Acute Appendicitis Diagnosis and Treatment in 2009: Part I

The emergency department assessment of appendicitis has sure changed a lot in the past 30 years. I remember when the presence of less than one day of right lower quadrant pain, nausea, vomiting, localized tenderness and guarding, and a white count of 13,000 was enough to get the surgeon out of bed and the patient into the operating room. Conversely, patients with less than "classic findings" were either admitted for serial examinations or told to go home and come back in 12 hours for re-examination. In both circumstances, there was an understood and acceptable "miss rate" a number of patients taken to the operating room with the clinical diagnosis of acute appendicitis would have a normal appendix on pathologic examination, and some patients would have appendicitis diagnosed on their second emergency department visit. We all understood and accepted these facts as we exercised our clinical judgment to balance the risks of operating too leniently and removing more normal appendices or operating too strictly and increasing the rate of perforation and abscess formation.

Not anymore. Now, it seems as if a surgeon will not come in until the distended and inflamed appendix is visualized on advanced imaging modalities. Likewise, patient expectations and retrospective professional judgment often criticize the emergency physician for missing even one case of the most obscure presentation of acute appendicitis. Like much of our popular culture, we want the diagnosis of appendicitis to be right, and right now. We don't easily tolerate uncertainty or delays.

Like a good book, the story of acute appendicitis deserves periodic re-reading. In the first of a two-part series, this issue will discuss the presentation and diagnosis of acute appendicitis, with an emphasis on the use of current imaging modalities.

—J. Stephan Stapczynski, MD, FACEP, Editor

Epidemiology and Overview

Acute appendicitis is the most common surgical emergency in the United States, with an occurrence rate of about 80-90 per 100,000 persons each year.1 Because almost all patients with strong clinical evidence of appendicitis undergo appendectomy, the occurrence rate of acute appendicitis is based on the pathologic examination of the removed appendix. However, not all removed specimens demonstrate disease. A study of appendectomies performed between 1997 to 2003 in the United Kingdom is typical of this observation.2 Overall, only 65% of cases showed pathologic evidence of acute appendicitis. The peak incidence of pathologically confirmed acute appendicitis was in the second decade of life. There was evidence of perforation in 14% of all patients, with a significantly higher rate in those older than 70 years of age. The negative ("no pathologic evidence of acute appendicitis") appendectomy rate was 29% in all patients, with a significantly higher rate in female patients and in the 11- to 30-year-old group.

Making the diagnosis of appendicitis in a timely manner is important to prevent unnecessary morbidity and mortality and limit potential medico-legal exposure from a risk management standpoint. Missed appendicitis is one of the most common reasons for malpractice litigation in emergency medicine.3 In a recent review of a large insurance company database of malpractice claims, appendicitis was second only to meningitis as the most common diagnosis involved in pediatric malpractice claims.3

Anatomy

The appendix is an outpouching of the cecum, usually located in the right lower quadrant. Unlike the adjacent bowel, the appendix contains lymphoid follicles, but no immunologic function has ever been demonstrated. The exact position is variable; it may be retrocecal, pelvic, subcecal, preilial, postilial, or paracolic. In a classic study of 10,000 post-mortem cases, retrocecal was the most common location (65%).4 The length is 2-20 cm, with an average length of 9 cm. The lumen is small relative to its length.

Sixty-nine percent of cases of perforated appendicitis involved a retrocolic location of the appendix in one study.5 It commonly has been thought that the presence of overlying bowel delays the development of pain and detection of tenderness when the appendix is in this retrocecal location and leads to potential diagnostic delays. Like other aspects of conventional wisdom, this belief is not supported by the published data; a retrocecal location for acute appendicitis does not differ in the duration of symptoms, presenting signs and symptoms, initial white blood cell count, or rate of perforation compared with an anterior location.6,7 As discussed later, a non-anterior location of acute appendicitis may present with additional symptoms or signs, but usually not different ones.

The innervation is from the autonomic nervous system. No somatic pain fibers are found in the appendix itself. The pain is poorly localized initially; when the adjacent parietal peritoneum becomes inflamed, the somatic pain fibers are activated and the pain becomes more localized.

