Association of pancreatitis with administration of contrast medium and intravenous lipid emulsion in a patient with the acquired immunodeficiency syndrome. (Case Report).

Abstract: Computed tomography is widely used to diagnose acute pancreatitis. Iodinated contrast medium lengthens the duration of pancreatitis and may increase the incidence of local or systemic complications. Total parenteral nutrition including IV lipid emulsion plays an important role in the management of patients with pancreatitis. Induction of pancreatitis by IV lipid emulsion is exceedingly rare. We report a 30-year-old patient with the acquired immunodeficiency syndrome in whom pancreatitis was exacerbated by oral and IV contrast medium and also by IV lipid emulsion in the absence of hypertriglyceridemia. Exclusion of the lipid emulsion resulted in prompt reduction of lipase levels on three separate occasions. This case is the first to implicate IV lipid emulsion in the exacerbation of pancreatitis in a patient with acquired immunodeficiency syndrome and normal baseline triglyceride levels. Thus, this case report suggests that we must exercise caution in the use of contrast medium and IV lipids in the d iagnosis and management of acute pancreatitis.

Key Words: acquired immunodeficiency syndrome, contrast medium, hypertriglyceridemia, intravenous lipid emulsion, lipase, lipids, pancreatitis, total parenteral nutrition

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Pancreatitis is an inflammatory condition of the exocrine pancreas resulting from injury to pancreatic acinar cells. The major causes of pancreatitis include alcohol ingestion, cholelithiasis, hypercalcemia, trauma, drugs, and hyperlipidemia. (1,2) In patients with acquired immunodeficiency syndrome (AIDS), pancreatitis may develop from a variety of causes including antiretroviral drugs, opportunistic infections of the pancreas, and AIDS-associated neoplasms. (24) The incidence of pancreatitis among the general population increased 10-fold from the 1960s to the 1980s. There are no effective treatments, and those aimed at resting the pancreas have not altered the course of the disease favorably. (2)

Computed tomography (CT) is widely used in the diagnosis and staging of acute pancreatitis. Previous studies have shown that IV contrast medium increases the severity and mortality in an experimental model of acute pancreatitis in rats. (5) A subsequent study showed that the duration of acute pancreatitis was longer in patients who received contrast medium. (6) A recent study showed an increased incidence of local and/or systemic complications in patients with mild acute pancreatitis after they received iodinated contrast medium for computed tomography. (7)

Patients with acute pancreatitis are managed with supportive care, bowel rest, IV (IV) fluids, antiemetics, pain control, and sometimes antibiotics. The majority of patients recover within a few days, but in prolonged cases of pancreatitis, total parenteral nutrition (TPN) is used to meet the patient's nutritional requirements. (8) Lipid emulsions such as Intralipid (Cutter Laboratories, Inc., Berkeley, CA) are used in TPN formulations to provide calories and essential fatty acids. (9) Although severe hyperlipidemia has been identified as one of the causes, this association remains poorly understood. (10)

Studies involving more than 100 patients have shown the safety of IV fat as a component of TPN. (11) Yet, 3 reports involving 4 patients have suggested that IV lipid emulsion was responsible for inducing or exacerbating pancreatitis. (12-14) These patients either had alcoholic pancreatitis or inflammatory bowel disease with pancreatitis. One report suggested that hypertriglyceridemia resulting from higher concentration of lipid emulsion caused the pancreatitis. (12)

We report a case of acute pancreatitis in a patient with AIDS whose exacerbations were clearly associated with administration of contrast medium and IV lipid emulsion. This report, in conjunction with the other reports mentioned, builds a strong case in favor of carefully monitoring the use of contrast medium and lipid emulsions in the diagnosis and management of patients with pancreatitis.

Case Report

A 30-year-old woman with a history of AIDS presented with abdominal pain, fever, vomiting, and diarrhea for 2 days. She also complained of intermittent cough, fatigue, and progressive weight loss during a 2-year period. She had been diagnosed with human immunodeficiency virus infection (HIV) 8 years earlier, and she had taken antiretroviral therapy for most of that time. Her medications at the time of presentation were valacyclovir, stavudine, abacavir, didanosine, trimethoprim-sulfamethoxazole, prednisone, and famotidine.

At admission, she had a temperature of 103[degrees]F, heart rate of 130 beats/min, respiratory rate of 26/min, and blood pressure of 112/57 mm Hg. On chest auscultation, scattered crackles and wheezes were heard bilaterally. The abdomen was soft and diffusely tender with guarding but without rebound tenderness.

