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MEDICAL

however, is that some of our patients have a hypolipidaemia.

Professor Ziady: This question is from Dr Davidson of
Durban: 'Is it possible to clear the dialysing machine of
Australian antigen? What is the treatment and the prognosis of Australian antigenaemia?'
Dr Meyers: The answer for practical purposes to the first
question, is No. This is the reason why a patient who is
an Australian antigen carrier must have his own machine,
on which no other patient must be dialysed.
In answer to your second question, the patients who
have had a transplant, or those who become positive on
dialysis, are relatively protected. In all patient, hyperbilirubinaemia was only very mild or not present at all,
and there was no evidence of active disease in these
patients, but 'protected' must not be interpreted literally,
because there is evidence that, if you remove steroids (a
case has been reported where a patient with excellent
function developed a severe infection, and on withdrawal

10 March 1973

JOURNAL

of immunosuppressive drugs, a fulminant viral hepatitis developed), a severe fulminant infection may result. Also,
these so-called 'protected' patients may develop a chronic
persistent hepatitis; there is some evidence that even the
so-called 'healthy' carrier may over many years develop a
chronic persistent hepatitis. There is of course no treatment available.
Professor Ziady: This question is from Professor Retief
of Bloemfontein: 'Is there any place for the sulphonamide
drugs in the treatment of infections in renal disease?'
Dr Thatcher: We do not use the sulphonamide group of
drugs at all, largely because of the type of infection we
see, which i~ always very serious, but I think that sulphadimidine is one drug from tills group in willch excretion
is good even when there is poor renal function, and for
this type of case it may be indicated.
Professor Ziady: I should like to express our sincere
thanks to both speakers and questioners for a particularly
interesting part of this symposium.

Septic Abortion and Septic Shock

M.

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 can
occur any time during pregnancy. Shock induced by sepsis is of great prognostic significance, and once established, the mortality is high. It can occur with prolonged
ruptured membranes and chorio-amnionitis. Unfortunately
the great majority of sefltic cases are the result of nonmedical abortions. The responsibility of diagnosis and
treatment is often accepted too late, even in the sophisticated clinical centres. These patients with septic abortions may present with a variety of clinical pictures,
including septic shock. They require intensive therapy and
investigation. A heightened awareness of the potential
dangers of septic shock will only develop from an understanding of the basic pathophysiology, and its relationship
to the development of the clinical signs and symptoms.
Successful treatment depends largely on an effective
antibiotic regimen, and this requires an up-to-date knowledge of the nature and likely antibiotic sensitivity of the
causal organisms. The clinical situation,. however, demands
a rapid bedside choice, usually in the absence of laboratory findings. The use of heparin, as well as f1uid'3,

corticoids and early evacuation of the uterus, is imperative. The purpose of heparin is to prevent intravascular
coagulation and its sequelae. Effective management of
endotoxic shock and septic abortion can be achieved if
the treatment of this condition: (i) follows an established
plan; (H) is carried out by a team of interested specialists
which in conjunction with the attending physician, manage
all such patients; and (iii) includes the use of heparin.
If the patient fails to respond, further steps must be
taken. Total abdominal hysterectomy, with bilateral salpingo-oiiphorectomy may be performed as well as ligation
of the ovarian vessels as high as possible. Bacteraemic
shock syndromes, especially with Gram-negative organisms, have shown a considerable increase in recent
years For effective therapy; further knowledge is required
and at present the management of this condition presents
one 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 from
septic abortion, with and without septic shock. Because

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S.-A. MEDIESE TYDSKRIF

of this, it is imperative to undertake measures that

will effectively prevent. as well as treat this condition.

DEFINITION
Septic abortion may be defined as a pregnancy of less
than 20 weeks' gestation, in which the products of
conception are infected.' Septic shock or endotoxin shock.
on the other hand, is a syndrome resulting from sepsis
due to Gram-negative, Gram-positive and certain fungal
infections.' The most common organisms involved, are
Escherichia coli, Aerobacter aerogenes, Proteus mirabilis
or vulgaris and Pseudomonas aeruginosa.
In obstetrics and gynaecology, one may encounter
endotoxin shock with septic abortion, and premature rupture of foetal membranes, in other words, chorio-amnionitis. It has also been seen in postoperative infection, pelvic
abscesses after urinary tract infections, and accompanying
bacteraemia and septicaemia in medical patients. '.'

