Continuing Education Activity

Appendicitis during pregnancy is a condition in which the appendix becomes inflamed and infected. Its treatment consists of emergent surgery for the removal of the appendix. This activity reviews and describes the pathophysiology, etiology, epidemiology evaluation, management, and complications of appendicitis during pregnancy. As a common and serious condition that can develop anytime during pregnancy, it requires prompt diagnosis and treatment to avoid the high morbidity and mortality associated with this condition. The activity highlights the role of the interprofessional team in treating and improving care for patients with this condition.

Objectives:

• Describe the typical and atypical presentation of appendicitis during pregnancy.
• Summarize the management of pregnant patients with appendicitis.
• Review the common complications of appendicitis during pregnancy and their management.
• Explain the importance of improving care, collaboration, and communication among the interprofessional team in order to enhance the delivery of care and improve outcomes for pregnant patients diagnosed with appendicitis.

Introduction

Appendicitis is the most common general surgery problem during pregnancy. Its diagnosis represents a challenge, as its classic clinical presentation is not always present, its common symptoms are nonspecific and often associated with normal pregnancy, and the gravid state may mask the clinical picture. Also, obstetric causes may obscure the diagnosis, and physical examination of the pregnant patient may be difficult as a result of the gravid uterus and its effect on displacing the appendix within the abdomen. Furthermore, biochemical and laboratory indicators used to support the diagnosis of appendicitis may be unreliable during pregnancy.[1] General principles of pathophysiology, diagnosis, workup, and management for appendicitis during pregnancy follow the same pattern as in non-pregnant patients and are revised and discussed in the present review.

Etiology

The cause of appendicitis is usually an obstruction of the appendiceal lumen. This can be from an appendicolith (stone of the appendix) or some other mechanical etiologies. Appendiceal tumors such as carcinoid tumors, appendiceal adenocarcinoma, intestinal parasites, and hypertrophied lymphatic tissue are all known causes of appendiceal obstruction and appendicitis. Often, the exact etiology of acute appendicitis is unknown. When the appendiceal lumen gets obstructed, bacteria build up in the appendix and cause acute inflammation with perforation and abscess formation. One of the most popular misconceptions is the story of the death of Harry Houdini. After being unexpectedly punched in the abdomen, the rumor goes, his appendix ruptures, causing immediate sepsis and death. The facts are that Houdini did die from sepsis and peritonitis from a ruptured appendix, but it had no connection to him being struck in the abdomen. It was more related to widespread peritonitis and the limited availability of effective antibiotics at the time.[2][3] The appendix contains a combination of aerobic and anaerobic bacteria, including Escherichia coli and Bacteroides spp. However, recent studies utilizing next-generation sequencing revealed a significantly higher number of bacterial phyla in patients with complicated perforated appendicitis.

Epidemiology

Acute appendicitis is diagnosed in 1 in 800 to 1 in 1500 pregnancies, with a higher incidence during the second trimester.[4][5] Maternal morbidity and mortality following appendectomy are low and comparable to non-pregnant women.[6] The risk of fetal loss during uncomplicated appendectomies is 2%; however, in the presence of generalized peritonitis and peritoneal abscess, the fetal loss may increase to 6%.[7] In the presence of free perforation, the risk of fetal loss may rise to 36%.[8] The incidence of preterm labor due to appendectomy is 4%, and 11% in complicated cases. The association between negative appendectomy to preterm labor and fetal loss is 10% and 4%, respectively.[7]

Pathophysiology

The obstruction of the appendix results in increased intraluminal pressure and distention due to ongoing mucus secretion as well as gas production by bacteria that lie within the appendix; this results in progressive impairment of the venous drainage, causing first mucosal ischemia, followed by full-thickness ischemia, and ultimately perforation of the appendiceal wall. Stasis distal to the obstruction allows bacterial overgrowth within the appendix, resulting in the release of a larger bacterial inoculum to the peritoneal cavity in cases of perforated appendicitis.[9] Distention of the appendix is responsible for the initial visceral and vague abdominal pain often described by the affected patient. The pain typically does not localize to the right lower quadrant until the tip becomes inflamed and irritates the adjacent parietal peritoneum or perforation, resulting in localized peritonitis.

