Glycopyrrolate during sevoflurane-remifentanil-based anaesthesia for cardiac catheterization of children with congenital heart disease

Background. Remifentanil is recommended for use in procedureswith painful intraoperative stimuli but minimal postoperativepain. However, bradycardia and hypotension are known side-effects.We evaluated haemodynamic effects of i.v. glycopyrrolate duringremifentanil–sevoflurane anaesthesia for cardiac catheterizationof children with congenital heart disease. Methods. Forty-five children undergoing general anaesthesiawith remifentanil and sevoflurane were randomly allocated toreceive either saline, glycopyrrolate 6 µg kg^–1or glycopyrrolate 12 µg kg^–1. After induction ofanaesthesia with sevoflurane, i.v. placebo or glycopyrrolatewas administered. An infusion of remifentanil at the rate of0.15 µg kg^–1min^–1 was started, sevofluranecontinued at 0.6 MAC and cisatracurium 0.2 mg kg^–1 wasgiven. Heart rate (HR) and non-invasive arterial pressures weremonitored and noted every minute for the first 10 min and thenevery 2.5 min for subsequent maximum of 45 min. Results. Baseline HR [mean (SD)] of 117 (20) beats min^–1decreased significantly from 12.5 min onwards after startingthe remifentanil infusion in the control group [106 (18) at12.5 min and 99 (16) beats min^–1 at 45 min]. In the groupsreceiving glycopyrrolate, no significant decrease in HR wasnoticed. Glycopyrrolate at 12 µg kg^–1 induced tachycardiabetween 5 and 9 min after administration. Systolic and diastolicarterial pressures decreased gradually, but there were no significantdifferences in the pressures between groups. Conclusion. I.V. glycopyrrolate 6 µg kg^–1 preventsbradycardia during general anaesthesia with remifentanil andsevoflurane for cardiac catheterization in children with congenitalheart disease. Administering 12 µg kg^–1 of glycopyrrolatetemporarily induces tachycardia and offers no additional advantage.     

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).     

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 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)     

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)      

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     

Sedative, haemodynamic and respiratory effects of dexmedetomidine in children undergoing magnetic resonance imaging examination: preliminary results

Background. We evaluated the sedative, haemodynamic and respiratoryeffects of dexmedetomidine and compared them with those of midazolamin children undergoing magnetic resonance imaging (MRI) procedures. Methods. Eighty children aged between 1 and 7 yr were randomlyallocated to receive sedation with either dexmedetomidine (groupD, n=40) or midazolam (group M, n=40). The loading dose of thestudy drugs was administered for 10 min (dexmedetomidine 1 µgkg^–1 or midazolam 0.2 mg kg^–1) followed by continuousinfusion (dexmedetomidine 0.5 µg kg^–1 h^–1or midazolam 6 µg kg^–1 min^–1). Inadequatesedation was defined as difficulty in completing the procedurebecause of the child's movement during MRI. The children whowere inadequately sedated were given a single dose of rescuemidazolam and/or propofol intravenously. Mean arterial pressure(MAP), heart rate (HR), peripheral oxygen saturation (     

HAEMODYNAMIC EFFECTS OF DOPAMINE AND DOPAMINE COMBINED WITH NITROGLYCERIN IN PATIENTS SUBJECTED TO CORONARY BYPASS SURGERY

The haemodynamic effects of dopamine and dopamine with nitroglycerinwere evaluated in eight patients with coronary heart diseasewho underwent aortocoronary bypass surgery. The study was performedunder anaesthesia and before surgery. Dopamine 8 µg kg^–1min^–1 alone produced a marked increase of the cardiacindex from 2.47 to 3.47 litre min^–1 m^–2 but onlysmall changes in heart rate (from 65 to 68 beat min^–1).This improvement in cardiac performance was accompanied by anincrease of the mean pulmonary artery pressure from 10.9 to21.3 mm Hg and in the left ventricular filling pressure from6.1 to 13.8 mm Hg with unchanged systemic and pulmonary vascularresistance. Mean arterial pressure increased from 72 to 103mm Hg. Simultaneous infusion of dopamine (8 µg kg^–1min^–1 and nitroglycerin (mean dose 0.5 µg kg^–1min^–1) resulted in a favourable reduction of mean pulmonaryartery pressure (from 21.3 to 14.4 mm Hg) and of left ventricularfilling pressure (from 13.8 to 7.9 mm Hg). Cardiac index (from3.47 to 3.34 litre min^–1 m^–2) and mean arterialpressure (from 103 to 95 mm Hg) were not reduced to the sameextent by the addition of nitroglycerin. The combined treatmentof dopamine with nitroglycerin seems to be of value in patientswith pre-existing high lseft ventricular filling pressure orwith pulmonary hypertension.     

