Introduction
Acute lower gastrointestinal bleeding (LGIB) has an estimated incidence of 33/100 000
but is associated with greater resource use than upper GI bleeding [1]. The management of LGIB involves determining the source of bleeding in order to
direct the most appropriate intervention to achieve hemostasis. There are multiple
choices of intervention, including flexible sigmoidoscopy, colonoscopy, computed tomographic
angiography (CTA), mesenteric angiography, and nuclear scintigraphy. The diagnostic
and subsequent therapeutic yields are unclear and are likely to be influenced by multiple
patient factors [2]
[3] and the timing of intervention [4]. There is little evidence in the literature informing the optimal use of these interventions;
hence, the development of recommendations in guidelines is limited [5].
As well as diagnosis, endoscopy offers endotherapy, including adrenaline injection,
thermocoagulation or clipping. Extravasation of contrast on CTA or mesenteric angiography
may identify bleeding that is amenable to embolization. Compared with colonoscopy,
CTA is better tolerated by patients but may identify a source only where there is
active bleeding [6]. Delays between CTA and angiography may lead to a blush on CTA becoming nonapparent
on a subsequent mesenteric angiogram [7].
Given uncertainties around the optimum initial approach to investigation and management,
we conducted a systematic review of the diagnostic and therapeutic yields of flexible
sigmoidoscopy, colonoscopy, CTA, and mesenteric angiography for LGIB. This takes the
form of several direct head-to-head comparisons between modalities, each of which
is reported separately, aiming to mirror the clinical questions encountered by clinicians
involved in the acute management of LGIB.
Patients and methods
This review was registered on the PROSPERO register of systematic reviews (CRD42016025100)
and conducted in accordance with the preferred reporting items for systematic review
and meta-analysis (PRISMA) statement [8] and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) group [9].
Search strategy
We searched MEDLINE, PubMed, EMBASE, CDSR, CENTRAL, DARE, HTA, NHSEED, ClinicalTrials.gov,
and the WHO International Clinical Trials Registry Platform for articles published
between 1 January 2000 and 12 November 2015 without language restrictions (see Appendix 1 for search strategy). The search was limited to publications since 2000 owing to
the more recent adoption of CTA and therapeutic endoscopy, reflective of modern day
practice.
Study eligibility
Eligible studies were randomized controlled trials (RCTs) and cohort studies (nonrandomized
studies of intervention [NRSIs]). As there is variation in the reporting quality of
NRSIs, those with a cohort design without methodological concordance were screened
to ascertain whether they met the criteria to be categorized as a cohort study as
described by Dekkers et al. [10].
Adults hospitalized with acute LGIB of any cause were eligible. Studies of upper GI
bleeding or pediatric populations were ineligible. LGIB was defined as “the onset
of hematochezia originating from either the colon or the rectum” [5]. This can manifest as red or maroon blood, or melena [11]. As the focus of this review was the immediate investigation and treatment of LGIB,
studies of patients who had completed first-line investigations (colonoscopy, esophagogastroduodenoscopy,
and radiological studies) without a proven source of bleeding, such as those with
obscure GI bleeding [12], were excluded.
Interventions included flexible sigmoidoscopy, colonoscopy, CTA, mesenteric angiography,
therapeutic endoscopy, and mesenteric embolization. Comparisons were grouped into
three themes: choice of investigation, timing of investigation, and choice of treatment.
Choice of investigation comparisons comprised: flexible sigmoidoscopy vs. CTA, colonoscopy
vs. CTA, colonoscopy/flexible sigmoidoscopy vs. other (e. g. standard care), CTA vs.
other. Timing of investigation comprised early vs. late flexible sigmoidoscopy, colonoscopy,
CTA, and mesenteric angiography in relation to presentation with bleeding. To maximize
study eligibility we did not pre-specify “early” and “late.” Choice of treatment comprised
endoscopic hemostasis vs. embolization, endoscopic hemostasis vs. other (e. g. surgery),
and embolization vs. other. Specific types of endoscopic therapy were also compared.
Where applicable, subgroups populated by hemodynamic status were also compared.
Outcomes
Primary outcomes were diagnostic and therapeutic yields. Therapeutic yield was defined
as the proportion of participants that received hemostatic therapy, either during
or after the intervention. Secondary outcomes were rebleeding, red blood cell transfusion,
length of hospital stay, mortality, and complications related to the intervention.
Two reviewers screened studies and extracted data independently. Study screening and
data extraction were performed using Covidence Systematic Review Software (Veritas
Heath Innovation Ltd., Melbourne, Australia).
Risk of bias in RCTs and NRSIs was assessed using the Cochrane risk of bias tool [13] and the Newcastle-Ottawa Scale [14], respectively.
Statistical analysis
Continuous outcomes were compared using mean difference and 95 % confidence intervals
(CIs). Dichotomous outcomes were analyzed using risk ratio (RR) and 95 %CI for RCTs,
and odds ratio (OR) and 95 %CI for NRSIs. Where the number of observed events was
small, Peto OR and 95 %CI were used.
RCTs and NRSIs were analyzed separately [13]. NRSIs were deemed comparable if they had a Newcastle-Ottawa score ≥ 8 [15]. Meta-analysis was conducted to calculate pooled RR, OR or mean difference, and
95 %CI for each comparator. Statistical heterogeneity was analyzed using I
2 statistics, and values > 50 % were considered to be significantly heterogeneous [16]. We used random effects modeling for all NRSIs and presented OR regardless of heterogeneity.
No tests for funnel plot asymmetry were undertaken, as the number of studies in each
comparison was fewer than 10 [13]. Meta-analysis was undertaken using Review Manager 5.3 (Cochrane Collaboration,
Copenhagen, Denmark).
Results
Searches identified 5879 potentially eligible references and 40 from 2410 prescreened
records ([Fig. 1]). On full-text review, 507 studies were excluded (reasons shown in [Fig. 1]) leaving 2 RCTs, 13 NRSIs, and 2 ongoing studies, including 6 conference abstracts
[17]
[18]
[19]
[20]
[21]
[22].
Fig. 1 PRISMA flow chart. UGIB, upper gastrointestinal bleeding.
