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Ulysses Syndrome: The Modern-day Odyssey of Pediatric Patients With Uncomplicated Acute Appendicitis

Mylonas, Konstantinos, S., MD; Masiakos, Peter, T., MD, MS, FACS, FAAP

doi: 10.1097/SLA.0000000000002686
Surgical Perspectives

Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Reprints: Peter T. Masiakos, MS, MD, FACS, FAAP, Associate Professor of Surgery, Harvard Medical School, Division of Pediatric Surgery, Massachusetts General Hospital, Warren 11, 55 Fruit Street, Boston, MA 02114. E-mail:

Disclosure: The authors declare no conflicts of interest.

Ulysses, the King of Ithaca, began his odyssey after being unwillingly recruited to fight in the Trojan War. Upon victory, he sailed for home to be reunited with his beloved wife, Penelope, and his son, Telemachus. What would have been a 3-week trip, turned into a 10-year ordeal filled with unexpected peril and ample misfortune. His unwavering desire to complete his journey or “nostos,” is the central theme of the tale.

Ulysses syndrome, common, yet rarely discussed, is the medical phenomenon characterized by a series of physical and psychological disorders that follow the discovery of a false-positive result.1 Named after the Homeric protagonist, the syndrome is specifically used to describe a patient, who, despite being generally healthy at the onset of a medical evaluation, is subjected to the ordeal of repetitive laboratory testing, imaging, and unnecessary interventions, ultimately finding themselves back where they started with no diagnosis; possibly sustaining an avoidable iatrogenic injury and experiencing some degree of mental anguish along the way. Pediatric patients who present to the emergency department (ED) with vague abdominal pain may experience Ulysses syndrome when the search for a diagnosis results in findings concerning for uncomplicated acute appendicitis (UAA).

In the past, such patients would be hydrated, observed for symptom resolution if clinical suspicion was low, or undergo an expeditious operation to remove an inflamed appendix. And sometimes, the surgeon would remove a “white” appendix.

Because clinicians have been unable to accurately diagnose all cases of pediatric UAA, we have actively searched for methods to improve our accuracy and distinguish those patients we should take to the operating room from those we should not. Clinical decision rules and selective radiography have helped to reduce the negative appendectomy rates that once approached 10% for males and up to 30% for females, to less than 5% in recent years.2 Still, from time to time, we remove an uninflamed appendix and feel vanquished when we do.

Although one could argue that the clinical examination done by experienced surgeons in concert with selective laboratory testing has similar sensitivity to computed tomography (CT),3 there are patients who present with vague symptoms and inconsistent histories causing many clinicians to depend on advanced imaging to confirm or refute their clinical findings. As the sensitivity of imaging has improved, we now detect findings that we may not have been able to see previously (explaining in part the reduction of false positive appendectomies). Radiology reports including terms like “early” or “tip” appendicitis,4 along with statements like “clinical correlation is recommended,” may be helpful in dissociating positive from negative appendixes, but these statements may have introduced another unintended level of uncertainty to the quest for a definitive diagnosis in patients with equivocal clinical histories and/or abdominal examinations.

Despite the favorable outcomes seen after laparoscopic appendectomy, a nonoperative trend for the treatment of UAA has recently emerged. This paradigm shift is driven by our desire to minimize negative appendectomy rates and avoid potential risks associated with surgery and anesthesia.5 Successful management of traditional “surgical diseases” with antibiotics, such as diverticulitis and necrotizing enterocolitis, has also been used as an argument in support of attempting to treat appendicitis nonsurgically.5 Driven by our need to deliver some form of treatment in the setting of radiographic suspicion of UAA (at times regardless of the clinical examination), surgeons will either choose to operate based on the CT findings or to admit for serial examinations. Recently, however, an increasing number of surgeons are choosing to treat these patients with antibiotics alone. In the past 6 years, nonoperative management (NOM) of pediatric UAA has increased by 20.4%, even though its long-term efficacy and cost-effectiveness have not been clearly defined.6

Nonoperative management has been championed as an attractive and potentially safe alternative to conventional laparoscopic appendectomy.6,7 But in choosing this approach, we may inadvertently convert a safe operation that definitively treats appendicitis, or a brief hospital stay for observation in those cases where the pain resolves without surgery, into an epic ordeal for our patients.

Recent data from over 4000 children treated with antibiotics in 45 pediatric hospitals across the United States suggest that during a 12-month follow-up period, 11.2% of patients experience repeat ED visits, 8.9% undergo additional advanced imaging, 43.7% are re-admitted to the hospital, and 46% ultimately receive an appendectomy.6 These data suggest that providers and parents have a heightened concern over the risk of recurrent appendicitis and that when these patients return to the ED, surgeons may be more inclined to operate with or without further evaluation.

Additionally, a population-based analysis using data from the California Office of Statewide Health Planning database reported on 231,678 patients with UAA and found significantly longer length of hospital stay (HLOS) with NOM when accounting for subsequent hospitalizations.7 A recently published randomized controlled trial in adult patients comparing NOM to supportive care (intravenous fluids, analgesia, and antipyretics, as necessary) found no difference between the 2 modalities while reporting longer HLOS and higher cost for the nonoperative approach.8 Ultimately, attempting to treat appendicitis with antibiotics may result in “a much longer Odyssey” for patients; one that is complicated by multiple readmissions, long hospitalizations, increased antimicrobial resistance, and antibiotics-related morbidity. Furthermore, in the era of global re-alignment towards pay-for-performance reimbursement paradigms, prolonging patient hospitalization for observation and antibiotic administration could be problematic not only for patients themselves but also for our healthcare system.

Equally concerning are the results of 1 published pediatric randomized controlled trial comparing surgery with antibiotics, in which 29% of patients who underwent an appendectomy after NOM over concerns for recurrence had a histologically normal appendix.9 Could it be that some patients may never have had appendicitis to begin with, but instead were caught in a web of unnecessary investigations and interventions to treat a false-positive imaging finding in the context of their abdominal pain?

Despite the lack of granular data supporting NOM as a tenable alternative to surgery, the likelihood of patients requesting a nonoperative approach may continue to increase in the years to come. In the context of respecting patient autonomy, clinicians should present available evidence in a clear and unbiased manner to ensure that both the potential benefits and the uncertainties surrounding this approach are fully understood. That said, in our journey to optimize the management of patients with suspected appendicitis, we should continue to depend on sound clinical judgment and granular data to direct safe patient care decisions while we await the results of the prospective trials which have been designed to determine whether NOM provides equal or superior results to appendectomy (NCT02271932, NCT02447224, NCT02991937). For now, we should remember that technology has its limitations and that advanced imaging should only be utilized when truly indicated.10

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10. Rosen MP, Ding A, Blake MA, et al. ACR Appropriateness Criteria(R) right lower quadrant pain: suspected appendicitis. J Am Coll Radiol 2011; 8:749–755.

antibiotics; children; early appendicitis; nonoperative management; pediatric patients; tip appendicitis; ulysses syndrome; uncomplicated acute appendicitis

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