several studies show that serious gastrointestinal complications , particularly upper gastrointestinal ( gi ) bleeding , follow cardiac surgery and these complications can lead to high rates of morbidity and mortality .
in addition , ueki and colleagues reported that secretion of gastric juice increased significantly from 3.8    1.3 to 12.4    4.0  ml / h after induction of extracorporeal circulation .
aspirin and anti - platelet drugs are commonly used for patients with coronary heart disease .
proton pump inhibitor ( ppi ) and h2 antagonists are recommended for the prevention of nonsteroidal antiinflammatory drugs ( nsaids)-related ulcer .
however , long - term h2 antagonist medication produces a reduction in antisecretory efficacy or tolerance .
we have previously reported that patients receiving h2 antagonists for more than 4 weeks show resistance to preanesthetic h2 antagonist treatment , used for acid aspiration pneumonia prophylaxis .
if patients develop tolerance then preanesthetic h2 antagonist medication would be essentially useless and an alternative would be required .
in contrast , ppis may be a suitable alternative as they produce a similar or more potent anti - secretory effect on gastric acid secretion than h2 antagonists .
these reports also suggest that tolerance to ppi treatment would not develop as ppis inhibit the h / k - adenosine triphosphatase pump , which is the final step in gastric acid secretion from the parietal cell .
thus , we hypothesized that ppi may be more effective for prophylaxis of perioperartive stress - induced gi bleeding and acid aspiration pneumonia than h2 antagonist in patients undergoing cardiac surgeries with cpb .
therefore , in the present study , to test our hypothesis , we have compared the antisecretory effects of a preanesthetic h2 antagonist ( roxatidine ) and a ppi ( rabeprazole ) in patients undergoing cardiac surgery and also compared gastric ph and volume in patients with and without cpb .
with university ethics committee approval and informed consent , 45 adult patients undergoing cardiac surgery were recruited in the study .
number of patients in each group was determined by power analysis using our previous study data .
thirty patients undergoing cardiac surgery under cpb were randomly assigned to two groups : cpb - h2 and cpb - ppi group ( n  =  15 each ) .
another 15 patients were scheduled to undergoing off - pump coronary artery bypass grafting ( opcab ) surgery ( opcab - h2 group ) . in the cpb - h2 and opcab - h2 groups ,
patients were given roxatidine 75  mg orally at 9:00 pm on the day before the surgery and 2  h before the induction of anesthesia .
in the cpb - ppi group , patients were premedicated with rabeprazole 20  mg orally at 9:00 pm on the day before the surgery and 2  h before the induction of anesthesia . because only roxatidine has been approved as an oral preanesthetic h2 antagonist by our ministry of health , labor and welfare in japan , famotidine or ranitidine was not used .
all patients were hospitalized for at least the night before surgery and were fasted from the first anesthetic premedication ( i.e. , 9:00 pm ) .
anesthesia was induced with propofol 0.51.5  mg / kg , ketamine 0.51.0  mg / kg , and fentanyl 5  g / kg and maintained with propofol 37  mgkgh , ketamine 0.51.0  mgkgh , and fentanyl 48 g / kg .
the trachea was intubated after muscle relaxation facilitated with vecuronium 0.1  mg / kg iv .
muscle relaxation was maintained with an iv bolus of vecuronium that was given 1  mg every 30  min .
a gastric tube ( argyle salem sump tube , japan sherwood , tokyo , japan ) was placed into the stomach twice after tracheal intubation and the end of surgery as the first gastric tube was removed before insertion of transesophageal echocardiography probe .
the position of tip of gastric tube was verified by auscultation of the epigastrium during insufflation of air .
gastric fluid was obtained by aspiration using a 10 or 50  ml syringe while changing the patient s position ( supine , trendelenburg and reverse trendelenburg , and right and left 20 degree semilateral positions ) and with insufflation of 50  ml air plus upper - abdominal massage .
the volume of gastric contents was recorded as well as the ph value , measured using a ph meter with 0.01 ph unit precision over the entire ph range ( ecoscan ph5 ph6 ; iuchi seieido co. , ltd . ,
arterial blood was collected simultaneously and centrifuged at 3,000  rpm for 10  min at 10c to separate plasma , which was kept frozen at 70c until assay .
plasma gastrin concentrations were analyzed using a commercially available enzyme - linked immunosorbent assay ( peninsula laboratories inc .
, san carlos , ca ) with a minimum sensitivity , inter- and intraassay coefficient of variation of 7.27  pg / ml , 6.5% and 3.7% , respectively .
statistical analysis was performed using factorial or repeated one way anova and paired or unpaired t test as appropriate , with p<0.05 considered significant .
there were no significant differences between groups with respect to sex , age , height , and weight except duration of anesthesia and surgery .
gastric ph and volume at the end of surgery in opcab - h2 groups was significantly lower and higher than those in both cpb - h2 and cpb - ppi groups , respectively although those variables did not differ between groups after the induction of anesthesia ( fig .  1 a and b ) .
plasma gastrin and maximal blood lactate levels were also significantly lower in opcab - h2 group than those in both cpb - h2 and cpb - ppi groups ( fig .  1 c and d ) .
in addition , there was a significant correlation between gastric fluid volume and maximal blood lactate level ( fig .  2 ; r  =  0.596 ;
there were fewer patients showing critical factors for acid aspiration pneumonia ( ph<2.5 or gastric fluid volume>25  ml ) in the opcab - h2 group ( table  3 ) .