Characteristics of reviewed studies
There was a lack of data across all interventions and comparators, notably no RCTs
or NRSIs comparing embolization with endoscopic hemostasis. There were no studies
that included flexible sigmoidoscopy as a comparator. Comparisons between colonoscopy
and CTA were limited to nonrandomized data ([Table 1]). A total of 10 studies compared different interventions and five examined different
timings of the same intervention. Case definitions of LGIB are included in Appendix 2. A total of 11 studies included patients with LGIB of any cause [4]
[18]
[19]
[20]
[23]
[24]
[25]
[26]
[27]
[28]
[29] and four were limited to patients with diverticular bleeding [17]
[21]
[22]
[30]. The number of participants enrolled in each study ranged from 72 to 100 in the
RCTs, and from 27 to 326 in the NRSIs.
Table 1
Summary of evidence by comparison investigated and study methodology.
Comparator
|
RCTs [ref]
|
NRSIs [ref]
|
Ongoing trials
|
Choice of investigation
|
Flexible sigmoidoscopy vs. CTA
|
None
|
None
|
|
Flexible sigmoidoscopy vs. other
|
None
|
None
|
|
Colonoscopy vs. CTA
|
None
|
Nagata 2015 [26]
Yabutani 2014 [21]
|
|
Colonoscopy vs. other (e. g. standard care)
|
Green 2005 [4]
|
Yamaguchi 2006 [23]
|
|
CTA vs. other
|
None
|
Ketwaroo 2012 [18]
Sun 2011 [20]
Jacovides 2015 [25]
|
|
Diagnostic mesenteric angiography vs. other
|
None
|
None
|
|
Timing of first-line investigation
|
Colonoscopy: Early (< 24 hours) vs. late (> 24 hours)
|
Laine 2010
|
Abeldawi 2014 [24]
Nagata 2016 [27]
Strate 2003 [28]
Rodriguez-Moranta 2007 [19]
|
|
Radiology: A) Urgent CTA vs. nonurgent B) Urgent mesenteric angiography vs. nonurgent
|
None None
|
None None
|
|
Choice of treatment
|
Therapeutic endoscopy vs. mesenteric embolization
|
None
|
None
|
|
Therapeutic endoscopy vs. other
|
None
|
Jensen 2000 [30]
|
Matsuhashi JPRN-UMIN000008287
|
Embolization vs. other
|
None
|
None
|
|
Endoscopic agent A vs. B
|
None
|
Nakano 2015 [22]
Ishii 2011 [17]
|
Barkun NCT02135627
|
RCT, randomized controlled trials; NRSI, nonrandomized studies of intervention; CTA,
computed tomographic angiography.
Most studies were conducted in older patients and, where reported, anticoagulant,
nonsteroidal anti-inflammatory drugs, and particularly antiplatelet use was common.
Only four studies reported baseline hemodynamic status [4]
[26]
[27]
[29].
Choice of investigation
Colonoscopy vs. CTA
No RCTs compared colonoscopy with CTA. The two eligible NRSIs were retrospective,
one comparing early colonoscopy and CTA (within 24 hours of admission) with early
colonoscopy alone in 223 participants [26], and one comparing early colonoscopy with CTA (timings not defined) in a single
cohort of 57 patients with diverticular bleeding who underwent both tests [21].
The was no difference in the diagnostic yield of CTA combined with colonoscopy vs.
colonoscopy alone (OR 1.31, 95 %CI 0.26 to 6.63), although the diagnosis of lesions
with active bleeding, adherent clot or visible vessels was higher in the CTA group
(OR 2.14, 95 %CI 1.16 to 3.95, 223 participants) [26]. Patients in this group subsequently received more endoscopic hemostatic treatment
(OR 3.47, 95 %CI 1.74 to 6.91), but there was no difference in terms of rebleeding
(OR 1.08, 95 %CI 0.51 to 2.28) or the number of participants receiving transfusion
(OR 1.71, 95 %CI 0.86 to 3.39). Mortality, length of hospital stay, and complications
were not reported. The study by Yabutani et al. [21] described only diagnostic yield, demonstrating no difference between CTA and colonoscopy
(OR 1.36, 95 %CI 0.63 to 2.95, 57 participants).
Colonoscopy vs. other
We identified one RCT [4] that randomized 100 patients to colonoscopy within 8 hours or standard care (red
cell scanning, angiography or elective colonoscopy). The diagnostic yield was higher
in the group randomized to urgent colonoscopy (RR 1.91, 95 %CI 1.03 to 3.53), but
there was no difference in therapeutic yield (endoscopic hemostasis or vasopressin
infusion at angiography: RR 1.7, 95 %CI 0.87 to 3.34) or rebleeding (RR 0.73, 95 %CI
0.37 to 1.44), although volume of transfusion was smaller in the urgent colonoscopy
group (mean difference – 0.8 units, 95 %CI – 0.62 to – 0.98). We identified one NRSI
[23]: a study of 111 participants who underwent ultrasound followed by colonoscopy. The
diagnostic yield of colonoscopy was superior to that of ultrasound (OR 3.78, 95 %CI
2.07 to 6.91).
CTA vs. other
No RCTs were identified. The three eligible NRSIs all compared CTA with nuclear scintigraphy;
two retrospective cohort studies of 92 – 99 participants [18]
[20], and one before and after study of a protocol that prioritized CTA over nuclear
scintigraphy in 161 participants [25]. Ketwaroo et al. [18] demonstrated a higher diagnostic yield with the use of CTA (OR 4.03, 95 %CI 1.67
to 9.72, 92 participants) but the study by Sun et al. [20] reported no difference between modalities (OR 0.49, 95 %CI 0.20 to 1.21, 99 participants).
Neither study reported therapeutic yield for both study arms or any of the secondary
outcomes. The protocol study by Jacovides et al. [25] demonstrated no difference in diagnostic yield (OR 0.85, 95 %CI 0.33 to 2.19), therapeutic
yield (defined as embolization during first mesenteric angiography, OR 1.10, 95 %CI
0.55 to 2.20) or length of hospital stay (mean difference 3 days, 95 %CI – 16.58 to
22.58).
Diagnostic mesenteric angiography vs. other
We found no studies that included mesenteric angiography as a first-line intervention.
Timing of first-line investigation
Colonoscopy
One RCT [29], one prospective [19], and three retrospective NRSIs [24]
[27]
[28] compared early and late colonoscopy. The RCT by Laine et al. included 72 patients.
The NRSI ranged from 57 to 326 participants. Early colonoscopy was defined as within
12 hours by one study [29] and within 24 hours by three studies [19]
[24]
[27]. One study subdivided cohorts into consecutive 12 hours groups [28]. For the purpose of this comparison, early colonoscopy is defined as that performed
within 24 hours of admission.
