Vs 1.0; 8/2020

Pancreas Transplant Anesthesia pearls and Pancreatectomy with Islet Cell Auto-transplant pearls

Kate Kronish MD, Ryutaro Hirose MD, and Andrew Posselt MD

Pancreas Transplant

Patient Demographics and Epidemiology

Pancreas transplants are primarily performed in patients with DM1, but increasingly for DM2 as well (almost 15%). Pancreas transplant alone (PTA) is usually for patients with brittle IDDM with episodes of hypoglycemic unawareness, very poorly controlled blood glucose (BG), and other diabetic complications other than renal dysfunction. SPK is for IDDM with diabetic nephropathy.

Waitlist candidates are relatively younger than kidney transplant alone candidates, with <30% age 50+, compared to almost 70% of kidney transplant candidates age 50 and older. However, the age of pancreas transplant recipients has been increasing in recent years.

Major co-morbidities include the microvascular and macrovascular complications of DM. These patients are high risk for coronary artery disease (even if relatively young and asymptomatic). All patients need pre-transplant cardiac testing including EKG, TTE and a stress test.

Disease Background and Procedural Description

The first successful pancreas transplant was in the 1960s. There are 3 types of pancreas transplants performed: pancreas transplant alone (PTA), simultaneous pancreas kidney transplant (SPK), and pancreas after kidney (PAK, usually living donor kidney transplant has occurred previously). Some centers also perform islet cell cadaveric transplants. This should not be confused with pancreatectomy with islet cell auto-transplant, which is performed for chronic pancreatitis, not for diabetes. (The anesthetic management of these cases is discussed at the bottom of this document.)

Over 1000 pancreas transplants were performed in 2018 of all 3 types. The majority are SPKs (~80%). Overall, pancreas transplants have decreased over the past two decades, due to better medical management of diabetes (DM). You may notice pancreas transplants scheduled and then cancelled due to poor quality. The donor discard rate in the U.S. is > 20%.

Outcomes

Successful pancreas transplant can significantly improve glucose control, frequently achieving insulin independence, and can stop or reverse the chronic microvascular complications of diabetes.

There is variable reporting for graft outcomes with pancreas transplant. Kidney outcomes in SPK are superior to deceased donor kidney transplant alone, presumably due to higher quality grafts chosen for SPK. 1-year mortality is 1-3% for all types of pancreas transplant. 10-year mortality is 20-25%, primarily due to cardiovascular causes of death.

Kate Kronish, MD Vs 1.0; 8/2020

Preoperative Assessment

Preoperative Preparation

Intraoperative management:

Access/Fluid and Monitors

Lines and Monitors-. Standard ASA monitors + Arterial line for maintenance of adequate perfusion pressure to graft, and for frequent blood draws. 2 PIVs, at least one large bore PIV. 18 g Naso-gastric tube. Both iliac arteries will be clamped sequentially, so BP cuffs will not be useful during the clamp time.

Glucose monitoring – Check BG q1 hour before unclamping of new pancreas transplant, then q30 min after that. Always communicate glucose values and planned insulin treatment with attending anesthesiologist and surgeon! Caution that after unclamping of the new functioning pancreas, glucose may drop rapidly. Please QC glucometer before start of case.

Fluids – Please use 5% albumin over crystalloid to help prevent pancreas allograft edema (unfortunately no good supporting data for this, however.) Consider insensible losses due to long duration of surgery with open abdomen. Blood loss may occur; 2 units pRBCs should be in the OR, and more if patient is anemic or additional concerns.

Anesthetic Technique

Induction – GETA with full muscle relaxation required. Consider RSI with cricoid pressure given diabetic gastroparesis, consider also metoclopramide.

Special Medications – Important medications include immunosuppression (all pancreas recipients receive thymoglobulin induction + methylprednisolone), mannitol, heparin, insulin (1 unit/mL bag), dextrose, 5% albumin, cisatracurium if renal failure. Discuss plan for timing and doses of these important meds at time out. Monitor for hypotension and hypoxemia due to reaction to thymoglobulin – alert surgeon and consider stopping thymoglobulin should this occur. You will need filters for mannitol and thymoglobulin, Alaris pump + tubing for thymoglobulin.

