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ticularly peak-expiratory-flow measurements at

work, can be applied in any circumstances whereoccupational respiratory disease is a possibility.The increasing simplicity and decreasing cost ofdevices to measure peak expiratory flow put suchtechniques easily in the grasp of any doctor with apatient who may have occupational lung symp-toms. More detailed study may later be necessaryunder controlled laboratory conditions, but thefirst necessity is to follow up clues in the historyand, whenever possible, to pursue them at work. Alarge-scale investigation has shown a major prob-lem with colophony fumes in an electronic factory.How many radio construction enthusiasts and one-man television repairers also suffer from colophonyasthma? Since colophony is a derivative of pineresin, does colophony asthma come in the samegroup as the woodworker’s asthma caused by dustfrom western red cedar, iroko, and other hard-woods ? The immunological details of the colophonyreaction need to be clarified. Drugs such as sodiumcromoglycate and salbutamol are of temporaryvalue in management, but prevention is much moreimportant. Efficient exhaust ventilation is a first

step, and a search for a safer flux will be a long-term objective.

Amniotic-fluid Embolism

OVER the fifty years from 1928 to 1977 maternalmortality fell in England and Wales from 4.4 per1000 births to 0.13. Changes during the

past twenty years may have been less striking,but the major pillars on the histograms (abortion,pulmonary thromboembolism, haemorrhage, andtoxaemia) have gradually been whittled down. In1977 toxxmia, ectopic pregnancy, and pulmonarythromboembolism headed the list, but four othercauses now vie for prominence because their ratesare not decreasing: sepsis, cardiac disease, aneesthe-sia, and amniotic-fluid embolism. Of the majorcauses of maternal mortality, it is only of amniotic-fluid embolism that it can be said that "This causeof maternal death remains unpredictable and large-ly unpreventable".1 MORGAN’S review2 reveals thatof 272 reported cases 86% were fatal. In Englandand Wales the incidence of amniotic-fluid embolismis steady at approximately 1 case for every 80 000deliveries (8 cases per year). Large American seriesgive higher rates.3,4 To have any impact on mortal-ity from this disorder clinicians will ask the follow-

1. Department of Health and Social Security. Extracted from report on confi-dential enquiries into maternal deaths in England and Wales 1970-72.H.M. Stationery Office London.

2. Morgan M. Amniotic fluid embolism. Anœsthesia 1979; 34: 20-32.3. Barno A, Freeman DW. Amniotic fluid embolism. Am J Obstet Gynec 1959;

77: 1199-10.4. Anderson DG. Amniotic fluid embolism. A re-evaluation. Am J Obstet Gynec

1967; 98: 336-48.

ing questions: can amniotic-fluid embolism berecognised clinically and can the suspected diag-nosis be confirmed in life; are the predisposing fac-tors known; is the pathogenesis understood; howshould the patient be managed; and is specific ther-apy available? Not all can yet be answered.The clinical picture is not one that the witness-

ing obstetrician will forget: profound cardiovascu-lar shock and respiratory difficulty with deepcyanosis, often accompanied by uterine atony andhaemorrhage, were the features described bySTEINER and LUSHBAUGH in 1941.5 Dyspnoea,cyanosis, collapse, haemorrhage, and coma featureto varying degrees, although bleeding is noted inonly half the cases and is not always confined to theuterus. 10% of cases may present with convulsionsand 12% with hxmorrhage before collapse leads tocoma.2 The respiratory embarrassment begins asair hunger and the chest is clear at first. However,pulmonary redema often develops subsequently.Bronchospasm is rare. A small number of patientshave prodromal symptoms such as vomiting, shiv-ering, or convulsions. A confident clinical diagnosiscan usually be made, but amniotic-fluid embolismhas been confused with eclampsia (in fittingpatients), accidental haemorrhage, uterine rupture,severe supine hypotension, acid aspiration syn-drome, and pulmonary thromboembolism. If the pa-tient survives, long-term ill-effects are rare. If not,then the pathologist can confirm the diagnosis byfinding, in the pulmonary arterioles, epithelialsquames from fetal skin, lanugo hair, fat from ver-nix caseosa, mucin presumed to be from the fetalgastrointestinal tract, and, occasionally, bile frommeconium contamination of the amniotic fluid.STEINER and LUSHBAUGH5 provided a clear clinico-pathological correlation, and the post-mortem fea-tures are unique to patients with the clinical pic-ture of amniotic-fluid embolism.6 6 Detectingamniotic material in the lungs may require specialstains, such as those for fat, alcian-green phloxinfor squames, or Mowry’s colloidal iron for acid

mucopolysaccharide in mucus. In life, hypofibrino-genaemia, platelet consumption, depletion of factorsV and VIII, and other features of disseminated in-travascular coagulation provide strong supportiveevidence of the diagnosis, but are not specific. As-piration of blood from the right atrium via themandatory central-venous-pressure (CVP) line willallow a positive diagnosis. In 1947 GROSS andBENZ7 demonstrated an extra-flocculant layer, oncentrifuged blood collected immediately post mor-tem, and this finding has been applied to life.8 The

