Pancreas Transplantation at Mayo: II. Operative and Perioperative Management

JAMES D. PERKINS, M.D.,* Section of Transplantation Surgery; GLENN A. FROMME, M.D., BRADLY J. NARR, M.D., Department of Anesthesiology; PETER A. SOUTHORN, M.B.,B.S., Critical Care Service; CHRISTOPHER L. MARSH, M.D.,* STEPHEN R MUNN, M.D.,t Section of Transplantation Surgery; DONALD E. ENGEN, M.D., Department of Urology; SYLVESTER STERIOFF, M.D., Section of Transplantation Surgery

Better perioperat ive and operat ive management techniques have contributed to an improvement in the success rate of pancreas transplantat ion. Because of a shortage of donor organs, the criteria for acceptabi l i ty of the allograft have b e e n l iberalized, and the deve lopment of t echniques such as combined l iver and pancreas procurement has increased allograft availabil ity. Mtgor advances have b e e n made in organ preservat ion. Currently, pancreas allografts can rout inely be s tored for 18 to 24 hours . The technique of pancreat icoduodenal transplantat ion wi th a duodenocystos tomy for the exocr ine drainage is wide ly used. Exper ience w i th anesthet ic and intensive-care uni t management of these pat ients i s accumulat ing. With the evolut ion of pancreas transplantat ion and wi th the he lp of the excel lent transplant centers in our area, w e deve loped a pancreas transplantat ion protocol and performed transplanta­t ion based on this protocol in 16 rec ipients at the Mayo Clinic from October 1987 through December 1988.

The improvement in the success rate' of pan­creas transplantation h a s been attributable in part to the development of better perioperative and operative management techniques. The specific areas of development include selection of donors, procurement and preservation proce­dures, engraftment procedures, and anesthetic and intensive-care management .

•Current address: University of Washington, Seattle, Washington.

tCurrent address: Auckland Hospital, Auckland, New Zealand.

Address reprint requests to Dr. Sylvester Sterioff, Section of Transplantation Surgery, Mayo Clinic, Rochester, MN 55905.

Most donors who are suitable for kidney dona­tion are also acceptable for pancreas donation. ̂ In older donors, however, problems can arise when advanced atherosclerosis has extended beyond the origin of the celiac and superior mesenteric arteries but not to the renal arter­ies.^ Contraindications to pancreas donation are diabetes mell i tus (type I or type II), chronic pancreatitis, and a previous pancreatic surgical procedure or pancreatic trauma.* Relative contraindications include alcoholism and bouts of recurrent acute pancreatitis. Increased blood glucose and serum amylase levels probably have no deleterious effect on allograft function.^ In donors with a negative history, the condition of the graft at the t ime of procurement is the single most important factor in selection.

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484 PANCREAS TRANSPLANTATION Mayo Clin Proc, April 1990, Vol 65

Donor pancreatectomy techniques have been described previous ly / The increasing use of the pancreaticoduodenal allograft has led to re­finement of this technique."'' The most im­portant detail i s avoidance of excessive trauma to the pancreas. Us ing the spleen as a handle to facilitate exposure is a valuable technique. Conflicts have occurred between liver and pan­creas transplantation programs regarding pro­curement of liver and pancreaticoduodenal grafts from the same donor. Although conventional wisdom suggested that this could not be done, several groups have demonstrated the feasibil­ity of combined pancreaticoduodenal and liver procurement from the same donor.*

One aspect of pancreas transplantation in which considerable progress has been made is preservation of the allograft. When the Collins preservation solution was used, the preser­vation t ime was limited to less than 6 hours. This restriction precluded distant procure­ments , detailed t i ssue typing, and sharing of pancreas allografts between transplant cen­ters.''••'^ Furthermore, use of the Collins pres­ervation solution was associated with an increased thrombosis rate thought to be attrib­utable to ischemic damage to the pancreas graft;.'" With the development of silica gel-filtered plas­ma (SGFP-III) and the University of Wiscon­sin (UW) solution, pancreas allografts routinely have been stored for 18 to 24 hours ." Thus, the foregoing problems are eliminated. Some transplant centers that use these solutions have a 0% thrombosis rate, which is thought to be due to decreased edema in the pancreas graft.

Lillehei's group^" performed the first vascu­larized pancreas transplantations in human s and was the first to use a pancreaticoduodenal allograft. The primary difficulty with pancreas transplantation was successful management of the exocrine drainage. Because of excessive complications relating to the transplanted duo­denal segment, several other techniques have been used. Usually, segmental grafts were used, and ductal ligation, obliteration of the ducts by polymers, and even open peritoneal drainage were attempted.

