Anaesthesia, 1979, Volume 34, pages 20-32 REVIEW ARTICLE

Amniotic fluid embolism

M. M O R G A N

Amniotic fluid embolism is a rare occurrence, but has been described as ‘the most dangerous and untreatable condition in obstetrics’.’ This review was prompted by the admission of three such patients to the intensive care unit of this hospital,2 and is based on reports of 272 cases in the English l i t e r a t ~ r e . ~ - ~ ~ Entry of amniotic fluid into the maternal circulation was first reported in 1926.95 In the following year, amniotic fluid was injected intravenously into animals in an attempt to discover the aetiology of pre-eclamptic toxaemia, but although pathological effects were observed, the possibility of a clinical entity was not recogn i ~ e d The . ~ ~importance of the condition was first emphasised by Steiner & Lushbaughg4who described the clinical and pathological features of eight women who died suddenly during labour or the immediate post-partum period. They also showed experimentally in animals that intravascular amniotic fluid resulted in profound disturbances in cardiorespiratory function, but it was some years later before the effects on the blood clotting mechanism were described.

Amniotic fluid The volume of amniotic fluid increases from an average of 50 ml at 12 weeks to lo00 ml at 38 weeks, after which it decreases. The volume necessary to enter the circulation to cause

recognisable clinical effects is not known. The pH of the fluid is around neutral. The composition of amniotic fluid is shown in Table l.97 In early pregnancy, amniotic fluid represents a dialysate of maternal serum and the electrolyte concentration is approximately the same as that found in maternal blood. A s pregnancy advances, amniotic fluid becomes progressively more hypotonic due to dilution with fetal urine. Potassium levels, however, remain the same throughout pregnancy. The type and concentration of amino acids are of the same order as maternal serum. Fibrinogen is not present in amniotic fluid. At term, the concentration of urea, uric acid and creatinine is about twice Table

1.

Composition of amniotic fluid (after Ostergard ”)

Electrolytes

Na, K, Ca, Mg, Fe. PO4, C1, S, Mn, Zn Nitrogenous Amino acids, urea, uric acid, creatinine, proteins Glucose, vitamins, enzymes, steroid hormones Lipids Fatty acids, phospholipids, cholesterol Prostaglandins El, Ez. FlayFza Epithelial squames, Elements of fetal origin lanugo hairs, vernix caseosa, mucin, meconium 6.9-7.1 5 PH

M. Morgan, MB, BS, DA, FFARCS, Senior Lecturer and Honorary Cohsultant, Department of Anaesthetics, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS.

20

0003-2409/79/01oooO20$02.00

0 1979 Blackwell Scientific Publications

Amniotic fluid embolism that of maternal serum, but bilirubin is not present in normal patients. Prostaglandins (PG) of the E and F groups are present in amniotic fluid, the amounts depending on the stage of pregnancy. During early gestation only the E type are present. During labour, there is a large increase in PGF2,, which is not present at term in the amniotic fluid of women who are not in labour.9BPGFl also increases during labour, while E l falls. Various elements of fetal origin are present, namely squames from the skin, occasional lanugo hairs, mucin from the gut and, on occasion, bile containing meconium.

21

must be taken not to label all patients who collapse during labour with the diagnosis. Predisposing factors

Amniotic fluid embolism is said to occur most commonly in elderly multiparous patients, who have large babies, foiiowing a short tumultuous labour associated with the use of uterine ~ t i m u l a n t s . The ~ ~ ~incidence ~ ~ ~ ~of~ these ~ ' ~ ~ various features in the cases reviewed is shown in Table 2. While the majority of patients were multiparous and elderly in obstetric terms(mean age 32 years), the youngest recorded case was a 15-year-old primiparous patient. Incidence and mortality Tumultuous labour or tetanic uterine contractions were only recorded in 28% of patients. The frequency of amniotic fluid embolism was initially put at 1 in 8000 by Steiner & LushAlthough there is an alleged association with the use of uterine stimulants to accelerate b a ~ g halthough ,~~ they later suggested that this l a b o ~ r , their ~ * ~ use ~ was mentioned in only was probably an o v e r e ~ t i m a t e while , ~ ~ Lewis99 22% of cases. In view of the very wide use of put the incidence at 1 in 80 OOO. Various figures accelerated labour and the rarity of amniotic between these two extremes have subsequently been quoted in the l i t e r a t ~ r e . ~ ~ * ~ ~ * ~ ~fluid embolism, it must be concluded that there The mortality of the condition is very is no direct association between the two. high.47*100 Of the 272 cases reviewed here, only Traumatic delivery and large babies are also thirty-nine survived, which represents a mortality said to be predisposing f a ~ t o r s , but ~ ~there *~~~ would appear to be no justification for this rate of 86%. It is the commonest cause of death in labour, during delivery and the immediate statement and the mean weight of the babies post-partum period.62-101The condition was where they were recorded, was 3.33 kg. An association is also said to exist between responsible for twenty-four deaths in England amniotic fluid embolism and fetal death.27p35*100 and Wales between 1970 and 1972 (7% of all It would seem, however, that the former is maternal deaths) which was a mortality rate of not caused by death of the fetus, but rather that 10.4 per million maternities.102 the baby dies as a result of the gross disturbance Amniotic fluid embolism must therefore be of maternal physiology that results from the regarded as being very rare, although many cases are probably undiagnosed, particularly catastrophe. The membranes of dead fetuses as sections from several parts of the lungs and that have been retained in utero for 2-3 weeks special stains are required to demonstrate the have been shown to be more permeable than presence of fetal rnaterial.'O3 Nevertheless, care normal and also to have reduced strength and elasticity. lo4 There is no evidence, however, that this occurs as an acute phenomenon and Table 2. Classical presenting features and incidence in a search of the literature does not indicate an cases reviewed. Discrepancies in numbers are due to not all the facts being mentioned in every case association between intra-uterine death and amniotic fluid embolism. Full term pregnancy in the presence of an Mean 32 years Age 15-48 years Parity Primips. (12%) 33 intra-uterine contraceptive device is not comMultips. 226 (88%) mon, but four proven cases of amniotic fluid In labour 244 (90%) embolism have occurred under such circumTumultuous 77 (28%) s t a n c e ~ . ~ -This ~ ~ *does " ~ raise the question of Uterine stimulants 59 (22%) Weight of babies 1 . 3 6 4 9 kg Mean 3.33 kg an association between the two, but in view of Survived 39 (14%) the rarity of both events, as yet there is no Died 233 (22%) proven association between them. Intra-amniotic injection of saline or glucose

