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

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.

\ 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

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.