a restrictive fluid regimen has been recommended in thoracic surgery because acute lung injury ( ali ) is known to correlate with the amount of fluid administration during operations . one study suggests that , for every 500  ml increase in perioperative fluids , there is an odds ratio ( or ) of 1.17 for developing ali after lung resection . slinger suggested that fluid should be restricted just to the point of maintaining a urine output of 0.5  ml / kg / h and vasoactive agents may be used if tissue perfusion is inadequate . therefore , restriction of fluid administration and treatment of hypotension , which is not caused by major hemorrhage , with vasoactive agents , could be a basic concept in thoracic anesthesia . patients undergoing lung resection surgery usually receive one - lung ventilation ( olv ) . during olv , a significant decrease in cerebral oxygenation can occur . because the goal of hemodynamic optimization is to improve oxygen delivery to major organs , understanding how the administration of vasoactive agents affects cerebral perfusion and oxygenation , the most important organ in the body , would be of major clinical relevance , especially during olv . however , there are no data comparing vasoactive drugs in terms of maintaining cerebral oxygenation during thoracic surgery . therefore , we compared 2 commonly used agents , phenylephrine and dopamine , continuous infusion with respect to maintaining regional cerebral oxygen saturation ( rsco2 ) during olv in major thoracic surgery . our hypothesis is that dopamine continuous infusion provides higher rsco2 during olv than phenylephrine continuous infusion . the primary aim of our study was to investigate the effects of phenylephrine and dopamine continuous infusion on rsco2 during olv . as secondary outcome , we identified the hemodynamic variables which are responsible for the changes in rsco2 in major thoracic surgery . this was a parallel - design , 1:1 allocation , randomized , double - blind ( participants , assessors of outcomes ) controlled study . after approval by the institutional review board of samsung medical center , seoul , republic of korea , 63 patients undergoing elective thoracic surgery for lung cancer in a tertiary care academic center , from january 2013 to december 2013 , were recruited , and written informed consent was obtained from each patient . eligibility criteria were : age > 18 years , elective lobectomy or bilobectomy , american society of anesthesiologists ( asa ) physical status i  iii , and presenting with at least a 20% decrease in mean arterial pressure ( map ) during anesthesia . exclusion criteria were : forced expiratory volume in 1  second < 60% of predicted values , cerebrovascular disease , poorly controlled hypertension ( systolic arterial pressure 160  mm hg ) , poorly controlled diabetes mellitus ( blood glucose 200  mg / dl ) , diuretics or antidepressant use before operation , and renal insufficiency ( creatinine > 1.5  mg / dl ) . the patients were randomly assigned to the dopamine ( d ) or phenylephrine ( p ) groups using the computerized random number generator program ( www.randomizer.org ) . an enclosed assignment in a sequentially numbered , opaque , sealed envelope was allocated to each patient . this envelope was opened only by 1 author ( hja ) at the theatre , and the card inside determined whether the patient was in the d or p group . the anesthesiologists who maintained blood pressure within 20% of baseline with the allocated drug were neither involved in data collection nor in interpretation of test results . after the patient 's arrival in the operating theatre , a bis monitor ( aspect medical system , norwood , ma ) and 2 near - infrared spectroscopy ( nirs ) probes ( invos 5100c : somanetics corp . , troy , mi ) , 1 on each side of the forehead , were placed , in addition to the other routine monitors . after inducing anesthesia with fentanyl ( 1.52  g / kg ) , propofol ( 23  mg / kg ) , and rocuronium ( 0.8  mg / kg ) , all patients were intubated with a double lumen endotracheal tube ( mallinckrodt , covidien , mansfield , ma ) and maintained with balanced anesthesia using desflurance 1mac and remifentanil ( 0.050.2 the depth of anesthesia was maintained similarly between bis 40 and 55 in both groups . the remifentanil infusion rate was based on the patient 's age , asa physical status , and bis monitoring . a radial arterial catheter and an esophageal doppler probe ( cardioq , deltex medical , uk ) were placed after tracheal intubation . baseline map was a value recorded when the patients arrived to the operating room and were stabilized for 10  minutes . the drug was started when the map decreased more than 20% of baseline after anesthesia . dopamine was started at 5  g / kg / min and phenylephrine at 1  g / kg / min , and the infusion was adjusted for map to stay within 20% of baseline . spo2 was maintained above 94% by adjustment of positive end - expiratory pressure ( peep ) and fio2 during olv . invos 5100c employs a dual - detector system to subtract a shallow light path from a deep light path , allowing the derivation of the average oxyhemoglobin saturation in a volume of tissue about 2.5 to 3.0  cm below the skin . the device displays an approximation of venous - weighted hemoglobin saturation in tissue deep to the sensor . mean values of right and left optodes were analyzed . cardiac output ( co ) and stroke volume ( sv ) sv is obtained by multiplying the blood flow distance and the cross - sectional area of the aorta . arterial blood gas was analyzed at baseline , 15  minutes after induction ( tlvb ) , 30 and 60  minutes after olv ( olv30 , olv60 ) , and 15  minutes after the restart of two - lung ventilation ( tlva ) . all hemodynamic and rsco2 data were retrieved from the monitor after each case by the primary investigator who was not involved in anesthesia . the values of baseline , tlvb , olv30 , olv60 , and tlva were recorded . an intravenous infusion of lactated ringer solution was maintained at 5  ml / kg / h throughout anesthesia . packed red blood cell was transfused if the hemoglobin concentration fell below 8  g / dl . pressure - controlled ventilation was used with a tidal volume of 6  ml / kg of predicted body weight and a ventilatory frequency of 8 to 12  bpm , with a target etco2 between 35 and 45  mm hg . the arterial o2 saturation was monitored by a finger pulse oximeter ( nellcor , covidien , mansfield , ma ) . postoperative complications within 48  hours , the duration of mechanical ventilation , and icu stay were compared between the 2 groups . acute kidney injury ( aki ) was measured by acute kidney injury network ( akin ) score . postoperative delirium was monitored by the confusion assessment method in intensive care unit ( cam - icu ) . trained icu nurses who were unaware of the study allocation assessed delirium every hour until icu discharge . since no previous study exists , we referred a bolus study of similar vasoactives for sample size calculation , in which the mean difference of rsco2 was 10% between bolus phenylephrine and bolus ephedrine ( p  <  0.05 ) . we conducted a pilot study to obtain standard deviations ( sds ) of continuous infusions under olv which were 7% and 9% in the d and p groups , respectively ( n  =  5 , each group ) . as a result , a sample size of 25 in each group was required with alpha level 0.05 and statistical power 80% . considering a dropout rate of 20% , we chose a sample size of 30 per group . the mixed - effect model was used to conduct within - group comparison across different time points . between - group comparison was done at each time point by student t test or mann  whitney u test , as appropriate . results presented as mean    sd for data normally distributed , and median ( interquartile range [ iqr ] ) for data not normally distributed and a value of p value 0.05 was considered statistically significant . data were analyzed by the software program sas 9.4 ( sas institute , inc . , cary , nc ) . after approval by the institutional review board of samsung medical center , seoul , republic of korea , 63 patients undergoing elective thoracic surgery for lung cancer in a tertiary care academic center , from january 2013 to december 2013 , were recruited , and written informed consent was obtained from each patient . eligibility criteria were : age > 18 years , elective lobectomy or bilobectomy , american society of anesthesiologists ( asa ) physical status i  iii , and presenting with at least a 20% decrease in mean arterial pressure ( map ) during anesthesia . exclusion criteria were : forced expiratory volume in 1  second < 60% of predicted values , cerebrovascular disease , poorly controlled hypertension ( systolic arterial pressure 160  mm hg ) , poorly controlled diabetes mellitus ( blood glucose 200  mg / dl ) , diuretics or antidepressant use before operation , and renal insufficiency ( creatinine > 1.5  