How Is Hypertriglyceridemia Treated When Suspected in Causing Acute Pancreatitis?
Hypertriglyceridemia is seen in 12% to 22% of patients presenting with acute pancreatitis. The triglycerides should only be considered the etiology when the level is over 1000 mg/dL. In these patients, the level should be rechecked 10 to 14 days after the attack of acute pancreatitis to confirm the elevation. In the setting of acute pancreatitis, the triglyceride level fluctuates for a variety of reasons. While the etiology remains unclear, proposed mechanisms in which an elevated triglyceride level causes acute pancreatitis include pancreatic acinar cell damage by free fatty acids, activation by pancreatic lipase resulting in a cascade of activated trypsinogen, and a deficiency of lipoprotein lipase and a defect in lipoprotein receptors. It is important to recognize this etiology of acute pancreatitis since initiation of proper treatment is essential for improving outcome and, more importantly, preventing recurrent attacks and the subsequent development of chronic pancreatitis.
When should we suspect hyperlipidemic pancreatitis? Three clinical syndromes have been described: (1) the poorly controlled obese diabetic with history of hypertriglyceridemia, (2) the alcoholic found to have hypertriglyceridemia or lactescent serum upon admission, and (3) the nondiabetic, nonalcoholic, nonobese patient with drug- or diet-induced hypertriglyceridemia. Hence, look for patients with a genetic predisposition such as type V hyperlipidemia (elevation of chylomicrons and very-low-density lipoprotein [VLDL]) and coexisting secondary causes of hypertriglyceridemia such as alcohol use, diabetes, hypothyroidism, uremia, nephritic syndrome, or rapid weight gain.
It is important for clinicians to obtain a good medication history since drugs that raise plasma triglycerides, such as alcohol, thiazides and loop diuretics, beta-blockers, estrogens in oral contraceptives or in post-menopausal therapy, tamoxifen, glucocorticoids, retinoids, ketogenic diets, protease inhibitors, and cimetidine, have all been implicated. Be aware of the pregnant patient since mortality from pancreatitis is even higher (20%) and you may not suspect hyperlipidemia but cholelithiasis as the etiology of acute pancreatitis. During the third trimester of pregnancy, increased synthesis of triglycerides occurs along with VLDL secretion, hyperinsulinemia, and decreased levels of apolipoprotein CII (apo-CII). Hence, with a pre-existing hyperlipidemic state, she may develop severe acute pancreatitis.
What lab values should you expect? Chylomicrons are present in plasma when triglyceride levels exceed 1000 mg/dL and are clinically significant from 1000 mg/dL to 2000 mg/dL or greater than 11.3 mmol/L. Frequently, patients have lipemic serum with normal to mildly elevated amylase and lipase and with some evidence of pancreatic inflammation on imaging studies. Hyponatremia is a frequent finding and reflects pseudohyponatremia secondary to hyperlipidemia. The lack of sensitivity and low levels of initial serum pancreatic enzymes reported may be due to the presence of an inhibitor in the blood and measuring elevated serum amylase/creatinine clearance ratios or delayed triglyceride clearance may be beneficial, but no current studies validate this.
In the acute setting, presentation of hypertriglyceridemic pancreatitis varies from mild to moderate to severe. As supportive care is initiated—nothing-by-mouth, intravenous fluids, pain management—abdominal pain may diminish and triglyceride levels may fall within the first 24 hours. However, cases of fulminant pancreatitis, pancreatic pseudocysts and abscesses, chronic pancreatitis with and without steatorrhea, and acute recurrent pancreatitis have been reported. Therefore, it is key to introduce lipid-lowering agents such as statins or fibrates early with the goal of decreasing serum triglyceride levels to less than 500 mg/dL. If the patient is diabetic, then strict glucose control with insulin is necessary. When there is no appreciable reduction in serum triglycerides, plasma exchange (replacing the patient’s plasma with human albumin or fresh frozen plasma) has been used to lower excessive lipid levels, to supplement lipoprotein lipase and apolipoprotein, and to alter the cytokine balance and decrease inflammation. Studies have found that plasmaphoresis lowers plasma lipids by two-thirds in about 2 hours (triglycerides by 66%, cholesterol by 62%) and clears them to less than 1000 mg/dL with improvement of abdominal pain. However, experience with plasmaphoresis is limited in hyperlipidemic pancreatitis patients even though it is an established treatment for familial hypercholesterolemia. Some studies also advocate the use of heparin and insulin to stimulate lipoprotein lipase and chylomicron degradation, thereby decreasing triglyceride levels with resolution of pancreatitis. The data, however, are limited.
How should we manage these patients once they are discharged? Focus on preventing recurrent attacks of acute pancreatitis with chronic lipid-lowering medications and diet modification. Maintenance therapy with gemfibrozil 600 mg bid, clofibrate 1 g bid, nicotinic acid 500 mg qd increased to 3 to 6 g qd as well as omega-3 fatty acids with 5% to 15% total calories fish oil should be employed. Diet modification with substitution of saturated fat with polyunsaturated fat and starch and fiber for sucrose-containing foods should be initiated. Strict glycemic control should be maintained in diabetic patients and weight loss with aerobic exercise encouraged. Pancreatic serine proteinases such as gabexate mesylate which decreases pancreatic stimulation through feedback inhibition and loxiglumide, a cholecystokinin receptor antagonist, have been suggested for use until triglyceride levels fall to less than 500 mg. However, no ultrasound study supports this practice. Some suggest that plasmaphoresis performed every 4 weeks decreases the incidence of pancreatitis but this too is controversial.
In summary, proper management of hypertriglyceridemic pancreatitis lies in the ability to recognize the disease (resist the temptation to label as idiopathic pancreatitis) and to lower serum triglycerides early in its course. Start lipid-lowering medications as an inpatient and continue prevention of hyperchylomicronemia as an outpatient. Encourage dietary restriction of triglycerides, weight loss, diabetic control, exercise, and the avoidance of alcohol and drugs known to increase serum triglycerides. With this in mind, we can work toward decreasing the incidence of hypertriglyceridemic pancreatitis and improving the outcome.
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