In the early 1980s, Starzl and associates^' reintroduced the concept of pancreaticoduode­nal transplantation. They transplanted a large segment of duodenum and jejunum that drained the exocrine secretions through the recipient's jejunum. In many patients, this approach was complicated by a protein-losing enteropathy. In 1973, Gliedman and coUeagues^^ introduced the concept of the urinary drainage of the exocrine secretions. With a segmental graft, they used a pancreatic duct-to-ureter anastomosis for this urinary drainage. Subsequently, Sollinger and Belzer^^ described a duodenal button technique for exocrine drainage to the urinary bladder. This technique was associated with a high rate of technical complications because of the diffi­culty of the anastomosis . This pancreaticoduo­denal technique was modified by Corry and co­workers'''^'' to include a segment of duodenum that was used for the duodenocystostomy. The result was a lower complication rate than with use of the other techniques.^^

The perioperative management of the diabe­tes in patients who undergo pancreas transplan­tation is similar to the treatment of diabetes in patients who have undergone other major opera­tions; important factors are maintenance of metabolic stability, avoidance of hypoglycemia, and prevention of excessive hyperglycemia and ketosis.^" Theoretic evidence indicates that the better the glycemic control, the better the allo­graft; function.^'' The perioperative manage­ment of anesthes ia is especially focused on en­suring cardiovascular integrity and viability of the transplanted organs.

Herein we describe a protocol for pancreas transplantation that we have developed on the basis of the evolution of pancreas transplanta­tion, the combined experience of the excellent transplantation centers in our area, and our own early experience.

MAYO P A N C R E A S T R A N S P L A N T A T I O N P R O T O C O L Donor Criteria.—^The history, physical, and laboratory criteria for potential pancreas donors are similar to those for kidney donors (Table 1). For a combined liver and pancreas procurement.

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Table 1.—Preoperative History, Physical , and Laboratory Criteria for Potent ia l

Pancreas Allograft Donors

History and physical examination Weight >30 kg if procurement of pancreas only; >50 kg

if combined liver and pancreas procurement <55 years old No cancer except skin or brain No sepsis No hepatitis No history of tuberculosis or syphilis No history of recent intravenous drug abuse No history of chronic alcoholism No history of diabetes No first-degree relatives with diabetes No history of pancreatitis No previous splenectomy No severe chronic hypertension Previous abdominal surgical procedure acceptable if in

an area removed from the pancreas Laboratory examination

If blood glucose value substantially above normal, glycosylated hemoglobin level must be normal

If serum amylase >3 times normal, measure isoenzymes; avoid if pancreatic fraction is increased

Negative tests for hepatitis, syphilis, and human immunodeficiency virus

we require the donor to weigh at least 50 kg, to prevent difficulty in the anastomosis of the splenic artery to the internal iliac artery. Although the upper age limit is flexible, atherosclerosis may involve the superior mesenteric artery and ce­liac axis in an older donor and may thus make this reconstruction difficult. With procurement from an older donor, the vesse ls mus t be thor­oughly examined before the recipient's opera­tion is scheduled. The most critical operative criteria for deciding on the use of the allograft are the following: normal appearance of the pancreas on gross inspection; no severe edema of the pancreas; no petechial pancreatic hemor­rhage; no peripancreatic hematoma; and no capsular tear.

Prerequisites for successful pancreas procure­ment are an optimal condition and hemody­namic stability of the donor. Maintenance of normothermia is imperative. Because of the high incidence of stress-induced hyperglycemia, blood glucose levels are maintained at less than 100 mg/dl by administration of short-acting

insulin. Pancreatic edema is decreased by intra­venous administration of albumin (75 to 100 g) during the procurement. An antibiotic solution (gentamicin, polymyxin, and cefazolin) is ad­ministered through a nasogastric tube at 200 ml/ h to decrease the duodenal bacterial flora and the risk of contamination during transection of the duodenum.

Graft Procurement.—When the liver is not also procured, the pancreaticoduodenal allograft procurement is similar to that described by Corry and a s s o c i a t e s . " I n brief, the body ana tail of the pancreas are mobilized, and the spleen is used as a handle. An aortic segment is cleared of lymphatic and neural t issue, including the celiac axis and superior mesenteric artery. The dissec­tion is then extended through the hepatoduode­nal l igament near the edge of the liver. The proper hepatic artery, the common bile duct, and the Ijrmphatic and neural t i ssue are ligated. The entire length of the portal vein is mobilized for inclusion with the pancreaticoduodenal graft. The arterial supply includes an aortic patch that encompasses the celiac axis and superior mesen­teric artery.

We have reported our technique for procuring pancreaticoduodenal and liver allografts con­comitantly.^"'^ In brief, the area around the superior mesenteric artery first is cleared by careful ligation of the Ijmtiphatic structures on the pancreas side of the graft. Then the body and tail of the pancreas are mobilized (recently, this has been accomplished with electrocautery). The celiac axis, the superior mesenteric artery, and a segment of the aorta above the celiac axis are cleared of lymphatic and neural t issue. Next, the hepatoduodenal l igament is dissected at the edge of the duodenum. The common bile duct is ligated, and the gastroduodenal artery is ligated jus t after its origin fi-om the common hepatic artery. The portal vein is mobilized for only 2 cm above the edge of the duodenum. The common hepatic artery and the celiac Eixis are completely mobilized fi^om the pancreas graft and the supe­rior mesenteric artery. The area around the base of the splenic artery is completely cleared of surrounding t issue. A duodenal segment en­compassing the head of the pancreas is created

486 PANCREAS TRANSPLANTATION Mayo Clin Proc, April 1990, Vol 65

by transecting the duodenum just below the pylorus and below the head of the pancreas; care should be taken to avoid the uncinate process. The pancreaticoduodenal allograft includes a 5-to 8-cm segment of the duodenum, the splenic artery, the superior mesenteric artery, a 1- to 2-cm segment of the portal vein, and the spleen, which is used as a handle. The common iliac artery with the bifurcation of the internal and external iliac arteries also is procured for later vascular reconstruction.