Early recovery after remifentanil-pronounced compared with propofol-pronounced total intravenous anaesthesia for short painful procedures

Background. We compared recovery from high-dose propofol/low-doseremifentanil (‘propofol-pronounced’) compared withhigh-dose remifentanil/low-dose propofol (‘remifentanil-pronounced’)anaesthesia. Methods. Adult patients having panendoscopy, microlaryngoscopy,or tonsillectomy were randomly assigned to receive either propofol-pronounced(propofol 100 µg kg^–1 min^–1; remifentanil0.15 µg kg^–1 min^–1) or remifentanil-pronounced(propofol 50 µg kg^–1 min^–1; remifentanil 0.45µg kg^–1 min^–1) anaesthesia. In both groups,the procedure was started with remifentanil 0.4 µg kg^–1,propofol 2 mg kg^–1, and mivacurium 0.2 mg kg^–1.Cardiovascular measurements and EEG bispectral index (BIS) wererecorded. To maintain comparable anaesthetic depth, additionalpropofol (0.5 mg kg^–1) was given if BIS values were greaterthan 55 and remifentanil (0.4 µg kg^–1) if heartrate or arterial pressure was greater than 110% of pre-anaestheticvalues. Results. Patient and surgical characteristics, cardiovascularmeasurements, and BIS values were similar in both groups. Therewere no differences in recovery times between the groups (timeto extubation: 12.7 (4.5) vs 12.0 (3.6) min, readiness for transferto the recovery ward: 14.4 (4.4) vs. 13.7 (3.6) min, mean (SD)). Conclusions. In patients having short painful surgery, lesspropofol does not give faster recovery as long as the same anaestheticlevel (as indicated by BIS and clinical signs) is maintainedby more remifentanil. However, recovery times were less variablefollowing remifentanil-pronounced anaesthesia suggesting a morepredictable recovery. Br J Anaesth 2003; 91: 580–2     

Questioning the cardiocirculatory excitatory effects of opioids under volatile anaesthesia

Background. Opioid-induced hyperalgesia has been demonstratedin awake animals. We observed an increased haemodynamic reactivityin response to noxious stimuli in rats under sevoflurane anaesthesiatreated with a very low dose of sufentanil. The aim of thisinvestigation was to determine whether the two phenomena sharea common origin: an opioid-induced excitatory reaction. To addressthis, we administered several drugs with proven efficacy inopioid hyperalgesia to rats presenting with haemodynamic hyper-reactivity. Methods. The MACbar of sevoflurane was measured in controlsand in animals treated with sufentanil 0.005 µg kg^–1min^–1 before and after administration of i.v. (0.25, 0.5mg kg^–1) and intrathecal (i.t.) (250 µg) ketamine,i.v. (0.5, 1 mg kg^–1) and i.t. (30 µg) MK-801(NMDAantagonist), i.v. (0.1, 0.5 mg kg^–1) naloxone, i.v. (10mg kg^–1) and i.t. (50, 100 µg) ketorolac or i.t.(100, 150 µg) meloxicam (COX-2 inhibitor). Results. Sufentanil 0.005 µg kg^–1 min^–1 significantlyincreased MACbar (3.2 (SD 0.3) versus 1.9 (0.3) vol%). Withthe exception of naloxone, all drugs displayed a significantMACbar-sparing effect (>50%) in controls. Naloxone completelyprevented haemodynamic hyperactivity. Two patterns of reactionwere recorded for the other drugs: either hyper-reactivity wassuppressed and the MACbar-sparing effect was maintained (i.t.ketamine, i.t. MK-801, i.t. ketorolac [100 µg], i.t. meloxicam[150 µg]) or hyper-reactivity was blocked but MACbar-sparingeffect was lost (i.v. ketamine [0.5 mg kg^–1], i.v. MK-801[0.5, 1 mg kg^–1], i.v. ketorolac [10 µg kg^–1],i.t. ketorolac [50 µg], i.t. meloxicam [100 µg]). Conclusions. We have demonstrated that low-dose sufentanil-inducedhaemodynamic hyper-reactivity is an excitatory µ-opiate-relatedphenomenon. This effect is reversed by drugs effective in treatingopiate-induced hyperalgesia.     

