EFFECTS OF NITROUS OXIDE AND VOLATILE ANAESTHETICS ON CEREBRAL BLOOD FLOW

Nitrous oxide and halogenated anaesthetic agents are often administeredconcurrently during neuroanaesthesia. To assess the interactiveeffects of these agents on cerebral blood flow (CBF), we havemeasured CBF by ¹⁴C-iodoantipyrine autoradiography, in normocapnicrats receiving either 0.5 or 1.0 MAC of volatile agent alone(halothane or isoflurane) or 0.5 MAC of volatile agent+0.5 MACnitrous oxide. CBF (global and regional) was significantly greaterat 1.0 MAC compared with 0.5 MAC, regardless of how 1.0 MACwas achieved (agent alone or agent+nitrous oxide) (P < 0.05).The addition of 0.5 MAC nitrous oxide to 0.5 MAC halothane resultedin flows similar to those produced by 1.0 MAC halothane alone.In contrast, the addition of nitrous oxide to 0.5 MAC isofluraneresulated in flow values significantly greater than those measuredduring 1.0 MAC isoflurane alone. We conclude that the use ofnitrous oxide, as opposed to an increased dose of volatile agent,has no advantage in respect of minimizing anaesthetic-inducedincreases in cerebral blood flow.     

Effect of 1 or 2 MAC isoflurane with or without ketanserin on cerebral blood flow autoregulation in man

We have studied the effect of 1 or 2 MAC isoflurane with orwithout ketanserin on cerebral blood flow (CBF), cerebral oxygenmetabolism (CMRO₂) and CBF autoregulation in 20 adult patientsundergoing lumbar disc surgery. Ten patients received ketanserinand 10 isotonic saline. CBF measurements were started after1 h of infusion of saline or ketanserin. The patients were anaesthetizedwith thiopentone 5 mg kg^–1 followed by isoflurane. During1 MAC of isoflurane, baseline values were recorded and thenCBF autoregulation was examined (mean arterial pressure increasedby about 30% with angiotensin). The sequence was repeated with2 MAC of isoflurane. CBF was measured by the i.v. xenon-133technique. CMRo₂ was calculated as the product of CBF and thecerebral arterio-venous oxygen content difference. Ketanserinhad no effect on CBF, CMRo² or CBF autoregulation during isofluraneanaesthesia, therefore all patients were pooled for evaluationof the effect of isoflurane. Increasing isoflurane anaesthesiafrom 1 to 2 MAC increased mean CBF from 41 to 49 ml /100 g min^–1(P<: 0.01) and decreased mean CMRo₂ from 1.5 to 1.1 ml/100g min^–1 (P < 0.001) and thus abolished the couplingbetween flow and metabolism. The CBF autoregulation test indicatedthat autoregulation was disrupted at 2 MAC, but not during 1MAC isoflurane anaesthesia. (Br. J. Anaesth. 1994; 72: 66–71)     

Effects of xenon anaesthesia on the circulatory response to hypoventilation

Background. Circulatory response to hypoventilation is aimedat eliminating carbon dioxide and maintaining oxygen delivery(DO₂) by increasing cardiac output (CO). The hypothesis thatthis increase is more pronounced with xenon than with isofluraneanaesthesia was tested in pigs. Methods. Twenty pigs received anaesthesia with xenon 0.55 MAC/remifentanil0.5 µg kg^–1 min^–1 (group X, n=10) or isoflurane0.55 MAC/remifentanil 0.5 µg kg^–1min^–1 (groupI, n=10). CO, heart rate (HR), mean arterial pressure (MAP)and left ventricular fractional area change (FAC) were measuredat baseline, after 5 and 15 min of hypoventilation and after5, 15 and 30 min of restored ventilation. Results. CO increased by 10–20% with both anaesthetics,with an equivalent rise in HR, maintaining DO₂ in spite of a20% reduction in arterial oxygen content. Decreased left ventricular(LV) afterload during hypoventilation increased FAC, and thiswas more marked with xenon (0.60–0.66, P<0.05 comparedwith baseline and isoflurane). This difference is attributedto negative inotropic effects of isoflurane. Increased pulmonaryvascular resistance during hypoventilation was found with bothanaesthetics. Conclusion. The cardiovascular effects observed in this modelof moderate hypoventilation were sufficient to maintain DO₂.Although the haemodynamic response appeared more pronouncedwith xenon, differences were not clinically relevant. An increasein FAC with xenon is attributed to its lack of negative inotropiceffects.     