The background etiology of the obstruction might differ in the different age groups. While lymphoid hyperplasia is essential, this results in inflammation, localized ischemia, perforation, and the development of a contained abscess or frank perforation with resultant peritonitis. This obstruction may be caused by lymphoid hyperplasia, infections (parasitic), fecaliths, or benign or malignant tumors. When an obstruction is the cause of appendicitis, it leads to an increase in intraluminal and intramural pressure, resulting in small vessel occlusion and lymphatic stasis. Once obstructed, the appendix fills with mucus and becomes distended, and as lymphatic and vascular compromise advances, the wall of the appendix becomes ischemic and necrotic. Bacterial overgrowth occurs in the obstructed appendix, with aerobic organisms predominating in early appendicitis and mixed aerobes and anaerobes later in the course. Common organisms include Escherichia coli, Peptostreptococcus, Bacteroides, and Pseudomonas. Once significant inflammation and necrosis occur, the appendix is at risk of perforation, leading to a localized abscess and sometimes frank peritonitis.[10] The most common position of the appendix is retrocecal. While the anatomical position of the root of the appendix is mostly constant, tail positions can vary. Possible positions include retrocecal, subcecal, pre-and post-ileal, and pelvic.

Histopathology

Microscopic findings in acute appendicitis include the proliferation of neutrophils of the muscularis propria. The degree and extent of inflammation are directly proportionate to the severity of the infection and duration of the disease. As this condition progresses, extra appendiceal fat and surrounding tissues become involved in the inflammatory process. 

History and Physical

In the classic scenario of appendicitis, the patient first describes periumbilical pain that migrates to the right lower quadrant. Following the onset of pain, anorexia, nausea, vomiting, fever may develop. Non-classic symptoms include malaise, heartburn, flatulence, constipation, and diarrhea.[11][9][12][13][14][15] The abdominal examination usually reveals tenderness, rebound tenderness, and involuntary guarding on palpation of the right lower quadrant. The location of the tenderness is classically over the McBurney point, which is located one-third the distance between the anterior superior iliac spine (ASIS) and the umbilicus. Diffuse peritonitis or abdominal wall rigidity is strongly suggestive of appendiceal perforation.[11][9] When the appendix is in the retrocecal region, pain is usually described as dull rather than localized, and it will be elicited more likely by rectal or vaginal examination than by abdominal examination. Accordingly, a pelvic appendix may cause tenderness below McBurney's point, urinary frequency, dysuria, tenesmus, and diarrhea.[11][9][12][13][14][15]

 Findings are often subtle, especially in early appendicitis. As inflammation progresses, signs of peritoneal inflammation develop. Signs include:

• Right lower quadrant guarding and rebound tenderness over McBurney's point (1.5 to 2 inches from the anterior superior iliac spine (ASIS) on a straight line from the ASIS to the umbilicus)
• Rovsing's sign (right lower quadrant pain elicited by palpation of the left lower quadrant)
• Dunphy's sign (increased abdominal pain with coughing)

Other associated signs such as the psoas sign (pain on external rotation or passive extension of the right hip suggesting retrocecal appendicitis) or obturator sign (pain on internal rotation of the right hip suggesting pelvic appendicitis) are rare. The time course of symptoms is variable but typically progresses from early appendicitis at 12 to 24 hours to perforation at greater than 48 hours. Seventy-five percent of patients present within 24 hours of the onset of symptoms. The risk of rupture is variable but is about 2% at 36 hours and increases about 5% every 12 hours after that.

