Pancreas transplantation

Pancreas transplantation is a form of pancreatic β-cell replacement that restores normal blood sugar levels, or normoglycemia, in patients with diabetes. Because recipients trade the need for insulin injections for immunosuppressants, pancreas transplantation is performed primarily in patients with type 1 diabetes with renal failure and who are thus candidates for kidney transplantation; about 90% of pancreas transplants are performed together with kidney transplantation. In many centers, failure of standard treatment and a history of unexplained hypoglycemia are also criteria for choosing this treatment option. Relative contraindications include age over 55 years, significant cardiovascular atherosclerotic disease, history of myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary interventions, or a positive stress test; these factors significantly increase the perioperative risk.

Pancreas transplantation includes simultaneous pancreas-kidney transplantation (SPK), pancreas-after-kidney transplantation (PAK), and pancreas-only transplantation. The advantages of SPK include simultaneous exposure of both organs to immunosuppressants, potential protection of the transplanted kidney from the adverse effects of hyperglycemia, and the ability to monitor kidney rejection; kidneys are more susceptible to rejection than the pancreas, whose rejection is difficult to monitor. The advantage of PAK is the ability to optimize HLA matching and timing of kidney transplantation when using a living donor organ. Pancreas transplantation is used primarily for patients who do not have end-stage renal disease but have severe complications of diabetes, including poor blood glucose control.

Donors are recently deceased patients aged 10–55 years with no history of glucose intolerance and no history of alcohol abuse. For SPK, the pancreas and kidneys are collected from the same donor, and the restrictions on organ procurement are the same as for kidney donation. A small number (< 1%) of segmental transplants from living donors are performed, but the procedure carries significant risks to the donor (e.g., splenic infarction, abscess, pancreatitis, pancreatic leakage and pseudocyst, secondary diabetes), limiting its widespread use.

At present, the overall two-year survival rate of cadaveric pancreas transplants reaches 83%. The main criterion for success is the optimal functional state of the transplanted organ, and the secondary criteria are the age of donors over 45-50 years and general hemodynamic instability. The existing experience of transplanting a part of the pancreas from a living related donor is also quite optimistic. The one-year survival rate of the transplant is 68%, and the 10-year survival rate is 38%.

However, the best results of pancreas transplantation in patients with diabetic nephropathy are obtained with simultaneous kidney and pancreas transplantation.

The specifics of anesthetic support for pancreas transplantation are generally typical for this category of endocrinological patients. Pancreas transplantation is usually indicated for patients with diabetes mellitus with the most severe, rapidly progressing course of the disease and complications.

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Anatomical and physiological features of the pancreas and pathophysiological changes in case of its insufficient function

The severe condition of patients with diabetes mellitus who are indicated for pancreas transplantation is caused by acute or chronic insulin deficiency. Acute insulin deficiency causes the development of rapid decompensation of carbohydrate and other types of metabolism and is accompanied by a diabetic symptom complex in the form of hyperglycemia, glucosuria, polydipsia, weight loss together with hyperphagia, ketoacidosis. A sufficiently long course of diabetes leads to systemic vascular damage - diabetic microangiopathy. Specific damage to the retinal vessels - diabetic retinopathy is characterized by the development of microaneurysms, hemorrhages and proliferation of endothelial cells.

Diabetic nephropathy is manifested by proteinuria, hypertension with the subsequent development of chronic renal failure.

Diabetic neuropathy is a specific lesion of the nervous system, which can manifest itself in symmetrical multiple lesions of the peripheral nerves, lesions of one or more nerve trunks, the development of diabetic foot syndrome, and the formation of trophic ulcers of the shins and feet.

Due to decreased immunity, patients with diabetes mellitus often have a large number of concomitant diseases: frequent acute respiratory infections, pneumonia, infectious diseases of the kidneys and urinary tract. There is a decrease in the exocrine function of the stomach, intestines, pancreas, hypotension and hypokinesia of the gallbladder, constipation. Often there is a decrease in fertility in young women and growth disorders in children.

