For the Next Upper GI Bleed, Azithromycin?

Earlier this week, I was tasked with helping a teenager with an upper GI bleed.  I was surprised to learn that our hospital did not have IV erythromycin available due to a shortage.  A potential alternative is azithromycin.

The following is a 2017 ACG abstract (D Issa et al): A Comparison of Azithromycin to Erythromycin Infusions in Improving Visualization of Endoscopy for Upper Gastrointestinal Bleeding

Introduction: Several studies show the use of intravenous erythromycin prior to upper endoscopy for upper gastrointestinal bleeding (GIB) improves visualization and decreases the need for second look endoscopy. Erythromycin requires reconstitution delaying administration in emergency procedures. Azithromycin is more readily available as it is part of pneumonia treatment protocols and does not require reconstitution. Physiologic studies show azithromycin produces motility effects similar to that of erythromycin.

Aim: To assess the effect of azithromycin in improving the quality of endoscopic visualization in upper GIB compared to erythromycin.

Methods: We performed a retrospective analysis of patients admitted with acute upper GIB who underwent emergent endoscopy and were ordered either erythromycin or azithromycin before procedure. Primary outcome of the quality of visualization was assessed by two gastroenterologists, blinded to the choice of infusion, using a scoring system ranging from 0 to 8 with a maximum of 2 points assigned to each of the fundus, body, antrum and bulb. Secondary outcomes included time elapsed between administering the infusion and starting the procedure, length of hospital stay, blood transfusions, and procedure-related complications.

Results: The study included 31 patients in the erythromycin group and 18 patients in the azithromycin group. Mean age was 57 years and 68% were male. The overall median visualization score was significantly higher in the azithromycin group compared to that of the erythromycin group {7.0 (1.5) vs. 6.0 (3.0), respectively; P=0.02}. Time between administration of azithromycin and starting the procedure was longer than that of erythromycin but did not meet statistical significance (67 vs 48.5 minutes, respectively; P = 0.92). Length of hospital stay was comparable between the two groups after adjusting for the admission primary diagnosis (6.0 days for azithromycin vs. 7.0 days for erythromycin; P=0.48). Four patients were ordered erythromycin but this was not administered on time whereas all patient who were ordered azithromycin started the infusion prior to the procedure. Procedure immediate complications, need for second look endoscopy and number of transfused blood units did not differ between the groups.

Discussion: Azithromycin infusion before endoscopy for upper GIB was associated with better visualization than that of erythromycin, the current standard of care. Randomized trials are needed to validate these findings.

Here is a link to a summary from Gastro and Endoscopy News: Azithromycin Appears Worthy Stand-In For Erythromycin in Upper GI Bleeding

There have been prior publications showing that azithromycin, like erythromycin, has prokinetic properties: Broad J, Sanger GJ. The antibiotic azithromycin is a motilin receptor agonist in human stomach: comparison with erythromycinBr J Pharmacol. 2013 Apr;168(8):1859-67.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Learned Fear of Gastrointestinal Sensations Plus Two

Briefly noted: The authors of a recent study (E Ceunen et al. Clin Gastroenterol Hepatol 2016; 14: 1552-58) set out to study whether it is likely that healthy adults could learn to fear “innocuous visceral sensations.”  Fifty-two healthy subjects received  2 types of esophageal balloon distentions –one that was perceptible and non-painful and one that was painful.  Not surprisingly, when the researchers paired these two interventions in the experimental group, the experimental group learned to fear the innocuous stimulation as well as the painful distention.  This study provides theoretical support for one mechanism that could trigger ongoing functional gastrointestinal symptoms and a potential rationale for therapies, like cognitive behavioral therapy, which attempt to extinguish these symptoms.

In a retrospective study (AM Moon et al. Clin Gastroenterol 2016; 14: 1629-37) with 6451 patients with cirrhosis (mean age 60.6 yrs), the authors note that use of antibiotics during upper gastrointestinal bleeding (which is currently recommended) is associated with reduced mortality by ~30% at 30 days.  Despite its benefit, this intervention is often overlooked.  In the current study, only 48.6% of admissions received timely antibiotics; however, during the course of the study, the rate of antibiotic use improved from 30.6% in 2005 to 58.1% in 2013.

