Acute Pancreatitis 369 cysts, hemorrhage, thrombophlebitis, and abcess formation [36] and provide guidance for directed sampling of abscess cavities (Figures 27.1 & 27.2 ). CT is also useful in differentiating pancre- atitis from other intra - abdominal pathologies. The role of ultrasound is typically quite limited in the initial evaluation of patients who have pancreatitis, because the pan- creas often is obscured by bowel gas. Additionally, the pancreas may have an entirely normal sonographic appearance in the acute phase. In patients suspected of having acute pancreatitis, the primary role of ultrasound is to assess for gallstones and biliary obstruction [36] . Differential d iagnosis Abdominal complaints in pregnancy present unique diagnostic challenges (Table 27.3 ). Non - obstetric conditions include acute rated these fi ndings, noting no difference in amylase activity related to pregnancy. Lipase levels were also studied, and no signifi cant difference was found between the second and third trimesters or compared with non - pregnant controls, although one study noted a lower lipase level in the fi rst trimester [34] . Mean values of lipase in 175 women were approximately 12 IU/L, with none exceeding 30 IU/L. As a screening tool for acute pancreatitis, urinary trypsino- gen - 2 has also been evaluated in the general population. Using a dipstick test for urinary trypsinogen - 2, Kemppainen et al. [35] evaluated 500 consecutive patients presenting to the emergency room with abdominal pain. The authors found 94% sensitivity and 95% specifi city in detecting acute pancreatitis. While requir- ing further study, the 99% negative predictive value achieved with this urinary dipstick test may prove a useful adjunctive test to standard serum evaluation of amylase and lipase. Leukocytosis, hyperglycemia, hyperbilirubinemia, abnormal coagulation tests, and elevated liver enzymes may also be present. Although other diseases can result in abnormal values, amylase and lipase remain the cornerstone of diagnosis. These values are typically elevated more than threefold over normal. Radiologic e valuation While the diagnosis of acute pancreatitis is based on clinical sus- picion, physical examination, and elevated amylase and lipase, radiologic tests aid in the confi rmation of acute pancreatitis and can be used to monitor the development and progression of complications. A plain fi lm of the abdomen may show dilation of an isolated loop of intestine (sentinel loop) adjacent to the pancreas. Pleural effusions may be detected on chest X - ray. Computed tomography (CT) is considered the radiographic procedure of choice for determining the extent or the severity of the pancreatitis [36] . Since CT is unhindered by bowel gas pat- terns, CT scans can demonstrate pancreatic necrosis, pseudo- L Figure 27.1 Computed tomography scan demonstrating necrosis in the head of the pancreas (curved arrow) and free fl uid in the anterior pararenal space (straight arrow). (Courtesy of Dr Paula Woodward.) Figure 27.2 Computed tomography scan demonstrating pseudocyst in the tail of the pancreas (arrow). (Courtesy of Dr Paula Woodward.) Table 27.3 Differential diagnosis of acute pancreatitis. Non - obstetric conditions Acute cholecystitis Appendicitis Biliary colic Intestinal obstruction Duodenal ulcer Splenic rupture Mesenteric vascular occlusion Perinephric abscess Pneumonia Pulmonary embolus Myocardial infarction Diabetic ketoacidosis Obstetric conditions Pre - eclampsia Ruptured ectopic pregnancy Hyperemesis gravidarum Chapter 27 370 atitis. Utilizing color charts, Mayer and McMahon [43] identifi ed 90% of the patients who subsequently died and 72% of patients with severe morbidity. Biochemical indicators that have been evaluated as predictors of severity of disease include C - reactive protein [44 – 46] , tryp- sinogen activation peptide [47 – 49] , procalcitonin [50,51] , throm- bomodulin [45] , and serum amyloid A [46] . Only C - reactive protein is currently used clinically, but is limited in that it is predictive only after 48 – 72 hours following onset of symptoms. While interleukin - 6, trypsinogen activation peptide and granulo- cyte nuclear elastase all show promise in acutely identifying patients destined for a severe clinical course, they await confi rma- tory trials and widespread acceptance into routine clinical use. Compared with scoring systems and laboratory markers, con- trast - enhanced CT scans offer broader information regarding intra - abdominal anatomy. Location and extent of necrosis are identifi ed and can be serially evaluated (see Figure 27.1 ). Infection within pseudocysts is suggested by evidence of gas production. This test, however, may be limited in its availability and is diffi cult to obtain in severely ill patients. cholecystitis, duodenal