Graft Preservation and Storage.—For preservation of the graft, we have used both SGFP-III obtained from the University of Min­nesota" and, more recently, UW solution.'* When SGFP-III is used, the aorta is flushed with EuroCoUins solution. Great care should be taken to limit the amount of EuroCoUins solution that is flushed into the pancreas by removing it as soon as possible. Once it is on the back table, the pancreas is flushed with SGFP-III until the venous effluent is clear. With use of U W solu­tion, however, the aorta is flushed, and the pancreas is flushed en bloc with the kidneys and the liver. After removal of the pancreas to the back table, only a l imited amount of flushing is needed until the venous effluent is clear. For both flush solutions, the height of the reservoir is l imited to 30 cm above the graft. The segment of duodenum is opened on the antimesenteric side and flushed first with a neomycin solution and then with the preservation solution. After the flushing, the graft is submerged in its pres­ervation solution and put in a plastic bowl that is wrapped in plastic, and the bowl is placed on ice to be transported in an ice chest. The target ischemia t ime is less than 24 hours; less than 18 hours is preferred.

Donor-Recipient Combinations.—For all donors, a lymphocytotoxic crossmatch to all ABO-compatible recipients is performed. When possible, the best human leukocyte antigen match is chosen. Also, the cytomegalovirus s tatus is taken into account for donor-recipient pairing; if possible, a negative cytomegalovirus recipient is matched with a negative c3^omega-lovirus donor. After these aspects, the duration of t ime on the wait ing list and the highest per­

cent reactive antibody level are used to break t ies for pairing.

Anesthetic Management.—During the evaluation phase for pancreatic transplanta­tion, each potential recipient is interviewed and assessed for possible problems in anesthetic management . Particular attention is paid to the vascular s tatus to limit the possibility of peri­operative myocardial infarction.

After admission to the hospital for transplan­tation, the patient should receive nothing by mouth, and a peripheral intravenous line is started with half-isotonic saline (0.38% NaCl) wi th 5% dextrose at 50 ml/h. A triple-lumen cen­tral venous catheter is placed. Glucose levels are obtained by reflectance meter every hour until transplantation. An infusion of insulin (250 ml of isotonic saline containing 25 U of regular h u m a n insulin) is commenced in accordance with our insulin infusion protocol (Table 2).

The first blood sample for serum glucose analysis is withdrawn at the t ime of arrival of the patient in the operating room. The patient is placed on a heat ing blanket, and pneumatic antithrombotic compression devices are applied and activated. Gastric regurgitation is pre­vented at induction of anesthesia by using cri­coid pressure until endotracheal intubation is accomplished. The patient is intubated and mechanically ventilated. Anesthesia is main­tained with incremental doses of fentanyl and isoflurane. The muscle relaxation necessary for surgical intervention is maintained with vecu­ronium bromide or atracurium besylate. The initial monitoring includes a lead electrocar­diogram, noninvasive blood pressure measure-

Table 2.—^Insulin Infusion Protocol for Pancreas Transplantat ion

Blood glucose (mg/dl)

Insulin infusion rate (U/h)

>250 3.0 200-249 2.5 150-199 2.0 120-149 1.5 100-119 1.0

70-99 0.5 <70 0.2

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ments, pulse oximetry, and central venous pres­sure monitoring in patients with a triple-lumen central venous pressure catheter. After induc­tion of anesthesia , m a s s spectrometry of in­spired and expired gases is initiated, direct arte­rial monitoring is begun, and a triple-lumen central venous pressure catheter is placed if this had not been done preoperatively.

Serum glucose values are determined at 30-minute intervals throughout the operation and at 10-minute intervals for the first hour after circulation in the pancreas is reestablished. Arterial blood gases are measured shortly after induction of anesthes ia and immediately before and 10 minutes and 1 hour after circulation in the pancreas is reestablished.

Patients undergoing combined pancreas and kidney transplantation receive half-isotonic saline without dextrose intravenously as main­tenance fluid. Those who have normal renal function and are receiving only a pancreas trans­plant are given lactated Ringer's solution with­out dextrose. The central venous pressure is maintained between 12 and 18 m m Hg. Lost blood is replaced with packed erythrocytes and albumin. The serum glucose value is main­tained as close as possible to 70 to 100 mg/dl by continuous infusion of insulin (Table 2). Dex­trose-containing solutions are added and the insulin infusion is discontinued when the pa­tient has severe hypoglycemia (blood glucose less than 50 mg/dl). At the completion of the procedure, all patients remain intubated and are transported, with electrocardiographic and direct arterial pressure monitoring, to a nuclear medicine laboratory adjacent to the intensive-care unit for a scan of the kidneys and pancreas before admission to the intensive-care unit.