5. Steiner PE, Lushbaugh CC. Maternal pulmonary embolism by amnioticfluid as a cause of obstetric shock and unexpected death in obstetricsJAMA 1941; 117: 1245-54, 1340-45.

6. Roche WD, Norris HJ. Detection and significance of maternal pulmonaryamniotic fluid embolism. Obstet Gynec 1974; 43: 729-31.

7. Gross P, Benz EJ. Pulmonary embolism by amniotic fluid. Report of 3 caseswith a new diagnostic procedure. Surg Gynec Obstet 1947; 85: 315-20

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finding of fetal squames in maternal sputum cyto-logy can be corroborative and lung scans may showevidence of perfusion defects compatible withembolism in patients surviving the initial insult.

Predisposing factors do not seem to be specific. Theolder multiparous patient who is at term or just beyondit seems most at risk. The notion that large babies andobstructed labour increase the risk is not supported bythe figures, but tumultuous or tetanic contractions arecommon (28% in MORGAN’S analysis2) and labour isoften rapid. Oxytocin use was noted in 22% of cases.Amniotic-fluid embolism usually occurs during delivery.3 probable cases have been described in the mid-trimes-ter, 2 during evacuation for missed abortion and 1 spon-taneously in a threatened abortion.9-11

Despite STEINER and LUSHBAUGH’S experiments pro-ducing shock, cyanosis, pulmonary oedema, and death indogs and rabbits by injecting human amniotic fluid, thepathogenesis of the clinical syndrome remains unsolved.Amniotic fluid probably enters uterine veins throughtears in fetal membranes above the presenting part andthen finds its way into the maternal circulation vialacerations of the lower segment and cervix (SMIBERT12demonstrated disruption of the birth canal in 70% of hisseries) or by shelving under the placental margin to entermaternal venous sinuses (premature placental separa-tion was noted in 45% of cases just before collapse in theseries reported by PETERSON and TnYLOxl3). The mech-anism whereby, with the fetal presenting part wedged inthe pelvis, excessive contractions drive liquor into thematernal circulation is plausible, but it is noted in onlya minority of cases. The clinical syndrome is associatedwith amniotic-fluid transport to the lungs, but three con-troversial observations await explanation. Animal exper-iments incriminate particles in the amniotic fluid as thecause of cyanosis, respiratory difficulty, and shock, yetmucin is the most common agent identified in pulmon-ary vessels post mortem. Mucin is presumed to arisefrom the fetal gastrointestinal tract, though meconiumstaining of liquor is not the rule; mucin can hardly beincriminated in mid-trimester cases and nor can fetal

squames. ADAMSON et a1.14, critical of much of the exper-imental work, injected late-pregnancy autologousamniotic fluid into pregnant rhesus monkeys; cardiovas-cular performance, acid-base studies, oxygenation ofmother or fetus, and fibrinogen concentration did notchange and there were no long-term effects. They con-cluded that amniotic-fluid embolism was a misnomer.

8. Schaerf RHM, de Campo T, Civetta JM. Hæmodynamic alterations andrapid diagnosis in a case of amniotic fluid embolus. Anesthesiology 1977;46: 155-57.

9. Woodfield DG, Galloway RK, Smart GE. Coagulation defect associated withpresumed amniotic fluid embolism in the mid-trimester of pregnancy. JObstet Gynæc Brit Cmmwlth 1971; 78: 423-29.

10. Lees DE, Shin Y, MacNamara TE. Probable amniotic fluid embolism duringcurettage for a missed abortion: a case report. Anaesth Analg 1977; 56:739-42.

11. Stromme WB, Fromke VL. Amniotic fluid embolism and disseminated intra-vascular coagulation after evaluation of missed abortion. Obstet Gynec1978; 52: suppl 1: 76S-80S.

12. Smibert J. Amniotic fluid embolism. A clinical review of twenty cases. AustNZ J Obstet Gynæc 1976; 7: 1-12.

13. Peterson EP, Taylor HB. Amniotic fluid embolism. An analysis of 40 cases.Obstet Gynæc 1970; 35: 787-93.

14. Adamsons K, Mueller-Heubach E, Myers RE. The innocuousness of amnio-tic fluid infusion in the pregnant rhesus monkey. Am J Obstet Gynec1971; 109: 988-84.