ulcer (including perforation), appendici- tis, splenic rupture, perinephric abscess, mesenteric vascular occlusion, pneumonia, diabetic ketoacidosis, biliary colic, and intestinal obstruction. In the pregnant patient, pre - eclampsia, hyperemesis gravidarum, and ruptured ectopic pregnancy must be added to the differential diagnosis. Preeclampsia may mimic pancreatitis with upper abdominal pain, nausea, and vomiting. Concomitant hypertension, protein- uria, and edema, however, will usually be present. Hyperemesis gravidarum most often affects patients in the fi rst trimester, without a signifi cant component of pain. Ruptured ectopic preg- nancy may produce symptoms similar to those seen in acute pancreatitis. Hemoperitoneum can occur with either and may require laparotomy for diagnosis. But ruptured ectopics are not typically associated with an elevated lipase. Prognostic i ndicators Several methods utilizing clinical and laboratory data have been developed to indicate the severity of acute pancreatitis and allow refi nement of prognosis [37 – 39] . The most widely used criteria were developed by Ranson (Table 27.4 ). The number of criteria met correlates with the mortality risk for the individual. For non - gallstone pancreatitis, patients with fewer than three signs have rates of mortality less than 3% and morbidity less than 5%. Patients with three or more positive signs carry a 62% mortality rate and a 90% morbidity rate. Utilizing a modifi ed set of criteria for gallstone pancreatitis, individuals with fewer than three signs have a 1.5% mortality rate, while those with three or more signs demonstrate a 29% mortality rate. Critics of this system cite poor sensitivity, specifi city, delayed assessment (due to the labs required at 48 hours), and inability to perform repeated assess- ments as major deterrents to its usefulness. Another method of clinically evaluating the severity of several types of critical illnesses, including pancreatitis, is the Acute Physiology and Chronic Health Evaluation (APACHE) III criteria [40] . Unlike Ranson ’ s criteria [37 – 39] , the APACHE assessment [40] can be updated and the patient ’ s course monitored on a continuing basis. This system evaluates several variables, both biochemical and physiologic, and calculates scores based on devi- ation from normal values. A 5 - point increase in score is indepen- dently associated with a statistically signifi cant increase in the relative risk of hospital death within a specifi c disease category. Within 24 hours of admission, 95% of patients admitted to the intensive care unit could be given a risk estimate for death within 3% of that actually observed [40] . Although more complex and computer dependent, the APACHE scoring system appears more accurate than Ranson ’ s criteria in predicting morbidity [41] . The addition of body mass index seems to improve prediction as obesity predicts severity [42] . Several single prognostic indicators have been investigated in order to achieve early identifi cation of pancreatic necrosis. Paracentesis can be performed; return of dark, prune - colored fl uid is characteristic of necrotizing pancre- Table 27.4 Clinical indicators of poor prognosis: Ranson ’ s criteria [36 – 38] . Non - gallstone pancreatitis On admission Age > 55 y WBC > 16 000/mm 3 Glucose > 200 mg/dL LDH > 350 IU/L AST > 250 IU/L Within 48 h Decrease in hematocrit > 10% Increase in BUN > 5 mg/dL Calcium < 8 mg/dL P a O 2 < 60 mmHg Base defi cit > 4 mmol/L Fluid defi cit > 6 L Gallstone pancreatitis On admission Age > 70 y WBC > 18 000/mm 3 Glucose > 220 mg/dL LDH > 400 IU/L AST > 250 IU/L Within 48 h Decrease in hematocrit > 10% Increase in BUN > 2 mg/dL Calcium < 8 mg/dL Base defi cit > 5 mmol/L Fluid defi cit > 4 L AST, aspartate amino transferase; BUN, blood urea nitrogen ; LDH, lactic dehydrogenase. Acute Pancreatitis 371 from antibiotic administration [59] . A study of 74 patients with acute necrotizing pancreatitis treated with prophylactic imipe- nem demonstrated a signifi cantly decreased incidence of pancre- atic sepsis (12% vs 30%) [60] . Similar results were observed by Sainio and colleagues [61] . While further studies are needed to better defi ne both patient and antibiotic selection, antibiotic pro- phylaxis appears to be indicated in patients at high risk for septic complications such as pancreatic necrosis. Antienzyme and hormonal therapies have been designed to reduce the severity of disease by halting the production of pan- creatic enzymes and the subsequent cascade activation of the complement, kallikrein – kinin, fi brinolytic, and coagulation systems. Studies evaluating atropine, calcitonin, glucagon, soma- tostatin, and the enzyme inhibitors, aprotinin and gabexate, however, have not shown improved morbidity or mortality