Gastric mucosal pH does not reflect changes in splanchnic blood flow after cardiac surgery

Despite the widespread use of gastric tonometry to assess splanchnicoxygen transport, no human data are available on the relationshipbetween splanchnic blood flow, splanchnic oxygen delivery andgastric mucosal pH. We have studied the effect of splanchnicblood flow and oxygen delivery on gastric mucosal pH after cardiacsurgery. During the first postoperative hours of intensive care,dopexamine was infused to increase cardiac output in eight patients,while six patients served as controls. Gastric mucosal pH (gastrictonometry), splanchnic blood flow and splanchnic oxygen deliveryand consumption (dye dilution) were measured. Dopexamine administrationsignificantly increased splanchnic blood flow (0.72 vs 1 .02litre min^–1 m^–2 (P < 0.05) and oxygen delivery(117 vs 161 ml min^–1 m^–2 (P < 0.05) comparedwith base line values. However, splanchnic oxygen consumptionremained unchanged and gastric mucosal pH levels decreased (7.30vs 7.25) (P < 0.05). The proportion of splanchnic blood flowof cardiac output did not change in response to infusion ofdopexamine, that is dopexamine did not favour blood flow distributionto the splanchnic region. In the control group there were nochanges in splanchnic blood flow and oxygen delivery, whilesplanchnic oxygen consumption increased (36 vs 39 ml min^–1m^–2 (P < 0.05) and gastric mucosal pH tended to decrease(7.33 vs 7.29) (ns). We conclude that after cardiac surgerygastric mucosal pH did not reflect changes in splanchnic bloodflow and oxygen delivery suggesting heterogeneous or inadequateblood flow distribution within the splanchnic region.      

Does the optimization of cardiac output by fluid loading increase splanchnic blood flow?

We studied the effects of increasing cardiac output by fluidloading on splanchnic blood flow in patients with haemodynamicallystabilized septic shock. Eight patients (five female, 39–86yr) were assessed using a transpulmonary thermo-dye-dilutiontechnique for the measurement of cardiac index (CI) intrathoracicblood volume (ITBV) as a marker of cardiac preload and totalblood volume (TBV). Splanchnic blood flow was measured by thesteady state indocyanine-green technique using a hepatic venouscatheter. Gastric mucosal blood flow was estimated by regionalcarbon dioxide tension (PR_CO2). Hydroxyethyl starch was infusedto increase cardiac output while mean arterial pressure waskept constant. In parallel, mean norepinephrine dosage couldbe reduced from 0.59 to 0.33 µg kg^–1 min^–1.Mean (SD) TBV index increased from 2549 (365) to 3125 (447)ml m^–2, as did ITBV index from 888 (167) to 1075 (266)ml m^–2 and CI from 3.6 (1.0) to 4.6 (1.0) litre min^–1m^–2. Despite marked individual differences, splanchnicblood flow did not change significantly neither absolutely (from1.09 (0.96) to 1.19 (0.91) litre min^–1 m^–2) norfractionally as part of CI (from 28.4 (19.5) to 24.9 (16.3)%).Gastric mucosal PR_CO2 increased from 7.7 (2.6) to 8.3 (3.1)kPa. The PCO₂-gap, the difference between regional and end-tidalPCO₂, increased slightly from 3.2 (2.7) to 3.4 (3.1) kPa. Thus,an increase in cardiac output as a result of fluid loading isnot necessarily associated with an increase in splanchnic bloodflow in patients with stabilized septic shock. Br J Anaesth 2001; 86: 657–62     

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)     

Pharmacokinetics of the three isomers of mivacurium and pharmacodynamics of the chiral mixture in hepatic cirrhosis