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.     

Continuous infusions of propofol administered to dogs: effects on ICG and propofol disposition

We have studied the effects of stepwise increasing infusionrates of propofol 200–500 µg kg^–1 min^–1on blood concentrations of propofol and the disposition andclearance of a bolus dose of indocyanine green (ICG) 0.5 mgkg^–1 in 10 acutely instrumented dogs. Drug concentrationsand ICG clearance were measured 30 min after each change ofinfusion rate and after reverting for 60 min to the basal propofolinfusion rate. Increasing infusion rates resulted in significantprolongation of the elimination half-life of ICG and decreasein ICG clearance at the largest infusion rate (500 µgkg^–1 min^–1) compared with the basal rate. Similarly,there were greater than predicted blood concentrations of propofolat the largest infusion rate. When the infusion rate revertedto 200 µg kg^–1 min^–1, and continued for 60min, there was a significant difference between the initialblood concentration of propofol at this basal infusion rateand this latter value (P < 0.01). These changes reflect thepersistent myocardial depression observed during the recoveryphase. (Br. J. Anaesth. 1994; 72: 451–455) Presented in part at the Annual Meeting of the American Societyof Anesthesiologists, October 1990, Las Vegas, U.S.A.     

NEUROMUSCULAR AND CARDIOVASCULAR EFFECTS OF DOXACURIUM IN CHILDERN ANAESTHETIZED WITH HALOTHANE

The neuromuscular and cardiovascular effects of doxacurium chloride(BW A938U) were evaluated in 27 children (2–12 yr) anaesthetizedwith 1% halothane and nitrous oxide in oxygen. In nine childrenthe incremental technique was used to establish a cumulativedose-response curve by train-of-four stimulation. The remainingchildren received either 30 or 50 µg kg^–1 of thedrug as a single bolus. The median ED₅₀ and ED ₉₅ of doxacuriumin children were 19 and 32 µg kg^–1, respectively.No clinically significant change in heart rate or arterial pressureoccurred. Following doxacurium 30 µg kg^–1 and 50µg kg^–1, recovery to 25% of control occurred in25 (SEM 6) and 44 (3) min, respectively. The recovery index(25–75% of control) was 27 (2) min. The duration of actionof doxacurium is similar to that of tubocurarine and dimethyl-tubocurarinein children. Compared with adults, children seem to requiremore doxacurium (µg kg^–1) to achieve a comparabledegree of neuromuscular depression, and they recover more rapidly. Presented in part at the American Society of AnesthesiologistsAnnual Meeting, October 1987, and the International AnesthesiaResearch Society Meeting, March 1988.     

PULMONARY VASCULAR EFFECTS OF TRINITROGLYCERIN AND ISOSORBIDE DINITRATE AFTER CARDIOPULMONARY BYPASS

We have compared the systemic and right ventricular haemodynamiceffects of trinitroglycerin (TNG) and isosorbide dinitrate (ISDN)in patients recovering from coronary artery bypass grafting.Each of the 16 patients was given increasing i.v. doses of thetwo nitrates in a random order and double blind fashion untilthe target of a 25% decrease in mean pulmonary artery pressure(MPAP) was achieved. Total doses of TNG 9 (6–12) µgkg^–1 (mean, 95% confidence interval) and ISDN 148 (76–220)µg kg^–1 were given during infusions of 22 (18–25)min and 34 (28–41) min duration, respectively. The targetdecrease in MPAP was produced with infusion rates of TNG 0.5(0.4–0.7) µg kg^–1 min^–1 and ISDN 5.8(4.1–7.5) µg kg^–1 min^–1 These dosesproduced similar acute decreases in MPAP and similar effectson pulmonary and systemic vascular resistances and systemicand right ventricular haemodynamic variables. We conclude thatTNG is more than 10 times as potent as ISDN in its acute haemodynamic effects in cardiac surgical patients in the immediatepostoperative period. Both nitrates have relatively greatereffect on the pulmonary than the systemic vasculature. (Br.J. Anaesth. 1993; 71:720–724) Presented in part at the Annual Meeting of the Society of CardiovascularAnesthesiologists, San Antonio, Texas, May 1991.     

