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ACUTE STRESS GASTRITIS:
EVOLUTION IN AN INTENSIVE CARE UNIT
by
John R. KEYSERLINGK, MD
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A thesis submitted to the Faculty of Graduate Studies . and Res~arch in partial fUlfiU,lment of the
requirements for the degree of Master of Science
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Department of Experimental Surgery, Royal Victoria Hospital and McGill University,
Montréal, Québec, Canada
Project Supervisor - Harry S. Himal, Mp
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August, L978
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-' John R. KeyserÜngk M.Sc. Experimental Medicine
ACUTE STRESS GASTRITIS
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Tb Mireille and Dominique
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ABgTRACT .~ )
acut~ gastr~~ ll}ucosal 'c'ha~s' have ' '-.
X wide variety of
been reported ln the acutély ill patient. In an at~empt to 1
gain information cpncerning. the incidence, severity and
evolution of these changes, 20'critically il1 patients in
an Intensive Care.Unit underwept 2 successi~e detailed
esophago-gastro-duodenoscopies., An endoscopy seoring 'syst~m 1
was developed to aid in corftI:'p.r ing the endoscopie find ing'l?
Early endoscopie evaluation revealed the presence of
gastric mucosal changes compatible ,with 'acute stress gastriti~ 6
in each of the 20 patients studied. The sevèrity of these
, changes was most propounced in ,the trauma patients. There
was a rapid and significant improvement in the overall mean ~
endoscopie score by day 5 to "J post acute in jury . Worseni~g.
of this score was a~sociated with persistent sepsis.
Efficient management <;tnd close monitoring of these patients
is postulàted as being the major cause leading to the ràpïd
clearing of acute stress gastritis and for thé appar~nt
decreas'€- in its clin'ical expression: acute hemorrhagic • 1
stress gastritis. '
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ont été rapporté...es chez
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a~ions mucosales aignes
'ent m~lade de façon aigue. ,
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Dans le but de gagner
dence, la sé"ér~ et
d'i formation concernant 'l'inci-. '\~
l'évolution delle,es changements, 20
malades aigus, dans ane unité de soi~s intensifs, ,ont subi
2 oesophagd-gastro-duodénoscopies d~ta~llées successive~ . . , , . , Un système de pointage endoscopique a'"été d~velopp~ dans le ,
but de mieux comparer les· trouvailles endoscopiques •
. L', éVÇll uation endoséopiqUè précoce a révélé la présènce .
de changements de la muqueuse cQmpatibles avec une gastrite .
aigue de stIess chez chacun des 20 ~atients étudiés. Les
changements les plus sévères étaient chez les patients
traumatiques. ,Il Y avait une·amélioratiop rapide et signifi
cative dans le pointage endoscopique moyen de 5 ~ 7 jours
après l'insulte initiale. Le traitement efficac~ et une sur-, 7
veillance' très étroite 'de ces patients sont considérps comme
étan~ les causes. majeures dont découle l'amélioration rapide \.
de la gastrite ,aigue de s~.ress ainsi que la diminution
apparente de son ~xpression clinique: hemorrhagie de gastrite
aigue de stress.
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First of aH, l would like to ext?ress my gratitude to
my project supervisor, Dr. FI.S. Himal, who offered me the
opportunity to help s~t up a project that would prove to be
extremely stimulating and beneficial tû me in many respects. ~ 1
The possibility Of working on a clinical study concerning
intensive Care Management was particularly attractive, this
being a field of special interest to me. He painstakingly
"passed on" to me, in true professional style, the art of
endoscopy. His constant enthusiasrn and encouragement were
much appreciated as was his supervision and verification of
both the protocol and thesis . . l would also like to extend special tha~ks to
Dr. Robert Elie for his invaluable advice and teaching
con'cerning methodology. and statistics.
TO, the nurses of the Surgical Intensive Care Unit of
the Royal Victoria H~spital, and in particular to Ms. Mary ,
Lee MacNeil, the endoscopy,unit nurse, go my sincere thanks
for their constant cooperation and support.
l am most grateful to the librarians of both the Royal
victoria Ho'Spltal and the McGill Medical Libniry for their
assistance in providing the necessary literature. Special
thanks are extended to Miss Lucille Lavigeur of St. Mary 1 s
Medical Library for her help anq advice.
l would like to thank also Mr. Robert Laporte of
Olyrnpus Co. for furnishing us with.important.technical
assistance and advice, Mr. Ronald Handfield of CFCF television
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for lending us the necessary cinernatographic equipm~nt and
also Mr. Hugh Sheppard of Smith Kline and French for
providing us witH Cimetidine.
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Finàl~y, sincere thanks ta Mrs. Chris Bundesen for her
excellent work in typing and correcting the text .
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TABLE OF CONTENTS
ABSTRACT
ACKNOWLEDGMENTS
TABLE OF CONTENTS
LIST OF FIGURES A~D TABLES
CHAPTER l INTRODUCTION ~
CHAPTER 2 REVIEW OF THE LITERATURE ,/
2.1 Historical Notes
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3 , 2.2 Terminology 8
2.3 Inciden,ce of acute stress gas"tritis 9
2.4 Pathogenesis 24
2.4.1 Alteration of effective mucosal 25 perfusion
2.4.2 Alteration of gastric mucosal 26
2.4.3
function
Intraluminal factors: bile
CHAPTER 3 MATERIALS'AND METHODS
3.1
3.2
3.~ ,
·3.4
3.5
3.6
3.7
Clinical Material
Factors Studied
.Endoscopy
Endoscopy~Technique
Endoscopie Scoring
Cimetidine Proto col
Statistical Analysis
CHAP TER 4 RESULTS
4.1 Initial Endoscopy Results . \
acid and
4.'2' Evolution of' ~ndosco~~\ Findings",
4.2.1 Total sàmple
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, 4.2.2 Trauma versus. non-trauma
4.2.3 Severi ty o~ trauma
4.2.4 Site of trauma
4.2.5 Colon in jury versus non-colon in jury
4.2.6 Number of prime factors
4.3 Cimetidine
CHAPTER 5 DISCUSSION
CHAPTER 6 CONCLUSION
REFERENCES
TABLES AND FIGURES
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60
60
61
61
62
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64
82
83
103
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Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
'Figure 9
Figure 10
Figure II
Figure 12
, Figure 13
Table 1
- Table 2
Table 3
~/ Table 4 .'
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"Table 6
f'ablé 7 if,
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LIST Or FIGURES AND TABLES
Section of an acute stress uloer showing active infl~ation
Pathophysiology of acute stress gastritis n
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Intrace11ular processes in the formation of hydrochloric acid
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Schema of gastric mucosal,barrier '" 106
Pathophysio1ogy following gastric 107 mucosa1 breakdown
Photomicrogrqph of normal gastric mucosa 108
Photomicrograph of altered su,rface 109 epithe1ial ce1ls
Gastroscopie appearance of mucosal 110 pallor and mottling (early acute stress gastritis) .
Gastroscopic appearance of an acute III focal mU,cosal hemorrhag:e
" 'Gastroscopic appearance of an acute mucosa1 erosion
Gastroscopic appearance of an acute mucosal ulceration
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113
Evolution of erîdoscopy score in SICU 114 samp1e
Spontaneous -regress ion 'of endoscopy 126 score in ~on-Cimetidine group
Summary of clinical qamp1e 115
Sununary of prime ,fictors and endoscopic 116 f indings
Criteria for prime factors 118
Characteri"stics of samp1e - . 119
pr ime factors and mean endoscopy, score 120 - ,
Evolution "of mean endoscopy sc'ore 121 1
Relationship .between 'evolution of 122 endoscopy. score and severity of trauma
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Table 8
Table 9
Table 10
Table 11
Table 12
Table 13
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Trauma group endoscopy 0
saore - in 123 relation to site of trauma
C Evolution of mean endoscopy score in 124 non trauma patients wi th and wl.i. thout colon resection
1 Evolution of endoscopy score in relation 124 to colon in jury
Relation bétween endoscopy score and 125 number of prime factors
Effect of Cimetidine on evolution of 126 endoscopy score in trauma patients
Summary of septic patiénts 127
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CHAPTER l INTRODUCTION
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CHAPTER l INTR0I;>UC'flON
The suddeh on-set of massive gastr·ic bleeding in an '
already severely ill pat~ènt is always a dramatic event.
Considered as one of the cascading steps in the sequential
multiple systems failure often seen in the critically ill •
patient, acute gastric mucosal breakdown and hemorrhage has
attracted much attention during the laIt decades.
Using the most recent principles of Surgical Intensive
Care Unit management, patients who might have otherwise
succumbed early to ,their precipitating illness are now given
the ?pportunity to survive one system failure after another.
Having successfully controlled and/or corrected a trauma
patient's hypovolemic shock, respiratory and renal failureo
and sepsis, the treating surgeon's frustration in the face
of an ill-tolerated acute gastric hemorrhage is weIl
understood. f
l , Why shçuld such a patient, with no previous indication
of gastric gisease, suddenly develop a life threatening
gastric hernorrhage? How does the gastric mucosa react to
severe rernote in jury? What is the. incidence of these changes?
Who is at greateat risk? , etc. These and many other questions
concerning this tascinating phenomenon re~ain only partially t '
answ~red and have stimulated this thesis.
Just as with many other complex system failures, there
is no concens,:\s as to the exact nature and pathophYS,iology
of acute gastric hernorrhage. This is'reflected by the wide ,~
variety of terms used to describe the changes, ranging from
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"stress ulcer syndrome" to "acute hemorrhagic qastritis".
~he purpose of the first half of this thesis i5 ta attempt
to minimize the ~pparent confusion and gain sorne unified
concepts concerning this enti ty. Th~'erIn "acute stress ~
gastri~is" is proposed.
The actual study, b&sed on seriaI prospective endo
scopie findings in a 4Ple of severely ill patients, will"
" attempt
compare
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these findi4gs
of the above-stated questiops and
with those of earlier reports.
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CHAPTER 2 REVIEW OF THE LITERATURE
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CHAPTER·2 REVIEW OF THE LITERATURE
2.1 HISTORICAL NOTES
The gastric mucosa's potential to undergo a wide variety
of~acute changes was weIl establ,isl;1ed by the late l8th 1
century. Descript.ions 'of t'hese changes ranged from fo,ca1
hemorrhages and superficial localized erosions as ~~scribed
by Morgagni in "De Alvi Prof1uvius agitur Incruentis & .. 1 ?
Cruentis'" written in 1761 (1), to tot'àl dissolution of the
gastric mucosa, termed "gastric ma1acia" by John Hunter in (2) -~
1772 . ' The latter, after having observed the·erosion of ~'-:
a dead man's~st~mach, supposedthe proaess to have started
~ ~~ing life as a result of disease. Unable to relate it to
any-of the patient's known disorders, he prpposed that the
stomach, part1ially deprived of its
no longer resist the residual f~ow
principle of a d~namic equi1ibrium
"living prirtciple", \
of gast~ic juices.
between ~struct1ve and
protective elements of the stomach is still pertinent to the -/. "
pathogEmesis ,'of acutf 's,tress ~astriti~o t~ this date.
The 19th centur~ witnessed'an increasing number of
reports., mostly anecdotal and simple observations, describing 1 •
gastric rnucosal' lesions'4nexpectèd1y noted in patient.s
p dying of diseaseS that did ~~t seern to have(any
r~lationship ~ith the gastriè mucosal changes.' In 1816 "
Treille, according to w~ngensteen(3), reported the
of multiple gastric erosions in' soldiers who had died'from
septic wdunds but, understandably, no direct 1ink
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e between tne erosions a~d r the sepsis. Baron Guillaume r' •
Dup ytren(4) preceGed' c}r~ing by 10 years when, in 183?,
in his· Ç1i!~c,al 'lectures o~ surgery, the
devel' pment of acute gastriè and duodenal lesions following . ,
cutane us ~hermal ipjurYl' Curling(5), however, prese~ting rJ :\
10 case of duodenal ulce~ation and hemorrhage in p~eviously i -
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hea1 thy urn patlen~s" postu,lated the "exit>tence "of .~, • '" ' "\ir
connection between injury to the skin and the disease 'of :·the -
up'per,i~stro-intestina1 tr_act". He was the first to descr.ibe ....
the' ulceration as a bgmplication of burns. Burned patients
were thus the first grou~o be associated with acute
gastro-intestinal lesions. In 1855, ROkitansky(6) describ~d
acute gastro-intestinal ùlceration 'in conjunction with
intracranial disease. ae suggested that tnese acute les iOns t.", '
were 'possibly due to "diseased innervation of tl1e st9m~ch,
Owing to a morbid condition of the vagus, and to extreme
.acidification of the ga:stric juicè". Cushing 1 s c1assic
paper P ), dea1ing with the sarne relationship, did not appear
unt'il 1932. He present'ed 9 pati'ents with acute ulceration
involving the esophagu~ in 4, the stomach in 6 and the
duodenum in '1.. He under1ined the possible importance~f
bil~ and a~1d in the pathogenes~~ of these lesions as weIl
as the irritation of the parasy.mpath~tic syst~ (possibly .'
from vaga1 re1ease due to syrnpathetic paralysis), which
was capab1è on causing contractions and hence ischemia,"
, Increasing ~wareness of the susceptibi1ity of the ,
gastro-duodena~ mucosa to operative trauma ,and stress
associated diseases was gain~d as the nurnber of reports
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describing this phenomenon increased~ ---~Itî" 1867, Billroth (8) , . /
reporte~.the first case of postoperative gastro-duodenal
'ulaeration ip a 42 Yea.r old man who"becatne septic after an
,~successful attempt tp ~em~ve a substerna1
Parrot (9) in 1875 and Di~~~afo~(lO) ~n 1910
widespread acute gastro-intestinal n~crosis
goitre. Both
d~scribed
and .. u1ceration,
the former in an Il month 'old 'infant who had die~ of '
bronchopneumonia and the latter'in patienbs who had died . p l lD~ , r~
of pneutnonia, strangulated hernia and' appendicitis '('~toxi-• j
.0 infectious processes"). Parrot used the term "gal?trite
catarrhale pseudomembraneuse Il whi±e Dieulafoy, noting tl;lat.
gastric ,acidity was diminishé~ or absent, cal1ed his findings
"exulceratio simplex". Penner and Bernheim (11) in 1939", , ,r
reviewing previous rep~rts of postoperatfve esophago-, ,
gastro-duodenal lesions, found' that thèse lesions appeared
after a great vàriety of procedures, ran~in~ from herniorraphy
to resection of rectal tumors. Ba~~'on their own series,
the y specu'lated that the ulcerations resulted, from initial
'engorgement and permeabilitV hf submucosal ,capi).l~r.ies
and venules with subsequent stasis and ischemic necrosis
/ of the mucosa supp,lied by the" affected 'vessels. (1 • f
/' Trauma, .poth civilian and military, ,has b~,en associated
/ . , (12J with upper gastro-intestinal lesi,ons. In 1948 F;:~e~en et al. .-
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r,eported 27 cases of acute gastro-duod~nal ulcer or ~.rosion
JOllOWing long b"one .fracttires àm~ng' 143; cases ov~i::' a period
lf 2'6, ye:rs. He noted fat' enlboli in 'the ga~tric:mu~,osal 1nd su!>nucos.l vessels of, hese c.se's. Me.rs (l3t reported
8 cases of gastro-duodenal ulceration among 375 patients whp
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) underwent autopsy fo11~~~ long bone fractures for an
incidance of 2.16%. He also, emphasized the role of fat
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C embalism in the etiology of th~s process. Recent milit?-ry
conflicts such as' the Korean and Vietnam wars have, despite
their terrible consequences, offered an "jdeal natural
-setting" for the study of acute stress gastro-intestinal
lesions, and data co!lected during such conflicts(14) have ~ l
helped to clarify. certain aspects of this phenomerion. ,-
,Further elucidation of the etiologic mechanism of acute
stress mucosal lesions was hampered by the lack of any easy
method to directly assess these changes in vivo. Clinical
observations and conclusions were limi ted to the study-"of ,.
either surgical or auto~sy specimens. The chemical data
was often taken ftom patients who, bleeding in an appropriate
clinical "stress situation", were assurned to have "de hovo"
stress lesions of-the upper gastro-intestinal tract(14).
For these reasons, as weIl as because of the inherent
complexity of this entity with the ever ~anging wlde variety
of fActors assailing the criticaliy ill ~tienta under
investigatïon, often Qonf~icting data woJld,app~ar only ,
adding to the ever increasing confusion •
.. '. HenGe the sea.rch began for an appropria te animal
experimental model where app:r;opriate "stress situations l '
could be reproduced under more cdn~rolled conditions and
early
intestinal tract could be carr~ed out. -
intro,duced the restraint rat model in 19'56.
appearance of ulcera'tions in the glandular portion of the
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• stomach in 42 of 44 tested'anim ls after'wrapping these rats
in wire mesh for 20 hr. "They p oposed that these lesions
ap~eared through vascular, endocrine or neurologie pathways. " 0
Selective rat models were set up to/study the influence of,
amongst other factors, burns (by dipping rats in scalding
water) (16), hemOrrhag~7), acute renal failure(18) and
.hypophysectomy(19)
, " As much as these and other experimental models using
rabbits{2\.O), dogs(2l) 1 pigs (22) and pr,imates (23) offered new
insight into the pathophysiology of stress lesians,
pa~ticularly as ta the effect of certain individual factor~ . - . the results ,obtained, as in clinical studies, varied
dramatically. The lack of uniformity could often be traced b '
back' to slight deviations 'in the experimental methbds(24):
seasanal ,variations (maximum incidence in December and
minimum incidence i~~June) (25) and even social factors
related ~a the animaIs involved(26). Above aIl, even using
h · I,h·, t d'; , l d l Id b' 'f' d t e most sop ~st~ca e an~a 'mo e , one, wou e Just~ ~e
in questioning th~ ,PliCàbility" of the results obtained
ta humans on 'the basis of species difference alone, p~rticularly
in the s.tudy of su ch a-multifactorial entity. -Clinical studies were given a boost with the advent of"
the ~ndoscépe permitting direct in vivo observation of the
gastric mucosa. Rudolf Shindler, who' introduced the first , . lens-se~iflexible gastroscope in 1932 (27) / emphasised the e,arly
acute muco~al changes, such as edema and petechiae, the
latter th9ught to be due to capillary fragility or cha~ges in ,
the clotting mechanism. ~
He differentiated betwee~e~echial
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hemo~hages and erosions by defining the former as
subepithe1ia1 1esions that had the potential to be sloughed
by gastric acidity 'to become e~osions (28). Thesé are ,~
extrémely important concepts that have been used in our
presént study.
In 1958', Hirschovitz et al (29) introduced the complete1y
flexible fiberscope based on the technique of transmitti~g
light waves and ~ptica1 images through a bund1e, 5;16 inch
in diameter and 1 m long, composed of glass fibers of hair
thickness. This instrument; in adequately trained hands,
permitted c~ose scrutiny of the esophagus, stomach and
duodenum.. ~echnical improvements permitted documentation
--- of visual fihdings with both pootos and films. as well as
televi~ion monitoring. Clinical investigation into stress
gastro-intestinal lesions have now been given-the'expértise .
to obviate the major obstacle facing prior investigators,
the lack of direct in ~ visu,alization o_f these lesions • . Endoscopie findings in seriously i11 patients, where
the "stress model" is designed by nature, offers new poteri'tial
tô shed light on th~ nature,'~volution and management of
acute stress lesions.