Several practical scores have been defined to facilitate the prompt diagnosis of acute appendicitis, mainly based on the history and physical examination, accompanied by laboratory tests and imaging measures, including abdominal ultrasonography. Accordingly, evaluation of patients with suspicious signs and symptoms suggestive of acute appendicitis has been widely undertaken with Alvarado criteria since 1986. The highest score among Alvarado criteria is allocated to the tenderness in the right iliac fossa, leukocytosis, and each of the other predicted symptoms, including migratory right iliac fossa pain, nausea, and or vomiting, and anorexia, hold one score. Moreover, positive findings in the remaining indexes of physical examination, including fever and rebound tenderness in the right iliac fossa, would hold a similar score of one.[16] 

Gravid women are less likely to have a classic presentation of appendicitis than age-matched nonpregnant women, especially in the late stages of pregnancy; however, the majority of pregnant women will still present abdominal pain, close to the McBurney point. As the location of the appendix may migrate cephalad with the enlarging uterus, pain may be described in the right flank or even in the right upper quadrant as pregnancy advances.[17][18][19][20][21][15]

Abdominal tenderness may be less prominent during pregnancy because the gravid uterus lifts the anterior abdominal wall away from the inflamed appendix. In the pregnant patient, the uterus may also inhibit contact between the omentum and the inflamed appendix.[22][23][24]

Evaluation

Laboratory Workup

As opposed to most of the non-pregnant patients with appendicitis who have a preoperative leukocytosis (greater than 10000 cells/microL) and a neutrophilic predominance, leukocytosis as high as 16900 cell/microL may be a normal finding in pregnant women, and during labor, the count may rise as high as 29000 cells/microL, with a slight neutrophilic predominance.[25][26][27][28][29][30] Therefore the presence of leukocytosis is an unreliable indicator in the workup of appendicitis. 

Microscopic hematuria and pyuria may occur when the inflamed appendix is close to the bladder or ureter, but these findings are not specific and are generally reported in less than 20 percent of patients.[31]

Mild elevations in serum bilirubin (total bilirubin over 1.0 mg/dL) have been described as a marker for appendiceal perforation (70% sensitivity and 86% specificity). However, clinicians should not use this finding alone as a diagnostic tool.[32] An elevated c-reactive protein level occurs in appendicitis, but it is a nonspecific sign of inflammation. Some studies evaluated the use of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to be added to the routine diagnostic methods in the diagnostic course of acute appendicitis during pregnancy, and the results were suggestive of increased accuracy of the diagnosis of acute appendicitis in this group of patients.[33]

Imaging

Due to the risks of negative appendectomies, routine imaging is recommended in all pregnant patients with suspected appendicitis to obtain accuracy in diagnosis. The initial study of choice is ultrasound with graded compression of the right lower quadrant starting at the point of maximal tenderness and scanning between the border of the pelvis, iliac artery, and psoas muscle. Ultrasound has the advantage of being pregnancy-safe and easily available.[34] Ultrasound is also helpful for providing information on fetal well-being and obstetric causes of abdominal pain. The criteria for US diagnosis are the same as in the nonpregnant patient; the inflamed appendix appears enlarged (greater than 6 mm), immobile, and noncompressible.[34][35] However, ultrasound is a user-dependent tool, and the presence of the gravid uterus during pregnancy will reduce ultrasound sensitivity (78%) and specificity (83%).[34]

If ultrasound findings are inconclusive, magnetic resonance imaging (MRI) without gadolinium contrast remains a safe alternative for confirmation or exclusion of appendicitis during pregnancy, as it provides good soft-tissue resolution and lacks ionizing radiation with excellent sensitivity and specificity that remains intact in the pregnant patient. Routine use of MRI in pregnant patients reduces the negative appendectomy rate by almost 50% and does not increase the rate of perforation. When available, the liberal use of MRI in pregnant patients suspected to have acute appendicitis is recommended for these reasons. When MRI is not available or is available only on a limited basis, the decision about any delay in appendectomy to obtain an MRI study requires all available clinical and imaging information available, as the potential consequences associated with both negative appendectomy and appendiceal perforation are severe.[34] MRI has been shown to perform relatively well in a few limited retrospective studies ranging from 97 to 100% sensitive.[36][37]

Although debatable, the use of CT scanning might be permissible when ultrasound is inconclusive, and MRI is not available. The use of CT scanning reduces the rate of negative appendectomy significantly compared to clinical assessment alone or combined with ultrasound imaging, and some authors conclude that it should be used if ultrasound findings are equivocal. Arguably, the amount of radiation during a limited CT scan is below the threshold required to cause fetal malformations, and most cases of appendicitis in pregnancy occur in later stages of pregnancy when organogenesis is already complete. If it is decided to use CT during pregnancy for inconclusive cases, care should be taken to perform a study as limited as possible with no intravenous administration of contrast material.[34][38][31][39]