mg / dl ) . the patients were randomly assigned to the dopamine ( d ) or phenylephrine ( p ) groups using the computerized random number generator program ( www.randomizer.org ) . an enclosed assignment in a sequentially numbered , opaque , this envelope was opened only by 1 author ( hja ) at the theatre , and the card inside determined whether the patient was in the d or p group . the anesthesiologists who maintained blood pressure within 20% of baseline with the allocated drug were neither involved in data collection nor in interpretation of test results . after the patient 's arrival in the operating theatre , a bis monitor ( aspect medical system , norwood , ma ) and 2 near - infrared spectroscopy ( nirs ) probes ( invos 5100c : somanetics corp . , troy , mi ) , 1 on each side of the forehead , were placed , in addition to the other routine monitors . after inducing anesthesia with fentanyl ( 1.52  g / kg ) , propofol ( 23  mg / kg ) , and rocuronium ( 0.8  mg / kg ) , all patients were intubated with a double lumen endotracheal tube ( mallinckrodt , covidien , mansfield , ma ) and maintained with balanced anesthesia using desflurance 1mac and remifentanil ( 0.050.2 the depth of anesthesia was maintained similarly between bis 40 and 55 in both groups . the remifentanil infusion rate was based on the patient 's age , asa physical status , and bis monitoring . a radial arterial catheter and an esophageal doppler probe ( cardioq , deltex medical , uk ) were placed after tracheal intubation . baseline map was a value recorded when the patients arrived to the operating room and were stabilized for 10  minutes . the drug was started when the map decreased more than 20% of baseline after anesthesia . dopamine was started at 5  g / kg / min and phenylephrine at 1  g / kg / min , and the infusion was adjusted for map to stay within 20% of baseline . spo2 was maintained above 94% by adjustment of positive end - expiratory pressure ( peep ) and fio2 during olv . invos 5100c employs a dual - detector system to subtract a shallow light path from a deep light path , allowing the derivation of the average oxyhemoglobin saturation in a volume of tissue about 2.5 to 3.0  cm below the skin . the device displays an approximation of venous - weighted hemoglobin saturation in tissue deep to the sensor . mean values of right and left optodes were analyzed . cardiac output ( co ) and stroke volume ( sv ) sv is obtained by multiplying the blood flow distance and the cross - sectional area of the aorta . arterial blood gas was analyzed at baseline , 15  minutes after induction ( tlvb ) , 30 and 60  minutes after olv ( olv30 , olv60 ) , and 15  minutes after the restart of two - lung ventilation ( tlva ) . all hemodynamic and rsco2 data were retrieved from the monitor after each case by the primary investigator who was not involved in anesthesia . the values of baseline , tlvb , olv30 , olv60 , and tlva were recorded . an intravenous infusion of lactated ringer solution was maintained at 5  ml / kg / h throughout anesthesia . packed red blood cell was transfused if the hemoglobin concentration fell below 8  g / dl . pressure - controlled ventilation was used with a tidal volume of 6  ml / kg of predicted body weight and a ventilatory frequency of 8 to 12  bpm , with a target etco2 between 35 and 45  mm hg . the arterial o2 saturation was monitored by a finger pulse oximeter ( nellcor , covidien , mansfield , ma ) . postoperative complications within 48  hours , the duration of mechanical ventilation , and icu stay were compared between the 2 groups . acute kidney injury ( aki ) was measured by acute kidney injury network ( akin ) score . postoperative delirium was monitored by the confusion assessment method in intensive care unit ( cam - icu ) . trained icu nurses who were unaware of the study allocation assessed delirium every hour until icu discharge . since no previous study exists , we referred a bolus study of similar vasoactives for sample size calculation , in which the mean difference of rsco2 was 10% between bolus phenylephrine and bolus ephedrine ( p  <  0.05 ) . we conducted a pilot study to obtain standard deviations ( sds ) of continuous infusions under olv which were 7% and 9% in the d and p groups , respectively ( n  =  5 , each group ) . we used 15% sds for both groups as a more conservative approach . as a result , a sample size of 25 in each group was required with alpha level 0.05 and statistical power 80% . considering