in severe acute pancreatitis [4,26] . Octreotide, a somatostatin ana- logue, has received considerable attention as a means to improve the course of acute pancreatitis. Five randomized trials have been performed [62 – 66] which failed to demonstrate a clinical benefi t. Surgical t herapy Although supportive measures are the mainstay of therapy, surgi- cal intervention also has a place in the management of acute pancreatitis. The exact role, timing, and form of surgery remain a matter of debate. The one clear indication for surgery is for diagnosis of an acute abdomen. An uncertain diagnosis mandates exploration for possible surgically correctable conditions. Two other situations also may require surgery: gallstone pancreatitis and select anatomic or infectious complications. The goals of biliary surgery in cases of gallstone pancreatitis are to prevent recurrence and to decrease morbidity and mortality by removing the instigating agent. Cholecystectomy and bile duct exploration are not performed, however, during the acute episode. Because nearly 95% of stones pass during the fi rst week of illness, the utility of surgery early in the illness does not weigh heavily against the high mortality rates that have been reported for early biliary surgery [67] . While not indicated in the acute phase of illness, biliary surgery should be performed after the acute pancreatitis subsides, prior to discharge from the hospital. An alternative to open surgical removal of bile duct stones has been developed utilizing ERCP. Combined with endoscopic sphincterotomy, ERCP offers both diagnostic and therapeutic advantages in the critically ill patient [68,69] . If performed within the fi rst 72 hours of illness, this procedure has been shown to decrease morbidity and length of hospital stay in patients with severe pancreatitis [69,70] . ERCP has been used in a number of pregnant patients without complications and has been found advantageous in the avoidance of the potential risks of major surgery during pregnancy [71 – 76] . ERCP during pregnancy is used to treat choledocholithiasis [69] . Choledocholithiasis that causes cholangitis and pancreatitis during pregnancy increases the risk of morbidity and mortality for both the fetus and mother. ERCP is safe during pregnancy Management Treatment of acute pancreatitis in pregnancy is similar to that of non - pregnant individuals. The initial treatment of acute pancre- atitis is supportive medical management. Because most cases are mild and self - limiting, this approach is largely successful. Correction of any underlying predisposing factors, such as avoid- ance or cessation of exacerbating factors like alcohol or drugs, early endoscopic retrograde cholangiopancreatography (ERCP) with obstructive jaundice, and reversal of hypercalcemia, is a basic principle to be observed. Assessment of prognostic indica- tors, as discussed earlier, permits appropriate surveillance. Patients with more severe disease should be transferred to an intensive care unit for continuous monitoring, because shock and pulmonary failure can present early in the course of disease and require prompt recognition and management. Medical therapy is comprised of fl uid and electrolyte manage- ment, adequate analgesia, and elimination of oral intake. Intravenous fl uid resuscitation is a vital component of treatment in both mild and severe cases. Restoration of intravascular volume and avoidance of hypotension is important for cardiovascular stability and renal perfusion. Electrolyte abnormalities are common, including hypokalemia and metabolic alkalosis from severe vomiting and hypocalcemia from fat saponifi cation. Serial assessment of electrolytes and appropriate replacement are essential. Parenteral analgesia is frequently necessary; mor- phine compounds, however, should be avoided secondary to their actions on the sphincter of Oddi. Oral intake is withheld for the duration of illness. Most patients with mild pancreatitis can be managed with intravenous fl uids. In contrast, nutrition should be implemented early in the hospital course of patients with severe disease. Enteral feeding may have advantages over parenteral. It has the potential benefi t of maintaining the intesti- nal barrier (it is felt that bacterial translocation is probably the major source of infection). Enteral nutrition also avoids catheter - related complications of parenteral nutrition such as line sepsis [52,53] . Nasogastric suction may be appropriate in a subset of patients with acute pancreatitis. Nasogastric suction, however, does not appear to infl uence duration of disease or its symptoms. Several studies have investigated the role of nasogastric suction in mild to moderate pancreatitis and found no difference in duration of abdominal pain, tenderness, nausea, and