COMPARISON OF I.V. GLYCOPYRROLATE AND ATROPINE IN THE PREVENTION OF BRADYCARDIA AND ARRHYTHMIAS FOLLOWING REPEATED DOSES OF SUXAMETHONIUM IN CHILDREN

The effectiveness of administration of grycopyrrolate 5 and10 µg kg^–1 and atropine 10 and 20 µg kg^–1i.v. immediately before the induction of anaesthesia, to preventarrhythmia and bradycardia following repeated doses of suxamethoniumin children, was studied. A control group was included for comparisonwith the lower dose range of grycopyrrolate and atropine. Afrequency of bradycardia of 50% was noted in the control group,but this was not significantly different from the frequencywith the active drugs. Bradycardia (defined as a decrease inheart rate to less than 50 beat min^–1) was prevented whenthe larger dose of either active drug was used. It is recommendedthat either glycopyrrolate 10 mg kg^–1 or atropine 20 µgkg^–1 i.v. should immediately precede induction of anaesthesia,in children, if the repeated administration of suzamethoniumis anticipated     

Cardiovascular responses to graded doses of three catecholamines during lactic and hydrochloric acidosis in dogs

We have studied the cardiovascular effects of incremental dosesof three catecholamines in dogs subjected to lactic (LAC) andhydrochloric (HCl) acidosis. Fifty-four dogs were allocatedrandomly to one of three groups: control, LAC and HCl acidosis(n = 18 each group). In the acidotic models, 2 mol litre^–1of lactic acid (4 ml kg^–1 h^–1 or 2 mol litre^–1of HCl (1 ml kg^–1 h^–1) was infused i.v. until arterialpH was reduced to 7.00±0.1. Within each group, six dogsreceived one of three different drugs in logarithmically incrementaldoses: adrenaline 0.1, 0.2, 0.4, 0.8, 1.6, 3.2 µg kg^–1min^–1, noradrenaline 0.1, 0.2, 0.4, 0.8, 1.6, 3.2 µgkg^–1 min^–1 and dobutamine 5, 10, 20, 40, 80, 160µg kg^–1 min^–1 Cardiovascular variables weremonitored, with periodic measurements of plasma electrolyteand lactate concentrations. The pH reduction induced by HClor lactic acid was associated with a statistically significantincrease in mean pulmonary arterial pressure (MPAP), prominentespecially in the LAC group where MPAP increased from mean 18(SD 5) to 27 (6) mm Hg. In the acidotic models, the reductionin myocardial responsiveness to adrenaline or noradrenalinewas more prominent than that for the control for correspondingdoses of drugs. In the LAC group mean cardiac index decreasedsignificantly from 5.2 (1.8) to 2.2 (0.7) litre min^–1m^–2 after infusion of adrenaline 3.2 µg kg^–1min^–1 and decreased from 5.1 (1.1 to 2.4 (0.9) litre min^–1m^–1 after infusion of noradrenaline 3.2 µg kg^–1min^–1. In contrast, dobut amine showed dose-dependentincreases in cardiac index and heart rate in control, as wellas acidotic groups. The acute HCl acidosis induced greater hyperkalaemiathan the lactic acidosis. (Br. J. Anaesth. 1995; 74: 583–590)      

FUNCTIONAL AND METABOLIC EFFECTS OF BUPIVACAINE AND LIGNOCAINE IN THE RAT HEART-LUNG PREPARATION

We have examined the effects of bupivacaine and lignocaine onmyocardial metabolism in the rat isolated heart-lung preparation.Bupivacaine 1, 5 or 25 µg ml^–1 or lignocaine 4,20 or 100 µg ml^–1 was administered 5 min after thestart of perfusion. Both bupivacaine 25 µg ml^–1and lignocaine 100 µg ml^–1 reduced heart rate significantly.Bupivacaine 25 µg ml^–1 was associated with a higherincidence of arrhythmias than the other groups. Three heartsin the bupivacaine 25 µg ml^–1 group (n = 8) andtwo hearts in the lignocaine 100 µg ml^–1 group (n= 8) failed (zero cardiac output) at the end of the experiment.Although there were no significant differences in myocardiallactate and glycogen concentrations between groups, ATP contentin the bupivacaine 25 µg ml^–1 and lignocaine 100µg ml^–1 groups was significantly less than thatin the control group. The results suggest that myocardial depressionand subsequent metabolic deterioration occurred with both thehigh doses of local anaesthetics; these findings do not accountfor the apparent increased cardiotoxicity of bupivacaine.     