a dropout rate of 20% , we chose a sample size of 30 per group . the mixed - effect model was used to conduct within - group comparison across different time points . between - group comparison was done at each time point by student t test or mann  whitney u test , as appropriate . results presented as mean    sd for data normally distributed , and median ( interquartile range [ iqr ] ) for data not normally distributed and a value of p value 0.05 was considered statistically significant . data were analyzed by the software program sas 9.4 ( sas institute , inc . , cary , nc ) . ten patients did not develop a lower than 20% decrease in map after anesthesia and were excluded from the study . fifty patients were able to finish the study ( group d , n  =  25 ; or group p , n  =  25 ; fig . there were no differences in demographic and operative data between the 2 groups except urine output . it was higher in the d group than in the p group during operation ( 420 [ 282720 ] vs 190 [ 90340 ] ml ; p  <  0.001 ) . amount of anesthetics , fluid , blood loss , and mean hemoglobin concentration were not different between the groups . mean doses of dopamine and phenylephrine during olv were 4.3    1.9 and 0.8    0.4  g / kg / min , respectively . the rsco2 , co , hr , and map just before the drug infusion were not different between the d and p groups ( rsco2 , 73    6% vs 72    7% ; co , 4.2    1.0 vs 3.9    0.8  l / min ; hr , 71    12 vs 71    13  bpm ; map , 63    6 vs 63    6  mm hg ) . patient characteristics the d group maintained higher rsco2 than the p group during olv ( olv30 , 73    6% vs 69    9% , p  =  0.12 ; olv60 , 71    6% vs 63    12% , p  =  0.03 ; olvmean , 72    6% vs 66    10% , p  =  0.01 ; table 3 ) . the trend of rsco2 over time was different between the groups ( p  =  0.03 ) and within group d ( p  =  0.01 ) and p ( p  <  0.01 ) . the rsco2 of baseline was higher than the rsco2 of olv60 ( p  <  0.001 ) and tlva ( p  =  0.02 ) . the rsco2 of olv30 was higher than the rsco2 of olv60 ( p  <  0.001 ) . in group d , the rsco2 of olv30 was higher than that of olv60 ( p  =  0.03 ) . in group p , the rsco2 of baseline , olv30 , and tlva were higher than that of olv60 ( p  <  0.01 , p  <  0.01 , p  =  0.03 , respectively ) . the number of patients whose rsco2 dropped > 20% from baseline was 0 and 6 ( 24% ) patients in the d and p groups , respectively ( p  =  0.02 ) . the lowest rsco2 was 65    6% and 60    10% in the d and p groups , respectively ( p  =  0.02 ; table 3 ) . regional cerebral oxygen saturation ( rsco2 ) during one - lung ventilation the d group showed a higher co and a lower map than the p group ( co , 4.7    1.0 vs 3.9    1.2  l / min ; map , 77    8 vs 85    8  mm hg ; p  =  0.02 , p  =  0.02 , respectively ; table 4 , figs . 2 and 3 ) . the co of olv30 , olv60 , and tlva were higher than that of baseline in the d group ( p  =  0.01 , p  <  0.01 , p  <  0.01 , respectively ) . the co of olv30 was higher than that of baseline in the p group ( p  =  0.04 ) ( fig . the map of tlvb , olv30 , olv60 , and tlva were lower than that of baseline in the d group ( p  <  0.001 , all ) . the map of olv30 was lower than that of baseline in the p group ( p  <  0.01 ) ( fig . 3 ) . hemodynamics and blood gas analysis during one - lung ventilation group means and standard deviation for cardiac output during operation . p  <  0.05 between the 2 groups ; p  <  0.05 versus baseline of group d ; p  <  0.05 versus baseline of group p. before infusion , just before the drug infusion ; olv30 , 30  min after one - lung ventilation ; olv60 , 60  min after one - lung ventilaton ; tlva , 15  minutes after the restart of two - lung ventilation . p  <  0.05 between the 2 groups ; p  <  0.05 versus baseline of group d ; p  <  0.05 versus baseline of group p. before infusion , just before the drug infusion ; tlvb , 15  minutes after induction ; olv30 , 30  min after one - lung ventilation ; olv60 , 60  min after one - lung ventilation ; tlva , 15  minutes after the restart of two - lung ventilation . other variables , such as fio2 , pao2 , paco2 , pao2/fio2 ( pf ratio ) , ph , temperature , and hemoglobin concentration , were not different between the groups . among variables , age , hemoglobin concentration , and co were correlated with rsco2 ( r  =  0.37 , 0.30 , and 0.31 ; p  =  0.01 , 0.03 , and 0.03 , respectively ) in the whole population . there was no correlation between rsco2 and other variables such as fio2 , pao2 , paco2 , spo2 , pf ratio , ph , bis , and olv duration ( fig . pearson correlation analysis showed cardiac output ( co ) ( a ) , age ( b ) , and hemoglobin concentration ( hb ) ( c ) were associated with rsco2 . there were no differences in the incidence of delirium ( 5 vs 6 ) , aki ( 2 vs 0 ) , arrhythmia ( 4 vs 1 ) , and mechanical ventilation ( 2 vs 3 ) between the d and p groups , respectively . duration of icu stay was similar ( 21.8 [ 18.3 , 25.9 ] vs 21.7 [ 18.0 , 24.6 ] h ) between the d and p groups . our study showed that dopamine is superior to phenylephrine in maintaining cerebral oxygen saturation for patients receiving olv during thoracic surgery . the cerebral blood flow ( cbf ) decreases passively if the map falls below the lower limit of cerebral autoregulation , exposing the patient to possible cerebral hypoperfusion and ultimately , a reduction in rsco2 . immediate reductions in cbf and rsco2 have been reported when the map drops below 80  mm hg . in our study , the map was higher in the p group than in the d group during olv . however , the mean rsco2 was significantly lower in the p group than in the d group , and the difference of rsco2 between the 2 groups increased as olv continued . only 3 studies have been published for the comparison of vasoactive drugs in relation to rsco2 . in 1 study , patients received phenylephrine ( 100  g intravenous [ iv ] ) or ephedrine ( 10  mg iv ) to restore map after anesthesia induction and rsco2 was monitored by invos cerebral oximeter . after administration of phenylephrine , map increased ( 51 to 81  mm hg ; p  <  0.001 ) , but rsco2 decreased by 14% ( from 70% to 60% ; p  <  0.05 ) . the administration of ephedrine led to a similar increase in map ( 53 to 79  mm hg ; p  <  0.001 ) and preserved rsco2 . another study was a 2-treatment cross - over trial using oxiplex ts cerebral oximeter ; 1 bolus dose of phenylephrine ( 100200  g iv ) and 1 bolus dose of ephedrine ( 520  mg iv ) . the rsco2 was significantly decreased after phenylephrine treatment ( 3.2% ; p  <  0.01 ) , but rsco2 was preserved after ephedrine treatment ( + 0.04% ; p  >  0.05 ) . in a comparison study between phenylephrine and norepinephrine using fore - sight cerebral oximeter , phenylephrine and norepinephrine caused an equivalent increase in map [   =  13 [ 822 ] and   =  13 ( 919 )  mm hg , respectively ) , and a similar decrease in cardiac index ( both   =  0.2    0.3  l / min / m ) and rsco2 [   =  4 [ 7 to 2]% and   =  4 [ 5 to 1)% , respectively ) . phenylephrine mainly increases vasomotor tone and dopamine mainly increases myocardial contractility and heart rate ( hr ) . brain barrier ; therefore direct action of either phenylephrine or dopamine on cerebral vessels would be negligible . therefore , we speculate that the administration of phenylephrine may have reduced co. reduced co by phenylephrine has been documented in both animals and humans . in animal experiments , phenylephrine increased arterial pressure by 30% , but decreased co by 30% , ejection fraction by 36% , and sv by 25% . the co , sv , and hr decreased significantly after phenylephrine treatment in anesthesia - induced hypotensive patients , whereas ephedrine preserved co and sv , and increased hr . phenylephrine leads to increased vagal tone as demonstrated by slowed hr , and this can also result in decrease in co. a significant linear relationship was shown between co and the middle cerebral artery mean flow velocity . cerebral arteries are innervated by sympathetic nerve fibers abundantly , originating from the superior cervical ganglion . activity of sympathetic nerves on cerebral vessels increases promptly after a phenylephrine - induced rapid increase in arterial pressure . in anesthetized patients , the phenylephrine bolus injection increased the map by 20% to 30% and caused a significant decrease in cbf . in the current study , age , hemoglobin ( hb ) concentration , and co , but not map , therefore , the distinctive effect of phenylephrine and dopamine on rsco2 may be mainly explained by their different impacts on co. in the study by meng et al , which compared phenylephrine and ephedrine boluses , co was identified to have the most significant association with rsco2 , and after taking co into consideration , the other physiological variables were not significantly associated with rsco2 . therefore , it seems that higher co is the key factor of higher rsco2 shown in the d group , compared