Postgrad. med. J. (April 1967) 43, 225-233.

Management of status asthmaticus

HARRY A. REESUniversity Department of Medicine, Royal Infirmary, Edinburgh

MortalityStatus asthmaticus is a term which is universally

used but not uniformly defined. It is generally takento mean an acute episode of 'bronchospasm', severeenough to cause distress to the patient and whichis not relieved by conventional 'bronchodilator'therapy.

Is status asthmaticus a transient event in the lifeof the asthmatic patient; can it be treated as a minorincident? I think the following data will convinceyou that nothing is farther from the truth. It consistsof the deaths in the Cardiff area for the years 1951to 1964 and I am grateful to Dr D. A. Williams forgenerously making it available to me. There were111 deaths over this period (Fig. 1), an average of

15

10

7 5

z

1951 53 55 57 59 61 63Yeaor

FIG. 1. Deaths from asthma in the Cardiff area from 1951to 1964. Thirty-eight at home, seventy-three in hospital(total 11 1).

1-8 per 100,000 population per annum and which iscomparable to the annual death rate from asthmain America of 1-6 per 100,000 (Derbes & Engelhardt,1946) but is much less than that reported by Williams(1953) of 7.07 per 100,000 for England and Wales.It appeared by 1960 that the problem was well undercontrol, but there has since been an upward trendin mortality. This is also seen in the Reports of theRegistrar General for England and Wales. Althoughdeath occurred at all ages in the Cardiff group, only5% were under the age of 20 years (Fig. 2). Thirty-nine per cent occurred between 20 and 50 years and51% between 51 and 70 years. The ratio of male-female deaths was 1:2 at most ages. Most had longhistories of asthma with frequent episodes of status

asthmaticus, but of great interest were a few whodied during an attack which did not appear to besevere and in some cases certainly not as severe asprevious ones. Most of us have had this startlingexperience. It is surprising that at post-mortem thelungs of these patients who died suddenly shouldshow the same appearance as those dying in statusasthmaticus (Walton, Penner & Wilt, 1951; andpersonal observation), and serves to illustrate thefallibility of clinical assessment in certain cases ofstatus asthmaticus.

30

z lO

<10 10-20 21-30 31-40 41-50 51-60 61-70 >70Age (years)

FIG. 2. Sex and age distribution of deaths. 0, Female;x, male; *, total.

Detailed study of mortality statistics, thoughinstructive, does not enable us to pick out theindividual who is at particular risk from statusasthmaticus.

PreventionIt follows that if the frequency and severity of

status asthmaticus could be reduced, then thereshould be an accompanying fall in mortality.Although there are no adequately controlled studiesit seems likely that the judicious use of long-termcorticosteroids and/or ACTH has helped to reducethe frequency of status asthmaticus. It should beemphasized that this form of therapy should only beemployed in intractable asthma when all othermeasures have failed. It was possible, using thisregime, to reduce the frequency from 42% to 4.4%

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Harry A. Rees

in a group of 317 patients receiving long-term cortico-steroid and/or ACTH therapy for longer than3 months (Rees & Williams, 1962). Some workersfavour an intermittent regime for so many days eachweek and this approach may be better in children.Although it should be possible to prevent statusasthmaticus with large doses of steroids used con-tinuously, the accompanying serious side-effects pre-clude this. Therefore the aim should be to use thesmallest dose of steroid which enables the person tolead a useful life and not to try to get him/hercompletely free of bronchospasm. In most cases thisis 5-10 mg of prednisone taken with 'broncho-dilators'. Patients on long-term corticosteroidsshould be reviewed frequently (Rees & Williams,1962).When increased 'bronchodilator' therapy fails to

control increasing 'bronchospasm' we have found ituseful to instruct the patient to increase the dose ofprednisone to 40 mg/day. Those subject to infectiveasthma are either given a reserve supply of an anti-biotic to take at the first sign of a chest cold, oradvised to increase the dose if they are receivinglong-term antibiotics. Ideally all patients in statusasthmaticus should be admitted at the onset of theepisode, but this may be impracticable. If, therefore,the 'bronchospasm' remains unaltered after 24 hr ofincreased steroids and, possibly, antibiotics, thepatient is advised to contact the general practitioner,who should arrange for hospital admission. We feelto persevere with treatment at home for longer than24 hr may be dangerous. Of the 111 deaths in theCardiff area, one-third occurred either at home or intransit to hospital and it is possible that some ofthese may have been avoided.You may well ask why mortality is rising despite

the wider use of corticosteroids? The problem iscomplex and there are several possible explanationsother than ineffectiveness of long-term steroidtherapy. It may be that the incidence of bronchialasthma is changing and that some asthmatic patientswho would have died some years before have hadtheir lives prolonged by the use of corticosteroids.Whatever the explanation, this further increase indeaths stresses that status asthmaticus is a seriousand sometimes fatal condition.

