Page 18 - Gastrointestinal Bleeding (Xuất huyết tiêu hóa)

292 PART III Symptoms, Signs, and Biopsychosocial Issues

Pharmacologic Therapy Whether a PPI should be given before or after EGD is uncer-
tain. Although some small randomized studies have not shown
Acid Suppression Medication that pre-endoscopy administration of a PPI improves clini-
In vitro studies have shown that a luminal gastric pH higher than cal outcomes (although the number of high-risk stigmata that
6.8 is required for normal clotting function (platelet aggregation require treatment is reduced), most modeling studies have sug-
and fibrin formation) and that a pH less than 5.4 almost abol- gested that pre-endoscopy administration of a PPI is cost-effec-
ishes platelet aggregation and plasma coagulation. 136 Platelet tive. 16,18,19,145,148 The optimal effective PPI dose after endoscopic
aggregates lyse at an acidic pH, an effect that is enhanced by the hemostasis is uncertain, with a meta-analysis finding no differ-
presence of pepsin; thus reducing the risk of acute bleeding and ence between high-dose IV continuous infusion of a PPI (80 mg
rebleeding from a peptic ulcer is theoretically possible by main- bolus followed by 8 mg/hr for 3 days) and nonhigh-dose intermit-
taining a gastric pH higher than 6. IV H2RAs can raise the intra- tent or oral administration (for 3 days). 150 Whether oral admin-
gastric pH acutely, but tolerance to these agents develops rapidly istration is as effective as IV administration of a PPI is unclear,
and the pH usually returns to 3 to 5 within 24 hours. Several although studies have shown that high-dose oral administration
studies have shown that in normal subjects, IV administration of a (e.g., omeprazole, 40 mg twice daily) reduces rebleeding to rates
PPI can consistently keep the gastric pH higher than 4 (and often that would be expected from endoscopic hemostasis. In fact, the
higher than 6) over a 72-hour infusion. 137,138 Trials of IV H2RAs increase in intragastric pH with high-dose oral PPI administra-
for the prevention of recurrent ulcer bleeding have shown no tion is almost identical (although delayed by 1 hour) to that with
definite benefit. 139,140 IV PPI administration. 141,151 Whether IV administration of a
Several studies have shown that PPIs are effective in reducing PPI alone is sufficient therapy (without endoscopic hemostasis)
rebleeding rates from peptic ulcer. In a study from India, patients in patients with recent UGI bleeding and some SRH, such as an
with endoscopic high-risk SRH (active bleeding, NBVV, clot, or NBVV, oozing, or clot, is controversial. In an Asian study, Sung
oozing) who did not undergo endoscopic hemostasis were ran- and colleagues reported that the 30-day rebleeding rate with IV
domized to omeprazole, 40 mg orally twice daily, or placebo. PPI administration alone (12%) was similar to that in previous
The rebleeding rate in the omeprazole-treated group was 11% studies of endoscopic hemostasis, although they also found that
compared with 36% in the placebo-treated group (P < 0.001). 141 the rebleeding rate with a combination of endoscopic therapy and
Another study from the same investigators showed that omepra- an IV PPI was even lower (1%). 152 Because almost all the major
zole, 40 mg orally twice daily for 5 days, decreased the rebleed- studies of PPIs in acute peptic ulcer bleeding have been con-
ing rate after endoscopic hemostasis with injection therapy for ducted in Asian populations, studies in non-Asian populations are
ulcers with active bleeding, an NBVV, or a clot from 21% in needed to confirm the Asian data. One large international study
the placebo-treated group to 7% in the oral omeprazole-treated has confirmed the benefit of high-dose IV PPI administration in
group (P = 0.02). 142 In a study from Hong Kong, patients who high-risk patients with active arterial bleeding, an NBVV, or an
had undergone successful endoscopic hemostasis for active bleed- adherent clot, but not oozing ulcer bleeding, in a predominantly
ing or an NBVV were randomized to high-dose IV omeprazole, white population. 135,153