INCIDENCE
The incidence of septic abortion varies from 5,8% to
34%, with a much higher incidence in the non-White
population. Although few cases of endotoxic shock are
seen by the average obstetrician and gynaecologist, it
complicates septic abortions in approximately 0,7% of
cases. It is vitally important to recognize because of
the high mortality rate, which can be as high as 90%3
The mortality statistics will, of course, depend on the
type of patient, the method of treatment, and how
early diagnosis is made. This prognosis should be
better, because:' (l) the patients are younger and have
a firm grasp of life; (it) they have a removable septic
focus; and (iiI) they respond we1l to treatment. Despite
these facts, the death t01l on patients with septic abortion
and endotoxic shock, remains high.'

PATHOPHYSIOLOGY"'"
Lillehei and his associates have advanced the currently
best accepted concept of pathophysiologic changes which
occur in the evolution of shock. This 'unified concept
of shock', states that regardless of the aetiology of the
shock, the basic haemodynamic anomaly is vasoconstriction. The vasoconstriction then initiates a predictable
chain of events, which occur mainly in the microcirculation. These events start off with:
1. Endotoxin which damages the platelets.

2. These damaged platelets slowly aggregate and

undergo degeneration with the formation of platelet
thrombi.
3. These platelets release substances which are involved in blood coagulation.
4. Fibrin mesh with red and white cell accumulation
obstructs capillary flow and provides a source of
micro-emboli.

5. Multiple emboli to the microcirculation of various

organ systems (lungs liver, kidney, intestines, etc.)
drastically slow circulation, with resultant sludging.
6. Initial vasoconstriction is f01l0wed by further
increases in hypoxia and acidosis, leading to paralysis of the venous and arteriolar sphincters.
7. Pooling of blood in the portal system creates a
relative hypovolaemia, with a diminished venous
return to the right heart.
8. This, in turn, leads to diminished cardiac output,
renal flow, coronary flow, and relative myocardial
ischaemia, all of which lead to further cardiovascular failure and hypotension. Thrombosis, microemboli and direct endotoxin damage to alveoli
and to the endothelium of the alveolar capillaries,
are conducive to the production of pulmonary
oedema.

DIAGNOSIS
A complete history and physical examination is a sine
qua non in diagnosis.'" On admission, the routine inveitigation consists of a complete blood count and urinalysis.
Gram-stained smear of cervical discharge and urine sediment are also examined. The products of conception,
preferably the curettage specimen, are sent, not only
for histopathologic examination, but also for bacteriologic
cultures in aerobic and anaerobic media and antibiotic
sensitivity. Further investigation may be needed in some
patients. If a routine investigation is to be carried out,
they will provide base line values, since endotoxic shock
may develop in any patient with criminal or septic
abortion, without warning. Thus, serum electrolyte, blood
urea, uric acid estimations, ECG and chest X-rays are
all useful. A plain film of the abdomen in the upright
position is indicated, to rule out the presence of gas
under the diaphragm, suggestive of uterine perforation,
or the possibility of a foreign body, such as a rubber
catheter in the peritoneal cavity.
Blood coagulation profile, arterial blood lactate levels
and gas analysis or blood volume determination should
be carried out in severely hypotensive patients and
repeated as often as necessary.

MANAGEMENT
Success in management of endotoxic shock with septic
abortion, depends on early diagnosis and prompt
treatment.
The treatment is best suited to the need of the
patient, and should be individualized in each case. One
cannot stress sufficiently the importance of immediate
action, since the first 3 - 4 hours are crucial for the
patient's survival. The patient should also be treated
according to a predetermined plan.

Medical Management
The aim of the medical management' is to control the
infection, by the use of appropriate antibiotics. The
hypovolaemia should be corrected by blood transfusions,
infusions of plasma, and plasma expanders of fluids.

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MED1CAL JOURNAL

Further uterine bleeding may be controlled with oxytocics,

until surgical evacuation of the uterus can be carried
out.

