwent modified Blalock-Taussig shunt procedures. At thevarious measuring stages there were no major changes in meanarterial pressure or heart rate. Arterial oxygen tensions andsaturation increased (P < 0.01) and the arterial to end-tidalcarbon dioxide difference (Pa_CO2–PE'_CO2) was significantlyreduced (P < 0.001) after completion of the shunt procedure.There was a significant increase in mean after chest closure (P < 0.001), which was seento correlate well with early clinical outcome. Two patientswho did not demonstrate any increase in over the course of the procedure had failed shunts.The limitations of use of the are discussed. A modified ratio of less than unity after surgery is strongly indicativeof inadequate palliation. Present address: Department of Anaesthesiology, University ofTexas Health Science Center at Dallas, 5323 Harry Hines Blvd,Dallas, Texas 75235, U.S.A.     

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     

PHARMACOKINETICS OF ALTHESIN

The fourth and sixth equations towards the bottom of the secondcolumn of this page should be amended, respectively, to:      

RELATIONSHIP OF VENTILATORY DEPRESSION TO STEADY-STATE BLOOD PETHIDINE CONCENTRATIONS

An i.v. infusion regimen was developed to permit rapid attainmentof steady-state blood pethidine concentrations (C_p26). In 10adult volunteers (12 studies) the relationship of pethidineC_p26 to the ventilatory effects of the drug were examined. Meanpethidine C_p26 ranged from 170 to 1320 ng ml_–1, with amedian C_p26 of 480 ng ml^–1. Increased end-tidal (PE' _co2)and mixed venous and decreased slope (I/Pco₂) and position(ISO-I) of the carbon dioxide response wereall significant (P<0.001) for C_P26. (1) 480 and (2) >480ng ml^-1. The averaged changes in PE'_co2, ,I/Pco₂, and ISO-I expressed as a per cent of respectivecontrol variables, were shown to be linear functions of C_P26.It is concluded that, under conditions of C_P26, significantventilarory depression occurs at blood pethidine concentrationsless than those required for analgesia. The possible significanceof these findings in volunteers is discussed in terms of thisapplication to the clinical setting of postoperative pain andits management after general anaesthesia.     

ENCLOSED AFFERENT RESERVOIR BREATHING SYSTEMS: Description and Clinical Evaluation

A new group of breathing systems, namely the Enclosed AfferentReservoir (EAR) systems, is described. They allow for the selectiveelimination of alveolar gas in association with both spontaneousand controlled ventilation. A comparison with the Bain systemin controlled ventilation demonstrates greater efficiency ineliminating carbon dioxide. A fresh gas flow (F) of 70 ml kg^–1 min^–1 using an EAR systemgave mild hypocarbia which equated to a F of 100 ml kg^–1 min^–1 using the Bainsystem. Smaller minute volumes of ventilation are required foroptimal performance than with the Bain system. The minimum recommendedminute volume of ventilation (l) should equal F plus anatomical deadspace ventilation (D^anat).The pattern of ventilation appears to have little influenceupon the efficiency of carbon dioxide elimination when usingan EAR system, whereas the Bain system does appear to be affected.     

HIGH FREQUENCY JET VENTILATION: THE INFLUENCE OF DIFFFERENT METHODS OF INJECTION ON RESPIRATORY PARAMETERS

Fourteen critically ill patients with ventilatory failure wereventilated with HFJV using a constant driving pressure of 3atm and a constant I: E ratio of 0.43. In six (group I) HFJV,using a frequency of 100 b.p.m., was delivered via a proximalinjector cannula. Four injector cannulae (i.d. 1.8, 1.6, 1.4and 1.2 mm, respectively) were used at random. In eight patients(group II), HFJV using three frequencies (100, 300 and 600 b.p.m.)was administered either via a 1.8-mm i.d. proximal injectorcannula (proximal injection), or via a Hi-Lo jet tracheal tube(distal injection). The following indices were measured in vivo:mean airway pressure (P_sw), mean pulmonary volume above apnoeicFRC (), mean alveolar pressure (clamps method) and arterial blood-gas tensions. Injected volume(Vinj), entrainment (E) and tidal volume (VT) were measuredin vitro using a water-sealed spirometer. Operating pressure(the pressure in the connecting tube) was measured directlyusing a high pressure calibrated transducer. In group I, Psw, Pao2 Vinj and VT significantly decreased whereas operating pressure and E significantly increasedwhen the internal diameter of the injector cannula was reduced.In group II, Psw, , E, VT and operating pressure significantly decreased, whereas Vinj increasedand Pao2 and Paco2 remained unchanged, when proximal injectionwas switched to distal injection. In both groups, a significantrelationship was found between operating pressure and E. Ata constant driving pressure, operating pressure increased withnarrow injector cannulae and increased frequency, and decreasedwhen proximal injection was switched for distal injection. Presented in part at the Annual Meeting of the American Societyof Anesthesiologists, New Orleans, October 1984.     

PHENOTYPING OF INDIVIDUALS SENSITIVE TO SUXAMETHONIUM: The Cholinesterase Research Unit at the Royal Postgraduate Medical School

Four hundred and thirty blood samples from suxamethonium-sensitiveindividuals have been phenotyped by the Cholinesterase ResearchUnit following its transfer from Exeter to the Hammersmith Hospital.The distribution of genotypes has been shown to be similar tothat found in Exeter. Screening for the and genes has not yielded any major differences in the gene frequencies ofsensitive individuals, even during pregnancy. The uneven sexdistribution of the patients, as well as other unusual pointsthat have arisen, are discussed. A new gene for the biosynthesisof cholinesterase has probably been identified.     