Although COURTNEY and ALLINGTON" showed thatamniotic fluid contains a factor-X-activating property,other workers’6 reported that this activity is insufficientin chorioamniotic fluid to cause significant intravascularcoagulation in the event of an amniotic fluid infusion, sothe strong thromboplastic activity noted in this syn-drome remains to be explained.

Our limited knowledge of the pathophysiology of thiscondition dictates attitudes to prevention, treatment,and further research. The traditional view is that theacute cardiorespiratory effects result from the combinedaction of partial mechanical occlusion and pulmonaryarteriolar vasospasm leading to acute cor pulmonale.Systemic vasodilation and, possibly, a direct or reflexmyocardial inhibition causes marked hypotension andperhaps contributes to pulmonary cedema. The coagula-tion defect is a consequence of disseminated intravascu-lar coagulation usually associated with uterine hmmor-rhage. One possibility warranting research is the role ofprostanoids. Prostaglandins in amniotic fluid increaseduring labour17, 18 and unstable products of the prosta-glandin-synthetase enzyme complex may convert to

thromboxanes, prostaglandins or prostacyelin, all withknown effects on uterine relaxation/contraction, vasodila-tion/vasoconstriction, and platelet aggregation/disaggre-gation. Many of the clinical features of amniotic-fluidembolism could be explained by various prostanoidactions, and the work of KITZMILLER and LUCAS,19 whofound that PGF2<x and liquor from labouring womenproduce a similar picture of hypotension and raised cen-tral venous pressure in cats, is encouraging.

The few reports on survivors provide no clearreasons for survival, other than reduced severity ofthe condition, and this, with our poor understand-ing of the pathogenesis, means that no specifictreatment is known. The first priority is the cardio-pulmonary derangement. Early intubation and

positive-pressure respiration are required. An intra-venous line is essential, but a CVP line is also

mandatory to guide fluid requirements and allowaccess to right atrial blood for accurate diagnosis.If the CVP remains very high, rotating tourniquetsand possibly venesection should be considered. Thevalue of digoxin, diuretics, antispasmodics, vaso-dilators, low-molecular-weight dextran, and hydro-cortisone is unclear. However, isoproterenolreverses the changes of experimental amniotic-fluidembolism in the sheep model2O and this drug has apositive inotropic effect on the myocardium. Atro-pine could counter cardiac depression from exces-sive vagal tone and the coronary and pulmonary

15. Courtney LD, Allington M. Effect of amniotic fluid on blood coagulation. BrJ H&oelig;mat 1972; 22: 353-55.

16. Phillips LL, Davidson EC. Procoagulant properties of amniotic fluid. Am JObstet Gynec 1972; 113: 911-19.

17. Karim SMM. Identification of prostaglandins in human amniotic fluid. JObstet Gyn&aelig;c Brit Cmnwlth 1966; 73: 903-08.

18. Mitchell MD, Keirse MJNC, Anderson ABM, Turnbull AC. ThromboxaneB2 in amniotic fluid before and during labour. Brit J Obstet Gyn&oelig;c 1978;85: 442-45.

19. Kitzmiller JL, Lucas WE. Studies on a model of amniotic fluid embolism.Obstet Gynec 1972; 39: 626-27.

20. Halmagyi DFJ, Starzecki B, Shearman RP. Experimental amniotic fluidembolism: mechanism and treatment. Am J Obstet Gynec 1962; 84:251-56.

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vasoconstriction. In rabbit experiments21 the indus-trial surfactant ’Pluronic F-68’ prevented andreversed shock from amniotic-fluid injection bypreventing aggregation of platelets around particu-late debris in the pulmonary circulation. Surfac-tants have not been tried clinically, but othermethods of reversing platelet aggregation mightusefully be studied. The coagulation disturbancehas traditionally been treated by replacement offibrinogen and fresh blood. Lately, heparin hasbeen advocated. Early reports8,10,11,22 suggest thatheparin 5000-10 000 units intravenously beforefibrinogen replacement may stop the enhancedfibrinolytic action which stems from simply provid-ing fibrinogen fuel for the fire. The theoreticaldanger of s-aminocaproic acid is the potential forwidespread spontaneous thromboses. Oxytocin in-fusion should be stopped and the uterus should beevacuated when the patient’s general condition iscontrolled. Sometimes uterine packing is required.Up to 40% of babies may be born alive since mostof the cases occur in the late first and second stagesof labour, and post mortem csesarean section canproduce live babies.

