Acute pancreatitis in pregnancy, including acute pancreatitis occurring in all stages of pregnancy and puerperium, has an incidence of 1/4000 to 1/1000; its rapid onset, rapid progression, and many complications can be misdiagnosed due to atypical clinical manifestations, and may endanger the lives of the mother and child. According to the current literature, it can occur in all stages of pregnancy and postpartum, and is more common in late pregnancy. With the improvement of living standards and changes in diet structure, the incidence has been on the rise in recent years.
The etiology of acute pancreatitis during pregnancy is diverse, and is basically the same as that of pancreatitis in the general population, commonly biliary, hyperlipidemic, other cases such as hyperparathyroidism leading to hypercalcemia induced acute pancreatitis, hypertensive syndrome of pregnancy causing long-term spasm of the pancreatic vessels and ischemic necrosis of the pancreas have also been reported. The identification of the etiology is a guide to the formulation of the treatment plan for acute pancreatitis.
Biliary pancreatitis during pregnancy is mostly associated with the metabolic changes in the maternal organism during pregnancy. In the middle and late stages of pregnancy, the cholesterol content of bile secreted by the liver increases while the amount of bile acids and phospholipids decreases, resulting in the formation of cholesterol supersaturated bile; the high level of estrogen in pregnant women reduces the tone of the smooth muscle of the gallbladder, which affects the contraction of the gallbladder and causes bile stasis; the increase in the size of the uterus increases the intra-abdominal pressure and the corresponding ectopic abdominal viscera, which compresses the duodenum and the biliary system and affects bile excretion. The above factors make gallstone more frequent during pregnancy, and obstruction of the common channel of the pancreaticobiliary duct in the Vater’s jugular abdomen causes bile reflux, activates pancreatic enzymes, and induces pancreatitis.
The secretion of prolactin, estrogen, glucocorticoids and other anti-insulin hormones gradually increases with the gestational weeks and reaches a peak in the late pregnancy, the activity of lipoprotein lipase decreases, insulin resistance, and the gradual increase of blood lipid levels in normal pregnant women is a normal physiological response to the strengthening of anabolism during pregnancy. However, in cases such as obesity, rapid growth in body mass, older age, combined gallstone disease, diabetes, preeclampsia and disorders of triacylglycerol metabolism, maternal plasma triacylglycerol, cholesterol, free fatty acids, lipoproteins and other concentrations increase significantly compared to pre-pregnancy, increasing blood viscosity and resistance to blood flow, making it easy to form microthrombi and causing serious obstruction of pancreatic microcirculation, which can also directly induce pancreatitis. Once the complication of necrotizing pancreatitis, the combination of hypertriglyceridemia, fatty acids, cholesterol and the unique hormonal changes during pregnancy will make the condition more dangerous and the consequences more serious.
Second, the clinical manifestations of acute pancreatitis in pregnancy nausea, vomiting, epigastric pain are the three major symptoms of acute pancreatitis in pregnancy, the pain is mostly persistent distension in the upper middle abdomen or left epigastric pain radiating to the back, no relief after vomiting, some patients have greasy diet before the attack. The possibility of acute pancreatitis should be considered for any epigastric pain during pregnancy, because its abdominal pain can be mild or even atypical, while nausea and vomiting are more severe and frequent in early pregnancy. In late pregnancy, especially at the stage of labor, the sudden onset of epigastric distension and pain from acute pancreatitis is often confused with contraction pain.
During pregnancy, the abdominal wall becomes less elastic and relaxed, and the pancreas behind the peritoneum is covered by the nudging gastrointestinal and omental membranes during pregnancy, so the signs of pancreatitis, such as abdominal pressure pain, rebound pain and masses, may not be typical during physical examination, but may only show deep pressure pain in the upper and middle abdomen and soreness in the lower back, and may have fever, diminished bowel sounds and abdominal distension, and biliary pancreatitis can be seen as yellow staining of the skin and sclera. In the middle and late stages of pregnancy, as the uterus increases, the abdominal cavity pressure rises and the diaphragm is elevated, while the blood volume of the pregnant woman increases up to 40% to 45% and the cardiac output increases, the heart rate and respiration increase at the onset, so monitoring needs to be strengthened to prevent? shock.