80-mg bolus followed by 8 mg/hr or placebo. The 30-day rebleed-
ing rate was 6.7% in the omeprazole-treated group, compared Somatostatin and Octreotide
with 22.5% in the placebo-treated group (P < 0.05). 143 The same A meta-analysis has suggested that IV administration of soma-
investigators from Hong Kong found that the 30-day rebleeding tostatin or its long-acting form, octreotide, decreases the risk
rate in patients with an adherent clot or NBVV who received of rebleeding from peptic ulcers when compared with placebo
IV omeprazole alone was 12%, compared with 1% in those who or an H2RA. 154 The proposed mechanisms of action include a
received IV omeprazole and underwent endoscopic hemostasis reduction in splanchnic and gastroduodenal mucosal blood flow,
(P < 0.05). 144 Another study from Hong Kong found that start- a decrease in GI motility, inhibition of gastric acid secretion,
ing IV omeprazole before EGD in patients with UGI bleeding inhibition of pepsin secretion, and gastric mucosal cytoprotective
resulted in a decrease in the number of high-risk stigmata found effects. These drugs have not been studied, however, in the era of
and the need for endoscopic therapy, but no difference in clinical endoscopic or PPI therapy and, therefore, cannot be considered
outcomes such as the number of units transfused, frequency of for routine use. 155 Somatostatin or octreotide can be considered
recurrent bleeding, or rates of surgery and death. 145 in patients with severe ongoing bleeding who are not responsive
Systematic and Cochrane reviews of the clinical effective- to endoscopic therapy, an IV PPI, or both, and are not surgi-
ness and cost-effectiveness of PPIs in acute UGI bleeding by cal candidates, although their effectiveness in these patients is
Leontiadis and colleagues have found that PPI treatment initi- uncertain. IV octreotide may also be useful in patients with portal
ated after endoscopic diagnosis of peptic ulcer bleeding signifi- hypertension and peptic ulcer hemorrhage as an adjunct to endo-
cantly reduces the rates of rebleeding and surgery compared with scopic hemostasis and a PPI (see Chapter 92).
placebo or H2RAs and that the benefit is more pronounced in
Asian than in non-Asian populations. 146-148 PPI treatment was Second-Look Endoscopy
associated with decreased mortality in the Asian studies as well
as in patients with high-risk endoscopic stigmata. The initiation Routine repeat, or second-look, endoscopy 24 hours after initial
of PPI treatment prior to endoscopy significantly reduced the endoscopic hemostasis, with additional endoscopic hemostasis
proportion of patients with SRH at index endoscopy compared if persistent high-risk endoscopic stigmata are found, has been
with placebo or H2RAs but did not reduce the rate of mortality, proposed as a way to improve patient outcomes. A meta-analy-
rebleeding, or surgery. sis of 4 prospective randomized trials of patients with PUD and
Caution is advised in generalizing the results of PPI trials in high-risk endoscopic stigmata revealed that second-look endos-
Asian patients with peptic ulcer hemorrhage to heterogeneous copy reduced the rates of rebleeding and surgery but not mor-
non-Asian populations. Asian patients are generally more respon- tality; however, the only trial in which high-dose PPI therapy
sive than heterogeneous populations or whites to PPIs. 149 Asian was administered to patients showed no benefit to second-look
patients have a smaller average parietal cell mass, are slower endoscopy, and most trials did not use what has become standard-
metabolizers of PPIs, and often have Hp infection, all of which of-care endoscopic hemostasis techniques. 156 Therefore routine
increase the effectiveness of PPIs. These factors may explain the second-look endoscopy is not recommended for most patients
lower mortality rates in Asians compared with non-Asians in meta- with peptic ulcer bleeding, 114 except in those in whom the initial
analyses of trials of PPI therapy for peptic ulcer hemorrhage. endoscopic examination was suboptimal because excessive blood