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Non-variceal upper gastrointestinal haemorrhage
  1. I L P Beales
  1. School of Health Policy and Practice, University of East Anglia, Norwich, Norfolk NR4 7TJ, UK; i.beales{at}uea.ac.uk

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I enjoyed reading the guidelines on non-variceal upper gastrointestinal haemorrhage (Gut 2002;51(suppl 4):V1–6) and would like to congratulate the British Society of Gastroenterology (BSG) on their production, and hope they will form the basis for continued improvements in the management of this condition. However, several areas of the guidelines require further comment and exploration before they can be accepted as a national “gold standard” by which the management of non-variceal haemorrhage should be judged.

The guidelines give a grade A recommendation for the use of endoscopic therapy to treat adherent clots. This is despite failure of individual randomised controlled trials of endoscopic versus no endoscopic therapy to demonstrate a benefit in this subgroup.1–4 The guidelines indicate the rationale for recommending endoscopic therapy is a meta-analysis of trials5; this is an incorrect interpretation of those results. The quoted meta-analysis showed that endoscopic therapy was of significant benefit in patients with active bleeding or a visible vessel but not in patients with adherent clots or flat spots.5 If this analysis is the sole basis on which endoscopic therapy is recommended in this situation, it might be reasonable to reconsider the grade A status.

While the use of endoscopic therapy for adherent clots remains unproved, it may be beneficial in certain circumstances, but the widespread applicability remains to be determined. For instance, Jensen et al used a specific technique of adrenaline infiltration around the clot, followed by progressive guillotining through the clot with a snare without electrocautery, followed by bipolar cautery to the clot remnant or underlying stigmata (not the technique suggested in the BSG guidelines). In a randomised controlled trial against active medical therapy, this approach was significantly better at reducing rebleeding (0/15 v 6/17).6 However, the two groups were not particularly well matched, with more patients having their index bleed while already an inpatient being enrolled in the medical arm, possibly tipping the benefit towards the endoscopic therapy arm. The rebleeding rate in the treatment arm was zero, which is rather lower than that seen in most other trials of endoscopic therapy and even one single rebleed in the endoscopic arm would have abolished the statistical significance of the result.

Difficulties in deciding on a treatment policy may also arise following different approaches to removal of the adherent clot. The rebleeding rate probably depends on the definition of adherence, and a clot that withstands prolonged forcible attempts at washing is likely to carry a different risk from one seen still to be adherent after only a couple of squirts with a syringe. Laine et al used irrigation of adherent clots for five minutes with a bipolar probe, and adherent clot remained in 57% of cases. The rebleeding rate in this group was only 8%.7 Endoscopic therapy has not been shown to be effective in this subgroup of tightly adherent clots. Thus the approach to adherent clots is not as clear and unequivocal as implied in the BSG guidelines and further discussion of the recommendations on the use of washing and specific endoscopic therapies should be considered.

The guidelines also strongly endorse the use of high dose continuous intravenous proton pump inhibitor (PPI) therapy after endoscopic therapy. This opinion has clearly been swayed by the trial from Hong Kong by Lau and colleagues.8 While the design and outcomes of this exemplary work are not in question, it would be wise to consider the applicability to a UK population before widely endorsing the extra costs involved in the wholesale adoption of this therapy. The omeprazole treated group were younger than those treated in the UK for acute non-variceal bleeding and had significantly lower numbers of patients taking non-steroidal anti-inflammatory drugs (NSAIDs) (32.5% v 68%) and with important comorbidity (25% v 60%).9 In addition, there are pharmacokinetic and pharmacodynamic issues that suggest there might be a difference in responses between this trial group and a standard UK bleeding population. Asians and Orientals have a lower parietal cell mass than Europeans10 and PPI therapy would be expected to be more effective. Omeprazole is predominantly metabolised and inactivated by cytochrome P450 2C19 (CYP2C19). The activity of this enzyme is genetically determined and those with low activity variants (poor metabolisers) have a fivefold increased exposure to omeprazole and consequently significantly greater acid inhibition compared with wild-type variants (extensive metabolisers). Poor metabolisers are uncommon in Northwest European White populations (3%) but much more common in Orientals (up to 23%).11–13 Thus the impressive results may not directly translate to a major benefit in the UK.

Perhaps the most convincing argument for avoiding blanket use of high dose PPI was provided by Udd et al’s randomised controlled study of omeprazole 20 mg once daily compared with the endorsed high dose continuous regimen. Sample size was comparable with that of Lau et al and powered to detect equivalence. The study enrolled Europeans with apparently similar demographics to UK patients (57% on NSAIDs, comorbidity in 74–79%). Rates of rebleeding, surgery, and mortality were equivalent in the two treatment groups.14

The publication and dissemination of the BSG guidelines should enhance practice but it is important that all of the recommendations are not accepted and implemented uncritically and further discussion and refinement are encouraged.

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