When assessing diagnostic yield, three studies categorized diverticula [27]
[28]
[29] or hemorrhoids [28]
[29] as a definite (based on the presence of active bleeding or stigmata of recent hemorrhage)
or presumptive (presence of diverticulosis or hemorrhoids without bleeding in absence
of other potential bleeding sources) cause of bleeding. Rodriguez-Moranta et al. [19] reported only definite diagnoses, but did not define these, and Albeldawi et al.
[24] did not define diagnosis.
When presumptive and definite diagnoses are included in diagnostic yield, no difference
was observed between early vs. late colonoscopy in the RCT (RR 1.17, 95 %CI 0.87 to
1.56) or pooled analysis of the NRSIs (OR 0.68, 95 %CI 0.31 to 1.49, 3 studies, 527
participants, I
2 = 9 %, [Fig. 2]). When diagnostic yield was limited to definite diagnoses, early colonoscopy was
associated with a higher diagnostic yield in the NRSIs (OR 1.86, 95 %CI 1.21 to 2.86,
3 studies, 527 participants I
2 = 42 %, [Fig. 2]), although this was not significant in the RCT (RR 1.12, 95 %CI 0.70 to 1.78).
Fig. 2 Forest plot of comparison of nonrandomized studies of intervention. Upper: Presumptive
plus definite diagnoses. Lower: Definite diagnoses only. Definitive diagnoses were
defined by the presence of stigmata of recent hemorrhage or active bleeding, plus
the diagnosis of an underlying cause. CI, confidence interval; M-H, Mantel-Haenszel.
All studies defined therapeutic yield as the number of participants receiving endoscopic
therapy. All employed endoscopic hemostasis with a minimum of three available modalities
(clipping, banding, thermocoagulation, argon plasma coagulation, adrenaline injection),
the specific type depending on pathology and endoscopist preference. The therapeutic
yield was superior in the early colonoscopy group in the pooled analysis of the NRSIs
(OR 3.08, 95 %CI 1.93 to 4.90, 4 studies, 707 participants I
2 = 7 %, [Fig. 3a]), but no different in the RCT (RR 1.0, 95 %CI 0.36 to 2.81).
Fig. 3 Forest of plot of comparison of nonrandomized studies of intervention. a Therapeutic yield. b Length of hospital stay. CI, confidence interval; M-H, Mantel-Haenszel.
Rebleeding was reported in the RCT [29] and two NRSIs [24]
[27], but all varied in their definition ([Table 2]) so were not pooled. There was no difference in rebleeding between early and late
colonoscopy in the RCT (RR 1.6, 95 %CI 0.58 to 4.43, 72 participants), or the NRSIs
(Nagata et al. OR 1.96, 95 %CI 0.94 to 4.11, 326 participants, and Albeldawi et al.
OR 0.7, 95 %CI 0.2 to 2.44, 57 participants).
Table 2
Interstudy variability of the definition of rebleeding.
Study [ref]
|
Definition of rebleeding
|
Green 2005 [4]
|
Hematochezia (defined as any one of > 3 bloody bowel movements in < 8 hours, ICU admission,
> 5 % decrease in Hct in < 12 hours, transfusion of > 3 units RBC, hemodynamic instability
in previous 6 hours defined as angina, syncope, pre-syncope, orthostatic vital signs,
MAP < 80 mmHg or HR > 110) after clinical cessation of the index bleeding event
|
Laine 2010 [29]
|
Hematochezia persisting for > 24 hours, recurrent hematochezia after initial resolution
(e. g. brown stool followed by hematochezia), HR > 100 or SBP < 100 mmHg after hemodynamic
stability for ≥ 1 hour, or hemoglobin drop > 2 g/dL after stable hemoglobin values ≥ 3
hours apart
|
Nagata 2016 [27]
|
Significant amounts of fresh bloody or wine-colored stools after index colonoscopy
with unstable vital signs; SBP ≤ 90 mmHg or HR ≥ 110 or the need for blood transfusion
|
Strate 2003 [28]
|
Blood per rectum after 24 hours of stability accompanied by a drop in Hct ≥ 20 %,
and/or a requirement of additional blood transfusions
|
Abeldawi 2014 [24]
|
After clinical cessation of index bleeding event during hospitalization
|
Nagata 2015 [26]
|
Significant fresh bloody or wine-colored stool accompanied by unstable vital signs;
SBP ≤ 90 mmHg or HR ≥ 110 and nonresponse to ≥ 2 units transfused blood
|
Jensen 2000 [30]
|
Self-limited or recurrent hematochezia that required no more than an additional 2
units of packed red cells or continued or recurrent hematochezia that required at
least 3 units of packed red cells
|
Ishii 2011 [17]
|
Clinical evidence of recurrent bleeding
|
ICU, intensive care unit; Hct, hematocrit; RBC, red blood cells; MAP, mean arterial
pressure; HR, heart rate; SBP, systolic blood pressure.
Transfusion was reported in the RCT [29] and one NRSI [27]; patients in the early group of the RCT received more transfusions (mean difference
0.8 units, 95 %CI 0.65 to 0.95, 72 participants), but in the NRSI there was no difference
in the number of participants receiving transfusion (OR 1.00, 95 %CI 0.62 to 1.63,
326 participants).
Mean length of hospital stay was reported in three studies [19]
[27]
[29]. Early colonoscopy was associated with a shorter hospital stay in NRSIs (mean difference
2.64 days, 95 %CI 1.54 to 3.73, two studies, 506 participants, I
2 = 0 %) and in the RCT (mean difference 0.40 days, 95 %CI 0.06 to 0.74, 72 participants)
([Fig. 3b]).
Adverse events were reported in two studies [27]
[29]. Laine et al. [29] reported one perforation in the late colonoscopy group (RR 0.33, 95 %CI 0.01 to
7.92). Nagata et al. [27] reported no major colonoscopy-related adverse events in either cohort. Mortality
was reported in two studies [24]
[29]. There were no deaths in the study by Albeldawi et al. [24], but there were two deaths in the urgent colonoscopy arm in the RCT by Laine et
al. (RR 5.00, 95 %CI 0.25 to 1.00). One patient developed a fatal intracranial hemorrhage,
and the other required prolonged hospitalization due to medical co-morbidities and
died after a cardiorespiratory arrest.
CTA and mesenteric angiography
We found no studies comparing early vs. late CTA or mesenteric angiography.
Choice of treatment
Therapeutic endoscopy vs. mesenteric embolization
We found no studies.