Other novel measures such as glomectomy(Curran et al., 1966), hypnotherapy (Maher-Lough-nan et al., 1962) and treatment in a pressure-chamber (Tromp, 1964) have only a limited applica-tion.

Therapy of acute attackMy terms of reference are the 'medical' treatment,

and the Liverpool group will discuss their resultswith assisted ventilation. In an attempt to gain abetter understanding of status asthmaticus we havebeen monitoring the arterial gas tensions and pH

(Rees, Millar & Donald, 1967). It is in the light ofthese findings that I propose to discuss conventionaltherapy, which is listed below:

1. Oxygen2. Bronchodilators3. Corticosteroids and/or ACTH4. Antibiotics5. Fluid replacement6. Sedation7. Other measures

1. OxygenThe main limiting factors to the administration of

oxygen for the relief of hypoxaemia in patients withchronic lung disease are the loss of chemoreceptordrive when the hypoxaemia is relieved, and thepossibility of atelectasis. All the patients we studiedwere hypoxaemic, and the patient illustrated inFig. 3 is an example. Arterial oxygen tensions(Pao2) as low as 30 mmHg were common in thosewho were obviously severely ill. In the severely illpatient it is likely that the cardiac output is reduced,which will interfere with the delivery of the availableoxygen to the tissues. Some of this group werehypercapnic. They were also acidotic from respiratoryand metabolic causes. In a situation where life isjeopardized by lack of oxygen, the possibility ofatelectasis is more theoretical than real. It wouldappear that vast shunting of blood may occurthrough the lungs of patients in status asthmaticus.This is, perhaps, not surprising in view of the wide-spread bronchiolar plugging which is well seen atpost-mortem.Where facilities exist for monitoring arterial gas

tensions, it is relatively easy to adjust the concentra-tion of oxygen that is administered. Controlledoxygen through an Edinburgh or Venturi mask ornasal spectacles is indicated for the hypercapnicpatient. It is not known what constitutes a safe levelof Pao2 or, more important, what is a safe level oftissue oxygen tension. We aim to maintain the Pao2above 50 mmHg and in most cases this can safelybe achieved with oxygen delivered through a Poly-mask. It is advisable to bubble the oxygen throughwater in an attempt to maintain hydration of theairways and so to prevent the bronchiolar plugs ofmucus, etc., becoming tenacious. The flow rate atthe mask is lower than that registered on the flow-meter, particularly at the lower ranges, because ofthe resistance to oxygen as it bubbles through thewater. Most hospitals have apparatus for measuringPco2 and pH and if it is not possible to obtainarterial blood, then properly 'arterialized' venousblood (Harrison & Galloon, 1965) may be a usefulguide. Alternatively, mixed venous Pco2 may bemeasured by the rebreathing technique (Campbell &Howell, 1962) and if the concentration of bicarbon-ate is also determined the pH can be deduced from

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Management of status asthmaticus 227

the Henderson-Hasselbalch equation. Where nofacilities exist.for making measurements of the Pco2and/or pH, then increasing flow rates of oxygenshould be administered, starting at 1 1/min andassessing the clinical response closely. At the firstsign of drowsiness the administration of oxygenshould be temporarily discontinued while respiratorystimulants are given and oxygen then restarted atlower flow rates.

