Publisher's copy made available with the permission of the publisher © Australian Society of AnaesthetistsTheoretically, if the cardiac output were increased in the presence of a given intrapulmonary shunt, the arterial saturation should improve as the venous oxygen extraction per ml of blood decreases if the total oxygen consumption remains constant. Previous work demonstrated that this was not achieved with adrenaline or isoprenaline as increased shunting negated any benefit from improved cardiac output and mixed venous oxygen content. However, pharmacological stimulation of cardiac output and venous oxygen without any increase in shunt should achieve the goal of improved arterial oxygenation. To test this hypothesis, seven pigs were subjected to one-lung ventilation and infused on separate occasions, with dopamine and with dobutamine in random order to increase the cardiac output. The mixed venous oxygen content, shunt fraction, oxygen consumption and arterial oxygen saturation were measured. With both dopamine and dobutamine there was a consistent rise in venous oxygen content. However, with dopamine, the mean shunt rose from 28% to 42% and with dobutamine, the mean shunt rose from 45% to 59% (both changes P<0.01). With dopamine, the mean arterial oxygen saturation fell by 4.7%, and with dobutamine by 2.9%, but neither fall was statistically significant. It is concluded that any benefit to arterial saturation which might occur from a dopamine- or dobutamine-induced increase in mixed venous oxygen content during one-lung ventilation is offset by increased shunting. During one-lung anaesthesia, there would appear to be no benefit to arterial saturation in increasing cardiac output with an infusion of either dopamine or dobutamine.W. J. Russell, M. F. Jameshttp://www.aaic.net.au/Article.asp?D=200331

Furman W.R.

Karzai W.

Marin J.L.

Russell W.J.

Anaesthesia and Intensive Care

English

Russell, W.

James, M.