Cerebral effects of nitrous oxide during isoflurane-induced hypotension in the pig

We have studied the effects of nitrous oxide on cerebral bloodflow (CBF), cerebral blood flow velocity (CBFV) and intracranialpressure (ICP) during isoflurane-induced hypotension in 10 pigs.CBF was measured using laser Doppler flowmetry, CBFV in theright middle cerebral artery was calculated using Doppler ultrasoundand ICP was measured using an extradural ICP monitor. Each animalwas studied under four conditions, examined sequentially: (i)mean intra-arterial pressure (MAP) 85 mm Hg, maintained withisoflurane, (ii) MAP 50–55 mm Hg, induced by isofluraneonly, (iii) MAP 85 mm Hg, maintained with isoflurane and 50%nitrous oxide, and (iv) MAP 50–55 mm Hg, induced by isofluraneand 50% nitrous oxide. No significant differences were notedbetween conditions with respect to ICP. There was a significantdifference in CBF during condition (ii) compared with (i) (mean75(SD 21) vs 100(0) %) and during condition (iv) compared with(iii) (90(26) vs 109(13)%). Animals under condition (iv) exhibiteda 20% reduction in CBFV compared with those under condition(iii) (57 vs 69 cm s^–1). For animals under normotensiveconditions, addition of nitrous oxide to isoflurane resultedin a 16% increase in CBFV (69 vs 60 cm s^–1). Comparingisoflurane-induced hypotension ((ii) vs (iv)), there was nostatistical difference in either CBF or CBFV on addition of50% nitrous oxide. The correlation between changes in CBF andCBFV was not significant. We conclude that the use of nitrousoxide during isoflurane-induced hypotension has no significanteffect on CBF, CBFV or ICP compared with the use of isofluranealone.     

HAEMODYNAMIC EFFECTS OF DILTIAZEM DURING FENTANYL-NITROUS OXIDE ANAESTHESIA: An In Vivo Study in the Dog

The haemodynamic effects of diltiazem were studied in six dogsduring fentanyl-nitrous oxide (in oxygen) anaesthesia. A bolusof diltiazem 300 µg kg^–1 was given, followed byinfusions at 30, 60 and 90 µg kg^–1 min^–1 whichproduced plasma diltiazem concentrations of 392±30, 908±54and 1483±134 ng ml^–1, respectively. Diltiazem significantlyreduced systemic vascular resistance index, mean arterial pressure,heart rate and PR interval. The decrease in afterload increasedcardiac index, since there was little change in myocardial contractility(LV dP/dt). Five dogs developed second degree atrioventricular(AV) block in association with the highest dose. Administrationof calcium chloride 20 mg kg^–1 did not reverse the haemodynamicor electrophysiological effects of diltiazem. Isoprenaline increasedheart rate and restored sinus rhythm in four dogs with AV block. Presented in part at the 59th International Anesthesia ResearchSociety Congress, Houston, Texas, 1985.     

