Gary D. V. Hankins, MD
George R. Saade, MD
• Hypertriglyceridemia-Induced Pancreatitis
• Abdominal Compartment Syndrome
INTRODUCTION
Acute pancreatitis is rare during pregnancy. The reported incidence varies from 1/1000 to 1/4000 pregnancies.1
The most common etiologies of pancreatitis include gallstone disease and alcohol abuse.2 During pregnancy, symptomatic gallstone disease is the leading cause. Other less common causes include hypercalcemia, hypertriglyceridemia, trauma, ischemia, pancreatic tumors leading to pancreatic duct obstruction, and medications, such as thiazides and azathioprine. An association between acute pancreatitis and preeclampsia has been described.3 The mechanism for the latter is unclear but may be related to severe vasoconstriction with resultant pancreatic ischemia.
Close to 20% of cases are considered to be idiopathic; many of these cases likely have a genetic predisposition.4
The pathophysiology of acute pancreatitis relates to local activation of pancreatic enzymes (eg, trypsinogen to trypsin), leading to pancreatic tissue injury with a massive inflammatory response that may result in severe vasodilation, increased vascular permeability with third spacing, and multiorgan failure.
DIAGNOSIS
Pancreatitis should be suspected in patients presenting with constant epigastric pain associated with nausea and vomiting. The pain typically radiates to the back and precedes nausea and vomiting. The intensity of the pain is usually severe. The diagnosis during pregnancy may be more challenging, as some of the symptoms may be associated with physiological changes of pregnancy. During the second half of pregnancy, such presentation always warrants a workup for preeclampsia.
Serum amylase and lipase are the most commonly used laboratory parameters. Amylase usually rises within hours of the event and returns to normal values in 3 to 5 days.5 Amylase is nonspecific and may also be elevated in multiple extrapancreatic conditions, such as salivary gland disease, appendicitis, cholecystitis, renal injury, peptic ulcer disease, and bowel pathology. Serum lipase is more specific than amylase and remains elevated for longer periods of time. Despite the increased specificity, lipase may also be elevated in renal injury and extrapancreatic abdominal pathology, such as appendicitis and cholecystitis.6 Imaging studies are rarely necessary to establish the diagnosis, as the diagnosis in most cases is easily made with the clinical presentation coupled with elevated lipase values. Pancreatic imaging may be indicated in cases where the diagnosis is unclear or when there is failure to improve within 2 to 3 days after presentation. Contrast-enhanced computed tomography might be used; during pregnancy, the use of magnetic resonance may be more appropriate (no ionizing radiation exposure), as it may diagnose pancreatic necrosis even without the use of gadolinium.7
All patients with acute pancreatitis should undergo an abdominal ultrasound to identify gallstone disease as the etiology. In cases of a normal ultrasound and no history of alcohol abuse, a serum triglyceride level should be obtained and considered the cause of pancreatitis if more than 1000 mg/dL.8
Once the diagnosis is established, the clinician should attempt to classify the disease as mild or severe pancreatitis. Up to 80% of cases will be mild, and the patient will improve within the next 48 hours. Mild cases have no organ failure and no necrosis of the pancreas.9 Severe cases (20%) will develop end-organ failure secondary to massive inflammation (eg, acute kidney injury, acute respiratory distress syndrome, confusion, hypotension, disseminated intravascular coagulation) and/or necrosis of the pancreas. The use of scoring systems to predict the development of severe pancreatitis upon clinical presentation is of limited value and may delay appropriate management interventions, as they may take up to 48 hours to become accurate. Clinical decisions should not be made based solely upon arbitrary severity scoring systems. Obesity, advanced age, elevated blood urea nitrogen and hematocrit (indicating hemoconcentration from severe third spacing of fluid), and end-organ damage (elevated creatinine, hypoxia, confusion) are associated with poor outcomes.
MANAGEMENT
All patients with acute pancreatitis should receive initial aggressive fluid therapy with crystalloids (normal saline or Ringer lactate). The presence of hypotension will require bolus therapy with either crystalloids or colloids (albumin). If blood pressure is stable, maintenance fluids at 200 to 500 mL/h may be necessary during the first 12 to 24 hours of presentation. Aggressive hydration should be undertaken carefully in patients with acute kidney injury, pulmonary edema, or history of cardiac disease. Pain management should be provided with narcotic agents to maintain the patient’s comfort.
Prophylactic antibiotics are not indicated in acute pancreatitis.6 Antibiotics should be reserved for those cases in which infected necrosis of the pancreas is suspected (infected necrosis is suspected in patients who fail to improve or deteriorate 7 to 10 days after the onset of the disease). Upon clinical suspicion of infected necrosis, two approaches exist. Some experts recommend performing a computed tomography–guided fine-needle aspiration of the necrotic tissue to obtain cultures for gram stain and guiding antibiotic therapy accordingly. Others recommend starting empiric antibiotics with agents that have good pancreatic penetration (carbapenems, quinolones, metronidazole).6,10 During pregnancy, the use of empiric antibiotics is preferred to avoid invasive procedures requiring ionizing radiation. The use of empiric antifungal coverage is not recommended.11 Antifungal coverage may be required if response to initial broad-spectrum antibiotics fails.