Engraftment.—^We use a pancreaticoduode­nal graft with the exocrine drainage through a duodenocystostomy, similar to the Iowa tech­nique'''^'' but with some modifications. If the pancreas has not been procured with the liver, no vessel reconstruction is necessary. If the pancreas has been procured in combination with the liver, however, the splenic artery and supe­rior mesenteric artery mus t be reconstructed. We prefer to use the left common iliac artery

with the Y of the internal iliac and external iliac artery for reconstruction. Before reconstruc­tion, the ends of the Y are made as short as possible; the internal iliac artery is anastomosed end-to-end to the splenic artery, and the exter­nal iliac artery is anastomosed end-to-end to the superior mesenteric artery. The end of the common iliac artery is left long for further revi­sion during the engraftment. Usually, no exten­sion is needed for the portal vein.

In a combined kidney and pancreas trans­plantation, if the recipient has had no prior transplantation, the preferred placements are the pancreas in the right lower quadrant and the kidney in the left lower quadrant. We perform a bilateral curvilinear lower abdominal incision with an S extension above the right iliac crest. This incision is continued through the fascia bilaterally at the start of the procedure, a tech­nique that aids greatly in the exposure of both iliac vessel areas. Both grafts are placed ex-traperitoneally. If the recipient has previously undergone a renal transplantation on the right, we use a midline incision and place the pancreas intraperitoneally on the left.

The vessels are completely mobilized; care should be taken to ligate all lymphatic struc­tures and to maintain excellent hemostasis . The common iliac artery from its origin from the aorta, the internal iliac artery 2 to 3 cm after branching from the common iliac artery, and the entire length of the external iliac artery are mobilized. Most important, the common iliac and external iliac veins are completely mobi­lized. Several branches, including the internal iliac vein, are ligated and divided. All venous branches are suture ligated, both distally and proximally. This complete mobilization aids in the placement of the venous anastomosis; no portal extension is necessary, and no kinking of a vein of extended length can result. The graft location is determined by carefully placing the duodenum so that it gently touches the posterior part of the bladder and the portal vein on the mobilized iliac vein without bending of the head of the pancreas. The artery is anastomosed cephalad from the venous anastomosis. The portal vein is made as short as possible and

488 PANCREAS TRANSPLANTATION Mayo Clin Proc, April 1990, Vol 65

anastomosed end-to-side to the mobiUzed iUac vein. If reconstructed, the artery is shortened to be placed on the iliac artery without ten­sion. The reconstructed artery or the Carrel patch encompassing the orifice of the celiac and superior mesenteric arteries is anastomosed, end-to-side, usual ly to the distal common iliac artery.

After the circulation has been reestablished and hemostas is has been achieved, the allograft splenectomy is performed. The splenic artery and splenic vein are doubly ligated.

The duodenum is then anastomosed to the bladder, which had previously been completely mobilized both posteriorly and laterally. This anastomosis is performed between the postero­lateral aspect of the bladder and the ant imesen­teric surface of the duodenum (Fig. 1). The outer layer is sutured with interrupted 2-0 polydi-oxanone, and the inner layer is sutured with running 3-0 polydioxanone.

In a combined kidney and pancreas trans­plantation, the kidney is then transplanted on the opposite side. Before closure, the incisions are irrigated copiously with amphotericin Β solution and an antibiotic solution. Two drains are placed on either side of the pancreas.

Medical Management.—The immunosup­pressive management is quadruple therapy with Minnesota antilymphoblastic globulin for in­duction and cyclosporine, prednisone, and azathi-oprine for maintenance therapy. This regimen is described elsewhere in this s e r i e s . A n t i c o ­agulation management is one aspirin tablet daily for the first 2 weeks and then one per week. Oral selective bowel decontamination is started pre­operatively and continued for 21 days.^* The antibiotics used perioperatively include cefotax­ime (1 g intravenously every 8 hours) and van­comycin (1 g intravenously every 12 hours) for a total of 48 hours of coverage.

Intensive-Care Management.—The imme­diate postoperative care of the transplant recipi­ents can usually be managed by the monitoring and interventional skills available in most postsurgical intensive-care units . Specific care should be directed toward ensuring cardiovascu­lar integrity.

Fig. 1. Diagram of pancreaticoduodenal transplant with duodenum anastomosed to posterolateral aspect of urinary bladder.

Monitoring for Surgical Complications.— Radionuclide scans of the kidneys and pancreas are performed on days 7 ,14 , and 21 to assess the blood flow to the pancreas (and to the kidney if it was transplanted). Ultrasonograms of the pan­creas are obtained on days 3 , 7, 14, and 21 to detect potential collections of fluid or abscesses. A cystogram to confirm the integrity of the duodenocystostomy and the stapled duodenal ends is obtained on day 7. Wound complications are graded as minor (drainage only), moderate (opened with packing), or major (fascial disrup­tion). Serum lipase and amylase levels are determined daily for the first week and then every other day for the second week; pancreati­t is is considered present if these values are more than 2 t imes the baseline values.