We have studied the pharmokinetics of cis-trans, trans-transand cis-cis mivacurium in 10 healthy subjects and 11 patientswith mild or moderate hepatic cirrhosis, during nitrous oxide-oxygen-isofluraneanaesthesia. Mivacurium 15µgkg^–1 min^–1 wasinfused for 10 min (total dose 0.15 mg kg^–1) and the plasmaconcentration of the three isomers measured at regular intervalsfor 190 min. The electromyographic response to the drug wasalso measured. Compartmental analysis of the resulting isomerprofiles was undertaken: one- and two-compartment models werefitted to derive clearance, volume of distribution and half-life.Clearance of the cis-trans and trans-trans isomers was reducedsignificantly in the cirrhotic compared with the healthy group:cis-trans (median (range)) 44 (15–121) ml kg^–1 min^–1vs 95 (57–213) ml kg^–1 min^–1 (P<0.05);trans-trans 32 (12–64) ml kg^–1 min^–1 vs 70(34–101) ml kg^–1 min^–1 (P<0.05). The differencein the clearance of the cis-cis isomer in the cirrhotic (4.2(2.9–12.1) ml kg^–1 min^–1) compared with thehealthy group (5.2 (2.9–8.9) ml kg^–1 min^–1)was not significant with this sample size. Clearance of eachisomer correlated significantly with plasma cholinesterase activity:cis-trans r = 0.73, P<0.001; trans-trans r=0.69, P<0.001;cis-cis r = 0.48, P<0.05. Terminal half-life was prolongedsignificantly for the cis-trans and trans-trans isomers in thecirrhotic patients compared with the healthy subjects: cis-trans2.5 (1.3–64.6) min vs 1.5 (0.7–2.2) min (P<0.05);trans-trans 11.1 (2.8–36.9) min vs 2.3 (1.2–7.8)min (P<0.001), but was not statistically significant forthe cis-cis isomer: 60.8 (8.7–155) min vs 50.3 (12.6–237)min. Volume of distribution was similar for all three isomersin the healthy and cirrhotic groups. Onset and recovery fromneuromuscular block were slower in the cirrhotic compared withthe healthy group: time to 90% depression of T1/T0 6.8 (5.8–11.5)min vs 5.9 (5.3–10.3) min (P<0.05); recovery index(25–75% recovery of T1/T0) 11.8 (5.6–26.3) min vs7.4 (4.7–9.6) min (P<0.01). There was a significantnegative correlation between all recovery variables and plasmacholinesterase activity.      

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.     

Combination of external chest wall oscillation with continuous positive airway pressure

We studied the effects of continuous positive airway pressure(CPAP) on pulmonary gas exchange during external chest walloscillation (ECWO), and the relationship with obesity, in ninepatients with normal body weight (group ‘N’) and10 obese patients (group ‘O’). During ECWO withCPAP 5, Pa_CO2 decreased in group ‘O’ (6.0 (SD 0.8)to 5.6 (0.5) kPa, P<0.05), whereas it increased in group‘N’ at all levels (P<0.01). Arterial PO₂ (P<0.001)was greater and Pa_CO2 (P<0.01) less in group ‘N’during CPPV and ECWO plus CPAP. We also compared the haemodynamiceffects of ECWO plus CPAP with those of continuous positivepressure ventilation (CPPV). ECWO plus CPAP and CPPV were appliedfor 30 min to 6 ASA III patients. Cardiac output (CI 2.7 (0.5)vs 2.1 (0.2) litre min^–1 m^–2, P<0.05) and strokevolume (SVI 49 (9) vs 32 (6) ml m^–2, P<0.05) were greaterduring ECWO plus CPAP than with CPPV. ECWO is less effectivein obese individuals than in those with normal body weight,and the effect of CPAP in overweight individuals is small. Br J Anaesth 2001; 87: 441–6     

Simultaneous measurement of cardiac output by thermodilution, thoracic electrical bioimpedance and Doppler ultrasound