2.2 TERMINOLOGY
1 A review of the li terature quickly revea,ls that there
is no concensus concerning the most appropriate te~ or
definition that will faithfully ref1ect the wide rangé of
precipitating fact~rs, the complex pathophysiology and the
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endoscopie appearance of the acute stress induced gastric ,
mucosal changes. This lack of concensus has bot~rresulted
from and added to the confusion surrounding this multi
facetted entity. Walt(30) stated that the common)y used
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term "stress ulcer" is inept insofar that the gastric mucosal
-changes often clear up before the stage of ulceration is
attained. The,pot-pourri of terms such as acute gastric
lesions(3l), erosive gastrrtis(32), acute hemo~rhagic - . (33) .' 1 l' (34) gastr.l tlS , acute gastrlc mucosa eSl.ons , acute
gastro-intestinal focal necrosis,syndrome(35), diffu~e . ,
hemorrhagic gastritis(36) etc. do not have identical
significance from one author to the next, often making . compa~ison of obtained data difficult, or at least, tenuous.
The ideal term woùld eliminate those lesions not ,directly 1
due to an acute stress situation and yet not be 50
re~~rictive to belittle the complexity of this phenomenon.
The term Acute Stress Gastritis has been chosen in this \
thesis for reasons that have been expounded in the literat~re.
ACUTE The word "Acute" is used in ·an attempt to
undetline the importance of differentiating be1ween
re,activated prior peptic ulcer -dis.ease and acute _ "de nova Il ,
, stress les ions that have progressed to what appèar to be
• fully fledged ulcers. '(37)' (38) 1
Hinèhey et al and Skillman et al h~we 1 1
emphasized ,the poten:ial for p!e-existing peptfc ulcer
disease tO be reactivated in acute illnes~I.'· Fromm (39) has 1
stated that approximately 30% of patients wh,o bled during a '
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, stressful situation have pre-éxisting peptic ulcer disease.
Bei{, Manni~ and Be~l(40) reported that 10 of 3~ patie~ts
who develôped postoperative gastro-duodenal hemorrhage had
pre-existing ulcer disease. In these 10 patients, 6 were
found to be bleeding from duodenal ulceration, 3 from
gastric ulceration and 1 from a marginal ulcere Despite
variable opinions concerning different aspects of acute
stress gastritis, most authors agree that every effort should
be made to weed ou't the cases of reacti vated chronic ulcers
and differentiate them from acute ulcera. Skillman et al (41) ~
noted that, contrary-to acute stress lesions, chTonic gastric ,1 • ~
'fcers were almerst invariably located in the antrum or at (
the antral fundic junction, and suggested that the former -
had an entirely different pathogenesis to either chronic
gastr~c or duodenal' ulcer disease. Katz et al (42) were
criticai of authors such as Palmer (43) , who did not make ,.' this distinction and pointed out that erosions that have
progressed ta what endoscopically appeared to be acute gastric
ulcers were characteristical1y acute mueo~al 1esions, being
sha~l~w and unvisualized by careful x-ray examination.
Chronic gastric ulcer is a true peptic ulceration, while
the acute ulcer w,il1 heal without scarring. Fromm (39) ,
however, pointed out that these mucosal lesions rnight
eventually extend beyo.nd the muscularis mucosa ta become
authentic acute ulcers. Both chronic and acute gastric
lesions can coexist, the latter often being the only source
of ~leeding. I~ thes~ cases, endoscopie distinction can be
difficult(42~. In contrast to the acute gast~ie u~ce~ation,
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, : ',acute "de novo" stress duodenal invol vement was usually
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limited to duodenitis and only rarely progressed to stress
duodenal ulceration in prolonged and intense stress
, . (39) l d . l d sltllat1.0nS . Ear y an sequent1.a en oscopy as weIl as
selecting patients who were essentially healthy prior to the ,
acute stress situation can help the investigator to distinguish
between the chronic reactivated and .acute lesions. Although,
for the sake of'clarity, it is worthwhile eliminating
reactivated peptic ulcer for this entity, it'should be
stated that the pathogenesis might be similar and the
hemorrhagic potential
devastating(56) .
1v of a reactivated peptic ulcer can be
STRESS Selye'S concept of stress with increased pituitary. -
,and adrenal activity was long considered aS a possible
explanation of the association of gastric ulcers with a large
varietyof diseases(37). He demonstrated that acute gastric
ulcers ~re an integral and prominent part of the alarm
reaction resulting from various disease states ranging from
fatigue and,emotional stress through infection; shock and
anoxia to burns and intracr~nial lesi6ns(44). AS' pointe9 put
by bo~h Baue(45) and Le Gall (46), the gastro-intestinal
system is another ~ictim of the syndrome of MUltiple,
Progressive or Sequential Systema Failure. Despite the fact
that the word stress itself has been given a wide variety- of
connotations (35) , it appropriately describes the clinical
setting in which our seriously ill surgical patients find
themselves. The advantage of using such an alI-inclusive"
/
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12.
term, however, has been partially offset by the fact that
many authors have not been selective enough and have
incl4ded in their "stress lesions", -those that were caused
by su ch ga,stric irritants as aspirin (ASA), steroids, digitalis,
antiinflarnmatory drugs and alcoho1(47, 48). This unfortunate
misunderstanding stems from the fact that these agents can
produce an endoscopie appearance, called "exogenous chemical
gastritis" by Berry and Adomavicius (49), that can closely
resemble acute stress lesions, except for its lack of
preference for the acid secreting portion as is the case for - ,
the initial stress 'preci~i tated changés (31). As Sugawa et al (50)
pointed out, lesions caused by ASA and alcohol usually involve
aIl segments of the stomach at
the typical proximal to distal
stress gastritis.
the beginning and do not show
progres~n il} .cute
Most authors, such a~ Lucas et al (51), Ivey(52) and Silen
and ,Skil~man(53), made it clear that lesions caused by
chemical irritants should not be included when the term stress
is used,~if for ~o other reason than that these agents affect
the gastric muco'sa locaJ,ly from the l uminal side and bypass
many of the complex steps that eventually le ad to mucosal
breakdown when stress is involved. Cheung et al(S4) have
~shown that chemical gast~itis is typically associated with
.early massive breakdown of the,'gastric mucosal barrier as
weIl as with a remarkable increase in mucosal blood flow,
while acute stres's gastri tis, as will be pointed out later,
is prirnarily a lesion tha~ originates from ineffective
perfusion and secondary cellular injury with exacerbation of
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13.
On the other hand, sorne authors such as Fitts et al (55)
appear to be oV'erly restrictive in the clinical application
of the term stress. He reserved the term "stress ulcer" for
the acute gastro-intestinal u,lcers that occurred follawing
elective operations, trauma, sepsis, rnyocardial infarction
and hemorrhagic shock, specifically excluding patients with
thermal and central nervous system trauma. Other reputed
".,- authors (33, 53) have also claimed that the gast-ra-duodenal, .. lesions associated wi th thermal 'trauma (Curling' s ulcer) and
cranial traUlJla (Cushing' s ulcer) have a different patho-
physiology than those resul ting from other stress si tua tians ,
because the former are associated with increased acid
secretion, are deeper and have a high potential for
perforation which is not the case in the latter. However,
Czaja et al(56), who have made major contributions to the
field of acute ga~tric lesions in the burn patient, stated J. . •
that, al though Curl~ng' 5 ulcerat~on originally referred
only ta the acqte ulcerati ve disease of the duodenum after
thermal in jury 1 this definition has been expanded in the
literature ta include gastric ulcers as weIl as erosive
disease of the stomÇich and duodenum. His study confirrned
that these ulcers evolved on a baçkground of diffuse mucosa1
in jury. Sevitt (57) noted an increasing incidence of gastric
rather than duodena1 ulcers with- increasing burn area. He
found acute gastr~c ~rQ6.ions in 14.1% of 291 burn $ubjects
at necrospy, and duodena1 ulcers in 8.9%. O'Neil et al <,58)
failed to relate the incidence of ulceration in burn patients
- ,
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14.
to the amount" of acid. They found that many burn patients i
• actually had ,,:"ery low gastric é/-cid leve1s.
, (59) À recent paper by Rosenthal et .al found both
superficial and ulcerative gastric disease in a series of
burn patients who had low acid secretions, indicating that
acid leve1 alon~ is no more primar ily pathogenetic in burn
les ions than in other trauma groups.
'Stremple (60), reporting on data co11ected from 36
civilian trauma patients, noted that patients with crania1
'" . . . . (61, 62) h d 1nJ ur1es, ln contrast to prevlous J.nves tlgators ,a
a decrease in bath acid and pepsin output with no significant
increase in serum gastrin. The gastric secretory profile
was essentially identical to other trauma groups studied.
O'Neil et al (21) noted hyposecretiotl of gastric acid in a f
chronic experimental model representing an intracranial
lesion w ith inereased intraerania1 pressure. Sibilly and
Krivosic (63) noted that endoscopie .findings in head trauma
patients were similar to that seen in other trauma groups.
There does not, therefore, appear to be suffieient
justification to distinguish between the pathophysio1ogy ù
-leading to acute gastric lesions in head and thermal trauma
from that in oth~ stress situations. Both thermal and head \
trauma patients might differ .slightly from other tiaUJlla .. -j
gr~~~ in' 50 far as the degree and persistence of stress,
but they are subject 1;:0 the same factors such as hypotension,
shoek, sepsis ete. as are other surgica1 stress patients.
(
1·
15.
GASTRITIS There 'is no subject in gastroenterology that
has been more widely discussed or remains more controversial ,
than gastritis, whether acute or chronic, ~ainly because of -
the discrepancies between on the onè hand clinical,
gastroscopie, and roentgeno16gic observations and on the other
hand histologie findings in corresponding tissue specimens. ),
Mucosa~ changes, as seen through the endoscope, compatible .J /
with a diagnosis of "endoscopie acute gastritis" are as
Tollows: localized or diffuse hyperemia, edema, petechiae,
mucosal hemorrhages and tihy hemorrhagic or grey erosions . (49)
resembling ulcers . This same description can be used to
describe the spectrum of acute stress induced lesions(64),
hence the appropriateness of the term gastritis in our
terminology. Gastritis also implies that functionally the
mucosal resistance of the stomach is abnormal(52), which is
one of the hallmarks of stress induced mucosal changes. The
confusion surrounding this term stems from the frequent lack , ,of'histologi:'c confirmation of acute- inflammation in cases of
endoscopie 'gastrit,is (49). As Robbins (47) points out, in
cases of non stress acute gastritis, there may be only
occasional seattered leucocytic infiltration whereas.- in stress
gastritis, depending upo~ the duration of the ulceration,
t-bere may be sorne .imflammatory infiltration in the margins ,-
and base. Both Stremple et al (35) and Sk'illman and Silen (38)
also reported acute inflammation in acute stress ulcers in'
their series. (47) .' (33)· ;./-' . Robbins and Ivey both emphas~sed
that the~istologic criteria tor differentiating stress and
non stress gastritis are exceedingly rare. Microscopie
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16.
studies carried out on specimens demonstrating acute post
traumàtic generalized erosions from Stremple ét aIls series
showed focal necrosis of the superficial epithelium between
areas of epithelial regeneration, granulation tissue and
Il . Il' . fI . ( 35) new'co agen as we as 1ntense ln ammatory react10n
(Fig. 1). This is a departure from'the long respected rule
that stress induced lesions are uniformly devoid of any
inflammatory reaction(30). This still applies to the majority
of stress indu'ced les ions which remain confined to the mucosa (147) .
Under certai~ conditions however, these mucosal lesions can, in
a matter of days, progress beyond the muscularis mucosae(3S).
This distinc~ion is beyond the scope of endoscopy and can only
be assumed from the gross appearance of the le l'lion . Under
adequate ~onditions, the gastric mucosa has a remarkable
potential to renew itself in 2-4 days(SO) . ~
Skillman and Silen(38)1.,
• describe the stress induced lesions as primarily ulcerati,ve and
, only secondarily inflammatory. This typical, but not uniform,
lack of inflammation may be related t6 the difference of '~
mucosal perfus,ion in stress versus non stress gastritis. \
Both
Menguy and Masters(20) and Moody et k1(64) have shown ,that
aspirin, alcohol and bile salts cause a re~~~~â~re increàse ... ,. ,.;--
in blood flow along' wi th formation of erosions, wher,eas .. hemorrhagic and emto~oxic shock produce a marked d~creasé in
mucosal bloOd flow as me?S~red by radioactive .mic~osPheres (65) .
Since stress gas~ritis is a diagnosis made by both . clinical and endoscopie ,evaluatiol'}::;rather than on histologÏ:.c
findings, the term gastritis has the advantage of being non /'
restrictive so as ta encompass the early insidious. endoscopic_ , "
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17.
findings such as mucosal erythema, petechial
and focal hemorrhages upon whrcn notorious
erosions and ulcers(38). Early a d sequential endoscopie
examinations have indieated that
as much a part of stress gastriti
apparent ero~ion{5l), defined as ,
not going beyond the ~usculàris m ~
to do so(66). Stress gastritis
erosions and ulcers or hemorrhage
might be
mucos'a might be pr ,1
preakdown of the g stric
erosions and ulcers (67) .
preference of these lesions to a , '
he early mueosal changes are
more clinically
in the mueosal layer ., the potentia1
before
ave appeared(63). This
chemie changes in the .. d periods without
appearance of
conf ers the
secreting po~tion of the stomach reading, under
appropriate conditions to the remainder 0 the stomaeh(~O).
In conclusion the ~rm acute stress g stritis qdequately
deseribes the acute and complex gastric muco al changes
seen in the patient sub{ected to an acute stre s situàtion,
without putting ~ndue emphasis on the terms ero ion,'ulcer
or hemorrhage as in the case in the literature. t is
partieularly appropri~te in this age of endo~copy w,ere
milder subelinical les ions are easily visible .
. . '
2.3 INCIDENCE OF ACUTE STRESS GASTRITIS
In 1972 Stremple et al(14) pointed out that the enor.mous
variations in réported incidence of the "acute 'stress u1cer",
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t~end pro~uct of acute stress gastritis, was,probab~y
rèla\ed to variations in the type of pat'ient studied and ,in
the 'criteria for diagnosis. In a civilian population the .. '
variability of age, sex, pre-existing i11ness and nature of
in jury tend to make comparison of observation difficult.
Evidently the incidence will vary from one study to the next
§epending on the patient population studied and the.vigor
with which these les'ions are sought. ~Q.s):, c1inical st~dies,
particu1arl~ when done without the aid of endoscopy,
underestimate the true incidence of 'stress gastritis since \
""" its recognition then rèquires gastro-intestinal b1eeding or
perforation (64) .
Autopsy s,~ries, surprisingly enough .at first glance, /
als'o underestimat~ t~e prevalence of this disep.se in the . -
aC~,tely il! patient. This can be rationalized both ort the
basis.that these series are nonselective and that a~ute
stress gastritis is primari1y a disease of ,the actively and
acutely ,~ll p"atient rather than the moribu~d patient. The
great majority of the former will recover both their hea1th 1
and their normal gastric mucosal appearance while ~n the
latter cases, the,decrease in,muco$al resistance probably , ,
para11e1s the decrease of a~gressive e~ements essential
the formation of overt stre~a~tritis. Suff:Lce /it to
mention 4 pertinent autopsy series. In 1952 Woldman (~,8)
reported 139' cases of acute 'uf~ers fr<?m a series of 943
consecutive autopsies, representing a 14.7% incidence.
to
He
noted that the incidence was greates~ in those cases with
burns, trauma, septicemia, pancreatic disease anq per!tonitis.
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/ (35) Stremple et al ,reviewing 2 pr~vious series consisting
of 10,134 consecutive autopsies, reported an incidence of,
acute gast;q-intestina1 ulceration that varied'from 3.6 to
6.2% . In a third series, consi-sting of' 4,102 aùtopsies,
perfo~med between 1948 and ~953, Fletcher and Harkins(69)
repôrted an incidence of acute upper gastro-intestinàl u cers
of 1%. Once again, burns, peritonitis,"along with congest~
failure and myocardial infarction appeared to be the
principal culprits. They concluded that the syndrome of
secondary acute peptic ulceration, when associated w,ith these
conditions, is much more common than had ,been' realized.
Finally, Moody et al ('64) reported only 59 cases of ,erosive
gastritis frottl among 2,600 consecutive ,cfl-,utopsies performed at 1
the University of Al.3bama Medical Center from 1963 to 1968.
These figures tend ~o support the theory that in recent
years stress gastrit}s, particularly in its initial,sta:~,
falls mainly under the scrutiny of the endoscopist more often
th an the pathologiste
There ls general agreement amongst authors that the
increased frequency of bleeding secondary to str~,ss induced
lesions of the gastric mucosa no"ted in the sixties and early
seventies was related to thé prpgress made ~n the'fields of
acute resuscitation and ~ubs·equent Intensive Care Unit, ~
management (37, 70). During this period 1_ numerous clinical
studies not'using prospective endoscopiç evaluàtion,
extrapolated the incidence 'of acute stress gast'ritis from
the incidence of 'acute gastro-inte~tinal hemorrhage in their , -
acutely i11 patien·ts '. Different investigators have different ,
tu' 'ri t 1'-
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criteria for the diagnosis of acute gastro-intestinal
b1eeding.' Despi te the fact that it is impossible to
de termine how many of the cases reported were rea11y bona '
fide cases of stress gastritis, because most recovered with
conservative rnanagEmeQ,t wi thout endoscopic documentation, i t ' /
is worthwhile,reporting sorne of their figures. A 7%
incidence \Pf clinically significant gastro-in,testinal b1eeding
was found ~n 780 consecutivé patients admitted to a combihed
medical an~ ~urgica1 intensive care unit of the University
Hospital, University of Pittsburg, from January 1971 to
January, 1977 (35). Fromm (39) stated that the iJlcidence O'f
postoperative gastro-intestinal bleeding after elective
surg,ica1 proc!!dures ranges widely from 0.1 to 22%, and, as
Goodman and Frey (71) reported, the incidence ls highest after
e1ective gastro-intestinal tract sur~ery; hypotension and
sepsis were nQted to be important predisposing factors.
Hummel, discussing McAlhaney e~ al'~ burn 'seri~s, (72~
reported 57 cases of significant upper gastro-intestinal
bleedin<} out of 468' burn patients admitted, to the ~hriners.
Burns Institute in Cincinnati. Czaja,et al reported an 11-22%
incidence of brisk hemorrhage in patients with bums
involving more than 35% of total body surface(32, ~6).
O'Neil et al reported a correlation between the incidenëe of
bleeding and the percentage pf ~urn area(SB). ~e~d inju~y
was' -associated witli a 50% incidence of severe gastro
intestinal bleeding in Stremple's series(35) while Davis /
et al (73) recorded a o .7% incidence of hemorrhage in a 1
series of 7,000 patients who had undergone neurosurgical. . .
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procedures. They pointed out that Central Nervous '-System
pathology was not a requisite for these lesions since they
were encountered'following such procedures as laminectomy, l ' 1
hemilarninectomy and trigeminal neurectomy. They proposed
that the;:;e lesions _represent an extreme pathophysiologic
response to the physical stress of surgery, wherever it~ \
21.
location. Combat" trauma statistics from Vietnam, reported by \
McNamara and Stremple{74), indicate that 3% of a series ,
2,297 U.S-. army soldiers developed clinically evident
gastro-intestinal bleeding'and ~hat stress ga~tritis was
responsible for 3 of 100 consecutive trauma deaths. The
highest incidence of bleeding in'relation to site of injqry
were in intraabdominal and spinal cord injuries yet the
differen~s were npt statistically significant(35).