A SIMPLIFIED APPROACH TO THE EFFECT KINETICS OF ATRACURIUM

The combination of the Hill equation, which describes the concentration—effectrelation, with the monoexponential function for the terminaldecline of plasma concentration, yields a compound time constant,. This constant is a combination of the terminal elimination half-life () and the exponent (s) of the Hill equation and maybe used to describe the time course of recovery from neuromuscularblock. The constant may be estimated by non-linear curve fittingto f, the effect expressed as fraction of maximal effect, orby linear regression of the logit function of f. The methodswere validated using plasma concentration and effect data fromseven patients administered atracurium. The two methods utilizingeffect data alone yielded values of 4.2 (0.7) min and 4.3 (0.5)min (mean (SEM)), respectively, for compared with 4.1 (0.6) min when the constant was calculatedusing plasma concentration data for and curve fitting to the concentration—effect data todetermine s. These methods offer and objective measure of therate of recovery and a means of testing if redistribution orelimination is the primary process in the termination of drugeffect.     

VENTILATORY RESPONSES TO CARBON DIOXIDE IN CHILDREN DURING NITROUS OXIDE-HALOTHANE ANAESTHESIA

The ventilatory response to carbon dioxide was studied in 12unpremedicated children, aged 20–68 months, weighing between10 and 20 kg, under nitrous oxide-halothane anaesthesia. Tidalvolume (VT) and end-tidal carbon dioxide tension (PE'_CO2) werecontinuously measured by pneumotachograph and capnograph. Minuteventilation (), respiratory rate (f), mean in-spiratory flow (VT) and effective inspiratorycycle (T1/T^tot) were calculated during anaesthesia at threedifferent inspired halothane concentrations (0.5, 7 and 1.5%).The ventilatory response to carbon dioxide was determined byrelating the increase in ventilation during exposure to 2% carbondioxide to the change in end-tidal carbon dioxide concentration.When the inspired concentration of halothane increased, therewere significant decreases in , VT, , and a significant increase in PE'_CO2 The slope of the carbon dioxide response under lightnitrous oxide-halothane anaesthesia (0.5% halothane) was relativelyflat (18.64 ml min^–1 kg^– mm Hg^-1) when comparedwith the mean values published for anaesthetized adults, childrenor neonates. When the inspired concentration of halothane wasincreased, the slope decreased significantly (39% of initialvalue at 1 % inspired halothane, 26% at 1.5%). The additionof carbon dioxide produced significant increases in , VT and but no change in respiratory rate. No statistical differencewas observed in the slope of carbon dioxide response betweenthe initial and "control" periods which were measured at thesame inspired halothane concentration (0.5%).     

Effects of milrinone on jugular bulb oxygen saturation and cerebrovascular carbon dioxide reactivity in patients undergoing coronary artery bypass graft surgery

Background. Jugular bulb oxygen saturation () is a surrogate marker for global cerebral oxygenation. The effectof milrinone on and the cerebrovascular carbon dioxide reactivity (CCO2R) was investigated. Methods. Thirty patients scheduled for coronary artery bypassgraft surgery (CABG) were studied prospectively. After sternotomy,normoventilation (at T₁; =4.7–5.0 kPa) and hyperventilation (at T₂; =3.3–3.7 kPa) were induced and the changes in () and (), and (CCO₂R) were measured. After normoventilationwas re-established (at T₃), milrinone 50 µg kg^–1was given (at T₄), followed by hyperventilation (at T₅), and, and CCO₂R were measured. Results. After milrinone administration at normoventilation(T₃ and T₄), cardiac index and mixed venous oxygen saturationincreased, while mean arterial pressure and systemic vascularresistance index decreased, without a significant change in. Before milrinone administration (T₁ andT₂), hyperventilation decreased and , and showed positive linear correlation with . After milrinone administration (T₄ and T₅), hyperventilation decreased and , and showed positive linear correlation with . There was no significant difference in CCO₂R before and after milrinone administration(13.3 (5.7)% kPa^–1 and 12.3 (3.9)% kPa^–1, respectively). Conclusions. Although milrinone induced significant haemodynamicchanges, and CCO₂R were unchanged duringits administration.     

THE CONCEPT OF DEADSPACE WITH SPECIAL REFERENCE TO THE SINGLE BREATH TEST FOR CARBON DIOXIDE

We present a review and a theoretical analysis of factors determiningairway deadspace (VD^aw) and alveolar deadspace (VD^alv), thetwo constituents of physiological deadspace (VD^phys). VD^aw isthe volume of gas between the lips and the alveolar/fresh gasinterface, the location of which is determined by inspiratoryflow pattern and airway geometry. VD^alv can be caused by incompletealveolar gas mixing and associated / mismatching within the terminal respiratoryunits, temporal / mismatching within units, spatial / mismatching between units, and venous admixture. Most causes of VD^phys are influencedby inspiratory flow pattern and the time available for gas diffusionand distribution. Analysis can be made from the single breathtest for carbon dioxide (SBT–CO₂) which is the plot offraction of carbon dioxide in expired gas against expired volume.The common causes of VD^alv are associated with a sloping SBT-CO₂phase III. Combination of SBT-CO₂ with PaCO₂ yields VD^phys andVD^alv. A sloping phase III with a negative arterial-end-tidalPco₂ gradient implies compensation by perfusion for early emptying,overventilated alveoli.     

ERRATA

Delete: "During infusions of alfentanil... can be derived". Insert: "During infusions of fentanyl at 3 µg kg^–1h^–1,the plasma concentration was 3.28±0.54 ng ml^–1,from which a clearance of 15.2 litre kg^–1 min^–1can be derived." Page 123. Formula for A (ml min^–1) should be: A (ml min^–1) = Page 258, line 13. The dose of pancuronium should have been0.1 ng kg^–1 and not 0.001 ng kg^–1 as printed.