cpb patients ( cpb - h2 and cpb - ppi groups ) had higher gastric ph and volume compared to those in the opcab - h2 group .
if h2 antagonist and ppi were effective , gastric fluid volume should have been reduced with higher ph . thus , higher gastric ph may not imply that these anti - acid agents suppressed gastric acid secretion .
several reports indicate that the cpb causes intestinal hypoperfusion which impairs small intestinal transport and increases intestinal permeability .
tsunooka and colleagues reported that serum diamine oxidase activity , an index of small intestinal ischemia , rose significantly during the cpb in patients undergoing coronary artery bypass grafting .
similarly , blood lactate was significantly higher in the cpb groups than that in the opcab group in the present study . as lactate production increases as a consequence of tissue hypoxia
as there was a significant correlation between gastric fluid volume and maximal blood lactate levels in the present study , intestinal hypoperfusion due to cpb could increase gi microvascular permeability to increase gastric fluid volume .
therefore , either gastric fluid volume or blood lactate may be an index of gi tract hypoperfusion .
critical factors for acid aspiration pneumonia in adults have been considered to comprise gastric ph below 2.5 and a fluid volume above 25  ml . in the present study , 12 and 10 of 15
patients with more than 25  ml of gastric contents in the cpb - h2 and cpb - ppi groups have a higher postoperative risk of acid aspiration pneumonia . into the opcab - h2 group
thus , gastric tube should be inserted after removal of transesophageal echocardiographic probe . to determine the precise mechanism regarding the increase of gastric fluid volume by cpb
, we should have placed the gastric tube just after termination of cpb rather than just before the end of surgery in the present study . however , as opcab - h2 group data clearly suggest that an increase in gastric fluid volume may be due to cpb as cardiac surgery per se would not increase gastric fluid volume .
the present data indicate that both h2 antagonist and ppi can not inhibit an increase in gastric fluid volume .
if neither are given , most of patients would have a high risk of acid aspiration pneumonia during the induction of anesthesia as we previously found that patients without prophylaxis showed low gastric ph ( 2.2    1.2 ) and high volume ( 20    18  ml ) .
in addition , the chief gi complication following cpb is gi bleeding secondary to gastric or duodenal ulceration .
which anti - acid agent is suitable to suppress gastric acidity in patients undergoing cardiac surgery h2 antagonist or ppi ?
wagner and colleagues reported that perioperative administration of famotidine ( h2 antagonist ) suppresses gastric secretion in cardiac patients .
hata and colleagues compared three agents ( n  =  70 each ) : teprenone 150  mg / day ( mucosal protection ) , ranitidine 300  mg / day ( h2 antagonist ) and rabeprazol 10  mg / day ( ppi ) to prevent postoperative the upper gi complicationsin patients undergoing cardiac surgery with cpb .
they found that the incidences of hemorrhagic gastritis and active ulceration were significantly lower in patients with rabeprazole .
therefore , preanesthetic ppi may be the most appropriate anti - acid for patients undergoing cardiac surgery with cpb . in conclusion
, the present study suggests that both gastric fluid volume and blood lactate level may predict the degree of gi tract hypoperfusion . as cpb often increases gastric fluid volume more than 25  ml , gastric tube should be placed before the end of surgery .
 major physiological stress occurs during cardiac surgery with cardiopulmonary bypass . 
 this is related to hypothermia and artificial organ perfusion . 
 thus , serious gastrointestinal complications , particularly upper gastrointestinal bleeding , sometimes follow cardiac surgery . 
 we have compared the antisecretory effects of a preanesthetic h2 antagonist ( roxatidine , cardiopulmonary bypass - h2 group , n  =  15 ) and a proton pump inhibitor ( rabeprazole , cardiopulmonary bypass - ppi group , n  =  15 ) in patients undergoing cardiac surgery with cardiopulmonary bypass , and also compared in patients undergoing a off - pump coronary artery bypass graft surgery ( off - pump cardiopulmonary bypass - h2 group , n  =  15 ) . 
 gastric ph ( 5.14    0.61 ) and gastric fluid volume ( 13.2    2.4  ml ) at the end of surgery in off - pump cardiopulmonary bypass - h2 groups was significantly lower and higher than those in both cardiopulmonary bypass - h2 ( 6.25    0.54 , 51.3    8.0  ml ) and cardiopulmonary bypass - ppi ( 7.29    0.13 , 63.5    14.8  ml ) groups , respectively although those variables did not differ between groups after the induction of anesthesia . 
 plasma gastrin ( 142    7  pg / ml ) at the end of surgery and maximal blood lactate levels ( 1.50   0.61  mm ) in off - pump cardiopulmonary bypass - h2 group were also significantly lower than those in both cardiopulmonary bypass - h2 ( 455    96  pg / ml , 3.97    0.80  mm ) and cardiopulmonary bypass - ppi ( 525    27  pg / ml , 3.15    0.44  mm ) groups , respectively . 
 in addition , there was a significant correlation between gastric fluid volume and maximal blood lactate ( r  =  0.596 ) . in conclusion 
 , cardiopulmonary bypass may cause an increase in gastric fluid volume which neither h2 antagonist nor ppi suppresses . 
 a significant correlation between gastric fluid volume and maximal blood lactate suggests that gastric fluid volume may predict degree of gastrointestinal tract hypoperfusion . 
Introduction
Materials and Methods
Results
Discussion