22

M. Morgan

been reported at the time of Caesarean is used to induce abortion or labour when the section. 1 6 . 2 0 , 2 8,45.41.49 fetus is known to be dead. Embolization of amniotic fluid has followed this m a n o e u ~ r e . ~ ~ ~Endocervical ~~ veins are lacerated during Such injections cause a marked rise in normal labour and this is believed to be the intra-uterine pressure and values considerably site of entry by some.13 Attwoodlo3 believes higher than those found during contractions in that small, incomplete, lower uterine tears normal labour have been recorded.'05 It is which occur frequently during normal labour are associated with lethal amniotic fluid possible that this could force amniotic fluid into the maternal circulation. Support for this embolism, rather than the large complete theory comes from the work of Talbert er u1.'06 tears. The former are not important if they who found that significant amounts of '''1 remain covered with membranes and there is labelled albumen were transferred from amniofree escape of amniotic fluid. However, if the tic fluid into the maternal circulation following forewaters have ruptured and the fetal head intra-amniotic injection of hypertonic saline. forms a plug, then each uterine contraction may Transient changes in the clotting profile of cause an increase in pressure behind the head maternal blood have also been found after this and fluid could be forced into the maternal procedure. l o l Furthermore, death from trophocirculation. blastic embolization in the lungs has occurred in a patient with a hydatidiform mole following Clinical features intra-amniotic injection of hypertonic saline. I o 8 Closed abdominal injury has been associated The incidence of the presenting symptoms and associated features is shown in Table 3. There with a proven case of amniotic fluid embolism, although this was not the cause of death in this are four cardinal signs of amniotic fluid empatient, which occurred 20 days after the bolism-respiratory distress, cyanosis, cardiooriginal injury.3o The most inexplicable case vascular collapse and coma.62 Of the 272 cases is that of a patient 20 weeks pregnant who reviewed here, cardiorespiratory collapse was suddenly collapsed with all the features of invariable. In 5 1 % respiratory difficulty with amniotic fluid embolization, namely respiratory cyanosis was the initial indication of the difficulty, cyanosis, hypotension and incoagucondition, while in 27% the presenting feature lable blood. 3 3 The pregnancy was terminated was a fall in blood pressure out of all proportion by hysterotomy 82 h after the event, when the to any blood loss. Ten per cent of patients fetus was dead, there was no retro-placental presented with convulsions before the developbleeding and no liquor present. ment of cardiorespiratory symptoms. Classically it is stated that if the patient survives for more than 1 h then there will be evidence of a haemorrhagic tendency and Entry into maternal circulation hypofibrir~ogenaemia,~'.~~*~~ but in 12% of the In order for amniotic fluid to enter the maternal cases reviewed here bleeding was the presenting circulation there must be a tear in the memsymptom.2-11 In a further 100 patients who branes. Landinglog suggested that entry into the circulation occurred when uterine or Table 3. Clinical features of cases reviewed. Discrepandecidual vessels were abnormally opened, as in cies in numbers are due to not all the facts being mentioned in every case placenta accreta, Caesarean section, ruptured uterus and retained placenta. Rupture of the uterus in association with Presenting symptoms 133 (51%) Respiratory amniotic fluid embolism has been described Cardiovascular 68 (27%) 9 - 8 1 * 8 4while on numerous occasions1 Convulsions 28 (10%) Smibert' described injury to the uterus during Haernorrhage 34 (1 2%) delivery in 50% of cases. The site of entry might Associated features Bleeding diathesis 100 (37%) be caused by trauma from minor intra-uterine Pulmonary oederna 66 (24%) manipulations such as rupturing the memBronchospasrn 3 (1%) b r a n e ~or~ ~ insertion of a catheter for pressure recordings.a6 Several cases have also 59s61

* 6 3 3 1

Amniotic fluid embolism survived the initial insult, haemorrhage was associated with a major coagulation disorder. It is now believed that amniotic fluid embolism is always associated with some form of disseminated intravascular although there may be no obvious sign of bleeding.2 Pulmonary oedema was noted in sixty-six patients (24",), but appears to have been due to over-vigorous attempts at resuscitation rather than as a primary entity. Bronchospasm, however, was usually conspicuous by its absence, being mentioned in only three patients. The mortality rate (86%) was very high. Twenty-five per cent of the patients were dead within I hr of the initial symptoms. Prodromal symptoms heralding the initial entry of amniotic fluid into the circulation are said to be rare and ir~significant.~~ Sudden chills were recorded in nineteen patients (7%), but these are not uncommon and can result from a number of causes, The rarity of amniotic fluid embolism makes it impossible to relate the entry of fluid into the circulation to symptoms which commonly occur in obstetric patients, e.g. vomiting and shivering. Acute renal failure has been described in patients who survive the initial insult and was due to prolonged hypotension.2'55*60 Serious long term complications have been few; they include loss of vision in one eye36and hemiplegia.39 The number of survivors have been few, but there are no reports of any long term pulmonary complications. Experimentally it has been shown that only lanugo hairs produce any reaction within the lungs, and this is mild. I It is also uncommon to find lanugo hairs in the lungs of patients with amniotic fluid embolism.'03 It is thusvery unlikely that embolization of amniotic fluid is a causal factor in primary pulmonary hypertension as has been suggested, although the latter is much commoner in women. 2 . Dogs subjected to amniotic fluid emboli did not have pulmonary hypertension 10 months after the event.L14 Two of the survivors have had further uneventful pregnancies. 2 * 3 Diagnosis A definitive diagnosis of amniotic fluid embolism can only be made by finding elements of the fluid in the maternal circulation. The

23

presence of amniotic fluid within the lungs is always a pathological finding and never a physiological e ~ e n t . ~* ~ . ~Experimental ~. work involving the introduction of maternal red cells labelled with 'ICr into the amniotic fluid prior to labour has shown that none normally escapes into the maternal circulation during labour or delivery. 6 6 At post-mortem it is occasionally possible to confirm the diagnosis macroscopically by finding particles of vernix caseosa in the blood in the right side of the h e a ~ t . ~Essentially, ~.'~~ however, the diagnosis rests on microscopic examination of the lungs. The components of the embolism are: (1) epithelial squames from the fetal skin; (2) lanugo hairs, which are the rarest element to be found; (3) fat from the vernix caseosa; (4) mucin from the fetal gut; ( 5 ) bile containing meconium. Attwood103 has stressed the importance of taking sections from all parts of the lungs and other workers have also pointed out that the elements of the emboli are not readily seen with the usual haematoxylin and eosin stains.115-116 In fatal cases, amniotic fluid material can usually be found in coronary arteries, kidney and brain.38.90*103Rarely fibrin thrombi have been demonstrated in the pulmonary vessels. Clinically, the condition can be diagnosed with confidence. It has been pointed out that if all autopsied cases are collected and compared, then the clinical features of the syndrome are remarkably unif01-m~~ and that the presence of amniotic fluid in the lungs can be correlated with a particular group of symptoms and signs, I as have been described here. Confirmation of the diagnosis can be made by finding amniotic fluid material in the right side of the heart. This was first demonstrated by Gross & Benzgl in a post-mortem specimen of incoagulable blood taken from a woman who collapsed and died during labour. Since then a definitive diagnosis has been made in life by aspiration of blood from a central venous pressure line and examination of a smear for amniotic fluid.'*JO The diagnosis in a further case was confirmed by finding fetal squames in maternal sputum stained with Nile blue.31 A straight chest X-ray is of little help and may be normal despite a severe clinical p i ~ t u r e . ~ ~ - ~ ' Lung scanning may aid in confirming the diagn~sis.~~~*~"

24

M. Morgan Differential diagnosis

This would include any condition which causes acute cardiorespiratory failure and excessive bleeding during labour and the immediate postpartum period. Particularly important is thrombotic pulmonary embolism, which is usually accompanied by chest pain, and air embolism which might be associated with placenta praevia or blood transfusion under pressure. Acute left ventricular failure from any cause should be considered, but there would be evidence of pre-existing disease in such patients. Acid aspiration syndrome"' may produce similar features, but is invariably accompanied by bronchospasm, which was only mentioned in three out of the 270 patients. Some of the cases described as amniotic fluid embolism in the literature certainly have more of the features of Mendelson's syndrome. The diagnosis should be considered in any patient in whom severe haemorrhage is associated with a coagulation disorder, and in particular with abruptio placentae which may also be accompanied by a consumptive coagulopathy. The presence of convulsions has led to the erroneous diagnosis of eclampsia,68 but in these patients the blood pressure should be raised, whereas shock is invariable in amniotic fluid embolism. With increasing use of epidural analgesia in labour the condition must be differentiated from toxic reactions to local analgesic drugs should convulsions occur. * s t