Pathophysiology

The classic hypothesis describes obstruction of the lumen by a fecalith or lymphoid hyperplasia that causes an increase in intraluminal pressure. This leads to venous hypertension and ischemia of the appediceal wall, with resultant bacterial invasion of the appendix with necrosis and perforation. However, luminal obstruction is found only in a minority of cases. Additionally, direct measurement of the intraluminal pressure at appendectomy reveals an elevated pressure in only a few cases.8

The reality is that any one of several inciting events such as luminal obstruction, bacterial or viral enteric infection, or trauma may initiate the breakdown of the appendiceal mucosa, resulting in bacterial invasion from normal flora and appendicitis. Fecaliths are found only in 8-44% of cases of acute appendicitis.9-11 Lymphoid hyperplasia is more common in noninflamed appendixes than in acute appendicitis.12

In 75% of appendicitis cases, well defined superficial mucosal ulceration is seen. Mucosal ulceration is a more consistent finding than dilatation of the appendix or fecaliths and is found earlier in the course of acute appendicitis.13

No specific infectious agent has been linked to appendicitis, although lymphoid hyperplasia can occur due to any number of infectious agents, including viral, salmonella, or shigella. Flora in the normal appendix are similar to that in the colon, including a variety of facultative aerobic and anaerobic bacteria such as E. coli, Strep. viridans, Bacteroides species and Pseudomonas species.14

Clinical Presentation

The cornerstone of the diagnosis of acute appendicitis traditionally has been the combination of history and physical examination. Timely diagnosis of appendicitis is important, as the delay in diagnosis and treatment can transform a simple case of appendicitis into a complex case of perforation and abscess. Unfortunately, the overall accuracy of the clinical examination in diagnosing acute appendicitis has been reported to be 70-87%. This falls to 54-70% in children and 50-70% in women of child-bearing age.15-17 Clinical diagnosis alone in women is particularly problematic due to the possibility of multiple alternate diagnoses that may have a similar presentation. Elderly patients and children may present diagnostic challenges as well.

Classically, the pain begins in the umbilical or epigastric region of the abdomen. It usually is vague and nagging in character, sometimes described by patients as similar to intestinal gas or the need to defecate. The pain later becomes more intense and, usually between 12-24 hours, localizes to the right lower quadrant. Migration of the pain from the epigastric or mid-abdomen to the right lower quadrant is common in appendicitis.16 This pain is of visceral origin, and it radiates to the part of the abdomen supplied by somatic sensory fibers associated with the same segment of the spinal cord that receives visceral sensory fibers from the associated visceral organ.19 Afferent sensory nerve fibers from the appendix accompany the sympathetic nerve fibers to the T10 segment of the spinal cord. This explains why the onset pain often is in the epigastric region.19

Nausea and/or anorexia in a previously healthy person are so common that appendicitis may be considered unlikely if both of these are absent. Vomiting also occurs frequently with appendicitis, but characteristically only several hours after the onset of pain.

Physical examination of a patient with suspected appendicitis begins with an examination of the vital signs. Fever is variably present in uncomplicated cases of appendicitis.20 One prospective case series found that temperatures greater than 99°F had only a 47% sensitivity and 64% specificity for appendicitis. This implies that the presence of a fever makes the diagnosis of uncomplicated appendicitis less likely.20 The presence of a fever may indicate perforation and abscess formation. Other vital signs should be normal unless more severe disease is present and the patient is becoming septic. In that case, variable degrees of tachycardia, hypotension, and tachypnea may be present.

Abdominal tenderness is the most common finding on examination and occurs in more than 95% of patients with appendicitis.21 The point of maximal tenderness usually lies directly above the inflamed appendix, most commonly at McBurney's point. The appendix may rotate and lie at any point around the base of the cecum. This may change the location of maximal tenderness. Once perforation occurs, the pain usually becomes more intense and more diffuse.22

Signs classically associated with appendicitis include the psoas, obturator, and Rovsing's signs. However, the psoas and obturator signs occur in fewer than 10% of patients with appendicitis, and their absence does not exclude the diagnosis.21 The presence or absence of any of these signs should not be used to rule out the diagnosis of appendicitis.

Peritoneal signs may become apparent on examination as the peritoneum becomes inflamed. Early in the disease course, peritonitis will be localized to the area overlying the appendix. When the appendix ruptures, tenderness and peritoneal findings become more generalized. Lin et al conducted a retrospective chart review of 202 patients with surgically proven appendicitis and found that peritoneal signs were 63.5% sensitive and 57.3% specific for appendiceal rupture.23 Another study of adults presenting with right lower quadrant pain found that rebound and percussion tenderness, respectively, were the most sensitive (82%) and specific (86%) ways to detect peritoneal irritation on examination.24 Physical examination may be least useful in certain populations such as young children, the elderly, immunocompromised patients, and pregnant patients as their physical examination may be misleading. These patients will be discussed in a subsequent section.