A recent retrospective study (N Goossens et al. Clin Gastroenterol 2016; 14: 1619-28) with 492 subjects showed that histologic NASH (in 12% of cohort) was associated with increased risk of death in patients who underwent bariatric surgery compared to patients without NASH.  Overall, bariatric surgery reduced the risk of death during the study period with HR of 0.54; the median follow-up was 10.2 years, with surgery taking place 1997-2004.  However, in patients with NASH the HR 0.90 which indicated that there was not a significant reduction in the risk of death.

Bar Harbor, ME (low tide)

Bar Harbor, ME (low tide)

Electronic Order Sets Can Improve Care

It is recognized that checklists can improve medical care as well as help you remember to pick up butter when you go shopping.  So, it is not surprising that a standardized electronic order set can improve patient care.  A recent prospective observational study has shown that implementation of an electronic order set improved the care of 123 patients with cirrhosis who presented with upper gastrointestinal hemorrhage (Clin Gastroenterol Hepatol 2013; 11: 1342-1348).

This study was conducted from 2011 to 2012.

Key findings:

  • Administration of antibiotics increased in patients in whom the order set was used: 100% compared with 89%. A previous Cochrane meta-analysis has noted a mortality risk reduction of nearly 20% in patients who received prophylactic antibiotics in this setting.
  • Order set usage was associated with quicker administration of antibiotics: 3h28min compared with 10h4min.
  • Time for octreotide administration was reduced in patients with the order set: 2h16min vs 6h21min.
  • Mortality was not reduced in this study by using an order set.  In fact, in those who used an order set there were 7 mortalities (out of 61) compared with only 2 mortalities (out of 62) who did not use order sets.

Order set use was at the discretion of the treating physician.  This could have led to selection bias.

Bottomline: Use of a standardized order set improved adherence and timeliness of recommended therapies.

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Endoscopy Module -Postgraduate Course Notes

Advances in Hemostasis for Upper GI Bleeding Brad Barth, MD, MPH  (page 77)

Upper GI Bleeding

Effect of IV PPI on patients with UGI bleeding PRIOR to EGD

  • 6 trials including 2223 patients
  • No significant difference in mortality, rebleeding or need for surgery compared to controls
  • DID significantly reduce rates of high risk stigmata identified on EGD
  • DID significantly decrease the need for endoscopic therapy
  • Reference: Sreedharan A, Martin J, Leontiadis G, et al. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database of Systematic Reviews 2010

 

Upper GI Bleeding – Proton Pump Inhibitors/Prokinetics

  • Omeprazole 1 mg/kg q 12 hours  (Solana, et al. J Pediatr 2013:162:776-82)
  • Proposed PPI drip dose: 1 mg/kg bolus followed by 0.1 mg/kg/hour infusion
  • IV erythromycin or metoclopramide; infuse 20-120 minutes prior to endoscopy in patients with acute UGIB; decreased need for repeat endoscopy to determine cause and site of bleeding. Prokinetic did NOT affect transfusion requirements, duration of stay, need for surgery. Reference: Barkun et al. Prokinetics in acute upper GI bleeding:a metaanalysis. GIE 2010;17:126-132

Upper GI Bleeding —Other points:

  • Epinephrine alone is RARELY enough
  • Non bleeding adherent clot has 8-35% chance of rebleeding in adults. Consider removing it CAREFULLY!
  • A conservative transfusion strategy is usually appropriate

Useful References

Surveillance Endoscopies: The established, the debated, and the unknown –Mitchell Shub, M.D. (page 85)

“Beware of false knowledge; it is more dangerous than ignorance.” —George Bernard Shaw

Familial Adenomatous Polyposis

Surveillance protocol: Age of initial evaluation/Type of procedure/Frequency

  • Colon 10 – 12 y of age (Sooner: family h/o aggressive disease) -Flex sig or Colonoscopy, 1 – 2 y
  • Upper GI tract 20 – 25 y or at initial colonoscopy
  • EGD and side viewing scope, 1 – 3 y
  • Post-colectomy (pouch) 6 – 12 mo. after surgery, Flex sig 1 y (6 mo. If retained rectum)
  • Small bowel: capsule or MRI, frequency unknown