with the p group . other variables which can possibly influence rsco2 such as fio2 , spo2 , pao2 , paco2 , ph , temperature , and depth of anesthesia , were controlled during olv in this study , and there were no differences between the groups . low rsco2 measured by nirs was associated with an increase of neurological damage , cognitive impairment , or postoperative complications during cardiac and thoracic surgery . however , there is no proven cut - off value of rsco2 below which cerebral ischemia may occur because there is substantial inter and intrapatient variability in rsco2 . in our study , incidence of delirium defined by cam - icu was not different between the 2 groups , and there were no postoperative cerebrovascular incidents . urine output was higher in the d group during operation , but the incidence of aki was not different between the 2 groups . , this study was a monocentric approach of hemodynamic control to compare inotrope and vasopressor ; therefore , it does not exactly reflect clinical practice which employs multimodal approach for hemodynamic control . inotropes including dopamine have several side effects , such as increasing oxygen consumption of the heart muscle and leading to tachycardia , arrhythmia , and a higher risk for cardiac events . therefore , risk  benefit balance should be taken into consideration , and individualized approach is required for each patient . secondly , we did not measure cbf directly , but rather oxygenation of the brain . usually , changes in rsco2 parallel those in middle cerebral artery flow velocity ( mcav ) . an important role of cbf is to provide adequate oxygenation for the brain ; therefore monitoring rsco2 instead of middle cerebral artery flow may be more relevant . vasoactive drugs could affect the diameter of the aorta , thus making esophageal doppler measurement less accurate . however , esophageal doppler is less invasive than pulmonary artery catheter and more accurate than most of the noninvasive co monitors under the influence of vasopressors . invos 5100c is supposed to measure rsco2 of 2.5 to 3.0  cm below the skin . however , a control group that would not receive any treatment when blood pressure decreases was considered unethical . in previous reports , rsco2 dropped significantly when no drug intervention was given to treat hypotension during olv . in summary , cerebral oxygenation decreases after phenylephrine administration , but is maintained after dopamine continuous infusion in thoracic surgery patients undergoing olv . the higher co shown with the dopamine infusion may be beneficial in terms of maintaining cerebral oxygenation during olv . we suggest that the increase in map is not a prerequisite to secure cerebral oxygenation , and co should be increased to keep the optimum range of cerebral oxygenation .
abstractfluid is usually restricted during thoracic surgery , and vasoactive agents are often administered to maintain blood pressure . 
 one - lung ventilation ( olv ) decreases arterial oxygenation ; thus oxygen delivery to the brain can be decreased . in this study , we compared phenylephrine and dopamine with respect to maintaining cerebral oxygenation during olv in major thoracic surgery.sixty-three patients undergoing lobectomies were randomly assigned to the dopamine ( d ) or phenylephrine ( p ) group . 
 the patients mean arterial pressure was maintained within 20% of baseline by a continuous infusion of dopamine or phenylephrine . 
 maintenance fluid was kept at 5  ml / kg / h . the depth of anesthesia was maintained with desflurane 1mac and remifentanil infusion under bispectral index guidance . regional cerebral oxygen saturation ( rsco2 ) and 
 hemodynamic variables were recorded using near - infrared spectroscopy and esophageal cardiac doppler.the rsco2 was higher in the d group than the p group during olv ( olv 60  min : 71    6% vs 63    12% ; p  =  0.03 ) . the number of patients whose rsco2 dropped more than 20% from baseline was 0 and 6 in the d and p groups , respectively ( p  =  0.02 ) . 
 the d group showed higher cardiac output , but lower mean arterial pressure than the p group ( 4.7    1.0 vs 3.9    1.2  l / min ; 76.7    8.1 vs 84.5    7.5  mm hg ; p  =  0.02 , p  =  0.02 ) . among the variables , age , hemoglobin concentration , and cardiac output were associated with rsco2 by correlation analysis.dopamine was superior to phenylephrine in maintaining cerebral oxygenation during olv in thoracic surgery .