Effect of remifentanil infusion rate on stress response to the pre-bypass phase of paediatric cardiac surgery

Background. Opioids are used routinely to eliminate the stressresponse in the pre-bypass phase of paediatric cardiac surgery.Remifentanil is a unique opioid allowing a rapidly titratableeffect. No data are available regarding a suitable remifentanildose regimen for obtunding stress and cardiovascular responsesto such surgery. Methods. We recruited 49 infants and children under 5 yr oldwho were randomized to receive one of four remifentanil infusionrates (0.25, 1.0, 2.5, or 5.0 µg kg^–1 min^–1).Blood samples were obtained at induction, pre-surgery, 5 minafter opening the chest, and immediately pre-bypass. Whole bloodglucose was measured at all time points while cortisol and neuropeptideY (NPY) were measured in the first and last samples. Heart rateand arterial pressure were also recorded. Results. There was a significant increase in whole blood glucose5 min after opening the chest and pre-bypass (P=0.009, P=0.002)in patients receiving remifentanil 0.25 µg kg^–1min^–1, but not in those receiving higher doses. Increasedremifentanil dosage was associated with reduced plasma cortisolduring surgery (P<0.001). Baseline NPY showed considerablevariation and there was no association between pre-bypass NPYand remifentanil dose. There was a significantly higher heartrate at the pre-bypass stage of surgery in the remifentanil0.25 µg kg^–1 min^–1 group compared with higherdoses (P=0.0006). Four out of five neonates with complex cardiacconditions showed severe bradycardia associated with remifentanil. Conclusions. In infants and children under 5 yr, remifentanilinfusions of 1.0 µg kg^–1 min^–1 and greatercan suppress the glucose increase and tachycardia associatedwith the pre-bypass phase of cardiac surgery, while 0.25 µgkg^–1 min^–1 does not. Remifentanil should be usedwith caution in neonates with complex congenital heart disease. Br J Anaesth 2004; 92: 187–94     

Dobutamine-induced dissociation between changes in splanchnic blood flow and gastric intramucosal pH after cardiac surgery

