Several recommendations below are mostly based on expert opinion only and not confirmed by double blind/randomized controlled trials. The difficulties in performing such studies in critically ill pregnant patients are obvious.
The topic of prophylactic use of antibiotics is very controversial and the choice of antibiotic in pregnancy is difficult. However, in suspected cholangitis there is no controversy with regards to the need for appropriate antibiotic therapy. Patients with mild AP, normal CBD size with no evidence for cholangitis do not need antibiotics. In a pregnant patient there are concerns with regard to the antibiotic being transplacentally transferred to the fetus with a risk of teratogenicity. Metronidazole passes freely across the placenta. However, recent studies do not show any association with an increased risk of teratogenic effects with metronidazole[53,54]. Imipenem (N-formimidoyl thienamycin), belonging to the carbapenem class of antibiotics, has a broad spectrum of activity. It is currently classified as a category C in terms of its risk to the fetus. Although limited animal studies have shown no teratogenic risk or adverse fetal effects, data in humans are not available. Quinolones have been classified as category C because adverse effects have been noted in some animal studies. However, there are no adequate studies in humans; the benefits may outweigh the risks. Ampicillin-sulbactam and piperacillin/tazobactam are classified as category B with no evidence of risk in humans. Regardless of initial drug regimen, therapy should be modified to reflect the organisms recovered in blood cultures and the clinical status of the patient.
Management of underlying cause
Management of gallstones: In a pregnant woman with gallstones and CBD stones a major decision is on choice of procedure to clear the CBD of stones. The second decision is on timing and approach to cholecystectomy. Factors which influence the decision include the trimester of pregnancy, presence or absence of CBD dilatation, cholangitis, and the severity of AP. AP patients with gallstones need to be evaluated for early cholecystectomy to prevent recurrence of AP later on in the pregnancy when it could be more serious and dangerous[25-27]. It is a well respected surgical concept that the second trimester is the best period for surgery since during this period organogenesis is complete and the uterus is not big enough to obliterate the surgical view for laparoscopic approach. It has also been recognized that cholecystectomy during the second trimester is safe for both the mother and the fetus[10,12,57].
Laparoscopic cholecystectomy in pregnant women offers all of the advantages of laparoscopic surgery in non-pregnant patients - reduced hospital stay, decreased narcotic use and a quick return to a regular diet compared to open surgery in pregnant women. In the second trimester the gravid uterus does not interfere with visualization of the operative field. The indications for surgery in pregnancy are severity of symptoms, obstructive jaundice, acute cholecystitis intractable to medical treatment and peritonitis.
Four retrospective studies comparing open cholecystectomy vs laparoscopic cholecystectomy did not find any significant difference in maternal or fetal outcomes. Gouldman et al reviewed the available world literature on laparoscopic cholecystectomy in pregnancy and found 107 patients who had cholecystectomy during pregnancy. Most had been performed in the second trimester, with 10 and 16 patients in the first and third trimesters, respectively. Premature labor was rare, with only 2 of the 16 reported patients (12.5%) in the third trimester developing preterm labor, and these were successfully treated with tocolytics. Overall results were good with excellent maternal (100%) and fetal (96%) survival. There is a recent view that states when surgical intervention is warranted, laparoscopic cholecystectomy can be safely performed in any trimester but it is a minority view. Performance of cholecystectomy is desirable in the second trimester as organogenesis is complete, and spontaneous abortions are less frequent than in the first trimester.
ERCP with sphincterotomy and clearance of bile duct stones is indicated in patients with severe AP, with cholangitis, with strong evidence of persistent biliary obstruction, and in those who are post cholecystectomy as well as patients who are poor candidates for surgical therapy. Pregnant women in the first and third trimester who are not ideal candidates for cholecystectomy fall in the last category. Biliary sphincterotomy rather than cholecystectomy may be appropriate when CBD stones are detected and cholecystectomy has to be delayed because of pregnancy. The effectiveness of ES in preventing further episodes of biliary pancreatitis, as an alternative to cholecystectomy in high risk patients has been demonstrated[48,62-69]. The indication for ERCP in patients with severe pancreatitis without significant cholestasis is controversial. At this time there is no evidence that therapeutic ERCP is required in all patients with biliary sludge during pregnancy.
The role of therapeutic ES in the management of pregnant patients with AP without CBD stones continues to be controversial. Some advocate biliary stent placement rather than performing sphincterotomy and stone extraction and therefore, eliminating complications that accompany sphincterotomy. Farca et al placed 10-French biliary stents without sphincterotomy in 10 patients, all of whom had uncomplicated pregnancies with normal deliveries. All underwent repeat ERCP with stent extraction and sphincterotomy post-partum and 8 had stones extracted. In 2 patients, the stent remained in place for 7 and 8 mo, respectively, without the development of occlusion and or cholangitis. However, stenting carries risks of stent occlusion and cholangitis and the need for a second procedure.
Hyperlipidemic pancreatitis: Hypertriglyceridemia is the second most common cause of AP, when the serum triglyceride is > 1000 mg/dL. In the third trimester of pregnancy, there is a three-fold rise in serum triglyceride levels. This is thought to be due to estrogen-induced increases in triglyceride synthesis and very low-density lipoprotein secretion. Hypertriglyceridemia may be more severe in persons with familial hyperlipidemia, predisposing them to develop pancreatitis. Rarer causes of AP that need to be considered in the differential diagnosis are hyperemesis during the first trimester; hyperparathyroidism; preeclampsia; and genetic mutations[74-76] and acute fatty liver of pregnancy. AP can also complicate the course of thrombotic thrombocytopenic purpura during pregnancy and pregnancy induced hypertension. Medication and alcoholism are extremely rare causes of AP in pregnancy.
No formal recommendations exist for gestational hypertriglyceridemia treatment in pregnancy at present. Treatment of hyperlipidemic AP is mostly supportive. These treatments include low fat diet[79,80], antihyperlipidemic therapy[79,80], insulin[79-81] (to increase lipoprotein lipase activity), heparin[79-81] (to increase lipoprotein lipase activity), and even plasmapheresis[79,82].