Initial laboratory evaluation showed an increase in amylase, lipase, alkaline phosphatase, and lactate dehydrogenase levels (Table 1). The serum trypsin level, a more specific marker for pancreatitis, was 780.7 ng/ml (normal, 10-57 ng/ml) (Table 1). Contrast-enhanced computed tomography of the abdomen showed a normal pancreas and mesenteric lymphadenopathy. Abdominal ultrasonography did not show cholelithiasis. At 48 hours after admission, the Ranson score was 1. This case was categorized as "mild acute pancreatitis" according to the Atlanta clinical classification system. (15)

The patient was managed with bowel rest, IV hydration, electrolyte replacement, and analgesics. The antiretroviral agents and trimethoprim-sulfamethoxazole were withheld, since they had been implicated in pancreatitis. (2,4) Clinical presentation and serial lipase levels (Fig. 1) were used to monitor the course of the pancreatitis. Lipase levels increased from 405 to 1,489 U on Day 3 due to IV (Omnipaque; Nycomed, Inc., Roskilde, Denmark) and oral (Gastroview; Mallinckrodt, Inc., St. Louis, MO) administration of iodinated contrast media for CT of the abdomen.

On Day 6, TPN (peripheral line) consisting of ProcalAmine (McGaw, Inc., Irvine, CA) and lipid emulsion (Intralipid; Pharmacia & Upjohn, Kalamazoo, MI) was initiated. Lipase continued to increase to 2,265 U. The lipid emulsion was withheld, and lipase levels decreased (Fig. 1). Baseline triglyceride levels measured before initiation of TPN (central line) were within normal limits at 181 mg/dl on Day 10 (data not shown). Since the patient's overall nutritional status was poor, lipid emulsion was reintroduced on Day 13 to provide essential fatty acids, with a concomitant increase in lipase levels. The lipid emulsion was discontinued and, as previously, the lipase level decreased. Abdominal symptoms had improved from initial presentation. Unfortunately, lipase levels rose to 1,475 U on Day 25, in association with abdominal pain due to the accidental administration of oral iodinated contrast medium for repeated CT. After careful consideration of the poor nutritional status, we decided to give a one-time small dose of lipid emulsion to supplement essential fatty acids. There was a small but prompt rise in lipase levels for the third successive time. At this point, the triglyceride level was recorded at 359 mg/dl (data not shown).

The patient was also treated with imipenem/cilastatin, cefotaxime, ciprofloxacin, ethambutol, and azithromycin for pneumonia and bacteremia due to Nocardia farcinica, Pseudomonas aeruginosa, and Mycobacterium avium complex (MAC). These antibiotics were used continuously during the hospital stay and did not affect serum lipase levels.

Discussion

In this AIDS patient with acute pancreatitis, exacerbations of serum pancreatic enzymes were clearly associated with iodinated contrast medium and IV lipids. Infectious agents or drugs are known to cause pancreatitis in patients with HIV infection. The pancreatitis in our patient on presentation was probably due to didanosine in combination with trimethoprim-sulfamethoxazole. (2, 4) Multiple elevations of lipase levels later were clearly due to IV lipid emulsion because its withdrawal led to a decline in the levels of lipase. A confounding factor was the role of opportunistic infections that required antimicrobial therapy. We did not clinically detect any association between her multiple infections and pancreatitis. The antimicrobials we administered had not been reported to exacerbate pancreatitis or to influence lipase levels.

Mild acute pancreatitis is reversible and has not been extensively studied because of its short and relatively benign course. The initial lesion is an edema involving connective tissue between the lobules of acinar cells associated with an infiltrate of polymorphonuclear leukocytes. There is no damage to acinar cells, fat necrosis, or hemorrhage, all of which characterize the more severe form called acute hemorrhagic pancreatitis.

Parenteral lipid is well tolerated in the healthy human, but studies in canines have shown that the infusion of large quantities of free fatty acids produces pancreatic hemorrhage and edema. (16, 17) The pathophysiology underlying iodinated contrast medium and lipid emulsion-mediated exacerbation of pancreatitis is unclear. The most plausible explanation is that mild acute pancreatitis is associated with a defect in the intracellular compartmentation of proenzymes in acinar cells and damaged pancreatic vasculature. Iodinated contrast medium and lipid emulsion may extravasate through damaged vasculature and cause the inappropriate activation of pancreatic proenzymes by an undetermined mechanism.

An alternative mechanism to explain the effect of lipid emulsion was iatrogenic hypertriglyceridemia. Hypertriglyceridemia-induced pancreatitis occurs when triglyceride levels range from 1,000 to 7,000 mg/dl. In our patient, triglyceride levels were below 400 mg/dl when measured on two occasions. Therefore, it is unlikely that hypertriglyceridemia was the underlying cause of lipase increases. In addition, we have not been able to determine whether the effects of contrast medium and lipid emulsion are independent, additive, or synergistic. Further studies involving a greater number of patients are indicated to address all of these issues.