Third, the diagnosis of acute pancreatitis in pregnancy and the assessment of the condition of acute pancreatitis in pregnancy contains the following four questions.
(1) How to confirm the diagnosis of acute pancreatitis (how to diagnose and exclude other diseases)?
(2) How severe is acute pancreatitis?
(3) What is the cause of the disease?
(4) What stage of pregnancy is the patient in? The diagnosis of acute pancreatitis requires a combination of past medical history, clinical manifestations, laboratory and imaging studies. For patients with a history of biliary tract disease, pancreatitis, diabetes mellitus, or familial hyperlipidemia before pregnancy, the possibility of acute pancreatitis attack should be considered once there is an acute onset of abdominal pain during pregnancy.
As mentioned earlier, the presence of three major symptoms of nausea, vomiting and epigastric pain strongly suggests acute pancreatitis during pregnancy, but because the symptoms and signs of abdominal pain during an attack are not typical, they need to be differentiated from acute pneumonia, penetrating duodenal ulcer, splenic rupture, acute appendicitis, ectopic pregnancy rupture, severe pregnancy vomiting and pre-eclampsia.
Among the laboratory tests, the commonly used indicator is blood and urine amylase. Serum amylase usually exceeds 3 times the upper limit of normal value within 24 h of onset of disease and peaks after 48 h, while urinary amylase increases. The elevation of blood lipase is later than serum amylase, usually starts 24-72h after onset and lasts 7-10d. It is valuable for patients who present late after onset, and is less interfered by pregnancy and has high specificity. A transient increase in blood amylase followed by a rapid decrease can also be caused by massive necrosis of pancreatic tissue and must be judged in the context of the patient’s changing condition. Abnormal liver enzymes and elevated bilirubin suggest the possibility of biliary pancreatitis. Some patients with hyperlipidemia may have celiac-like changes in plasma specimens, and timely measurement of lipid levels can clarify the cause as early as possible. Acute pancreatitis is likely to occur when triacylglycerol is >11.3 mmol/L, and needs to be reduced to below 5.6 mmol/L within a short period of time. Severe hypercalcemia suggests hyperparathyroidism, while persistent elevated blood glucose and hypocalcemia suggest a serious condition.
Reliable imaging data are important for diagnosis. Ultrasound examination of the abdomen is preferred during pregnancy. It can show swelling of the pancreas and accumulation of peripancreatic fluid exudation, as well as gallbladder stones and bile duct dilatation, but is easily disturbed by gastrointestinal gas, especially for those who are obese. Pregnant women also need ultrasound to assess the fetal gestational age and growth level for early detection of obstetric abnormalities such as intrauterine distress and intrauterine fetal death. Currently, the most accurate imaging test to assess the condition of pancreatitis is enhanced CT, and the use of CT during pregnancy is limited by the effects of radiation on the fetus. The International Society for Radiological Protection believes that the teratogenic risk of radiation below 0.05 Gy is negligible compared to other risk factors during pregnancy. The radiation dose to the fetus from CT of the upper abdomen can be less than 0.01 Gy, and the radiation dose from CT of the lower abdomen and pelvis (layer spacing 7.5 mm) can be less than 0.03 Gy. For late pregnancy with severe symptoms, CT results are needed to assess the condition of the pancreas in the abdominal cavity and decide whether to terminate the pregnancy, and on balance, abdominal CT can still be chosen.
The severity grading of acute pancreatitis, with organ dysfunction, or local complications such as necrosis, abscess or pseudocyst, or both, with APACHE II score of 8 and above, is assessed as acute severe pancreatitis; those with organ dysfunction despite adequate fluid resuscitation within 72h of onset are classified as fulminant acute pancreatitis. Severe pancreatitis and fulminant pancreatitis treatment has its own specificity, early diagnosis is conducive to timely intervention of surgical treatment.