Four recent studies us~ng prospective evdoscopy have
helped in the quest to determine the actual incidence of .. stress gastritis in gropps of non specifie, head and thermal
trauma as weIl as septic patients. (51 J In 19~1, Lucas et al
reported that sincè 1967 over 300 patien~s on the emergency
service at Detroit General Hospital had required transfusion ~
for stress gastric bleeding secondary'to multiple organ
in jury or severe sepsis. Sequentia~ photograph~c stùdies of
the gastric mucosa obtained through a fiberoptic gastrocamera -
were studied prior and subsequent to bleeding in 42 patients o
who later died. They found in aIl of these patients a wide 1
spectrurn of les ions consisting within the first 24 hr of
interspersed areas of pallor and hyperem}a with the
appearance of petechial and erosions by 48 hr. These lesions , .
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22.
were located almost exclusivel,y in the proximal body of the
stomach. However, with the progression of the disease, they
spread distally to involve the entire b9dy of the stomach.
With recovery, the sequence was reversed~ These tindings
are compatible with our description of acute stress gastritis.
McAlhaney et al(75),performed,gastro-duodenoscopy in
9 patients within 5 days ~fter major thermal trauma and noted
~hat gastroduodenal lesions were pr?sent in 7 patients (78%)
on initial endosco~ic examination. The spectrum of gastro-\
dupdenal' disease included su erficia1 gastric mucosal lesions,
éonsisting of areas of eryth ma, mucosal hemorrhage and
discrete erosions in aIl 7, 9 stric ulcer in l, superficial
duodenal lesions ("erosive du and duodenal
ulcers in 2 patients. Both of the latter had coexistent
extensive gastric and duodenal mucosal lesions and one of
these duode~al ulcers was judg d to be a reactivated chronic
peptic ulce~ on the basis of
Sibilly and Krivosc (63)
scarring.
mitted 62 'head trauma
patients to a single gastroscop c exarnin'ation b~tween' the
3rd and- 15th days aft~r in jury. Sixty-o~e of thèse 62
patients prese,nted findings simi to the 2 prev,ious~ authors, o
cQnsi"sting of mild stress gastri is in 20- (i.e. rnucosal
erythema and petechial) a~d mère dvanced stress gastritis
(Le. erythema', petechial, erosio s a!ld ulcer) in' the '
remainïng 41 patients. They under' ed the near 100% incidence
of, stress gastri tis i'n he ad trauma atients despi te, the fact
that ctlly 10%' of the patients went n to bleed clipically.
Le Gall et al (75) performed 42 gastro-duodenoscopic
. ~
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23.
, examinations on 14 selected patients with documented sepsis
during a? 8 month periode Their data clearly established
that aIl the patients with sepsis had acute gastro-duodenal
muçosal disease. In the few patients who were studied
serially, gastro-duodenal disease became worse as sepsis
persisted. ~n the other hand, they noted a dramatic improvement
when focal infection and septicemia were eradicated.
It is fascinating to note that just as the surgical
endoscopist has established that nearly aIl acutely ill
patients have evidence of stress gastritis, the clinical
manifèstation of the disease apPears to be declining. At a
t . t . . . ( 30) . l d recen SympOS1um on s ress gastr~t~s 1 M~nguy, 81 en an
Wal t aIl commente'd on the decrease in the incidence of stress
induced hemorrhage over the last 5 yr. Skill~~n(77) also .
commented on this recent decline but warned that it still
occurs and when it does it is frequently the final
complication resulting in the patient's death. Richardson and • (36) Aust noted that the number of operations required for
diffuse hemorrhagic stxess gastritis had decreased
dramatical1y, falling from 15 in 1971 to approximate1y 4 in
1975 despite an overa11 increase in the number of total , (72) "
. 'oper.ations during this same periode Hummel , noted that. the
incidenc~ of gastrointestinal '(~I<) bleeding in burn patients at the
Shriner.s Burns' Institute in CincinnÇi.ti dropped from 5% in ,.
1972 to 2% in 1974 and 1975 dèspite a steapy admission. rate .
~It is tetnpting to speculate that this decrease resul ts,J::r;-om
our greater experience in the treatment of· severely ill
patients gained over the last 10 yr, particularly in the, field •
(
1
24.
of acute stress gastritis.
2.4 PATHOGENESrS
Acute stress gastritis encompasses the dynamic and
usually complex gastric mucosal changes noted in acutely ill
patients. These patients can be found in a wide· variety of
clinical situations ranging from post surgery through sepsis,
as weIl as respiratory, cardiac, liver and renal failure to
post al:Jdominal, bone 1 head or thermal trauma. They may be
subjected, for varying lengths of time, to a barrage of
factors, sorne. of which have been postulated to have
pathogenetic significance in the genesis of acutè stress
gastri tis. The çonstant· and. uncontrollable interaction of 't"J
many of thE!se factors (Fig. 2) in clinical studies makes i t
difficult to assess the importa!lce' of any one particular'
factor. Hence the importance of datà gained from controlled ~
animal models. The sum effect of these factors must overcome
the patient 1 s tomplex defense mechanism-(78) introducing an . additional variable (66) • If this happens, there results an
upset of the delicate balance between tpe protective elements' . . and destructive elemerrts surrounding the target organ, i.e.
the ~astric mucosa, which resides in a particularly hostile
envirorunent.
As Kawarda et al(79) ~e stated there is no single
etiological factor in the genesis of acute stress gastritis.
However, on reviewing the l~têrature, three postulated
factors are more consistent with experirnental data and
L
"
provide the-basic framework for the appearance and
progress ion of this entity: They are: 1) alteration of
effective mucosal perfusiol'l, 2) alteration of mucosal
function, 3) intral uminal contents.
Controversy still exists concerning the rSlative
importance of these factors and there is available
experimental da ta tha t downplays one or another, hôwever,
their respective importance cannot be denied and there
remains li ttle doubt that when present simul taneously,
stress gastritis will occur. AlI three are interrelated a
but ~ill be reviewed individually for convenience.
2.4.1 Alteration of Effective Mucosal Perfusion
25.
Virchow in lB53 suggested that ischemia was one of the
mGlst important factors in 'the pathogenesis of gastr ic
,(80) , (20) mucosal stress leslons . Menguy and Masters stated
that e~ery scheme since that tirne hfis included the fact that
stress gastritis is in sc;>me way initially linked' to changes
in the rnucosal microcirculation. Even the more recent . articles concerned wi th acute stress gastritis emphasize the
fact that mucosal ischemia is the initiating and f)lndamental
factor in the pathogenesis (53, S.l,~ 82) and is vital to
subsequent events if perpetuated(66). As liinchey et-al (37) ,
'Lucas et al (?6) and Stremple et al (35) J?Ointèd out; it is
,feasible tha t the majority of the varied clinical events
known to l~d to stress gastritis, be i t surgery, head or
thermal trauma, hemorrhage, sepsis etc., contribute to
-mucosal breakdown through their influence upon mucosal
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perfusion. The effective systemic hypovolemia, often
translent and subclinical, a~sociated with these events leads , \j
~o splanchnic vasoconstriction- and the opening of submucosal
arterlovenous shunts und~r sympathetic control which in turn,
particularly when sustained, can rob the gastric mucosa of
its much needed nutrition to the point of cellular hypoxia
and then death(84). Both Lucas et al (66) and Stremple et al (35)
~u99~st tnat the reactive hyperemia that follows resuscitation
is responsible for the actual bleeding. CNS in jury, or even
severe pain alone, could lead to mucosal damage by using the
autonomie ~ervous system's efferent pathways, the~eby
bypassing systemic hypovolernia(37).
In 1964 Harjola and Sivula(85) noted, after inducing
hernorrhagic shock of 15 min.duration in a very elaborate
rabbit model, that 1) gastric mucosa becomes
pale in consequence of general vasoconstr~ctioni 2) ..several
large diffuse pale patches appear and disappear completely
~fter the restoration of blooî volume; and 3) sharply
defined, intensely pale spots appear at the beginning of
blood letting and that hemorrhages ensued in the'se spots
'after restoration of blood. They concluded that the intènsely
pale spots corresponded to areas of tissue anoxia and that
capill~ry breakdown in these areas lead to hemorrhage after
reinfusion. Stre:mple et al (35), having noted the 'occasional
presence of ,prganizeÇl thrombi in the subrnucosal vessels .'
distant from the necrotic areas as weIl as the lack of
inflammation, reemphasized the possible-contributory role
vascular occlusion ~o the ischemia while Pruitt(30) felt
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that the ischemia, infarction and lack of inflanunation was
mainly due to shunting, having seen open ateriovenous,shunts
in a few fortuitous sections. Lucas et al (66), describing
endoscopie changes in acutely ill patients, noted that the
focal areas of pallor seen shortly after hypotension and
shock were caused by decreas~d gastric mucosal bloodtflow.
Czaja et al (56), reporting on early endoscopie findings
in a group of adul t patients w ith burns 1, most with associated
hypotension, stated that the development of mucosal lesions
within hours after in jury suggested the possibility of an
acute ischemic insult to the gastro-duodenal mucosa. Several
of the macular les ions noted on the anemic folds had central
are as of pallor. The ischemic theory was supported ny their
histologie findings. In a more recent article(32), these
same authors, having found histologie evidence of focal
mucosal infa~ctio~ necrosis as early as 5 l:r post burn,
suggested that syrnpathetic discharge or catecholamine release
was responsible for the abrupt shunting of blood away from
the gastric mucosa.
Hottenro~ et al (83), in an article published in 1978,
emphasized the role of ischemia by subjecting 10 conscious
piglets to hemorrhagic shock for 3 hr. Nine surviving
piglets showed severe stress induc~d gastric mucosal les ions
in the gastric fundus and corpus. They measured total as
weIl as regional gastric blood flow using 8 micron radioactive
microspheres before-control-and during shock. Total gastric
flow fell a1most 90% during shock and there ,was a
significantly higher flow reduction in the mucosa of the
....
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~ 1
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28.
corpus and fundus, where almost aIl of the st~ess lesions
were found. Measurement of blood flow within these les ions
demonstrated a fall approximatel~ to zero. They postulated
that ischemia related t~ sympathetic stimulation renders the ,
gastric mucosa more susceptible to other injurious factors ..
Sepsis h~s long been associated with stress gastritis.
Beil, Mannix and BeaI (40) reported tha.t 26 of their 35
patients who developed postoperative gastro-intestinal
bleeding had documented sepsi.s. Le Gall et al (76), rev,iewing
this association, pointed out that the incidence of sepsis
in patients with stress les ions ranges from 29 to 83% . .
Endoscopie examinations do ne in their own series o~ severe!y
septic patients,revealed, tn association with acute lesions,
a pale, ,ischemic and marbled gastric mucosa, which, they felt,
'strongly supportèd the ischemiQ pathogenesis. Neither of
these groups ventured to say whether ,sepsis w.as ~erely
c~existent or actually etiol?gical. This apparent ." ~ association, has prompted sorne very interesting and
controversial studies ·pertaining to the possible' role of ..
mucosal ischemia in stress gastritis. In the initial
experimental models, sepsis .was induced by the administration
of Escherichia coli endotoxin because of its potential to , (85)' ,
cause shock. In 1958, Lillehei and MacLean reported
"intestinal vascoconstriction and hemorrhagic intestinal
necrosis' atter administering Escherichia coli endotoxin.
They noted that the mucosa of t\1e bowel, which was first
remarkably pale, gradually became congested until fluid,
,first crear and later bloody, leaked int9 the lumen of the
!
1
t
'-
l' 29.
bowel.
In a more recent experiment, Richardson et a1(65)
induced shock in 10 piglets with intravenously administered
Escherichia coli endotoxine Endotoxin caused a redistribution
• of gastric b100d f1ow, measured by counting cerium Ce 141
labeled microspheres~ which did not paraI leI cardiac output
change. Ischemia was maximum in the corpus where flow per gm
decreased 67.7% and stress ulcers deve10ped only in this
region in aIl shocked animaIs. Cheung et al(B7) noted that
intraarterial infusion of Escherichia coli endotoxin in do~s
caused a significant d~crease in total,gastric blood flow
and in the functiona1 distribution of flow to th~ mucosa
measured in an exteriorized canine fundic pouch using the
gamma-labeled mic~osphere technique. There wa$ no significant
arteriovenous shunting of the microspheres. Having found ,
evidence of mucosal barrier breakdown, the y postu1ated that ,
their model indicates that mucosal ischemia can 0ccur and . ~..:
may represent a mechanism in the development of gastric
les ions in endàtoxemia even in the absence of systemic 1
hypotension.
However, the whole concept of mucosal ischemia being at ,
the base of stress induced lesions in general and in septic
associated cases in p~ticular was challenged by Lucàs et ~1(88) , ' , ifl 1976. They refuted the validity of extrapolating 1
Richard~on et aIls-and Cheung et aIls fïndings from their )
septic,models to septic man. In effect, they noted that
contrary to the hyperdynamic state with increased cardiac
output and decreased peripheral resistance characteristically J
li:
.' ,
. , • J
c
#
30.
< produced by sepsis in man, endotoxin tends to produce a
hypodynamic state with decreas~d flow and increased
resi~tartce. Their septic model therefore consisted of
injecting Pasteurella multocidà into the de~p shank muscles
of 12 pigs. Red based erosions were noted primarily in the u
pody and 'fundus of the stomach 18 hr later. Cardiac output,'
total g~stric b\èod flow and regional blood flow to the
.f~ndus, body ~nd an t.ruin, measured wi th radioactive microspheres,
aIl showed parallel increase. They suggested thérefore, that
acute stress gastritis, at least wh~n aS60ciated with the
early hyperdynamic phase of sepsis, may'be due to ineffective 1
perfusion of t~e involved tissues due to phsyiologic shunting.
In effect, 'Wilson (89.) pointed out that early sepsis, which is
usually hyperdynarnic, is accompanied by increased capillary .
perfusion and A/V shunting, leading to interstitial edema and,
if sepsis persists, frank mucosal ischemia. Lucas et al(88)
claimed that the incre~sed gastric secretion and increased -
acid output seen in septic ftates are other indications of
increased gastric mucosal blood floWi this, however, is a-
tenuous argument because, despite the assumption that 1
reduction in blood flow leads ta a reduction in secretion(90),
M~in and Whittle(91) have demons~rated that augmentation of
mucosal blood flow does ?ot, by its~lf, produce ~? increase in
Secretory activity. In effe,ct, ,Jacobson et al (92) have . ' stated that increas,ed mucosal blood flow, such as reported
by Lûcas et al(88). in~ s~psis, ia a response to inqreased ,
gastric secretion possibly resulting from the action of
metabolites of.the actively secreting,oxyntic glands stimulated :1:\-
, .. :
--------~-"-{ -, .>:J).-:c""' •• ""' .. _....; .. 'Li-' -"'-]',.:..I:..lIniIil~!l!ltIllLioll-I&IK. .... f",~~""--4;..!'.,~'4.i';.I~,. ..... ~~~~~~I~.i.\ .. t".~~~l,i..\oioj'~,,"",_~ .... ~' .... ~~ .. , ~4,~ ~ Il
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by sepsis. The secondarily. increased mucosal blood flow might \ '
then not only be ineffective but insufficient to meet the ~
highly increased metabolic demands of the'stimulated fundic , (88) .
mucosa. Alternatively, Lucas et al suggested th~t the
gastric blood flow may be carrying injurious agents as yet
unidentified, which cause a direct cell~lar insult, thereby
producing damage within OE on the surface of the gastric
mucosa.
rn conclusion, experimental, histologie and endoscopie
data appear to implicate decreased mucosal perfusion as the
central pathogenetic factor through which aIl other factors
(surgery, trauma etc.) exert their deleterious effects on
the gastric mucosa. Sepsis on the Qther hand appears to be
s~ightly'more complex and appears to alter the effect~ve
perfusion of the gastric mucosa creating a situation of
relative ischemia. As Skillman and Silen(38) pointéd out,
reduced or ineffective mucosal blood flow reduces 'the
mucosa's capacity to effectively wash away back diffused HT
ions, thereby enhancing mucosal damage.
, 2.4.2 Alteration of Gastric Mucosal Function,
In order to gain a better perspective into any
alteration of gastric mucosal function it would be
appropriate to rapidry review pertinent aspects of Igastric 1
mucosal histology and the physiologie cOntrol of gastric ,
mucosal secretion.
The gastric mucosa can be divided into three parps: the
, cardiac gli)nd' area r •
forms'a 1-3 cm wide strip beginning at '\ \ r--\ ,-.\-
\ \
,>
.1 1
1
, ' !
1
, 1.
, '
the esophagQgastric junctio~; the fundus, also known as
the parietal cell 0-': oxyntic gland area which is primarily o
respons,tble for secretion of acid and pepsin and occupies v
32.
the proximal three-fourths of the gastric mucosa; finally,
the antrum or pyloric gland area, which occupies the distal
one-fourth of the ~tomach(34). ·Of particular importance
to acute stress g~tritis is the fundus which is \the m~st metab~licallY aclive area 9f the stornach and the lnost ,
(- J vulnèrable to' ,stress gastritis (93). A .simP~e ~ol1nnar
f . • <i, ,
mucosa lin~s 'he lumen of t~e stoma~h in this area and
continues ,in~'the lining of the gastric pi ts, which di~ _.' 1
into the bqCiy of the mucosa to a distance of 'about one-fourth , \
of its thiékness. Into the bottom of the gastric pits open
t~e f~dic glands, which compose the major portion of the )
!Jo !~ muc::osa and .. extend downwards to the muscularis mucosae. In
~he py~oric gland area, t~e gastric pits are deepe~ t~an in ( \
the f,undic' reg~on and, arè lined almost exclusively by \ \
O' •
glandular cells similar to the ~ucous neck cells of the
.. fund± glands.· The lining of the lumen of the stomach in ~.
this ar a is still simple coiumnar mucous'epithelium(94).
The,p tput of gastrïc juice in a ,normal fasting subjec~ .. va~ies between,SOO a~d 1500 ml a day_ and is composed of
différent substances.' Mucus, s~creted by the mucous cel~s
, \
,of both the fundic and pyloric gland areas, is a heterogenous -,
mixture of glycoproteins anQ does not protect the mucosa
against hydrogen ions by any other method than possibly by
lubrication. Its physiological function in' acute stres~
gastritis is obscure (3?) •
\ " \
,
l ••
L
33.
, Parietal.cells, predominantly found in the upper portion
of the' fundic gland area, are responsible for the ~ 1
secretion of hydrochloric acid (approx}mat~ly 150 mg!l) .
Chief cells, found in the deeper portion of the fundic glands
'1 (and to a lesser extent in the' pyloric area) , secrete
pepsinogen, which is the precursor of pepsin whose role
remains unclear in acute stress gastriti~(3B), but whose'
activity is abolished at a pH greater than 5(95). t
Gastric acid secretion 'can be considered of primary c ' •
importance both as a reflection of normal mucosal function
as weIl as a factor in the genesis of stress gastritis. It
is beyond the scope of this thesis to extensively review the
complex physiology of gastric acid secretion, however, certain
aspëcts pertinent,to both the pathophysiology and eventual
management of acute stress gast~itis are worth? of mention.
The vagal antral phase, t~aditionally known as the cephalic
and gast~ic phases of acid secretion but combined here l '- (90)
because of considerable qyerlap ',comprises the acid
secretion under t~~influence of the vagi, gastrin and the 1 \
propo,sed infi uenee 0 f histamine. \ .