Pa thogenesis The entry of amniotic fluid into the pulmonary circulation will have three principal acute effects : (1) Pulmonary vascular obstruction, resulting in sudden decreases in left atrial pressure and cardiac output, with consequent hypotension. (2) Pulmonary hypertension with acute cor pulmonale. (3) Gross ventilation/perfusion inequality with resultant severe anoxia, which in turn would account for cyanosis, tachypnoea, disturbances in mental function and convulsions. Sudden replacement of the pulmonary blood by amniotic fluid would also contribute initially to the anoxia. Although it might be thought that all the

above could be explained by sudden obstruction of the pulmonary circulation by particulate matter in the amniotic fluid, this is not so. Little experimental work has been performed on the problem and much remains to be done before the physiological changes in amniotic fluid embolism can be fully explained. Several explanations for the findings have been put forward. Anaphylactic shock

Steiner & Lushbaughg4 likened the effects of amniotic fluid embolism to anaphylactic shock and suggested that this would be caused by the fetal elements present, and have attributed death to an 'anaphylactoid reaction'. Several other authors were of a similar opinion.7 I . 8 4 . 9 1 , 1 2 0 A true anaphylactic reaction implies sensitisation, but the evidence for this is slight. Experiments involving the intravenous injection of amniotic fluid into dogs resulted in insignificant findings when the volume injected was less than 110 ml.lz'Thusnoeffectwasseenwhen 15 ml of homologous amniotic fluid was injected, but when a further 15 ml aliquot which had been kept frozen for 1 month was given, it caused hypotension, fibrinogenopenia and thrombocytopenia of several hours duration. The authors suggested that the animal had become sensitised and that this might occur in humans. However, amniotic fluid does not normally enter the maternal circulation.66 Furthermore, experimental work on sheep showed that whereas fresh filtered amniotic fluid intravenously was without effect, when kept at 0°C for 5 days it produced marked changes in pulmonary and systemic arterial pressures and cardiac output.'22 Thus storage of amniotic fluid may cause changes in its composition with consequent alteration in its physiological effects. M e i g ~described ~~ in detail the pulmonary histology in a rapidly fatal case of amniotic* fluid embolism. The picture was one of intense phagocytic activity apparently directed at granular material in meconium, which was found in large amounts in vessels of all sizes. He suggested that this fine granular material may be the provoking agent of an anaphylactoid reaction and also the cause of failure of blood clotting by causing colloidal defibrination.

Amniotic fluid embolism The evidence for an anaphylactoid type reaction, however, is slight. The clinical picture of amniotic fluid embolism is quite unlike that of a histamine mediated reaction (e.g. bronchospasm is a rare event) and the amount of histamine in amniotic fluid is negligible.'O' It would therefore be reasonable to question whether anaphylaxis plays any part in the pathogenesis of amniotic fluid embolism. Pulmonary vasculrir obstruction

Obstruction of the pulmonary circulation by the particulate matter of amniotic fluid could be an explanation of the observed features of the condition. Results of animal experiments have been conflicting owing to the different range of techniques and animals that have been used. The initial experimental work of Steiner & L ~ s h b a u g hshowed ~~ that there was a relationship between the particulate content of the amniotic fluid and a lethal outcome, a finding which was supported by other^.'^ In 1960, Jacques and his colleagues'23 were the first to show experimentally in dogs that pulmonary hypertension developed rapidly following aniniotic fluid embolism regardless of the sex of the dog, or whether the amniotic fluid was autologous, homologous or human. Halmagyi et ~ 1 . demonstrated ' ~ ~ in sheep that unfiltered amniotic fluid caused a rise in pulmonary artery pressure and pulmonary vascular resistance, an increase in venous admixture, dyspnoea and a fall in lung compliance. When the particulate matter was removed by filtration, these changes did not occur. They therefore came to the conclusion that the particulate matter was responsible for the physiological changes seen in the condition. Experiments in dogs by Attwood & Downing' l 4 showed that intravenous injection of amniotic fluid caused a marked drop in systemic arterial pressure and a large rise in pulmonary vascular resistance. These responses were greatest with fluids containing a high particulate content, but also occurred with filtered fluid. In experiments with rabbits, MacMillan' 2 4 showed that the cardiorespiratory effects were related to the number of fetal squames, but doubted that pulmonary embolism by particulate matter could be the sole cause of death. He calculated the number of cells required to kill a rabbit and extrapolated the results to humans. As human

25

liquor contains an average of 560 cells/ml at term, then the volume of liquor which would hold a lethal number of cells would be 7 litres, which is far in excess of the volume of liquor present. The results of these workers would therefore suggest that some humoral mechanism may play a part in the pathogenesis of amniotic fluid embolism. Rodgers, Staroscik & Reis'25*126injected 150-500 ml of filtered, autogenous amniotic fluid into ewes and showed that there was no effect on myocardial contractility as assessed by force-velocity relations, peak isovolumetric left ventricular pressure and dpldt,,,,.. By isolating and perfusing the systemic and pulmonary circulations separately, they showed that amniotic fluid caused a fall in systemic vascular resistance and a profound rise in pulmonary vascular resistance. As all particulate matter and meconium had been removed from the amniotic fluid by filtration, it seemed likely that a vasoactive substance was responsible for the observed circulatory failure. Similar experiments' 27 involving intravenous administration of autogenous amniotic fluid into term ewes resulted in a fall in arterial blood pressure and systemic vascular resistance, with a marked decrease in cardiac output in most instances. There was a marked increase in pulmonary arterial and right atrial pressures, but no change in left atrial or pulmonary wedge pressures. These findings suggested that the pulmonary vasoconstriction was pre-capillary and as they occurred with both filtered and unfiltered amniotic fluid, they would support the view that a potent vasoactive material was involved. None of these findings account for the pulmonary oedema that is sometimes reported. Spence & Mason,'l8 however, found that 2.5 ml/kg of fresh autologous amniotic fluid injected into pregnant rabbits was not lethal and did not significantly alter cardiorespiratory function. When autologous cell-free placental extract was injected all the rabbits died within 2 min so that there was n o time for any physiological measurements to be made. They therefore suggested that amniotic fluid has t o be contaminated with material of placental origin in order to cause the changes found in amniotic fluid embolism. Some clarification of the conflicting results has been obtained from the work of Kitzmiller

26

M . Morgatt

& Lucas.129 They took amniotic fluid from normal women at 37 weeks of pregnancy who were not in labour and from women who were in labour. When injected into cats in a volume of 3 ml/kg, five out of seven animals who received amniotic fluid from labouring women showed an acute transient fall in blood pressure and rise in central venous pressure, whereas this only occurred in one out of the seven animals who received amniotic fluid from the nonlabouring women. They found that intravenous injection of PGF2, into cats reproduced the former results. This prostaglandin is only present in human amniotic fluid during labour .” Reeves and his colleagues13 0 injected amniotic fluid from Jersey cows into Jersey calves and found an increase in pulmonary artery, but not pulmonary wedge, pressure. Cardiac output did not change. They showed that a lipid extract of amniotic fluid caused pulmonary hypertension and found that in most experiments these effects could be prevented by aspirin, which is a potent inhibitor of prostaglandin synthesis.I3I The apparently conflicting results of these animal experiments could be related to the different prostaglandin content of amniotic fluid at different stages of gestation and labour. Their type and amounts vary according to the stage of pregnancy and their circulatory effects differ in different animal species.132-134 These reasons might also explain why some workers have found no harmful effects following intravenous administration of amniotic fluid. l 3 ’-I 3 7 I t should also be remembered that although PGF2. is the most prominent in amniotic fluid during others are also present and therefore the effects of entry into the circulation are due to a mixture of prostaglandins.