Adelaide Research & Scholarship

Anaesthesia and Intensive Care, Vol. 32, No. 5, October 2004Anaesth Intensive Care 2004; 32: 644-648The Effects on Arterial Haemoglobin Oxygen Saturation andon Shunt of Increasing Cardiac Output with Dopamine orDobutamine During One-lung VentilationW. J. RUSSELL*, M. F. JAMES†Department of Anaesthesia, University of Cape Town, South AfricaSUMMARYTheoretically, if the cardiac output were increased in the presence of a given intrapulmonary shunt, the arterialsaturation should improve as the venous oxygen extraction per ml of blood decreases if the total oxygen consumptionremains constant. Previous work demonstrated that this was not achieved with adrenaline or isoprenaline asincreased shunting negated any benefit from improved cardiac output and mixed venous oxygen content. However,pharmacological stimulation of cardiac output and venous oxygen without any increase in shunt should achieve thegoal of improved arterial oxygenation. To test this hypothesis, seven pigs were subjected to one-lung ventilation andinfused on separate occasions, with dopamine and with dobutamine in random order to increase the cardiac output.The mixed venous oxygen content, shunt fraction, oxygen consumption and arterial oxygen saturation were measured. With both dopamine and dobutamine there was a consistent rise in venous oxygen content. However, withdopamine, the mean shunt rose from 28% to 42% and with dobutamine, the mean shunt rose from 45% to 59%(both changes P<0.01). With dopamine, the mean arterial oxygen saturation fell by 4.7%, and with dobutamine by2.9%, but neither fall was statistically significant.It is concluded that any benefit to arterial saturation which might occur from a dopamine- or dobutamine-inducedincrease in mixed venous oxygen content during one-lung ventilation is offset by increased shunting. During one-lunganaesthesia, there would appear to be no benefit to arterial saturation in increasing cardiac output with an infusionof either dopamine or dobutamine.Key Words: LUNG: shunting. VENTILATION: one-lung. HEART: dopamine, dobutamine, cardiac output. OXYGEN: saturationThe use of one-lung ventilation for many intra-thoracic procedures is common. Occasionally, in spiteof an optimal position of the double-lumen tube,major arterial desaturation occurs. With 100% in-spired oxygen and a given oxygen consumption, thedegree of arterial desaturation is dependent on onlytwo factors, the shunt fraction and oxygen content ofthe mixed venous blood. For a given shunt fraction,the saturation in the arterial blood will rise as themixed venous oxygen content rises. Thus one possibleapproach to minimizing the impact on the arterialsaturation could be to elevate the mixed venousoxygen content as high as possible.The oxygen content of mixed venous blood isdetermined by the initial level of arterial oxygen con-tent, the tissue oxygen uptake and the cardiac output.If the oxygen tissue uptake (oxygen consumption)remains unaltered, increasing the cardiac outputshould result in a higher mixed venous oxygen con-tent and, if the shunt remains constant, a betterarterial oxygen saturation as a secondary conse-quence. Thus the arterial saturation during one-lunganaesthesia should improve if the cardiac outputwere increased without increasing the shunt fraction.Previous attempts to do this by increasing the cardiacoutput with either adrenaline or isoprenaline failed toimprove the arterial saturation, mainly because therewas an increased shunt fraction in parallel with therise in cardiac output, together with an increase inmetabolic rate1. However, increasing cardiac outputwithout altering the shunt fraction or peripheraloxygen consumption should be beneficial if the cor-rect agent were found. To further test this hypothesiswe stimulated the cardiac output with dopamine or*Visiting Fellow.†Professor and Head.Address for reprints: Dr W. J. Russell, Department ofAnaesthesia and Intensive Care, Royal Adelaide Hospital, NorthTerrace, Adelaide, S.A. 5000.Accepted for publication on May 24, 2004.dobutamine in pigs who were being ventilated on onelung under general anaesthesia.METHODSThe animal ethics committee of the University of Cape Town approved this study in advance. Pigsweighing between 23 and 29 kg were premedicatedintramuscularly with ketamine 300 mg, diazepam 2.5 mg and atropine 0.6 mg. After the pig was verydrowsy, a cannula was inserted into an ear vein andthiopentone administered intravenously until theanimal was unconscious. The pig’s trachea was thenintubated with a 7.0 mm cuffed tracheal tube. Onceventilation was established, pancuronium 8 mg wasadministered and the lungs ventilated with oxygenand 1% halothane. Arterial cannulation was estab-lished by a cut-down into the right carotid artery.After carotid artery cannulation, a pulmonary arterycatheter