CLINICAL AND HAEMODYNAMIC EFFECTS OF MILRINONE IN THE TREATMENT OF LOW CARDIAC OUTPUT AFTER CARDIAC SURGERY

We have studied the haemodynamic effects of i.v. milrinone.a newphosphodiesterase inhibitor, in patients with low cardiacoutput after cardiac surgery. Thirty-five patients with a cardiacindex (Cl) < 2.5 litre min^–1 m^–2 and a pulmonarycapillary wedge pressure (PCWP) > 8 mm Hg were given a loadingdose of milrinone 50 µg kg^–1 followed by an infusionat one of three rates: 0.375 fig kg^–1 min^–1, 0.5fig kg^–1 min^–1 or 0.75 µg kg^–1 min^–1for 12 h. After 1 h there were increases in Cl (35%) (P<0.001), heart rate (13%) (P< 0.01) and stroke volume index(19%) (P< 0.005). There were decreases in mean arterial pressure(12%) (P< 0.01), systemic vascular resistance (35%) (P<0.001) and PCWP (24%) (P< 0.05). Pulmonary vascular resistancewas unchanged or reduced and left ventricular stroke work indexwas unchanged or increased. The haemodynamic improvements weresustained throughout the infusion period. Milrinone was toleratedwell: three patients developed tachycardia > 125 beat min^–1,one patient developed atrial fibrillation and one patient hada short run of atrial bigemini. We conclude that milrinone isa useful agent in the treatment of patients with a reduced cardiacoutput after cardiac surgery.     

EFFECT OF I.V. LIGNOCAINE ON PAIN AND THE ENDOCRINE METABOLIC RESPONSES AFTER SURGERY

Pain intensity, and blood glucose and plasma cortisol concentrationswere measured following abdominal hysterectomy in 18 patientsallocated randomly to receive either i.v. lignocaine 1.5 mgkg^–1 plus 2 mg kg^–1 h^–1, or saline. The administrationof lignocaine resulted in plasma conentrations between 1.5 and2.0 µg ml^–1 during the 2-h study period. However,the administration of lignocaine i.v. had no effect on the intensityof pain after surgery, or on the adrenocortical and hyperglycaemicresponses to surgery.     

Differential effects of thiopental on methacholine- and serotonin-induced bronchoconstriction in dogs

Background. Thiopental sometimes causes bronchospasm duringinduction of anaesthesia. In addition, we have reported previouslythat thiopental produced transient bronchospasm, which was blockedby atropine pretreatment, and worsened histamine-induced bronchoconstrictionin dogs. Previous in vitro reports suggest that synthesis ofcontractile cyclooxygenase products, such as thromboxane A₂,may be involved in the mechanism of bronchospasm. However, thein vivo spastic effects have not been defined comprehensively. Methods. Twenty-seven mongrel dogs were anaesthetized with pentobarbital.Bronchoconstriction was elicited with methacholine (0.5 µg kg^–1+5.0µg kg^–1 min^–1; Mch group, n=7) orserotonin (10 µg kg^–1+1 mg kg^–1 h^–1;5HT group, n=20), and assessed as percentage changes in bronchialcross-sectional area (BCA, basal=100%) using a bronchoscope.In the 5HT group, dogs were subdivided into four groups of fiveeach: S-5HT, I-5HT, 5HT-S and 5HT-A. In the S-5HT and I-5HTgroups, 30 min before serotonin infusion dogs were given salineand indomethacin respectively at 5 mg kg^–1 i.v. Inall groups, 30 min after bronchoconstrictor infusion started,dogs were given thiopental at doses between 0 (saline) and 20mg kg^–1. In the 5HT-S and 5HT-A groups, dogs weregiven saline or atropine 0.2 mg kg^–1 i.v. 5 min afterthiopental 20 mg kg^–1. Results. Methacholine and serotonin reduced BCA by about 50and 40% respectively. Thiopental 20 mg kg^–1 increasedand decreased BCA by about 20 and 10% in the Mch and 5HT groupsrespectively. Indomethacin and atropine did not attenuate thepotentiation of serotonin bronchoconstriction produced by thiopental. Conclusion. The present study indicates that thiopental mayattenuate or worsen bronchoconstriction induced by muscarinicor serotonin receptor stimulation, respectively. The synthesisof contractile cyclooxygenase products and cholinergic stimulationmay not be involved in the contractile effect of thiopentalon serotonin bronchoconstriction. Br J Anaesth 2003; 91: 379–84     