R E S U L T S Sixteen patients received pancreaticoduodenal allografts at the Mayo Clinic from October 1987 through December 1988. The mean age of the donors (eight m e n and eight women) was 33.1 years (Table 3). The cause of brain death was closed head injury in eight, cerebrovascular accident in five, and gunshot wound to the head in three. Their mean initial blood glucose value

Mayo Clin Proc, April 1990, Vol 65 PANCREAS TRANSPLANTATION 489

Table 3.—Biochemical Variables, Preservat ion Solut ions, Ischemia Times, and Type of Procurement for 16 Pancreat icoduodenal Allograft Donors*

Initial serum values Preser­ Arterial Age (yr) Cause of Glucose Amylase vation Ischemia recon­

Case and sex death (mg/dl) (U/L) solution time (h) struction

1 22 F CHI, MVA 154 74 SGFP-III 9.6 Y graft 2 25 Μ GSW (head) 157 35 SGFP-III 12.0 Y graft 3 39 Μ CHI 212 69 SGFP-III 16.9 Y graft 4 38 Μ GSW (head) 210 254 SGFP-III 19.0 Y graft 5 27 F SAH 167 4,030t SGFP-III 17.3 Y graft 6 44 F SAH 170 84 SGFP-III 8.9 Y graft 7 32 Μ CHI, MVA 180 • . , SGFP-III 16.9 Y graft 8 47 Μ SAH 119 48 SGFP-III 15.0 Y graft* 9§ 47 Μ CVA 182 45 UW 29.8 None

10§ 30 F CHI (fall) 150 1,736 UW 18.9 None 11 16 F CHI, MVA 104 43 UW 13.1 Y graft 12§ 18 F CHI, MVA 164 199 UW 13.6 None 13§ 49 Μ CHI 133 362/ UW 17.8 None^ 14 27 Μ GSW (head) 180 50 UW 12.8 Y graft 15 44 F SAH 147 68 UW 19.2 Y graft* 16 25 F CHI, MVA 167 57 UW 18.8 Y graft

*CHI = closed head injury; CVA = cerebrovascular accident; GSW = gunshot wound; MVA = motor vehicle accident; SAH = subarachnoid hemorrhage; SGFP-III = silica gel-filtered plasma; UW = University of Wisconsin solution,

tisoenzymes: pancreatic, 454 U/L; salivary, 3,576 U/L. ^Severe atherosclerosis of superior mesenteric artery and iliac vessels. §Only pancreas procurement in these patients. In all others, both liver and pancreas procurement. ^ e r u m lipase, 13 U/L. f Brawny, edematous pancreas.

was above normal, at 162 mg/dl (range, 104 to 212 mg/dl), and the initial serum amylase value had a wide range—from 35 to 4,030 U/liter. The allograft donor with the serum amylase value of 4,030 U/liter had serum amylase isoenzjmie values of 454 U/liter pancreatic and 3,576 U/ liter salivary.

Of these 16 allografts, 8 were preserved with SGFP-III and 8 with UW solution (Table 3). The data were collected for at least 7 days in 15 patients to allow comparison of the efficacies of SGFP-III and UW solution (8 SGFP-III and 7 UW). The mean ischemia t imes were 14.4 hours (range, 8.9 to 19.0 hours) with SGFP-III and 18.0 hours (range, 12.8 to 29.8 hours) with U W (P = 0.18). Urine and serum amylase values were not significantly different (Fig. 2 and 3). Graft pancreatitis was clinically apparent in three of the eight patients who received a graft pre­served with SGFP-III and in one of the seven whose graft was preserved with U W solution.

Since the initiation of our pancreas transplan­tation program, we have participated in 36

combined liver and pancreas procurements. (Kidney allografts were procured in all instances and heart allografts in most.) Of these organs, 31 livers have been transplanted. The procure­ment of three livers was aborted because of a prior laceration in one and gross edema on initia­tion of the procurement in two; in addition, two livers were not procured because of technical complications during the procedure. No differ­ence in liver allograft function was noted be­tween these livers and a group of livers procured without a pancreas.'^ Of the 36 combined liver and pancreas procurements, 30 pancreases were transplanted. Three pancreases were not pro­cured because a right hepatic artery was pres­ent, two other pancreases were not used because no recipients were found after t issue typing and crossmatching, and one pancreas could not be used because of technical complications during the procedure. Twelve pancreases from com­bined liver and pancreas procurement were transplanted in our own program, and all 12 were reconstructed with the donor common iliac

490 PANCREAS TRANSPLANTATION Mayo Clin Proc, April 1990, Vol 65

1 —

€ 5,000

© CO 4,000 —

c ο oS 3,000 ϋ

0) 2.000 UW

>> ε 1,000

SGFP-III 1

φ c

0 1

^ 0 1 2 3 4 5 6 -r

Time after transplantation, days

Fig. 2. Urinary amylase excretion rates after preservation of allograft in silica gel-filtered plasma {SGFP-III) or Uni­versity of Wisconsin solution {UW). Data are shown as means ± SE.

artery Y graft (Table 3). No venous reconstruc­tion was necessary. Four other pancreases in our program were procured without a liver. No difference in the function of the pancreases was evident between these two groups.

