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432 S.A. MEDICAL JOURNAL 10 March 1973
however, is that some of our patients have a
hypolipi-daemia.
Professor Ziady: This question is from Dr Davidson ofDurban: 'Is
it possible to clear the dialysing machine ofAustralian antigen?
What is the treatment and the prog-nosis of Australian
antigenaemia?'
Dr Meyers: The answer for practical purposes to the
firstquestion, is No. This is the reason why a patient who isan
Australian antigen carrier must have his own machine,on which no
other patient must be dialysed.
In answer to your second question, the patients whohave had a
transplant, or those who become positive ondialysis, are relatively
protected. In all patient, hyper-bilirubinaemia was only very mild
or not present at all,and there was no evidence of active disease
in thesepatients, but 'protected' must not be interpreted
literally,because there is evidence that, if you remove steroids
(acase has been reported where a patient with excellentfunction
developed a severe infection, and on withdrawal
of immunosuppressive drugs, a fulminant viral hepatitis
de-veloped), a severe fulminant infection may result. Also,these
so-called 'protected' patients may develop a chronicpersistent
hepatitis; there is some evidence that even theso-called 'healthy'
carrier may over many years develop achronic persistent hepatitis.
There is of course no treat-ment available.
Professor Ziady: This question is from Professor Retiefof
Bloemfontein: 'Is there any place for the sulphonamidedrugs in the
treatment of infections in renal disease?'Dr Thatcher: We do not
use the sulphonamide group ofdrugs at all, largely because of the
type of infection wesee, which i~ always very serious, but I think
that sulpha-dimidine is one drug from tills group in willch
excretionis good even when there is poor renal function, and
forthis type of case it may be indicated.
Professor Ziady: I should like to express our sincerethanks to
both speakers and questioners for a particularlyinteresting part of
this symposium.
Septic Abortion and Septic ShockM. BOTES, M.B. CH.B. UNIV.
PRET., F.e.O. AND G. (S.A.), M.MED. (0. ET G.) UNIV. PRET.,
Department of Obstetrics
and Gynaecology, University of Pretoria
SUMMARY
Intra-uterine sepsis is a life-threatening condition that
canoccur any time during pregnancy. Shock induced by sep-sis is of
great prognostic significance, and once estab-lished, the mortality
is high. It can occur with prolongedruptured membranes and
chorio-amnionitis. Unfortunatelythe great majority of sefltic cases
are the result of non-medical abortions. The responsibility of
diagnosis andtreatment is often accepted too late, even in the
sophis-ticated clinical centres. These patients with septic
abor-tions may present with a variety of clinical
pictures,including septic shock. They require intensive therapy
andinvestigation. A heightened awareness of the potentialdangers of
septic shock will only develop from an under-standing of the basic
pathophysiology, and its relationshipto the development of the
clinical signs and symptoms.Successful treatment depends largely on
an effectiveantibiotic regimen, and this requires an up-to-date
know-ledge of the nature and likely antibiotic sensitivity of
thecausal organisms. The clinical situation,. however, demandsa
rapid bedside choice, usually in the absence of labo-ratory
findings. The use of heparin, as well as f1uid'3,
corticoids and early evacuation of the uterus, is impera-tive.
The purpose of heparin is to prevent intravascularcoagulation and
its sequelae. Effective management ofendotoxic shock and septic
abortion can be achieved ifthe treatment of this condition: (i)
follows an establishedplan; (H) is carried out by a team of
interested specialistswhich in conjunction with the attending
physician, manageall such patients; and (iii) includes the use of
heparin.
If the patient fails to respond, further steps must betaken.
Total abdominal hysterectomy, with bilateral
sal-pingo-oiiphorectomy may be performed as well as ligationof the
ovarian vessels as high as possible. Bacteraemicshock syndromes,
especially with Gram-negative orga-nisms, have shown a considerable
increase in recentyears For effective therapy; further knowledge is
requiredand at present the management of this condition presentsone
of the great challenges in medicine.