To evaluate the accuracy of two non-invasive techniques forcardiac output (CO) measurement, we have measured CO simultaneouslyby thoracic electrical bioimpedance (TEB), pulsed Doppler ultrasound(DU) and standard thermodilution methods (TD) under differentclinical conditions. Measurements were made in 10 patients:(I) during steady state anaesthesia with controlled IPPV ventilation(n = 131), spread over the entire ventilatory cycle; (II) duringapnoea (n = 56); (III) during spontaneous breathing (n = 152)in the intensive care unit. Mean (SD) cardiac output valueswere: (I) CO_TD 3.5 (1.0) litre min^–1, CO_TEB 3.4 (0.7)litre min^–1 CO_DU 2.8 (0.7) litre min^–1; (II) CO_TD3.6 (0.6) litre min^–1, CO_TEB 3.5 (0.4) litre min^–1,CO_DU 2.9 (0.7) litre min^–1; (III) CO_TD 7.7 (1.5) litremin^–1, CO_TEB 7.6 (1.9) litre min^–1, CO_DU 5.2 (1.4)litre min^–1. The mean percentage deviation of TEB fromTD ranged from –2.2% to 1.4% and that of DU from TD wasfrom –16% to –32%. There were no statistically significantdifferences between TD and TEB, but TD and DU differed significantlyduring IPPV, apnoea and spontaneous ventilation (P < 0.0001).(Br. J. Anaesth. 1994; 72:133–138) ^*Department of Anaesthesiology, Caritas Krankenhaus, Werkstr.1, 66763 Dillingen/Saar, Germany      

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.     

Effects of mid-line thoracotomy on the interaction between mechanical ventilation and cardiac filling during cardiac surgery

Background. Mid-line thoracotomy is a standard approach forcardiac surgery. However, little is known how this surgicalapproach affects the interaction between the circulation andmechanical ventilation. We studied how mid-line thoracotomyaffects cardiac filling volumes and cardiovascular haemodynamics,particularly variations in stroke volume and pulse pressurecaused by mechanical ventilation. Methods. We studied 19 patients during elective coronary arterybypass surgery. Before and after mid-line thoracotomy, we measuredarterial pressure, cardiac index (CI) and global end-diastolicvolume index (GEDVI) by thermodilution, left ventricular end-diastolicarea index (LVEDAI) by transoesophageal echocardiography andthe variations in left ventricular stroke volume and pulse pressureduring ventilation by arterial pulse contour analysis. Results. After thoracotomy, CI increased from 2.3 (0.4) to 2.9(0.6) litre min^–1 m^–2, GEDVI increased from 605(110) to 640 (94) litre min^–1 m^–2, and LVEDAI increasedfrom 9.2 (3.7) to 11.2 (4.1) cm² m^–2. All these changeswere significant. In contrast, stroke volume variation (SVV)decreased from 10 (3) to 6 (2)% and pulse pressure variation(PPV) decreased from 11 (3) to 5 (3)%. Before thoracotomy, SVVand PPV significantly correlated with GEDVI (both P<0.01).When the chest was open, similar significant correlations ofSVV (P<0.001) and PPV (P<0.01) were found with GEDVI. Conclusion. Thoracotomy increases cardiac filling and preload.Further, thoracotomy reduces the effect of mechanical ventilationon left ventricular stroke volume. However, also under openchest conditions, SVV and PPV are preload-dependent. Br J Anaesth 2004; 92: 808–13     

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)      

Assessing fluid responsiveness during open chest conditions

Background. Measurement of ventilation-induced left ventricularstroke volume variations (SVV) or pulse pressure variations(PPV) is useful to optimize preload in patients after cardiacsurgery. The aim of this study was to investigate the abilityof SVV and PPV measured by arterial pulse contour analysis toassess fluid responsiveness in patients undergoing coronaryartery bypass surgery during open-chest conditions. Methods. We studied 22 patients immediately after midline sternotomy.We determined SVV, PPV, left ventricular end-diastolic areaindex by transoesophageal echocardiography, global end-diastolicvolume index and cardiac index by thermodilution before andafter removal of blood 500 ml and after volume substitutionwith hydroxyethyl starch 6%, 500 ml. Results. Blood removal resulted in a significant increase inSVV from 6.7 (2.2) to 12.7 (3.8)%. PPV increased from 5.2 (2.5)to 11.9 (4.6)% (both P<0.001). Cardiac index decreased from2.9 (0.6) to 2.3 (0.5) litres min^–1 m^–2 and globalend-diastolic volume index decreased from 650 (98) to 565 (98)ml m^–2 (both P<0.025). Left ventricular end-diastolicarea index did not change significantly. After fluid loadingSVV decreased significantly to 6.8 (2.2)% and PPV decreasedto 5.4 (2.1)% (both P<0.001). Concomitantly, cardiac indexincreased significantly to 3.3 (0.5) litres min^–1 m^–2(P<0.001) and global end-diastolic volume index increasedsignificantly to 663 (104) ml m^–2 (P<0.005). Left ventricularend-diastolic area index did not change significantly. We founda significant correlation between the increase in cardiac indexcaused by fluid loading and SVV as well as PPV before fluidloading (SVV, R=0.74, P<0.001; PPV, R=0.61, P<0.005).No correlations were found between values of global end-diastolicvolume index or left ventricular end-diastolic area index beforefluid loading and the increase in cardiac index. Conclusion. Measurement of SVV or PPV allows assessment of fluidresponsiveness in hypovolaemic patients under open-chest andopen-pericardium conditions. Thus, measuring heart–lunginteractions may improve haemodynamic management during surgicalprocedures requiring mid-line sternotomy.     