The 16 pancreaticoduodenal transplantations performed at the Mayo Clinic from October 1987 through December 1988 were to 14 male and 2 female recipients (Table 4). Their mean age was 36 years (range, 21 to 47 years). Thirteen pa­tients received a combined kidney and pancreas transplant, and three received a pancreas after a prior successful kidney transplantation.

Anesthesia was well tolerated in all patients. In the 128 total hours of anesthesia , two hypo­tensive episodes necessitated treatment other than fluid boluses—ephedrine was given intra­venously in both cases. No electrocardiographic ST-segment changes were noted in any patient.

For maintenance of central venous pressure between 12 and 18 m m Hg, a mean of3 ,650 ml of half-isotonic saline and a mean of 1,350 ml of lactated Ringer's solution without dextrose were given per recipient. Three patients received 250 to 500 ml of albumin solution, and nine patients required packed erythrocyte transfusions (range.

1 to 4 units). Blood loss ranged from 200 to 1,300 ml. Seven patients required no intraoperative blood transfusions. Arterial blood gas studies revealed stable acid-base equilibrium (except for mild metabolic acidosis) and respiratory values. Four patients required 50 to 100 meq of sodium bicarbonate for treatment of metabolic acidosis.

The intraoperative glucose value was the most dynamic variable. The degree of control of blood glucose concentration preoperatively varied among the recipients. Initial serum glucose levels measured in the operating room ranged from 58 to 199 mg/dl. With the insulin infusion protocol used during the procedure, each patient achieved a steady state of serum glucose level jus t before reestablishment of circulation in the pancreas; immediately thereafter, a statistically significant (P<0.05) increase in serum glucose was observed^** (Fig. 4). This increase responded to adjustment of the infusion of insulin, al­though 120 to 240 minutes was needed to achieve the same degree of control as before circulation was reestablished. Intraoperative hypoglyce­mia (serum glucose less than 50 mg/dl) occurred in six cases and was treated with infusion of dextrose, cessation of infusion of insulin, or both.

Several variables were closely monitored in the intensive-care unit (Table 5). On arrival in the unit, the patients were modestly hypother­mic (mean temperature, 35.3°C). Patients who

300 h

ε Ε

I

• SGFP-I Ο UW

m i m m 2 3 4 5 6 7

Days after transplantation

Fig. 3. Serum amylase values after preservation of allograft in silica gel-filtered plasma {SGFP-III) or University of Wisconsin solution {UW). Data are shown as means ± SE.

Mayo Clin Proc, April 1990, Vol 65 PANCREAS TRANSPLANTATION 491

Table 4.—Type of Transplant, Urinary Amylase Excret ion Rate, and Surgical Complications* in 16 Pancreat icoduodenal Transplantat ions at the Mayo Clinict

Urinary amylase (U/h) Wound complication

Age (yr) Pancreas Day Day Type and Days Pancreatitis Case and sex placement 7 30 treatment postop (postop days)

1 30 Μ ΕΡ 2,849 5,872 Moderate Open packing

22 8-21

2 37 Μ ΕΡ 2,958 5,777 31: 47 Μ ΕΡ 2,661 4,064 Major

Closure 8

28 4 45 Μ IP 3,280 CMV pan­

creatitis 5 40 Μ ΕΡ 1,720 3,497 6t 45 Μ IP 3,850 9,135 7 27 Μ ΕΡ 5,420 6,134 8-20 8 39 Μ ΕΡ 2,376 4,142 Minor 8 9 28 F ΕΡ 1,030 1,873

Rejection resolved

Moderate Closure

10 10

10 29 F ΕΡ 3,484 3,897 . t · 8 11 38 Μ ΕΡ 4,432 Rejection 12 21 Μ ΕΡ 3,653 5,110 8-17 13 27 Μ ΕΡ 735 1,166 Major

Closure 23 23

§

14* 36 Μ IP 1,848 Rejection 15 44 Μ ΕΡ 3,773 5,902 Minor 21 12 16 37 Μ ΕΡ ... ...

*No recipient had thrombosis. A duodenal fistula developed in case 13. tCMV = cytomegalovirus; EP = extraperitoneal; IP = intraperitoneal; postop = postoperative. *These patients received only a pancreas transplant; all others received both a kidney and a pancreas transplant. §Severe biopsy-proven pancreatitis.

underwent a combined kidney and pancreas transplantation had lower body temperatures (mean temperature, 35°C) than did those who received only a pancreas transplant (mean temperature, 36°C). All patients were normo-thermic at 8 hours after admission to the inten­sive-care unit. Hypertension that necessitated treatment developed in 11 patients during the first 24 hours in the intensive-care unit. One patient was readmitted to the intensive-care unit because of severe hypertension. The con­tinuous infusion of insulin (Table 2) to maintain blood glucose at 70 to 100 mg/dl was continued in all patients. The usual patient required a con­tinuous rate of less than 1 U of insul in per hour to maintain blood glucose at less than 100 mg/dl. Four patients, one on two occasions, needed bolus infusions of 6 g of glucose because of a blood glucose value of less than 60 mg/dl (during more

than 400 patient-hours of continuous infusion of insulin).