elevated pancreatic enzymes or time to resumption of oral feeding [54 – 56] . Therefore, nasogastric suction should be utilized on an elective basis for symptomatic relief for those patients with severe emesis or ileus. Prophylactic antibiotics also have been advocated in an effort to prevent the development of infectious complications. Mild cases of pancreatitis do not appear to benefi t from antibiotic prophylaxis, although studies are few [57,58] . In contrast, severe cases with pancreatic necrosis have a high rate (40%) of bacterial contamination and represent a subset of patients that may benefi t Chapter 27 372 situations, however, merit special consideration in pregnancy: the treatment of biliary disease and hypertriglyceridemia. The management of biliary disease in pregnancy raises the issue of timing of surgery. On resolution of acute pancreatitis, chole- cystectomy is typically performed in a non - pregnant patient prior to discharge from the hospital. Some advocate continued conser- vative management in pregnancy to avoid operative complica- tions and fetal morbidity. A high relapse rate (72%), however, is often encountered [5,82] . For patients presenting in the fi rst tri- mester, this may be as high as 88%. Surgical intervention decreases the incidence of relapse and the risk of systemic complications. Several studies support the use of second - trimester cholecys- tectomy for cholecystitis or pancreatitis [1,3,5,83,84] . The second trimester appears optimal in order to avoid medication effect on organogenesis and a possible increased rate of spontaneous abor- tion in the fi rst trimester [1,3,5,83,84] . Third - trimester patients are best managed conservatively because they are close to the postpartum period when operative risks are reduced. Cholecystectomy may be performed by laparotomy or open lapa- roscopy. The open technique for the laparoscopic approach is often best, in order to avoid puncture of the gravid uterus with blind trocar insertion. Fetal loss following cholecystectomy was once reported to be as high as 15% [85] . Many earlier reports, however, included patients undergoing surgery in the fi rst trimester suffering spon- taneous abortion many weeks postoperatively. Because at least 15% of all pregnancies are now known to end in spontaneous abortion, and preterm labor is seen in up to 10% of all continuing pregnancies, it would appear that the actual rate of complications related to surgery probably approaches nil, a fi gure confi rmed by several recent studies [5,86,87] . A review of studies from 1963 to 1987, evaluating fetal loss in patients undergoing cholecystec- tomy, revealed an 8% spontaneous abortion rate and an 8% rate of premature labor [86] . In a similar manner, laparoscopic cho- lecystectomy in the second trimester has been reported in a small number of patients, with no increase in fetal or maternal morbid- ity or mortality [88,89] . Treatment of hypertriglyceridemia in pregnancy is aimed pri- marily at prevention of pancreatitis. Fats should be limited to fewer than 20 g/day. This restrictive diet, however, is not palatable and is diffi cult for patients to maintain. Sanderson and associates [90] reported successful management of hypertrigliceridemia during an episode of pancreatitis and the remainder of gestation by utilizing intravenous fl uid therapy to provide calories in the form of 5% dextrose and restricting oral intake to clear liquids. Total parenteral nutrition offers another therapeutic approach when dietary adjustments are inadequate to prevent excessive triglyceride elevations. Plasma exchange and immunospecifi c apheresis also have been investigated and have suggested that long - term extracorporeal elimination of lipoproteins may offer a safe and effective method of prevention and treatment of hyper- triglyceridemic pancreatitis in pregnancy [91] . Fish oil supple- ment ( > 3 g/day) can also be quite effective in lowering triglycerides [92,93] . and may be performed with modifi ed techniques to reduce radia- tion exposure to the fetus and without fl uoroscopy [75,76] . If there is radiation exposure during ERCP, the dosimetry should be routinely recorded. Surgery for early and late complications of pancreatitis has also been the subject of controversy. A few situations appear to be clear indications for surgical intervention, such as acute, life - threatening hemorrhage. However, the timing and type of surgi- cal procedures for later complications, such as sterile necrosis, pseudocyst, and abscess, are less straightforward. Using the devel- opment or persistence of organ failure despite 72 hours of inten- sive medical therapy as indications for surgery, Gotzinger and colleagues [77] reported on 340 patients who underwent surgical exploration for acute pancreatitis. Control