EFFECTS OF I.A. LIGNOCAINE ON ADRENALINE-INDUCED VASOCONSTRICTION

The effects of i.a. administered lignocaine on the in vivo responseof the vascular bed supplied by the lingual, external maxillaryand posterior auricular branches of the common carotid arterywere studied in the rat. Infusions of lignocaine in concentrationsof 10–1000 µg ml^–1 administered at the rateof 0.05 ml min^–1 for 10 min did not affect vascular resistanceor arterial pressure in the common carotid artery. However,following such infusions, the increase of vascular resistancecaused by bolus doses of adrenaline (20–120 ng in 0.1ml) was inhibited, indicating lignocaine-adrenaline antagonism.Responses to adrenaline remained significantly depressed 60min after the termination of a 100-µg ml^–1 or higherlignocaine infusion. ^* Present address: Turner Dental School, University of Manchester,Bridgeford Street, Manchester M15.     

MYOCARDIAL ISCHAEMIA AND SPINAL ANALGESIA IN PATIENTS WITH ANGINA PECTORIS

We have studied prospectively myocardial ischaemic events byHolter monitoring of ST-segment depression in patients withangina pectoris given spinal analgesia for minor surgery comparedwith a reference day of normal daily activities. Monitoringwas undertaken continuously for 24 h on both days, startingjust before anaesthesia on the day of surgery. On the referenceday, seven of 14 patients had 27 ischaemic events with meanmax ST-depression of 0.15 mV and total duration of 143 min,compared with 10 of 14 patients with 70 ischaemic events withmean max ST-depression of 0.22 mV and total duration of 1078min (P <0.01 for all). On the day of surgery, the first ichaemicevent occurred a mean 338 min (range 75–480 min) afterspinal analgesia, and the duration of all first events was 480min. On this day, the first ischaemic event was associated withincreased heart rate (103 beat min^–1 (range 66–131beat min^–1) compared with 92 (60–122) beat min^–1during all events (P = 0.011)). In patients with angina pectoris,myocardial ischaernia did not occur immediately after the onsetof spinal analgesia, but several hours later, correspondingto the cessation of block. This could be explained by increasedcardiac pre- and afterload, probably further aggravated by thevolume load. (Br. J. Anaesth. 1993; 71: 472–475)     

EFFECTS OF I.V. LIGNOCAINE ON PSYCHOLOGICAL PERFORMANCE AND SUBJECTIVE STATE IN HEALTHY VOLUNTEERS

In order to assess the effects of different doses of lignocaineon performance, nine healthy volunteers aged 21–34 yrreceived i. v. infusions of saline, low and high dose lignocaine(mean plasma concentrations 0.92 and 1.78 µg ml^–1,respectively) in a double-blind randomized order. The Digit-SymbolSubstitution Test (DSST) and Visual Analogue Scales (VAS) wereperformed repeatedly and a battery of performance tests once.The median (lower, upper quartile) number of correct responsesfor the DSST during the infusion period was: placebo 69 (67,77); low 74 (71, 80); high 66 (61, 75) (P < 0.001, GeneralLinear Models; all pairwise comparisons P < 0.05). None ofthe measures in the full battery showed any significant changes.VAS showed that subjects felt more interested (P < 0.05),drowsy (P < 0.01), dizzy, tense, abnormal, drunk and muzzy(P < 0.001) with lignocaine than with placebo. These resultsconfirm that lignocaine can produce acute performance effects(both improvements and impairments). Subjects were clearly awareof the presence of lignocaine. suggesting that subjective reportsmay be a useful indicator of its CNS effects.     