The patients were maintained on mechanical ventilation until they were awake, had protec­tive airway reflexes, and were medically stable. On the average, the patients were extubated 10.7 hours after admission to the intensive-care unit. The mean stay for these patients was 39.1 hours. Four patients were in the intensive-care unit for less than 24 hours.

One patient had electrocardiographic changes that were consistent with myocardial infarction, but these findings were not confirmed by serial cardiac isoenzjrme values. No other patient had s igns of myocardial ischemia despite the propen­sity for development of hypertension. None of the patients had a dysrhythmia. No problems with acid-base or electrolyte imbalance were encountered.

492 PANCREAS TRANSPLANTATION Mayo Clin Proc, April 1990, Vol 65

Ο Ο 3 Ο)

I I

220

200

180 5 Ε 160

140 I-120

100

80

60

40

• Significantly different • P<0.05

-400 -200 0 200

Time relative to re-establishment of blood flow to pancreas

400

Fig. 4. Serum glucose levels during pancreaticoduodenal transplantation. The vertical lines depict range of values. On horizontal axis, time is shown in minutes.

The mean urinary amylase excretion was 2,938 U/h at 1 week after transplantation; in those who had no rejection episodes or cjrtomegalovirus infection, this measurement was 4,972 U/h at 1 month. Among the 13 patients in whom pancre­ases were placed extraperitoneally, 6 wound complications occurred—2 minor, 2 moderate, and 2 major necessitat ing fascial debridement and repair. Five of these wound complications eventually were closed primarily, and one was packed open for approximately 6 weeks. In one patient, a duodenal fistula developed at the pyloric end; this complication was treated by open exploration and closure of the fistula. No grafts were lost as a result of wound complica­tions. No venous or arterial thrombosis oc­curred. Severe pancreatitis, confirmed histo­logically, developed in one patient. On the basis of laboratory findings, five patients had episodes of pancreatitis approximately 8 to 12 days after transplantation; these episodes resolved in 9 to 13 days without complications. One patient had rupture of a pseudoaneurysm at the splenic-internal iliac artery reconstruction site. The resulting hematoma was contained in the ex­

traperitoneal space, and the vessels were con­trolled during abdominal exploration. The arte­rial anastomosis was successfully reconstructed.

D I S C U S S I O N The increasing success of pancreas transplanta­tion during the past few years' is due in part to the improvement in the operative and peri­operative management . We are fortunate to be located near several active, successful pancreas transplantation centers (University of Minne­sota, University of Wisconsin, and University of Iowa). We have learned from each of these centers, which helped us in developing a man­agement protocol for our program.

Because of the shortage of donor organs, be­fore our institution could undertake pancreas transplantation, we had to refine a method for procurement of both the pancreas and the liver from the same donor. Our evidence suggests that this combined procurement technique does not result in poor function of the allografts. We have had no increase in liver or pancreas allo­graft loss or dysfunction in comparison with procurement of the liver or the pancreas singly.

Mayo Clin Proc, April 1990, Vol 65 PANCREAS TRANSPLANTATION 493

Table 5.—Variables Measured in Intensive-Care Unit in 16 Pancreat icoduodenal Transplantat ions at the Mayo Clinic*

Temperature (°C) High BP Hypoglycemia Time ICU At At for 24 h necessitating intubated stay

Case arrival 8 h mm Hg Treated treatment (h) (h) Comment

1 35.1 36.7 170 Yes (NaN)

No 8 34

2 35.5 36.5 125 No Yes 17.5 28 3t 34.6 36.2 165 Yes No 8.3 36 4 35.0 36.5 170 Yes

(NaN) Yes 39 87 Readmitted for severe

hypertension 5 35.7 37.0 135 No No 10 19 6t 36.8 37.2 230 Yes No 11.5 38 7 36.5 165 Yes No 6 59 ECG changes; CK

isoenzymes normal 8 35.4 37.0 170 Yes No 8.5 56 9 34.5 36.0 130 No Yes 4.5 46 Severe hypoglycemia;

no insulin infusion 10 ... ... ICU records not found 11 34.4 36.5 195 Yes No 2" 22 12 35.8 37.5 150 Yes Yes 2.5 18 Hypoglycemia; no

insulin infusion initiated

13 34.7 37.5 180 Yes No 1.5 40 14t 36.6 37.6 120 No No 10 49 15 35.5 36.7 170 Yes No 19 35 16 34.0 35.9 185 Yes No 11.7 19

*BP = blood pressure; CK = creatine kinase; ECG = electrocardiographic; ICU = intensive-care unit; NaN = sodium nitroprusside.

tThese patients received only a pancreas transplant; all others received both a kidney and a pancreas transplant.

We have had only one complication related to the pancreas vascular reconstruction—a ruptured pseudoaneurysm at the splenic artery-internal iliac artery anastomosis—but this did not result in loss of the graft. The one case of fistula at the pyloric end of the duodenum possibly was re­lated to decreased blood flow caused by ligation of the gastroduodenal artery or to graft edema and complications associated with the use of staples. We believe that the combined procure­ment technique is safe and has expanded the availability of liver and pancreas allografts.