of pancreatic necrosis (total removal of necrotic tissue) was accomplished in 73% of patients, requiring an average of 2.1 operations. Mortality was 100% in patients in whom surgical control of necrosis could not be accomplished versus 19% in those patients who did achieve surgical control of necrosis. Arterial hemorrhage occurs in 2% of patients with severe pan- creatitis. Necrosis and erosion into surrounding arteries of the gastrointestinal tract result in massive intra - abdominal or retro- peritoneal hemorrhage. Arteriographic embolization followed by surgical debridement and artery ligation improved survival from 0% to 40% [78] . In contrast, the development of sterile pancreatic necrosis is not an automatic indication for surgery, because up to 70% of cases will resolve spontaneously. While few studies have been performed, no benefi t for early debridement has been dem- onstrated [79,80] . The formation of pseudocysts may mandate surgical debride- ment based on clinical characteristics. Occurring in as many as 10 – 20% of patients with severe acute pancreatitis, pseudocysts resolve in approximately 50% of cases [26] . Surgery is performed if symptoms of hemorrhage, infection, or compression develop or if the pseudocyst exceeds 5 – 6 cm or persists longer than 6 weeks. Internal drainage represents the superior surgical approach, although percutaneous drainage may temporize a criti- cally ill patient. Fluid should be collected for culture to rule out infection. Finally, pancreatic abscess formation occurs in 2 – 4% of patients with severe pancreatitis and is 100% lethal if left und- rained. Although percutaneous drainage may be temporizing, the catheter often becomes occluded secondary to the thick purulent effl uent. With early and aggressive surgical debridement, mortal- ity is reduced to 5% [81] . Either transperitoneal or retroperito- neal approaches may be appropriate. Postoperatively, 20% will require reoperation for incomplete drainage, ongoing infection, fi stulas, or hemorrhage [81] . Considerations in p regnancy Treatment of pancreatitis does not differ in the pregnant patient. Supportive measures are identical to those of the non - pregnant patient, and severe complications are managed aggressively. Two Acute Pancreatitis 373 23 Montes A , Walden CE , Knopp RH , et al. Physiologic and supraphysi- ologic increases in lipoprotein lipids and apoproteins in late preg- nancy and postpartum . 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Bacterial contamination of pancreatic necrosis: a prospective clinical study . Gastroenterology 1986 ; 91 : 433 – 438 . 60 Pederzoli P , Bassi C , Vesentini S , Campedelli A . A randomized mul- ticenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem . Surg Gynecol Obstet 1993 ; 176 : 480 – 483 . 61 Sainio V , Kemppainen E , Puolakkainen P , et al. Early antibiotic treat- ment in acute necrotizing pancreatitis . Lancet 1995 ; 346 : 663 . 62 Beechey - Newman N . Controlled trial of high - dose octreotide in treat- ment of acute pancreatitis . Dig Dis Sci 1993 ; 38 : 644 – 647 . 63 Paran H , Neufeld D , May A , et al. Preliminary report of a prospective randomized study of octreotide in the treatment of severe acute pan- creatitis . J Am Coll Surg 1995 ; 181 : 121 – 124 . 64 McKay C , Baxter J , Imrie C . A randomized, controlled trial of octreo- tide in the management of patients with acute pancreatitis . Int J Pancreatol 1997 ; 21 : 13 – 19 . 65 Karakoyunlar O , Sivrel E , Tani N , Denecli AG . High - dose octreotide in the management of acute pancreatitis . Hepatogastroenterology 1999 ; 46 : 1968 – 1972 . 6 6 U h l W , B u c h l e r M W , Malfertheiner P , et al. A randomized, double - blind, multicentre trial of octreotide in moderate to severe acute pancreatitis . Gut 1999 ; 45 : 97 – 104 . Acute Pancreatitis 375 9 1 S w o b o d a K , D e r fl er K , Koppensteiner R , et al. Extracorporeal lipid elimination for treatment of gestational hyperlipidemic pancreatitis . Gastroenterology 1993 ; 104 : 1527 – 1531 . 92 Nestel P , Connor WE , Reardon MF , et al. Suppression by diets rich in fi sh oil of very low density lipoprotein production in man . J Clin Invest 1984 ; 74 : 72 . 93 Harris WS , Connor WE , Illingworth DR , et al. Effects of fi sh oil on VLDL triglyceride kinetics in humans . J Lipid Res 1990 ; 31 : 1549 . 87 Kort B , Katz VL , Watson WJ . The effect of nonobstetric operation during pregnancy . Surg Gynecol Obstet 1993 ; 177 : 371 – 376 . 88 Morrell DG , Mullins JR , Harrison PB . Laparoscopic cholecystectomy during pregnancy in symptomatic patients . Surgery 1992 ; 112 : 856 – 859 . 89 Elerding SC . Laparoscopic cholecystectomy in pregnancy . Am J Surg 1993 ; 165 : 625 – 627 . 90 Sanderson SL , Iverius P , Wilson DE . Successful hyperlipemic preg- nancy . JAMA 1991 ; 265 : 1858 – 1860 . 