Treatment / Management

Usually, the curative treatment of acute appendicitis is appendectomy. Perioperative antibiotic treatment should provide coverage for Gram-negative and Gram-positive bacteria (usually with a second-generation cephalosporin) and coverage for anaerobes (clindamycin or metronidazole). Delaying surgical intervention for more than 24 hours after the symptoms first appear increases the risk of perforation.[40][41][42]

If an appendiceal perforation is present, the management will depend on the nature of the perforation. A free perforation that causes the dissemination of pus and fecal material into the peritoneal cavity will likely result in a very ill-looking and septic patient with an increased risk of preterm labor and delivery and fetal loss. These patients require urgent laparotomy for appendectomy with irrigation and drainage of the peritoneal cavity.[8][7]

Nonpregnant patients that present with a long duration of symptoms (more than five days) and have findings of a contained perforation (phlegmon or abscess) are usually treated initially with antibiotics, intravenous fluids, and bowel rest. Since the appendiceal process has already been walled-off, most patients will present a good clinical response to nonoperative management. Immediate surgery in these patients correlates with increased morbidity because of the presence of adhesions and inflammation that requires extensive dissection that may lead to injury of adjacent structures. There may be the development of serious postoperative complications such as abscesses or enterocutaneous fistulae, requiring reoperation for more extensive resections, and the need for colostomies. Therefore, in these patients, a nonoperative approach is a reasonable option as long as they are not ill-appearing. Although there is solid evidence to support this approach to contained perforation in nonpregnant individuals, the evidence regarding pregnant women is sparse.[43] For this reason, when a walled-off perforation of the appendix occurs in a pregnant woman, it is advisable to proceed with caution and monitor these patients in the hospital to avoid sepsis, preterm labor, or fetal loss. Information regarding interventional drainage of appendiceal abscesses in pregnant patients is not available.

The two mainstream approaches for appendectomy are laparoscopic and open techniques. No randomized trials have been performed to suggest that one technique is better than another; therefore, the choice of technique should have its basis on the patient's clinical status and preferences, gestational age, and the surgeon's experience level. However, current guidelines state that laparoscopic appendectomy is the standard of care in pregnant patients as it is safe, allows easier identification of the variable location of the appendix, and offers an opportunity for an evaluation of the abdomen for any associated pathologic process.[44]

Some of the recommendations for the laparoscopic technique are modifications that include a slight left lateral positioning of the patient (during the second half of pregnancy), the use of an open-access approach (Hasson technique) for initial trocar placement to avoid injury to the gravid uterus, limiting intraabdominal insufflation pressure to less than 12 mmHg, and adjustment of port position for fundal height.[45][46] 

When performing an open appendectomy technique in a pregnant woman, a transverse incision is made at the point of maximal tenderness and not necessarily at McBurney point.[18][19] When the diagnosis is less certain, a lower midline vertical incision may be a possible option since it allows exposure of the abdomen for diagnosis and treatment of other surgical conditions that mimic appendicitis. 

Differential Diagnosis

The differential diagnosis of suspected acute appendicitis during pregnancy includes disorders typically considered in non-pregnant individuals. Therefore the clinician should consider cecal diverticulitis, Meckel diverticulitis, acute ileitis, inflammatory bowel disease (Crohn and ulcerative colitis), renal colic, and urinary tract infections. Gynecological conditions in the differential diagnosis include tubo-ovarian abscess, pelvic inflammatory disease, ruptured ovarian cyst, ovarian and Fallopian tube torsion. 

Also, and more importantly, pregnancy-related causes of lower abdominal pain, fever, leukocytosis, nausea/vomiting, and changes in bowel function need to be considered, such as placental abruption, uterine rupture, preeclampsia, HELLP (hemolysis, elevated liver function tests, low platelets) syndrome. During early pregnancy, ectopic pregnancy requires exclusion. Also, consider round ligament syndrome as a possibility. This condition is a common cause of mild right lower quadrant pain in early pregnancy.