S. Air. Med. J., 47, 432 (1973).
Septic abortion is synonymous with induced abortion.A great
disparity exists between the mortality fromseptic abortion, with
and without septic shock. Because
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la Maart 1973 S.-A. MEDIESE TYDSKRIF 433
of this, it is imperative to undertake measures thatwill
effectively prevent. as well as treat this condition.
DEFINITION
Septic abortion may be defined as a pregnancy of lessthan 20
weeks' gestation, in which the products ofconception are infected.'
Septic shock or endotoxin shock.on the other hand, is a syndrome
resulting from sepsisdue to Gram-negative, Gram-positive and
certain fungalinfections.' The most common organisms involved,
areEscherichia coli, Aerobacter aerogenes, Proteus mirabilisor
vulgaris and Pseudomonas aeruginosa.
In obstetrics and gynaecology, one may encounterendotoxin shock
with septic abortion, and premature rup-ture of foetal membranes,
in other words, chorio-amnioni-tis. It has also been seen in
postoperative infection, pelvicabscesses after urinary tract
infections, and accompanyingbacteraemia and septicaemia in medical
patients. '.'
INCIDENCE
The incidence of septic abortion varies from 5,8% to34%, with a
much higher incidence in the non-Whitepopulation. Although few
cases of endotoxic shock areseen by the average obstetrician and
gynaecologist, itcomplicates septic abortions in approximately 0,7%
ofcases. It is vitally important to recognize because ofthe high
mortality rate, which can be as high as 90%3The mortality
statistics will, of course, depend on thetype of patient, the
method of treatment, and howearly diagnosis is made. This prognosis
should bebetter, because:' (l) the patients are younger and havea
firm grasp of life; (it) they have a removable septicfocus; and
(iiI) they respond we1l to treatment. Despitethese facts, the death
t01l on patients with septic abortionand endotoxic shock, remains
high.'
PATHOPHYSIOLOGY"'"
Lillehei and his associates have advanced the currentlybest
accepted concept of pathophysiologic changes whichoccur in the
evolution of shock. This 'unified conceptof shock', states that
regardless of the aetiology of theshock, the basic haemodynamic
anomaly is vasocons-triction. The vasoconstriction then initiates a
predictablechain of events, which occur mainly in the
microcircu-lation. These events start off with:
1. Endotoxin which damages the platelets.2. These damaged
platelets slowly aggregate and
undergo degeneration with the formation of plateletthrombi.
3. These platelets release substances which are in-volved in
blood coagulation.
4. Fibrin mesh with red and white cell accumulationobstructs
capillary flow and provides a source ofmicro-emboli.
5. Multiple emboli to the microcirculation of variousorgan
systems (lungs liver, kidney, intestines, etc.)drastically slow
circulation, with resultant sludging.
6. Initial vasoconstriction is f01l0wed by furtherincreases in
hypoxia and acidosis, leading to para-lysis of the venous and
arteriolar sphincters.
7. Pooling of blood in the portal system creates arelative
hypovolaemia, with a diminished venousreturn to the right
heart.
8. This, in turn, leads to diminished cardiac output,renal flow,
coronary flow, and relative myocardialischaemia, all of which lead
to further cardiovas-cular failure and hypotension. Thrombosis,
micro-emboli and direct endotoxin damage to alveoliand to the
endothelium of the alveolar capillaries,are conducive to the
production of pulmonaryoedema.