Gastric intramucosal acidosis, a sign of splanchnic tissue hypoxia,is common after cardiac surgery. We tested the hypothesis thatan increase in splanchnic blood flow induced by dobutamine improvessplanchnic tissue oxygenation after cardiac surgery. We measuredchanges in gastric intramucosal pH, splanchnic blood flow andoxygen transport in response to increased systemic flow inducedby dobutamine (mean 4.4 (range 3.0–7.0) µg kg^–1min^–1) after coronary artery bypass. We studied 22 stablepostoperative patients who were allocated randomly to receivedobutamine (n = 11) or to serve as controls (n = 11). Dobutaminewas given also to a separate group with a low cardiac indexafter operation (n = 6). The end-point was to increase cardiacindex by at least 25% and to exceed 2 litre min^–1 m^–2.Dobutamine consistently increased mean splanchnic blood flow(control 0.6 (SD0.2) vs 0.7 (0.2) litre min^–1 m^–2(P<0.05); normal cardiac output and dobutamine 0.7 (0.2)vs 1.1 (0.4) litre min^–1 m^–2 (P<0.01); low cardiacoutput and dobutamine 0.4 (0.1) vs 0.7 (0.1) litre min^–1m^–2 (P<0.05)) and oxygen delivery (control 102 (29)vs 111 (28) ml min^–1 m^–2 (ns); normal cardiac outputand dobutamine 106 (27) vs 156 (47) ml min^–1 m^–2(P < 0.01); low cardiac output and dobutamine 75 (21) vs110 (26) ml min^–1 m^–2 (P<0.05)) but had no effecton splanchnic oxygen consumption (control 44 (10) vs 49 (10)ml min^–1 m^–2 (ns); normal cardiac output and dobutamine45(12) vs 51 (17) ml min^–1 m^–2 (ns); low cardiacoutput and dobutamine 37 (9) vs 40 (9) ml min^–1 m^–2(ns)). Despite this, dobutamine reduced gastric intramucosalpH in all patients with low cardiac output (7.33 (0.12) vs 7.25(0.06)(P<0.05)) and in 50% of patients with stable haemodynamics(7.37(0.07) vs 7.34(0.06) (ns)). In contrast, gastric intramucosalpH remained stable in the control group (7.34 (0.05) vs 7.34(0.04) (ns)).We conclude that dobutamine resulted in a dissociationbetween splanchnic oxygen delivery and gastric mucosal tissueoxygenation, suggesting inappropriate distribution of bloodflow within the splanchnic region. (Br. J. Anaesth. 1995; 74:277–282)     

PHARMACOKINETICS OF THE INFUSION OF ALFENTANIL IN MAN

The pharmacokinetics of alfentanil under the conditions of anempirically derived 1 -h continuous infusion of 3µg kg^–1min^–1, with a bolus of 80 µg kg^–1, both i.v.,were determined in five patients. The distribution half-life(mean±SD) (7.4±3.1 min), elimination half-life(86.7 ± 15.8 min), apparent volume of distribution, V^area(0.44±0.15 litre kg^–1) and elimination clearance(3.33 ± 0.75 ml kg^–1 min^–1) were nimilarto those previously reported for a single bolus of alfentanil.These values for apparent volume of distribution and clearancecan be used to calculate correct bolus and infusion doses tomaintain any desired steady state plasma concentration usingstandard formulae: for example, to maintain a steady state plasmaconcentration of 400 ng ml^–1, a bolus doseof 176 µgkg^–1 and an infusion of 1.3 µg kg^–1min wouldbe required.     

PHARMACOKINETICS OF PROPOFOL INFUSIONS IN PATIENTS WITH CIRRHOSIS

We have compared the pharmacokinetics of propofol as an infusionin 10 control and 10 patients with cirrhosis. Anaesthesia wasinduced within 3–4 min during administration of an infusionof propofol 21 mg kg^–1 h^–1. After 5 min, the infusionwas decreased in a stepwise manner to 12 mg kg^–1 h^–1and subsequently 6 mg kg^–1 h^–1. The mean recoverytime after discontinuation of the infusion was significantlylonger in the cirrhotic group; however, when patients openedtheir eyes, blood concentrations of propofol were similar inboth groups (1 µg ml^–1). Pharmacokinetic analysiswas performed from the beginning of infusion to 8 h after termination.Total body clearance was not reduced significantly in cirrhotic(1.56 (SD 0.48) litre min^–1)compared with control (1.75(0.32) litre min^–1) patients. The volume of distributionat steady state was significantly greater in patients with cirrhosisthan in control patients (202 (82) litre vs 121 (49) litre).However, this difference did not change terminal eliminationhalf-life. The pharmacokinetics of propofol given by infusionto maintain general anaesthesia were not affected markedly bymoderate cirrhosis.     