Conclusion

This report highlights the possibility that some patients with pancreatitis may react adversely to the use of both oral or IV contrast medium and IV lipid emulsion. Hence, all patients with pancreatitis receiving iodinated contrast medium or IV lipid emulsion, irrespective of the presence or absence of hypertriglyceridemia, should be carefully monitored. In the event of pancreatitis worsening due to IV lipid emulsion, its use should be restricted to providing essential fatty acids, especially in a nutritionally deficient patient. Based on our report and others, (7,12-14) we believe that the recovery period and hospital stay can be shortened by avoiding the use of iodinated contrast medium and lowering the concentration or eliminating IV lipid in TPN. Further research is clearly indicated to resolve this issue and help in drafting improved pancreatitis management guidelines.

[FIGURE 1 OMITTED]

Table 1

Laboratory values at admission

Parameter (normal value)                 Value

Platelets (150,000-440,000/          461,000
 [mm.sup.3])
Hemoglobin (12-16 g/dl)                    9.9
Hematocrit (35-47%)                       29.5
Leukocytes (4,500-11,000/                 16.9
 [mm.sup.3])
Glucose (70-105 mg/dl)                    61
Blood urea nitrogen (6-20 mg/dl)           4.0
Creatinine (0.6-1.1 mg/dl)                 0.7
Sodium (135-145 mEq/L)                   125
Ca ++ (8.5-10.4 mg/dl)                     8.2
Amylase (<115 U/L)                       148
Lipase (<82 U/L)                         406
Serum trypsin (10.0-57.0 ng/ml)          780.7
Alkaline phosphatase (41-110 U/L)        173
Lactate dehydrogenase (122-240 U/L)      305
SGOT (10-31 U/L)                          17
SGPT (0-31 U/L)                            4.0

Accepted November 19, 2001.

References

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(5.) Foitzik T, Bassi DG, Schmidt J, et al. Intravenous Contrast medium accentuates thc severity of acute necrotizing pancreatitis in the rat. Gastroenterology 1994;106:207-214.

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(8.) Marulendra S, Kirby DF. Nutrition support in acute pancreatitis. Nutr Clin Pract 1995;10:45-53.

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(10.) Cameron JL, Capuzzi DM, Zuidema GD, Margolis S. Acute pancreatitis with Hyperlipemia: The incidence of lipid abnormalities in acute pancreatitis. Ann Surg 1973;177:483-489.

(11.) Leibowitz AB, O'Sullivan P, Iberti TJ: Intravenous fat emulsions and the pancreas: A review. Mt Sinai J Med 1992;59:38-42.

(12.) Noseworthy J, Colodny AH, Eraklis AJ. Pancreatitis and intravenous fat: An association in patients with inflammatory bowel disease. J Pediatr Surg 1983;18:269-272.

(13.) Lashner BA, Kirsner JB, Hanauer SB. Acute pancreatitis associated with high-concentration lipid emulsion during total parenteral nutrition therapy for Crohn's disease. Gastroenterology 1986;90:1039-1041.

(14.) Buckspan R, Woltering E, Waterhouse G. Pancreatitis induced by intravenous infusion of a fat emulsion in an alcoholic patient. South Med J 1984;77:251-252.

(15.) Bradley EL. A clinically based classification system for acute pancreatitis. Arch Surg 1993;128:586-590.

(16.) Edelman K, Valenzuela JE. Effect of intravenous lipid on human pancreatic secretion. Gastroenterology 1983;85:1063-1066.

(17.) Saharia P, Margolis S, Zuidema GD, Cameron JL. Acute pancreatitis with hyperlipidemia: Studies with an isolated perfused canine pancreas. Surgery 1977;82:60-67.

RELATED ARTICLE: Key Points

Discontinuance of contrast or intravenous lipids led to a prompt decline in lipase levels and clinical improvement.

Both intravenous and oral contrast medium showed elevated lipase levels and worsened pancreatitis in a patient with acquired immunodeficiency syndrome. Intravenous lipid emulsion used in total parenteral nutrition also elevates lipase levels.

From the Division of General Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC. (Dr. Wiese is now with the Department of Medicine, Wayne State University, Detroit, MI.)

Reprint requests to Vijaykumar S. Kasi, MD, PhD, Division of Internal Medicine, Pitt County Memorial Hospital, Teaching Annex Room 344, 600 Moye Blvd., Greenville, NC 27858.

Copyright [c] 2003 by The Southern Medical Association 0038-4348/03/9601-0066