Haemodynamic effects of the lateral decubitus position and the kidney rest lateral decubitus position during anaesthesia

We measured the haemodynamic effects of changing from the supineposition to the lateral decubitus (lateral) position, and thento the kidney rest lateral decubitus (kidney) position in 12patients undergoing nephrectomy under isoflurane anaesthesia.Eight control patients undergoing pulmonary surgery remainedin the lateral position. The lateral position produced no significantchanges. In the kidney position, however, significant reductionsoccurred in the mean arterial (P<0.01), right atrial (P<0.05)and pulmonary artery wedge pressures (P<0.01). There werealso significant reductions in cardiac index (from 3.04 ( 0.21) to 2.44 (0.26) litre min^–1 m^–2,P<0.01) and stroke volume index (from 40 (5) to 31 (5) mlbeat^–1 m^–2, P<0.01). The systemic vascular resistanceindex increased significantly (P<0.05). Cardiac output wasprobably reduced by a decrease in venous return and an increasein systemic vascular resistance.     

Effects of hyperventilation on the inspiratory to end-tidal oxygen difference

We assessed the inspiratory to end-tidal oxygen difference during voluntary hyperventilation in 10 healthy male volunteers.The oxygen difference was measured with a fast-response paramagneticdifferential oxygen sensor. As simultaneous changes in metabolismand cardiac output also influence oxygen uptake was measuredwith indirect calorimetry and noninvasive transthoracic electricalbioimpedance was used for measurement of cardiac output. Aftera rest period, subjects were instructed to double their minuteventilation volume (VE) and after 5 min triple their restingVE for another 5 min. decreased from a zero value of 6.4 kPato 3.9 kPa at 5min (P < 0.01) and 2.9kPa at 10min (P <0.01). At 15min (i.e. 5min after the end of hyperventilation)there was an increase in to 8.3 kPa (P < 0.05). Regressionanalysis between (kPa) and VE (litre m^–2 min^–1)gave the formula: , r = –0.92, n = 158. Oxygen uptakeand cardiac output did not change significantly during hyperventilation,but decreased in the post-hyperventilation period. An oxygendifference of more than 8 kPa was associated with significantarterial desaturation.     

INFLUENCE OF CARDIAC OUTPUT ON THE CORRELATION BETWEEN MIXED VENOUS AND CENTRAL VENOUS OXYGEN SATURATION

The influence of cardiac output on the correlation between centralvenous oxygen saturation and mixed venous oxygen saturationwas assessed in 51 patients who had both a pulmonary arterycatheter and separate central venous catheter in situ. Seventy-sixpaired samples were taken from the catheters and oxygen saturationmeasured immediately in a Ciba Corning 2500 Co-oximeter. Cardiacoutput was measured using a standard thermodilution technique.The data were separated into groups with low cardiac index (<2.5 litre min^–1 m^–2; n = 20). medium cardiac index(2.5–4.0 litre min^–1 m^–2; n = 36) and highcardiac index (> 4.0 litre min^–1 m^–2; n = 20).The correlation coefficients of the three groups were: low cardiacindex 0.95, medium cardiac index 0.88 and high cardiac index0.95 (P < .001 for all three groups). All measurements weremade before any x-ray and necessary repositioning of the centralvenous catheter. These results suggest that central venous oxygensaturation is a useful estimate of mixed venous oxygen saturationand that the influence of cardiac output on that estimate isminimal.     