Therapeutic endoscopy vs. other
One NRSI compared endoscopic therapy (adrenaline injection or thermocoagulation) with
a historical control comprising conservative or surgical treatment in patients with
diverticular bleeding [30]. Patients who received endoscopic treatment were less likely to require surgery
for bleeding (Peto OR 0.14, 95 %CI 0.02 to 0.88, 27 participants), rebleed (Peto OR
0.10, 95 %CI 0.02 to 0.51) or receive a transfusion (Peto OR 0.10, 95 %CI 0.02 to
0.51). We identified one ongoing RCT comparing endoscopic therapy with barium impaction
for diverticular bleeding (Matsuhashi et al, JPRN-UMIN000008287).
Mode of endoscopic hemostasis
No RCTs were identified. Two retrospective NRSIs were identified, both comparing endoscopic
band ligation with endoclipping in diverticular bleeding [17]
[22]. The primary outcome in both studies was re-bleeding; Ishii et al. [17] reported 60-day rates of 1/16 (6.2 %) for endoscopic band ligation and 16/48 (33.3 %)
for endoclipping, although this was not significantly different (OR 7.50, 95 %CI 0.91
to 61.94, 64 participants). In the endoclipping group, seven patients required radiological
control of bleeding vs. none in the endoscopic band ligation group; however, this
was not significant (Peto OR 4.37, 95 %CI 0.72 to 26.37). Nakano et al. [22] followed patients for 2 years and also found that large numbers of patients re-bled
in each group (endoscopic band ligation 24/50, 48.0 %; endoclipping 18/39, 46.2 %),
although there was no difference between the two modalities (OR 0.93 95 %CI 0.40 to
2.15, 89 participants). Need for further procedure was not reported. No patient experienced
complications related to endoscopy in either study.
We identified one ongoing RCT comparing TC-325 (Hemospray) monotherapy at endoscopy
with standard endoscopic therapy in patients with upper GI bleeding or LGIB due to
malignancy (Barkun et al., NCT02135627).
Hemodynamic status
We identified no RCTs, NRSIs or ongoing trials that compared flexible sigmoidoscopy,
colonoscopy, CTA or mesenteric angiography in groups stratified by hemodynamic status.
Assessment of methodological quality
Both RCTs were deemed at high or unclear risk of bias due to blinding ([Table 3]). Laine et al. stated that their trial was not blinded. Green et al. also stated
that the physicians caring for the patients were not blinded and gave no detail on
blinding of outcome assessors. The nature of the interventions used in these studies
makes blinding difficult. For subjective outcomes such as diagnostic yield this may
introduce significant bias.
Table 3
Assessment of methodological quality (Cochrane risk of bias for RCTs, Newcastle-Ottawa
for NRSIs).
RCT [ref]
|
Sequence generation
|
Allocation concealment
|
Blinding of participants and personnel
|
Blinding of outcome assessors
|
Incomplete outcome data
|
Selective outcome reporting
|
Other
|
Green 2005 [4]
|
Low
|
Unclear
|
High
|
Unclear
|
Low
|
Unclear
|
Low
|
Laine 2010 [29]
|
Low
|
Low
|
High
|
High
|
Low
|
Low
|
High
|
NRSI [ref]
|
Representativeness (1)
|
Selection of non-exposed (1)
|
Ascertainment of exposure (1)
|
Outcome of interest not present at start of study (1)
|
Comparability (2)
|
Assessment of outcome (1)
|
Follow-up long enough and adequate (2)
|
Adeldawi 2014 [24]
|
1
|
1
|
1
|
1
|
1/0
|
1
|
1/1
|
Ishii 2011 [17]
|
0
|
1
|
1
|
1
|
0/0
|
1
|
1/1
|
Jacovides 2015 [25]
|
1
|
1
|
1
|
0
|
0/1
|
1
|
1/1
|
Jensen 2000 [30]
|
0
|
1
|
1
|
1
|
0/0
|
1
|
1/1
|
Nagata 2016 [27]
|
1
|
1
|
1
|
1
|
1/1
|
1
|
1/1
|
Nagata 2015 [26]
|
1
|
1
|
1
|
1
|
1/0
|
1
|
1/1
|
Nakano 2015 [22]
|
0
|
1
|
1
|
1
|
0/0
|
1
|
1/0
|
Sun 2011 [20]
|
0
|
0
|
1
|
1
|
0/0
|
1
|
1/1
|
Yabutani 2014 [21]
|
0
|
1
|
1
|
0
|
1/1
|
1
|
1/1
|
Yamaguchi 2006 [23]
|
1
|
1
|
1
|
1
|
1/1
|
1
|
1/1
|
Ketwaroo 2012 [18]
|
0
|
0
|
1
|
1
|
0/0
|
1
|
1/1
|
Strate 2003 [28]
|
1
|
1
|
1
|
1
|
1/1
|
1
|
1/1
|
Rodriguez-Moranta 2007 [19]
|
1
|
1
|
1
|
1
|
1/1
|
1
|
1/1
|
Rebleeding may also be subject to bias due to lack of blinding. Additionally, there
was considerable interstudy variation in the definition of rebleeding in the eight
studies that reported this outcome ([Table 2]). Most studies used a definition that included a period of clinical stability [4]
[28]
[29], although some did not define the criteria that would need to be met to establish
a new bleeding event [17]
[24]. Three studies characterized rebleeding by the persistence of ongoing signs of bleeding
without a period of stability [26]
[27]
[30], but these definitions may have also captured patients with failed hemostatic intervention,
rather than true rebleeding.
One study did not define rebleeding [22].
The study by Laine et al. was subject to “other” source of bias, as it was terminated
early because the hospital changed its protocol on allowing colonoscopy in the emergency
room, although the reasons for this were not given.
Risk of bias in the NRSIs was assessed using the Newcastle-Ottawa scale. The two most
common areas of poor performance in the NRSIs were selection of participants, particularly
representativeness of the exposed, and comparability of cohorts. Six studies scored
poorly for representativeness of LGIB as they studied a single pathology [17]
[21]
[22]
[30] or a single intervention that was related to severity of bleeding [18]
[20]. This limits interstudy comparability and the generalizability of these results
to the LGIB population as a whole.
Three studies did not include data on whether they adjusted for confounders [17]
[18]
[20], one study provided no data on confounders and also populated one treatment arm
using an intervention that is likely to be related to severity of bleeding (endoscopic
hemostasis) [30], and one study compared baseline demographics for each group, but did not include
cardiovascular parameters or baseline transfusion requirements [22]. There are likely to be significant baseline imbalances between the cohorts in these
studies. None were deemed of sufficient quality to permit data synthesis.
