May 20, 2022

CODA: Do appendicoliths increase the chances of appendectomy after antibiotics?

Patients with appendicoliths are twice as likely to need an appendectomy within 30 days

The presence of appendicolitis in the appendix nearly doubled the chances of patients needing an appendectomy within 30 days of antibiotic treatment for appendicitis. Meanwhile, other more traditional clinical identifiers of severe appendicitis had no association with appendectomy, according to results from a secondary analysis of the trial comparing the outcomes of antibiotic drugs and appendectomy. (CODA).

In late 2020, results from the CODA trial suggested that, for some patients, antibiotics could be as effective as an appendectomy for the treatment of appendicitis, with approximately 70% of participants completely avoiding surgery at 90 days; however, in further analysis, CODA researchers found that this number fell to just over 50% in four years, with the rest eventually requiring surgery.

To best support decision-making in acute appendicitis, it is necessary to understand which clinical and radiographic features are related to the risk of appendectomy following antibiotic treatment for appendicitis, David R. Flum, MD , MPH, from the University of Washington in Seattle, and other CODA researchers wrote in JAMA Surgery.

To find out, Flum and his colleagues went back to the well — extracting data from participants in the antibiotic arm of the CODA trial — to determine which demographics, clinical information about appendicitis stage, and radiographic features differed. between patients who required an appendectomy within 30 days. antibiotic treatment and those who did not.

Their results suggest a “significant and persistent association between radiographic evidence of an appendicolith” – a lump of inspissated and mineralized stool in the appendix – “and a 30-day appendectomy in participants starting antibiotics (an almost doubled likelihood) , even after controlling for physiological features and other radiographic findings.” In addition, several other factors generally presumed consistent with severe appendicitis, such as fever, high white blood cell count, and radiographic evidence of a perforation of the appendix, were not independently associated with a need for surgery.

“For more than a century, surgeons have sought patient characteristics to guide the treatment of appendicitis,” Flum and colleagues wrote. “Increasing evidence that antibiotics can be used to treat appendicitis has made the search for these factors even more relevant. Understanding which patients are at higher risk of appendectomy after starting antibiotics could be one way to guide treatment decisions.

Liane S. Feldman, MD, and Lawrence Lee, MD, PhD, both of the McGill University Health Center in Montreal, Canada, agreed, in a editorial accompanying the study, that these data appear to suggest that the presence of appendicolitis was the strongest determinant of failure of antibiotic treatment of appendicitis. However, they argued that, based on additional findings from CODA, this increased risk appears to be greatest during the first two days.

“Additional data now available from the CODA trial reported no difference in the rate of appendectomy with or without appendicolitis beyond 2 days up to 2 years,” they wrote. “Ultimately, nearly 50% of patients initially treated with antibiotics required appendectomy at 2 years, regardless of appendicolitis. However, what is also not known is whether the presence of an appendicolith biased the management decisions of the healthcare team. Did some surgeons have a lower threshold to operate based on surgical dogma on appendicoliths? Were they concerned about the possibility of more serious illness and potentially a more difficult operation if delayed? Or maybe appendicolith patients take longer to improve on antibiotics? »

Regardless, Lee and Feldman concluded that while the risk may be highest in the first 48 hours in patients with appendicolitis, “about half of all patients will eventually require appendectomy.” . Whether a patient with appendicitis, regardless of appendicolitis, opts for nonoperative management knowing that there is a 50% risk of eventual appendectomy should be a unique decision for each person.

The initial CODA trial was conducted at 25 U.S. medical centers from May 3, 2016 through February 5, 2020. CODA investigators randomized a total of 1,552 participants with acute appendicitis to receive either antibiotic treatment (n=776 ) or an appendectomy (n =776).

“Conditional logistic regression models were fitted to estimate associations between patient-specific factors and the odds of having an appendectomy within 30 days of starting antibiotics,” the study authors explained. “A sensitivity analysis was performed excluding participants who underwent appendectomy within 30 days for non-clinical reasons.”

