Gastroenterology – Emergency Medicine Literature of Note

More Anti-Antibiotics in Diverticulitis

It’s hard to believe I’ve covered this topic – the evidence for reducing antibiotic exposure in diverticulitis – as long ago as 2013. While it might not be the prudent thing to be the first adopter of a new medical practice, I’d have thought this idea could have had more traction, sooner.

This latest piece of evidence is a “pragmatic” randomized, placebo-controlled, double-blind trial of patients admitted for “non-complicated” diverticulitis. “Non-complicated” in this context means, effectively, non-perforated, and explicitly defined as Hinchey 1a grade. Patients were also excluded if they had multiple systemic inflammatory response criteria, immunosuppression, or other comorbid physical status. Those who received antibiotics were given a regimen including cefuroxime, metronidazole, and amoxicillin/clavulanic acid, while the opposing side received matching placebo.

The trial was rolled out across four hospitals between 2015 and 2019, including three in Auckland, New Zealand, and one in Sydney, Australia and ultimately included 180 participants. The primary outcome was length of hospital stay, the difference for which was not statistically significant at 40 hours for the antibiotic cohort and 46 hours for placebo. The authors tracked many adverse events, discontinuation reasons, and protocol terminations, and there was no clear pattern or apparent trend favoring either cohort, within the scope of the small sample.

After so many years, it would be lovely to finally see better guideline uptake in support of antibiotic stewardship for mild diverticulitis. It certainly seems consistent across all the various trials and cohorts by multiple groups across the world, now, there is minimal, if any, additive benefit – or, at the least, the harms from antibiotic use are similar to those whose diverticulitis progresses left untreated.

“Antibiotics Do Not Reduce Length of Hospital Stay for Uncomplicated Diverticulitis in a Pragmatic Double-Blind Randomized Trial”
https://reader.elsevier.com/reader/sd/pii/S1542356520304262

Choosing Wisely Hepatology, Eh?

The Choosing Wisely campaign is quite popular in theory, if not in practice – ranging widely across the specialties from Pediatric Hospital Medicine to our own, beloved, Emergency Medicine.

This list is from the Canadian Association for the Study of the Liver, and two of their five recommendations are somewhat relevant to EM. Without further ado:

Statement 1: Don’t order serum ammonia to diagnose or manage hepatic encephalopathy

This was their most highly ranked recommendation when members were surveyed at their annual meeting. They cite multiple confounders regarding ammonia levels, factors affecting accuracy of the measurement, and state “elevated ammonia levels do not add any diagnostic, staging, or prognostic value.” The diagnosis, they feel, ought to be made based on clinical history and response to therapy alone.

Statement 2: Don’t routinely transfuse fresh frozen plasma, vitamin K, or platelets to reverse abnormal tests of coagulation in patients with cirrhosis prior to abdominal paracentesis, endoscopic variceal band ligation, or any other minor invasive procedures

This is another one of my favorite pet topics – transfusion intended to “restore normal hemostasis” in a dysfunctional, but somewhat already rebalanced coagulation system. As they say, “Routine tests of coagulation do not reflect bleeding risk in patients with cirrhosis and bleeding complications of these procedures are rare.” In fact, I’ve seen several articles approaching even liver resection in the context of elevated coagulation parameters absent any major bleeding complications – so this ought certainly apply to minor procedures, including those in the Emergency Department.

No doubt the uptake of these recommendations will be highly variable among hospitals and specialty groups, but lists like these are great tools with which to start the conversation.

“Choosing Wisely Canada-Top Five List in Hepatology”
https://www.ncbi.nlm.nih.gov/pubmed/30596626

The Probiotic Hoax?

The concept of probiotic therapy is a compelling one: under duress from illness or adverse effects from medications, the gastrointestinal biome becomes altered. Orally repleting this biome to restore “normal balance” ought to improve morbidity. Sounds good, right? Unfortunately, plausibility is not the same as practical efficacy.

Other indications or specific contexts notwithstanding, this multi-center trial shows probiotics confer no advantage for progression of gastroenteritis in children. These authors conducted a randomized, double-blinded trial in six pediatric Emergency Departments in Canada, including 886 children presenting with fewer than 72 hours of infectious diarrheal symptoms. They each received a 5-day course of either Lactobacillus rhamnosus R0011 and L. helveticus R0052 or placebo. Short answer: about 25% of each cohort progressed to moderate-to-severe gastroenteritis, and the duration of diarrhea was a little over two days, regardless.

The authors note “5 out of 12 leading guidelines endorse the use of probiotics”, although it does not appear they have a citation regarding how many dentists would recommend. While these data do not generalize to all indications, nor potentially all possible probiotic formulations, these data certainly tilt the board away from “potentially useful” towards “probably not useful”. Adverse events were common and similar between groups, so probiotics are unlikely to be harmful in a population with normal baseline health status – but you might as well just visualize your money concurrently swirling along down the toilet.

