EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Patients with glycogen storage diseases pose unique management challenges to clinicians. These challenges are exacerbated whenever they undergo surgery as the basic anomaly in their glycogen storage pathways make them susceptible to organic acidosis, which may in turn complicate their preoperative, intraoperative, and postoperative course. Because of the rarity of these diseases, clinicians may not be aware of the specific management concerns. In the case reported here, a 37-year-old patient with glycogen storage disease type 1 underwent left hepatectomy for hepatic adenomatosis, which was complicated by intraoperative severe lactic acidosis that was successfully treated. After successful hepatectomy, the patient underwent liver transplant without major lactic acidosis or hemodynamic instability. Early recognition and aggressive management of blood sugar and lactic acidosis in patients with glycogen storage diseases can allow for successful outcomes even when complex surgical procedures are required.

Key words : Blood sugar, Hepatectomy, Lactic acidosis, Liver transplant

Of patients with glycogen storage disease, 90% have glycogen storage disease type 1 (GSD1), which has an incidence of 1 in 100 000 live births.¹ It is an autosomal recessive disorder of glucose metabolism due to deficiency of glucose-6-phosphatase enzyme; the disorder leads to glycogen build up in the liver, kidney, and intestines.

By 20 to 30 years of life, many patients with GSD1 develop hepatic adenomas that can hemorrhage and harbor malignancy in up to 10% of cases.² Hepatic adenomas are detected in 70% of patients over 25 years of age, with median age at diagnosis of 15 years.³

Once hepatic adenomas are observed, surveillance by ultrasonography every 3 to 6 months is recommended. Contrast-enhanced computed tomography or magnetic resonance imaging (MRI) is warranted if there are change to the appearance of lesions.³ These changes may indicate malignant transformation of the adenoma, and hepatic resection or liver transplant should be considered.

The aim of medical management is to maintain euglycemia and to prevent organic acidosis. Patients are advised to take frequent meals and uncooked cornstarch. By preventing the hypoglycemia, most patients will improve symptomatically.⁴ Liver transplant is indicated in patients with GSD1 when there is poor metabolic control, worsening hepatic adenomatosis, development of hepatocellular carcinoma, and/or liver failure.

A 37-year-old male patient with GSD1 presented for evaluation of multiple hepatic adenomas. Previous biopsy of these lesions was benign. An MRI of the abdomen showed massive hepatomegaly with smooth liver contour with extensive hepatic steatosis and without cirrhosis. Two arterial enhancing lesions, a 4 × 5-cm lesion in the left lateral segment and a 2.4 × 3.3-cm lesion in segment 4 along the falciform ligament, were reported (Figure 1); these lesions were consistent with hepatic adenoma. The patient was asymptomatic and managed his GSD1 with supplemental cornstarch. The patient had a past medical history of essential hypertension, hyperlipidemia, and nephrolithiasis. The institutional multidisciplinary liver tumor board recommended follow-up in 3 months with repeat imaging and resection of left lobe hepatic adenomas secondary to the malignant potential of these lesions.

On follow-up at 3 months, the surveillance MRI showed enlarging left hepatic lobe adenoma with features concerning for hepatocellular carcinoma. Because of the changes in size and the imaging characteristics, the decision was made to proceed with left hepatectomy.

The night before left hepatectomy, the patient had no food or drink. The operation was technically difficult due to massive hepatomegaly and was complicated by metabolic acidosis. The patient had persistent hypotension secondary to the metabolic acidosis, requiring significant inotropic support. Intraoperatively, the lactate level peaked at 25 mg/dL. The patient did not have hypoglycemia intraoperatively due to aggressive supplementation, and acidosis appeared immediately after skin incision, which persisted throughout the surgery.

After surgery, the patient was ventilated in the intensive care unit. His lactate level was 24 mg/dL and pH was 6.99, which were minimally responsive to sodium bicarbonate. Hence, continuous renal replacement therapy was initiated with an acetate bath to correct the pH, allowing the pressor requirement to decrease. This was conducting simultaneously with supportive management of blood sugar (with intravenous glucose administration and supplemental cornstarch feeding). Within 36 hours, the patient’s lactate level had decreased to 10 mg/dL and pH had normalized. Inotropic support was decreased, and the patient’s hemodynamic parameters had markedly improved. By postoperative day 2, lactate levels had normalized and the patient was weaned from inotropic support. Continuous renal replacement therapy was discontinued, and the patient was extubated on postoperative day 6. The patient was transferred to the inpatient floor on postoperative day 11 and discharged on postoperative day 18.

The pathology report showed multiple inflammatory hepatic adenomas with steatohepatitis morphology (Figure 2).

The patient was listed for liver transplant because of history of adenomatosis, GSD1, and his relatively young age. A 57-year-old hepatitis B core antibody-positive brain-dead male donor became available and was accepted for transplant.

The patient received intravenous 10% dextrose solution to ensure euglycemia the night before transplant. The infusion rate of dextrose was based on the patient’s basal metabolic rate, which was estimated using the Harris-Benedict equation. Glucose levels were closely monitored pretransplant, and 50% dextrose was given for blood sugar levels of less than 80 mg/dL to prevent glycogenolysis and subsequent lactic acidosis.