Surgical Oncology

Despite the non-significant annual incidence of appendiceal cancers, with 1.2 cases per 100000 in the United States still, almost 30% of this spectrum might present acutely. The most common appendiceal malignancies are gastroenteropancreatic neuroendocrine tumors (GEP-NETs), goblet cell carcinoma (GCC), colonic-type adenocarcinoma, and mucinous neoplasm.[47] 

Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

(GEP-NETs) are the most common histopathological subtypes. They might rarely metastasize to the liver and or lymph nodes. Therefore, in patients with suspicious GEP-NETs (carcinoid tumor), further evaluation of the liver and the ileocolic lymph node basin are essential. Basically, the primary tumor size dictates the demanding surgical steps. Accordingly, in the carcinoid tumors of less than 1-centimeter size, an appendectomy with negative margins is the only requested surgical management. Although in the carcinoid tumor of greater than 2 cm, a right hemicolectomy is indicated, the surgical plan in appendiceal carcinoid lesions of 1 to 2 cm is still equivocal. However,  in the presence of mesenteric invasion, and enlarged lymph nodes, and or equivocal surgical margins, right hemicolectomy is recommended.

Goblet Cell Carcinoma

Goblet cell carcinomas are a ubiquitous entity of appendiceal malignancies in that they share the diagnostic features of both appendiceal adenocarcinoma and neuroendocrine tumors. A comprehensive peritoneal evaluation with further peritoneal cancer index score (PCIS) documentation should be undertaken. Patients with a non-metastatic and an equal or higher than 2 cm size will benefit from a right hemicolectomy.[48]

Lymphoma

Non-Hodgkin lymphomas (NHL), and its subtypes, including mucosa-associated lymphoid tissue (MALT) lymphomas, might initially present with acute appendicitis. The surgical management in this extremely uncommon appendiceal malignancy is limited to a simple appendectomy. However, a comprehensive systemic evaluation to exclude any potential metastatic site should be included.[49]

Adenocarcinoma

Adenocarcinoma of the appendix, a rare appendiceal neoplasm with three various histopathological subtypes, is most commonly present with acute appendicitis. The standard treatment is performing a right hemicolectomy, irrespective of the tumor size and or the involvement of the lymph node basin.[50]

Mucocele and Mucinous Neoplasm

Appendiceal mucocele, which might be the result of a benign or malignant spectrum of mucosal hyperplasia, and various cystic formations, might present with acute appendicitis. Several pre-operative radiological features, including a well-encapsulated cystic structure in the right lower quadrant, would raise the impression of an appendiceal mucocele; however, definitive diagnosis requires intraoperative evaluation and histopathological reports. The preferred surgical management is an appendectomy with great cautionary measures to prevent capsular rupture. In terms of peritoneal spread, providing documentation of the peritoneal involvement, along with tissue diagnosis with biopsies, is recommended. Moreover, suspicious mucinous neoplasm of the appendix should be managed with the peritoneal examination and record the PCIS in the presence of mucin. Patient selection for the laparoscopic approach in the management of appendiceal mucocele is extremely important and is limited to those with radiologic features suggestive of a homogenous cyst.[51]

Prognosis

According to the observational series, the long-term prognosis for women who undergo appendectomy during pregnancy is generally good. Preexisting morbidities, not the surgery itself, are the greater risk factors for postoperative adverse obstetric events.[52][53] A higher rate of fetal loss with the laparoscopic approach in comparison with open appendectomy is predicted.

Complications

Untreated appendicitis can develop into severe complications with high morbidity, appendiceal perforation and will manifest as one of two outcomes: free perforation or contained or "walled-off" perforation. Open perforations cause the dissemination of pus and fecal material into the peritoneal cavity, which will likely result in a very ill-looking and septic patient with an increased risk of preterm labor and delivery and fetal loss. Contained perforations can cause peritoneal abscess or phlegmon that forms around a burst appendix and require extended antibiotic treatment and likely drainage. 

Complications of the surgery itself can be extensive and include infections (postoperative peritoneal abscess), bleeding, and damage to adjacent structures.