Discussion
There is considerable uncertainty regarding the optimal management of LGIB [5]. This is a comprehensive review encompassing all of the major diagnostic and treatment
modalities for LGIB, and demonstrating a lack of evidence across the majority of interventions.
The area with the most evidence is timing of colonoscopy, with meta-analysis suggesting
higher diagnostic yields, rates of hemostasis, and a reduction in the length of hospital
stay with early colonoscopy.
Colonoscopy has been recommended as the first-line diagnostic procedure for LGIB [5], but questions remain regarding its timing and suitability for all patients.
We found that the use of CTA with colonoscopy may enhance the identification of bleeding
lesions when compared with colonoscopy alone. Although this did translate into increased
use of hemostatic therapy, there was no or minimal impact upon clinically important
outcomes such as rebleeding or transfusion. CTA is often reserved for unstable patients
that do not respond to resuscitation [5], but we found no studies comparing it with other interventions in exclusively shocked
patients.
Although colonoscopy performed within 24 hours of admission was associated with higher
rates of diagnosis, hemostasis, and a reduction in length of hospital stay, there
was no evidence that it had any impact upon death or rebleeding. Paradoxically, there
was higher red blood cell transfusion in the early colonoscopy arm of the RCT, although
this may represent baseline imbalances between arms, as the initial hemoglobin was
also lower in the early arm [29]. Most of the studies on timing of colonoscopy were nonrandomized, and conducted
in patients who were subsequently diagnosed with diverticular bleeding, limiting the
generalizability of these findings. Timing of colonoscopy has been the focus of three
recent systematic reviews. Kouanda et al. and Seth et al. included RCTs and cohort
studies, but differed in their classification of several large database studies that
we rejected as case series, or restricted their search to English language studies
[31]
[32]. Nonetheless, the authors reported similar findings: there was no difference in
rates of rebleeding, death or transfusion. In contrast to the present review, Seth
et al. reported that there was no difference in therapeutic yield or hospital stay
with early colonoscopy. For therapeutic yield, the authors did not include data from
Albeldawi et al. in the meta-analysis, but the reasons for this are not clear. For
length of hospital stay, the authors pooled estimates from RCTs with NRSIs, which
may account for the different findings from the current review. Sengupta et al. used
a similar study classification system to that used in the present review, and also
pooled estimates from RCTs and NRSIs, but also reported no difference in clinical
outcomes with early colonoscopy [15].
The use of colonoscopy in real-life practice is variable. In a recent nationwide audit
of 143 hospitals in the UK, colonoscopy was performed in only 4 % patients with LGIB,
with a median waiting time of 4 days (range 2 – 8) [33]. As there were no major barriers identified to the routine availability of colonoscopy,
this is likely to reflect uncertainty regarding its utility in the acute setting.
In contrast to upper GI bleeding, colonoscopy in the acute setting can be challenging
to perform, requires rapid bowel preparation, and may be poorly tolerated by the patient.
Only two studies reported complications, but overall early colonoscopy appeared to
be safe. In one RCT, two patients who received urgent colonoscopy died [29]. Although neither was attributed to the intervention, the potential to cause harm
in patients with extensive co-morbidities should not be underestimated.
The impact of early colonoscopy on hospital stay has clear benefits. A microcosting
analysis of upper GI bleeding admissions reported an average cost of £ 2458 per patient,
most of which was due to the cost of the hospital bed [34]. Not all patients with LGIB will require urgent investigation, however. In the UK,
48 % of admitted patients have a benign course and require no inpatient investigation
[33]. The most frequent outpatient investigation is lower GI endoscopy, 70 % of which
is scheduled to be performed more than 2 weeks post-discharge [33]. The value of such delayed intervention requires further research.
Outcomes other than length of hospital stay must also be considered. Rebleeding following
endoscopic hemostasis was reported in 6 % – 48 % patients in the cohort studies [17]
[22]
[27], raising questions regarding the efficacy of endoscopic hemostasis. This is important
given the absence of evidence comparing it with other treatment options, notably embolization.
The two studies comparing modes of endoscopic hemostasis were limited to patients
with diverticular bleeding. Considering that bleeding stops spontaneously in over
80 % of patients [35], this may not be the group that will derive the most benefit.
There are important questions regarding the value of colonoscopy in LGIB beyond diagnosis.
Most therapeutic techniques originate in the upper GI tract and may be unsuitable
for lesions in the colon and rectum. Endotherapy relies on the identification of stigmata
of recent hemorrhage to localize and treat the bleeding source, but this can be subjective,
as demonstrated by the differing diagnostic yields between lesions that were defined
as a presumptive vs. a definitive source. This is particularly relevant to diverticular
bleeding, the most common cause of LGIB in the UK [33]. It can be difficult to identify the culprit diverticula, and treatment of one will
not guarantee prevention of bleeding from another. Evaluation of the current management
of LGIB is limited by the lack of baseline data for comparison: national observational
studies have only been conducted since 2000 [1]
[33]
[36], and there are currently no national guidelines on the management of LGIB in the
UK. It is therefore not possible to compare current management with historical practice
and to establish whether newer interventions such as CTA have made an impact.
There are several limitations to this review. Most evidence originates from NRSIs,
with significant bias, which limits the strength of the conclusions that can be drawn
from the review. More randomized data, particularly on the timing of colonoscopy,
are urgently required, especially in view of the recent publication of risk scores
focussing on increasing the outpatient management of LGIB [37]. Systematic review of NRSIs is limited by the variable description of study methodology,
making their classification difficult. This is evidenced by the different studies
that are included in reviews of the same topic with similar inclusion criteria [15]
[31]
[32]. A new study comparing CTA with colonoscopy was published [38] after the searches for the current review were completed in 2015, and the results
may be relevant to this topic and warrant an update of the present review in the future.
We limited the search to studies published since 2000, as before this date routine
use of endotherapy and embolization were in their infancy, and studies were mostly
limited to case reports and safety studies. Relevant studies published prior to this
period may have been missed therefore.
In summary, although there was a paucity of high-quality evidence across most interventions,
we found that colonoscopy within 24 hours had higher diagnostic and therapeutic yields,
and a shorter hospital stay. The value of colonoscopy after hospital discharge requires
further appraisal, in addition to further research into the identification of patients
who will gain the greatest benefit from early colonoscopy. Additional areas of research
should focus on the clinical outcomes of endoscopic hemostasis, particularly comparisons
with mesenteric embolization.