“Multicenter Trial of a Combination Probiotic for Children with Gastroenteritis”

https://www.nejm.org/doi/full/10.1056/NEJMoa1802597

That Lego is Gone

Lego, a portmanteau of Danish words meaning “play well”, are ubiquitous toys around the world. This means the bite-sized bits are equally prevalent in the hands of infants and toddlers around the world – and in their mouths. What goes in a toddler’s mouth goes into their stomach.

This brief study evaluates six toddlers – ahem, pediatricians – who each swallowed a Lego head:

These adult children subsequently searched stools for signs of the swallowed item, as well as performed an assessment of stool consistency. Most importantly, they were able to derive infantile acronyms for their assessments – the SHAT and FART scores.

One of the six participants was never able to locate the ingested Lego part, despite two weeks of stool searching. The other five found them in their second or third bowel movement, which, on average, was 1.71 days later. Stool consistency was unrelated to passage of the head.

Obviously, the generalizability and reliability of such a study is quite low, being adults and only six of them. Then, although these authors report “no complications”, they have not yet located one of the six heads – perhaps a future case report: “Acute appendicitis involving an unusual appendicolith”? At the least, a potential future IgNobel prize awardee.

“Everything is awesome: Don’t forget the Lego”
https://onlinelibrary.wiley.com/doi/full/10.1111/jpc.14309

Who Still Acutely Uses Fecal Occult Blood Tests?

If you trained or practiced in the last few decades, there’s no doubt you’ve performed hundreds, if not thousands, if not tens of thousands, of fecal occult blood tests. For many years, this has been part of some routine evaluations for suspected gastrointestinal bleeding or anemia without another adequately identified source.

However, this test is pointless, as these folks at Parkland succinctly illustrate. In evaluating the value of the FOBT in the acute clinical setting, they observe two features obviating its utility. First, they argue the test characteristics are utterly inadequate – there are confounders contributing to both false negatives and false positives, leading to either delays or inappropriate interventions. Then, they ultimately note ultimate clinical course depends on the the other presenting features rather than the result of the FOBT.

Specifically, Parkland went from nearly 8,000 FOBT (mostly in the Emergency Department) to zero.

You can too.

“Eliminating in-Hospital Fecal Occult Blood Testing: Our Experience with Disinvestment”

https://www.sciencedirect.com/science/article/pii/S0002934318302195

No Pictures of Poop Needed

I like this article – not because of any specific quality improvement reason relating to their intervention, but because it reminded me of something of which I perform too many.

It’s an easy trap to fall into, the – “well, let’s just see how much poop is in there” for diagnostic reassurance and to help persuade the family you’re doing relevant testing in the Emergency Department. However, here are the relevant passages from their introduction:

In a 2014 clinical guideline, the North American and European Societies of Pediatric Gastroenterology, Hepatology, and Nutrition found that the evidence supports not performing an AXR to diagnose functional constipation.

and

Recent studies showed that AXRs performed in the ED for constipation resulted in increased return visits to the ED for the same problem.

I feel some solace in knowing that 50 to 70% of ED visits for constipation may include an abdominal radiograph as part of their workflow – meaning I’m just, at least, part of the herd.

So, regardless of the point of their article – that a plan-do-act cycle of education and provider feedback successfully cut their rate of radiography from 60% to 20% – this is yet another misleading and/or unnecessary test to delete from our practice routine.

“Reducing Unnecessary Imaging for Patients With Constipation in the Pediatric Emergency Department.”
https://www.ncbi.nlm.nih.gov/pubmed/28615355

Antibiotics for Diverticulitis, the End Must Be Near

I’ve talked about the inflammatory vs. infectious theory for diverticulitis in a couple of my national and international presentations, and I’ve talked about the evidence supporting an observation-only strategy. Until now, that evidence was mostly a single-center randomized trial from Finland, followed by an observational report from the same.

Now, this non-treatment paradigm has migrated across the little river between Scandanavia and Europe, and has been taken up by the Dutch in this latest randomized trial. In this trial, 22 clinical sites randomized 570 patients with uncomplicated diverticulitis to either admission for antibiotic treatment, or observation and disposition per clinical stability. The antibiotic chosen was amoxicillin-clavulanic acid, with ciprofloxacin/metronidazole in the case of allergy. The primary outcome was time to recovery, with secondary outcomes relating to complications and recurrence.

Of the 570 randomized, ultimately, only 528 were analyzed. A handful were lost to follow-up, and then 35 patients withdrew from the study after allocation – 22 in the observation cohort and 13 in the antibiotics cohort. There were minor, potentially confounding differences between the two cohorts analyzed – about 8% more of the antibiotics cohort suffered from mild or severe comorbid disease.

Most patients selected for observation were admitted – with only 13% managed as outpatients. With respect to the primary outcome, there was no difference between cohorts in time to recovery. There were also few statistically significant differences in secondary outcomes, although the numbers suggest a small magnitude of harm relating to observation. Complications – ongoing diverticulitis within 6 months, need for sigmoid resection, and hospital readmission – all favored the antibiotic cohort by small, non-significant amounts. Conversely, morbidity numbers generally favored the observation cohort – relating mostly to antibiotic-related adverse effects.

Regardless, the sum of benefits and harms – in the context of the other evidence – supports antibiotic-free strategies for uncomplicated diverticulitis.

“Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis”
http://onlinelibrary.wiley.com/doi/10.1002/bjs.10309/abstract

The Slow Demise of Antibiotics for Diverticulitis

We have been prescribing antibiotics for diverticulitis for an eternity. Some patients, after all, do quite poorly without – and progress to perforation, sepsis, and death. Very few clamor for such an outcome. The question with diverticulitis has never been “antibiotics?”, only “inpatient or outpatient”?

Now, this dogmatic practice seems ripe to change.

This latest bit of published literature is an observational series from Sweden. These authors followed up their previously-published randomized trial with an initial foray into practice change, considering the consistent harms of antibiotic overuse. They prospectively enrolled 155 patients with CT-verified, uncomplicated diverticulitis and simply followed them after discharge without antibiotics. Management consisted solely of pain control, typically paracetamol (acetaminophen), an initial liquid diet, and then gradual progression to full diet as tolerated. Patients were followed daily by phone, at 1 week in clinic, and at 3 months again in clinic.

Of these 155 patients, there were a mere 4 treatment failures requiring admission. This treatment failure rate is similar to the ~2.5% rate expected with antibiotics. Two progressed to perforation and a third developed abscess – the last of which was apparent on re-review of the initial CT. Each patient with progression was treated with antibiotics as an inpatient and recovered.

This is, however, an observational trial, and there were another 66 patients diagnosed with uncomplicated diverticulitis in the same time period but missed for enrollment. This leads to concerns regarding selection bias, although the few presented clinical characteristics of the missed patients were similar to those included in the trial. Patients were also excluded on the basis of many comorbidities thought to increase the risk of treatment failure, and those treated as inpatients.

But, at the least, in this trial and those prior, there is clearly a cohort of uncomplicated diverticulitis that derives little benefit from antibiotics. And, furthermore, these few trials have not gone unnoticed: new guidelines in several countries, including the American Gastroenterological Association, have updates reflecting the validity of selective antibiotic use.

The evidence quality to date is still cumulatively low – but this is probably a treatment change paradigm just about ready for prime-time.

“Outpatient, non-antibiotic management in acute uncomplicated diverticulitis: a prospective study”
http://www.ncbi.nlm.nih.gov/pubmed/25989930

“American Gastroenterological Association Institute Guideline on the Management of Acute Diverticulitis”
http://www.ncbi.nlm.nih.gov/pubmed/26453777

Just Poop, It Doesn’t Matter How

Hepatic encephalopathy, a consequence of bacterial overgrowth and impaired ammonia metabolism, contributes to (as these authors say) nearly $2B in healthcare costs due to hospitalization in the United States alone. Typical, goal-oriented, modern therapy? Lactulose, a non-digestible sugar, resulting in increased bowel movement frequency.

These authors, appropriately, challenge established dogma – noting, perhaps, there are more effective strategies for clearing the bowels. As anyone who has undergone colonoscopy is aware, 4 liters of polyethylene glycol solution is the preferred – and highly-effective – bowel-cleansing method. These authors, therefore, compare standard lactulose therapy with a forced high-volume intake of PEG solution.

With 50 patients randomized in generally similar distribution to either lactulose or PEG, the PEG solution group more rapidly cleared mentation within 24 hours – with 21 of 25 randomized to PEG making at least 1 point improvement on the hepatic encephalopathy scoring algorithm, compared with 13 of 25 in the lactulose cohort. Victory! Of course, this sample is too small to truly account for any adverse effects. 8 serious adverse events occurred, include 3 deaths, although the authors feel none were related to the differences between treatment strategies. And, oddly, diarrhea was noted to be a more frequent adverse event in the PEG group.

Why is this odd? Because increased frequency of bowel movements is critical to treatment success in HES – and, frankly, if they’re not seeing enough stool output in the lactulose group, they might be doing it wrong. There’s no specific mention of outputs in the lactulose group, but, ideally, treatment of HES involves a rapid titration of lactulose to adequate stool volume, not a rigid treatment dose. As such, I might suggest this is a bit of a straw-man comparator between PEG and lactulose, with regard to tests of superiority.

But, I applaud simply thinking outside the box. Lactulose use has become somewhat dogmatic for the treatment of HES, when, clearly, the answer is just – poop, it doesn’t matter how.

Thanks to Rick Pescatore for forwarding this along.

“Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution for Treatment of Overt Hepatic Encephalopathy”
http://www.ncbi.nlm.nih.gov/pubmed/25243839

Merry Christmas!

If you truly must read literature on Christmas, then I direct you to thebmj, and a selection of articles from its Christmas issue:

“Televised medical talk shows—what they recommend and the evidence to support their recommendations: a prospective observational study”
http://www.bmj.com/content/349/bmj.g7346

“CARTOONS KILL: casualties in animated recreational theater in an objective observational new study of kids’ introduction to loss of life”
http://www.bmj.com/content/349/bmj.g7184

“When somebody loses weight, where does the fat go?”
http://www.bmj.com/content/349/bmj.g7257

“Are some diets “mass murder”?”
http://www.bmj.com/content/349/bmj.g7654