We have noted a low incidence of graft edema and pancreatitis. Currently, we are finding no difference in graft function with the two preser­vation solutions that we have used. In contrast with SGFP-III, the U W solution has the advan­tage that it can be used as an intra-aortic flush. We preserved a graft for 30 hours in the U W solution and had good results. This increased preservation t ime will aid in sharing of pancreas

allografts between transplantation centers and should allow better matching by t issue typing.

The technique of pancreaticoduodenal trans­plantation with a duodenocystostomy (the Iowa approach) has advantages over other tech­niques.''•^''•^^ With use of this technique and aspirin as the only anticoagulant, we have had no episodes of thrombosis. We have placed most of the pancreaticoduodenal allografts extraperi­toneally. This approach has resulted in a rela­tively high rate of wound complications but no severe morbidity and no graft loss. Usually, a cloudy wound discharge is evident on approxi­mately day 8 to 10, presumably from enzymes weeping from the pancreas allograft. Perhaps perioperative administration of somatostatin analogue would decrease this weeping and thus diminish the wound drainage problem; however, further laboratory investigation of this tech­nique is needed. The advantage of extraperi­toneal placement of the pancreas allograft is

494 PANCREAS TRANSPLANTATION Mayo Clin Proc, April 1990, Vol 65

simply avoidance of the peritoneal cavity. The hematoma from a ruptured pseudoaneurysm in one of our patients was contained; therefore, a controlled approach in repairing the anasto­mosis was possible. Most of the recipients re­sumed their oral diet in 3 to 4 days. Our patients have had no peripancreatic abscesses. Although contamination of the wound drainage fluid has occurred, no treatment has been necessary. The duodenal fistula that developed in one patient was easily repaired.

The key to avoiding problems in the anes­thetic management of pancreas transplant re­cipients is a thorough preoperative evaluation. Early experience with pancreas transplantation revealed the potential for myocardial complica­tions in this group of patients.^" In our series, all pat ients underwent extensive preoperative screening with thorough cardiac evaluation, including exercise thall ium ventriculography and coronary angiography when indicated. Our patients had no intraoperative episodes of myo­cardial ischemia, and the hemodynamics were remarkably stable. U s e of an insulin infusion algorithm resulted in a stable glucose level in­traoperatively. Once a steady state had been achieved in each patient, few alterations in the infusion of insulin were necessary except for immediately after circulation to the pancreas was reestablished. This reperfusion was fol­lowed by a 2- to 4-hour period of increased serum glucose concentration that necessitated an in­crease in the infusion of insulin until a new steady state was achieved. No such increase in serum glucose was seen after reestabl ishment of circulation to the donor kidney. We hypothesize that this previously undescribed increase in serum glucose concentration may represent re­lease of glucagon from the donor pancreas.

Aside from the dynamic intraoperative serum glucose changes, the other concerns to the anes­thesiologist intraoperatively are moderate fluid requirement, occasional mild metabolic acido­sis, and infrequent hypokalemia. Anesthes ia is well tolerated in this group of patients. Intraop­erative monitoring of glucose and arterial blood gases is necessary, and glucose management , consist ing primarily of non-glucose-containing

solutions and continuous infusion of insulin, results in stable glucose dynamics.

When we initiated our program, we ques­tioned whether the pancreas transplant recipi­ents would benefit from being admitted to the intensive-care unit postoperatively. Subse­quently, we have learned that several problems, including hypothermia and hypertension, can occur at this t ime, and close monitoring and intravenous treatment may be needed. In this population of patients with diabetes, myocardial ischemia should be diligently sought (even though this did not occur in our patients). The continu­ous infusion of insulin, which was maintained at a low rate, kept the patient normoglycemic in the immediate postoperative period. Thus, we con­clude that a short period of monitoring and support in the intensive-care unit is extremely beneficial for the avoidance of complications in the immediate postoperative period.

C O N C L U S I O N The successful management of pancreas trans­plantation in the operative and perioperative period at the Mayo Clinic has been encouraging. We have found the procedure with some modifi­cations to be safe and have had no graft loss due to technical or wound complications. With these results , we are encouraged to expand pancreas transplantation to a larger patient population.

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24. Nghiem DD, Corry RJ: Technique of simultaneous renal pancreatoduodenal transplantation with uri­nary drainage of pancreatic secretion. Am J Surg 153:405-406, 1987

25. D'Alessandro AM, Sollinger HW, Stratta RJ, Kalayoglu M, Pirsch JD, Belzer FO: Comparison between duodenal button and duodenal segment in pancreas transplantation. Transplantation 47:120-122, 1989

26. Albert! KGMM, Thomas DJB: The management of diabetes during surgery. BrJAnaesth 51:693-710, 1979

27. Cuthbertson RA, Koulmanda M, Mandel TE: Detri­mental effect of chronic diabetes on growth and func­tion of fetal islet isografts in mice. Transplantation 46:650-654, 1988

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