Peutz-Jeghers Syndrome: begin screening at age 8 years or when symptomatic with colonoscopy, EGD, and small bowel imaging (?capsule vs alternatives); then every 2-3 years

Juvenile Polyposis Syndrome: begin screening at age 10-15 years or when symptomatic with colonoscopy, EGD, and  possibly small bowel imaging (?capsule vs alternatives); then every 1-3 years

Discussed guidelines for IBD cancer surveillance and for Barrett’s esophagus

  • For UC, start surveillance 8-10 years after diagnosis.
  • For Crohn’s with ~1/2 colon (or more) involvement, follow same guidelines
  • For coexisting PSC, annual surveillance
  • Barrett’s esophagus in children: adenocarcinoma very rare, evidence lacking to develop surveillance schedule

Expanding the view: Update on Upper GI StricturesMark A. Gilger, M.D. (page 95)

Why balloons for kids (for dilatation)?

You can see what you’re doing

  • Blind pouches
  • Abnormal mucosa
  • Caustic injury
  • Epidermolysis bullosa
  • Already requires general anesthesia
  • Ability to wire through narrow strictures
  • Ability to use radiographic assistance

Tip: Can use vegetable spray (eg. Pam) to make advancement of balloon catheter easy

How to do balloon dilation

  • Inflate balloon to ½ desired initial atmospheres & re‐check placement
  • Begin dilation at to 1‐2 mm more than initial estimated stricture diameter
  • Hold for 1 minute/dilation
  • •ove balloon catheter in and out during dilation;  if balloon moves freely, increase diameter by 1mm.  If stricture moves with the balloon, hold x 1 minute, then done
  • Oh, oh, there’s blood! Good! No blood, no dilation.
  • After dilation, carefully advance endoscope through the stricture; if resistance stop, can try cork‐screw maneuver
  • Document everything; especially stricture location (CM from incisors), dilation diameters (to help you next time)

Adjunct therapy for recalcitrant strictures  –adjunct therapy to sustain dilation needs further study

  • Oral & intravenous corticosteriods
  • Injectable corticosteroids – Thins the mucosa, OK 1‐2 times, but not repeated
  • Mitomycin C
  • Acid reduction
  • Stents

Endoscopy in the high‐risk patient: Keeping your patient safeJenifer R. Lightdale, MD, MPH (page 63)

Safety of Pediatric GI Procedures

  • Peds‐CORI data from >10,000 procedures
  • Overall rate of complications 2.3%: risk of hypoxia 1.5%; risk of bleeding 0.3%

Examples of pediatric populations at increased risk for perforation

  • History of caustic ingestion
  • Esophageal atresia/tracheo‐esophageal fistula
  • Severe duodenitis
  • Severe ulcerative colitis
  • Patients with multiple co‐morbidities (i.e. Type I diabetes, cerbrovascular disease, peripheral vascular disease, renal insufficiency, liver disease)
  • Ehlers‐Danlos Syndrome (Vascular Type)

Pre‐procedure Assessment –lends itself to a checklist 

Thrombocytopenia -Current recommendations

  • EGD ok if platelets >20,000/mL
  • Biopsies ok if platelets >50,000/mL

Bleeding –discussed high risk conditions

Decreasing Risk of Perforation:

  • Avoiding excessive pressure
  • Avoiding premature cutting of a polyp – Coagulate before cutting
  • Avoiding blind intubation of the lumen

Decreasing Risks of Infection

  • SBE Prophylaxis– generally NOT indicated in diagnostic procedures. Congenital heart disease is complex & may be needed on a case‐by‐case basis
  • Single‐dose cephalexin has been shown to decrease peristomal infection during PEG placement
  • Prophylactic antibiotics recommended for cirrhotic patients admitted with GI hemorrhage

Postgraduate Course Syllabus (posted with permission) with complete slides of above lectures: PG Syllabus

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and specific medical management interventions should be confirmed by prescribing physician.  Application of the information in a particular situation remains the professional responsibility of the practitioner.