C~halie stim\lli are
mediat~ ta the. S'tomaeh by t~e vagus nerve through
acetYlC~line via two mechanisms: a direct stimulatin,g
effect on ~arietal cells and an indirect stimula'ting ~
influence on the parietal cé,lls mediated by vagally indu ed
release of g~strin by the antrum(34). Acetylch~linè a~d gastrin, which appear-toact independe~t1y of ea'ch other(96) ,
have a c ulative,stimulatory effect with acetylcholine that
the sum of either stimuli, so that true
(
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\ '
potentiation is aêhieved(48). Distention of the stomach
excites a vagovaga~ reflex that stimulates acetylcholine
release in the fundic and a~tral mucosa and hence further "
gastrin release(97) •
The possible physiologie role of histamine in gastric
acid secretion remains uhclear(52, 98), despite code's
postulate in 1955(99) that histamine is the final, common , "1"'- ~
local chemostimulator of the pa~~etal cells of the gastric
mucosa. It appears that the actions o~ histamine, gastrin
34.
and acetylcholine are interrelated. Fpr example, histamine - l,
and cholinergies 'and gastrin and hist~ine potentiate the
action of each other(98) and H2 antago~istsinhibit gastric
secretion stimu1ated by both nistamin 1 and pentagastrin. , (100)
Grossman and Kon,turek p,roposed th concept of adjacent
histamine and gàstrin receptors' so the blockade of one'
rèceptor changed the properties of other receptor.
Finally, quick mentJon should be ade of cyclic
J'S'-adenosine monophosphate (CAMP), w ich is_currently a
prime candidate for the'role of transd çer. However, since 1
Harris and'Alenso(lOI) reported that C produced acid,
secretion in frog gas~ric mucosa, much data
concerning its role in gastric acid 'ha appeared in the
li teratur,e (90, 102) ,
The actua1 intrace11ular proceêse the formation ,of •
gastric hydrochloric acid, of which mu h remains _unknown,
are depicted in Fig. 3. The energy required'for the active • l ,
transport process is provided for by,a~enosine~riphosp,hatase(103). , ,
1
Oespite" the milli~n-fold gradient in H~ concentration between
"'lt~"",,~';;,iIlilw~~»~ll»;'II!i~fI"l ..... ' .. .., .. ""'~a' ____ ~lij ... ;_.....,..;_~_ .... "'.i<oao!~~.,,''''':!~"' A-,"i'''''''' 'Ii-_,.;_ ,1 J - " .~ , 1 \
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35.
gastric lumen and blood, there is normally littlè back
diffusion of aci~ across 1:negastric mucosa" suggesting the
existence of sorne sort of mucosal barrier which, thorrgh
still not loca~ized anatomically, probably runs along the
apical cell borders,and the intercellular tight junctions(104)
(Fig. 4) .
The integrity of tht',active,transport of H+against this
high gradient as welt as ~he gastric muc~sal barrier depend
qn adéquate blood sUPPly(~' 90, 105) and energy levels, which
are frequently both inadequate in many clinical states
associated with acute stress lesions(38). Bounous et al (10,6)
identified the following defects in intestinal mucosal cells
after a hemorrhagic shock: -1) dépr~ssion of oxidative,
phosphorylation 2) a depression of ATP synthesis, 3)a defect în
adenosine incorporation into ATP and in the synthesis of
nucleic aci~, 4) a defect in cellular respirat~on, 5) a
cessation of mucus production, and 6) a permeability to
proteolytic enzymes. Both Davenport and Charre(107) and
l!'orte (108). have shown, h~wever, that the gastric mucosa can
achieve a h~gh 'but short-lived, rate of anaerobic glycolysis
in the face of reduced oxygen supply and tnat acid
secretion still occurs after 30-60 min. of anoxia. This " .
"unnecessary secretion" taxes the already reduced energy
suppl~ hastening metabolic death (3,0) •
The 10ss of the gastric mucosal barrier and excessive
back diffusion'of hydrogen ions have been implicated by
sorne aùthors as the prime' alterations of mucosa function
leading to ,acute stress gastri tis and therefore meri ts -
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further discussion .. The existence of the gastric mucosal .
barrier was postulat,ed by Teore11 'n 1933 (109). He
described it as the ability of al gastric mucosa to
restrict diffusion of hydrogen from the gastric lumen
into the m~cosa and of sodium ions from the mucosa into the
lumen. After instilling a measure amount of hydrochloric
àcid into the stomach of a cat lig ted at the pylorus and
cardia, he noticed a graduaI, decre se in intraluminal
hydrogen ion concentration and' an . ncr'ease of sodium
concentration while the volume of contents remained
the same. He concluded that hydro sodium ions were
exchanged for one another on a 1:1 asis(110) , however,
l . (Ill) d . . . l d' f h A tam~rand , stu y~ng sem~-~so te p1eces 0 t e
gastric corp~s of dogs, noted that ydrogen and sodium ions may
diffuse independently of one anothe
Chapman et al(112) noted that astric bacX diffusion
of hydrogen ions is a n~rmal proper~y of the gastric mucosa.
They found a mean back diffusion of 2.2!: 0.2 mEq.HtlS min.in' ,
7 sUbjects who were free from gastrointestinal disease. '
The list of drugs that will inprease the mucosal permeaBility
to hydrogen is now well,estab1ished(~2, 113, 114r. Ivey, ,
Den Besten'and-Clifton demonstrated increased back diffusion 'L (11:5) :-- of Hi' and C1- in the presence of a bile salt mixture •
t (105) Skillman et al , in a series of experiments.designed to
study the gastric mucosal barrier, noted that a short,period
of hemorrhagic shock (40 mm Hg for 15 min " Hn rabbi ts 1
'whose 'stomachs. had been previously'lig~ted at the cardia
and antrum, produced a disruptive effect on gastric mucosal
..
\
~ ---
L
barrier to hydroge'n 3 hr later that was simi1a~ ta that
produced by ASA, alcohol and bile salts., Multiple
37.
"'"" superficial fundal les ions were noted at the conclusion.' ~~~}
They also noteà,. an increased 10ss of hydrogen ions ~cr04s ~~
the mucosa of up to Il ,mEq/15 min in a group of ser~ous'y ill patients who had been freguently'hypotensive. They
stated that increased rates of back diffusion 'of Ht cannat be
predicted from standard tests of gastric secretory function
and that 'this' absorption of I{t in critically il1 patients is "-
important to the pathogenesis of acute str~ss gastri,tis.
Stremp.le e~ al (14), studyi.ng data collected prospecti vely
from 50 combat casua1 ties, n~ted a significant increase of
"leaked serum protein" '(albumin) in the gastric juiae prior
ta bleeding. They c1aimed that tnis was.due to inc~eased
Ht back diffusion through a diseased mucosal barrier with
re1ease of histamine and serotonin increasing capillary \
permeabi1ity and p~rmitting serum protein to appear in the
gastric 'lumen. Stremp1e(60~ 116) noted a greater gastric
sodium output in more seriousJ,y ill patients. He sug'gested 1
that the early protein leak and sodium output were on the
basis of early mucosa1 barrier breakdown with the low eqrly •
acid secretion due to increased hydro"gen back diffusion.
These f,indings were partieuiarly notable in those patients
who eventually t?led from proven acute stress gastritis. ,
Gastric mucosal integrity is usually evaluated by i
rneasuring Qet volume flux rates, net ionie secretions and
the net ionie flux rates of hydrogen, sodium, cbl'or~de- and "-
potassium, as weIl as Qy determining the gastric absorption
',1 n
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38.
of lithium ions which paralleis back diffusion of hyq~ogen
ions (117). Measurement of the potential difference (PD)
across the gastric mucosa is an alternative method(I04} .
Hogben(I~8) has shown that the PD in the-frog's stomach
in vitro is dependent on active transport of chloride, ions
into. the <lumen, against their concentration gradient (lumen
to mucosa). The permeability of the upper gastro-intestinal
tract to, chloride ions is in the following .. order: duodenum>
antrum) fundus. Th~ greatest PD can be found in the fundus
where chloride "leak" is least. This m~ght reflect the 1
higher energy consurnption of the fundus, site of predilection
for initial stress gastritiS", to maintain its more
sophisticated mucosal barrier intact and hence its greater
susceptibility ta breakdown in' condi tions of inefficient mucosal
blood flow(52). McAlhaney et al (72) studied the integrity
of the gastric mucosal barrier (GMB) in a series of patients
within 72 hr after severe burns. Ten gastro-intestinal
complications were dopum~n~ed in the group with a disrupted Q
mucosal barrier and only five complications dev,eloped in
patients with an intact GMB. They pointed out tllat these
. ~ complications (hemorrhage, perforat~on) could occur w.ith àn
apparently intact GMB, however progressive, mucosal damage and
occurrence of clinical complications were more often associated
with disrupti~n of the GMB.
-As in many other aspects concerl)ing the pathogenesis
of aèute stress 'gastritis, there exists a healthy Gontroversy .. regardilJ.g the exact role played by the GMB", While man y
authors, 'such, as those mentioned, implicated an altered GMB , '
i~~~'"'1~~~~~~~ .. t'1'" tE , .. nrht!tJIMI-' fWl~·'ii>--'"'--'~.-..NlIot.~j~:tt~/"#>-· ...... .i«"t","""",,!.l'w,,-,r~J.~I"-'-"""':i ';'O'p' ..... h .... ' ..... ·--' ... ~,' ... 4"' ... ' ....... _ ........ ,-;-, -rl--- - -., - t ~t .;.'
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39.
as a prime culprit, others have downplayed its eti0logical
significance. Moody and Aldrete(119) , working with
exteriorized ca~ine fundic segments, noted that endotoxin
and hemorrhagic shock induced erosions were 'not accompanied
by an increase in back diffusion of hydrogen ions. Both
Moody et al (64) and Stremp1e et al (35) questioned the
validity of Skillman et a1's(105) conclusion concerning
increased hydrogen back diffusion' in their shocked rabbits
previously mentioned. In effect, they pointed out that data
from Skillman et al's shocked rabbits indicated that the
GMB was intact'for the initial hour following ~he onset of
hypotension and that it was not determined whether the , 0
increased back diffusion of H~ did not fol10w rather than'
precipitate the lesions which have been noted minutes after
onset of shock(67). Fischer et al(120), in a recent study,
eva1uated the amount of hydrogen back diffusion in 12
trauma patients for 48 hr post tr~uma. When comparing his o
data with that found in 7 age-matched control pati$nts,
they found no difference in the gastric mucosal pe~eability , \ ~
to hydrogen ions, despite the subsequent deve1ppment o~
c1inically overt stre.s ulceration in 25% oi the i~jured
patie'nts. . ,
They concluded that increased back diffusion of
hydrogen ions does not prece de ,erosivè gastritis and does
not uniformly occur after 'the establishment o.f erosive
gastritis, however, it may contribute to the progression of
erosive gastrîtis to ulcerative gastritis, the later stages ~.
of- acute stress gastritis. Unfortunately, ,the integrity of
the gastric mucosa i~ the trauma patients was studied only ,
,f. L
(
o
40.
for the first 48 hr, while the patients who bled did 50 days
later and it is therefore possible that increased back
diffusion was a factor at any time after the 48 hr test
period. Also, endoscopy was not used as an adjuvant early
diagnostic procedure.
As Silen,and Skillman(53) and O'Brien et a~(12l) have
recently pointed out, it is possible and very likely that
the concept of ~isruption of a static gastric mucosal
barrier has given ~ise to much of the difficulty and
discrepancy. This is compounded by the different species
that served as animal models as well as by the variable
methods,used to study the barrier. The gastric mucosal
function~ state is of primary importance: a more active
secreting rnucosa with its greater alkaline tide is able to
withstand the back diffusion of more~Ht than an inhibited
mucosa with a poor blood supply. If the barrier iS,regarded
as adynamie phenomenon rather than a st~ic anatomie gate
of some ki~d, then its importance in the protection of the ;J
m~cçsa Decornes pararnount, whatever the absolute amount of H+
wnich disappears from the lumen. Since the presence of Ht~
i8 essential to the perpetuation and exacerbation of e~en
very early lesions~ even minimal back diffusion of H~ less
than could be perceived by those studies that did not note
an increase, could inflict damage on me~abolically inhibited
tissue momentarily unable to cope"with even such minute
quantities. Back diffused'H~ eventually acèumulates i;stead
of beinqpromptly dealt with and washed away by an adequate
.ucosal perfu:;ion. Once mucosal p'erfusion has been'
"" \ "
"I~n?!I~~'''~ .• ~~·'·'~~~__ __ j ----- ----,-----,----.-,---
'",c_ 1 ~ ~ ~- ~ ... -~--: '"'~ ·''''/T
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41. ..
, reestablished after resuscitation, then as Davenport
described(122), and a~ depicted in Fig. 5, accumulated acid
stirnu1ates the intramural plexus of th~ stomach and by this
means stimula~es the secretion of pepsinogen. Histamine
is liberated from mucosal stores and histamine-forming
capacity is increased and further acid secretion is stirnulated ~
at a time when injured mucosa is already unable to cope
with the existing acid load. ~jstarnine promotes vasodilation
and inèreased capillary filtration and fluid rapidly enters
and aè~umulates in the interstitial space. Histamine aiso
increases the perrneability of mucosal capillaries to plasma
protein, which is shed into the lumen. Finally acid may
rupture mucosal capillaries and then both interstitial
and intraluminal b1eeding can follow. Lucas et al (51)
a~tempted to relate this sequence of eve?ts to scanning ,
electron microscopy findings on the intra-operative biopsies
of.6 patients with proven stress ~rosions. They noted that
contrary to the normal intimate connections' between laterai
cell membranes and intact apical mucus (Fig. 6), there are
areas of "al tered empty" sürface epi theli{l.l cells which had
presumably discharged their apical mucus and defoltated
adjacent ta normal appearing cells - (Fig. 7). Moody et al (64)
propos~d that sorne surface cells at predetermined sites are
destined ta rapidly expel their apical m~cus wh~n confront~d
with decreased blood flow and hydrogen ions bn their ,
mucosal surface. These cells then ~~present a break in the
continuity of the integument and a site susceptible to 1
iurther destruction by-hydrogen ion ~ermeation with graduaI
, .
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1 1
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.1 42.
destruction·of adjacent cells. The focal natu~ of these
lesions, as noted both by Harjola and Sivula (85) and Lucas
et al{Sl), might further explain the lack of documented
increase in H~ back giffusion in hemorrhagic or endotoxic
shock; increased back diffusion rnight be lirnited to the
few focal areas of erosion that eventually enlarge and
initial decrease of mucosal perfusion decreases back'
_ absorption capacity of the 'mucosa (53). Davenport,(l22} has
shown th~t under adequate conditions a severely ruptured
mucosal barrier can recover in a feW' hours. J
, It is beyond the limitations of currently available ,
methodology to de termine when Hi- back diffusion, albeit
minute, overwhelms the already a1tered and injured mucosal
function secondary to alterèd nutrition, but the quality
and quantity of the intraluminal contents, as will be 'seen
in the'next chapter, will have a definite effect·on tipping
_. the delica te balance in favor of mucosal destruction.
2.4.3 Intraluminal Factors: Acid and Bile
Once the intrinsic' <;l,n?-- dynamic intracellular metabolism .;'> .... i 1
of the gastric mucosal cell \has been injured ~y ineffective . .
perfusion, the gastric ~ucosaothen becomes susceptible to
the very hostile intraluminal contents, such as acid and
bile: Whether it can contain these aggressive agent
avoid destruction will depend on.how fast it regàins 'i s
integritr as ~ell as on the content~ and conceft}tatio of
these agents.
. ' ...
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43.
Acid
The concept of hydrogen back,diffusion as weIl as the
sequence of events triggered when H+ accumulates in an
impaired mucosa have been discussed. The actual contribution .
of hydrogen to acute s-tress gastritis varies from one author . to the next. It ,ranges from being the main and essential
t'7'O) factor , through having the :r:ole 01: perpetuating and
exacerbating ischemic induced lesions(54), to finally having
only minimal if 'any importance in the whole process (123) .
The d.iscrepancies in emphasis of the importance given the
role of acid secretion in th~ initiation, perpetuation and
exacerbation o~ acute stress gastritis are related to the
variability in the results obtained frOID different studies;
this in turn is related to differences in patient sample,
timing and technique of gastric acid sampling. Finally, only -
net 'acid output ~an be evaluated, because the simultaneous
clinical evaluation of back diffused and intramucosal
stagnation of H~ is beyond the limitationa of current
methodol09y(120). Animal models have also shown variable ..----~-----\
results a~d even uniformity of res~~o not necessarily ----------~----mean app+icabilit~to~ only real human model: ,man."
~
However, results obtained from sorne studies are worthy of
mention.
'A series of studies done in seriously ill patients have
shown,an initial, decrease in recoverable net acid output
after inju~y that gradually increases to a relative , ' \ .- -
"hyper~ection Il in the days following resuscd. ta tion.
and ,Clark(61) noted this sequence whil~ prospectively
Watts
"
l
I~
1
44.
studying post intracranial trauma patients. Bleeding
. , -amongst their pat~ents started after the appearance of
hyperacidi ty, ,approximately 3-8 days post trauma. Stremple
et al~35) remarked that clinical bleeding in a series of
military trauma patients was related to the onset of
hyperacidity, which occurrèd by the 2nd 'or 3rd day following
combat trauma, after an initial low mean acid output for the
first 24 hr. Lucas et al (51) noted that ,the peak in acid
secretion'studied in 5 trauma patients usually oc~urred
between the 3rd and 5th days following severe trauma after an
initial ,post operative depression d4ring the first 2 days.
'Gastric secretion was initially low in patients with septic
shock but increased strikingly when the fluid and hemodynamic "
derangements were correc'ted in spi te of persistent sepsis.
They noted that the hypersecretion of acid and gastric
juice occurred in the days preceeding qleeding from erosions.
In a recent prospective 72 hr study of gastric acid secretion
conducted in 36 civilia~'trauma patients, Stremple(60)
reported a normal mean acid output in. the ~ore severely
inju~ed patients of 20t SE9 mEqjl2 hr during the initial_
12 hr period after trauma. ,However, the 12 hr output 1
'-
ihcrea~ed marked1y in the ,more severely injured to a mean of'
43% 6 mEq/12 hr between 24-36 hr after injury and continued
to" inc_rep.se at 72 hr when a mean of 6~~ 8 mgjl2 hr was reached. -
Patients with 1ess severe injuries had a relatively normal
mêan acid output.throùghout the,first 72 hr after trauma.
When mean l"eve1s of acid output of these patients were
separated as to the site of in jury, there waS a marked increase
-l. ... __ ...... 11I1 .... ". Ar n ... 1 .nt.ultt ....... tn r
l '
..::;.----
45.
between 24-36 hr in patients wi th abdominal injuries to a mean . , ' ,
of 55! 10 mg/12 hr, while patients wi th cranial injury always
had a normal or lower than normal me~n acid output. He also
noted that there was no evidence of a significant increase in / serum gastr~n.
O'Neil et al(124} ,not~d an initially "low"
secretion in a series of burn pàtients, and despîte a'lack of
correlatiqn between absolute hyperacidity and ulcerat,ion, he
noted that the return to a, normal, or a "relatiye" gastric
~yperSe~~ion seemed significant in those who developed
stress lesions. The initial decrease in recoverable acid
rnight be d\,1e to one or both the following facto:r:s:
1) decreased acid production secondary to persistent
ineffective rnucosal perfusion, 2) incre~sed back diffg?ion '!~
due to broken mucosal barr~er. ..
After return of adequate
rnuc"sal perfusion, aci~ secretiqn increa~ed and it was at thiS('('
point, as stated by Strernple et al(35), that the irij~red , , 'rnucosa was most susceptible to the acid wave. Further mucosal
breakdown eding would occur if rnucosal recovery
lagged.