Bleeding cliathesis

The first case report of amniotic fluid embolism which gave some indication of a derangement in the blood clotting mechamism was described in 1947,’’ when bleeding from venipuncture sites and the mouth were noted. The significance of this observation was not discussed. In 1949, amniotic fluid was shown to have haemostatic activity in uitro. L 3 8 In 1950, Weiner & ReidI4 described a patient with proven amniotic fluid embolism who bled excessively vaginally and also from

the mouth and gums. They proposed that amniotic fluid normally plays a role in coagulation of intra-uterine blood and that this assists in post-partum haeniostasis. When amniotic fluid enters the circulation it produces intravascular clotting, thus consuming fibrinogen. They suggested that heparin might be used t o neutralise the clotting activity of amniotic fluid. In 1952, Ratnoff & V ~ s b u r g h ’reported ~ the first case of amniotic fluid embolism in which excessive bleeding was shown to be accompanied by hypofibrinogenaeniia and increased fibrinolytic activity. The following year fibrinogen was first used in the treatment of a patient with amniotic fluid embolism, who survived.” The authors suggested the term amniotic fluid infusion rather than embolism would best describe the syndrome since they believed the basic insult to be intravascular clotting. They suggested that the extent of the latter would determine whether the patient would die immediately or recover temporarily. The finding of fibrin thrombi in post-mortem specimens in such patients is rare, but has been described,10.54Of interest is the case described by B ~ w m a n . When ’~ this patient collapsed during labour, a cut down at an ankle was attempted, but the vein was found to be full of clot. Later at post-mortem there were n o clots present and the blood was incoagulable. Experimental work by Hardaway & Mackay”’ attempted to demonstrate that certain types of shock were due to disseminated intravascular coagulation. They found that the immediate shock produced by injection of amniotic fluid into dogs was prevented by prior heparinisation. There was some evidence that the shock was due t o a decreased c a r p i x output secondary to acute cor pulmonale. Tbk might have been due to intravascular thrombi within the lungs plus vascular spasm. In thirty-four (12%) of the cases reviewed here, excess bleeding was the first indication of the catastrophe, while in a further 100 patients (37 7;) excessive bleeding developed after thab initial insult. Thus pathological bleeding occurred in about half the patients. It is stated that a bleeding diathesis develops if the patient survives more than 1 h,J3p48*62and it should be pointed out that 25% of the 272 patients were dead within one hour of the presenting symptoms. Beller1’O believes that every case of amniotic

Amniotic fluid embolism fluid embolism is associated with some form of disseminated intravascular coagulation. Amniotic fluid has been shown to contain an activator which might be the subof Factor X140--142 stance which triggers off the intravascular clotting. This Factor X activator increases in amount with increasing duration of gestation.I4' There is also marked activation of the fibrinolytic system' l o and fibrinolysis has been demonstrated clinically.z~50~s2 Prevention The rarity of the condition makes any prophylactic measures extremely difficult. Trauma to the uterus behind the presenting part must be avoided during such manoeuvres as rupturing the membranes or insertion of catheters for pressure recordings. During Caesarean section incisions in the placenta must be avoided. Excessive uterine activity should be reduced and this can be achieved by the use of B stimulating drugs given i n t r a v e n o u ~ l y ' ~or~ by inhalation. 1 4 4 Fenoterol hydrobromide has been used by this latter method and has the merit of simplicity and minimal cardiovascular effects. Treatment As there is no specific therapy for amniotic fluid embolism, treatment should be aimed at cardiopulmonary resuscitation, blood volume replacement and measures to combat any bleeding diathesis. Complications such as acute renal failure will require appropriate treatment. Anoxia is severe and oxygen therapy will be necessary, possibly combined with artificial ventilation. Hyperbaric oxygenation may be considered, but it may well be impractical and there are no reports of its use. As these patients are so young, and prior to the catastrophe very fit, every effort should be made to save :hem, including long term support with extracorporeal oxygenation.145 The presence of extensive disseminated intravascular coagulation, however, is an unfavourable prognostic sign in the treatment of acute pulmonary insufficiency by this method.14" NiceZS has used 30% ethyl alcohol nebulised with the aid of artificial ventilation in the successful treatment of a patient with amniotic fluid embolism and advocates this regime in the treatment of all

27

forms of fat embolism. Ethyl alcohol must be given intravenously at the same time. Although it is stated that attempts must be made to reduce pulmonary v a ~ o s p a s m , ~ ~ . ~ ~ there are no reports of this having been done. Drugs which have been suggested include papaverine, aminophylline, trinitroglycerine and even general anaesthetics. In experimental animals, atropine and papaverine have proved to be of use in t ~ e a t m e n t . ' ~If' prostaglandins are involved in the production of the increased pulmonary vascular resistance as seems likely from experimental work, I then consideration should be given to the intravenous (or possibly direct pulmonary arterial) administration of drugs such as indomethacin or aspirin. The latter has been shown to antagonise the increase in pulmonary artery pressure produced by amniotic fluid embolism in calves.'3o But it must be remembered that aspirin-like drugs antagonise the synthesis of prostaglandins and not their effects. A further point is that the lungs contain, and under certain circumstances release, material with vasoactive propertiesI4* and it is not known if these play a part in the pathogenesis of the condition. The above measures are mainly speculativeand more experimental work needs to be performed before they can be applied to humans. Attempts have been made experimentally in rabbits to reverse the microcirculatory changes that occur in amniotic fluid embolism.149 An industrial surfactant, pluronic F-68 (polyoxypropylene polyoxyethylene glycol) has been shown to reconstitute the mesenteric microcirculation after intra-arterial injection of unfiltered human amniotic fluid, and also to restore the systemic blood pressure. The same volume of low molecular weight dextran in these circumstances failed to d o either. Again, it is pure speculation whether such a method will be used in humans and whether the same results would be obtained in the pulmonary circulation. Pharmacological circulatory support will almost certainly be needed. In animals, isoprenaline, both intravenously and by aerosol, has been shown to produce a marked improvement in the circulation and to prolong the survival time. 22.1 47 Isoprenaline has been successfully used for circulatory support in LeetonI5O quotes Howqua as stating that he has successfully treated three

28

M. Morgan

consecutive cases of amniotic fluid embolism with an initial regime of hydrocortisone 100 mg plus isoprenaline 0.1 mg intravenously, continuing therapy with hydrocortisone 25 mg/kg/ 24 h together with isoprenaline 0.8 mg in 250 ml 5:(, dextrose by infusion. Kazmier and his colleagues2' in a discussion on the treatment of intravascular coagulation and fibrinolysis, state that there are patients in whom no fully effective treatment for the primary condition is available. As amniotic fluid embolism is such a condition, then the treatment of any bleedirrd diathesis should be adjusted to suit each individual and will depend on repeated laboratory evaluation of the clotting defect. A regime similar to that suggested by BellerL5' should be followed under such circumstances: (1) Laboratory evaluation; (2) whole blood replacement; (3) fibrinogen infusion in 2 g increments, with a further coagulation analysis after each dose; (4)fibrinolytic inhibitors (e.g. epsilon-aminocaproic acid; trasylol) should be given along with the fibrinogen (administration of the latter without a fibrinolytic inhibitor has been likened to 'pouring water into a sieve-very wasteful' ' "), the presence of fibrinogen degradation products is an indication for the use of antifibrinolytic agents; ( 5 ) heparin therapy should be considered when there is major bleeding in the presence of disseminated intravascular coagulation.