376 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 28 Acute Renal Failure Shad H. Deering 1 & Gail L. Seiken 2 1 Department of Obstetrics and Gynecology, Uniformed Services University of Health Sciences, Old Madigan Army Medical Center, Tacoma, WA, USA 2 Washington Nephrology Associates, Bethesda, MD, USA Introduction Renal failure is now an uncommon complication of pregnancy in developed countries, occurring in less than 1% of all pregnan- cies in developing countries, although specifi c diagnostic criteria have not always been well defi ned in the literature [1,2] . In fact, the incidence of acute renal failure (ARF) requiring dialysis is now not signifi cantly different in pregnant women in Western countries compared with the worldwide population. One large analysis reported that the incidence of ARF in pregnancy fell from 1 in 3000 to 1 in 18 000 between the years 1958 and 1994 [3] . In previous decades, rates of ARF as high as 20 – 40% were reported in pregnancy, largely attributed to the high incidence of septic abortion [4 – 6] . When ARF does occur in underdeveloped parts of the world, it is often secondary to limited prenatal/delivery care and illegal abortion. As the incidence of pregnancy - related ARF in developed coun- tries has sharply declined and treatment has improved, so have maternal mortality rates reported in most studies. This improve- ment is related to both earlier recognition and intervention, as well as availability of dialytic support. Stratta et al. reported no deaths over the last 7 years of their experience, as compared with previously reported rates as high as 31% [3] . This is in sharp contrast, however, to another study at an inner city hospital in Georgia from 1986 to 1996 which documented 15% maternal and 43% perinatal mortality rates, respectively, as well as data from India that suggest ARF in pregnancy may have a mortality rate as high as 50% [7] . These studies suggest that ARF in pregnancy remains a potentially devastating complication. Etiologies of a cute r enal f ailure The approach to the pregnant patient with ARF is similar to that of the non - pregnant patient, although diseases unique to preg- nancy (Table 28.1 ) must be considered in the differential diagno- sis [8] . Disorders causing ARF in pregnancy include prerenal azotemia, intrinsic renal disease, urinary obstruction, as well as pre - eclampsia, HELLP syndrome ( h emolysis, e levated l iver enzymes, l ow p latelets), acute fatty liver of pregnancy (AFLP), and postpartum renal failure, also known as postpartum hemo- lytic uremic syndrome (HUS). Bilateral renal cortical necrosis (BRCN) is another consideration in the evaluation of the preg- nant women with ARF, which, though not unique to the pregnant state, is seen overwhelmingly in pregnancy. In the past, a bimodal incidence of ARF was seen in preg- nancy, with a peak in the fi rst trimester corresponding to the high incidence of septic abortion, and a second peak in the third trimester corresponding to a number of other disorders seen uniquely in pregnancy. Currently, with the decrease in the number of septic abortions, the majority of ARF is now seen in the latter part of gestation. Additionally, accelerated loss of renal function, along with more diffi cult to control hyperten- sion and increased proteinuria, is seen in 10% of women enter- ing pregnancy with underlying moderate to severe renal insuffi ciency due to a variety of causes [9] . Although less common, signifi cant deterioration in renal function may also occur during pregnancy in women with underlying diabetic nephropathy [10] . Renal biopsy is infrequently performed during pregnancy as the clinical presentation and timing of renal failure is usually adequate to establish a diagnosis. A renal biopsy may be indi- cated in pregnancy if there is a sudden deterioration of renal function without a defi nite cause before 32 weeks of gestation, especially if a diagnosis of pre - eclampsia is in doubt and a pre- mature delivery may be avoided by the information obtained. A large retrospective study of over 1000 percutaneous renal biopsies performed during pregnancy between 1970 and 1996 reported a complication rate of 2.4% [11] . Another recent but smaller study of 18 renal biopsies performed in pregnancy and the early postpartum period reported a 38% incidence of renal hematoma, with nearly one - third of those affected requiring a blood transfusion [12] . Because of advances in neonatal inten- sive care and the favorable long - term prognosis for infants born after 32 weeks of gestation, renal biopsy is generally not Acute Renal Failure 377 period secondary to lacerations, uterine atony, or retained prod- ucts of conception. Hemorrhage with resultant hypotension was a major cause