Tuesday, August 27, 2013

Should we be ok letting the GI specialist sleep?


Variceal bleeding is a frightening condition seen infrequently in the ED, but when it shows its face it sparks high anxiety. It is one of the most rapid type of not compressible bleeding (unless you consider the blakemore), in my eyes it is comparable to intraperitoneal traumatic bleeding.  Can we as EP's simply rely on medical management and stabilization or is our gut right when we say, "where is G.I. , they've got to come in for this?" This is a debate, seemingly more one-sided as most of the literature on it is from gastroenterology journals and may be skewed toward our colleagues' opinion (our 'Annals' does not have a single paper with "esophageal varices" or "variceal" in the abstract or title). What is the right thing to do for our patients?

You can imagine, a "cushy" subspecialty like gastroenterology having private conversations amongst
each other at national conferences, discussing how they could convince the world that they need not speed over to the hospital at 4am for an emergent endoscopy.  Their desire to never be awoken from their slumber however has given birth to a hubris of new extremes.  With a massive review paper published in the Canadian Journal of Gastroenterology titled, "Emergency management of bleeding esophageal varices: Drugs, bands or sleep?"  they have comfortably convinced themselves that because the jury is still out, they will continue to sleep. 

In conclusion of this extensive study they authors state:
"Timing of definitive endoscopic treatment has not been clearly defined. Delaying endoscopic treatment may make it easier to perform in a clear, bloodless field, especially for band ligation. Current data suggest no difference in control of hemorrhage or mortality in the setting of pharmacological therapy if endoscopic treatment is delayed up to 48 h. Therefore, to the probable delight of gastroenterologists on call, we recommend that emergency endoscopic treatment (less than 6 h from presentation) be reserved for continuing bleeding resistant to initial pharmacological treatment."

The interesting thing is that they confidently make a very serious, consequence-heavy "recommendation" to delay emergent endoscopy several paragraphs after this one (within their limitations section) :
"Excellent meta-analyses are available for octreotide, terlipressin and comparisons with sclerotherapy; however, pharmacological treatment and band ligation have not been directly compared. Therefore, while band ligation may appear to be superior to other methods of treatment, this conclusion is still premature."
As well as, and perhaps more strikingly after this one:
"The only study to directly address timing was by Shemesh et al (), who analyzed whether emergency sclerotherapy was more effective than stabilization and elective sclerotherapy ... Emergency therapy stopped all acute bleeding and resulted in decreased rebleeding in hospital (4.7% versus 17.1%, P=0.027) and by one year (7.0% versus 17.1%, P=0.027). There was an insignificant trend showing improved mortality in hospital and at one, three and five years after follow-up in the emergency sclerotherapy group."
The above was within their "can or should we wait" section. Aside from the casual mention of the ONLY study that EVER addressed emergency endoscopic intervention (scleropathy in the study) vs. stabilization and waiting, they also appear to believe that "band ligation may appear to be superior to other methods." This was clearly pointed out in their mention of a meta-analysis by Gross et al (Endoscopy. 2001 Sep; 33(9):737-46) showing banding more successful than pharmacologic treatment (without timing directly compared). 

Shockingly (phh), they have a small section of the review boasting combined pharmacologic and endoscopic therapy as improving mortality and "initial control of bleeding" (once again without specified timing). This was from a meta-analysis in Hepatology. (Hepatology. 2002 Mar; 35(3):609-15)

It appears their main reasoning for recommending delayed endoscopic therapy is the lack of evidence to the contrary at the moment. They point to various end-point, inclusion criterion, timing, and dosing differences amongst the studies they used. One study they use to demonstrate "no difference in bleeding or mortality" between emergent and delayed endoscopy firstly used scleropathy (which they deem inferior to ligation) and secondly although it had no statistically significant differences in end points it does have some trends that are notable. (Lancet. 1993 Sep 11; 342(8872):637-41)
Of note, scleropathy now has been almost entirely abandoned as "standard of care" as Villanueva et al demonstrate in this study from 2008.


What's new:

New literature appears to support our "gut" that waiting and watching these variceal bleeders decompensate in our ED is not ideal management:

(2012 Paper:) A prospective cohort study published in 2012 revealed statistically significantly differences in bleeding and mortality.  "In hematemesis patients, 6-week re-bleeding rate (18.9% vs. 38.9%, p=0.028) and mortality (27% vs. 52.8%, p=0.031) were lower in those with early (≤ 12 h) than delayed (>12h) endoscopy."

(2005 and 2010 Papers):  Consensus papers from the international expert "Baveno" consensus group which has standardized the methodology of studying variceal hemorrhage recommends performing endoscopy "as soon as possible."

Likely adding to the G.I. chatter in support of staying in bed:

(2009 Paper): Cheung et al conclude no clinical difference in bleeding or mortality in 4 vs. 8 vs 12 hour endoscopy. However, these were all hemodynamically stable bleeders. No patient with unstable hemodynamics was included.
Of note, this study is listed as being cited in 24 other peer reviewed articles. We always have to keep in mind the inclusion criteria. I think this study can essentially be written off, as the debate we are having is whether the sickest, most unstable (requiring crystalloid and blood resuscitation, and medications) should be getting emergent endoscopy.


Also interesting: 

The NNT review for Octreotide is pretty sobering as well. No mortality benefit from their perspective.


I believe that yes, this is still a controversy. Until a well done, multi-centered RCT is performed comparing apples and apples, with timing being the only variant, we may not ever have a solid answer. Until then, I think that there is plenty of good science as well as expert consensus recommending emergent, "as soon as possible" endoscopic therapy of acute variceal bleeders. I will continue to fight for this, for my patient in the ED exanguinating from above and below while awaiting midnight consultation.

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