Summary and conclusions The statement that amniotic fluid embolism is the most dangerous and untreatable condition in obstetrics appears to be true. I t must be suspected in any patient who collapses o r bleeds excessively during labour o r the immediate post-partum period. Attempts should be made to secure a definitive diagnosis in life by examination of blood obtained from the right side of the heart and the sputum for elements of amniotic fluid. Lung scanning is a useful aid to diagnosis. The principal factors that have been implicated in the clinical syndrome of amniotic fluid embolism are anaphylaxis, vascular obstruction by particulate matter, vascular spasm due t o prostaglandins and possibly some other vasoactive substances, and the possibility that all the changes could be explained by disseminated intravascular coagulation as a primary event.

Further work is required to elucidate the relative contributions of these various factors. Due to the suddeness of the catastrophe and the very high mortality, haemodynamic data in humans is virtually non-existent. With improved methods of resuscitation it is to be hoped that the mortality rate will be reduced and that such data will become available. In this way it might become possible to apply the results of animal research and indicate the most effective method of treatment.

Key words EMBOLISM; amniotic fluid. PREGNANCY; amniotic fluid embolism. Acknowledgments The author is extremely grateful to Miss Debbie Rodrigues for secretarial assistance.

References 1 . COURTNEY, L.D. (1973) Amniotic fluid embolism. Journal oJ' the Irish Medical Association, 66, 5 1 . 2. LUMLEY, J . , OWEN,R. & MORGAN,M. (1978) Amniotic fluid embolism. Report of three cases. Anaesthesia, 34, 33. 3. GREGORY, M . G . & CLAYTON, E.M. (1975) Embolism. Obstetrics and Gynecology, 45, 236 4. MCLEOD, A.G.W. (1972) Fatal amniotic fluid embolism in Dade county: an unusual incidence. American Journal of Obstetrics and Gynecology, 113, 1103.

5. SMIBERT. J . (1967) Amniotic fluid embolism. A clinical review of twenty cases. Ausfralian and New Zealand Journal of Obstetrics and Gynecology, 7,l. 6. LYNN, J.M. (1967) Amniotic fluid embolism. Journal of the American Osteopathic Association, 67, 43. 7. JOSEY, W.E. ( I 966) Hypofibrinogenemia complicating uterine rupture. Relationship t o amniotic fluid embolism. American Journal of Obstetrics and Gynecology, 94, 29. 8. GEOOHEGAN, F.J., O'DRISCOLL, M.K.&COMERFORD J.B. (1964) Amniotic fluid infusion. Journal of Obstetrics and Gynaecology of the British Empire, 71, 673. 9. AGUILLON, A., ANDJUS,T., GRAYSON, A. & RACE, G.J. (1962) Amniotic fluid embolism: a review. Obstetrical and Gynecological Survey, 17, 619. 10. TULLER, M.A. (t957) Amniotic fluid embolism, afibrinogenemia aqd disseminated fibrin thrombosis. Case report and review o f the literature. American Journal of Obstetrics and Gynecology, 73, 213. 11. MCKAY,D.G., LITTLEJOHN, T.W. JR. & SCHOENBuCHER, A.K. (I 955) Acquired fibrinogenopenia following tumultuous labour and pitocin induction. Report of a case. Obstetrics and Gynecology, 5, 85.

Amniotic fluid embolism 12. NAVORI,C.A. & WISSLER,R.W. (1954) Severe

hemorrhage and maternal death associated with amniotic fluid embolism. American Journal of Obstetrics and G ~ I I P C O ~61, O R432. ~. 13. REID,D.E., WEINER, A.E. & ROBY,C.C. (1953) lntravascular clotting and afibrinogenemia. The presumptive lethal factors in the syndrome of amniotic embolism. American Journal of Obstetrics and Gynecology, 66, 465. 14. WEINER, A.E. & REID,D.E. (1950)The pathogenesis of amniotic fluid embolism. 111. Coagulant activity of amniotic fluid. New England Journal of Medicine, 243, 597. IS. MALLORY, G.K., BLACKBURN, N., SPARLING, H.J. & NICKERSON, D.A. (1950)Maternal pulmonary embolism by amniotic fluid. Report of three cases and discussion of the literature. New England Journal of Medicine, 243, 583. 16. BARRON, S.S., STURLEY, R.F. & LINDSAY,D.T. (1949)Amniotic fluid and meconium embolism. Minnesota Medicine, 32, 70. 17. HEMMINGS, C.T. (1947) Maternal pulmonary embolism by contents of the amniotic fluid. American Journal of Obstetrics and Gynecology, 53,303.

18. SCHAERF, R.H.M., DE CAMPO,T. & CIVETTA, J.M. (1977)Hemodynamic alterations and rapid diagnosis in a case of amniotic-fluid embolism. Anesthesiology, 46, 155. 19. JEWETT, J.F. (1976)Induction of labor and amniotic-fluid infusion. New EnglandJournal of Medicine, 294, 548. 20. RESNIK,R., SWARTZ,W.H., PLUMER,M.H., M.E. (1976) BENIRSCHKE, K. & STRATTHAUS, Amniotic fluid embolism with survival. Obstetrics and Gynecology, 41, 295. 21. SICURANZA, B.J. &TISDALL, L.H. (1975)Amniotic fluid embolism. Respiratory problem. New York State Journal of Medicine, 15, 1517. 22. THOMSEN, R.J. (1975)Pregnancy in the presence of an intrauterine contraceptive device and amniotic fluid embolism : a possible association. American Journal of Obstetrics and Gynecology, 121,279. 23. ABOULEISH, E. (1973) Amniotic fluid embolism: report of a fatal case. Anesthesia and Analgesia: Current Researches, 53, 549. 24. KAZMIER, F.J.. BOWIE,E.J.W., HAGEDORN, A.B. & OWEN,C.A. (1974)Treatment of intravascular coagulation and fibrinolysis (ICF) syndromes. Mayo Clinic Proceedings, 49, 665. 25. NICE,G.W. (1974)Alcohol in fat embolism. Use of alcohol by intermittent positive pressure breathing. Journal of the Kansas Medical Society, 75, 306. 26. CHUNG,A.F. & MERKATZ,I.R. (1973) Survival following amniotic fluid embolism with early heparinization. Obstetrics and Gynecology, 42,809. 27. GREGORY,M.G. & CLAYTON,E.M. (1973) Amniotic fluid embolism. Obstetrics and Gynecology, 42,236. 28. HARBISON, R.G. (1973)Amniotic fluid embolism. Medical Journal of Australia, 2, 687. 29. HEWITT,S.R. (1973) Maternal mortality-amniotic fluid embolism successfully treated. Journal of the Irish Medical Association, 66, 50. 30. OLCOTT,C., ROBINSON, A.J., MAXWELL, T.M. & GRIFFIN, H.A. (1973) Amniotic fluid embolism

29

and disseminated intravascular coagulation after blunt abdominal trauma. Journal of Trauma, 13, 737. 31. TUCK, C.S. (1972) Amniotic fluid e m u s . Proceedings of the Royal Society of Medicine, 65,