If the appendix lies in an atypical location, the clinical presentation may change. For appendices that are retrocolic or retrocecal, right groin pain may be present. Guarding may be absent due to protection from the overlying cecum.25 If the appendix is subcecal or pelvic in location, suprapubic or urinary frequency may be prominent. Diarrhea may be present due to rectal irritation, and abdominal tenderness may be minimal. If the appendix is pre-ileal or post-ileal, signs and symptoms may be minimal. Vomiting and diarrhea may present due to irritation of the distal ileum.25

A digital rectal examination (DRE) may be a useful screening tool for suspected anorectal or urologic pathology or gynecologic disorders, but its usefulness in supporting or refuting the diagnosis of appendicitis is questionable.26 The DRE often is uncomfortable or even painful for the patient and, in most cases, the DRE offers no additional diagnostic information.21,27 In a study by Dixon et al., 39-50% of patients with rectal tenderness or mass had appendicitis. However, 36-38% of patients with a normal rectal examination also had the disease.28 A pelvic examination should be performed for all women of child-bearing age.

Diagnostic Strategy

No major medical association or professional organization currently endorses a standardized pathway for the evaluation of patients with suspected appendicitis.29 The path to diagnosis for patients with possible appendicitis varies, depending in the sex and age of the patient, experience of the physician, desires of the surgical consultant, and local practice patterns. The major decision point involves which patients need imaging and, of those, what is the best study.

Are clinical scoring systems useful?

Several scoring systems exist with the goal of identifying patients in whom the diagnosis of appendicitis is likely. These systems are intended as guides to help determine when to obtain an immediate surgical consultation, when imaging is warranted, or when it is advisable to continue to search for another, more likely, diagnosis. The most widely know scoring system, the Alvarado system, assigns value to symptoms (migration, anorexia-acetone, n/v), clinical signs (right lower quadrant tenderness, rebound pain, temperature > 37.3ºC) and laboratory findings (leukocytosis, left shift) for a possible combined score of 10. Patients with Alvarado scores > 7 or < 3 have a likelihood of acute appendicitis of 77-93% and 4-6%, respectively.30 (See Table 1.)

Most scoring systems have been developed for use in the adult population. However, retrospective design, lack of clinical evaluation, addition of other diagnostic modalities, and small sample size made the creation of a diagnostic clinical score for use in children challenging.31 In 2002, Samuel introduced a pediatric appendicitis score (PAS) on the basis of a cohort of children 4-15 years old.32 The sensitivity was 100%, specificity was 92%, PPV 96%, and the NPV 99%. A score > 6 was highly associated with appendicitis. Goldman et al validated this rule in a study of 849 children. They found that a cutoff score of < 2 (found in 73% of children without appendicitis) had high validity for ruling out appendicitis, and a score of > 7 (found in 61% of children with appendicitis) had a high validity for predicting the presence of appendicitis. Children with PAS of 3-6 (37% with appendicitis and 23% without appendicitis in this study) should undergo further investigation such as observation, ultrasonography, or CT.31 (See Table 2.)

Imaging

When imaging is deemed necessary, the choice of ultrasound, CT, or MRI depends on the patient, institutional preference, and local expertise. Ultrasound and CT are the most commonly available and widely used modalities, although MRI is gaining acceptance for use in pregnant women. Ultrasound is widely available, easy to repeat in a serial manner to follow resolution or progression of disease, and is free of ionizing radiation. However, ultrasound is less sensitive than CT and technically more difficult to perform. MRI is expensive, time consuming, and not as widely available for emergency department patients, but it can make the diagnosis in pregnant patients with a non-diagnostic ultrasound. Each of these modalities will be discussed.

There is great interest in the literature in the accuracy of CT scan to diagnose acute appendicitis, with the goal of preventing unnecessary negative laparotomies. However, the rates of negative laparotomy and perforated appendicitis have not changed during the past decade,33 despite the introduction of CT. Does CT decrease the negative appendectomy rate? Some say yes, others no.34-40 Routine CT offers no advantage in patients with classic appendicitis presentation.41,42 These patients should have surgical consultation without imaging. A more targeted utilization is recommended with imaging only in equivocal cases or patient groups with multiple possible alternate diagnoses, such as women, children, and the elderly. Women of childbearing age may benefit from pre-operative imaging CT or ultrasound, as many conditions simulate appendicitis. The accuracy of clinical evaluation only in this group is 65%, compared to 82% in the rest of the population.43 (See Tables 3 and 4.) (See Figures 1-6.)







