Keywords
acute pancreatitis - hypertriglyceridemia - pregnancy
Introduction
Acute pancreatitis (AP) is distributed across a range of gestational ages, with significantly
more cases presenting later in gestation: 24% in the first trimester, 33% in the second
trimester, and 43% in the third trimester. It is associated with preterm delivery
and other adverse mother and fetal outcomes.[1] Circulating triglyceride (TG) levels increased two- to fourfold in pregnancy, principally
in the third trimester, due to increased TG-rich lipoprotein production and decreased
lipoprotein lipase (LPL) activity.[2] AP is conventionally thought to be triggered when TG levels exceed 1,000 mg/dL (11.3 mmol/L).[3]
[4]
There are reports of fetal death secondary to AP in pregnancy due to hypertriglyceridemia
(HTG).[5] Maternal mortality has also been reported as a complication.[6]
The presentation of AP secondary to HTG is similar to that of AP secondary to other
causes, with the primary symptom of abdominal pain, nausea, and vomiting. The International
Association of Pancreatology and American Pancreatic Association recommended that
two out of three of the following criteria must be met for the diagnosis of AP. These
criteria are clinical (upper abdominal pain), laboratory (serum amylase or lipase
more than three upper limits of normal), and suggestive imaging.[7]
[8] Here, we present a case of a pregnant Saudi admitted for AP secondary to HTG.
Case Report
A 27-year-old Saudi female is known to have hyperlipidemia on atorvastatin, which
was stopped 3 years before her first uneventful pregnancy. A first-trimester abortion
followed her first pregnancy with no records at our institution. She presented to
our emergency department at 30 weeks' gestation, complaining of left upper quadrant
and epigastric pain for 4 days associated with nausea and vomiting. There were no
gallbladder stones or alcohol consumption histories, and the systemic review was unremarkable.
She was not using any medication before admission and did not use oral contraceptive
pills in the last 4 years. She has a family history of hyperlipidemia (paternal).
There was no family history suggestive of AP.
On physical examination, she was conscious, alert, and oriented to time, person, and
place. Her pulse rate was 108, oxygen saturation was 97% on room air, blood pressure
was 132/78, temperature was 36.9°C, respiratory rate was 22, body mass index was 30,
and her glucose level was 5 mmol/L. She had moderate tenderness over the epigastric
area, no rebound tenderness, and no organomegaly. There was no eruptive xanthoma or
xanthelasmas. The rest of her examinations were unremarkable. Laboratory tests on
admission are shown in [Table 1]. Abdominal ultrasound showed no gallstones; the pancreas appeared heterogeneous,
hypoechoic, and bulky, with minimal peripancreatic fluid suggestive of early pancreatitis
changes.
Table 1
Patient's laboratory data on admission
|
Parameters
|
Patient's results
|
Reference values
|
|
White blood cell count
|
12
|
4–11 × 10^9
|
|
Hemoglobin
|
93
|
120–160
|
|
Hematocrit
|
0.27
|
0.360–0.540
|
|
Platelets
|
303
|
150–400 × 10^9
|
|
Aspartate aminotransferase (u/L)
|
7
|
5–34
|
|
Alanine aminotransferase (u/L)
|
5
|
5–55
|
|
Total bilirubin (μmol/L)
|
5.1
|
3.4–20.5
|
|
Lactic acid (mmol/l)
|
2.6
|
0.5–2.20
|
|
Thyroid-stimulating hormone (mIU/L)
|
1.05
|
0.35–4.94
|
|
Sodium (mmol/L)
|
130
|
136–145
|
|
Potassium (mmol/L)
|
2.6
|
3.5–5.1
|
|
Urea (mmol/L)
|
1.3
|
2.5–6.7
|
|
Creatinine (μmol/L)
|
45
|
50–98
|
|
Amylase (u/L)
|
93
|
25–125
|
|
Urine amylase
|
> 3,010
|
24–400 U/L
|
|
Lipase (u/L)
|
515
|
8–78
|
|
Triglycerides (mmol/L)
|
58
|
< 1.7
|
|
Total cholesterol (mmol/L)
|
24.9
|
< 5.18
|
|
LDL-cholesterol (mmol/L)
|
0.58
|
< 2.6
|
|
HDL-cholesterol (mmol/L)
|
0.29
|
> 1.55
|
Abbreviations: HDL, high-density lipoprotein; LDL, low-density lipoprotein.