HAEMODYNAMIC EFFECTS OF THE PHOSPHODIESTERASE INHIBITOR ENOXIMONE IN COMPARISON WITH DOBUTAMINE IN ESMOLOL-TREATED CARDIAC SURGERY PATIENTS

In a randomized study, the haemodynamic effects of the new phosphodiesterase-III-inhibitor,enoximone, were compared with dobutamine in acutely ß-adrenoceptorblocked patients. Twenty patients scheduled for aorto-coronarybypass grafting suffering from tachycardia (heart rate (HR)> 100 beat min^–1) were treated by infusion of esmolol,an ultra-short acting, selective ß₁-blocker. Twentyminutes after the start of esmolo, either enoximone 0.5 mg kg^–1as a bolus (n = 10) or dobutamine 5 µg kg^–1 min^–1was administered. Haemodynamic effects were monitored for 40min, including measurement of left ventricular haemodynamics.Esmolol reduced HR (–27%) and dP/dt_max (–38%) significantlyin both groups. Cardiac index (Cl) was decreased also. Enoximoneincreased Cl (+35%) and dP/dt_max (+39%) significantly, whileno change in dobutamine-treated patients was observed. Systemicvascular resistance increased only in the dobutamine group (+44%).     

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 prophylactic bronchodilator treatment with i.v. carperitide on airway resistance and lung compliance after tracheal intubation

Background. Lung resistance increases after induction of anaesthesia.We hypothesized that prophylactic bronchodilation with i.v.carperitide before tracheal intubation would decrease airwayresistance and increase lung compliance after placement of thetracheal tube in both smokers and nonsmokers. Methods. Ninety-seven adults aged between 24 and 59 yr wererandomized to receive i.v. normal saline (0.9% saline) (control)or carperitide, 0.2 µg kg^–1 min^–1 throughoutthe study. The 97 patients included smokers and nonsmokers.Thus the patients were allocated to one of the four groups:smokers who received normal saline (n=21), nonsmokers who receivednormal saline (n=27), smokers who received carperitide (n=19)or nonsmokers who received carperitide (n=30). Thirty minutesafter starting normal saline or carperitide infusion, we administeredthiamylal 5 mg kg^–1 and fentanyl 5 µg kg^–1to induce general anaesthesia and vecuronium 0.3 mg kg^–1for muscle relaxation. Continuous infusion of thiamylal 15 mgkg^–1 h^–1 followed anaesthetic induction. Mean airwayresistance (R_awm), expiratory airway resistance (R_awe) and dynamiclung compliance (C_dyn) were determined 4, 8, 12 and 16 min aftertracheal intubation and compared between the four groups. Results. At 4 min after intubation, R_awm and R_awe were higherand C_dyn lower in smokers than in nonsmokers in the controlgroup. R_awm and R_awe were lower and C_dyn higher in smokers inthe carperitide group than in smokers in the control group.R_awm and R_awe were lower in nonsmokers in the carperitide groupthan in nonsmokers in the control group. Conclusions. Marked bronchoconstriction occurred in the controlgroups (smokers and nonsmokers) 4 min after tracheal intubation.Prophylactic treatment with carperitide before induction ofanaesthesia and tracheal intubation was advantageous, particularlyin smokers.     

Propofol-alfentanil vs propofol-remifentanil for posterior spinal fusion including wake-up test

Background. Wake-up test can be used during posterior spinalfusion (PSF) to ensure that spinal function remains intact.This study aims at assessing the characteristics of the wake-uptest during propofol–alfentanil (PA) vs propofol–remifentanil(PR) infusions for PSF surgery. Methods. Sixty patients with scoliosis and candidates for PSFsurgery were randomly allocated in either alfentanil (PA) orremifentanil (PR) group. After an i.v. bolus of alfentanil 30µg kg^–1 in the PA group or remifentanil 1 µgkg^–1 in the PR group, anaesthesia was induced with thiopentaland atracurium. During maintenance, opioid infusion consistedof alfentanil 1 µg kg^–1 min^–1 or remifentanil0.2 µg kg^–1 min^–1, in the PA group and thePR group, respectively. All patients received propofol 50 µgkg^–1 min^–1. Atracurium was given to maintain therequired surgical relaxation. At the surgeon's request, allinfusions were discontinued. Patients were asked to move theirhands and feet. Time from anaesthetic discontinuation to spontaneousventilation (T₁), and from then until movement of the handsand feet (T₂), and its quality were recorded. Results. The average T₁ and T₂ were significantly shorter inthe PR group [3.6 (2.5) and 4.1 (2) min] than the PA group [6.1(4) and 7.5 (4.5) min]. Quality of wake-up test, however, didnot show significant difference between the two groups studied. Conclusion. Wake-up test can be conducted faster with remifentanilcompared with alfentanil infusion during PSF surgery.     