94. 32. MEIGS, L.C. (1971) Amniotic fluid embolism. Pulmonary histopathologic findings in a rapidly fatal occurrence of amniotic fluid embolism. American Journal of Obstetrics and Gynecology, 111, 1069. 33. WOODFIELD, D.G., GALLOWAY, R.K. & SMART, G.E. (1971) Coagulation defect associated with presumed amniotic fluid embolism in the midtimester of pregnancy. Journal of Obstetrics and Gynaecology of the British Commonwealth, 18,423. 34. COURTNEY, L.D. (1970)Amniotic fluid embolism. British Medical Journal, 1, 545. 35. PETERSON, E.P. & TAYLOR, H.B. (1970)Amniotic fluid embolism. An analysis of 40 cases. Obstetrics and Gynecology, 35, 787. 36. FISCHBEIN, F.I. (1969) Ischemic retinopathy following amniotic fluid embolization. American Journal of Ophthalmology, 61, 351. 37. HATCH,M.C. (1969) Maternal deaths associated with induction of labor. New York State Journalof Medicine, 68. 599. 38. LIBAN,E. & RAZ, S. (1969) A clinicopathologic study of fourteen cases of amniotic fluid embolism. American Journal of Clinical Pathology, 51, 477. 39. GOLDSTEIN, P.J. (1968) Amniotic fluid embolism complicating intrauterine saline abortion. American Journal of Obstetrics and Gynecology, 101,850. 40. HOLLAND, A.J.C. (1968)Amniotic fluid embolism. Anaesthesia, 23, 273. 41. LUCAS,W.E. & JACKSON,N.D. (1968) Maternal mortality in US naval hospitals. Obstetrics and Gynecology, 32,60. 42. SCOTT, R.B. (1968) Critical illnesses and deaths associated with intrauterine devices. Obstetrics and Gynecology, 31, 322. 43. ANDERSON, D.G. (1967)Amniotic fluid embolism. A re-evaluation. American Journal of Obstetrics and Gynecology, 98, 336. 44. PHILLIP,R.S. (1967) Amniotic fluid embolism. New York State Journal of Medicine, 61, 2085. 45. KIRCHER,K.F.,ROBERTS, W.D. &TYE,J.G. (1966) Nonfatal amniotic pulmonary embolism. American Journal of Roentgenology, Radium Therapy and Nuclear Medicine, 98, 434. 46. NICHOLS,G.P. & RANEY,E.H. (1966)Postpartum confusion: heart failure or amniotic fluid embolism? Archives of Internal Medicine, 111, 807. 47. WILLOCKS,J., MONE, J.G. & THOMSON, W.J. (1966) Amniotic fluid embolism: case with biochemical findings. British Medical Journal, 2, 1181. 48. RUSSELL,W.S. & JONES, W.N. (1965) Amniotic fluid embolism. A review of the syndrome with a report of 4 cases. Obstetrics and Gynecology, 26, 476. 49. SETO, M. & GUSTAFSON.D.C. (1965) Amniotic fluid embolism with placenta previa and Cesarean section: a case report and clinical review. Pacific Medicine and Surgery, 13, 258.

30

M. Morgan

50. SKJBDT, P. (1965) Amniotic fluid embolism. A case 67. investigated by coagulation and fibrinolysis studies. Acta obstetrica et Gynecologica scandin68. auica, 44, 437. 51. BROOKS,S.E.N., HAYES,J.A., PEDLOW,P.R.B. & MASSON,A.F. (1964) Three unusual cases of 69. embolism (fat, air and amniotic fluid). West Indian Medical Journal, 13, 266. 52. CLAYTOR, W.R. & CLARK, J.F.J. (1964) Anmiotic 70. fluid embolus with hyofibrinogenemia and maternal death. Journal of’ the National Medical Association, 56, 51 6 53. COPE,1. (1964) Amniotic fluid embolism. Report 71. of a case with survival of mother and child. Journal of Obstetrics and Gynaecology of the British Empire, 11, 112. 72. 54. DE BASTOS,M. & SRINIVASAN, K . (1964) Afibrinogenemia secondary to pulmonary amniotic fluid embolism. New York State Journalof Medicine, 64, I 1 19. 73. 55. LEE, H.A. & FRAMPTON, J. (1964) Case of intraamniotic glucose induction followed by nonfatal 74. amniotic fluid embolism and acute renal failure. American Journal of Obstetrics and Gynecology, 90, 554. 75. 56. PHILLIPS,O.C., WEIGEL,J.E. JR & MCCARTHY, J.J. JR (1964) Amniotic fluid embolus. Fundamental considerations and a report of 2 cases. Obstetrics and Gynecology, 24, 43 1. 57. ATTWOOD,H.D. & ROME,R.M. (1963) Amniotic 76. embolism and uterine rupture. Australian and New Zealand Journal of Obstetrics and Gynaecology, 3, 73. 58. CORNELL,S.H. (1963) Amniotic pulmonary 77. embolism. American Journal of Roentgeqology, Radium Therapy and Nuclear Medicine, 89, 1084. 59. SCOTT,M.M. (1963) Cardiopulmonary considerations in nonfatal amniotic fluid embolism. 78. Journal of the American Medical Association, 183, 989. 60. FINESTONE, A.J. & BEECHAM, C.T. (1961) Recovery from amniotic fluid embolism, hypofibrinogene79. mia and acute renal failure. Obstetrics and Gynecology, 11, 486. 61. JOSEY,W.E., PATTERSON, W.M., WOOD, H.E. & 80 JENNINCS, C.L. JR (1961) Hypofibrinogenemia and presumptive amniotic fluid embolism associated with rupture of the uterus. American Journal of’ Obstetrics and Gynecology, 82, 172. 81. S.M. & MOYA,F. (1961) Amniotic fluid 62. SHNIDER, embolism. Anesthesiology, 22, 108. 6 3 . RARNO, A. & FREEMAN, D.W. (1959) Amniotic fluid embolism. American Journal of Obstetrics and 82. Gynecology, 11, 1199. 64. CAWLEY,L.P., DOUGLASS, R.C. & SCHNEIDER, C.L. (1959) Nonfatal pulmonary amniotic 83. embolism. An unusual transplacental path of entry. Obstetrics and Gynecology, 14, 615. 65. SHELLEY, R.J., DENNISON, A.D., JR. & THOMPSON, 84. J.V. (1959) Pulmonary embolism by amniotic fluid. Diseases of the Chest, 36. 616. J.A. (1958) Studies to 66. SPARR,R.A. & PRITCHARD, detect the escape of amniotic fluid into the maternal circulation during parturition. Surgery, Gyne85. cology and Obstetrics, 107, 560.