MODIFICATION OF CENTRAL NERVOUS SYSTEM EFFECTS OF LAUDANOSINE BY INHALATION ANAESTHETICS

To determine the effect of inhalation anaesthetics on the plasmaconcentration of laudanosine necessary to produce CNS excitation,we administered laudanosine 0.5 mg kg^–1 min^–1 i.v.to 40 rabbits under eight study conditions: 1.0 or 0.7% halothane,1.6% isoflurane, 2.0% enflurane, during normocapnia and hypocapnia;70% nitrous oxide, alone and with 1.0% halothane, and room air(control). At the onset of purposeless, unco-ordinated movementsof the entire body, blood samples were obtained to determinethe CNS excitation-threshold plasma concentration (ETPC) oflaudanosine. During normocapnia, 1.0% halothane, 1.6% isofluraneand 2.0% enflurane increased ETPC (mean (SD) 11.8 (2.5), 11.3(2.8) and 9.1 (1.4) µg ml^–1, respectively) fromcontrol (5.0 (0.9) µg ml^–1). ETPC during enfluraneanaesthesia did not change significantly with hypocapnia. Nitrousoxide, alone or in combination with halothane, did not changeETPC. The combination of nitrous oxide with 1.0% halothane significantlydecreased ETPC to less than that for halothane alone (6.7 (1.2)v. 11.8 (2.5) µg ml^–1, respectively). ^*Present address: Department of Anesthesia, Peking Medical College,Beijing, People's Republic of China.     

MEASUREMENT OF THE RATES OF NITROUS OXIDE UPTAKE AND NITROGEN EXCRETION IN MAN

Using a completely closed anaesthetic circuit, nitrous oxideuptake and nitrogen excretion were measured simultaneously inpatients undergoing nitrous oxide in oxygen anaesthesia forabdominal surgery. The results have been compared with standardmodels of uptake and excretion. Mean nitrous oxide uptake wasmeasured and did not exceed 400 ml min^–1 (normalized to70-kg man) and was not less than 60 ml min at 100 min^–1after the start of nitrous oxide in oxygen anaesthesia. Nitrogenexcretion did not exceed 100 ml min^–1 and was measurable(8ml min^–1) at 100 min. The persistence of nitrogen excretioncontrasts with other published data obtained with intact volunteersand this suggests that exposure at surgery of abdominal tissues,including fat, affect substantially the rates of excretion anduptake after 70 min.     

PROLONGED INFUSION OF SUXAMETHONIUM IN INFANTS AND CHILDREN

The neuromuscular blockade produced by a prolonged (> 90min) continuous infusion of suxamethonium and measured withtrain-of-four stimulation was studied in 20 infants and 20 childrenduring nitrous oxide and halothane in oxygen anaesthesia. Theresults were compared with a previous study in adults. Suxamethoniumrequirement was increased in infants and children. Mean peakinfusion rates were 297 and 284 µg kg^–1 min^–1in infants and children, compared with 134 µg kg^–1min^–1 in adults. An initial tachyphylaxis was followedby bradyphylaxis, and the peak requirement occurred earlierin infants than in children and adults (40 v. 80–100 min).Phase II block developed during the tachyphylaxis. Recoveryof neuromuscular activity commenced after stopping the infusionand was accelerated with neostigmine.     

CONTINUOUS INFUSION OF MIVACURIUM IN CHILDREN

Mivacurium is a new short-acting competitive neuromuscular blockingagent. Infusion requirements for the maintenance of a stable90–99% muscle twitch depression were determined in 28children anaesthetized with nitrous oxide and 1% halothane (inspired)in oxygen or nitrous oxide in oxygen and opioid. Neuromuscularblock was assessed by monitoring the force of contraction ofthe adductor of the thumb during train-of-four (TOF) stimulationat 0.1 Hz. Infusion rate and twitch depression were analysedfrom 15 to 75 min and from 75 to 135 min after the start ofthe infusion. In the first period of evaluation, the mean infusionrequirement was 10.4 (SEM 0.92) µg kg^–1 min^–1during the halothane anaesthesia and 13 (1.4) µg kg^–1min^–1 during the opioid anaesthesia (P < 0.05). Thisdifference was present also during the second 60-min period.There was no significant correlation between infusion ratesrequired to maintain > 90% depression of the first twitch(T1) of the TOF and plasma cholinesterase concentrations. Regardlessof the anaesthetic regimen, children recovered rapidly afterdiscontinuing the infusion. The recovery index (25–75% recovery of T1) for all patients was 5.4 (0.57) min with nosignificant differences between the groups.     