There are two schools of thought regarding the use of CT scan for the diagnosis of acute appendicitis: one supporting its routine use due to the decreased incidence of negative appendectomies,44-51 and the other one against its routine use, reserving it for selected cases due to the increased cost, radiation exposure, and delay in surgical management.52-55 A systematic review of 23 studies (19 of which were prospective) included individual results of 3474 patients undergoing CT scanning for suspected appendicitis. CT scan results were correlated with pathologic findings or clinical follow-up. The aggregated specificity and negative predictive value among all modes of CT scanning were similar (specificity range 95-98%, NPV range 94-99%). There was a greater range of values in sensitivity (83-97%) and positive predictive values (86-98%) among modes of CT scanning.56 CT scan protocols using enteric and IV contrast encompassing the entire abdomen and pelvis in general had the best accuracy. The primary role for CT is for those patients with an equivocal clinical assessment and to identify those patients with complications such as perforation or abscess who may need initial non-operative management.

Much controversy exists as to the best CT technique to diagnose appendicitis, with arguments for and against oral contrast, rectal contrast, IV contrast, triple contrast, and no contrast at all.57 IV combined with oral contrast is currently the most common technique used for abdominal CT.58 The abdomen also can be evaluated for other pathology with this technique.

Is oral contrast necessary?

The focus of early CT imaging of the abdomen and pelvis was aimed at mitigating the degradation of image quality that occurred due to respiratory motion, slow data acquisition, and bowel peristalsis. Oral contrast was added to help overcome these limitations and has been in use since the early stages of CT development. It helped delineate soft tissue planes between intraperitoneal structures. The introduction of rapid helical scanning and, more recently, multidetector devices, has made the utility of oral contrast media uncertain.58 Now, the focus is on development of protocols that may streamline the flow of the patients through the busy ED.

The theoretic advantage of oral contrast is that it opacifies the cecum, allowing for the assessment of appendiceal obstruction. Inflammatory conditions of the bowel often manifest with abnormalities in the fat of the peritoneal cavity and omentum. The stranding and hazy fat changes aid localization of pathology and should be detectable with or without oral contrast. Opacification of the rectum and sigmoid colon also help distinguish pelvic organs, such as ovaries, from adjacent bowel loops. Lack of retroperitoneal and intra-abdominal fat may make identification of the appendicitis and surrounding inflammation difficult without oral or IV contrast.

The drawback of oral contrast is that the patient must drink the contrast or have it given through the NG tube, requiring 45-60 minutes to reach the cecum post-ingestion. This increases scan time by 1-2 hours.59-61 Additionally, the patient may vomit or have ileus, thus making the contrast ingestion problematic. Rectal contrast may fail to reach the cecum or increase the risk of perforation due to increased hydrostatic pressure. Unenhanced CT has sensitivities reported from 96%, specificities of 99%, and diagnostic accuracy of 97%.62

Mun et al evaluated 173 patients undergoing CT for evaluation of possible appendicitis using their protocol of only IV contrast in patients who had an equivocal examination. CT diagnosis of appendicitis was made in 59 patients, with 56 of these being true positives. The three false positives were in female patients and were diagnosed with salpingitis, terminal ileitis, and normal appendix. All of the 114 patients with negative CT scans were true negatives by alternative diagnosis or one week negative clinical follow-up. The sensitivity of CT with IV contrast only in this study was 100% with a specificity of 97%. The positive predictive value was 95%, and the negative predictive value was 100%.63

Is any contrast necessary?

The use of IV contrast facilitates visualization of the bowel wall. In a clinically suspect population, the sensitivity of unenhanced CT is 96%, specificity of 99%, and accuracy of 97%.57-65 However, alternative diagnoses are achieved in only 35% of patients.64 In a recent study of patients with normal appendices, the use of IV contrast did not aid in the identification of the appendix over scans without IV contrast.66 However, the presence of ample intra-abdominal fat was helpful in making the diagnosis when oral contrast was not used. The diagnosis of appendicitis is harder to make via unenhanced CT without ample intra-abdominal fat, so the patient's body habitus should be taken into consideration when choosing which CT modality to employ.

Disadvantages of IV contrast include exacerbation of renal insufficiency, anaphylactic reactions, and the need for a larger caliber IV.

What does it mean when the appendix is not visualized on CT?

In a considerable number of CT scans obtained for right lower quadrant pain, the appendix is not seen. In two recent studies, this occurred in 13% and 14% of patients.67,68 Ganguli et al retrospectively reviewed CT scans using oral and IV contrast. Of the 400 exams, the appendix was not visualized in 59 of these. In 49 of the 59 patients, the pain resolved or another diagnosis was found. Nine patients were lost to follow-up. One patient presented 9 weeks later with appendicitis. The authors concluded that the non-visualized appendix was 98% sensitive for the absence of appendicitis (95% CI; 71-100%).5 Nikolaidis et al recommended that non-visualization of the appendix on CT may be used safely to exclude acute appendicitis.68

When does CT miss appendicitis?