Appendix 1: Search strategy
Appendix 1: Search strategy
The following databases were searched for systematic reviews, RCTs and observational
(cohort) studies, from 2000 onwards, on 12.11.15:
MEDLINE (OvidSP, 1946 onwards)
PubMed (epublications only)
Embase (OvidSP, 1974 onwards)
CDSR, CENTRAL, DARE, HTA & NHSEED (The Cochrane Library 2015, Issue 3)
Transfusion Evidence Library
Ongoing Trials:
ClinicalTrials.gov 159 refs
WHO International Clinical Trials Registry Platform: 36 refs
N.B. The Data Providers of the ICTRP Search Portal currently are:
Australian New Zealand Clinical Trials Registry (ANZCTR)
Brazilian Clinical Trials Registry (ReBec)
Chinese Clinical Trial Register (ChiCTR)
Clinical Research Information Service (CRiS), Republic of Korea
ClinicalTrials.gov
Clinical Trials Registry – India (CTRI)
Cuban Public Registry of Clinical Trials (RPCEC)
EU Clinical Trials Register (EU-CTR)
German Clinical Trials Register (DRKS)
Iranian Registry of Clinical Trials (IRCT)
ISRCTN.org
Japan Primary Registries Network (JPRN)
Pan African Clinical Trial Registry (PACTR)
Sri Lanka Clinical Trials Registry (SLCTR)
The Netherlands National Trial Register (NTR)
Searches retrieved 10,667 references plus 195 ongoing trials, which were reduced to
8,260 refs plus 87 ongoing trials when duplicates had been removed.
SEARCH STRATEGIES
MEDLINE (OvidSP)
-
exp Lower Gastrointestinal Tract/
-
exp Intestines/
-
Gastrointestinal Tract/
-
exp Mesenteric Arteries/
-
(lower gastrointestinal tract* or lower gastro-intestinal tract* or lower GI tract*
or large intestin* or small intestin* or mesenteric arter*).tw,kf.
-
or/1 – 5
-
(h?emorrhag* or bleed* or re-bleed* or rebleed* or blood loss*).mp.
-
6 and 7
-
exp Gastrointestinal Hemorrhage/
-
((anal or anus or rectum or rectal or colon or colonic or colorectal or cecum or caecum
or jejunum or cloaca or gut or ileum or diverticula* or lower intestin* or large intestin*
or small intestin* or bowel or lower gastrointestinal or lower gastro-intestinal or
lower GI or mesenteric) adj6 (h?emorrhag* or bleed* or re-bleed* or rebleed* or blood
loss*)).tw,kf.
-
(hematochezia or mel?ena or colonic angiodysplasia or proctorrhagi* or rectocolic*
or rectorrhagi*).tw,kf.
-
or/8 – 11
-
exp Colonoscopy/
-
Proctoscopy/
-
(colonoscop* or coloscop* or sigmoidoscop* or proctoscop* or rectoscop* or enteroscop*
or anuscop*).tw,kf.
-
Endoscopy, Gastrointestinal/
-
Capsule Endoscopy/
-
(endoscop* adj3 (capsule or video or lower or mesenteric or colon* or bowel)).tw,kf.
-
pillcam.tw,kf.
-
or/13 – 19
-
Colonography, Computed Tomographic/
-
((CT or computed or tomograph* or virtual) adj2 (colonograph* or colonoscop* or pneumocolon*)).tw,kf.
-
Tomography, X-Ray Computed/
-
Radiology, Interventional/
-
(tomograph* angiogra* or CTA or CT angiogra* or mesenteric angiogra* or GI angiogra*
or (radiolog* adj2 (diagnos* or intervention*))).tw,kf.
-
Angiography/
-
or/21 – 26
-
Hemostasis, Endoscopic/
-
((therap* or treatment* or h?emosta* or epinephrine or adrenaline or cyanoacrylate
or inject* or band* or electrocauter* or argon plasma or thermal coagulat* or thermocoagulat*
or thermo-coagulat* or heater probe* or argon coagulat* or laser coagulat* or YAG
laser or ablat* or h?emoclip* or h?emospray or sclerotherap*) adj10 endoscop*).tw,kf.
-
(endotherap* or endoclip* or over-the-scope clip*).tw,kf.
-
20 or 28 or 29 or 30
-
Embolization, Therapeutic/
-
(emboli?ation or emboli?ed or embolotherap* or angioemboli* or microemoboli*).tw,kf.
-
27 or 32 or 33
-
12 and (31 or 34)
-
limit 35 to yr = "2000 -Current"
EMBASE (OvidSP)
-
exp Large Intestine/
-
exp Small Intestine/
-
exp Anus/
-
exp Mesenteric Artery/
-
Intestine/
-
Gastrointestinal Tract/
-
(lower gastrointestinal tract* or lower gastro-intestinal tract* or lower GI tract*
or large intestin* or small intestin* or mesenteric arter*).tw.
-
1 or 2 or 4 or 5 or 6 or 7
-
(h?emorrhag* or bleed* or re-bleed* or rebleed*or blood loss*).mp.
-
Bleeding/
-
9 or 10
-
8 and 11
-
Gastrointestinal Hemorrhage/ or Colon Hemorrhage/ or Hemorrhagic Colitis/ or Intestinal
Bleeding/ or Intestine Hematoma/ or Large Intestine Hemorrhage/ or Melena/ or Rectum
Hemorrhage/ or Small Intestine Hemorrhage/
-
((anal or anus or rectum or rectal or colon or colonic or colorectal or cecum or caecum
or jejunum or cloaca or gut or ileum or diverticula* or lower intestin* or large intestin*
or small intestin* or bowel or lower gastrointestinal or lower gastro-intestinal or
lower GI or mesenteric) adj6 (h?emorrhag* or bleed* or re-bleed* or rebleed* or blood
loss*)).tw.
-
(hematochezia or mel?ena or colonic angiodysplasia or proctorrhagi* or rectocolic*
or rectorrhagi*).tw.
-
or/12 – 15
-
Intestine Endoscopy/ or Capsule Endoscopy/ or Colonoscopy/ or Push Enteroscopy/ or
Rectoscopy/ or Sigmoidoscopy/
-
Gastrointestinal Endoscopy/
-
(colonoscop* or coloscop* or sigmoidoscop* or proctoscop* or rectoscop* or enteroscop*
or anuscop* or pillcam*).tw.