Rosenthal ~_a_l_(59) found en~oscopic evidence of
stress gastritis in burn patients with 16w
acid secretioIi. In ~ group of 10' patients· whose condition,
stro~gly. sugges les ions would be l~kely to
develop and who'underwe~t d~ily acid levels, .ul~ers app~ared ~
in 3 of these 0, however acid determination prior to _ '\
bleeding indic ted only minimal hourly acid outputs (125)
erspective.concerning the role of acid in the , ..
. .
1
J 46.
pathogenesis of acute stress gastritis can be ~ained by
briefly re'l.iewing s~udies wher~ intra1umina1 acid has been .
adequately neutral·ized. By neutra1izing 'intragastric , ,
acidity, Davenport was able ta return the gastric mucosai
barrier to normal and stop intragastric bleeding wi,thin an
h 'ft ,.' d d" ", oh 'd (126) , , our a er asplrln ln uce l~JMry ln t e og . Slmonlan
and Curtis (70) obtained an 89% control of hemorrhageln 1-
patients blj:!eding from erasions ,by instilling antacid buffer •
through a nasogastric (NG) tube in sufficient quantities
to maintain gastric pH at 7. Mead and Fe1k(127) deGreased \
the ipçidence of post cardiac and thoracic surgical gastro-
~ntestinal bleeding from 22% to 2% by insti tuting a
prophy1actic antacid regimen: McAlhaney et 'al (72) noted - - ~--------.
that only 1 of 24 burn patients developed a significant _ b
upper gastric intestinal bleed whi1e on prophylactic antacids > ,
- (gastr.i.c pH màintained at 7) in contrast to 7 ,of 24 patients .
(29%) receiving no antacid! SHen reported in ~u-\,(128)
that after starting a prophylactic antacid regimen
the gastric pH above 5), not a 'sing1,e patient needed •
operated upon fot'str~ss 1cer in over 600 admissions to ~
their surgical intensiv 1
.~eported rapid and dram . ,
series 0f critic~llY,ill .. ~~ute stress gastritis. ,'. '
hav~ stopped spontaneously b
MacDOnald et al(129)
i ~ the-lcontrol of
s with endoscopically proven . note that bleeding might
. . ., that hi's findings
underlined 'the importance -of e genesis of b1eeding , (130)
from st~s erosions. ,. Burlansi and Parr al so _reported ,
,0 C'.
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, (
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47.
that 67% of a series .of seriously ill patients bleeding
from stress induced gastr c les ions were controlled with the
administration of cimetidine given eithèF intravenously or
orally until the patient re~ov ' ed from his underlying
illness. In a contralled trial i volving 46 patients with
" (131) • fulminant 'hepatic failura, MacDouga et al randomly
gave 25 patients enough intravenous ci etidine to main tain
an intragastr~c' pH abovë(S\lwhile the ôthe - 21 patients a "
-'served as controls. Only ~ patient bled in he treated
group, whereas 11 of the 21 controls de'veloped bleeding
CP ( 0.001). AlI 12 cases' af bleeding were fram , 1
endoscopically proven fundal erosions.
It is safe to conclud~ that current clinical gast ic
acid secretion studies oan give only a loose a'pproximation
of the role of acid, however data accumulated t~date tends "
to indicate that gastric,acid is an essential etiological
factor, 'if not in' early acute stress gastritis, at least
in the perpetuation and exacerbation of this process.
!
Bile
Despi te the fact that bile reflux and pylo~_ic
sphincter incompetence· ,have been reported to Re, normal
physiologie v~riants and do not necessariIy entail gastric
di~ease (132, 133), bile salts have been shown to destro~
. "" the narmal,gastric mucosal ~rrier, i~ man, hence its
\, c tributory role in the pa~ogenesis of aeute stress
'\;rast i tis (llS) •
\'
'I
1
,: ".
'1
(
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48.
Con~rary to Skillman et al's(lOS) f"ndings that the
comb:\.na tion of severe shock' and ac,id ,,>
to produèe gastric lesions in washed
e were sufficient
i Istom~chs tha t
had been ligated at both the pylorus and "cardia, Hamza and
Den ~eSten (134) noted that in ttre-ir dog odel with an occluded
pylorus and mean' blood pz;essure maintain d at 40-50 DUn Hg for J ,
41 hr, the association of both acid and ile salts was
necess9ry for gastric mucosal lesions t
Shirazi ~et al(135) noted that the combi
appear. Safaie-
gastrii.c
mucosal ischemia, bile salts ànd aci4 l d to acute ga~tric
lesions and the removal of any one. of t ese 'factors failed
to produce mucosal ulceration. Himal e al (136) concluded,
using in vivo explants of canine antrum placed.in lueite -,--chambers,_ that' the insti,1lation of bile or, HCl alone did
not cause acute gastrie erosions 'wherea the insfillation
of' both produced aC,)lte erosions. ,Rimal <13,7) pointed out that l ,
acute gastric erosions secondary to bille or duodenal refl ux
oqeur only in hypotensive animaIs with Ideçreased gastric
mueosal blood flow. O'Brien, and Silen <;138) noted that bile '/
salts instilled into denervated cani~elfundic pouches caused
a reduction in gastric mucosal blood fiow. They noted thàt /
1
solutions containing 40 mM and,lO mM sq>diurn tau~ocholate in
80 mEq per litér of H'" 'decreased the Glt~F (gastric mucosal
- blood 'perfusign) using the aminopyrine clearance technique' te ~
19.6% and 49% of -control values respec ively. This could
exacerbate the already inefficient saI pez;fusion or,
early acute stress gastritis.
Guilbert et al (139) noted "that te gastric
. ,
(
,g' -
L
'in their
') hernorrhagic shock canine model was always prece ded
49.
, ,
,~y reflux of duodenal contents into the stom~ch and that " ,
both t:he occlusion of the pylorus as well as the inhibition
of the trypsin in the chyme prevented the development of 1
gas'tric ulceration. They also 'l1oted that under the influence
of shock, duùdenal and intestinal chyme, in .the process of
refluxing, appear tO br ing i-nt? the stomach high levels of
hydrolytic lysosomal enzymes derived "from the necrosing
intestinal mucosa. Stremple et al (35) reported from their
trauma series that bile may be important to mucosal damages
sinèe twice as much blood was present in those patiènts
who had evidence of bile pigment in t~e gastric contents.
" However, clinically significant gastro-intestinal bleeding
or an increased amount of leaked se:J:"um,.protein (reflecting
mucosal barrier breakdown) did not correlate wi th the
quantitative estimation of biliverdin in the gastriLc juice.
They suggested that quantification of the amount of bile
refl-ux would be a better ,measurement of the importance of ,
this factor. Since ileus and' duodenal reflux, even if not
noted during trànsient ~ndoscopic exam,ination, is common in
the acutely nI patient (38) 1 the already impaired gastric
mucosa is then persistently bathed with duodenal contents
and bile then has a greater opportunity to exercise i ts
destructive mec;:hanisms. The gastric mucosal barri~r is then,
broken from both the serosal and' lumenal sides' permi-tt-ing
acid to accumulate and overpower the s'luggish mucosa. The , -
stage is then' set for persistent mucosal d~age and th~
.development of 'full blown acu-te stress gastritis u'ntil one , " ,
( or aIl of these three interrelated factors are con troll
1
.......
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CHAPTER 3 MATERIALS AND METHODS
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51.
CHAPTER 3 MATERIALS,AND METHODS
In order to properly evaluate the incidence and
evolution of acute stress gastri tis, as weIl as the possible
effects of certain pre-defined factors in this process,
several prerequisites are necessary. First of aIl, in or der
to gain maximum uniformity, the observations should be ;
()
limited to patients whose gastric mucosal changes are
effectively due to acute stress gastri tis and not to sorne
predisposing condition such as a jctivated peptic ulcer
due to recent ingestion of sorne chemical gastric irritant.
This requirement is adequately fulfilled by judicious
or
patient selection. Secondly, direct and clear ~ vivo
visualization of the entire gastric mucosa must be available
both during the early and later phase of the acute illness.
This can be accomplished with the use of a fiberoptü:
panendoscope. The endoscopictindings, often quite complex,
need to be standardized to becorne comparable; hertce an
endoscopy scoring system needs to be established. FiQall~
~
if any attempt is to be made to correlate the severity of
acute stress gastritis with certain postulated factors,
close monitoringo (at no additio'nal cost!) of the selected "
-'---patients becomes essential. This can be best accomplished
in an intensive care unit where not only is routine '. monitoring available, but also post endoscopy monitorinc;J,
which is essential in view of the 'risk of this technique
in already compromi~ed patients.
, ,
L
52.
3.1 ·Clinical Material
Admission into the study was thus limited. ta surgical
intensive care unlt patients who were both essentially weIl
prior to the onset of their acute~ illness and whose acute
'illness began less than 72 hr prior 'ta their admission into
the unit. Particular attention was applied to eliminate
patients who had any recent or past history of esophago-
gastro-duodenal disease or any recent excessive ingestion
,of any ag~nt (ASA, steroids, phenylbutazone, alcohol,
anticoagulants etc.) that might affect the gastric mucosal
endoscopie appearance. Patients with ehranic liver or lung -.'
disease were eliminated. Of a total of 36 patients (12
female and 24 male), who met these initial criteria, 9 were
eliminated prior ta either the initial or second endoscopy
for any of the following reasons: refusal by either the
patient or the patient' s family to consent to the endoscopie
procedure; persistent objection towards the procedure by
either the patient's surgeon or nurse,'or because the patient's
condition was judged to be too precarious ta tolerate endoscopy.
Because of technical difficulties with either the endoscopie
intubation or the apparatus itself, a further 7 patients
were eliminated. Finally, the clinical :;ample consisted
of 20 patients who were divided into two groups: a trauma
group (2 females "and 10 males with a mean age of 31."6t 4.36)
and a non-t:raumà group (3 females and 5 males with a mean age
of 52.4:t 6.03). The prirnar~ condition leading to th~ir
admission to the surgical intensive care unit can be found
in Tables 1 and '2.
1. ~~.'lII""'IiI.~·"""t'<'llllt.t""'Ii~~'1""'9lAOI"'?f""-"',_jôiiliil ____ II,\:i\l~"","",,;Qi;I1o;~_~~~ .. "P.::;>!il:~t4i~>, • t~c:.,· ----'~---="'----
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53.
3.2 Factors Studied.
Monitoring of these patients included hourly vital
signs, frequent arterial blood gas determinatiort;s, repeated " \
blood, sputum, wound, urine etc. dultures. A host of routine
laboratory tests wére carried out daily, i-ncluding complete 1
blood counts, renal and hepatic function tests and these
were supplemented by more specifie tests such as coagulation
?tudies when indicated. Particular attention was directed
at determin:0'Lg the presence of ~certain "primary" factors .. that may have sorne etiological significance in the genesis
of acute stress gastritis. These factors were:, hypotension,
hypoxia, sepsis, renal failure and necessity of meehanical \
ventilation. The criteria of these primary factors are
descr ibed in Table :3.
3. 3 Endoscopy
Prio~ to performing an endoscopie examination, the -- '-::..!
patient's'progress was closely scrutinized so as to rule
où~ any gross contradiction, sueh as'a fresh myocardial 1.J
infarçtion, any recent cprdiovascular,instability or a
recently qeveioped coagulopathy. The procedure was then 1
diseu~ed wi'bh tl'l.e SUl7'9'ical Inten~ive care Unit staff 50
as to aseertain the patient's àbility to withstand an
endoscopie examination as weIl· as to eliminate any h~therto
unknown eontrapietions. The patient was then informed of
the projeet and given a full deseript~on of the procedure ~
by a third party who then obta'ined the necessary consent.
411 &bMn.'
) : ,
,
, .
L.
r
54.
If the patient 1 s state of consciousness was al tered, the
information was given to and consent obtained from the
inuuediate family. These steps ~ere ,.me,ticulously adhered
to so as to minimize the increased risk of such a procedure o
when done in critically iii patients. Initial endoscopy
was performed on the 2nd or 3rd day,after the onset of
acute illness and repeated between the 5th' ilnd 7:t.,h days. ~~
3.4 End?scoPY Technique
Patients were kept fasting the night prior to endoscopy.
Endoscopy was performed in the Surgical Intensiv"Care Unit
with the patient in the 1eft,lateral decubitus positio~.
When the patient's condition (multiple fractures, chest
tubes etc.) precluded such posi tioning, the procedure was
performed in the right or dorsal decul;li tus positions. The
nasogastJic tube, if present, was left in place. ,Ten to
20 mg valium were 'given as a' slow .. intravenous infusion with
the dosage being tapéred to the patient's age, size, condition,
recent medication and resPQI)se to the slow1y infused va,lium.
An Olympus GIF (gastro-intestinal foreward viewi~g
fiberscope) panenùoscope, type B2, was used. Comp~ete
examination,' as described by Tsuneoko (140), was carried ouf. ~ .'
of the esophagus, aIl areas of the stomach. Gastric
dilation was main'tained at levels suffic.ient to maintain ,
partial flattening of" th~ fundal folds 50 as to increase
uniformityand facilitate visualization of smal1er lesions.
General appearance of the gastric mucosa was noted, for
, . • ji';j."httalf.J!N~ilII_#t:"'-'1!' ~1~i>'lIIi!''''HI'L!Ur1.tj1' o/,-,I::tI"1 _ .. (~ 1I~I'!!~li. Il li
{ \
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diffuse changes (pallor, mottlin9, erythema etc.) and then
the type, size, location, color and nwnber of the focal
lesions were noted. Presence or absence of oozing or e
bleeding was ascertained. -The duodenum w'as intubated and
55.
examined whenever possible. A weIl informed second observer,
familiar with the endoseopy seoring system was present
throughout the procedure and had simultaneous ~ccess ta the .".
endoscopie view through the teaching scope. Numerous still
photographs 'of the gastric mucosa were takeh using a 35 nun • ~ 0 1
Olympus camera ~ These were supplement-ed wi th cinegastro- , photography of pertinent areas using a 16 mm Bolieu cinecamera
mounted directly on the gastroscopy lens. Biopsies were not '\
taken.
3.5 Endoscopie Seoring System
An endoscopie scoring system was .... developed 50 as to . " 3"
, . promote .clarity, uniformi.ty and comparabiHty, of the
endoscopie findings. Points were allotted in respect to
" the type of gastric mucosal change visualized
Endoscopie finding
A) diffuse changes: ~ Mucosal pallor, congestion erythema or mottling ,(Fig., 8)
" B) Focal mucosal petechiae or mucosal
,hemorrhages (Fig. 9)
C) Focal cÙcula~ red or black based mucosal erosions (Fig. IO) 0
D) Mucosal' ulceration (Fig. 11)
l,-
Score'
t ~
,
r 2
3
4
a .,7. M n 141. 4 j • .,.i~ •• fIt.II!liaMtil1tdt'Jt~,liit,.d~*"** t i' Mt ;""'1 # ~ •• f u .. i'v .. , .
:
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56.
The final endoscopie score depended upon the lesion or
combination of lesions noted sitnultaneously by bath ,/""/ 1
obserVers .. The simultaneous presence of. erosions ,on a
ba,?kground ofo
"endoscopi,c gastritis U(erythemaJ mucosal , hemorrhages) would calI for a score of 6. The presence of
aIl these changes at the ,same exarnination amounted to a full'
blown picture.of stress gastritis and resulted in the
maximum score of 10. A score of less than 4 was defined as
mild acute stress ga'strit;is, less than 7 moderate and 7
and over severe stress gastritis. Availabilityof
photographie or cinematographic confirmation inereased
objectivity of thë findings.
3.6 Cimetidine Protocol
There was no interference with the patient management,
which was under the control of the treating surgeon and the lfI
Surgical Intensive Care 'Unit house staf/_ However, antacids
under, any form were withheld throughout the study pe~iod
(1 week) except in 4 trauma patients whose initiàl
endosc'opic' examination 'revealéa. the presence of blood' 1
active!y oQzing from fundal érosions and/or ulcers. These
patients were prompt1y started on the H2 antagonist
Cimetidine protocol. Four-hourly gas~ric aspirates were
checked for pH using Nitrazine paper. If the pH was above
3, 3QO mg of dimetidine were given in an ).ntravenous
infusioQ over a 10 min periode rf the, pH ,dippèd below 3,
the do-se was do\ll;)led to 600 mg giyen in the same fashion.
" ' .... :t ... l~ h •• ,.',[ .. ·,,'~'pfi~r p'!f ..... tlli --.~~~~ ... ~~*,\,'L't <.;;~ ÉIz
. ..,
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57.
This was continued until the second endoscopy on the 5th ta
7th day.
J 3.7 Statistïcal Analysis
rp..he differences between groups (Tables 4 c& 6' and Fig. 13)
were tested for significance using Fisher's exact probability
text or x2 for non-parametric measurernents (normal data) (141) .
Serni 9uantitative and quantitative data were analysed .
through variance and covariance analyses.
Classification of the subjects in Table 6 according to
the nature qf injury (trauma or non-trauma) as weIL as "
between the first and second endoscopie examinations led to
the 2x2 factorial design(142).
The Mean and SEM (Standard Error of Mean) are presented
for each sul;>group. The significanc~ or non-significance df 'c'
the evolution of any given group was tested by using the
Student-T test for paired values (mean of the individual
differenees) (143, 144)
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CHAPTER 4 RESULTS
~~"'~""_iIlMôliiOl"'''.''''''iI''III*'''UIi1'fIiW.l.''''.''''·''' .... , .. , ..... ,tlilll •. _ .. IIIoi· ..... IiI ........ ' .......... ' .. T.,'"', ... , ... ,_._. __ .............. "", ... __ .. _ .... __ : •. 8'" .. _ .. : ... ~~.-.2,~,_,_'"'"
"
" CHAPTER IV' RESULTS
~enty S~rgical Intensive Care Unit patients, 15 male
pnd 5 femalè, with à mean age of 40.55, consented to and
successfully underwent an initial and a second endoscopie
examination. Sixteen,of these patients remained free of
any clinical or endosçopic, evidence of gastro-i'ntestina1 ;
bleeding. Initial endoscopie examination documented mild
muco.sal oodng in 4 trauma patients. None of these 20
patients needed or received'any blood transfusions. The
58.
c~inical outcome of these patients was successfu1 in 18 of '\
these patients, being discharge~ from the Surgica1 Intensive
ca~e Unit within 14 days. Howeve~, 2 (T12 and'NTl ) patients
expired, b'oth of Overwhelming sepsis. The patients were
divided into a trauma group_ (N - 12) and a non-trauma ~roup
(N - B). Pertinent c1inical data can be found in Tables l
and 2.
4.1 Initial Endoscopy Results
- The initial 'series of endopcopic examinatibns done on
~he 2nd or 3rd day after ~nsët of acute illness revealed - ,
~bnormal_mucosal findings in aIl 20 patients, albeit mild i
in 2 patients (TIO a~a NT6). A summary of the individua1 -
endoscopie findings in relation to the "pr:i"me factors" is
presented in Table 2. The overall me an initial endoscopy
score was 5.55t .67. The trauma group had a rne~n initial' "
endoscopy' score' of 6.6:t 0.78, while the mean sc:ore for the
non-traÙlna group was 1.87;!. 0.21. Seventy-f ive percent of
: . . '~
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,
trauma patients were found to have mucosa1 erosion anèD/or
ulcerations, while the early ~osal ch~nges in t~e. non- '
trauma gro~p were limiteâ to mucosal rnottling and/or
hemorrhages in aIl but 3 non-trauma patients.
59,.