Antibiotics
The initial choice of antibiotics depends upon the
infective organism and the known antibiotic sensitivity
record. Antibiotics are given, despite the possibility that
broad-spectrum drugs may temporarily free more endotoxin. Blood culture, though positive in only 25 - 50%
of patients, should be taken as a routine along with
other indicated cultures. However, since there is an
inherent delay in obtaining the results of cultures,
antimicrobial therapy must be instituted 'blindly' before
culture data are known. In the great majority of cases,
Gram-negative infection with E. coli or Proteus species
will be suspected, and at present at the H. F. Verwoerd
Hospital, a combination of ampicillin and gentamicin
is favoured as initial therapy, to cover the first 24 hours.
The subsequent treatment depends on the bacteriological
findings and the patient's response. Cephalothin can be
used intravenously"" daily as a substitute for ampicillin,
and has the advantage of being effective against penicillinase-producing staphylococci. However this agent is
not effective against enterococci. Gentamicin, like kanamycin, is an aminoglycoside and active against a broad
spectrum of Gram-negative rods and also many strains
of staphylococci. Both agents are extremely stable,
excreted entirely by glomerular filtration, and ototoxic
when present in the serum in high concentration. Therefore, these agents must be administered with caution
and at reduced dosage in the azotaemic patient. Determination of serum creatinine should be done every
other day while the patient is receiving gentamicin or
kanamycin. The big advantage of cephalothin sodium,
is that it is a broad-spectrum antibiotic that can be given
in the presence of oliguria and renal insufficiency.

Blood Transfusion
Since many patients with septic abortion have
considerable blood loss, compatible blood should be
available. The patients should preferably be transfused
before they are taken to the operating room, and before
anaesthesia is begun.

Fluids and Electrolytes

Initially 5% dextrose in saline should be given. The
amount is judged by the patient's needs. In calculating
the patient's fluid intake, the central venous pressure,
urinary output and blood volume estimation should be
taken into account. Every attempt should be made to
correct the fluid and electrolyte imbalance, but patients
should not be overtreated. Pulmonary oedema can be
prevented if the patient's central venous pressure is
monitored continuously, and the infusion rate adjusted
to keep the central venous pressure in the range of
8 - 15 cm of water. Another precaution is to use the
fluid stress test for determining whether tne patient is
hypovolaemic or in a state of intense vasospasm.

10 March 1973

Oxytocics
Relatively 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 and
bleeding is controlled. The smaller, firmly contracted
uterus minimizes the chance of accidental perforation
during subsequent uterine curettage.
Medical management of the critically ill patient may
tax the judgement of even the most experienced clinician.
The following is an outline of the method of treatment
which is used:
1. Ensure adequate oxygenation. The patient's airway
should be clear. Oxygen is given by tent or by intermittent positive pressure breathing machines. Tracheostomy 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 determinations, central venous pressure, and the urinary output
measurements. Although a Foley's catheter increases the
possibility of infection, the disadvantage is outweighed
by its value in maintaining accurate intake-output records.
3. If the vital signs (blood pressure, pulse rate, respiration
and urinary output) fail to improve, and the patient is
in the 'warm hypotensive' phase, a metaraminol infusion
should be considered (Aramine 100 - 500 mg in 1000 ml
of dextrose in saline).' The rate of infusion should be
adjusted to bring the patient's systolic blood pressure
to 80 - 100 mmHg. Metaraminol is usually regarded as
a vasopressant agent, but has both alpha-mimetic and
beta-mimetic effect. The use of relatively pure betamimetic drugs, such as isoproterenol (Isuprel), should
be restricted to the 'cold hypotensive phase' of endotoxic
shock, and the use must be supplemented by adequate
volume replacement with saline, dextran or plasma, as
guided by the central venous pressure.'
4. Corticosteroids in pharmacological doses (dexamethasone 3 mg per kilogram per day, or Solu-Cortef
50 mg per kilogram per day or methylprednisolone
sodium succinate 15 mg per kilogram per day) should
be given. The steroids possibly act as: (a) vasodilators,
(b) immunosuppressive agents, and (c) catecholamine
inhibitors.' After an initial 'bolus' dose, corticosteroid
should be given as a continuous infusion. This can be
stopped abruptly after 48 - 72 hours, without any apparent adrenocortical depression in the patient.
5. Patients with evidence of congestive heart failure
and/ or pulmonary oedema, should be given a rapidly
acting digitalis preparation. If the pulse rate is above
120/min, the patient should be digitalized.
6. .Heparin should be used as a routine in the
management of septic abortion, since the main underlying
pathology is platelet aggregation leading to intravascular
coagulation. Heparin's platelet anti-aggregation ability,
and its antithrombin characteristics, perform an important function in the prevention or management of
endotoxin shock. An initial dose of 5 000 units is given
intravenously and, since intravenous therapy is continuous with central venous pressure monitoring, thereafter
the heparin is administered intravenously at the rate