Of the 776 participants who started antibiotic treatment (mean [SD] 38.3 years old [13.4] year; 286 [37%] women 490 [63%] men), 735 had results at 30 days; of these, 154 (21%) underwent appendectomy within the first 30 days.

Flum and her colleagues found that female sex (odds ratio [OR] 1.53; 95% CI, 1.01-2.31) and radiographic findings of larger appendicular diameter (OR per 1 mm increase, 1.09; 95% CI, 1.00-1.18) were associated with an increased risk of patients requiring appendectomy within 30 days. However, the presence of appendicolitis had by far the largest effect (OR, 1.99; 95% CI, 1.28-3.10), a finding that held true in the analysis of sensitivity of only appendectomies performed for clinical reasons (adjusted OR, 2.41; 95% CI, 1.49-3.91).

As for other characteristics, such as fever, nausea, comorbidities, and advanced age, none were significantly related to the likelihood of a 30-day appendectomy. “The nearly doubled likelihood of appendectomy in people with appendicolith suggests that, at least for patients interested in the antibiotic treatment option, obtaining information about the status of the appendicolith may be important” , the study authors wrote. “For these patients, given the presumed role of imaging in identifying appendicolitis, the use of CT scans instead of ultrasound as part of the diagnostic evaluation of appendicitis may be a best option.”

This last point may prove difficult, because while 97% of participants in the CODA trial were diagnosed with MDD, ultrasound is likely the dominant choice for diagnosis in the United States and elsewhere.

“When determining treatment in light of appendicolitis, clinicians and patients should consider the risk of appendectomy in the context of several outcomes, such as overall well-being, time to relief of symptoms, time spent in health care, safety events, and time away from work – all parameters for which appendicolith was associated with poorer outcomes, albeit with low event frequencies “For some patients, this added risk may make antibiotics a less attractive option, while for others, these risks may be outweighed by the benefits of potentially avoiding urgent surgery.” many patients in the CODA trial indicated that they would prefer antibiotic treatment “even though they were in a subgroup with up to 75% change in appendectomy after antibiotics.”

An unexpected finding, the study authors added, was the association of female gender with appendectomy in the adjusted analysis.

“In examining associations between gender and clinical outcomes, there is vigorous debate about potential pathways, such as biological, social, or otherwise, that may be involved,” Flum and the authors wrote. “The CODA trial did not include data that could shed light on this question; therefore, we caution against applying this finding in clinical decision-making. Women were more likely to have a negative appendectomy. This finding may also be associated with factors that we could not or did not investigate, such as misdiagnosis on initial admission, adequacy of pain control, concerns about impact of appendicitis on fertility or previous experiences with the healthcare system that may have influenced the 5 participants’ decision to undergo an appendectomy. Underrecognition and undertreatment of acute abdominal pain in women may also have been a factor.

Study limitations included an inability to determine which appendectomies were a consequence of antibiotic failure as opposed to other unmeasured reasons, such as poor pain control; the analysis does not make it possible to exclude a recurrence of appendicitis beyond 30 days; the study may not be generalizable to patients who meet the CODA exclusion criteria; study authors did not include demographic variables that could be considered barriers to health care; and these results represent exploratory models and should not be used for an individual patient until the results are confirmed by further testing.

  1. The presence of appendicolitis in the appendix nearly doubled the odds of patients requiring an appendectomy within 30 days of receiving antibiotic treatment for appendicitis, according to a secondary analysis of the CODA study.

  2. Other standard features of severe appendicitis, including comorbidities, fever, and leukocytosis, were unrelated to antibiotic failure.

John McKenna, Associate Editor, BreakingMED™

This study was supported by a grant from the Patient-Centered Outcomes Research Institute.

Study co-author Price said he was a consultant for Kerecis, Acera and Medline. Co-author Thompson said he served as a reviewer for the Shriner’s Research Fund and received a personal honorarium from UpToDate. Co-author Evans said he received personal fees from Tetraphase Pharmaceuticals outside of the submitted work. Co-author Winchell said he received a personal fee from Stryker.

Lee pointed to grants from Johnson & Johnson and personal expenses from Stryker.

Cat ID: 188

Subject ID: 77188730188192925159