The distribution of certain previous1y defined "prime "
is p:çesented in Table 4,.
attempt to de termine whether the presence of
any. these factors had any main effect on the initial
" endo~copy score, the mean endoscovy score"obtâined from , '.
patients with that particu1ar factor was compared with the
'm~an endoscopy score'of the rernainder of the samp1e (Table 5).
Except for hypoxia, the presence' of a postu1atéd "prime '>
factor" was. consistentl~ associated -with
score than the remaining-sample who were
partir.~lar factor.
4.2 Evolution of EndoscopX Findings
4.2.1 Total sample'
a lower endoscopy
free ;~at "
')
1
) .
The overal1 (N - 20) èvo1ution of the individua1
endoscopie scores is depicted in Fig. 1. There was a
,si"gnificant decrease in the overall meal) endoscopy score of ' f
5.55 ~ .q7 obtained early (2nd or 3rd day) when compared to "
"the overall (N - 20) mean of 2.85 t .65 tabulated from the,
second en'doscopic examination done on the 5th-'7th days "
after onset of acute illness (p <. .01). This evo1ution is
depicte4 i~ Fig. 12.
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4.2.2 Trauma vs non-trauma
i \ "
60.
When the endoscopie eV~lution,is ~etermined_separatelY . ,
for, bath the tra~a and non-trauma groùp~ (Table"" 6) '. the
me an score decreased from 6.16! 0.,78 ta 2.58::t 0.78 in the former
(N - 12),and fram 4.87,tO.21 tp 3.20.tO.13 in~the latter .'
(N 8) • Despite the higher initial score in the trauma group
~s~s the non-t~~um~ group, there was a more notable
-improvement in the former so that the overall trauma score
(bath initial and second~ was nearly identical ta the
overall non ... trauma group score, 4.29: .76 and 4.06! .19
respectively. There was no interaction between this
evolution of the~ two groups, meaning that there was no ,
significant difference between the evolution of bath groups,
however, the decrease in the endoscopie score was
'v
significant in the trauma group (p (,0.5) and nan-significant
in the non-traumà group. There was a correspondi~g decrease
in the percentage of patients with erosions and ulcers:
75 to 16% in the trauma group and 'from 37-25% in the non-
tr~uma group.
4.2~3 Severity of trauma
using a trauma score system,(145) 1 where 1 point is
al10tted ta injury of each of the following'regions: head,
chest, abdomen, pelvis and long bone (excluding radius and
, tibia), the endoscopy sco're ev:olution wa_s eomp~red with
severity of trauma. The mean endoscopie score is seen
ta decrease significantly (Table 7) in bath the low trauma
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point (1-2 points) group and in the higher trauma point
(3-5 points) groups. In the former (N - 5), the mean
61.
score went from 5.671" 1.48 to 1.83.! .31 (p ( 0.05) while in
the latter (N - 6), the endoscopy score decreased from
+ ' 5. 60 _' 1. 60 to 2.0!. 90 (p < 0.05)". ,
4.2.4 Site of trauma
f The evolutio~ of the mean endoscopy score in' relation ,
'1
. ;
-e
',. to site of injury is presented in Table 8.' There did not
appear to be any signifièant difference between the site
injured and the initial endoscopy score. A pigh percentage
of patients with head (80%), chest (75%), pelvic (100%)
and long bone injury were founq to have either erosions 9r .. ulcers ai: ini tia,l endoscopy. The relative proportion of
ulcers versus erosions is reflected by a slightly higher
endoscopy score. Only abdominal inj~ries were associated " with a non-significant improvement in the endoscopy score'
\(T = 1.94)'. Injury to any of the other sites did not have a
dampening effect on the favorable and significant improvement·
in the endoscopy score .•
4.2."5 r
Colon versus non-colbn injury
There was a significant improvement in the endoscopy
score of non-trauma p~tients who ~id not undergo colon
resection (4.25 to 1.75), while there was only minimal
improvement in the patients who had undergone colon ~esection 1
as part of ;heir acute illness (Table 9). The mean second
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62.
endoscopy score latter grqup (4.75) was notably
higher than the overa mean second endoscopy'score of the
abdominal injury grou (2.92") ,,-when evolution of endoscopy
score was compared 'be een 'both tr~uma and non-trauma
patients (Table 10) with colon in jury, a similar pattern
was noted. 1
4.2.6 Number of rime factors
The number cumented factors had no effect on
the initial, endoscopy, those with only 0-2 factors
showed s~gninicant imp ovement by the second endoscopy
examination, groups fr 6.00 to 2.53! .76 (Table Il).
There was no significa improvement in the group of
patients with 3-5 fact rs, who started off with a below 1
average score of 4.71 but had a second mean endoscopy score
of 3.42, above the ov~riall mean s'econd score of 2.82.
1
,
4.3 Cimetidine
As stated earlier,1 4 trauma patients (T 2 , T3, T6, T7),
representative of the remainder of the trauma group, bot~
in mean age, severity of trauma as weIl as number of prime
f,actors, were put' on ~ Cimetidine' protocol after their
initial endoscQPy documented mild mucosal ooz~ng.
In an attempt to de termine the effect of this antàcid
given ~t d~ses capable of maintaining intragastric pH above "
3 (l.B to 2.1 gmjI.V. daily, the evolution of the endoscopy
1
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score of these 4 pati~nts was compared with that of the
remaining trauma patients who received no antacids ,
througho~t the observa~ion periode The Cimetidine group
showed significant improvernent going from an above average
score of 7 ta a be10w average score of 2.75 with cessation ~ ,
of'bleeding by the second endoscopy ex am done 2-5 days after
the initial exarnination. However, a near para11e1
irnprovement was noted in the remainder of the trauma group
in whom actual oozing was not documented (Table 12)"
When these',4 trauma, pàtients with above average initial
endoscopy scores were removed, there remained a near
significant improvement (Fig. 13) in the mean endoscopy
score (p(O.6) of the 16 patients, decreasing from 5.19 on
the initial endoscopy ta 2.88 on the second endoscopYr'
Finally no correlation cou1d be found between the first
and second endoscopy score (p < .28 and .21 respectively),
underlining the potential of the gastric mucasal appearance " ')
to change radiçally for the .better or for the worse from thé
initial ta the second endoscopie examination.
1 1 ~
CHAPTER 5 DISCUSSION
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64.
CHAPTER 5 DISCUSSION
The strength of any observation to be drawn from the
res~lts just described depends heavily upon the methods and
materials involved with the collection of the data. This
dictum applies to any clinical research project b~t becomes
even more pertinent when dealing with such a controversial
and multifactorial entit.y as acute stress gastritis.
Having emphasized, in the earlier chapters, the.import~nce
of clarifying and simplifying the terminology and the
pathogenesis of this entity, it appeared only consistent to
institute a simple and reliable method in attempting to . ,
gain more information concernirg its incidence and
\ evolution~ The flexible fiberoptic endoscope by itself
meets the essential criteria of offering direct and total ,
in vivo observation of the target organ while its technique
can be mastered with a sufficient instruction and experience.
Unfortunately, however, the procedure is an invasive
'one. There thus arises a dilemma where the patient who is
most prone to develop the full spectrum of acute stress
gastritis, i.e. the i~tensive care unit pqtient, aiso
presents the least toleranee to any invasive procedure,
ineluding ~ndoscopy. This dilemma can be-partially solved
tiy exereising judgement and acquiring the right teehnique.~
For additional uniformity ànd 'to minimise diseomfort and
risk to ~he patient" 2 endoscopie examinations, if pertormed
at an id-eal time sequer-ce, ean provi,de adequate, data to
gain pertinent info~ation eoneerning bot? the ~neidence
and evolution of acute stress gastritis. Understandably few
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65.
severely ill patients will consent or.toierate 3 or more
such procedures over a short time span. Out" of 3 e- potential -
candidates, who filled the criteriâ for admiss'ion into the
study, 20 underwent bath initial and sec~nd endoscopic' , ,
examination, an aeeeptanee of 52~ whieh eompare~ favorably , (75)' "
to that of MeAlhaney et al where 7 seriously ill patients
out of'l8 eonsented to a single endoscopie examination., ,
With~this instrument ~nd its optional photographie
accessories, the pre~ence of early gastrie mucosal changes
€an now be doeumented and their evolution followed long /
before they becom~ clinieally evident. The endoscope is thus
tailor ~ade for researeh into aeute stress gastri tis, an 4!
entity that· re~àins essentially sub-clinieal. We no longer
depend' on, the ra:çe <'!iclinical expr~ssion ta obtain pertinent '
clinical dâ'ta. Since, as stated in the chaptel= on
terrninolbgy, acute stress gastritis includes aIl stages of
the de. novo gastric rnucosal changes, that appear seconc;iary to l "
the acute stress situation, the endoscope is undoubtedlyo the
best,available method to observe anQ monitor this process. , • 0
It is also the essential rnethod, without whieh, in this day , l ,,' of "seeing ois.~elieving", there is little hope of " \
unscrambling the'existing confusions. Its reliability has
been unoerlined by c~aja et al(32), who noted a ne~r 90~
correlation be,tween their endoscopie and pathological t-,
findinq8 in a series of a:cut.ely i11 patients. This should
hé 'CQria1dered' in the ,light of the, fact that, contrary t..o the
previou~ endo.copie .t~ie. wh.re endoscopy was done ~i ther 1 l ,
only ODce or et r~, our proto col c~lled for endoscopi~
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examination to be done at previously specHied times.
The rationale for doing the initial endoscopiy
'examination on either the 2nd or 3rd day post onset of
acute illness is based ,on available data from previous'
studies: 1) Stremple et af(l4, 60) stated that both the
gastfic acid output and the gastric mucosal barrier breakdown
peaked during the 36-72 hr period after severe injurY1 this ,
was the period when the mucosa was most susceptiële to
overt injurY1 2) Altemeier et al (146) noted that gastro-
intestinal hemorrhage occurred.frequently between the ,12bh
and 48th' hr after onset of sepsis; 3~ Sugawa et al (50) -
,PÇlïnted out tha,t; there 'was a noticeabl~ wôrsening in the
endoscopie appearance of the gastric mucosa examined 48 hr
after the:onset of acute illness w?en compared with that
seen in the first 48 hr. They also hoted that the early
~ndoscopic" les ions cleared up in ~' matter ot, days iQ patients " f
whose initial illness was successf~ly managed;,finally
- 4) Le Gall et al (76) co~nted that th'eir endoscoPi~ findings in septic patients were often elassified as
stage l or II in thé ~irst 2' post, sepsis days but reached
stage III and IV,after the 3rd o~ 4th post septic, day.
E~doscopy ,done on day 2 or 3 post injury could thefefore he"
predicted to yield more information abou~ early lesions. ,
This-appeared to be compatibie with our data where all
~ndoscoJ(iC exami.nations do'ne ,on- day 2 or 3 showed sorne
i~de'x of acute, gastritis and th,ere_ was subsequent
improv~ent in àll but the cases of persistent sepais
(NT]. and "12)'
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The adequa~e ipterpretation of the endoscopy findings
is evidently as essential as the actual procedure'in this
setting. Compiling the data made ayailable by authors who
pave described their random endoscopic findings in acutely
67.
---ill patients, a certain pattern is seen to emerge. Firstly,
early mucosal cha?ges have been noted as soon as a few '
hours followipg injury (72) If 'T~is complies with the early ,
mucosal changes noted i~,the animat model'as early as 30 min
, after hYp?,tensi(~m (~~). These early changes cons~st ..
essentially of loss of the normal orange-red color of the ( 49) (50) ,
proximal gastric mucosa .' Both Sugawa et al and
Lucas et al(SI, 60) described thei~ earl~ endoscopie o
" findings, within 24 hr of in jury, as "interspersed foci of
pallor, conge~tion, mottling and hyperemia almost
exclusiv~ly c~nfin~d to the proximal stomach". :aerry (49)
noted that the e,arliest changes consisted of patchy or
diffuse areas of ~yperemia and ,edema. Sibilly and Krivosc (63) (75)' .• 0 .
and McAlhaney et al all described,.ea'fly endoscopic ,_, 1
changes consisting of widespread macroscopic. çongest~on
and confluent areas of erytherna confined to the fundus.
âistologic 'examination of these are as revealed micro
vascular congestion and e~ema. On the' background of these -
dif fuse mucosal, qhanges, the more discre te les ions woutd 'J-'
sequential:'ly appe~r, often wit~in ~'48 ~r of injury and would
<consist of petechiae or focal intramucosal hemorrhages •.
The third di~tinct 1esion to appear was the rnucosal erosion.
'Rqesch and Ottenjann (147), quoting SChindler, noted that the, ~
erosion can be endos?opica11y_differentiated from petechiae ..
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or mucosal hemo':r:rhages by the presence of a still intact
mucosal surfàce in the former. Erosions consist of small
round discrete and shallow areas of epithelial d#:Ptions
measuring initia1ly 1-2 mm in diameter. Stremple et 'al(35)
noted that they appear as a slightly depressed well-
defined or circular defect, usually measuring less than
5 mm in-diameter and often situated on the crest of a
ruga1 fold. Histologically, an erosion is a focal area of
necrosis confin~d to the mucosa. These lesion~ can increase
in size or depth, number and often ,change from.an ihitial
red color to black~ The final distinction to be made is
that between" a focal circurnscribed erosion and a mucosal , ...
ulceration. T~e term appear~ confusing bec~use the term-
"gp.stric" u1cer c1assiqa1ly imp1ies penetration of the
muscularis mucosae(48). This is impossible to confirm on
endoscopy a10ne and rests with the patho"logist (14-8)
However, numerous authors have histological C9nfirmation of J '
frank acute stress ulceration(52, 54,114). Lucas et al(S4)
defines these lesions as the final expression of the
process, measuring from a few mm up,to 10 cm, while
Stremple describes them, as irregu1ar funda1 mucosal defects
of-ten. filled wit,h grey material with peripheral hyperemla.
The term mucosal ulceration therefore under1ines the
endoscopie distinction between these larger irregular
lesi~s and their parent les ion, the small round well
defined erosio~, 'without ,necessarily implying destrûction
of the musc~is mucosae. This complies with Robbin'sCl49)
definition of an uLcer: a local defect or excavation of
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the surface of an organ or tissue, which is produced by the
sloughing (shedding) of inflarnmatory necrotic'~issue.
The endoscopie distinction between a focal pinpoint erosion
and ulceration is important to make since Stremple et al(52)
stated that rnucosal ulcerations are the clinically
important les ions because they have the potential to produce
massive bleeding. McAlhaney et al(72) clairns that bleeding
from erosions alone -is rarely life-:threatenin'g, which can
be the case when discrete gastric ulcerations appear.
The endoscopie score used in this' study reflects this
sequential progression. Hence, the diffuse early mucosal
"changes ~re given 1 point. The mucosal petechiae and
hemorrhages are next in sev~rity and-are thus given 2 points.
If the oprocess continues 'to evolve, the more notorious
. erosions appeat. The superficial layers of. the mrlcosa ... -
have sloughed off. This lesion is given 3 points. Finally, - ,
\ l
the "end lesion,r, mucosal ulceration is given 4 points.
Thus, points ,ar~ allotted according to the r~lative severity
of the whole spectre of le~ions instead 9f putting ~mphasis
only on the absence or presence br erosions and ulcerations.
It is interesting to note t~at each in~tial endoscopic
examination done between 48 and 72 hr after onset of aeute
illness showed sorne evidence of changes compatible'with
acute stress gastritis. compa~ison of these early findings
wi th previous reports is often diffiçult,: In effect many
authors either do not report the earlier diffuse stress
changes or report findings collected from endoscopic
,~ examinations apre'ad out over an unspecified time span. 'These
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findin~s are consistent with the 78% of mu osaI changes
reported by McAlhaney et al (75) in his series of 7 patients
with more than 25% burns and who were endoscoped within
5 days of thermal trauméJ-. Sibilly and Kr'iyosc (63) "
'\ rèported that 61 of 62 head trauma patients presented
findings compatip~e with ~cute stress gastritis on a single
endoscopic examination done bet~een day 3 a d 15. In the
• s~cries repo'rted in this thesis, diff4se cha~ es, ·consistàng
of pallor, mottling and erythema wede visib e in aIl 1
patients except one (TIO ) where, defpite doc 1
pypot~nsion on admission 48 hr ea~~ier, t~e mucosa . 1
maintained its normal appearance' eicept for • 1 1
mucosal petechiae.' The:e appea~edl to be- a pa tern whereby . 1 \_
peteqhiae would be usually noted ~n the of mucosal , 1
, ! i pallor, erythema or mottling. l' This of
1· i 1
progression 'tas evident in so Ifar :as focal ero and
ulcers' appeared only on a backgrou'nd of diffus superficial • _ 0
changes described earlier as nendo$copic gastri. is".
Eleven of these 20 patients (refle9~d in an ov~rall mean" endoscoPY ,score of 5.55) were found to ave
\ i
and 5 of had 'in ~dition, d~ve1oped mucosal , .
initial
erosions
ulcerations. se findings tend to',\ support the concept of
s~quential appe rance' 'of these lesio~~ in' accordance with
their severity as proposed in this thesis. Knowledge of
this sequence further distin~uish losalized and
linear ~uces~l changes' secondary te a~;indwelling NG tube
where the background diffuse fundal gastritis is not seen.
Petechiae, erosibns and mucoaal ulcera were confined te
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the fundus, however diffuse antral mottling and particularly .
erythema was noted in 9 cases at initial ~ndescopy. The
predilection of early acute stress gastritis for the acid "
secretïng portion of the stornach has been one of the
hallrnarks qf t~is disease. The defiriite explanation for
this has thus far eluded researchers, however, many theori , ,
have,been advanced and have been'presented in the chapter
on pathogenesis,. The antral involvement re'veals an
interesting aspect of acute stress gastritis. Port y-rive
percent of' the initial endoscopie examinations showed
diffuse antral changes, while only 4 (20%) of these also
dernonstrated antral rnucosal hemorrhages and none had any
focal erosion or ulcers. This wou~d suggest that,
although the antrum may be mOderately susceptible to the
early diffuse changes seen in acute stress gastritis, it has
a rernarkably greater resistance against the evolvement of
th~se early lesions into eros~ons and ulcers. Lucas et al(51)
noted antral involvement consisting of' erytherna and
erosions i.11 3 of 42 trauma patients, who underwent early
fib~roptic gastrocamera exarnination. McA~haney et al(75)
reported that antra1 lesions were encountered in 45~ (N ,- 4) of . '
patients endoscoped early after burns. Both these authors
stated, as wa~ the case here, that is01ated antral
involvement does not occur and only follows extensive . ' proximal (fundal) changes.
Despite overall irnprovernent of t~e second endoscopy ,
score, diffuse antral,erytherna was visible in ,6 of the 20
patients particyla~ly in those patients with persistent
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sepsis (T 8' TI2 ). Both of these had both 'antral eros ions 0
and e,rythema, congestion and petechiae in the duodena~, cap!
compatible with "Duodenitis ". The duodenal mucosa appeared
normal in the remainder of the endoscopie examinations.
These,finqings tend to irnply a diptal progression of the
,rnucosal changes in the face of persistent acute illness.
Actual. rnu,cosal oozing was noted in 4 trauma patients
at initial endoscopy. In 3 of these patients oozing was
seen welling up from srnall found red fundal erosions.
One patient (T6) admitt~d with hypoxic encephalopathy
secondary to severe head and neck in jury, was noted to be
obzing from both fundal erosions and mucosal ulcera~ions.