of pregnancy - associated ARF in 7% of patients studied at the Necker Hospital, and was a contributing factor in as many as 79% of cases in other studies [1] . A more recent study implicated postpartum hemorrhage in nearly 10% of ARF cases, and placental abruption in another 4% [7] . Patients with pre - eclampsia may be particularly susceptible to ARF associated with hemorrhage due to pre - existing alterations in maternal physiology, including decreased intravascular volume, heightened vascular responsiveness to catecholamines and angiotensin II, and altered prostaglandin synthesis [14] . In a study of 31 patients with pre - eclampsia and acute renal failure, Sibai and colleagues reported that 90% had experienced some form of signifi cant hemorrhage [15] . Intrinsic r enal d isease Acute renal failure may result from a variety of intrinsic renal diseases similar to those in the non - pregnant patient. Involvement of the glomeruli may predominate in one of the many primary or secondary glomerulonephritides. The renal tubules and inter- stitium are the primary areas of injury in acute tubular necrosis (ATN) and acute interstitial nephritis (AIN). Both clinical pre- sentation and examination of the urinary sediment can provide valuable clues to the diagnosis, although renal biopsy may even- tually be required to distinguish among the many glomerular diseases and to predict prognosis (Table 28.3 ). Acute g lomerulonephritis The numerous causes of acute glomerulonephritis (GN) include primary glomerular disease such as poststreptococcal GN, mem- branoproliferative GN, idiopathic rapidly progressive (or cres- centic) GN (RPGN), as well as secondary glomerular diseases such as lupus nephritis, systemic vasculitis, and bacterial endo- carditis (Table 28.4 ). The classic presentation of acute GN is that of hypertension, edema and volume overload, nephrotic range proteinuria, and an active urinary sediment with red blood cell casts (Table 28.3 ). In performed after this gestational age as prolongation of preg- nancy is less of a concern. Prerenal a zotemia Prerenal azotemia is the result of decreased renal perfusion, due to either true intravascular volume depletion, decreased cardiac output, or altered renal perfusion. The latter can be seen with cirrhosis, nephrotic syndrome, renal artery stenosis, or the use of non - steroidal anti - infl ammatory agents. By defi nition, prerenal azotemia is readily reversible with restoration of renal perfusion. Early in pregnancy, hyperemesis gravidarum is one of the more common causes of ARF secondary to profound volume depletion resulting from poor oral intake and vomiting. Similarly, any gas- trointestinal illness with vomiting or diarrhea, excessive use of cathartics or laxatives, or bulimia may result in prerenal azote- mia. Generally, these disorders are readily apparent on the basis of history and laboratory fi ndings. However, eating disorders, which occur in up to 1% of pregnancies, are often diffi cult to diagnose and require a high index of suspicion [13] . To prevent the development of fi xed renal tubular injury, prerenal azotemia, due to hemorrhage or other causes, must be treated aggressively with blood product support and fl uid resuscitation. Laboratory studies that may be of benefi t in establishing the diagnosis of prerenal azotemia include urinary electrolytes and osmolality (Table 28.2 ). The urine sodium is typically low, as is the fractional excretion of sodium [(urine Na + /serum Na + )/ (urine creatinine/serum creatinine) × 100%], refl ecting a sodium - avid state, and urine osmolality is high, indicating intact urine concentrating ability. A low urine chloride may also provide a clue to surreptitious vomiting. Uterine hemorrhage is an important cause of hypovolemia and subsequent prerenal azotemia late in pregnancy. Although usually presenting as profuse vaginal bleeding, hemorrhage from placen- tal abruption may be concealed or may occur in the postpartum Table 28.1 Differential diagnosis of acute renal failure in pregnancy. Prerenal azotemia Acute tubular necrosis Acute interstitial nephritis Acute glomerulonephritis Obstruction Pre - eclampsia * HELLP syndrome * Acute fatty liver of pregnancy * Postpartum renal failure Pyelonephritis Bilateral renal cortical necrosis * These occur almost exclusively after 20 weeks gestation, and mostly in the third trimester of pregnancy. Table 28.2 Laboratory evaluation of acute renal failure. Prerenal azotemia Acute tubular necrosis BUN: creatinine ratio > 20 : 1 10 : 1 Urine Na + (mEq/L) < 20 > 40 Fractional excretion of Na + (FENa + ) < 1% > 2% Urine osmolality (mosm/kg H 2 O) > 500 < 350 Urine sp gr > 1.020 1.010 Urine sediment Bland Granular casts, renal tubular epithelial cells Chapter 28 378 is usually avoided in pregnancy, it may