DIAGNOSIS
A complete history and physical examination is a sinequa non in
diagnosis.'" On admission, the routine invei-tigation consists of a
complete blood count and urinalysis.Gram-stained smear of cervical
discharge and urine se-diment are also examined. The products of
conception,preferably the curettage specimen, are sent, not onlyfor
histopathologic examination, but also for bacteriologiccultures in
aerobic and anaerobic media and antibioticsensitivity. Further
investigation may be needed in somepatients. If a routine
investigation is to be carried out,they will provide base line
values, since endotoxic shockmay develop in any patient with
criminal or septicabortion, without warning. Thus, serum
electrolyte, bloodurea, uric acid estimations, ECG and chest X-rays
areall useful. A plain film of the abdomen in the uprightposition
is indicated, to rule out the presence of gasunder the diaphragm,
suggestive of uterine perforation,or the possibility of a foreign
body, such as a rubbercatheter in the peritoneal cavity.
Blood coagulation profile, arterial blood lactate levelsand gas
analysis or blood volume determination shouldbe carried out in
severely hypotensive patients andrepeated as often as
necessary.
MANAGEMENT
Success in management of endotoxic shock with septicabortion,
depends on early diagnosis and prompttreatment.
The treatment is best suited to the need of thepatient, and
should be individualized in each case. Onecannot stress
sufficiently the importance of immediateaction, since the first 3 -
4 hours are crucial for thepatient's survival. The patient should
also be treatedaccording to a predetermined plan.
Medical ManagementThe aim of the medical management' is to
control the
infection, by the use of appropriate antibiotics.
Thehypovolaemia should be corrected by blood transfusions,infusions
of plasma, and plasma expanders of fluids.
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\ 434 S.A. MED1CAL JOURNAL 10 March 1973Further uterine bleeding
may be controlled with oxytocics,until surgical evacuation of the
uterus can be carriedout.
AntibioticsThe initial choice of antibiotics depends upon
the
infective organism and the known antibiotic sensitivityrecord.
Antibiotics are given, despite the possibility thatbroad-spectrum
drugs may temporarily free more endo-toxin. Blood culture, though
positive in only 25 - 50%of patients, should be taken as a routine
along withother indicated cultures. However, since there is
aninherent delay in obtaining the results of cultures,antimicrobial
therapy must be instituted 'blindly' beforeculture data are known.
In the great majority of cases,Gram-negative infection with E. coli
or Proteus specieswill be suspected, and at present at the H. F.
VerwoerdHospital, a combination of ampicillin and gentamicinis
favoured as initial therapy, to cover the first 24 hours.The
subsequent treatment depends on the bacteriologicalfindings and the
patient's response. Cephalothin can beused intravenously"" daily as
a substitute for ampicillin,and has the advantage of being
effective against peni-cillinase-producing staphylococci. However
this agent isnot effective against enterococci. Gentamicin, like
kana-mycin, is an aminoglycoside and active against a broadspectrum
of Gram-negative rods and also many strainsof staphylococci. Both
agents are extremely stable,excreted entirely by glomerular
filtration, and ototoxicwhen present in the serum in high
concentration. There-fore, these agents must be administered with
cautionand at reduced dosage in the azotaemic patient.
Deter-mination of serum creatinine should be done everyother day
while the patient is receiving gentamicin orkanamycin. The big
advantage of cephalothin sodium,is that it is a broad-spectrum
antibiotic that can be givenin the presence of oliguria and renal
insufficiency.
Blood TransfusionSince many patients with septic abortion
have
considerable blood loss, compatible blood should beavailable.
The patients should preferably be transfusedbefore they are taken
to the operating room, and beforeanaesthesia is begun.
Fluids and ElectrolytesInitially 5% dextrose in saline should be
given. The
amount is judged by the patient's needs. In calculatingthe
patient's fluid intake, the central venous pressure,urinary output
and blood volume estimation should betaken into account. Every
attempt should be made tocorrect the fluid and electrolyte
imbalance, but patientsshould not be overtreated. Pulmonary oedema
can beprevented if the patient's central venous pressure
ismonitored continuously, and the infusion rate adjustedto keep the
central venous pressure in the range of8 - 15 cm of water. Another
precaution is to use thefluid stress test for determining whether
tne patient ishypovolaemic or in a state of intense vasospasm.