The most common reason for a false-negative diagnosis of appendicitis is related to a paucity of intra-abdominal fat. Intra-abdominal fat (IAF) serves as a natural contrast agent, allowing inflammatory changes to be noted easily, even when subtle.69 A small pediatric study found a significant difference in appendix visualization rates between patients with low and medium amounts of fat and showed that appendix visualization improved in older patients.70 This finding was confirmed by others who showed a trend toward more IAF and better appendix visualization in children older than 10 years.71-73 Conversely, a lack of IAF may contribute to more indeterminate CT interpretations72,73 and more diagnostic errors.69 Levine showed that 96% of patients with incorrect CT interpretations had little IAF.69 The practical problem for the ordering clinician is that a patient's IAF (which is determined during CT interpretation) is unknown at the time the CT is ordered. Thus, how can one decide which CT protocol to use for any given patient? Further study in this area is needed.

Appendicitis with inflammatory changes in the right lower quadrant may cause reactive dilatation of the small bowel. This dilatation may be enough to mimic a small-bowel obstruction, resulting in a missed diagnosis of the underlying problem, which is the inflamed appendix. The dilated small bowel impedes the flow of oral contrast, thus causing suboptimal opacification of the cecum. In Levine's study, 38% of patients with missed appendicitis had small bowel dilatation.69 Inadequate bowel opacification led to misses as well in this study.

Tsao et al retrospectively studied 1078 children with appendicitis, including subsets of who did or didn't have pre-operative CT. They found the positive predictive value of CT was 91.8%, while the PPV for clinical evaluation without imaging was 90.8%.

For patients who have a clinical picture suggestive of appendicitis, a negative CT scan may be misleading and does not rule out the diagnosis. Often, the question is not when to order a CT scan to diagnose acute appendicitis, but rather when to rely on a CT scan to make the diagnosis. The data suggest that CT scan is a very accurate test to rule in acute appendicitis when the study is positive. When the study is inconclusive or negative, however, the diagnosis is not always excluded and, perhaps, when the CT is negative or indeterminate, the ED provider should request attending interpretation, as this is superior to that of a resident.74

Ultrasound. (See Figure 7.) The lack of ionizing radiation is the primary reason ultrasound is used as a diagnostic modality in the evaluation of acute appendicitis, primarily in pregnant women and children.

With the patient supine, the transducer is used to compress the right lower quadrant during imaging. Gentle pressure is applied with the transducer to displace the air-filled bowel loops. Slow graded compression is started at the point of maximal tenderness. This allows the adjacent bowel to move out of the right lower quadrant.

The inflamed appendix is relatively fixed and can be imaged by this technique in most cases. Transverse images are most useful. Visualize that it is an elongated, blind-ending structure to differentiate it from the adjacent terminal ileum.

The appendix appears as an elongated, blind-ending structure. Unlike normal bowel, the inflamed appendix is fixed, non-mobile, compressible, and appears round on transverse images. The inflamed fat appears brightly echogenic and noncompressible. With perforation, the contour of the appendix is irregular or a periappendiceal fluid collection may be seen. The appendix is more easily visualized when it is inflamed. With an experienced sonologist with modern equipment, non-visualization of the appendix has an NPV of 90%.75 A perforated appendix is easy to miss as it decompresses when perforation occurs.

A recent systematic review with meta-analysis of six studies that evaluated graded compression US and CT in the same adult and adolescent patient population found that CT increased the diagnostic certainty more than US.76 The positive likelihood ratios (LR+) were 9.29 for CT versus 4.50 for US, and the negative likelihood ratios (LR-) were 0.10 for CT versus 0.27 for US.76

CT is more sensitive and specific than ultrasound in patients suspected of having acute appendicitis with an equivocal presentation. Furthermore, CT has relative advantages in obese patients, a group in which ultrasound had definite limitations.

MRI. Like ultrasound, the greatest benefit of MRI is that it avoids ionizing radiation, which is important mainly in pregnant patients. Its main drawbacks are limited emergent availability, high cost, and long study time. There are no known adverse human effects related to non-contrast MRI. However, gadolinium should be avoided, especially in the first trimester, as it easily crosses into the fetal circulation. The usefulness of MRI will be discussed under the pregnancy section.

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