was floated into position via the right ex-ternal or internal jugular vein. Halothane administra-tion was varied between 0.5% and 2% as determinedby the arterial blood pressure and heart rate. Addi-tional pancuronium 2 mg and ketamine 100 mg wereadministered every half hour to ensure an adequatedepth of anaesthesia. Nasopharyngeal temperaturewas monitored and the temperature maintainedbetween 35.5 and 37.5°C with hot air warming. Heartrate (ECG) and blood pressure were monitored con-tinuously and recorded every minute directly fromthe monitor.Once monitoring had been established, a tracheos-tomy was made and the tracheal tube was replaced by a 35 Fr left-sided double-lumen endobronchialtube through the tracheostomy. The bronchial cuff was  inflated to achieve a seal in the trachea. The lung inflation pressure was noted (usually about 25 cmH2O) and with the cuff inflated, the tubeadvanced about 1 cm with each breath. Placement ofthe tube in the left main bronchus was evidenced by afirm resistance to further advancement, a fall in lungcompliance (as seen by a sharp rise in inflation pres-sure for the set tidal volume), asymmetry of chestmovement and of breath sounds and a sharp fall inarterial oxygen saturation. Once this was achieved,the cuff was deflated and the tube moved in a further15 mm. The tube was then sutured to the skin toreduce further movement.Ventilation was adjusted to achieve a PaCO2 be-tween 30 and 45 mmHg. Once this was done, cardiacoutput was measured in triplicate by cold thermodilu-tion. Duplicate arterial and mixed venous samples foranalysis of PO2, oxygen saturation and PCO2 weretaken and measured on a Radiometer ABL505 bloodgas analyser. After these samples, the cardiac outputwas again measured in triplicate. With the measure-ment of blood gases, the haemoglobin content ofeach of the samples was also determined. The shuntfraction was calculated with the standard equationsusing an estimated alveolar oxygen pressure of 760 mmHg less water vapour and arterial CO2 ten-sion i.e. alveolar PO2=713–PaCO2, and alveolarcapillary oxygen content was calculated as 1.34 ml xHb (g/100 ml)+0.003 ml x alveolar PO2 (mmHg).Oxygen consumption was calculated as the differencebetween the arterial and venous oxygen content mul-tiplied by the averaged pre-sample and post-samplecardiac outputs.Cardiac output was then increased by an intra-venous infusion of dopamine or dobutamine. Thefirst drug used on each pair of pigs was selected ran-domly by the toss of a coin; the second pig of the pairreceived the opposite sequence of sympathomimeticdrugs.The rate of drug infusion was adjusted every twominutes. The aim was to achieve at least a 40%increase in cardiac output. Once a satisfactory in-crease in cardiac output had been achieved, the infu-sion was maintained for 10 minutes and a triplicateset of cardiac output measurements was taken. Thiswas followed by arterial and mixed venous bloodsamples taken in duplicate, and finally a further set oftriplicate cardiac output measurements.The sympathomimetic infusion was then ceasedand the heart rate and cardiac output allowed tosettle, usually within ±10% of the previous controlvalues. After 15 minutes the cardiac output and bloodgases were again measured. The second infusion wasthen commenced to the same target increase incardiac output. Once the values had been stable for10 minutes, cardiac output and blood gases wereagain measured. The infusion was then stopped and 15 minutes later, baseline values were againmeasured. Changes in output and other parameterswere measured against the average value of thepreceding and following control states.At the end of the experiment the pig was killed withan overdose of thiopentone and intravenous air. Thebronchial tree and lungs were subjected to a postmortem examination to ensure that ventilation ofonly the left lung had been achieved. Statistical analysis was done using Statview 5.0(SAS Institute Inc, Cary, NC, U.S.A.) and Instat 2(GraphPad Software Inc. San Diego CA, U.S.A.). Forcomparisons of the two treatments, a paired t test was used. The three controls were compared withANOVA. For all probabilities, a two-tailed test wasused with significance set at P=0.05. 