Comparison of effects of remifentanil and alfentanil on cardiovascular response to tracheal intubation in hypertensive patients

In a randomized double-blind study, we compared the effect ofremifentanil and alfentanil on the cardiovascular response tolaryngoscopy and tracheal intubation in patients on long-termtreatment for hypertension. Forty ASA II–III patientswere allocated to receive (i) remifentanil 0.5 µg kg^–1followed by an infusion of 0.1 µg kg min^–1 or (ii)alfentanil 10 µg kg^–1 followed by an infusion ofsaline; all patients received glycopyrrolate 200 µg beforethe study drug. Anaesthesia was induced with propofol and rocuroniumand maintained with 1% isoflurane and 66% nitrous oxide in oxygen.Laryngoscopy and tracheal intubation were performed after establishmentof neuromuscular block. Arterial pressure and heart rate (HR)were measured non-invasively at 1 min intervals from 3 minbefore induction until 5 min after intubation. Systolic(SAP), diastolic and mean arterial pressure decreased significantlyafter induction in both groups (P<0.05). Maximum increasesin mean SAP after laryngoscopy and intubation were 35 and 41mm Hg in the remifentanil and alfentanil groups, respectively.After intubation, arterial pressure did not increase above baselinevalues in either group. HR remained stable after induction ofanaesthesia, but increased above baseline values after intubation.Mean maximum HR was 87 beats min^–1 for the remifentanilgroup (12 beats min^–1 above baseline; P=0.065) and 89beats min^–1 for the alfentanil group (15 beats min^–1above baseline; P<0.05). There were no significant differencesbetween groups in HR or arterial pressure at any time. Therewere no incidences of bradycardia. Seven patients in the remifentanilgroup and four in the alfentanil group received ephedrine forhypotension (i.e. SAP<100 mm Hg). Br J Anaesth 2001; 86: 90–3     

EFFECT OF Paco2 ON CEREBRAL BLOOD FLOW DISTRIBUTION DURING HALOTHANE COMPARED WITH ISOFLURANE ANAESTHESIA IN THE RAT

In order to examine anaesthetic effects on the distributionof cerebral blood flow (CBF) during normo- and hypocapnia, maleadult Sprague-Dawley rats were allocated randomly to four groupsin a 2x2 factorial design, using PaC(,2 value and anaestheticagent as between-group factors. Animals were anaesthetized witheither 1.38%isoflurane (inspired) or 1.05% halothane (inspired)and the lungs ventilated mechanically at either normocapnia(PaC0) 5.1–5.6kPa) or hypocapnia (?aCOl 3.1–3.3kPa) for 1 h. CBF was measured using 14C-iodoantipyrine autoradio-graphy.Local CBF in selected cortical and subcortical regions of interestand area - weighted mean global CBF were calculated. Data werecompared by analysis of variance. Normocapnic (mean (SE)) CBFfor halothane (n = 6) and isoflurane (n = 7) was 120 (8) ml/100g min^–1 (Paco, 5.6 (0.49) kPa) and 117 (9) mil 100 g min^–1(PaC0} 5.4 (0.5) kPa), respectively. Hypocapnic CBF for halothane(n = 6) and isoflurane (n = 6) was 82 (7) ml/100 g min^–1(PaC0} 3.3 (0.12) kPa) and 82 (6) ml/ 100 g min^–1 (PaCOl3.2(0.12) kPa), respectively. Hypocapnia reduced global CBF forboth groups by 30% (P < 0.001), but there was no differencebetween anaesthetic agents (P >0.8). Hypocapnia decreasedCBF in all local structures examined. Although subcortical structureshad similar CBF at both normocapnia and hypocapnia, CBF in threecortical samples was greater (P <0.05) in both the normocapnicand hypocapnic halothane groups than the corresponding isofluranegroups. The CBF reactivity to changes in PaC0] was similar forboth agents (approximately 2 ml/100 g min^–1 mm Hg). Weconclude that halothane is a selective cortical vasodilatorcompared with isoflurane, but both agents have similar effectson global CBF and local and global CBF reactivity to changesin Paco     