SCOFIELD, F. & BEAIRD, J.B. (1957) Fatal embolism by amniotic fluid in the lungs. Report of a case. American Journal of Clinical Pathology, 28, 400. ATTWOOD, H.D. (1956) Fatal pulmonary embolism by amniotic fluid. Journal of Clinical Pathology, 9, 38. PRITCHAKD, J.A. & DUGAN,R.J. (1956) Presumed amniotic fluid embolism with recovery. Ohio Medical Journal, 52, 379 BOWMAN, J.A. (1955) Amniotic fluid embolism. Case report. American Journal of Obstetrics and Gynecology, 69, 905. GRAHAM, H.K. (1955) Amniotic fluid embolism. American Journal of’0bsteirics and Gynecology, 10, 657. HODCKINSON, C.P., LUZADRE, J.H.. PIFER, P.W., SWINEHEART, L.A. & REMP,D.G. (1955) Hypofibrinogenemia and defects of coagulation. Obstetrics and Gynecology, 5, 465. JEWETT,J.F. (1955) Amniotic fluid embolism with laceration of the uterus. New England Journal of Medicine, 252, 1144. STONE,S., KOUCKY,R. & LELAND,H.R. (1955) A fatal case of amniotic fluid embolism. American Journal of Obstetrics and Gynecology, 10, 660. DENNISS, R.G.. GOLDIE,W. & POLSON,C.J. (1954) Amniotic fluid embolism. A report of two fatalities. Journal of Obstetrics and Gynaecology of the British Empire, 61, 620. MARTIN,R.E. & FANCEP, H. (1954) Pulmonary amniotic fluid embolism. Report of a fatal case. American Journal of Obstetrics and Gynecology, 61, 1148. CRON,R.S., KILKENNY, G.S.. WIRTHWEIN. C. & EVRARD,J.R. (1952) Amniotic fluid embolism. American Journal of Obstetrics and Gynecology, 64, 1360. HAGER,H.F. & DAVIES,S.D. (1952) Nonfatal maternal pulmonary embolism by amniotic fluid. American Journal of Obstetrics and Gynecology, 63, 901. RATNOFF.O.D. & VOSBURGH, G.J. (1952) Observations on the clotting defect in amniotic fluid embolism. New England Journal of Medicine, 241, 970. SLUDER,H.M., CHARLOTTE. N.C. & LOCK,F.R. (1952) Sudden maternal death associated with amniotic fluid embolism. American Journal of Obstetrics and Gynecology, 64, 1 18. BOUTON,S.M. JR & SAUNDERS, J.R. (1951) Pulmonary embolism by amniotic fluid. Report of a case with review of the literature. American Journal of Clinical Pathology, 21, 566. MARCUSE, P.M. & DUSON,C.K. (1951) Pulmonary embolism due to amniotic fluid. American Journal of Obstetrics and Gynecology, 61, 695. BOWDEN, K. &ABRAHAM, E. (1950) Sudden death in labour from amniotic fluid embolism. Medical Journal of Australia, 2, 935. KISTNER,R.W., GRAF,W.R. & JOHNSTONE, R.E. (1950) Pulmonary embolism by particulate matter of the amniotic fluid: a report of two cases with a review of the literature. Obstetrical and Gynecological Survey, 5,629. SCHENKEN, J.R., SLAUGHTER, G.P. & DEMAY,G.H.

Amniotic fluid embolism (1950) Maternal pulmonary embolism of amniotic fluid. American Journal of Clinical Pathology. 20. 147. 86. SHOTTON.D.M. & TAYLOR,C.W. (1949) Pulmonary embolism by amniotic Huid. (A report of a

87.

88.

89.

90.

91.

92.

93.

94.

95. 96.

97.

98.

99.

100. 101.

102.

103.

104.

fatal case, together with a review of the literature.) Joirrnnl of Obstetrics nnd Gynaecology of’ the British Empire, 56, 46. STEINER, P.E., LUSHBAUGH, C.C. & FRANK,H.A. (1949) Fatal obstetric shock from pulmonary emboli of amniotic fluid. American Journal oJ Obstetrics and Gynaecology, 58, 802. JENNINCS, E.R. & STOFER,B.E. (1948) Pulmonary emboli composed of contents of amniotic fluid. Archioes of Pathology, 45, 616. WYATT,J.P. & GOLDENBERG, H. (1948) Amniotic fluid embolism. Report of a fatal case. Archiws of Pathology, 45, 366. WATKINS,E.L. (1948) Sudden maternal death from amniotic fluid embolism. American Journal of Obstetrics and Gynecology, 56, 994. GROSS,P. & BENZ,E.J. (1947) Pulmonary enibolism by amniotic fluid. Report of 3 cases with a new diagnostic procedure. Surgery, Gynecology und Obstetrics, 85, 3 15. SELTZER,L.M. & STHUMAN, W. (1947) Nonfatal pulmonary embolism by amniotic fluid contents with report of a possible case. American Journal of Obstetrics and Gynecology, 54, 1038. LUSHBAUGH, C.C. & STEINER,P.E. (1942) Additional observations o n maternal pulmonary embolism by amniotic fluid. American Journal of Obstetrics and Gynecology, 43, 833. STEINER,P.E. & LUSHBAUGH, C.C. (1941) Maternal pulmonary embolism by amniotic fluid as a cause of obstetric shock and unexpected deaths in obstetrics. Journal of the American Medical Association, 117, 1245 and 1340. MEYER,J.R. (1926) Embolis pulmonar-caseosa. Brazil-Medico, 2 , 301. WARDEN,R.M. (1927) Amniotic fluid as a possible factor in the etiology of eclampsia. American Journal oJObstetrics and Gynecology, 14,292. OSTERGARD.D.R. (1970) T h e physiology and clinical importance of amniotic fluid. A review. Obstetrical and Gynecological Surcwy, 25, 297. KARIM,S.M.M. & DEVLIN,J. (1967) Prostaglandin content of amniotic fluid during pregnancy and labour. Journal of Obstetrics and Gynaecology of the British Commonwealth, 14, 230. LEWIS,T.L.T. (1964) Progress in Clinical Obstetrics and Gynaecology, 2nd edn, p. 48. Churchill, London. COURTNEY, L.D. (1974) Amniotic fluid embolism. Obstetrical and Gynecological Suroey, 29, 169. GUHA-RAY, D.K. (1976) Maternal mortality in an urban hospital. A fifteen year survey. Obstetrics and Gynecology, 41, 430. DEPARTMENT OF HEALTHAND SOCIAL SECURITY (1 975) Report on confidential enquiries into maternal deaths in England and Wales 1970-1972. Report on Health and Social Subjects, 1 I. HMSO, London. ATTWOOD,H . D . (1972) Amniotic fluid embolism. Pathology Annual, 7 , 145. COURTNEY,L.D., BOXALL,R.R. & CHILD, P.

31

(1971) Permeability of membranes of dead fetus. Briti.di Me(lica1 Journal, 1, 492. 105. T U R N B U L LA.C. , & ANDERSON,A.B.M. (1965)

106.

107.

108.

109.

110.

111.

Changes in uterine contractility following intraamniotic injection of hypertonic saline to induce therapeutic abortion. Jorrrnul of’ Obstetrics nnd Gynaecology of the British Commoniveolth, 12. 7 5 5 . TALBERT. L.M.. ADCOCK, D.F.. WEISS, A.E., EASTERLING, W.E. & ODOM,M.H. (1973) Studies on the pathogenesis of clotting defects during salt induced abortions. American Journal of Obstetrics and Gynecology, 115, 656. STANDER,R.W., FLEJSA,H.C., GLIJECK,H.1. & KISKER,T.C. (1971) Changes in maternal coagulation factors after intra-amniotic injection of hypertonic saline. Obstetrics and Gynecology, 3 7 , 660. FROST. A.C.G. (1967) Death following intrauterine injection of hypertonic saline solution with hydatidiform mole. Americaq Journal OJ Obstetrics and Gynecology, 101, 342. LANDING, B.J. (1950) The pathogenesis o f aniniotic-fluid embolism. 11. Uterine factors. New England Journal of Medicine, 243, 590. BELLER.F.K. (1974) Disseminated intravascular coagulation and consumption coagulopathy in obstetrics. Obstetrics and Gyni,cology Annual. 3 , 267. ATTWOOD,H.D. (1964) A histological study of experimental amniotic-fluid and meconium embolism in dogs. Journal 0JPatholog.v (ind Bacteriology.