DOSE REQUIREMENTS OF PROPOFOL BY INFUSION DURING NITROUS OXIDE ANAESTHESIA IN MAN: II: Patients Premedicated with Lorazepam

The infusion rate of propofol required to supplement 67% nitrousoxide in oxygen to maintain surgical anaesthesia was determinedin 72 patients premedicated with lorazepam. Following an inductiondose of propofol 2 mg kg^–1, groups of eight patients receivedan infusion of propofol varying from 60 to 200 µg kg^–1.Probit analysis was used to determine the ED₅₀ (130 µgkg^minus;1 min^–1; 95% confidence limits: 106–167µg kg^–1 min^–1) and ED₉₅ (348 µg kg^–1min^–1; 95% confidence limits: 233–1296 µgkg^–1 min^–1;) for propofol infusion. Whole bloodpropofol concentrations at the time of surgical incision correlatedstrongly with the infusion rate, giving an EC₅₀ value of 2.5µg ml ^–1, and an EC₉₅ value of 5.92 µg ml^–1.There was no significant correlation between the rate of infusionof propofol, or the total propofol dose, and the times to responseto command, or to recall of birthdate.     

EFFECT OF DOBUTAMINE ON OXYGEN SUPPLY AND UPTAKE IN HEALTHY VOLUNTEERS

We have measured the changes in Vo₂ and the Vo₂; D_o2 relationshipduringinfusion of dobutamine in healthy volunteers. Nine healthy,adult, non-obese, male physicians were infused with an incrementalinfusion of dobutamine starting at 2.5 µg kg^–1 min^–1increasing to 5.0 and then 7.5 y.g kg^–1 min^–1 for15 min each. Vo ₂ and cardiac index were measured every fiveminutes. Vo₂/(VO₂ m^–2) increased from a baseline of 128(SEM 6.1) ml min^–1 m^–2 to 159 (8.0)ml min¹ m^–2(P< 0.05) at 7.5 fig kg^–1 min^–1. The correspondingchanges for Do₂l (Do₂m^–2) were from 643 (35) ml min^–1m^–2 to 1240 (142) ml min^–1 m^–2 (P<0.05).The coefficient of correlation for pairs of Vo₂ and DO₂ values,at baseline and each dobutamine infusion in individual subjects,range from 0.89 to 0.99 (mean 0.95, SD 0.03). Dobutamine haspotent calorigenic effects; demonstration of a positive correlationbetween Vo₂ and Do₂ after infusion of dobutamine does not necessarilyimply an underlying tissue oxygen debt.     

PHARMACOKINETICS OF ALFENTANIL DURING AND AFTER A FIXED RATE INFUSION

Twenty-nine patients (age range 14–81 yr) undergoing orthopaedicsurgery received alfentanil 100 µg kg^–1 given astwo i.v. boluses followed by a fixed rate infusion of 1 µgkg^–1 min^–1 for 44–445 min. Additional 1-mgbolus doses of alfentanil were administered as required. Plasmasamples were assayed for alfentanil using radio-immunoassay.Pharmacokinetic parameters were estimated by a model-independentapproach and by curve-fitting. Regression analysis showed nostatistical relationship between T, CI or Vd and the durationof the infusion, total dose or body weight. We found no significantcorrelation between age and T of alfentanil for patients youngerthan 40 yr. For patients older than 40 yr, T increased linearlywith age. There was no significant decrease in Cl with age,although the lower values for CI (100–200 ml min^–1)were generally found in subjects older than 60 yr. The presentstudy demonstrated that a 100-µg kg^–1 loading doseand a 1-µg kg^–1 min^–1 infusion may be appropriatefor analgesia in general surgical procedures.     

Tramadol does not modify the Bispectral Index during anaesthesia with sevoflurane and remifentanil