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Preoperative preparation and assessment of the patient's condition before surgery

Preoperative examination includes a thorough examination of the organs and systems most susceptible to diabetes. It is important to identify signs of coronary heart disease, peripheral neuropathy, the degree of nephropathy and retinopathy. Joint stiffness may complicate laryngoscopy and tracheal intubation. The presence of vagal neuropathy may indicate a slowdown in the evacuation of solid food from the stomach.

Before surgery, such patients undergo biochemical tests, including a glucose tolerance test; determination of the level of C-peptide in urine and plasma, determination of blood glucose (glycemic control index during the previous months) and insulin antibodies to islet cells. To exclude cholelithiasis, an ultrasound of the gallbladder is performed.

In addition to continuous preoperative plasma glucose monitoring, mechanical and antimicrobial bowel preparation is usually undertaken.

Premedication

The premedication regimen is no different from that used for transplantation of other organs.

Basic methods of anesthesia

When choosing an anesthesia method, preference is given to OA combined with prolonged EA. RAA provides adequate postoperative analgesia, early activation of patients, and a significantly lower number of postoperative complications. Induction of anesthesia:

Midazolam IV 5-10 mg, single dose

+

Hexobarbital IV 3-5 mg/kg, single dose or Thiopental sodium IV 3-5 mg/kg, single dose

+

Fentanyl IV 3.5-4 mcg/kg, single dose or Propofol IV 2 mg/kg, single dose

+

Fentanyl intravenously 3.5-4 mcg/kg, single dose.

Muscle relaxation:

Atracurium besylate IV 25-50 mg (0.4-0.7 mg/kg), single dose or Pipecuronium bromide IV 4-6 mg (0.07-0.09 mg/kg), single dose or Cisatracurium besylate IV 10-15 mg (0.15-0.3 mg/kg), single dose. Maintenance of anesthesia: (isoflurane-based general balanced anesthesia)

Isoflurane inhalation 0.6-2 MAC I (in minimal-flow mode)

+

Dinitrogen oxide with oxygen by inhalation (0.3: 0.2 l/min)

+

Fentanyl IV bolus 0.1-0.2 mg, frequency of administration is determined by clinical appropriateness

+

Midazolam IV bolus 0.5-1 mg, frequency of administration is determined by clinical appropriateness or (TVA) Propofol IV 1.2-3 mg/kg/h, frequency of administration is determined by clinical appropriateness

+

Fentanyl 4-7 mcg/kg/h, frequency of administration is determined by clinical appropriateness or (general combined anesthesia based on prolonged epidural block) Lidocaine 2% solution, epidural 2.5-4 mg/kg/h

+

I Bupivacaine 0.5% solution, epidural 1-2 mg/kg/h Fentanyl IV bolus 0.1 mg, frequency of administration is determined by clinical appropriateness Midazolam IV bolus 1 mg, frequency of administration is determined by clinical appropriateness. Muscle relaxation:

Atracurium besylate IV 1-1.5 mg/kg/h or Pipecuronium bromide IV 0.03-0.04 mg/kg/h or Cisatracurium besylate IV 0.5-0.75 mg/kg/h.

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Adjuvant therapy

One of the important conditions for the survival of pancreas and kidney transplants is maintaining a high CVP of 15-20 mm Hg. Therefore, it is important to conduct correct infusion therapy, in which the main components of the colloidal component are 25% albumin solution, 10% HES solution and dextran with an average molecular weight of 30,000-40,000, and crystalloids (30 ml/kg) are administered in the form of sodium chloride/calcium chloride/potassium chloride and 5% glucose with insulin:

Albumin, 10-20% solution, intravenously 1-2 ml/kg, the frequency of administration is determined by clinical appropriateness or

Hydroxyethyl starch, 10% solution, intravenously 1-2 ml/kg, the frequency of administration is determined by clinical appropriateness or

Dextran, average molecular weight 30,000-40,000 IV 1-2 ml/kg, frequency of administration is determined by clinical appropriateness

Dextrose, 5% solution, intravenously 30 ml/kg, the frequency of administration is determined by clinical appropriateness or

Sodium chloride/calcium chloride/potassium chloride intravenously 30 ml/kg, frequency of administration is determined by clinical appropriateness

Insulin intravenously 4-6 U, then the dose is selected individually.