OxytocicsRelatively large doses of oxytocin in 5% dextrose
in
saline, are usually necessary. After the oxytocin treatment.the
uterus expels most of the products of conception andbleeding is
controlled. The smaller, firmly contracteduterus minimizes the
chance of accidental perforationduring subsequent uterine
curettage.
Medical management of the critically ill patient maytax the
judgement of even the most experienced clinician.The following is
an outline of the method of treatmentwhich is used:
1. Ensure adequate oxygenation. The patient's airwayshould be
clear. Oxygen is given by tent or by inter-mittent positive
pressure breathing machines. Tracheos-tomy may be life-saving in
some patients.
2. Correct hypovolaemia by whole blood transfusions.dextran,
plasma, or infusion of 5 % dextrose in saline,being guided by the
haematocrit, blood volume deter-minations, central venous pressure,
and the urinary outputmeasurements. Although a Foley's catheter
increases thepossibility of infection, the disadvantage is
outweighedby its value in maintaining accurate intake-output
records.
3. If the vital signs (blood pressure, pulse rate,
respirationand urinary output) fail to improve, and the patient
isin the 'warm hypotensive' phase, a metaraminol infusionshould be
considered (Aramine 100 - 500 mg in 1000 mlof dextrose in saline).'
The rate of infusion should beadjusted to bring the patient's
systolic blood pressureto 80 - 100 mmHg. Metaraminol is usually
regarded asa vasopressant agent, but has both alpha-mimetic
andbeta-mimetic effect. The use of relatively pure beta-mimetic
drugs, such as isoproterenol (Isuprel), shouldbe restricted to the
'cold hypotensive phase' of endotoxicshock, and the use must be
supplemented by adequatevolume replacement with saline, dextran or
plasma, asguided by the central venous pressure.'
4. Corticosteroids in pharmacological doses (dexame-thasone 3 mg
per kilogram per day, or Solu-Cortef50 mg per kilogram per day or
methylprednisolonesodium succinate 15 mg per kilogram per day)
shouldbe given. The steroids possibly act as: (a) vasodilators,(b)
immunosuppressive agents, and (c) catecholamineinhibitors.' After
an initial 'bolus' dose, corticosteroidshould be given as a
continuous infusion. This can bestopped abruptly after 48 - 72
hours, without any appa-rent adrenocortical depression in the
patient.
5. Patients with evidence of congestive heart failureand/ or
pulmonary oedema, should be given a rapidlyacting digitalis
preparation. If the pulse rate is above120/min, the patient should
be digitalized.
6. .Heparin should be used as a routine in themanagement of
septic abortion, since the main underlyingpathology is platelet
aggregation leading to intravascularcoagulation. Heparin's platelet
anti-aggregation ability,and its antithrombin characteristics,
perform an im-portant function in the prevention or management
ofendotoxin shock. An initial dose of 5 000 units is
givenintravenously and, since intravenous therapy is contin-uous
with central venous pressure monitoring, thereafterthe heparin is
administered intravenously at the rate
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10 Maart 1973 S.-A. MEDIESE TYDSKRIF 435
of 500 - 700 units per hour. Clotting time should bemaintained
at approximately twice that of the normalcontrol. It is,
admittedly, very difficult to properlyevaluate the role of anyone
therapeutic agent, forexample heparin, in the management of septic
abortion.Frequently, by the time the decision is made to
includeheparin, many of the other agents and procedures willhave
already been utilized. It is readily apparent that,in most
instances, these agents will be effective in themanagement of this
problem. In experimental animals,both the prevention and resolution
of existing thrombo-embolic phenomena have been observed with the
useof heparin. The real importance would be difficult toprove,
because it would take either a very large seriesmanaged
identically, except for heparin, or a statisticallysignificant
reduction in incidence of endotoxin shockin septic abortion, in
order to provide definite proofof the value of heparin. 1
Surgical Management
The above-mentioned medical management will notbe completely
effective as long as the infected products ofconception remain
within the uterus, since they providea continuing source .of
endotoxin and bacterial infusion.It is, therefore, imperative that
the uterus be evacuated.It is recommended that an intravenous
infusion ofoxytocin (20 units per 1 000 ml of solution) be
givenwhile the patient is prepared for operation. It should notbe
used instead of, or for the purpose of postponinga dilatation and
curettage, nor should it be given togain time until the
'antibiotics have a chance to work'.Vacuum curettage with oxytocin
makes evacuation safer.Once uterine size is diminished, sharp
curettage canfollow. The patient's condition will usually
improvesteadily once a dilatation and curettage has been per-formed
and the supporting medical management has beeninstituted. No
bleeding complications from a dilatationand curettage have been
noted with the simultaneous useof heparin. If within 6 - 12 hours
after an initial curettagethe patient's condition does not improve
greatly, hysterec-tomy should be undertaken. Hysterectomy or
exploratorylaparotomy, is indicated under the following
conditions:
1. Failure to respond to medical treatment anddilatation and
curettage.