-
(endoscop* adj3 (capsule or video or lower or mesenteric or colon* or bowel)).tw.
-
or/17 – 20
-
*Endoscopy/ and *Hemostasis/
-
((therap* or treatment* or h?emosta* or epinephrine or adrenaline or cyanoacrylate
or inject* or banded or banding or electrocauter* or argon plasma or thermal coagulat*
or thermocoagulat* or thermo-coagulat* or heater probe* or argon coagulat* or laser
coagulat* or YAG laser or ablat* or h?emoclip* or h?emospray or sclerotherap*) adj10
endoscop*).tw.
-
(endotherap* or endoclip* or over-the-scope clip*).tw.
-
or/21 – 24
-
Computed Tomographic Colonography/
-
((CT or computed or tomograph* or virtual) adj2 (colonograph* or colonoscop* or pneumocolon*)).tw.
-
Computer Assisted Tomography/
-
Interventional Radiology/
-
(tomograph* angiogra* or CTA or CT angiogra* or mesenteric angiogra* or GI angiogra*
or (radiolog* adj2 (diagnos* or intervention*))).tw.
-
Abdominal Angiography/ or Superior Mesenteric Angiography/
-
Pelvic Angiography/
-
or/26 – 32
-
Artificial Embolism/
-
(emboli?ation or emboli?ed or embolotherap* or angioemboli* or microemoboli*).tw.
-
or/33 – 35
-
16 and (25 or 36)
PubMed (epublications only)
#1 (lower gastrointestinal tract* OR lower gastro-intestinal tract* OR lower GI tract*
OR large intestin* OR small intestin* OR mesenteric arter*) AND (hemorrhag* OR haemorrhag*
OR bleed* OR re-bleed* OR rebleed* OR blood loss*)
#2 ((anal OR anus OR rectum OR rectal OR colon OR colonic OR colorectal OR cecum OR
caecum OR jejunum OR cloaca OR gut OR ileum OR diverticula* OR lower intestin* OR
large intestin* OR small intestin* OR bowel OR lower gastrointestinal OR lower gastro-intestinal
OR lower GI OR mesenteric) AND (hemorrhag* OR haemorrhage* OR bleed* OR re-bleed*
OR rebleed* OR blood loss*))
#3 (hematochezia OR melena OR melaena OR colonic angiodysplasia OR proctorrhagi* OR
rectocolic* OR rectorrhagi*)
#4 #1 OR #2 OR #3
#5 (colonoscop* OR coloscop* OR sigmoidoscop* OR proctoscop* OR rectoscop* OR anuscop*
OR pillcam OR endotherap* OR endoclip* OR over-the-scope clip*)
#6 ((capsule OR video OR lower OR mesenteric OR colon OR colonic OR bowel OR hemosta*
OR haemostat* OR epinephrine OR adrenaline OR cyanoacrylate OR inject* OR banded OR
banding OR electrocauter* OR argon plasma OR thermal coagulat* OR thermocoagulat*
OR thermo-coagulat* OR heater probe* OR argon coagulat* OR laser coagulat* OR YAG
laser OR ablat* OR hemoclip* OR hemospray OR sclerotherap*) AND endoscop*)
#7 #5 OR #6
#8 ((CT OR computed OR tomograph* OR virtual) AND (colonograph* OR colonoscop* OR
pneumocolon*))
#9 (tomograph* angiogra* OR CTA OR CT angiogra* OR mesenteric angiogra* OR GI angiogra*
OR (radiolog* AND (diagnos* OR intervention*)))
#10 (embolization OR embolized OR embolization OR embolised OR embolotherap* OR angioemboli*
OR microemoboli*)
#11 #8 OR #9 OR #10
#12 #4 and (#7 OR #11)
#13 ((random* OR blind* OR "control group" OR placebo* OR controlled OR cohort* OR
nonrandom* OR observational OR retrospective* OR prospective* OR comparative OR comparator
OR groups OR trial* OR "systematic review" OR "meta-analysis" OR metaanalysis OR "literature
search" OR medline OR cochrane OR embase) AND (publisher[sb] OR inprocess[sb] OR pubmednotmedline[sb]))
#14 #12 and #13
TRANSFUSION EVIDENCE LIBRARY
Clinical Specialty: Gastrointestinal Disorders
Subject Area: Red Cells
ClinicalTrials.gov
Conditions/Search Terms: GI bleeding OR lower gastrointestinal hemorrhage OR colorectal
bleeding OR colonic bleeding OR intestinal bleeding OR rectal bleeding OR mesenteric
bleeding OR hematochezia OR melena OR bowel bleeding OR diverticular bleeding
Interventions: endoscopy OR colonoscopy OR CT OR tomography OR proctoscopy OR endoclip
OR colonography OR angiography OR embolization OR capsule OR pillcam
ICTRP
Conditions/Search Terms: GI bleeding OR lower gastrointestinal hemorrhage OR colorectal
bleeding OR colonic bleeding OR intestinal bleeding OR rectal bleeding OR mesenteric
bleeding OR hematochezia OR melena OR bowel bleeding OR diverticular bleeding
Interventions: endoscopy OR colonoscopy OR CT OR tomography OR proctoscopy OR endoclip
OR colonography OR angiography OR embolization OR capsule OR pillcam
Results
Relevant references: 5850
Possibly irrelevant references: 2410 (contain one or more of the following words in
the title: upper (not lower), abdominal aortic aneurysm, cancer, malignan*, carcinoma*,
esophageal, duodenal, hepatic, cirrho*, stomach, liver, transplant*, varice*, pancreat*)
These have been screened by one reviewer (KO) and identified 40 possible relevant
references. These have been added to the ‘relevant references’ for full screening
by two reviewers.