Pain control – Pain control with primarily opioids + adjuvants (remember, high dose steroids also provide opioid-sparing effect). Some centers do TAP blocks or rectus sheath block. No epidural for these cases at UCSF due to concern for vasodilation/hypotension causing poor graft perfusion and possible need for heparin.

Key procedure related points :

Surgical notes /major stages & surgical concerns

Kate Kronish, MD Vs 1.0; 8/2020

Surgeons will first prepare the pancreas allograft on the back table. This can be tedious and painstaking and involves arterial reconstruction with a Y-graft of donor iliac artery.

Incision for SPK will be a long midline incision. Exposure of both right and left iliac vessels is required, followed by kidney implant and pancreas implant.

It is especially important to have dense musculoskeletal blockade while surgeons clamp and then sew in organs.

There may be significant bleeding upon unclamping of the pancreas allograft. Usually the pancreas/duodenum will be drained into recipient’s small intestine.

Postoperative considerations include GI motility due gastroparesis and bowel edema, pancreatic edema, bleeding, hypotension and hypoperfusion of new graft, and graft thrombosis. All patients go to the ICU for BP monitoring and frequent BG and Hb/Hct monitoring.

For SPK patients, please refer to renal transplant anesthesia pearls (https://anesthesia.ucsf.edu/clinical- resources/ucsf-anesthesia-resident-pearls-renal-transplant) for additional considerations for renal transplant in SPK.)

Potential Complications

Ergonomic Considerations

Duration of case

Kate Kronish, MD Vs 1.0; 8/2020

Total pancreatectomy with islet cell auto-transplant

Background is performed for patients with chronic pancreatitis who have failed medical treatment. They frequently have significant chronic opioid use. The spleen is also removed. The patient's own islet cells are preserved, isolated and purified, and then injected back into the patient's portal vein to ameliorate the surgical diabetes that is produced by a total pancreatectomy. Because the patient's own islet cells are used, immunosuppression is not required. Post-op over a period of months, about 80% of patients are able to wean fully off opioids, and 50-75% of patients achieve insulin independence.

Surgical notes Surgeons make a midline incision from xiphoid to below umbilicus. The right arm is usually tucked and left arm out. The pancreatectomy takes about 3 hours, after which there is a period of about 1.5 – 2h where we wait (with patient under GA) for the islet cells to be processed. There is no surgical stimulation at this time.

Islet cell infusion Infusion of the islets takes about 20 mins. Surgeons will measure portal pressures during the infusion – have an extra pressure transducer zeroed and ready. There may be some transient hypotension at the start of the infusion but this usually resolves. A total of 70 units/kg heparin is given at the start of the infusion – 35 units/kg are in the islet mix and 35 units/kg are given IV by the anesthesia provider.

Anesthetic plan -GETA with neuromuscular blockade. NG Tube. Consider A-line or use large PIV for frequent blood glucose monitoring. -Usual EBL 200-300. Chance of blood loss (if surgically difficult with extensive scarring). Consider ordering RBCs, but not necessary in the OR. 2 PIVs. -Fluid goals for the entire case are around 2-3 L. -BG should be checked every 20-30 mins after pancreas is out. Always communicate BG and insulin treatment plan with surgeon. OK to use Decadron for PONV. -Pain management: ESP bilateral catheters (placed in pre-op by the regional team). Dose the catheters intra-op + IV opioids + adjuncts (gabapentin + acetaminophen pre-op, consider ketamine, magnesium). Calculate the patient's baseline opioid requirement. Communicate plan with the pain service. -Extubate and go to ICU post-op for q1 hour glucose checks

Resources and References 1. https://srtr.transplant.hrsa.gov/annual_reports/2018/Pancreas.aspx OPTN/SRTR 2018 Annual Data Report: Pancreas 2. Anesthesia for Kidney and Pancreas Transplantation. Mittell and Wagener https://doi.org/10.1016/j.anclin.2017.04.005 3. Spiro M and Eilers H. Intraoperative Care of the Transplant Patient. Anesthesiology Clinics. 2013;31(4)705-721. 4. Halpern H et al. Anesthesia for Pancreas Transplantation Alone or Simultaneous With Kidney. Transplant Proc. 2004; 36(10):3105-6. 5. Lombardo C et al. Update on Pancreatic Transplantation on the Management of Diabetes. Minerva Med. 2017 Oct;108(5):405-418.

Kate Kronish, MD