In principle, the treatment of acute pancreatitis in pregnancy is basically the same as that of acute pancreatitis in non-pregnancy, but because of the combination of obstetric problems, it also has its own characteristics and requires the collaboration of obstetrics, neonatology and surgery to choose a treatment plan according to the severity of the disease, the stage of the disease, the stage of pregnancy, and the growth and development of the fetus.
(A) Light acute pancreatitis in pregnancy Light acute pancreatitis patients, the first choice of formal conservative treatment, early fasting, gastrointestinal decompression, intravenous fluids to regulate water-electrolyte balance and nutritional support, pancreatic inflammation is mostly self-limiting, and can maintain a safe pregnancy. Prophylactic antibiotics are not needed in the absence of bile duct dilatation and biliary tract infection. In case of biliary pancreatitis, it is recommended to perform cholecystectomy in the middle of pregnancy or after delivery to prevent recurrence, and cholecystectomy in the middle of pregnancy is safer for pregnant women and fetuses.
(B) Acute severe pancreatitis during pregnancy 1, removal of the cause of treatment: acute severe pancreatitis patients, surgical treatment emphasizes the timely removal of the cause of the disease at the early stage of onset (especially within 72h), blocking the body’s excessive inflammatory response to further expansion.
In biliary pancreatitis, if gallbladder stones combined with biliary obstruction are present, emergency bile duct evacuation is required. Emergency endoscopic retrograde cholangiopancreatography (ERCP) with Oddi sphincterotomy for stone extraction and nasobiliary drainage is indicated for severe pancreatitis, cholangitis, persistent biliary obstruction, recurrence of gallstones after cholecystectomy and those who cannot tolerate surgical treatment. Patients in early and late pregnancy who are less tolerant of open biliary surgery are recommended to undergo emergency ERCP to relieve biliary obstruction. Because of the fetal protection involved, there are higher technical requirements for the operator, requiring reduced fluoroscopy time, a lead suit to protect the pelvis, and a fluoroscopic exposure time of less than 1 min after contrast injection, usually about 15 s. If possible, a sphincterotomy without contrast injection of Oddi can also be used. ERCP and lumpectomy cholecystectomy or emergency surgical cholecystectomy bile duct exploration are feasible in patients in mid pregnancy, when the main purpose of surgery is to relieve biliary obstruction.
Patients with acute pancreatitis caused by hyperlipidemia should limit the use of fat emulsions and avoid the application of drugs that may elevate blood lipids, and pharmacological treatment should use small doses of low molecular heparin and insulin to increase lipoproteinase activity and accelerate the degradation of celiac particles, and apply lipid adsorption and plasma replacement to rapidly lower lipids and maintain blood lipids <5.65 mmol/L.
In acute pancreatitis during pregnancy, termination of pregnancy should be based mainly on non-obstetric factors, and emergency termination of pregnancy can be considered in late pregnancy: on the one hand, it can strive for fetal survival; on the other hand, it can alleviate the development of acute pancreatitis. Due to immature organ function development in preterm infants, mutual assistance and articulation between obstetrics and neonatal care unit is required, while drainage of the abdominal cavity, small omental sac and retroperitoneal space is decided by general surgery or pancreatic surgery. There are multiple considerations in the choice of incision, such as a median abdominal incision to expose both pelvic and abdominal cavities, or a curved lower abdominal incision in obstetrics to complete the cesarean section followed by a combined upper abdominal subcostal incision for abdominal exploration, drainage of the lesser omental sac and peripancreatic space by surgery. How to ensure the relative independence of obstetrics and surgery during the surgical operation and protect the function of pelvic and abdominal organs places high demands on the surgeon. Patients in early and mid pregnancy should be monitored more closely and early measures should be taken to expel the stillborn fetus once fetal death is detected. Pregnancy should be terminated as soon as possible in the following cases: (1) obvious signs of miscarriage or preterm labor; (2) fetal distress or stillbirth; (3) already at the stage of labor.