Most patients with acute pancreatitis will improve during the first 24 to 48 hours. Once pain, nausea, and vomiting are controlled, the patient should be fed enterally.12 Early enteral feeding results in decreased infectious complications and mortality.13 Either a clear liquid diet or a low-fat solid diet may be started safely.6 Early feeding results in bowel perfusion with concomitant maintenance of gut mucosa. The resultant bowel epithelium integrity prevents bacterial translocation and, thus, potential infection of the necrotic pancreas.
Similarly, patients with severe pancreatitis should be fed within 24 hours of admission to avoid prolonged bowel rest and bacterial translocation. Either the nasogastric or the nasojejunal routes are acceptable.14 Some experts recommend the use of semi-elemental low-fat formulas. Probiotics should be avoided in patients with pancreatitis, as they may increase the risk of bowel ischemia.
The use of total parenteral nutrition should be reserved for those patients who fail to tolerate enteral feedings despite placement of the feeding tube in the jejunum and use of low-fat semi-elemental formulas.
In cases of mild pancreatitis caused by gallstone disease, a cholecystectomy should be performed during the index hospitalization to prevent recurrent events.6 The ideal moment to perform such an operation during pregnancy is between 18 and 22 weeks. Individualized care is necessary when deciding the optimal timing for cholecystectomy during gestation. In cases of severe pancreatitis, cholecystectomy should be deferred until the severe inflammatory response subsides.15 In most cases of biliary pancreatitis, the stone is spontaneously passed to the intestine, obviating the need for endoscopic retrograde cholangiography (ERCP). In the absence of ongoing biliary tract obstruction (normal bilirubin and imaging), there is no need for ERCP. If acute cholangitis is suspected (fever, jaundice, and biliary obstruction), then the patient must undergo ERCP within the next 24 hours.6 The most common complication of ERCP is pancreatitis. Administering 100 mg of indomethacin per rectum after the procedure may decrease the latter.16 ERCP may be performed during pregnancy if required with minimal fetal risks.17
Surgical intervention for severe pancreatitis may be needed in selected cases. In patients with necrotic pancreatitis, debridement of necrotic tissue, if required, should be delayed for at least 4 weeks to allow liquefaction and development of a fibrous wall around the necrotic tissue (this will allow the surgeon to identify the necrotic tissue and differentiate it from normal pancreatic tissue).18
The presence of necrotic pancreatic tissue, even when infected, does not always warrant surgical debridement.19 Up to 20% of acute pancreatitis cases may be complicated by pancreatic necrosis, and 30% of these will develop infected necrosis (most secondary to bacterial translocation from the intestine).20 The presence of sterile necrosis does not require surgical intervention. The concept that all infected necrotic cases require surgical drainage has been challenged recently.6 Infected necrosis is suspected in those patients who fail to improve or deteriorate 7 to 10 days after the onset of the disease. Surgical debridement this early (within 2 to 4 weeks of disease onset) has been associated with increased mortality because no demarcation between necrotic and normal pancreatic tissue has developed yet.21
As discussed previously, these patients may undergo a computed tomography–guided fine-needle aspiration to diagnose infection or just receive empiric antibiotics. In stable patients, antibiotics may lead to resolution of the infection and avoid the need for surgical intervention.19 Surgical intervention will be required for those unstable patients with infected necrotic pancreatitis. Current guidelines recommend the use of minimally invasive techniques (percutaneous, endoscopic transgastric, laparoscopic) over open surgical necrosectomy.22 Asymptomatic pseudocysts do not require any intervention.6
Hypertriglyceridemia-Induced Pancreatitis
Patients with acute pancreatitis, a normal abdominal ultrasound, and no history of alcohol abuse should have their serum triglycerides measured because values above 1000 mg/dL may lead to acute pancreatitis. The pathophysiology is unclear, but increased viscosity with placental hypoperfusion may play a role.23 Besides the management principles described previously for other types of pancreatitis, these patients will require therapies aimed at rapidly reducing triglyceride levels, ideally to less than 500 mg/dL.24
The use of intravenous insulin with concomitant glucose infusions (in order to avoid iatrogenic hypoglycemia) decreases levels of triglycerides because insulin stimulates the activity of lipoprotein lipases, accelerating chylomicron degradation.24,25 An infusion of 0.1 units/kg/h used with normal saline and 5% dextrose (or higher if required) intravenously to maintain normoglycemia may be an adequate starting point.
Some reports advocate the use of heparin to reduce serum triglycerides, as heparin stimulates secretion of lipoprotein lipases from the endothelial cells.26 Unfortunately, the increased release of lipoprotein lipase is followed by liver clearance of the enzyme with subsequent aggravation of the enzyme deficit. Heparin is not recommended for the treatment of hypertriglyceridemia-induced pancreatitis.24 Plasmapheresis is very effective in rapidly lowering serum triglycerides, although data on mortality reduction is limited.27 In facilities where plasmapheresis is readily available, it should be considered early in the treatment of these patients.
Besides plasmapheresis and intravenous insulin, treatment commonly includes a low-fat diet (some cases require lipid-free total parenteral nutrition), omega-3 fatty acids, and lipid-lowering agents such as gemfibrozil and fenofibrate. Both fenofibrate and gemfibrozil have been used successfully during pregnancy.28,29 The risks and benefits of these lipid-lowering agents should be discussed with the patient before administration. Both medicines are considered FDA category C.
Table 22-1 summarizes the most important concepts in the management of acute pancreatitis.
TABLE 22-1 | Basic Recommendations in the Management of Acute Pancreatitis |