2. The uterus over 16 weeks in size.3. Long-standing uterine
infection with associated
oliguria.4. Superimposed Clostridium welchii infection.
5. Presence of a foreign body, such as a catheter inthe
peritoneal cavity due to uterine perforation,subsequent to criminal
interference.
6. When abortion has been attempted by the intra-uterine
injection of certain chemical agents (soaps,detergents, etc.).
7. Any time there is extensive parametrial cellulitisand pelvic
abscesses, with or without uterine per-foration. Bilateral
salpingo-oophorectomy shouldaccompany hysterectomy when performed,
in asmuch as the tubes are invariably involved in thesame process,
and will only serve to provide acontinued focus of infection, if
conserved.
8. In addition, whenever clinical deterioration of thepatient
occurs after the curettage (unremitting hightemperature, falling
blood pressure, oliguria), hys-terectomy is indicated.
COMMENTS
Septic abortion is synonymous with induced abortion;therefore,
regardless of the history obtained from the
. patient, investigation for a foreign body, intra-uterine
orintra-abdominal, is undertaken by pelvic examinationand X-ray
study. The finding of Gram-negative bacilliin an endocervical
smear, and the patient's condition,demand the execution of the
pre-arranged regimen formanagement or prevention of endotoxin
shock. Heparin,by preventing platelet aggregation which causes
stasisand secondary intravascular coagulation, is an importantpart
of our management programme. Microcirculatorycoagulopathy causes
derangement in several organ sys-tems. Therefore the use of
heparin, in addition tocorticoids in pharmacologic doses,
antibiotics, correctionof hypovolaemia and of acidosis, combined
with promptevacuation of the uterus, is essential for diminishing
thehigh mortality associated with endotoxin shock. Thesesteps have
proved to be effective measures in treating,and, even more
important, in preventing the developmentof endotoxin shock in
patients with septic abortion.
REFERENCES
I. Margulis, R. R., Dustin, R. W., Lovell, J. R., Robb, H. and
Jabs, C.,(1971): Obstet. and Gynee., 37, 475.
2. Cavanagh, D., Krishna, B. S., Ostapowicz, F. and Woods, R.
E.(1970): Aust. N.Z.J. Obstet. Gynaee., 10, 160.
3. Botes, M. (1970): Geneeskunde, 12, 241.4. Stewart, G. K. and
Goldstein, P. J. (1971): Obstet. and Gynee., 37,
510.5. Waxman, B. and Gambrill, R. (1972): Amer. J. Obstet.
Gynee., 112,
434.6. Reid, D. E., Frigoletto, F. D., TuUis, J. L., Hinman, J.
(1971):
Ibid., 111, 493.7. Roberts, J. M. and Laros, R. K. (1971):
Ibid., 110, 1041.