Ann Thorac Surg 1999;67:908-910
© 1999 The Society of Thoracic Surgeons
Original Articles
Beneficial effect of prostaglandin E1 on blood flow to the gastric tube after esophagectomy
Yasunori Matsuzaki, MDa,
Masao Edagawa, MDa,
Masayuki Maeda, MDa,
Tetsuya Shimizu, MDa,
Ryo Sekiya, MDa,
Kunihide Nakamura, MDa,
Toshio Onitsuka, MD, PhDa
a Department of Surgery II, Miyazaki Medical College, Miyazaki, Japan
Accepted for publication September 25, 1998.
Address reprint requests to Dr Matsuzaki, Department of Surgery II, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
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Abstract
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Background. A prospective study on the vasodilatory effect of prostaglandin E1 on blood flow to the gastric tube after esophagectomy is reported.
Methods. Twelve patients with thoracic esophageal cancer who underwent esophagectomy were enrolled in this study. In all patients, the esophagogastrostomy was performed in the cervical region, and the stomach was used for reconstruction. Immediately after the creation of the gastric tube, baseline blood flow was measured at the oral end, in the center, and at the pyloric ring of the gastric tube using a laser Doppler flowmeter. The prostaglandin E1 group (n = 6) was then infused with prostaglandin E1 until postoperative day 2; the control group (n = 6) received saline. At +5 minutes and +40 minutes after administration, blood flow was again measured at the same three sites.
Results. The control group did not show a significant increase of blood flow to any site over time. For the prostaglandin E1 group, blood flow at +40 minutes increased from the baseline measurements significantly at a rate of 63%, 39%, and 36%, respectively.
Conclusions. Prostaglandin E1 has a characteristic vasodilating effect on the area of impaired microcirculation of the gastric tube, thereby increasing blood flow to the affected area.Key Words: PGE1, esophageal reconstruction, blood flow, gastric tube, Laser Doppler flowmeter
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Introduction
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For patients with esophageal cancer, esophagectomy provides the best hope of cure, but is a major undertaking. Incisions are made in the abdomen, chest, or sometimes in the neck. Most of the esophagus is then removed, and the stomach can be pulled up to the neck and joined to the cervical esophagus. This long reconstruction tube is created by placing autosuture devices at the lesser curvature of the stomach. Leakage at the anastomotic site of the esophagogastrostomy can be a serious postoperative complication in these patients. The main cause of this problem is thought to be insufficient blood supply to the tissue [1], which is supplied solely by the right gastroepiploic artery. In this study, we evaluated the effect of the vasodilator prostaglandin E1 (PGE1) to determine whether subserosal blood flow to the long gastric tube was increased in the presence of PGE1.
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Material and methods
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Patients and preoperative assessments
From 1994 to 1997, 12 patients with thoracic esophageal cancer who underwent esophagectomy in our surgical service were enrolled in this study. Before operation, written informed consent was obtained regarding the study, and each patient was randomly assigned either to the PGE1 group (n = 6) or to the control group (n = 6) based on treatment to be received during operation. The clinical characteristics of these patients are summarized in Table 1. There were no significant differences between the two groups with regard to gender, age, tumor location, stage, and reconstruction route.
Operative technique
In all patients, the esophagogastrostomy was performed in the cervical region of the esophagus, and the stomach was used for reconstruction. A gastric tube supplied by the right gastroepiploic artery was created by using five or six autosuture devices at the lesser curvature. Immediately after the creation of the gastric tube, the size of the gastric tube and the distance of the esophagogastrostomy site from the pyloric ring were measured, and baseline blood flow readings were taken at the oral end, in the center between the oral end and the pyloric ring, and at the pyloric ring of the gastric tube using noncontact laser doppler tissue blood flowmetry (model ALF21N Laser Flowmeter, Advance Co, Tokyo, Japan). Patients assigned to the PGE1 group were then given PGE1 intravenously at a speed of 0.02 
/min. The dose of PGE1 was determined as that dose that would cause a 10% decrease in the patient’s systolic blood pressure. In 2 patients, the desired decrease was not obtained, and the speed was increased to 0.03 /min. In this study, PGE1 was infused continuously until postoperative day 2 to maintain anastomotic integrity. Those patients assigned to the control group received the same volume of saline intravenously. Blood flow to the gastric tube was continuously monitored using the two-channel recorder U-228 (Advance Co, Tokyo, Japan). At +5 minutes and +40 minutes after administration, blood flow was recorded at the same sites as for the baseline measurements. To minimize possible fluctuations in blood flow determinations, the same person applied the flowmetry probe at the same sites, at three different times for all patients.
Statistical analysis
All continuous variables are presented as the mean ± standard error. The unpaired t test was used to compare the size of the gastric tube and the distance of the esophagogastrostomy site from the pyloric ring. All recorded blood flow data were also subjected to analysis of variance. Statistical analysis was performed using the SPSS package (SPSS Inc, Chicago, IL). A p value of less than 0.05 was considered significant.