645 ARTERIAL SATURATION WITH INOTROPES IN ONE-LUNG VENTILATIONAnaesthesia and Intensive Care, Vol. 32, No. 5, October 2004RESULTSThe experimental protocol was completed in sevenpigs. All pigs had a direct bronchial airway from thetrachea to the right upper lobe and the final intuba-tion with the double-lumen tube completely excludedthe right lung. The results are presented as meanvalues with standard deviations.Cardiac OutputThe control cardiac outputs ranged from 2.2 to 4.5 l/min. The percentage increase in cardiac outputwith dopamine ranged from 59%% to 123%, and withdobutamine from 42% to 204%. Mixed Venous Oxygen ContentMixed venous oxygen content rose with alldopamine and dobutamine infusions. With dopamineit rose from a mean of 7.5 ml per 100 ml (SD 2.8 ml)to a mean of 9.3 ml per 100 ml (SD 2.8 ml). The meanincrease was 29% (range 2 to 87%, P=0.043). Themean increase with dobutamine was from 7.0 ml per100 ml (SD 2.1 ml) to a mean of 9.6 ml per 100 ml(SD 1.6 ml) with a mean increase of 44% (range 17%to 103%, P=0.0076).Overall, the rise in venous oxygen contentappeared to be linearly related to the increase incardiac output (r=0.54, Figure 1).Arterial Oxygen SaturationThe control arterial oxygen saturation varied from79.3% to 100%: the mean control saturation was94.2±5.2%. The mean control saturations for thedopamine and dobutamine were 95.6±2.4% and92.8±7.0% respectively (P=0.33). During dopamineinfusion, the arterial saturations varied from 79.1% to 99.8%, and the mean saturation was 91.0±7.6%.The mean change in saturation was –4.7±6.3%(P=0.098). During dobutamine infusion, the meanarterial saturations varied from 79.1% to 100%, andthe mean saturation was 89.9±7.2%. The meanchange in saturation was -2.9±5.5% (P=0.21).ShuntFor the whole group, the mean control shunt was27.8±8.6%. After the administration of dopamine,the mean shunt increased to 42.1±9.5%. The meandifference between the mean control shunt and the mean shunt during dopamine infusion was14.5±6.7% (paired t=5.7, P=0.0013, Figure 2). The mean control shunt prior to the administrationof dobutamine was 28.0±11.1%, which was notsignificantly different from the dopamine control(P=0.92). During the dobutamine infusion, the meanshunt increased to 45.4±15.0%, which was again notsignificantly different from the shunt during thedopamine infusion (P=0.62), but was significantlygreater than the control shunt. The mean differencein shunt from control for the dobutamine infusionswas 17.4±10.4% (paired t=4.4, P=0.0044, Figure 3).Oxygen ConsumptionFor the whole group, the mean control oxygen con-sumption was 180.8±43.8 ml/min. After the admini-stration of dopamine, the mean consumption in-creased to 230.9±52.7 ml/min (P=0.016). The meandifference between control and the oxygen consump-646 W. J. RUSSELL, M. F. JAMESAnaesthesia and Intensive Care, Vol. 32, No. 5, October 2004FIGURE 1: Relative change in mixed venous oxygen content withchanges in cardiac output. There is a rise in mixed venous oxygencontent as the cardiac output is increased. Regression line ∆Vo2=0.003 (∆CO)+0.036. The dark dots are dobutamine stimulationand the open circles are dopamine.FIGURE 2: The effect of dopamine infusion on shunt. In all pigs theshunt increased. The mean increase was 14.5±6.7% (mean±SD).Percentage Shunttion during dobutamine infusion was similar at61.7±48.6 ml/min (paired t=3.36, P=0.015). Thecombined results are shown in Figure 4.Other ChangesThree control measurements of shunt and oxygenconsumption were made on each animal; an initialmeasurement was made before the first infusion andthen two further measurements, one after each in-fusion. These control measurements of shunt andoxygen consumption were not significantly differenteach of the three times. (For shunt, one-way ANOVAwith repeat measures F=0.11, P=0.90; and foroxygen consumption one-way ANOVA with repeatmeasures F=0.30, P=0.75 respectively.)DISCUSSIONIt is clear that in this pig model, in spite of animproved mixed venous oxygen content, the use ofeither dopamine or dobutamine to boost cardiac out-put is associated with a significant increase in shunt-ing which impedes any improvement in arterialoxygen saturation. Thus four possible agents stimu-lating cardiac output and thus arterial saturation havebeen shown not to achieve this goal. The increasedshunt may be the result of strong inhibition of hypoxicvasoconstriction or a direct intra-pulmonary vaso-dilatation. Studies by Furman et al2 and Marin et al3have shown that isoprenaline and dobutamine havepulmonary vasodilator properties that may inhibithypoxic pulmonary vasoconstriction.Although it is possible that other cardiac stimulantsmay be able to increase the cardiac output withoutthe adverse effects, the present evidence suggests thatmost potent inotropes do increase oxygen consump-tion4. Of the presently available inotropic agents, evendopamine, which has been claimed not to increaseoxygen consumption5, did not improve oxygenation.Although neither the further desaturation withdopamine nor dobutamine treatment reached statis-tical significance, this might be clinically significant. Apost hoc power analysis indicated that with the differ-ence observed, 21 pigs would have to be treated forthe difference to reach statistical significance.Whether or not there is another inotropic agentthat would avoid increased intrapulmonary shuntingis open to question. However, it seems likely that anyagent with significant