PHARMACOKINETICS OF LIGNOCAINE IN CHILDREN AFTER INFILTRATION FOR CLEFT PALATE SURGERY

We have studied the pharmacokinetics of lignocaine in childrenafter local infiltration for cleft palate surgery. After inductionof anaesthesia, lignocaine 2.5 mg kg^–1 with adrenaline1.200000 was injected into the palate. Blood samples were collectedbefore and at 2, 5, 10, 15, 20, 30, 60 and 120 min after infiltration.Plasma concentrations of lignocaine were measured by a gas-liquidchromatographic technique. There were no signs of systemic toxicityon routine monitoring of the patients and the peak plasma concentrationswere less than the accepted toxic values. Mean half-life was72.9 (SEM9.9) min, similar to that found previously in adultsand children. However differences in mean clearance (24.6 (2.04)ml kg^–1 min^–1) and volume of distribution (0.80(0.07) litre kg^–1) were found between this and previousstudies.     

PHARMACOKINETICS OF I.V. AND RECTAL PETHIDINE IN CHILDREN UNDERGOING OPHTHALMIC SURGERY

We have studied the pharmacokinetics of i.v. and rectal pethidinein 20 children age 4–8 yr under going ophthalmic surgery.After i.v. administration, the clearance of pethidine was mean10.4 (SD 1.7) ml kg^–1 min^–1, volume of distributionat steady state 2.8 (0.6) litre kg^–1 and elimination haff-ilfe3.0 (0.5) h. After rectal administration, plasma pethidine concentrationsvaried greatly and peak concentrations appeared late, at 147(44) mm. The mean systemic bioavailabiity after rectal administration was approximately 55%. Because the bioavailabiityof rectal pethidine varies greatly, this route is not encouragedin the management of acute pain. (Br. J. Anaesth. 1993; 71:823–826)     

SELECTIVE DEPRESSION BY ALFENTANIL OF GROUP III AND IV SOMATOSYMPATHETIC REFLEXES IN THE DOG

The effect of alfentanil on sympathetic reflexes evoked by supramaximalelectrical stimulation of the radial nerve has been observedin five dogs anaesthetized with -chloralose, paralysed withsuxamethonium and artificially ventilated. In five dogs duringthe infusion of alfentanil at a rate of 20 µg kg^–1min^–1 the late long latency sympathetic response evokedby unmyelinated fibres (group IV, C) was abolished at a meandose of 68.8 (SE 2.85) µg kg^–1. The infusion ratewas then increased to 200 µg kg^–1 min^–1 andthe early, short latency response evoked by small myelinatedfibres (group III, A) was eliminated at mean total dose of 809(SE 72) µg kg^–1. When the infusion was stopped thegroup III reflex returned within 1–5 min and recoveryto approximately 50% of control for both reflexes occurred within15–60 min in different preparations. Mean arterial pressureand mean heart rate decreased from 140 (6) mm Hg and 132 (11)beat min^–1 to 100 (7) mm Hg and 70 (6) beat min^–1,respectively, by the time the group IV response was eliminated;that is, after a mean infusion time of 3.4 min. Thereafter,there was no further cardiovascular depression. Within 3 minof the administration of naloxone 2 mg i.v., the sympatheticreflexes, arterial pressure and heart rate returned to withincontrol values.     

Pretreatment with remifentanil to prevent withdrawal after rocuronium in children

Background. Pain from rocuronium injection is a common side-effectreported to occur in 50–80% of the patients. This randomized,double-blind, placebo-controlled study was designed to evaluatethe efficacy of pretreatment with i.v. remifentanil on preventionof withdrawal response during rocuronium injection in paediatricpatients. Methods. After obtaining parental consents, 70 paediatric patientswere randomly allocated into two groups to receive either i.v.remifentanil 1 µg kg^–1 (remifentanil group, n=35)or i.v. saline 5 ml (saline group, n=35). Anaesthesia was inducedwith thiopental sodium 2.5% (5 mg kg^–1) and the test drugwas injected over 30 s. One minute after the test drug injection,rocuronium 1% (0.6 mg kg^–1) was injected over 5 s andthe response was recorded. Mean arterial pressure (MAP) andheart rate were recorded on arrival in the operating theatre,before and 1 min after the tracheal intubation. Results. The overall incidence of withdrawal movements was significantlyhigher in the saline group (33 patients; 94%) than that in theremifentanil group (8 patients; 23%) (P<0.001). No patientin the remifentanil group showed generalized movement, whereas51% of patients in the saline group did. Remifentanil preventedsignificant increase in MAP after intubation. Conclusion. This study demonstrated that pretreatment with remifentanil1 µg kg^–1 provided a safe and simple method forreducing the incidence of rocuronium-associated withdrawal movementwith haemodynamic stability in children.     