The patient received standard monitoring per American Society of Anesthesiologists guidelines, and rapid sequence induction and intubation were performed using a McGrath video laryngoscope equipped with a number 3 blade. An arterial line was placed postinduction, and large-bore peripheral intravenous access was obtained with a 7.0F rapid infusion catheter. A 12F central line and a pulmonary artery catheter were placed for continuous cardiac output monitoring. A transesophageal echocardiogram probe was placed for real-time monitoring of cardiac function.

A baseline blood-gas measurement revealed euglycemia of 95 mg/dL with lactic acidosis of 2.5 mmol/L. A 10% dextrose solution and 150 mEq/L of sodium bicarbonate were continued during the transplant procedure, with frequent measurements of blood gases to detect hypoglycemia. After reperfusion, blood glucose level increased above 180 mg/dL. Once we were comfortable that the newly transplanted liver was participating in glucose regulation, the 10% dextrose solution was discontinued and an insulin infusion was started based on our institution’s insulin therapy guidelines. Glucose and lactate levels were frequently checked because of the increased risk of intraoperative hypoglycemia. Our patient’s glucose peaked at 338 mg/dL soon after the start of the neo-hepatic phase and decreased to normal levels with insulin therapy by hour 6 posttransplant. Lactate peaked at 9.9 mmol/L in the early neo-hepatic phase and normalized within 24 hours.

Estimated blood loss was less than 1 liter, and the patient’s intravascular volume was maintained close to normal physiologic levels, as measured by continuous cardiac output and transesophageal echocardiography. As such, the patient did not experience a significant rise in baseline serum creatinine level, and urine output was maintained at normal levels perioperatively. Intraoperative acidosis was mild with a pH nadir of 7.32 and base deficit peak of 2.3. Sodium and potassium levels remained within normal limits.

The patient was weaned from inotropes immediately and was extubated on posttransplant day 1. Lactate normalized almost immediately after transplant, and hepatic transaminases were only mildly elevated (alanine aminotransferase and aspartate aminotransferase of 425 U/L and 859 U/L, respectively). The patient was discharged on posttransplant day 4 with excellent hepatic function and continued to do well more than 1 year after transplant surgery.

In patients with a single adenoma or adenomas amenable to resection and whose surveillance imaging scans show increased suspicion of malignancy, hepatic resection is considered the standard of care.⁵

Liver transplant is considered for patients who have inflammatory hepatic adenomatosis, malignant imaging characteristics, are poor candidates for resection, and have lesions that do not regress with medical therapy.⁶ Liver transplant provides a definite cure for enzyme deficiency and greatly improves metabolic control, resulting in resolution of hypoglycemic episodes and lactic acidosis and improvements in hypertriglyceridemia and hyperuricemia.⁶ In their study, Boers and associates⁵ showed improvements in metabolic control and quality of life, including catch-up growth in children. The 1-year, 5-year, and 10-year survival rates after liver transplant in these patients have been shown to be 82%, 76%, and 64%, respectively.⁷ Patients can also return to a normal diet after liver transplant.

Renal failure was the most common complication reported by Boers and associates,⁵ which was demonstrated in 24% of patients, with 21% of these patients requiring dialysis. The renal dysfunction may be related to glycogen storage disease and may also result from the side effects of immunosuppression after liver transplant.

Patients with GSD1 who undergo elective or emergency surgery require special considerations because they are more prone to severe hypoglycemia and metabolic decompensation (severe metabolic acidosis, coma, and death). Periods of catabolism in patients with GSD1, as with our patient, should be avoided, as even short periods can lead to profound hypoglycemia, lactic acidosis, and seizures.⁸ Guidelines developed for the perioperative management of patients with glycogen storage disease focus on electrolyte balance, fluid and intravascular volume maintenance, and maintenance of euglycemia.⁹ Dextrose 10% with sodium additive is the fluid of choice; this combination is typically administered at 1.25 to 1.75 times the maintenance rate to allow adequate serum glucose levels.¹⁰ Dextrose 5% is not recommended due to the inadequate concentration of glucose, which can lead to adverse events.

The kidneys play a key role in lactate clearance in patients with GSD1.¹¹ Urinary clearance of lactate is decreased with evolving kidney injury. Careful planning for intraoperative, intravascular fluid maintenance should be done to ensure protection of the kidneys throughout the perioperative period. Typically, large-bore peripheral and central venous access is required to accommodate swift fluid replacement should the need arise. Any loss of kidney function, combined with a severe lactic acidosis, may require renal replacement therapy to clear elevated lactate levels.

Hypoglycemia and surgical stress can precipitate a severe organic acidosis that is resistant to treatment and can be challenging to manage intraoperatively. Aggressive preoperative and intraoperative management of blood sugar can allow even complex surgeries, such as liver transplant, to be performed. Furthermore, liver transplant is curative, reversing the metabolic derangements, removing premalignant tissues, and allowing for significant improvements in quality of life10; therefore, it should be considered in these patients.

In patients with glycogen storage disease, hepatectomy and liver transplant are important therapeutic options if sufficient consideration is given to perioperative management of hypoglycemia and organic acidosis.

Volume: 20 Issue: 6 June 2022

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