There were no signs of appendicitis, and obstetric ultrasound showed a viable single
fetus. The patient was admitted under obstetric care as a case of AP secondary to
HTG. Intravenous hydration was started with normal saline and potassium replacement.
Antiemetic and analgesics were initiated. Oral fenofibrate 200 mg once daily was administered.
Despite conventional treatment, the patient's symptoms persisted, and she had an Acute
Physiology and Chronic Health Evaluation II score of 11. She was transferred to the
medical intensive care unit on the second day. Insulin infusion was started at a rate
of 0.1 U/kg/hour with dextrose 5% and normal saline after adequate potassium replacement.
Insulin infusion was titrated based on blood glucose and monitored every hour. The
lipid profile was monitored daily. Triglycerides went down by 50% in the first 3 days
after the above infusion (58.8–29 mmol/L) and dropped by 81% by the seventh day to
11 mmol/L ([Table 2]).
Table 2
Lipid profile series after starting insulin infusion
|
Lipid profile
|
Baseline
|
Day 3
|
Day 7
|
Day 9
|
Day 12
|
|
Triglycerides (mmol/L)
|
58.8
|
29
|
11
|
8
|
7
|
|
Total cholesterol (mmol/L)
|
24.9
|
23
|
13
|
11
|
9
|
|
LDL-cholesterol (mmol/L)
|
1.68
|
2.7
|
4.55
|
5.38
|
4.8
|
|
HDL-cholesterol (mmol/L)
|
0.27
|
0.38
|
0.60
|
0.62
|
0.65
|
Abbreviations: HDL, high-density lipoprotein; LDL, low-density lipoprotein.
Regular insulin infusion was stopped after triglycerides dropped below 7 mmol/L (day
12). Her symptoms improved, and she was transferred to the general ward. Total hospital
stay was 48 days on a restricted fat diet, fenofibrate, and insulin infusion with
dextrose based on TG level target below 7 mmol/L. She had a total of 14 days of insulin
infusion overall. She had an uncomplicated vaginal delivery with labor induction at
37 weeks. She did not require any insulin infusion after delivery as her TG level
remained between 4 and 5 mmol/L. Her TG level was 1.47 mmol/L at discharge.
Discussion
The pathophysiological mechanism of AP secondary to HTG has not yet been fully elucidated.
A popular theory suggests that markedly TG-rich environments promote lipolysis by
pancreatic lipase. This results in increased liberation of high concentrations of
free fatty acids, which, in turn, inflict damage to the vascular endothelium and the
pancreatic acinar cells.[9] In vitro studies also suggested a role for fatty acid-induced mitochondrial toxicity
in the pathogenesis of HTG-induced pancreatitis.[10]
Lipid-lowering agents such as fenofibrate and gemfibrozil are category C during pregnancy.
However, some case reports reported that these medications were used in pregnancy
without complications. Doses used were in the form of fenofibrate 145 to 200 mg once
daily or gemfibrozil 600 mg twice daily.[11]
[12] These agents reduce plasma TG levels by 50% and raise HDL cholesterol by 20%. They
also decrease very-low-density lipoprotein secretion and increase lipolysis of plasma
triglycerides.[12] LPL is an enzyme produced by capillary endothelial cells of muscles and adipose
tissues, which hydrolyzes triglycerides to glycerol and fatty acids.[13] The activity of LPL is crucial for the clearance of triglycerides from the plasma.
Heparin and insulin stimulate LPL activity.[14]
Neutral protamine Hagedorn insulin has been reported to decrease TG from 3,616 to
1,246 mg/dL (65%) with a single dose of 10 units (0.15 U/kg).[15] Intravenous heparin was reported to be safe in several case reports at a dose of
10,000 to 15,000 U per day to decrease TG by 80 to 90% in 24 to 48 hours.[16] Apheresis was reported to decrease TG, with many case reports suggesting its safety
in pregnancy.[17] One study found that two consecutive plasma exchanges led to a remarkable reduction
in TG levels by 73 and 82%, respectively.[18]
Conclusion
AP in pregnancy carries considerable risks of preterm delivery, fetal loss, and maternal
mortality. TG-lowering agents, heparin, insulin, and apheresis appear to be effective
therapies in managing HTG-induced AP.[11] Their exact mechanism of action, effects, and safety need to be addressed more in
pregnancy. No clinical guidelines for HTG-induced AP exist to date. There is a great
need to establish these guidelines to properly guide health care practitioners in
managing this serious disease.