Consultations

Any suspected case of appendicitis in pregnancy requires an obstetrician consultation to rule out obstetric and gynecological causes of pain as well as to establish the well-being of the fetus before and after anesthesia.

Deterrence and Patient Education

The appendix is a thin pouch hanging down from the large intestine. When it gets infected and inflamed, it causes a condition called appendicitis. This condition can be very painful, and if left untreated, very serious, as the appendix can burst, causing a life-threatening infection. Fortunately, appendicitis, when caught on time, can be easily treatable.

Appendicitis usually first presents as severe abdominal pain. This pain can start near the belly button and then move to the lower right side. Other usual symptoms include loss of appetite, nausea and vomiting, and elevated fever. However, a wide variety of symptoms can be present, including an upset stomach, irregular bowel movements (constipation or diarrhea). During pregnancy, identification of the picture and its diagnosis might be challenging as many of these symptoms are present during a normal pregnancy. 

A clinician or clinician team will make the diagnosis of appendicitis through a thorough interview and physical examination. If necessary, they will order special tests such as an ultrasound or MRI to provide more precise information as to the source of the abdominal pain. It is crucial that during this time, a gynecologist should examine the pregnant patient.

When any of the symptoms listed above are present, it is imperative to seek medical care. The risk for the appendix to burst rises after the first 24 hours of the onset of the symptoms; therefore, early identification and treatment are of great importance and will directly impact the results of the patient's health and pregnancy. 

The treatment for appendicitis is surgery to remove the appendix that can be done in two ways: open surgery during which the appendix will be removed through a single incision that is large enough through which to pull the appendix or laparoscopic surgery in which thin instruments and a camera are introduced to the abdomen through a few small cuts to perform the surgery, and appendix removal occurs through one of the small openings. 

Treatment for a complicated or a "burst" appendix will probably be more complicated than it would be if it had not burst, as all the material spilled out of the appendix needs to be washed away. If an appendix did burst but a few days have passed, it is likely that the body already formed a pocket around the appendix blocking the infection. In this case, treatment consists of antibiotic therapy and close monitoring, and not having surgery right away. However, surgery will eventually be needed.

Treatment for simple appendicitis without surgery is not the standard of care, but it is conceivable to do so. However, the chances of appendicitis returning are high. Patients and their physicians should discuss alternatives, including risks for both the patient and the pregnancy itself.

Enhancing Healthcare Team Outcomes

Acute appendicitis during pregnancy poses a diagnostic dilemma. These patients may exhibit non-specific signs and symptoms such as vomiting, nausea, and leukocytosis. The cause of acute abdominal pain may be due to a myriad of diagnoses, including gynecological, obstetrical, gastrointestinal, urological, metabolic, and vascular etiologies. While the physical exam may reveal that the patient has a surgical abdomen, the cause is difficult to know without proper imaging studies. An interprofessional team best manages the disorder to ensure prompt diagnosis and treatment.

The general surgeon should always be involved in the care of pregnant patients with suspected appendicitis. However, it is essential to consult with an obstetrician and gynecologist to rule out problems related to the pregnancy and any other specialist according to clinical findings and suspicion.

The nurses are also vital members of the interprofessional group, as they will monitor the patient's vital signs. The nurses should refrain from administering pain medications until the surgeon has examined the patient.

In the postoperative period, the pharmacist will ensure that the patient is on the right analgesics, antiemetics, and appropriate antibiotics, perform a medication record check for drug interactions and verify dosing on all drugs administered.

The radiologist also plays a vital role in determining the cause. 

The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) guidelines state that laparoscopic appendectomy is safe in pregnancy and is the standard of care in pregnant patients.[44] These are evidence-based guidelines that are reviewed by an interprofessional expert committee. The current guidelines have been developed after an exhaustive review of current medical literature from peer-reviewed journals to determine the appropriateness of radiological imaging and treatment procedures by the committee. In cases where evidence is not definitive or minimal, expert opinion from the specialist may be utilized to recommend the type of imaging or treatment. [Level 1] With the unique challenges of appendicitis in pregnancy, an interprofessional team approach is the best path for guiding successful outcomes for both mother and unborn child. [Level 5]