This sarne patient had undergone endoscopy 24 hr earl~er 1
just after admiss~on to the Surgical Intensive .Care Unit and 1
"a normal gastric mucqsa was noted. The rapidi ty ti th whi9h
mucosal changes can appear is thus weIl illustrat d. AlI
fbur of these patients were noted to have intermittent red
tinged gastric a?pirates in the hQurs prior to their initial
endoscopy., Despite the fact that it cleared rapidly,on
minimal saline irrigation, it waS the only c.linicai
indication of acute stress gastritis.
Certain factors have b~en postulated as being of
particular etiological significance in the genesis of'
acute gastric m~c,osël,l resions: Skillman et al (38) stated
'that these~a~pear to be hypotension, sèpsis, respira~o~y
and renal fa~lure. v
As mentioned in the chapter on pathogEmesis, decreased .
and/or, al tered ~ucosal perfusion is a common pathway through
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which d~fferent acute cliniçal conditions exert, their
i~fluence on the gastric mucosa. (82) .
,Jama' j et al reported
a 5~% (11/19) incidence ~f acute gastric bleeding in 4
previously healthy patients with recent documented
hypotension or shock, defined as asystolie blood ~ressure
of,80 mm Hg or a decrease in blood pressure of greater than
60 ~ Hg with appropriate clinical findi'ngs. Goodman and
Frey (71) also ~mphasized that hypote~sion was the major' /
Ç> precipit-ating factor. This propos'ed favored relationship .1 • ,
could not; be verif ied' by ~his st\ftdy. In effect, although " /-, ". .
the me an initial endoscopy score of the group of patients
with do~umented hypote~~ion or shock was compatible with
moderate stress gastri:t.is (4.83), it was lOJ[er than the
mean sc ' tH'~' -~~\e~ ill pati~nts who did not " 7' ~ \
any dqêumenot~d '~ypot,entioA.'_~2~? This f inding is
comp~ tib1e th tha t o~ Le G9 l:1 et -al (7 6), who noted ~------_ .. /"-
have
that
the i'nciden e of acute lesions ,in patients who had had
ç;Iocumented s h .(72%)· was the' same as in other severelYI - ,
ill patient:s The rapid correction of hypotension
monitored patients is no doubt.partly ,
re1ated t the fact that it does not stand out amongst other
'faC~Qrs. 'In <?n1y tv/o patients (T3, NTl ) did hypoten~ion
-; remain uncorrected for more than one hour, and both of these , ,
_:~~ patients, had evidence of eros ions or ulcers .
.since Billroth (8) first proposed 'a possible association ,
. between sepsis and,ac~fe,gastro-intestinal 1esions, many
authors hav~ emphasized this ~articular relationship (150,
Katz and Siegel(153)'stated that these lesicns are found
151, 152)
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1 Concomitantly with a wide variety of infecting organisms.
There- is a consistently overwhelming preva1ence cf gram
negative Qrgani~ms(35, 41, 154), as was the case in this
74.
series (fable 13) " where 8 patients were, septic at t4e time
of ,initial endoscopy and 5 had positive 'blood cultures.
0re~ again, although s'epsis was associated with ~arly'
moderate stress gastritis, there was no differehee with the
mean initial score of the,non-septie group. Q'Neil et al (58)
were\'also unable to determine a "special" correlation "-
betw~en sepsis and acute mucosal les ions in th~ir series.
This is in great part related to prompt and vigorous
treatment of documented or suggested sepsis. The common
praetice of prophylactic antibiotic eoverage is evid,ent in
Table 2,. The particular effect of sepsis, however, was more
evident at the second e~doscopie examination. In this series',
of 20 patients, only 2 cases (TI2 , NTl ) showed, a notable
deterioration in the endoscopie score compatible with
se~re stress gastritis, while a third (NT2 ) f~iled to
follow ths distinct overall trend towards rapid clearing of
~he ear ly mueosal changes. AlI three of these patients '
were septic at the time of second endoscopy. These findings , '
suggest, as proposed by Le Gall et al (76), that it is in the
cases of pers istent sepsis, particularly of more than 4 days ,
dut"ation, rather than the rapid and successfully managed
ones, that mucosal changes are most notable.
, Respiratory insùfficiency and hypoxemia have long been
regarded as common clinical
àtress gastritis(41, 155)
factors in patients with aeute "
Stremple et al (35) , Hinchey •
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75.
et al(37), and Lucas et al (155) noted(that their patients
who developed acute s~ress he~orrha~e~ad hypoxemia or \
had been on artificial\resPiratory support prior to the
onset of bleeding. It has been suggested that hypoxemie,
as weIl as hypo and
v~ability and secretory
affect the mucosal cellular
fI (37, 156) ow .
In this series, --the mean initial endoscopy " ' , score of the
gr?up of patients
,15 min, indica ted
cumented hypoxemia lasting at least
cute gastritis and was nptably ,
higher than the re~t samples in which hypoxemia had
not been documented. Acut hypoxemia of sufficient
dur~tion ~s usually associ .- with hypotension as was the ,
case in this series, theref it affects directly two major
précipitating elements stress gastritis: decrease
mucosal bloed flow and impai, ed mucosal function. The
concomitant presence of aCià and bile will prec{pitate
severe mucosal changes. The \~an initial endoscopy score
of those patients who require~ mechanical ventilation at '
the time of endoscopy was S~~ar to the rest of the acutely
il1 samp1es. ,
The association qetween 9astr9-intestinal bleeding anq
acute renal failure has been expanded upon in the 1iterature \
(157, ,158) In one series of ttauma patients (35) , gastric
hemorrhage re1ated tp acute gastric lesions was attributed
,to acute renal failure. B1eeding had begun before reaching,
levels of severe uremia (BUN ...,
115 mg/lOO ml) in 17 of 19
patients. 'Amongst the 20 patients in the series reported,in
this thesis, 4 patients deve10ped early acute 10w or high
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output renal failure by day 5 that necessitated hemodialysis
in 2. The mean second endoscopy-score in these patients
was 4.5, compatible with moderate stress gastritis. Since,
as is usually the case, the 4 patients had concomitant /
, hypotension on admission, it is difficult to assess the
relative importance of renal failure itself. Renal failure
in' previously heal thy patients' is often an 'indication of
the severity of th~ initrating hypotension or shock. Close -
monitoring and early institution of hemodialysis can ~xplain
its apparent lack of influence on the mucosal appearance.
Le Gall et al (7,6) failed to note any overal+ difference in
endoscopie results between 2 g'roups of severely ill pati~,nts,
of~which one was receiving hemodialysis for acute renal
failure .
• Early .acute stress gastritis has been found in the , ..
presence of ail "prîme factors". However, endoscopy did not .\
reveal an overwhelming effect of any one of these factors.
The individual presence of any one of these factors is not
therefore a prerequisi te for .the appearance of acute. stress
gastritis. In effect, 2 trauma patients had an early
endqscopic score Qf 6 in the absence of any documented
p+ime factor. . The only common denominator in this series of patients -, .
was acute in jury. The complex me~h~nisms, underlined in .tpe·
preceding chapters, that lead to acute mucosal damage,' are
not necessarily reflected as a clinically perceptible
"prime factor". The threshold for the appearapce of acute
'stress 9astriti~ picked up by prospectiveoendoscopy is
~ 1
(
77.
relatively lower than that of clinically bleeding stress , ,
ulcerat10n and may be surpassed before the precipitating
injury is able to register clinical hypotension,' hypoxemia,
etc. The prompt correction of these conditions in an
Intensive Care Unit appears to diminish their postulated
potent;i.al to adversely influence the gastric mucosal
appearance. I~ appears from the data presented that severe
inj ury, meri ting admiss ion ta an Intens ive Care, Un~ t is
"invariably accompanied by early acute stress gastritis, the
intensity of which cannot be evaluated by relying on the
presence or absence of t;>reviously postulate~ prime factor!?
The combined, effect of these factors however, which often
reflects, 'the severity of the patient's condition, is better
reflected on the subsequent pendoscapic examination done on
day 5-7, where significant improvement was noted exclusively q
in those pati~ents with 2 or less factors (Table 11)'. 1
The Qverall rapid and significant improvement in the o ,
endoscopy score from day 2-3 to day 5-7 of the total sample 1
, 1 ~ 1
reflects the successfui control of the p're,cipi tat,Ülg' factors
:iJL the great majority of patients. By day 5-7, the mean
,number of prime factors @er.patient had been reduced from
1.80 ta .65. That endoscopy
course has been sugges têd b,y
findings parallel the, clinical ,
Suga~a et ;:ll ('69) .,however, the , 1
rapidity and uniformity of the clearing' of mucosal changeS\
iB much more evident in this series. , Given adequate suppo~t,
th~ gast;ic mucosa has a gr~at potentia~ for rapid recovery.
If the 3 patients with persistent sepsi~ were, removed, the
difference between the first and sècond" éndoscopy scor~ wOuld
" .L', _Jlr.r _____________ ... _________________ ,·_~ ________ _
"
'~
(
1-
-.....
78.
he even more striking .. ...
The greël;test improvement was noted in the trauma group
whose initial score was hotably ~igher than the non-trauma
group (Table 6). This group has previously been reported
as being at greatest- risk in t.he development of acute stress
bleeding. This could be explained by the often greater
acute insult suffered by these patients, as weIl as by the
delay before obtaining adequate medical attention.
Howe~er, t~is group, whose ~an age was 31 years versus 52
years in the non-trauma group, showed a remarkable clearing
,of the mucosal ~hanges after only a few days of crose
moni toring. This was refl'ected -in the s ignificant decrease
of rhe. endoscopie soore from ~.i6 to 2.5B (p" O~Oll .
The severi ty of tr~uma, as evaluated by our trauma
sc.or~ system d:Ld not appear to have any effect o~ ei ther , "\
the ,initial or seco~d endoscopy score- (Table 7). ,The oyerall
condition of the trauma patients admitted to thé Intensive ,./
"
Care Unit, is usually severe enough to precipitate moderate
to sev~re 'acute str~ss gastrH:is." The ve-ry s~ple sco:çing
syst~~used evidently does not reflect the presence or 0 ,
absence of associated factors or complications. Although a
more detailed and complex scoring system.~~ available(1~4),
the ~ore simpl~stic one used hère was sufficient to assel:!s
the severity of trauma for the purpose of this discussion •.
,
, '
~he typè and Jsite of injury'has b~en suggested tq
infl~e,nce the incidence df c:linicalV ~vident ,str~~s
hemorrhage (~5! 71, .1~O).. Howe~a8ed on the dat1.. obtained ' 11\ "'1 ..
from- rhi~ s'er'ies, there did not appear" to'be any significant
'')1 \
-'"
..
(\ :
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•
1
-~
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79.
" difference between tpe different sites of injury,and their
resp~ctive initial mean endo~copy score (Table 8). This is
not surprising since the same argument applies here as for
the influence of any particular factor: severe in jury
regardless of site (head, chest, abdomen, pelvis or long
bone) will cause sufficient acute stress gastritis 50 as to •
obviate any possibility of isolating the effect of any
one site versus ano~her. On ehe other hand, although
significant improvement was noted in aIl groups, this was
not the case in those patiepts with abdominal injuries. An •
explanation for this may be found in the nearly imperceptible
improvement of the patients with cqlon injuries (Tables 9 &
10). The particular relationship between col~n injury and ( .
severit~ of acute stress gastritis is in accordance with the
increased incidence of stress ulceration in trauma patients , (161) .
with colon injuries reported by Kunzman . Colon injur~
increases t~e risk of sepsis. Two (NTI ~nd NT 7) of the 3
patientp with persistent sepsis had colon resections done
under difficul t circumstances. This group (severely ill wi th'
colon in jury) appears to be at highest risk for the '1
~ . development ~f severe acute stress gastritis.
Four trauma patient's wno had evidence of mucosal oozing
on the initial endoscopie exarnination were given the H2
*' . , 'd' (76) h t receptor antagon~st c~metl lne . T e H2 recep or
'Vi ' (16'2) antagonist burimamide was introduced by Black et al in
" 1972 as a pÇl)tentt inAibj,tor of gastric aèid secretion.
Metiamide, a more ac'tive.. compound obtained by replacing a
m~thylene group (-C~2-) on Burimarnide with an isoteric
\
\ '
80.
thioether (-8-) ,link in the side chain as weIl as substitu,~ing
an electron releasing methyl group in the ring, was
extensively tested. The po~sibility of agranulocytosis
noted ln sorne animaIs on long term Metiamide led to the
replacement of the thione -5 sulphur atom by a cyanoimino
group =N.CN, hence the introduction of Cimdetidine(163).
Given intravenously, thus avoiding problems relate~ to , (90)
absorption, it acts probably at the cellular level to
greatly reduce acid production (165-167) • Four trauma cases
in which acute stress gastritis was accompanied by
endoscopically documented gastric mucosal oozing on initial
endoscopy were given a 4 hourly intravenous dose adjusted
to maintain gastric pH> 3. The mean endoscopy score of
these,4 patients, who were representative of the remainder . of the trauma group as far as mean age, mean number of
primary factors and mean trauma score were concerned,
decreased significantly by the second endoscopie examination
at which time no mucosal oozing could bé seen. However,
a po~tion of the apparent beneficial effects of Cimetidine
can be attributed to the over,all trend towards improvement
as seen in the rest of the sample and illustrated in both
Table 12 and Fig. 13. The near parallel improvement of
both the Cimetidine and non-Cimetidine groups would tend to
question the validity of the Wfdespread practice of massive
prophylactic antacid administration to aIl sèverely ill
patient~ in an Intensive Care Unit. Once again the
successful control of every "prime factor" in these 4
patientJ prior ta the second endoscopie examination can
\ "
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,,/ i 1
,
o
81.
be considered as the major reason for the rapid clearing of
the mucosàl changes. It is impossible to say w?ether
Cirnetidine decreased the risk of overt hemorrhage in these
4 patients. The only way to answer this,question would have ,
been to withhold antacjds in the faCe df documented mucosal
bleeding and such a situation presented an unsolvable ethical
problem at the time of this study.
/ f
1IJ8!11IlIi_"' __ ~,.lIiIId."inllili.lIl'iil~tIillilli!lI!"ll!IIlII., .... IiA*Ii.liliIiII_~_~~lIM\IIj~iIII~_iIIIlI_IIII~_I!!'I..'Ii1o!rlr.Ji8~ .. 1M ........ ~!""j -_ .... _1"HOIIII'MJ4i1111.ilIIl ... r"")I~nl~"I."I_i.1I!1N111\'">'I\I'~""~".fj"Iii!I"~"_._,ii..:4t.'ik\,.(\~_ ~'S~ f \
'i
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1
CONCLUSION 1·
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/
82.
CHAPTER 6 CONCLUSIONS J
1) Acute Stress Gastritis iS,present, to sorne extent, in "
all acutely ill patient$ within 72 hr of onset of
acute illness.
2) Rapid Control of Primary, Factors (hypotension, hypoxia,
sepsis, respiratory and' renal failure etc.)' lead to
rapid resolution of acute stress gastriti\.
3) Unçontrolled Sépsis is associated with persistence and
4)
5)
" exac~rbation of acute stres,s gastritis.
The H2 receptor antagoni~t Cirnetidine may prevent
severe b1eeding from acute stress gastr~tis, however,
its rol~as we11 as that ef other antacids, does not
appear to be more irn~ortant than the control of the
prime factors. '
The role of prophylactic antacids in severely ill
patients whose factors are controlled needs ta be
reevaluated.
\
\
, !
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"
,<
<-
" >, , ~>
---- 1 ~ '" ,1 f
"
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1
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1.
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L .~".hI )1=II'tI~i$f"_. 'fi 1 Il.'ll' ?7rtFi!lI'_~'''~'''1III! "! '~"UI", "'~ ',~$ ""'.."~-""."' .... _..,,,.~_.;;.~""-"'--' ""0' ."'. l , '"" . -- -~~--------~!~
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"
(
, .
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7 o. ~
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~,ftI'ijiIii~ __ ~~ _____ d_ .. IiI(i ... __ ~ ____ ~_ .. ~......u"·~~~""""~'(Il<,. ~""""',."". "-~ 1 --1
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1
l, 1
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1
1 '.'
'lF FIGURES liNO TABLES
"
~) 1-
a
.... ~i .. ~liIItW\oo\~~_liJllliH'U.lrlC_~~_' ..... ~'"~ ...... ;~~~ ... ~~,,'J,;~., ... ,,' • gO ".l,. .. ,. • _.; 4 ~
L
i'
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•
Fig. l At the base of an acute gastric ulcer fibrin and
numerou.s polymorphonuclear leukocy:tes inf il trate
the rnuscularis propri~, indicating that this
stress ulcer 8 days following combat trauma .! J
showed the ordinary inf1runmatory response
(hematoxylin-eosin, x40) .' From Stremp1e,
J • F ., Moû, H., Lev, R: and Glass, G. The
Stress ULcer Syndrome .
• April, 1973, p. 23.
---Curr. ·probl. Surg. 1
103 .
)
1 -. 1
. , 1
.. ,.
t 1 , J,
1
L
1
l , , 1
•
104.
F±g. 2 Patpophysiology of Acute Stress Gastritis~~
PATIENT
---___ &..ot-__ """,~ __ .~ __ _
..... -:.--____ __ t -..... 1 _-~ , RESPlRATORY ~---- FAlLURE
'" - - - - - 1
r--;e-A"~A-L-~-RE--'~ -~ ~EPS 1S r-I ETC.' 1
ri'
Sum of factors
altered muco~1 blood flow
lIeus
altered mucosal function 1
destructive ~mfID~
(Acid./ ) l D,uodena cont~nts
Bleeding
Serosal
Luminal
i .~ > " 1
i! 2 r fi. t
t ;J-
~
L
q
1 \
Fig. 3
O
Slood Gastric
parieta 1 cel!' Gastric lumen
cr -4~~ ___ -..o.--..;.;~~~ CI-Active 1tan$pOtt
H2 0 --I~--' ._ ..... _10004' ---.......... ......,.....,. H2 0
011fû$ion'
Intrace11ular processes in the formation of
gastric hydrochloric acid. From Way, L.W.
and Richards, V,. Current Surgical Diagnosis
and Treatment. 2nd Ed. 1975, p. 459.
105.
, .,
-, " '~ /~ '~.
, .
~ ,
~~~-----_-_._._.~_ •. ·_ ........ _·_· __ ..... a.~,~=-~I~-U
1
'C:>m'h Il .... 1.
1 .. '4' HIO
l 'Capillary " ~Endothelium
~.I~==::" Na+
:::;;'4;:====~'" FtCO'i
, BLOOD
VESSELS
Interstltial --...,' Graund Substance -'"
...
...
INTERSTITIAL SPA CE
Basal Cell Barder
Lateral Cell
Apical Cell Border
IN TRACELLULAR SPA CC ,
"
106.
No+
LUMEN
Fig.' 4 A schema of the physiologic'anatomy of the gastric
\ , )
~I
mucosa showing the g~stric mucosal barrier. Back
diffusion may occur through the tight cell junctions
or with cell,damage, through the epithelial cells
themselves. Fro~ Davenport, B.W. In: American
Physiological Society: Handbook o~ Physiology,
Section 6, Alimentary Canal. Ed. 'C.F. Cpde,
Baltimore, Williams & Wilkins Co., 1967, Vol. 2,
p. 763. "
L .$1 i .• :i!ll4ïii SI: iliSl'%
~--------------------------~
•
t
\
Fig. 5
1
"
_--1 ... Pepsin
• Blood plasma filtrate
Plasma prot~ins
Damaged barner -
.
,
Blood
Effects of intra1umina1 acid on a normal or broken . '
gastric -mùcosal 'barrier. If the barrier is intact,
back di~fusion of H+ is minimai and causes no ,harm.