METABOLIC GAS EXCHANGE DURING NITROUS OXIDE ANAESTHESIA WITH CONTROLLED VENTILATION

A system for metabolic gas exchange has been used during nitrousoxide-opioid anaesthesia incorporating a Servo Ventilator 900C and external analysers for oxygen and carbon dioxide. Oxygenconsumption and carbon dioxide excretion were calculated asdifferences in content between inspired and expired minute ventilation.Nitrous oxide uptake was calculated similarly, assuming it wasthe only other gas present in addition to oxygen and carbondioxide. The mean value for oxygen consumption was 3.25 ml kg^–1min^–1, declining by 8% during the 2 h of anaesthesia.The formula for the best fit curve of nitrous oxide uptake was18.3.t^–0.48 ml kg^–1 min^–1 when Fl_NO was 0.7.To simplify measurement procedures and avoid measurements ofexpiratory volume, we also calculated metabolic gas exchangewhen expiratory minute ventilation was expressed as a functionof inspiratory minute volume and nitrous oxide uptake. The lattervalue was obtained from the overall best fit curve for nitrousoxide uptake.     

COMPARISON OF THE NEUROMUSCULAR BLOCK INDUCED BY MIVACURIUM, SUXAMETHONIUM OR ATRACURIUM DURING NITROUS OXIDE-FENTANYL ANAESTHESIA

We compared the neuromuscular and cardiovascular changes followingadministration of mivacurium 0.15, 0.20 and 0.25 mg kg^–1,suxamethonium 1.0 mg kg^–1 or atracurium 0.5 mg kg^–1i.v. in 41 (ASA physical status I or II) patients during nitrousoxide—fentanyl anaesthesia. Mean onset times for totalablation of twitch response for mivacurium 0.15, 0.20 and 0.25mg kg^–1, were 2.5, 2.4 and 2.7 min, respectively, similarto that for atracurium (2.5 min), but longer than for suxamethonium(1.1 min) (P < 0.05). Mean times from administration of druguntil twitch response recovered to 10% of control were shorterfor each dose of mivacurium (15.6, 18.0 and 20.6 min, respectively)than for atracurium (40.0 min) and longer than for suxamethonium(7.7 min) (P < 0.05). Mean infusion rate required to maintaintwitch response at 5±4% control was 6.7 µg kg^–1min^–1 for mivacurium and 6.3 µg kg^–1 min^–1for atracurium. Following neostigmine 0.045 mg kg^–1, meantimes for twitch tension to recover from 10% to 90% of controlwere similar for mivacurium (9.7 min) and atracurium (10.5 min).Transient decreases in mean arterial pressure (> 20%) wereobserved in seven of 15 patients who received the two higherdoses of mivacurium. Presented in part at the Annual Scientific Meeting of the AmericanSociety of Anesthesiologists, San Francisco, October 1988.     

CLINICAL PHARMACOLOGY OF MIVACURIUM CHLORIDE (BW B1090U) INFUSION: COMPARISON WITH VECURONIUM AND ATRACURIUM

Mivacurium chloride (BWB1090U) is a new, short-acting non-depolarizingneuromuscular blocking agent. It is a synthetic bis-benzylisoquinoliniumdiester, which is hydrolysed rapidly by plasma cholinesterase.This study compares mivacurium, atracurium and vecuronium bycontinuous i.v. infusion. The duration of mivacurium infusionranged from 29.5 to 286 min. The steady state infusion ratesnecessary to maintain 95 (SEM 4)% twitch suppression were: mivacurium8.3 (0.7) µg kg^–1 min^–1; atracurium 7.9 (0.4)µg kg^–1 min^–1; vecuronium 1.2 (0.3) µgkg^–1 min^–1. Following infusions of mivacurium, variousrecovery times (for example: 25–75%, 6.9 (0.3) min; 25–95%,11.0 (0.4) min; 5–95% 14.5 (0.4) min) did not differ significantlyfrom those following single bolus doses. Recovery times followingcessation of mivacarium infusions were approximately 50% ofthose for equivalent durations of infusion of atracurium (10.9(0.3) min for 25–75% recovery and 26.6 (0.4) min for 5–95%recovery). For vecuronium, corresponding recovery times were13.8 (0.9) and 32.0 (1.2) min, respectively. Comparative recoverytimes for mivacurium were 40–50% of those for vecuronium.There was a significant correlation between the infusion rateof mivacurium required to maintain 95% twitch depression andthe plasma cholinesterase activity of individual subjects. Presented in part in Abstract form at the Annual Meeting, AmericanSociety of Anesthesiologist, Las Vegas, Nevada, 1986.     