Appendix 2: Study characteristics
Appendix 2: Study characteristics
Study (Country) [ref]
|
Design
|
Study years
|
Study population
|
Interventions
|
Participants, n
|
Age, mean ± SD, years
|
Shock[*], n (%)
|
Medications on admission, n (%)
|
Anticoagulants
|
Antiplatelets
|
NSAIDs
|
Green 2005 (USA) [4]
|
RCT
|
1993 – 1995
|
Patients admitted with hematochezia with clinical or laboratory evidence of significant
blood loss
|
Colonoscopy < 8 hours after admission
|
50
|
68 ± 3
|
30 (60.0)
|
NR
|
NR
|
29 (60.0)
|
Standard care: red cell scan if ongoing bleeding, colonoscopy
|
50
|
71 ± 4
|
34 (68.0)
|
NR
|
NR
|
26 (52.0)
|
Laine 2010 (USA) [29]
|
RCT
|
2002 – 2008
|
Patients admitted with hematochezia with a high-risk feature*
|
Colonoscopy < 12 hours after admission
|
36
|
52 ± 3
|
27 (75.0)
|
NR
|
NR
|
NR
|
Colonoscopy 36 – 60 hours after admission
|
36
|
52 ± 2
|
31 (86.1)
|
NR
|
NR
|
NR
|
Albeldawi 2014 (USA) [24]
|
Retrospective cohort
|
2011 – 2012
|
All acute LGIB
|
Colonoscopy < 24 hours after admission
|
24
|
66.8 ± 13.8
|
NR
|
2 (8.3)
|
13 (54.2)
|
2 (8.3)
|
Colonoscopy > 24 hours after admission
|
33
|
69.3 ± 11.1
|
NR
|
7 (21.2)
|
19 (57.6)
|
3 (9.1)
|
Ishii 2011 (Japan) [17]
|
Retrospective cohort
|
2004 – 2010 2009 – 2010
|
Patients with colonic diverticular hemorrhage
|
EBL
|
16
|
NR
|
NR
|
NR
|
NR
|
NR
|
Endoclipping
|
48
|
NR
|
NR
|
NR
|
NR
|
NR
|
Jacovides 2015 (USA) [25]
|
Historical control
|
2005 – 2012
|
All patients hospitalized with LGIB
|
Historical protocol: red cell scan, CTA or colonoscopy
|
78
|
68 ± 15
|
NR
|
NR
|
NR
|
NR
|
New protocol: CTA, colonoscopy
|
83
|
70 ± 15
|
NR
|
NR
|
NR
|
NR
|
Jensen 2000 (USA) [30]
|
Historical control
|
1986 – 1992 and 1994 – 1998
|
Patients with hematochezia and diverticulosis
|
Medical and surgical intervention
|
17
|
66 ± 3
|
NR
|
NR
|
NR
|
3
|
Medical and endoscopic therapy
|
10
|
67 ± 4
|
NR
|
NR
|
NR
|
3
|
Nagata 2016 (Japan) [27]
|
Retrospective cohort
|
2009 – 2014
|
All patients admitted with acute overt LGIB
|
Colonoscopy < 24 hours after admission
|
163
|
67.9 ± 17.4
|
17 (10.4)
|
9 (5.5)
|
63 (38.7)
|
23 (14.1)
|
Colonoscopy > 24 hours after admission
|
163
|
66.4 ± 16.9
|
19 (11.7)
|
6 (11.7)
|
54 (33.1)
|
20 (12.3)
|
Nagata 2015 (Japan) [26]
|
Retrospective Cohort
|
2008 – 2013
|
Patients admitted with LGIB who underwent colonoscopy
|
Urgent CTA then colonoscopy
|
126
|
68.3 ± 16.5
|
5 (4.0)
|
7 (5.6)
|
55 (43.7)
|
33
|
Colonoscopy < 24 hours after admission
|
97
|
67.7 ± 16.5
|
1 (1.0)
|
4 (4.1)
|
36 (37.1)
|
13 (13.4)
|
Nakano 2015 (Japan) [22]
|
Retrospective cohort
|
2004 – 2014
|
Patients undergoing endoscopic therapy for colonic diverticular hemorrhage
|
EBL
|
50
|
67 ± 13
|
NR
|
NR
|
15
|
4
|
Endoclipping
|
39
|
64 ± 13
|
NR
|
NR
|
13
|
3
|
Sun 2011 (USA) [20]
|
Retrospective cohort
|
2007 – 2008 and 2008 – 2010
|
All patients hospitalized with acute GI bleeding
|
CTA
|
53
|
NR
|
NR
|
NR
|
NR
|
NR
|
Red cell scan
|
46
|
NR
|
NR
|
NR
|
NR
|
NR
|
Yabutani 2014 (Japan) [21]
|
Single retrospective cohort
|
2010 – 2012
|
Patients diagnosed with diverticular bleeding
|
CTA and colonoscopy
|
57
|
NR
|
NR
|
NR
|
NR
|
NR
|
Yamaguchi 2006 (Japan) [23]
|
Single retrospective cohort
|
1999 – 2004
|
Consecutive patients with hematochezia
|
Ultrasound and colonoscopy
|
111
|
58 (range 18 – 96)
|
NR
|
NR
|
NR
|
NR
|
Ketwaroo 2012 (USA) [18]
|
Retrospective cohort
|
2010 – 2011
|
Suspected acute LGIB
|
CTA
|
46
|
68.2 ± 17
|
NR
|
NR
|
NR
|
NR
|
Red cell scan
|
46
|
70 ± 15
|
NR
|
NR
|
NR
|
NR
|
Strate 2003 (USA) [28]
|
Retrospective cohort – subgroup
|
1996 – 1999
|
All patients admitted with ICD-9 codes representing LGIB, or a wide range of diagnoses
associated with LGIB
|
Colonoscopy < 24 hours after admission
|
69
|
NR
|
NR
|
NR
|
NR
|
NR
|
Colonoscopy > 24 hours after admission
|
75
|
NR
|
NR
|
NR
|
NR
|
NR
|
Rodriguez- Moranta 2007 (Spain) 19]
|
Prospective cohort
|
2005 – 2006
|
Consecutive patients admitted with LGIB
|
Colonoscopy < 24 hours after admission
|
92
|
NR
|
NR
|
NR
|
NR
|
NR
|
Colonoscopy > 24 hours after admission
|
88
|
NR
|
NR
|
NR
|
NR
|
NR
|
CTA, computed tomographic angiography; EBL, endoscopic band ligation; GI, gastrointestinal;
ICD, International Classification of Diseases; LGIB, lower gastrointestinal bleeding;
NR, not reported; NSAID, nonsteroidal anti-inflammatory drug; RCT, randomized controlled
trial
* High risk features defined as heart rate > 100, systolic blood pressure < 100 mmHg,
orthostatic changes in systolic blood pressure > 20 mmHg or in heart rate > 20 beats/min,
blood transfusion, or drop in hemoglobin ≥ 1.5 g/dL within a 6-hour period.
Acknowledgment
James East was supported by the National Institute for Health Research (NIHR) Oxford
Biomedical Research Centre (BRC). The views expressed are those of the author(s) and
not necessarily those of the NHS, the NIHR or the Department of Health.