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Results
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Patients and postoperative complications
After esophagogastrostomy, the anastomosis in the cervical region of the esophagus was satisfactory in appearance in all patients. The PGE1 group did not experience any side effects normally associated with PGE1 treatment, such as excessive bleeding, disturbance in platelet function, or severe hypotension. One patient in the control group (17%) developed a minor leakage at cervical anastomosis postoperatively at day 10. This was cured by drainage at day 17. The remaining 11 patients did not experience any serious postoperative complications.
Esophageal reconstruction
Table 2 compares the size of the created gastric tube and the distance of the esophagogastrostomy site from the pyloric ring. There were no significant differences between the two groups. In our study, the mean size of the gastric tube was 3.2 cm in width and 34.4 cm in length, and the mean distance between the esophagogastrostomy site and the pyloric ring was 30.2 cm.
Blood flow measurements
For both groups, the baseline blood flow at the oral end of the gastric tube was the lowest among the three sites. Although the control group did not show a significant increase or decrease of blood flow to the gastric tube at any site over time, blood flow in the PGE1 group increased significantly at all three sites at +40 minutes.
As can be seen in Table 3 , the increase was most remarkable in blood flow to the oral end of the gastric tube. Although the control group increased only slightly from 10.2 ± 3.5 mL · min-1 · 100 g-1 at the baseline to 11.0 ± 4.6 mL · min-1 · 100 g-1 at +40 minutes, blood flow in the PGE1 group increased 63%, measuring 9.8 ± 3.8 mL · min-1 · 100 g-1 at the baseline and 16.0 ± 7.9 mL · min-1 · 100 g-1 at +40 minutes (p < 0.05). Blood flow to the center of the gastric tube showed a similar pattern (Table 3). Although there was no significant increase in the control group, blood flow in the PGE1 group increased from a baseline reading of 14.0 ± 4.1 mL · min-1 · 100 g-1 to 19.5 ± 7.0 mL · min-1 · 100 g-1 at +40 minutes, an increase of 39% (p < 0.05).
Blood flow around the pyloric ring (Table 3) exhibited the same characteristics as the other two sites. In the PGE1 group, blood flow increased 36%, measuring 18.2 ± 6.7 mL · min-1 · 100 g-1 at the baseline and 24.7 ± 7.9 mL · min-1 · 100 g-1 at +40 minutes (p < 0.05).
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Comment
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Leakage is considered to be one of the most serious complications after esophageal reconstruction [1]. Although the primary cause is thought to be inadequate blood supply to the tissue, local infection, tension at the anastomotic part, hypoproteinemia, and tissue ischemia are other important factors. With a long gastric tube, the possibility of leakage is increased because the tissue is supplied only by the right gastroepiploic artery. Because an anastomosis located in the cervical region requires a longer gastric tube than one located in the thoracic region, blood flow is more likely to be diminished at the higher site. We designed this study to determine whether the vasodilator PGE1 would have any beneficial effect on blood flow to the gastric tube created during esophageal reconstruction. We used a PGE1 dose that would decrease the systolic blood pressure by 10%.
Prostaglandin E1 is a powerful pulmonary and systemic vasodilator [2–4] and also inhibits platelet and leukocyte aggregation [2, 5, 6]. A prostanoid derived from arachidonic acid, PGE1 has been used in patients undergoing extracorporeal operation and in patients with severe liver disease. Although a variety of "cytoprotective" effects have been reported [7–10], they are not completely understood.
To maintain anastomotic integrity, PGE1 was given continuously until postoperative day 2. Although this period may seem a little short to prevent anastomotic breakdown that typically occurs 5 to 10 days after operation in this study, we focused on the improvement of impaired microcirculation in the first few days after poor blood supply or ischemia, as the new angiogenesis in the ischemic area usually occurs in a few days [11–14]. The other reason PGE1 was not given for a longer period of time is that the routine use of PGE1 infusion is more expensive.
To measure blood flow to the affected tissue, we used the laser Doppler flowmeter, which can measure blood flow at a depth of 1 to 2 mm beneath the tissue surface. For both groups, blood flow to the three sites decreased in proportion to the distance from the root of the right gastroepiploic artery and was the lowest at the oral end of the gastric tube. In the control group, blood flow gradually increased over time at all sites. This suggests that immediately after the creation of the gastric tube, blood flow to the stomach may decrease temporarily due to the surgical procedure or to muscle contraction, as is often seen in gastrointestinal procedures.
Although blood flow seemed to recover over time in the control group, our data demonstrated a significant increase in blood flow at +40 minutes in the PGE1 group. For these patients, blood flow to the oral end, center, and pyloric ring regions of the gastric tube increased from the baseline measurements at a rate of 63%, 39%, and 36%, respectively, suggesting that PGE1 has a characteristic vasodilating effect on the area of impaired microcirculation, yet does not dilate those vessels where the microcirculation is almost normal.
On the basis of these results, we believe that when used intravenously in a dose that decreases the systolic blood pressure by 10%, PGE1 produces a beneficial vasodilatory effect, thereby increasing blood flow to the long gastric tube created during esophageal reconstruction. An additional study will evaluate the effect of nitroprusside, another strong vasodilator, and the results will be compared with the present data.
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Abstract
Introduction