EFFECT OF HALOTHANE ON HYPOXIC AND HYPERCAPNIC VENTILATORY RESPONSES OF GOATS

We have measured the ventilatory responses to increased inspiredcarbon dioxide and to hypoxia in four goats awake and at 0.5%,1.0% and 1.25% end-tidal halothane concentration. While maintainingPE'_CO2 constant at each of three values (means 5.86, 6.45 and7.2 kPa), PE'_O2 was reduced rapidly from more than 25 kPa to5.3–6 kPa for 3 min to record the increase in ventilation.Eleven sets of these 24 steady state points were obtained (2PO₂ x 3 P_CO2 x 4 anaes. = 24). The mean isocapnic hypoxic ventilatoryresponse (HVR) was 6.52 (SD 2.58) litre min^–1 (n = 33)when awake, 5.62 (3.48) litre min^–1 at 0.5% end-tidalhalothane (ns), 3.05 (2.02) litre min^–1 at 1 % and 2.91(2.12) litre min^–1 at 1.25%, the last two being reducedsignificantly from awake and 0.5 % halothane (P < 0.05).With 1.25 % halothane, HVR was reduced to 44.5 (18.6)% of theawake HVR. However, when HVR was expressed as % increase inventilation produced by isocapnic hypoxia, it was 71 (19) %awake but 124 (65) % with 1.25% halothane, a significant increasewith halothane (P < 0.05). With 1.25% halothane, the carbondioxide response slope decreased to 36.4 (26.4) % of control;hypoxia did not increase the slope significantly. Whereas previousstudies in man have shown that halothane preferentially depresseshypoxic chemosensitivity and has a significant effect at 0.1MAC, in the goat the hypoxic and carbon dioxide chemosensitivitieswere depressed equally. At 0.5% end-tidal concentration (about0.5 MAC), halothane did not significantly depress hypoxic response.     

PHARMACOKINETICS OF ATRACURIUM AND LAUDANOSINE IN PATIENTS WITH HEPATIC CIRRHOSIS

The pharmacokinetic profiles of atracurium and one of its derivatives,laudanosine were studied following an i.v. bolus of atracurium0.6 mg kg^–1 administered to eight patients with hepaticcirrhosis and to seven healthy controls. The central volumeof distribution of atracurium was greater in the patients withcirrhosis (104.6 ml kg^–1) compared with the controls (69.6ml kg^–1) (P < 0.05), as was the total volume of distribution(281.8 ml kg^–1 and 202.1 ml kg^–1, respectively)(P < 0.05). There was no significant difference in the eliminationhalf-life of atracurium between the two groups. The total volumeof distribution of laudanosine was increased in cirrhotic patients(2.68 litre kg^–1) compared with healthy controls (1.97litre kg^–1) (P < 0.05), as was its elimination half-life(277 min in cirrhotic individuals; 168 min in controls) (P <0.05). There was no significant difference in the clearanceof laudanosine between the two groups.     

INFLUENCE OF CROHN'S DISEASE ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF ALFENTANIL