88,285. J.T., EDWARDS, J.E., BURCHELL, H.B., 112. SHEPHERD, SWAN, H.J.C. & WOOD, E.H. (1957) Clinical,

physiological and pathological considerations in patients with idiopathic pathological considerations in patients with idiopathic pulmonary hypertension. British Heart Journal, 19, 70. D.E. (1957) 113. EVANS,W., SHORT,D.S. & BEDFORD, Solitary pulmonary hypertension. British Hetrrt Jorrrnul, 19, 93. 114. ATTWOOD, H.D. & DOWNING. S.E. (1965) Experimental amniotic fluid and meconium embolism. Surgery, Gynecology and Obstetrics, 120, 255. 115. ROCHE, W.D. & NORRIS,H.J. (1974) Detection and significance of maternal amniotic Huid embolism. Obstetrics and Gynecology, 43, 729. W.B. & BUDD,J.W. (1965) Erroneous 116. THOMPSON, diagnoses of amniotic fluid embolism. Americnn Journal of Obstetrics and Gynecology. 91, 606. C.L. (1946) T h e aspiration of stom117. MENDELSON, ach contents into the lungs during obstetric anesthesia. American Journal of Obstrrrics and Gynecology, 52, 19 I . 118. ZIPSER, G. (1971) Amniotic fluid embolism. Medical Journal of Australia, 2, 953. J.E. & GOODMAN, P.H. 119. ARNOLD,H.R., GARDNER, (1961) Amniotic pulmonary embolism. Radiology, 77, 629. N.J. (1948) Editorial comment. Obstet120. EASTMAN, rical and Gynecological Surisey, 3, 35. M. & TURPINI,R.A. (1959) Fibrino121. STEFANINI, genopenic accident of pregnancy and delivery: a syndrome with multiple etiological mechanisms. Annals of rhe New York Academy o,f n::ences, 75, 601.

M . Morgan

32

122. HALMAGYI, D.F.J., STARZECKI, B. & SHEARMAN, 137. HUNTER, R.M., SCOTT,J.C., SCHNEIDER, J.P. & R.P. (1962) Experimental amniotic fluid embolism: KRIEGER,J.A. (1956) Experimental amniotic fluid mechanism and treatment. American Journal of infusion. A preliminary report. American Journal Obstetrics and Gynecology, 84, 25 I . of Obstetrics and Gynecology, 72, 75. 123. JACQUES, W.E., HAMPTON, J.W., BIRD, R.M., 138. WEINER, A.E., REID,D.E. & ROHY,C.C. (1949) B. (1960) Pulmonary BOLTEN, K.A. & RANDOLPH, The hemostatic activity of amniotic fluid. Science, hypertension and plasma thromboplastin anteN.Y., 110, 190. cedent deficiency in dogs. Experimental induction 139. HARDAWAY, R.M. & MACKAY,D.G. (1959)

by infusion of amniotic fluid. ArchiuesofPathology, 69, 248.

124. MACMILLAN, D. (1968) Experimental amniotic fluid infusion. Journal of Obstetrics and Gynarcology of the British Commonwealth, 75, 849. 125. RODOERS, B.M., STAROSCIK, R.N. & REIS, R.L. (1971) Effects of amniotic fluid on cardiac contractility and vascular resistance. American Journal of' Physiology, 220, 1979. 126. RODGERS, B.M., STAROSCIK, R.N. & REIS, R.L. (1969) Amniotic fluid embolism: Effects on

myocardial contractility and systemic and pulmonary vascular resistance. Surgical Forum, 20, 203.

Disseminated intravascular coagulation: a cause of shock. Annals of Surgery, 149, 462. 140. BELLER. F.K. & USZYS~KI, M. (1974) Disseminated intravascular coagulation in pregnancy. Clinical Obstetrics and Gynecology, 17, No. 4, 250. L.D. & ALLINGTON, M. (1972) Effect of 141. COURTNEY,

amniotic fluid on blood coagulation. British Journal of Haematology, 22, 353.

142. PHILLIPS, L.L. & DAVIDSON, E.C. (1972) Procoag-

ulant properties of amniotic fluid. American Journal of Obstetrics and Gynecology, 113, 91 I . 143. LUNELL,N.O., JOELSSON,I., BJBRKMAN, U., LAMB,P. & PERSSON, B. (1976) The use of sal-

127. REIS, R.L., PIERCE,W.S. & BEHRENDT, D.M. (1969) Hemodynamic effects of amniotic fluid

butarnol in obstetrics. Acta obstetrica et gynecologica scandinauica, 55, 333.

embolism. Surgery, Gynecology and Obstetrics,

144. LIPSHITZ, J. & BAILLIE, P. (1976) The etTects of

129, 45.

128. SPENCE,M.R. & MASON,K.G. (1974) Experi-

mental

amniotic fluid embolism in rabbits.

American Journal of Obstetrics and Gynecology,

119, 1073.

129. KITZMILLER, J.L. & LUCAS,W.E. (1972) Studies

on a model of amniotic fluid embolism. Obsterrics and Gynecology, 39, 626. 130. REEVES, I.T., DAOUD,F.S., ESTRIDGE, M., STONE, W.H. & MCGARY,D. (1974) Pulmonary pressor

effects of small amounts of bovine amniotic fluid. Respiration Physiology, 20, 23 I . 131. VANE, J. (1971) Inhibition of prostaglandin synthesis as a mechanism of action of aspirin like drugs. Nature, London, 231, 232, 132. HOLDCROFT, A. (1975) Prostaglandins-a review. Anaesthesia and Intensiue Care, 3, 105.

fenoterol hydrobromide (partusisten) aerosol on uterine activity and the cardiovascular system. British Journal of Obstetrics and Gynaecology, 83, 864. A. & LITWAK,R.S. (1966) Amniotic 145. ALTCHEK,

fluid pulmonary embolism. Obstetrics and Gynecology, 21, 885. 146. HILL,J.D., RATLIFF, J.L., FALLAT, R.J., TUCKER, H.J., LAMY,M., DIETRICH, H.P. & GERBODE, F. (1974) Prognostic factors in the treatment of acute respiratory insufficiency with long-term extracorporeal oxygenation. Journal of Thoracic and Cardiovascular Surgery, 68. 905. 147. DUTTA, D., BHARGAVA, K.C., CHAKRAVARTI, R.N. & DHALL,S.R. (1970) Therapeutic studies in

experimental amniotic fluid embolism in rabbits. American Journal of Obstetrics and Gynecology,

133. DUCHARME, D.W., WEEKS, J.R. & MONTGOMERY, 106, 1201. Y.S. & VANE,J.R. (1974) PharmacoR.G. (1968) Studies on the mechanism of the 148. BAKHLE,

hypertensive effect of prostaglandin

kinetic function of the pulmonary circulation.

of

Physiological Reuiews, 54, 1007.

F2.. Journal Pharmacology and Experimental Therapeutics,

160, 1. 134. ANGGARD, E. & BERGSTROM, S. (1963) Biological

effects of unsaturated trihydroxy acid (PGF2.) from normal swine lung. Acta physiologica scandinauica, 58, 1. 135. ADAMSONS, K., MUELLER-HEUBACH, E. & MYERS, R.E. (1971) The innocuousness of amniotic fluid infusion in the pregnant rhesus monkey. American Journal of Obstetrics and Gynecology, 109, 977. 136. STOLTE, L., V A N KESSEL, H., SEELEN, J., ESKES,T. & WAGATSUMA, T. (1967) Failure to produce the syndrome of amniotic fluid embolism by infusion of amniotic fluid and meconium into monkeys. American Journal of Obstetrics and Gynecology, 98, 694.

49. HYMES,A.C., ROBH, H.J. & MARGULIS. R.R. (1970) Influence of an industrial surfactant (pluronic F-68) on human amniotic fluid embolism. American Journal of Obstetrics and Gynecology, 107, 1217. 50. LEETON,J.F. (1974) Emergency complications of

the third stage of labour and early puerperium. In Obstetric Therapeutics (Ed. by D. F. Hawkins), p. 463. Bailliere Tindall, London. 151. BELLER,F.K. (1964) Treatment of coagulation disorders in pregnancy. Clinical Obstetrics and Gynecology, 7, 372. 152. COPE,1. (1971) Blood coagulation and thrombosis:

problems in obstetrics and gynaecology. Mrclicul Jorrrnal of Australia, 2, 983.