Comparison of the haemodynamic effects of dobutamine with enoximone after open heart surgery in small children

We have studied 28 children (mean age 13.6 months) undergoingelective cardiac surgery involving a myocardial ischaemic timegreater than 60 min. Thirteen received phenoxybenzamine 1 mgkg^–1 before cardiopulmonary bypass (CPB) and dobutamine10 µg kg^–1 min^–1 before discontinuation ofCPB; 15 received enoximone 0.5 mg kg^–1 followed by aninfusion of 10 µg kg^–1 min^–1 before discontinuationof CPB. Haemodynamic variables were measured at intervals for6 h after CPB. Two patients in each group required additionalinotropic support with adrenaline. Heart rates, right and leftatrial pressures, mean pulmonary artery pressures and systemicand pulmonary vascular resistance indices were similar in thetwo groups. Mean arterial pressure was significantly greaterin those receiving dobutamine (61.3 (SD 7.6) mm Hg) comparedwith enoximone (56.2 (5.3) mm Hg) (P < 0.05). Differencesin cardiac index (thermodilution) (dobutamine group 2.92 (0.62)litre min^–1 m^–2; enoximone group 2.55 (0.55) litremin^–1 m^–2) and left ventricular stroke work index(dobutamine group 13.1 (4.7) g m beat^–1 m^–2; enoximonegroup 10.4 (2.7) g m beat^–1 m^–2) were not statisticallysignificant. Enoximone may be used successfully in these patientsto assist discontinuation of CPB and maintain an acceptablehaemodynamic state in the early postoperative period but, whenused alone, conferred no advantage compared with the combinationof dobutamine and phenoxybenzamine. (Br. J. Anaesth. 1994; 72:77–81)     

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).     

Effects of three different dose regimens of magnesium on propofol requirements, haemodynamic variables and postoperative pain relief in gynaecological surgery

Background. In this double-blind, randomized, placebo-controlledstudy we compared the effects of three different dose regimensof magnesium on intraoperative propofol and atracurium requirements,and postoperative morphine consumption in patients undergoinggynaecological surgery. Methods. Eighty women were allocated to four equal groups. Thecontrol group received normal saline; magnesium groups received40 mg kg^–1 of magnesium before induction of anaesthesia,followed by i.v. infusion of normal saline, magnesium 10 mgkg^–1 h^–1 or magnesium 20 mg kg^–1 h^–1for the next 4 h. Propofol infusion was targeted to keep bispectralindex values between 45 and 55. Postoperative analgesia wasachieved using PCA with morphine. Results. Magnesium groups required significantly less propofol[mean (SD) 121.5 (13.3), 102.2 (8.0) and 101.3 (9.7) µgkg^–1 min^–1 respectively] than the control group(140.7 (16.5) µg kg^–1 min^–1). Atracurium usewas significantly higher in the control group than magnesiumgroups [0.4 (0.06) vs 0.34 (0.06), 0.35 (0.04), 0.34 (0.06)mg kg^–1 h^–1 respectively]. Morphine consumptionwas significantly higher in control group than magnesium groupson the first postoperative day [0.88 (0.14) vs 0.73 (0.17),0.59 (0.23), 0.53 (0.21) mg kg^–1 respectively]. The heartrate was lower in magnesium groups and 20 mg kg^–1 h^–1infusion group demonstrated the lowest values. Conclusion. Magnesium 40 mg kg^–1 bolus followed by 10mg kg^–1 h^–1 infusion leads to significant reductionsin intraoperative propofol, atracurium and postoperative morphineconsumption. Increasing magnesium dosage did not offer any advantages,but induced haemodynamic consequences.