Background. The aim of this study was to investigate the effectsof tramadol administered with ketorolac on the Bispectral Index(BIS) during anaesthesia with sevoflurane and remifentanil. Methods. Forty-six adult patients, ASA I–III, scheduledfor elective minor surgical procedures were studied. Patientswere premedicated with remifentanil infusion 0.4 µg kg^–1min^–1 and anaesthesia was induced 4–5 min laterwith propofol 1.5 mg kg^–1 and maintained with air–oxygen( 0.4), remifentanil 0.1–0.15 µg kg^–1 min^–1 and sevoflurane, adjusted to keep theBIS between 40 and 50. After 20 min of stable anaesthesia, thesubjects were allocated randomly to receive i.v. tramadol 1.5mg kg^–1 and i.v. ketorolac 0.3 mg kg^–1 (tramadolgroup) or saline (control group). BIS values, mean arterialpressure, heart rate and end-tidal carbon dioxide were recordedevery 5 min for 20 min. Results. Mean BIS values after tramadol administration werenot significantly different from those recorded in patientsreceiving saline throughout the period of observation. Therewere no patients who presented explicit recall of events underanaesthesia. No significant changes in mean arterial pressure,heart rate and end-tidal carbon dioxide were noted after tramadolinjection. Conclusion. Tramadol, given with ketorolac to prevent postoperativepain, during anaesthesia maintained with sevoflurane and remifentanilat BIS between 40 and 50, does not modify the BIS value.     

CARDIOVASCULAR AND RENAL HEMODYNAMIC EFFECTS OF DOPEXAMINE: COMPARISON WITH DOPAMINE

We have studied the effects of dopexamine and dopamine on systemicand renal haemodynamics in 20 male patients undergoing electivecoronary artery bypass surgery. Patients were allocated randomlyto two groups (n = 10) who were treated with incremental dosesof either dopexamine 1, 2 and 4 µg kg^–1 min^–1,or dopamine 2.5 and 5 µg kg^–1 min^–1, eachdose being maintained for 15 min. Measurements were performedbefore administration of the drug and at the end of the infusionperiod at each dose. Fentanyl and midazolam were used as anaestheticagents. Renal blood flow was measured with the argon washintechnique. Dopexamine 4 µg kg^–1 min^–1 producedan increase in cardiac index of 117% caused by a 65% reductionin afterload and an increase in heart rate by 61%. Dopamine5 µg kg^–1 min^–1 caused a 40% increase in cardiacindex as a result of an increase in stroke volume. Renal vascularresistance decreased more than systemic vascular resistancewith dopamine. With dopexamine, the increase in renal bloodflow (66%) was less than the increase in cardiac index, whilerenal vascular resistance and systemic vascular resistance declinedto almost the same extent. The results show that dopexamineexerts systemic and renal effects mainly via stimulation ofß₂-receptors. An action of dopexamine at renal DA₁-receptorscould not be demonstrated in this study.     

Low-dose remifentanil to suppress haemodynamic responses to noxious stimuli in cardiac surgery: a dose-finding study

Background: High-dose remifentanil (1–5 µg kg^–1 min^–1),commonly used for cardiac surgery, has been associated withmuscle rigidity, hypotension, bradycardia, and reduced cardiacoutput. The aim of this study was to determine an optimal lowerremifentanil dose, which should be accompanied by fewer adverseevents, that still effectively suppresses haemodynamic responsesto typical stressful stimuli (i.e. intubation, skin incision,and sternotomy). Methods: Total i.v. anaesthesia consisted of a target-controlled propofol(2 µg ml^–1) and a remifentanil infusion. Forty patientswere allocated to receive either a constant infusion of remifentanilat 0.1 µg kg^–1 min^–1 or up-titrations to 0.2,0.3, or 0.4 µg kg^–1 min^–1, respectively, 5min before each stimulus. Subsequently, changes in heart rateand mean arterial blood pressure were recorded for 8 min. Increasesexceeding 20% of baseline were considered to be of clinicalrelevance. Patients who exhibited these alterations were termedresponders. Results: The number of responders was less with the two higher remifentanildosages (P < 0.05) while propofol target doses could eitherbe kept at the same level or even be reduced without affectingthe plane of anaesthesia. Although single phenylephrine bolushad to be applied more frequently in these two groups (P <0.05), no severe haemodynamic depression was observed. Conclusions: Remifentanil at 0.3 and 0.4 µg kg^–1 min^–1in combination with a target-controlled propofol infusion inthe pre-bypass period is well tolerated. It appears to mitigatepotentially hazardous haemodynamic responses from stressfulstimuli equally well as higher doses when compared with datafrom the literature.