Laird Harrison

October 27, 2017

SAN DIEGO — By managing older, sicker patients' appendicitis without surgery, US physicians may be increasing their risk for death by a slight but statistically significant degree, data suggest.

"Mortality, we were surprised to find, was significantly higher in the patients managed nonoperatively," said lead author Isaiah Turnbull, MD, PhD, an assistant professor of surgery at Washington University in Saint Louis, Missouri.

Dr Turnbull presented the finding in a press conference and scientific session here at the American College of Surgeons (ACS) 2017 Clinical Congress.

US physicians have considered surgery the standard of care for appendicitis for a century, Dr Turnbull said.

But more recently, the realization that appendicitis may not always result in perforation led researchers to test treatment with antibiotics. Randomized controlled trials conducted in Europe have shown good results with this approach, and the ACS has advised that "antibiotic treatment might be used as an alternative for specific patients."

To see how these developments have affected care of appendicitis in the United States, Dr Turnbull and colleagues analyzed 952,443 appendicitis cases recorded in the National Inpatient Sample from 1998 to 2014. They found an accelerating trend toward more nonoperative treatment during the last decade, with the rate doubling from 2.3% to 4.9% during those 16 years.

"This increasing rate of nonoperative management suggests that [these] European data [have] been adopted by US surgeons," Dr Turnbull said.

Zeroing in on the years 2010 to 2014, they found that patients treated nonoperatively were more likely to die. These patients were also older, more likely to be diagnosed with peritonitis, had more total diagnoses, and had more comorbidities as measured by the Elixhauser-van Walraven comorbidity index. The differences were all statistically significant (P < .001).

Table. Nonoperative vs Operative Appendicitis Treatment 2010 to 2014

Demographics and Outcomes Surgery Within 48 Hours (n = 131,162) Nonoperative Management (n = 4694)
Age, years 40.9 49.2
Peritonitis, % 20.0 33.5
Number of diagnoses 3.83 5.71
Comorbidity score 0.78 1.35
Mean Total charges, $ 33,179 22,342
Mean length of stay, days 2.21 3.1
Mortality, % 0.08 0.5

Because it was not clear whether patients treated nonoperatively were more likely to die because of the treatment or other factors, the researchers analyzed the relationship of the factors using multivariate logistic regression.

They found that age, African-American race, number of diagnoses, comorbidities, and treatment type all independently increased the risk for death.

To further control for such factors, the researchers separated out two cohorts: one treated with surgery and the other treated without surgery, but matched for age, African-American race, comorbidity index, peritonitis, and number of diagnoses. Those treated with surgery had a mortality of 0.26% compared with 0.56% for those treated without surgery, a difference that was statistically significant (P < .05).

From these findings, the researchers theorized that US physicians are more likely to select older, sicker patients for nonsurgical management. That approach is not supported by the clinical trials that compared treatments, Dr Turnbull pointed out; the clinical trials specifically excluded older patients.

If anything, physicians should take the opposite approach because the weaker patients have less reserve; by the time antibiotic treatment fails, they may not be able to withstand surgery, he told Medscape Medical News. "I think that nonoperative treatment is safe and effective for young, healthy patents," he said.

More Things to Consider

The first author of one of the key clinical trials, Paulina Salminen, MD, PhD, told Medscape Medical News that patients older than 60 years were excluded because of concerns about an increased risk for appendiceal tumors.

At Turku University Hospital in Finland, where she is chief of acute care surgery, Dr Salminen does sometimes treat patients older than 60 years with antibiotics instead of surgery, as long as their appendicitis appears uncomplicated. She advises discussing the risk for recurrence with such patients and giving them the option of nonsurgical treatment. "If the patient is over 60, I would consider it, but with a lower threshold to surgery, as we don't have data on patients over 60," she said.

Comorbidities could tip her recommendation either way, she said. In cases of severe systemic illness possibly affecting the patient's ability to recover from infections, she would be more likely to recommend surgery. In contrast, a problem with the patient's lung might make the anesthesia required for surgery problematic.

She also pointed out that her study compared only uncomplicated cases of appendicitis; most complicated cases should be treated with surgery. In her study, patients were excluded if they had appendicolith, perforation, abscess, or suspicion of a tumor on computed tomography scan.

In contrast, Dr Turnbull and colleagues were only able to exclude patients with abscess and patients with percutaneous drainage. The National Inpatient Sample database did not show which other cases were complicated.

The new study is "timely," said scientific session moderator Sharmila Dissanaike, MD, professor of surgery at Texas Tech University in Lubbock. "It teaches us that in older, sicker patients with appendicitis, we should not think that antibiotics are equally good," she told Medscape Medical News.

However, the study leaves some questions unanswered, she said. She pointed out that a large database study cannot show cause and effect. The database does not show whether patients died from their appendicitis or some other cause, such as a heart condition, that could be related to the reasons for which surgery was avoided.

"What we had is administrative data," Dr Turnbull acknowledged. "We don't have clinical information. It's important to do clinical trials."

Cultural factors may also weigh into treatment decisions, Dr Dissanaike pointed out. For example, compared with Europe, patients in the United States might suffer more economically from missing work as a result of spending a long time in the hospital receiving antibiotics, she said.

Dr Dissanaike and Dr Turnbull have disclosed no relevant financial relationships. Dr Salminen reported receiving speaking fees from lecture fees from Merck, Roche and Lilly.

American College of Surgeons (ACS) 2017 Clinical Congress. Presented October 26, 2017.

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