HyperTAg causing Pancreatitis

Proposed approach to hypertriglyceridemic pancreatitis

Apheresis — Apheresis should be considered to remove triglycerides from serum if the patient does not have concurrent hyperglycemia and there are no contraindications, such as unstable vital signs or inability to tolerate central venous access.

Many case reports and series have described apheresis for HTGP [28-40]. One series of seven patients with an average level of 1406 mg/dL reported a 41 percent decrease in triglyceride levels after one plasma exchange session [35]. In another case report, triglycerides were lowered from 2410 to 138 mg/dL after three days of apheresis [40]. Neither report described the use of adjunctive therapy such as intravenous insulin, intravenous heparin, or oral statins.
The most common anticoagulant used during apheresis is heparin, but there are no data to recommend the appropriate apheresis replacement fluid (albumin versus fresh frozen plasma). When plasma exchange is compared with double membrane filtration apheresis, rates of removal of serum lipids have been lower with double membrane filtration apheresis [41].
The main concerns surrounding apheresis include cost and availability. After one cycle, serum triglyceride levels are re-checked and, if less than 500 mg/dL, apheresis is stopped. If the triglyceride rises (above 500 mg/dL), we generally re-treat with apheresis.
Early initiation of apheresis is likely to be beneficial. We generally proceed with apheresis as soon as possible. In a review of 10 patients with HTGP, nine patients received apheresis with IV heparin and insulin within 48 hours of the diagnosis of HTGP with successful outcomes [42].

Insulin — If apheresis is unavailable, if the patient cannot tolerate apheresis, or if the patient's serum glucose level is >500 mg/dL, we use intravenous insulin. Insulin decreases serum triglyceride levels by enhancing lipoprotein lipase activity, an enzyme that accelerates chylomicron metabolism to glycerol and fatty free acids [43,44]. Because HTGP often presents in patients with uncontrolled diabetes, insulin can decrease both triglyceride and glucose levels.

Intravenous insulin may be more effective than subcutaneous insulin in severe cases of HTGP [25,26]. Many regimens have been reported to lower triglyceride levels to less than 500 mg/dL over 3.5 to 4 days [25-27]. We typically initiate an intravenous infusion of regular insulin in 5 percent dextrose at a rate of 0.1 to 0.3 units/kg/hour to maintain blood sugar levels between 150 and 200 mg/dL.
Fingerstick glucose levels every four hours are suggested to ensure glucose control, and triglyceride levels should be monitored every 12 to 24 hours with adjustment of the insulin dosage as needed. Intravenous insulin should be stopped when triglyceride levels are <500 mg/dL, which typically occurs within several days.

Insulin and heparin — The role of heparin is controversial. Heparin stimulates the release of endothelial lipoprotein lipase into the circulation [45] and has been used without insulin to manage HTG [42,46,47]. Multiple case reports and series have described the use of heparin and insulin to lower HTG [21-24,48].

Studies have used varying doses of insulin and heparin administered by various routes [21,22,48]. As an example, in two reports subcutaneous heparin at 5000 units twice daily was used with intravenous insulin [22,48]. In both healthy volunteers and dialysis patients, low molecular weight heparin has been found to deplete lipoprotein lipase stores as efficiently as heparin and to retard the metabolism of triglyceride [49,50].
Despite the reported success of intravenous heparin in combination with insulin in HTG management, the use of heparin to treat HTGP has come under greater scrutiny. Heparin causes an initial rise in circulating lipoprotein lipase levels that is quickly followed by increased hepatic degradation of heparin [51]. This degradation contributes to further depletion of plasma stores of lipoprotein lipase and results in an increase of levels of chylomicrons [52]. The transient nature of the benefit seen with heparin raises question as to its use as monotherapy or in combination with insulin.

Antihyperlipidemic therapy — Antihyperlipidemic agents (eg, oral gemfibrozil 600 mg twice daily) should be initiated as adjuvant therapy in patients with HTGP. (See "Lipid lowering with fibric acid derivatives" and "Lipid lowering with diet or dietary supplements" and "Treatment of lipids (including hypercholesterolemia) in secondary prevention".)

Long-term therapy — Oral antihyperlipidemic agents and dietary fat restriction may be needed long-term to prevent recurrences of AP and prevent other complications of HTG. Periodic apheresis has been used with some success as continuing therapy after patients have recovered from their initial episode of AP, and particularly in patients who are noncompliant with diet and oral drug therapy [53]. (See "Lipid lowering with fibric acid derivatives" and "Lipid lowering with diet or dietary supplements" and "Treatment of lipids (including hypercholesterolemia) in secondary prevention".)

Pregnancy — The treatment of HTGP does not differ in pregnancy. Several case reports of gestational HTGP have described the use of apheresis [54,55], intravenous insulin and glucose with enteral restriction of triglyceride [56], intravenous heparin [42,46], low fat diet [57], and gemfibrozil. All resulted in the successful control of HTG and delivery of a healthy neonate