be encountered in the case of an intentional overdose. Antibiotics such as the penicillins and β - lactam antibiotics, and H 2 blockers are, however, used rou- tinely in pregnancy. Acute interstitial nephritis may also occur in association with viral infections, including cytomegalovirus and infectious mono- nucleosis, direct bacterial invasion, parasitic infections such as malaria and leptospirosis, and systemic diseases such as SLE and sarcoidosis (Table 28.5 ). Unlike acute GN, acute interstitial nephritis typically presents with modest proteinuria ( < 2 g/day), pyuria, eosinophiluria, hematuria, and white blood cell casts on urinalysis. Systemic manifestations may include fever, rash, arthralgias, and other signs of a hypersensitivity reaction in those patients with drug - induced interstitial nephritis. Hypertension and edema are infrequently seen with AIN, except in those cases of severe renal failure. Withdrawal of the offending agent or treat- ment of the underlying infection or disease usually results in improvement of renal function. In some cases of drug - induced or idiopathic AIN, steroids have been used with varying degrees of success. When history, physical examination, and laboratory evaluation are inadequate to establish a diagnosis, renal biopsy may be necessary. Acute t ubular n ecrosis Acute tubular necrosis may result from a variety of toxic expo- sures, including aminoglycosides, radiographic contrast, heavy metals, and several chemotherapeutic agents. Pigment - induced those women with pre - existing renal disease, these features are often noted in the fi rst two trimesters of gestation, although systemic lupus erythematosus (SLE) may manifest at any time during pregnancy. Laboratory analysis including serum comple- ment levels, antinuclear antibodies, antistreptolysin - O titers, antineutrophil cytoplasmic antibodies, and other autoantibodies may be helpful in establishing a diagnosis, although in most cases renal biopsy is eventually necessary. Pre - eclampsia may mimic acute glomerulonephritis in presentation, although serologic evaluation should be negative. It is important to attempt to dif- ferentiate between the two in order to avoid delivery at a very early gestational age as may be required for severe pre - eclampsia. Treatment of acute GN is largely supportive, including diuretics, antihypertensive agents, and occasionally dialysis. Depending on the underlying disease, corticosteroids or cytotoxic agents may be employed as well. Acute i nterstitial n ephritis ( AIN ) The most common cause of AIN is drug exposure and an exten- sive list of agents have been implicated. Among those more com- monly noted are the β - lactam antibiotics such as the semisynthetic penicillins, sulfa - based drugs, histamine H 2 blockers, and non - steroidal anti - infl ammatory agents (NSAIDs). While NSAID use Table 28.3 Acute renal failure: evaluation of intrinsic renal disease. Acute tubular necrosis Acute interstitial nephritis Acute glomerulonephritis Urine sediment Brown granular casts Hematuria, pyuria, eosinophils, WBC casts Hematuria, renal tubular cells RBC casts, oval fat bodies Proteinuria < 2 g/day < 2 g/day > 2 g/day, possible nephrotic syndrome FENa + > 2% > 2% < 1% Hypertension Uncommon Uncommon Common Systemic manifestations Hypotension, sepsis, hemorrhage Fever, skin rash, new medication Collagen - vascular disease, infection Table 28.4 Causes of glomerulonephritis. Primary Minimal change disease Focal segmental glomerulosclerosis IgA nephropathy Membranoproliferative glomerulonephritis Membranous nephropathy Poststreptococcal glomerulonephritis Secondary SLE Henoch – Sch ö nlein purpura Cryoglobulinemia Polyarteritis nodosa Wegener ’ s granulomatosis Hypersensitivity vasculitis Goodpasture ’ s syndrome Infection - related (i.e. shunt nephritis, endocarditis) Table 28.5 Causes of acute interstitial nephritis. Drug - induced Infection Viral: cytomegalovirus, infectious mononucleosis, hemorrhagic fever Bacterial: streptococcal infections, diphtheria, Legionnaires ’ disease Parasitic: malaria, leptospirosis, toxoplasmosis Systemic disease Sarcoidosis Systemic lupus erythematosus Sj ö gren ’ s syndrome Transplant rejection Leukemic or lymphomatous infi ltration Idiopathic . , Wilson DE . Successful hyperlipemic preg- nancy . JAMA 1991 ; 265 : 1858 – 1860 . 376 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy pancreatitis . Surg Gynecol Obstet 1974 ; 139 : 69 – 81 . 38 Ranson JC . The timing of biliary surgery in acute pancreatitis . Ann Surg 1979 ; 189 : 654 – 663 . 39 Imrie CW , Benjamin IS , Ferguson. pancreatitis in pregnancy . Surg Gynecol Obstet 1974 ; 139 : 879 – 882 . 9 Langmade CF , Edmondson HA . Acute pancreatitis during pregnancy and the postpartum period: a report of nine cases . Surg Gynecol