2, pancreatic rest therapy: while correcting the cause of pancreatitis, apply pancreatic rest therapy, temporary fasting, application of gastrointestinal decompression to reduce food and digestive fluid stimulation and reduce pancreatic enzyme secretion. Enteral nutrition is given through a spiral nasojejunal nutrition tube, which can maintain the normal function of the intestine and the energy needs of pregnant women. The application of acid suppressants and pancreatic enzyme inhibiting drugs is still controversial.
3, evacuation of the intestinal tract: such as maintaining pregnancy, evacuation of the intestinal tract is different from non-pregnant patients, the use of lactulose is safer for pregnant women, generally do not use raw rhubarb, magnesium sulfate, enema may stimulate the pelvic cavity, is contraindicated for pregnant patients, clean enema can be used as prenatal intestinal preparation.
4, correct metabolic disorders: the burden on the circulatory system increases during pregnancy, and fluctuations in hormone levels can easily lead to disorders in the internal environment. During the treatment of pancreatitis, timely formal fluid resuscitation, enhanced organ function maintenance, timely correction of hyperosmolarity, hyperglycemia and water-electrolyte disorders. Increase dynamic monitoring of blood glucose, electrolytes and blood gas changes, apply insulin to control blood glucose smoothly and correct metabolic disorders to reduce the impact on the fetus.
V. Questions a) Determination of the severity of the disease Acute pancreatitis during pregnancy requires appropriate treatment according to the severity of the disease, organ function involvement, and metabolic disorders. Currently, enhanced CT of the abdomen is not routinely used during pregnancy, ultrasound of the abdomen is easily disturbed by intestinal gas, and MRI cholangiopancreatography is still not a substitute for CT, so judging the progress of pancreatic lesions by imaging methods is limited and may not be timely enough. During the course of disease onset, clinical symptoms and signs do not change significantly, while there is a lag in the response of routine blood biochemical indexes to disease severity. For the determination of the efficacy of conservative treatment, the existence of monitoring indicators with good specificity and timeliness is still an important part of the current research.
(B) the safety of drug therapy U.S. FDA on growth inhibitor animal experiments on the safety of pregnancy graded B, omeprazole graded C. Considering that proton pump inhibitors may lead to a reduction in fetal body mass, the appropriate application of growth inhibitor and caution proton pump inhibitors in the treatment process. The safety of acid- and enzyme-inhibiting drugs still needs further verification.
The application of prophylactic antibiotics for severe pancreatitis, currently penicillin and three generations of cephalosporin antibiotics are safe for use in pregnancy, including ampicillin-sulbactam sodium and piperacillin-tazobactam. Imipenem belongs to carbapenem antibiotics, its antibacterial spectrum is wide, strong activity, can effectively penetrate the blood-pancreatic barrier, whether there are adverse effects on the fetus is still unclear, but for patients with severe infection benefits outweigh the disadvantages, can be used as appropriate.
The prognosis of acute pancreatitis in pregnancy is similar to that of acute pancreatitis in non-pregnancy. The risk of miscarriage is higher in early pregnancy and the survival rate of preterm infants is higher in late pregnancy.
As an obstetric emergency, acute pancreatitis in pregnancy may have atypical clinical symptoms and is dominated by cholestatic and hyperlipidemic etiologies, with emphasis on early removal of the cause, regulation of internal environmental disorders, and protection of maternal and fetal organ functions. The treatment of hyperlipidemia is limited by the need to protect the fetus during pregnancy, and the timing of pregnancy termination and surgical indications are difficult. Early prevention is emphasized. Patients with familial hyperlipidemia should have their lipid metabolism disorders corrected before pregnancy, and lipid changes should be monitored during pregnancy with appropriate dietary control; those with biliary tract disease should have the cause removed before pregnancy, and a large amount of fatty diet should be avoided during pregnancy. With the accumulation of clinical data and the strengthening of disease understanding, the treatment plan will be further improved.