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435

MEDIESE TYDSKRIF

of 500 - 700 units per hour. Clotting time should be

maintained at approximately twice that of the normal
control. It is, admittedly, very difficult to properly
evaluate the role of anyone therapeutic agent, for
example heparin, in the management of septic abortion.
Frequently, by the time the decision is made to include
heparin, many of the other agents and procedures will
have already been utilized. It is readily apparent that,
in most instances, these agents will be effective in the
management of this problem. In experimental animals,
both the prevention and resolution of existing thromboembolic phenomena have been observed with the use
of heparin. The real importance would be difficult to
prove, because it would take either a very large series
managed identically, except for heparin, or a statistically
significant reduction in incidence of endotoxin shock
in septic abortion, in order to provide definite proof
of the value of heparin. 1

5. Presence of a foreign body, such as a catheter in

the peritoneal cavity due to uterine perforation,
subsequent to criminal interference.
6. When abortion has been attempted by the intrauterine injection of certain chemical agents (soaps,
detergents, etc.).
7. Any time there is extensive parametrial cellulitis
and pelvic abscesses, with or without uterine perforation. Bilateral salpingo-oophorectomy should
accompany hysterectomy when performed, in as
much as the tubes are invariably involved in the
same process, and will only serve to provide a
continued focus of infection, if conserved.
8. In addition, whenever clinical deterioration of the
patient occurs after the curettage (unremitting high
temperature, falling blood pressure, oliguria), hysterectomy is indicated.

COMMENTS
Surgical Management
Septic abortion is synonymous with induced abortion;
The above-mentioned medical management will not therefore, regardless of the history obtained from the
be completely effective as long as the infected products of . patient, investigation for a foreign body, intra-uterine or
conception remain within the uterus, since they provide intra-abdominal, is undertaken by pelvic examination
a continuing source .of endotoxin and bacterial infusion. and X-ray study. The finding of Gram-negative bacilli
It is, therefore, imperative that the uterus be evacuated. in an endocervical smear, and the patient's condition,
It is recommended that an intravenous infusion of demand the execution of the pre-arranged regimen for
oxytocin (20 units per 1 000 ml of solution) be given management or prevention of endotoxin shock. Heparin,
while the patient is prepared for operation. It should not by preventing platelet aggregation which causes stasis
be used instead of, or for the purpose of postponing and secondary intravascular coagulation, is an important
a dilatation and curettage, nor should it be given to part of our management programme. Microcirculatory
gain time until the 'antibiotics have a chance to work'. coagulopathy causes derangement in several organ sysVacuum curettage with oxytocin makes evacuation safer. tems. Therefore the use of heparin, in addition to
Once uterine size is diminished, sharp curettage can corticoids in pharmacologic doses, antibiotics, correction
follow. The patient's condition will usually improve of hypovolaemia and of acidosis, combined with prompt
steadily once a dilatation and curettage has been per- evacuation of the uterus, is essential for diminishing the
formed and the supporting medical management has been high mortality associated with endotoxin shock. These
instituted. No bleeding complications from a dilatation steps have proved to be effective measures in treating,
and curettage have been noted with the simultaneous use and, even more important, in preventing the development
of heparin. If within 6 - 12 hours after an initial curettage of endotoxin shock in patients with septic abortion.
the patient's condition does not improve greatly, hysterectomy should be undertaken. Hysterectomy or exploratory
REFERENCES
laparotomy, is indicated under the following conditions:
I. Margulis, R. R., Dustin, R. W., Lovell, J. R., Robb, H. and Jabs, C.,
Obstet. and Gynee., 37, 475.
1. Failure to respond to medical treatment and 2. (1971):
Cavanagh, D., Krishna, B. S., Ostapowicz, F. and Woods, R. E.
(1970): Aust. N.Z.J. Obstet. Gynaee., 10, 160.
dilatation and curettage.
3. Botes, M. (1970): Geneeskunde, 12, 241.
4. Stewart, G. K. and Goldstein, P. J. (1971): Obstet. and Gynee., 37,
2. The uterus over 16 weeks in size.
510.
3. Long-standing uterine infection with associated 5. Waxman, B. and Gambrill, R. (1972): Amer. J. Obstet. Gynee., 112,
434.
oliguria.
6. Reid, D. E., Frigoletto, F. D., TuUis, J. L., Hinman, J. (1971):
Ibid., 111, 493.
4. Superimposed Clostridium welchii infection.
7. Roberts, J. M. and Laros, R. K. (1971): Ibid., 110, 1041.