When the barrier is disrupted, H" diJfus~s rapid1y
into.the submucosâ, histamine is ~eleased. loca~ly,
~and'cholïnergiG fibe+s are stimulated. From Way, ,
L.W t, and Rie rds" '(,J. Current Surgieal 'DiagnosiS" ,
and Treatment. 2nd Ed., 1975, p. 485.
, f" Plh' M'it.' ........... 1 ••• ., ••••• n" ( '1 ru' til _ 't Il lIiI t l'U .1.
.. -.."
>,
\
-. Fig. 6 A 3-D su~face view of the stomach mucosa shows màny
fOlds, gastric pits ~nd numerous.epithelial cel+s . (x35<Y). From "Lucas et al. "Stress" e'Gastric-
Bleeding, Arch. Surg~, 102: 268, 1971~ -
l'
" A_ ... ,,~_._ .... .......:.,..~~ ........ ~.,.w..~-~~_ .... ~t"'-_'~""""-": - . ,\. .. ,
108. . '
•
· .
Fig. 7 High magnification shows four alter~d surface
epithel,ial cells which exhibit membrane
\
disruption and loss of po~tionst of th~ir apical
region (x8,OOO).
Gastric Bleeding,
li' ,
1
F;rom Lucas tt. al~. '''Str~ss''
Arch. Surg. 102: 269 , 1,97l. ,
"
= a
1 109.
/
1 ,.
Fig. 8
\
Diff,u'se acute rnucosal changes
as seén through the.gastrosc0r':
mucosal pallor and mottli~1
. ,
110.
. .
1
•
. ,
FJ.g. 9 Acute focal mucosa~ hemorrhage
as seen through the gastrosco'I;'e
\ , .. \
" ~~. ,f .--.' ... ..., ... - t, ,_.
Ill.
) "~
. , .
"
, 1
1
l ,~
----'
, 112.
1
. ,
'1 1
1
! ,::,
·1 !
l ' 1
~
Fig. 10 Ac~te circular mucosa'l erosion
with s16ughing of overlying
epithelium as seen through the
gastroscope ,
c
1 •
, '
113.
o
Fig. Il Acute mucosal ulcerationowith
rim of hyperernia as seen
through the gastroscope
( .
\. i
(
) t Fig. 12 Evolution of endoscopy soore in SICU samp1e 0
10
9) i
, 8 ~
"
.'
7 1
6 "'
5
Initial Score
10
6
4 ~ 4
• " ,
\ 3 ;. 3
! 1 , i 1 l ,
2
r 3
r !
l 1 t j l • ~
·1
o . ' ~--:--------~----''"---
2-3 ~YS 5-7 Dl\YS
.,.
Final Score
10
6
INJURY 5
3
2
,1
o
114.
,
. ~
f
L
ll5 .
Table l Summary of Clinical Sample
TRAUMA GROUP N - 12 (2~ /10<1) mean age 31. 6 ~ 4.36 0
Patient Age Sex
49
21 F
19 M
60 M
32 M
23 M
20 M
33 M
25 M
28 M
29 M
53 M
Primary condition leading to SIeu admission
Multiple trauma: head injury MVA ' fractured ribs, pelvis,
tibia & humerus
Mul tiple trauma: head injury MVA fractured spine, pelvis,
radius
Mul tiple trauma: fractured c1avicle, MVA humeri, ribs & femur
Mul tiple trauma: MVA
Mul tiple trauma: MVA
fractured skull, hume rus , pelvis, tibia
fract'ured ribs liver laceration
Multiple trauma: head in jury (anoxie MVA encephalopathy) fractured
r ibs and femur
Multiple trauma: MVA
Mul tiple trauma:
fractured panoreas: distal panereatectomy
bi1ateral rib fractures, bilateral Pneumothoraces
Abdominal stab wounds: intraperitoneal hemorrhage
Abdom{nal & chest stab wounds: lacerated diaphragm! pericardium, liver, & colon
'Abdominal & chest stab wounds: lacerated diaphragm & pericardium, pneumothoraces
Chemical burns: 60% 2nd & 3rd degree
NON-TRAUMA GROUP N -'8 (3~ /5(j) m~an age 52.4! 6.03
51
74
40
36
74
60
55
28
F
F
F
M
M
M
,M
'M
Perforated left colon secondary to volvulus with peritoniti's
Acute cholan~is, pul,monary edema
Hypoxia post small<bowel resection
Açute ~emorrhagie papcreatit~ & shock
Hypotension (post abdominal perineal reseçtion)
Septic shock (post a/K amputation) -
Sepsis (post left hemi-eolectomy)
Perforated sigmoid colon & peritonitis
1 1, ,
" 0
-. !
"
..... . Table 2 Fac-rors and Endoscopy Scnre
A) 'l'AAl:.M\ GRŒJP 1 c Initial Endoscopy: 2nd or 3rd D3.;t
C Patient Trauna Pr:inary Factors Associated Factors ÉndoscoP;t Findings Points
• Tl 4 hyp:>'\=ffis ion N:i tube eryth.€roa(F+A)i- l - antibiotics erosians (F) 3
.; T2 3 nil NG tube erythema. (F A) l
mucosal harorrhage (F) ~ CI
rerl erosions* (F) 3
T3 ~ hypotensioo NG tubë rrottling (F) l mech. vent. antibiCltics mucosal harorrhage* (F) 2
erosions * (F) , 3
T4 3 nil N:i tube rrottling (FtA) 1 mucosal hemorrhages (F) l erosions (F) 3
TS 2 hyp:>tension NG tube erythana (r) l mucosal hemorrhages (F) 2 erosions (F) 3 IlUlOJsal ulceratiœs (F) 4
T6 3 hyp:>tension NG tube 1 l'MX>xia antibiotics 2 mech. vent. 3
cerations* (F) 4 '1' '
T7
l nil NG tube erythana (F) 1 antibiotics rrucosal hemorrhages (F) 2
erosions* (F) 3
Ta 2 llYIX>tensian NG tube pallor (F) l seH'is antiliiotics mucosal haoorrhages (F)_ 2 mech. vent.
T9 l nil NG tube lIDttlingS (F+A) l cmtibiotics ITU.lCX)sa1 laoorrh:lges (F) 2
TIO
2 hyp:>tension NG tube mucoSal hemorrha.ges (F) 2 .~ antibitoics
T:U 2 hyp:>t.ensian NG tube IOOttlin} (F) 1
lWIOxia harodialysis nucosal ooOOrrha.ges (F) 2 ; sepsis antiliiotics erosions (F) 3 /
mech. vent. nûlcosal ulcerations (F) 4 renal failllli'." ~
i ' l ;Of
nil NG tube' ltOttliD;J (F) , .
Tl2 60% 1 \ !
1"
~ b.uns antibiotics • nucosal œ.no~h3.gès (F) 2 f ~
erosions (FI 3
l ... - ,", ,.'
, -" ... ~-+ ....... ,. ..... --.., ..... _. --' . - ~ ~.'"' ...... -~ .... --....... r:", ,,~~ .. ~.~~ _"..1.. f-L
__ ~ ..... ,-,:Ù~ _l,
,
116.'
B) OON TRAUMA. ŒOOP
Init.ial Enoosropy .-Patient Primary Factors Associated Factors Encbscopy Findings Points Scnre
N1'1 hyp::>tension NG tube palior & erythera (F ... A) l 3 hyp:>xia steroids rnucosai ~rrhages(F) 2 ser:sis vasopressors rnech. vept. antibiotiçs -xena.l failure
Nl'2 hyIntension ~tube nottliÎlg (F+A) l 3 hyp:>xia antibiotics mocosal harorrhages (F) 2
ser:sis
hyp::>xia ~tube eryt.hEma & roottling (F) l mucosal herrorrhages (F) 2 10 erosions (F) 3 muoosai ulcerations (F)
Nl'4 hypJtension N:;tube nottl mg (Fl l 3 hypJxia antibiotics ID..lCOsal hatorrhage(F) 2
rrECh. vent. renal failure
Nl'S hyp:>tension antibiotics roottliflg (Fl 1 3 mocosal harorrhages (F) 2
Nl'6 hypJtension antibiotics pallar(F) 1 l ser:sis rrECh. vent.
~ Nr7 ser:sis NGtube erythana. (F ... A) l ~ I~
mocosal hem::>rrhage (F .... A) 2 6 erosiOns (P) 3
N'Fa hypJxia N:;tube nothling (F+A) l ser:sis antibiotics IIUlCOsal hsnorrœges (F+A) 2 10 erosions (F) 3
.. ,
IlUOOsal. ulcerations (F)
i
f ~ ~ r . t. La:.;Jem: sepsis antibiotics
~-
f-+F=Fûildus *=OOz),ng ~
A=Antnnn {JI! '1 1
0=DI.x>deIrum .' , ~~
mech. vent. = mech:mica! ventilaticn' a '1 ,
-- . , t e
r
.. (
~ "
~ ! ~ t " li
0
L
-
Pr:imary FactOrs
hyp:>tension sepsis renal failure
ni1
ni1
Il'eCh. vent. rena1 fëi.ilure
sepsis
sepsis
sepsis
Second EnCbscopy
Associated Factors
vasopressor antibiotics
antibitoics oral intake
oral intake
NG tube antibiotics
NPO
antibiotics oral intake
oral intake
• antibiotics oral intake
Endoscopy Firrling:s
erytlana (F.,.A) muoosai hemorrhages(FtArD) red & tilack erosions(F) red & black mucosal
ulcerations* (F)
llllCOsa1 harorrhages (F)
muoosa1 harorrhages (F)
nottling (F) It1\XX)sa1 henDrrhages CF)
erythema (F) mucosal harorrQages(F)
mnnal muoosa
eryt:.hara & 'nottling (hA) mucosal haIDrrhages (F) erosioris (F-tA)
1
nonral mucosa
_ l ,
Points
1 2 3
4
2
2
1 2
l 2
o
1 2 3
o
117.
Score
10*
2
2
3 '
3
o
6
o
a
t
1 ~ l'
1
[: 1
1
i
'" J5 ,~
'. " .' A5 ,.
J ~l f' if , '~
j,~ ,"
j
f'::'1 1
t
, .
~
f,
--" "'
-, Î ,. il' J
, J
Table 3
criteria tor prime factors studied
, ,
(l) Hyp::>tension: - cbcuœnted systolic blood pressure below 90 Mn Hg, noted by 2 observers for at least 30 min
and/or
(2) Hyp:nda:
(3) Sepsis:
.. (4Y 1œchanical
Ventilation
(5) Renal Fail~
- rapid drop of initially stable systelic blood pressure of nore i:han 20 rran Hg to below 100 nID Hg for at least 30 nrln
- docurrented arterial IJÜ2 belON 50 rrm Hg sither on room air, supplerœntal oxygen or while on Iœchanical ventilation on 2 successive occasions with at least a 15 min interval ,
- patient wi th a clinical infectious syndrorœ and wïth fX>sitive blood cùltures
and/or awropriate cultures (\'.Uund, peri toneal fluid, urme etc.)
- patient necessitating 'eiilier controlled or assisted nechanical ventilatory assistance
- Blood and urine tests CQffiPatible with ei ther lCM or high output renal failure. Diagnosis confirrœd by renal service
118.
Time delay
within 72 hr prior ta endoscopy
wi thin 72 l:rr prior ta endoscopy
within 24 hr prior ta 1 endosoopy(
rOf en soopy
/ , at tirre of ,~soopy
~ ~
" 1
j ,
t
f ~ ;,
,!
;
•
" fi .".
t t, ~ 3:. «: , <rL
t ;
',' / /'
.
·f , '1
Table 4
Characteristics of San'p1e - Re1ati ve Incidence of Prine Factors
119
TRAlMA NON-TRAlMA FISHER EXACT
SEX
l\GE*
prirœ Factors
HYPOrENSICN
HYPOXIA
SEPSIS
MEŒANlCAL VENTlIATICN
RENAL FAILURE
2~/lO6'
31.6t 4.36
7/12
2/12
2(12
3 t; /5 ri' ~ . 52.4! 6.03.
5/8
5/8 '
5/8
3/8
2/8
PROBABILITY
P ( .01*
"" 0.612
0.052
0.052
0.749
0.344
~an S.E.M. - pro~ility with the analysis of variance
-
F 8fT
1
~'
"
. \
/
lS6
i -1
, /
t
r
Table 5 ...
"Prim: factors" aJ)d Jœan initial enOOsropy scoré*
Patiénts with HYP~SION
Patients without HYP~ION
" Patients with SEPSIS
Patients without SEPSIS
'Patients with HYPoX~
Patients witlDut HYPOXIA
Patients with VENTilATION (f.Échani~) -
Patients without VENTI~!ON (Mechanical)
*Iœan and S.E.M •
NJ. of Patients
12
8
7
13
7
13
7
13
/
~an Endoscopy Srore
4.83:r .9"6
6.62 ~ 0.82
5.14! 1.36
5.76 t .77
7.00 '! .41
4.8, t .66
5.14! 1. 36
S.61.! .78
120
. l.. ,Gij5I1i1t Illil37_liltllll'." __ 'IiIlIIiIIlIltll •••• IIIII1I ••• ' .... ifIIIl!iJIi_.i~4.1I.'IIIIF ..... "_'''''!IIl .• :.,.1 ..... , .. , .... 1.1."''' _,., __ ....... -'." •• ""., ......... ""'!"'"_ .... __ ... or ...... 'IIt!Ii ..... ;U""" ......... " ............. ' ........ _""' __ ~~ .... "'_.,
1 -,.-
l,
,r
, , "
~
o
TRAIMA
N-= 12
N(N-TRAtMA'
N = 8
t-1I111J Iii i i
1
.
Table 6 EVolution of rrean endossoPY"srore* .'
IY\Y 2-3 DAY 5-7
X # of "prime factors" = 1.80 . x # of l'prirœ'' factors = .65
,
. 6.16!' 0.78
,
,
4.B7! 0.21 ,
-~,
.-
.. 5.55 t .67
(overall Iœan initial , soore) ,
S.E.M.
. -
i
, Î . ,
\ "
, 2.58 ~ 0.78
. . lfIT f"'F 1?!=: .....
ERC6 ms =
75% 16%
37% 25%
" "
-'"1::...
1
3.2o-! . 0.13
-
i
"- • . , 1 . ..
P <. .01 , ... 2.85" •• 65
(overaH i:œan second soore)
7'11.' l F
~
,
~
o'
.
121.
.. 4 .29! .76 (overal1 l trauna· nEan t score)
l ,. , '~
1 -
'~i
i f,
, :1 "
1 t è
, '1
4.06 t .19 r
"!'l _
(\
(overal1 non- ~ trauma rrean ~ score)
J
~
.../ ~ c'
'; 'i ~
\
"
\. . .
o
(
122.
Table 7
Pelationship be~ evolution of endcisccpy; score
and severity of traurra*
J!ay 2-3
5.67 t 1.48 c P (0.05
,
5.6t1.60 P < 0.05
"
s.~ .l;1.
j
D:ly 5-7
. 1.83.t ~ 31
1
"
-
2.0!.90
.1-2 tra1.lIlÉ. points
(N = 5)
'.
3-5 tratna points~'
(N = 6)
l, Q
1_IIIItIR _an .as b S ! ! ? Q au dl ]".11 P F \, IF l , 1.1 1 '
/
. '.
''Ji ~ '~tf
~ J , ".i.e j;" ,*?:~
o
J.. -
123.
Table B'
Trauma group enàoscopy soore* - in relatiôn to site of trauma
Patients with hea? injury (N-5)
Patients with chest injw:y (N-8)
, Patients with abdanina1 ' injury' (N-13)
Trama· with pelvic injw:Y (N-3)
Trauma with long bene injury (N-5)
~an' S.E.M.
,
Day 2-3
Endosqcpy Erosicn Soore* Œ.œr
5.80! 1.2 80%
6. 38 ! J. .16 75%
6.29! .97 54%
5.33~, .66 100%
6.40 ~ .97 100%
Day 5-7
EnCbsoopy Erosion Sro:œ* Ulcer
1.80 t .96 20% p( 0.5
3.l3t j1.11 12% p(-0.5
2.92 t : 70 .07% N. S •
2.00:t .94 20%'p (0.05
- - )
: .,
-
, ,
j
./ .(
o
" Table 9 Evolution of Jœan endosoopy soore in
•
ron trauma patients with and without oolon resection
5.50 t' 1.65
4~25t 1.97 p
,
l,
,
4. 75 !" 2 .1.3
0.01 1. 75:t 0.62
-
.
.
with Colon lèsection (N = 4) ,
Colon intact (N" = 4)
Table 1/ Evolution of nean encbsoopy soore of / , total sanple in relation ta the presence
/ / or a};lsence of colon injury'*
,
-Day 5-7
~ 1 -1
" ' , ,
1 "
... 1 5.67. 1.4~ 4.00-t 1.44
,
"
1
" Colon involved. (N'= B)
.
124.
-S.50t.75 P (.Cl! 2.36 :t .69 (bion not invoived eN = 12)
1 1
~ *Mean S.E.N.
'.
' .
• r \
i '
.J
-
l ~ >-
! t ;,
t J
!;J\
o
Table 11 FelatiCl1 between nurrber of prime factors of endoscopy score* evolution
Da.y 2-3" ta.y 5-7
T
, .
6.00± .74 P < 0.01 2.531" .76 0-2 Factors 1
(N = 13)
4. 7l~ 1. 38 3.42t 1.24 3-5 Factors eN = 7)
'--------_ .• ----.. _----'
~ S.E.M.
'f
125.
\
li, ;'i fj ~ \, l,
\ , , . . 4
,r
l J
• l ~ ) ~
,
1
-
Table 12 o:irparative evolution of the n:ean endosoopy score·in 2' groups of trauma patients - one given CiIœtidine and the othere where antacids were wi theld
,ray 2-3 Elu* Day 5-7 ElU
Cimetidine (N = 4) 7.0 100% 2.75 25%
Non:'Cllœtidine (N = 8) , 5.50 62% 2.50 12.5%
*ElU = Erosions and/or mucosal ulcers
P
Fig. 13 Spaytaneoilli' regression of encbsoopy score in non Cirretidine ~ (
IB'y 2:3 .r:ay 5-7
= Day 2-3 senre
0= D3.y 5-7 score ,
rI""------r--'---'- ------,r-------, 5.19t 0.837* 2.8St 0.837* ' ~ 4.069*
i p( .06,
"Mean S ~E .M., Fisher cœffi~t and probability •
J lb! .UI,' .t ,1 ;: ... , ,f
•• 11iI1 r a.iJlW ....
126.
ï .01
N.S~
• ;t .; If
'- " ,
) ;~
1 , ,~
l' "
-7 •
127.
r Table 13
Sunroary of septic patients
Patient Site Organism c
Ta blood Staph. Epide.rmidis chest tube dramage pseuOOnonas
-,
Tll wound - pseudorronas che st tutè dra:in,age pseuà:monas
T12 blood Klelsiella bum W\Q.unds Klelsie11a
, blDod bacteroides fr NTl .~ abdèminal' drainage E. coli ; ,
t bacteroides ;
NT2 i blood E. coli
NI'6 blood proteus f IDund proteus ... 1
NT? wamd E. coli
~ bacteroiàes <) Staph. Au:reUS
.r, NTa IDund pseudœonas
, ~ proteus
~ --~ ... :
t
1 ~
-,'
L-·_·-rl .... w., - ......... - . __ ....... '_·_ .... ·;· .. -... --~,:_,-.·_,.-t.<t~, .. 't-,-._~~, ______ ........ ____ R_-. ___ .. _ -
-1
1/
0: ,
~ . l-I
" :~
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