We have compared the dose requirements, pharma cokinetics andpharmacodynamics of alfentanil in 12 patients with Crohn's diseaseand 10 control patients undergoing abdominal surgery. Plasmaconcentrations of ₁-acid glycoprotein (AAG) and alfentanil proteinbinding were also measured. Anaesthesia was induced with aifentanil100 µg kg^–1 and thiopentone, and maintained withnitrous oxide in oxygen and aifentanil 25–200 µgkg^–1 h^–1 Arterial blood samples were obtained beforeand after each change in the aifentanil infusion rate and for6 h after stopping the infusion. Pharmacokinetic data were derivedusing non-compartmental methods. Alfentanil concen tration—effectdata were evaluated by non-linear regression, where effect waseither response or no response to surgical stimulation. Meanintra operative aifentanil requirement was greater in patientswith Crohn's disease (2.48 µg kg^–1 min^–1)than in control patients (1.35 µg kg^–1 min^–1)(P< 0.01). Mean elimination half-life, total plasma clearanceand steady state distribution volume in patients with Crohn'sdisease were comparable to those in control patients (80 vs81 min, 5.7 vs 6.4 ml kg^–1 min^–1 and 0.70 vs 0.68litre kg^–1, respectively). Mean plasma concentration atwhich the probability of no response was 50% for the intra-abdominalperiod of surgery was greater in the Crohn group (359 ng ml^–1)than in the control group (199 ng ml^–1 (P<0.02). PlasmaAAG concentrations were greater in the Crohn group, but thefree fraction of aifentanil was similar in both groups. Thisstudy indicates that the increased alfentanil requirement inpatients with Crohn's disease may be attributed to a changein pharmacodynamics. (Br. J. Anaesth. 1993; 71: 827–834)     

Volume kinetics of glucose 2.5% solution and insulin resistance after abdominal hysterectomy

Background. We hypothesized that volume kinetics can be usedto predict the rate of infusion of glucose 2.5% solution requiredto yield any predetermined plasma glucose level and degree ofplasma dilution during the postoperative period. Methods. In 15 women, mean age 50 yr (range 37–63), 2days after an abdominal hysterectomy, a volume kinetic analysiswas performed on an i.v. infusion of 12.5 ml kg^–1 (900ml) of glucose 2.5% given over 45 min. The insulin resistancewas measured by a glucose clamp, and it was compared with dailybioimpedance analyses, which indicated the hydration of theintra/extracellular body fluid spaces. Results. The clearance of glucose was 0.42 litre min^–1(0.60 litre min^–1 is normal) while the other five parametersin the kinetic model were similar to those obtained in healthyvolunteers. Computer simulations indicated that in a 70-kg female,at steady state, the rate of infusion (ml min^–1) shouldbe three times the allowed increase in plasma glucose (mmollitre^–1). To maintain a predetermined plasma dilutionthe corresponding rate factor was 160. The glucose uptake duringclamping was 3.9 mg kg^–1 min^–1 (7.0 is normal),which, during the second day after hysterectomy, correlatedwith the dehydration of the intracellular space (r=0.77; P<0.002)and with the protein catabolism as indicated by the urinaryexcretion of 3-methylhistidine (r=–0.76, P<0.002). Conclusion. The anaesthetist can prescribe postoperative administrationof glucose 2.5% to reach any desired plasma glucose level anddilution by using the two presented nomograms. Insulin resistancecorrelated with intracellular dehydration and protein catabolism.     

Rate of injection through whitacre needles affects distribution of spinal anaesthesia

A prospective, randomized, double-blind study was performedto investigate whether altering the rate of injection of localanaesthetic through a Whitacre needle had any effect on thespinal block achieved. Twenty patients scheduled for electiveurological surgery under spinal anaesthesia received an injectionof 3 ml of 0.5% plain bupivacaine either by hand (fast)over 10 s (18 ml min^–1) or by infusionpump (slow) over 3 min (1 ml min^–1). Allpatients were in the sitting position both during insertionof the spinal needle and for 3 min after the start of spinalinjection, and they then changed to the supine position. Theslow injection group achieved peak sensory block earlier, aftera median interval of 20 (95% confidence interval 12.5–30) minvs 30 (22.5–45) min (P<0.05) for the fast group. Thelevel of peak sensory block was similar: T3.5 (T2–T4.5)vs T4 (T1.5–T6.5). The time to lowest mean arterial pressureoccurred earlier in the slow group, at 10 (8 to 18) vs 20 (15–31) min(P<0.05). Duration of the motor block was shorter in theslow group: 180 (152–242) vs 270 (225–300). We concludethat a slow spinal injection of plain bupivacaine results ina block of more rapid onset and recovery. Br J Anaesth 2001; 86: 245–8     

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).