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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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82

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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 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"

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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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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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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.

(

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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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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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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 ,

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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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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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, 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 •

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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:

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#

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

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, '

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?) •

\ " \

,

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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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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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, 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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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

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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 ,

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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) •

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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.'

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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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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

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"

" 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

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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 _____________ ... _________________ ,·_~ ________ _

"

'~

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1-

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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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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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,

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 \

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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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REFERENCES

"

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---- 1 ~ '" ,1 f

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1.

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\ 1

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"

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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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t

.. l >

i t,

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J

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. .••• ,, __ sIIlWP,. ..... __ II." i f7W.~i""'" ....... '~"'" .. "'."..--,.---.,."' .,,., .. ~ ...... ~.:_ ... ' 1__ • ~ ~ ,_ ~

. . -.. , d .. •

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91.

Simonian, S.J. and Cvrtis, L.E. Treatment of Hemorrhagic

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75. \-

.. ,

Following Combat Injury: The Contribution of ~ .

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""'-"lliA'ti'it'Mtiofl.t\ilAi"êd"ritMïll1I,n'l.ill '.lM-.II' ...... !lIFl,III.tI_v 1'1 _rtli"I.Iû,I.N.iiiH.'iIl, ... ~~;m-".,.-_""iIm""" __ " '. " f' ~ _ ___ _ ___ ""__ _ 0_ ___ __ _' _________ ~_

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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 '.'

'lF FIGURES liNO TABLES

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a

.... ~i .. ~liIItW\oo\~~_liJllliH'U.lrlC_~~_' ..... ~'"~ ...... ;~~~ ... ~~,,'J,;~., ... ,,' • gO ".l,. .. ,. • _.; 4 ~

L

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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 .

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. , 1

.. ,.

t 1 , J,

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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

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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. . '

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· .

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

" :~