Treatment of ischaemic left ventricular dysfunction with milrinone or dobutamine administered during coronary artery stenosis in the presence of beta blockade in pigs

Background. This study examines the effects of phosphodiesterasetype III (PDEIII) inhibition vs beta stimulation on global functionof the left ventricle (LV) and systemic haemodynamics in a porcinemodel of acute coronary stenosis with beta blockade. Methods. A total of 18 adult swine were anaesthetized. Micromanometer-tippedcatheters were placed in the ascending aorta and LV. Two pairsof ultrasonic dimension transducers were placed in the subendocardiumon the short axis proximal to a left anterior descending (LAD)artery occluder and the long axis of the LV. Before ischaemia,i.v. esmolol was infused to decrease baseline heart rate (HR)by approximately 25%, and all animals received an esmolol infusion(150 µg kg^–1 min^–1). Ischaemia was producedby reducing the flow in the LAD artery by approximately 80%,from 17(4) to 3(2) ml min^–1. Animals were randomized toreceive (after esmolol) one of the following: no drug, shamonly (Group 1, n=6), control (C); 50 µg kg^–1 i.v.milrinone (Group 2, n=6) followed by 0.375 µg kg^–1min^–1 (M); or incremental doses of dobutamine (Group 3,n=6) every 10 min (5, 10 and 20 µg kg^–1 min^–1)(D). Left ventricular function data obtained included HR, arterialand LV pressures, cardiac output (CO), Emax and dP/dT. Measurementswere taken during five time periods: before ischaemia (at baseline,after esmolol) and every 10 min during ischaemia (at 10, 20and 30 min). Results. The effects of beta blockade and ischaemia had a significantimpact on contractility (Emax) in Group M and myocardial performance(left ventricular end-diastolic pressure, LVEDP) in all groups.Left ventricular function (Emax, CO, LVEDP and SVR) was betterpreserved when milrinone was added in Group M. A moderate doseof dobutamine (10 µg kg^–1 min^–1) increasedCO. Only the high dose (20 µg kg^–1 min^–1)improved contractility (Emax), but at the expense of increasedSVR. Also, LVEDP with either dose of dobutamine remained highand unchanged. Conclusions. From our limited findings, it would appear thatthere may, theoretically, be some benefit for using milrinonein preference to other inotropic drugs in the presence of betablockade. Milrinone administration should be considered in patientswith acute ischaemic LV dysfunction and preexisting beta blockadebefore using other inotropic drugs such as beta stimulants. Presented in part at: the 27th Annual Meeting of the Societyof Cardiovascular Anesthesiologists, May 14–18, 2005,Baltimore, MD, USA (Anesth Analg 2005; 100: 5CA60).     

NITROUS OXIDE ADMINISTRATION USING COMMONLY AVAILABLE OXYGEN THERAPY DEVICES

Administration of nitrous oxide is useful for providing sedationand analgesia. The therapeutic range for nitrous oxide is 20–30%.Several oxygen treatment devices have been used for administeringnitrous oxide, but little is known about the concentrationsof nitrous oxide and oxygen delivered to the trachea. We havestudied this, using an analogue lung model, with several oxygentherapy devices. With a 1:1 nitrous oxide-oxygen mixture inthe primary flow for all systems, end-expired nitrous oxideconcentrations varied between 6.5% and 34.3%. Therapeutic concentrationswere produced using the Hudson (nominal oxygen concentration60%) fixed-performance mask, the variable performance Hudsonmask at 4 litre min^–1, the MC masks at 4 and 6 litre min^–1and the nasal prongs at 6 and 8 litre min^–1. Simultaneousend-expired oxygen concentrations for all devices tested werewithin a safe range.