Immediately before removing the vascular clamps, 125 mg of methylprednisolone and 100 mg of furosemide are administered:

Methylprednisolone IV 125 mg, single dose

+

Furosemide intravenously 100 mg, once.

When administering insulin in the preoperative period, hypoglycemia should be avoided. The optimal level is considered to be mild hyperglycemia, which is corrected in the postoperative period if necessary.

Intraoperative monitoring of plasma glucose levels is very important. When correcting hyperglycemia during surgery, insulin is administered both as a bolus and as an infusion in a 5% glucose solution.

Currently, most pancreas transplants are performed using bladder drainage technology, which involves its extraperitoneal placement.

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How does a pancreas transplant work?

The donor is anticoagulated and a cold preservative solution is injected via the celiac artery. The pancreas is cooled in situ with ice-cold saline and removed en bloc with the liver (for transplantation into different recipients) and the second part of the duodenum containing the ampulla of Vater.

The donor pancreas is placed intraperitoneally and laterally in the lower abdomen. In SPK, the pancreas is placed in the right lower quadrant of the abdomen and the kidney in the left lower quadrant. The native pancreas remains in place. Anastomoses are formed between the donor splenic or superior mesenteric artery and the recipient iliac artery and between the donor portal vein and the recipient iliac vein. In this way, endocrine secretions are systematically released into the bloodstream, leading to hyperinsulinemia; sometimes anastomoses are formed between the pancreatic venous system and the portal vein, 'V additionally to restore normal physiological conditions, although this procedure is more traumatic and its advantages are not entirely clear. The duodenum is sutured to the apex of the gallbladder or to the jejunum to drain exocrine secretions.

Immunosuppressive therapy courses vary but typically include immunosuppressive Ig, calcineurin inhibitors, purine synthesis inhibitors, and glucocorticoids, the dose of which is gradually reduced by the 12th month. Despite adequate immunosuppression, rejection develops in 60-80% of patients, initially affecting the exocrine rather than endocrine apparatus. Compared with kidney-only transplantation, SPK has a higher risk of rejection, and rejection cases tend to develop later, recur more frequently, and be resistant to glucocorticoid therapy. Symptoms and objective signs are not specific.

In SPK and RAK, pancreatic rejection, diagnosed by an increase in serum creatinine, almost always accompanies renal rejection. After pancreas-only transplantation, a stable urinary amylase concentration in patients with normal urine flow rules out rejection; its decrease suggests some forms of graft dysfunction, but not specific for rejection. Therefore, early diagnosis is difficult. Diagnosis is based on ultrasound-guided cystoscopic transduodenal biopsy. Treatment is with antithymocyte globulin.

Early complications occur in 10-15% of patients and include wound infection and dehiscence, significant hematuria, intra-abdominal urinary leakage, reflux pancreatitis, recurrent urinary tract infections, small bowel obstruction, abdominal abscess, and graft thrombosis. Late complications are related to urinary loss of pancreatic NaHCO3, resulting in decreased circulating blood volume and non-anion gap metabolic acidosis. Hyperinsulinemia does not appear to adversely affect glucose and lipid metabolism.

What is the prognosis for pancreas transplantation?

At the end of 1 year, 78% of grafts and more than 90% of patients survive. It is unknown whether patients who undergo a procedure such as pancreas transplantation have a better survival rate than those who do not undergo transplantation; however, the major benefits of this procedure are the elimination of the need for insulin and stabilization or improvement of many complications of diabetes (eg, nephropathy, neuropathy). Graft survival is 95% in SPK, 74% in CAC, and 76% in pancreas-only transplantation; survival after CAC and pancreas-only transplantation is thought to be worse than after SPK because reliable markers of rejection are lacking.

Correction of disorders and assessment of the patient's condition after surgery

Intensive care is rarely required in the postoperative period, although careful monitoring of plasma glucose and the use of insulin infusions are necessary. Once oral feeding is resumed, insulin administration becomes unnecessary if graft function is preserved. A major advantage of the bladder drainage technique is the ability to monitor exocrine graft function, which deteriorates during rejection episodes. Urine pH may fall, reflecting decreased pancreatic bicarbonate secretion, and urine amylase levels may decrease. The most common postoperative complications are graft thrombosis and intra-abdominal infection.

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