ANAESTHESIA IN THE HYPERTENSIVE PATIENT

ANESTHETISTS find it difficult to win in the manage-ment of the hypertensive patient. If the patient has un-treated severe hypertension, the induction of anaesthesiawill often precipitate a sharp fall of blood-pressurewhich can have serious consequences because the circu-lation has become adapted to the increased tension. Ifthe patient has been treated with antihypertensiveagents for a long time, the blood-pressure will be nearernormal and the fall in tension associated with aneesthe-sia will be proportionately less and better tolerated,but the potent antihypertensive agents can inter-act with the anxsthetic drugs and produce severe hypo-tension and other unwanted effects such as serious

bradycardia. If the anaesthetist asks for the antihyper-tensive drugs to be withdrawn, this must be done 10-14days preoperatively to be effective, and during this per-iod symptoms of hypertension, and even severe compli-cations such as a stroke, may develop.What is the anaesthetist to do for the best? The recent

trend has been to keep patients on their routine doses ofantihypertensive drugs and to anticipate circulatoryproblems by careful monitoring during anaesthesia. It isinteresting, therefore, that Goldman and Caldera23 nowconclude, from a large prospective study of the risks ofanaesthesia in hypertensive patients, that effective intra--operative management may be more important thanpreoperative control of hypertension. They were unable

21. Hymes AC, Robb HJ, Margulis RR. Influence of an industrial surfactant(pluronic-F68) on human amniotic fluid embolism. J Obstet Gyn&oelig;c BritCmnwlth 1971; 78: 423-29.

22. Chung AF, Merkatz IR. Survival following amniotic fluid embolism withearly heparinization. Obstet Gynec 1973; 42: 809-14.

23. Goldman L, Caldera DL. Risks of general anesthesia and elective operationin the hypertensive patient. Anesthesiology 1979; 50: 285-92.

to identify significant differences between the mean low-est systolic pressures during anaesthesia in well-con-

trolled, poorly controlled, and untreated hypertensivepatients. Moreover, there were no differences in the pro-portions of patients who needed remedial measures suchas adrenergic agents or fluid challenges in these threegroups. Multivariate analysis showed that there were nocorrelations between preoperative systolic and diastolicblood-pressures and any of the following in the perioper-ative period: blood-pressure lability, cardiac arrhyth-mias, cardiac ischaemia, cardiac failure, and post-operative renal failure.

If Goldman and Caldera are right there is little justifi-cation for the last-minute postponement of routine sur-

gery on patients who are found during preoperative as-sessment by the anaesthetist to be at risk directly fromhypertension or indirectly from their antihypertensivemedication. Whilst the need for postponement could

largely be resolved by earlier communication with theanaesthetist, further studies are required to formulatethe best way of actually managing the surgical patientwhen he is known to be hypertensive.

THE GLOMERULUS

FiRST identified by Malpighi some two centuries ago,the renal glomerulus sits like a pinhead at one end of along, thin tubule. Some species can do without this in-conspicuous structure and many people must wonderwhy it so preoccupies nephrologists. But at a colloquiumorganised in June by Gabriel Richet at the Tenon Hospi-tal, Paris, its complexity and importance were veryobvious. The first part was concerned with the patho-physiology of glomerular filtration, the second with thenature of the control mechanisms which reside withinthe glomerulus itself. B. Aeikens (Hanover) gave a lucidaccount of the five-lobular structure of the rat glo-merular tuft, emphasising the profuse anastomoses

between lobules at the centre of the glomerulus. Filt-ration takes place principally at the glomerular base-ment membrane (GBM), and from embryological stu-dies this membrane seems to be derived both from

capillary endothelial cells and from visceral (as opposedto capsular) epithelial cells. Clearly, both categories ofcell should be taken into account when attempts aremade to explain the GBM lesions which characterise somany forms of nephritis.The great debate about which part of the capillary

wall plays the most important role in the control of per-meability to macromolecules continued with a paper byJ. Barietyl (Paris) recording the use of antiperoxidaseantibodies as ultrastructural tracers. This techniqueallows the investigator, in effect, to display electron-

microscopically the point in the glomerular capillarywall at which injected IgG antibodies are arrested. Bar-iety’s claim that in the normal rat the main barrier liesin the lamina densa of the GBM excited considerable

controversy. His emphasis on the role of the GBM was

1. Druet P, Bariety J, Lalliberte F, Bellon B, Belair M-F, Paing M. Distribu-tion of heterologous antiperoxidase antibodies and their fragments in thesuperficial renal cortex of normal Wistar-Munich rat. An ultrastructuralstudy. Lab Invest 1978; 39: 623-31.