beta-adrenergic activity wouldcause a similar degree of pulmonary vasodilatation,thus negating the ability of any improved venousoxygen content to achieve a higher arterial oxygensaturation.The correlation between the increase in cardiacoutput and the increased shunt suggests that increas-ing cardiac output by the use of β-adrenergic agentswill inevitably be offset by increases in shunt. Theresults of this study strongly suggest that any attemptto improve arterial saturation during one-lung anaes-thesia by stimulation of cardiac output with cate-cholamines is unlikely to be beneficial. However, itshould be borne in mind that these experiments wereconducted in animals with healthy lungs, and with alarge number of pulmonary segments not ventilated.It is possible that these results may not apply to quitethe same extent in patients in whom the excluded647 ARTERIAL SATURATION WITH INOTROPES IN ONE-LUNG VENTILATIONAnaesthesia and Intensive Care, Vol. 32, No. 5, October 2004FIGURE 3: The effect of dobutamine infusion on the shunt. In all pigs the shunt increased. The mean increase in shunt was17.4±10.4% (mean±SD).FIGURE 4: Change in oxygen consumption with dopamine anddobutamine infusions. The solid lines and solid dots show the con-trol and dopamine treatment oxygen consumptions; the meanincrease in oxygen consumption was 52.1±41.4 ml/min. Thedashed lines and open circles show the control and dobutaminetreatment oxygen consumption; the mean increase was 61.6±48.6 ml/min.Percentage ShuntOxygen Consumption ml/min648 W. J. RUSSELL, M. F. JAMESAnaesthesia and Intensive Care, Vol. 32, No. 5, October 2004lung is extensively diseased. Conceivably, in suchcases, where the collapsed lung may be minimallyresponsive to the vasodilator effects of inotropicagents, enhancement of cardiac output with inotropicsupport may benefit arterial oxygenation, through theincreased mixed venous oxygen content that we haveshown with all inotropes tested. The value of cate-cholamines with a greater vasoconstrictor effectremains to be investigated.In conclusion, although enhancing the cardiac output with a catecholamine infusion should theo-retically improve the arterial saturation during one-lung anaesthesia, our experiments in pigs do not sup-port this hypothesis. As with isoprenaline and adren-aline1, stimulation of cardiac output either withdopamine or dobutamine is associated with an in-creased shunt and therefore no improvement inarterial oxygenation. These two effects offset eachother and prevent any beneficial effect in arterialoxygenation.ACKNOWLEDGEMENTSThe authors wish to acknowledge the technical skill of Mr Brian Sassman in assisting with theseexperiments.REFERENCES1. Russell WJ, James MF. The effects on increasing cardiac outputwith adrenaline or isoprenaline on arterial haemoglobin oxygensaturation and shunt during one-lung ventilation. AnaesthIntensive Care 2000; 28:636-641.2. Furman WR, Summer WR, Kennedy TP, Sylvester JT. Com-parison of the effects of dobutamine, dopamine and isopro-terenol on hypoxic pulmonary vasoconstriction in the pig. CritCare Med 1982; 10:371-374.3. Marin JL, Orchard C, Chakrabarti MK, Sykes MK. Depressionof hypoxic pulmonary vasoconstriction in the dog by dopamineand isoprenaline. Br J Anaesth 1979; 51:303-312.4. Karzai W, Lötte A, Günnicker M, Vorgrimler-Karzai UM,Preibe H-J. Dobutamine increases oxygen consumption duringconstant flow cardiopulmonary bypass. Br J Anaesth 1996; 76:5-8.5. Karzai W, Günnicker M, Scharbert G, Vorgrimler-Karzai,UM,Preibe H-J. Effects of dopamine on oxygen consumption andgastric mucosal blood flow during cardiopulmonary bypass inhumans. Br J Anaesth 1996; 77:603-606.

Comparison of the effects of dobutamine, dopamine and isoproterenol on hypoxic pulmonary vasoconstriction in the pig. Crit Care Med

Depression of hypoxic pulmonary vasoconstriction in the dog by dopamine and isoprenaline.

Dobutamine increases oxygen consumption during constant flow cardiopulmonary bypass.

Preibe H-J. Effects of dopamine on oxygen consumption and gastric mucosal blood flow during cardiopulmonary bypass in humans.

The effects on increasing cardiac output with adrenaline or isoprenaline on arterial haemoglobin oxygen saturation and shunt during one-lung ventilation. Anaesth Intensive Care

The effects on arterial haemoglobin oxygen saturation and on shunt of increasing cardiac output with dopamine or dobutamine during one-lung ventilation

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The Effects on Arterial Haemoglobin Oxygen Saturation and on Shunt of Increasing Cardiac Output with Dopamine or Dobutamine during One-lung Ventilation

The effects on arterial haemoglobin oxygen saturation and on shunt of increasing cardiac output with dopamine or dobutamine during one-lung ventilation

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