Rector et al. (1960) have shown that it takes up to4 days for maximal reabsorption of bicarbonate tooccur in dogs. The chronic asthmatic patient, who isnormally hypo- or normocapnic, is unstrategically

70Day 11 ambulant

60 -

50n'~~~~"-'

~~EN~~~~~ 4 / ,~~_______Day7 ambulant

030 500mg am hylline i.v 50mg hydrocortisone i.v.- 50 mg hydrocortisone i.v. 0'5 mg adrenaline

o 28% 02(Venturi mask)~20 - 7-45

10 20mg oral 7A40 Iprednisone

0 7,350 2 3 4 5 6 7 8

Time (hr) day

FIG. 3. Results of arterial gas tensions and pH in one patient (J.L., female, 20 years old) during andfollowing treatment of acute status asthmaticus. Po2 (@), Pco2 (0), pH (x).

placed to meet any rapid increase in Paco2. We havetherefore set arbitrary safe limits of Paco2 of50 mmHg and of pH= 730, the latter probablybeing more important than the former. However,each case has to be judged on its own merits andsuch features as physical exhaustion, rapidity of risein Paco2, fall in pH, have all to be considered beforedeciding to institute assisted ventilation. Hyper-capnia is a grave prognostic sign and this has pre-viously been noted by Williams & Zohman (1960)and Feldman (1962). Where severe hypercapnia, i.e.Paco2 of 60 mmHg and/or severe acidosis, i.e.pH < 7.25, exists on admission, then there should beno delay in starting assisted ventilation. However,we do not feel that assisted ventilation is needed asfrequently as reported by Marchand & Van Hasselt(1966). Assisted ventilation is not without its com-plications, such as difficulty in maintaining anadequate circulation, infection, etc. Nevertheless, wefeel that in a situation where the risk of death is so

great, this form of therapy may be proved to bebeneficial.Of great interest and hitherto unrecognized, is the

fact that the hypoxaemia persists on breathing air formany days (Figs. 3 and 4) in the face of apparentclinical improvement. Additional hypoxaemia fromfurther acute bronchiolar obstruction could be lethal.The persisting hypoxaemia indicates the need tocontinue oxygen therapy for 2 weeks in most casesand the importance of having the patient in hospitalunder surveillance for 3 weeks. I have dealt withoxygen therapy at considerable length; I make noapology for it-it is of vital importance.

2. Bronchodilators(a) Adrenaline. This may be given subcutaneously

in doses of 05-1 -0 ml, 1:1000 solution over 10 min.Broom (1961) has advocated larger and more fre-quent doses intramuscularly but it has been welldemonstrated by Whelan & Young (1953) that,despite the continued intravenous infusion ofadrenaline, the maximal response was obtained at10 min and thereafter a return to the pre-injectionstate occurred. In view of the rapidity of action whengiven subcutaneously there is no point in taking thepotential risk of producing arrhythmias by giving itintravenously. To our immense surprise, we foundthat adrenaline produced no real change in Pao2even when there was subjective, and (in some casesin whom forced expiratory volume in 1 sec could berecorded) objective relief of airways obstruction(Fig. 5). There was no correlation between the so-called adrenaline-fast state and the level of systemicarterial pH. Furthermore, we have found that even

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228 Harry A. Rees

when the pH has been corrected using sodium bi-carbonate, as advocated by several groups includingMithoefer, Runser & Karetzsky (1965), the injectionof adrenaline has produced no real change in the

100-

90 '3598 - 19j3

'3

/ '

2 3 4 5 6 7 8 9 10 1 1 12 12+

DEayvFIG. 4. Serial arterial oxygen tensions measured in the same patients breathing air.

80E.B. Ad MW. Statusl1-2 M.R.'

Am Ae AdAmAo~60 m-.AAmA

Ad AEE A

402

-Day--Doy 2

3000-

> 2000U--

9 1000 - /2w 00

0 45 90 0 30 75 0 45 90Time (mini

FIG. 5. Changes in arterial oxygen tension (@) and forced expiratory volume (A) in 1 sec and vitalcapacity (oI) in three patients after 1-0 ml of 1:1000 adrenaline s.c. (Ad) and 05 g of aminophyllinei.v. (Am).

Pao2. That is not to say that the correction ofacidosis may not have other merits. During thecontinuous monitoring of the electrocardiogram for1 hr or so, when adrenaline has been given, atrialectopic beats were frequently seen. Many of the

patients had been using an isoprenaline inhaler atfrequent intervals shortly before admission. Thesuggestive findings of Lockett (1965) using a Starlingpreparation, that a combination of isoprenaline and

adrenaline may produce cardiac arrest makes itprudent to avoid this combination, although there is,as yet, little convincing clinical evidence for this view.It does seem rational to expect a myocardium that isinadequately oxygenated to be more 'irritable' and

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Management of status asthmaticus

thus to be more susceptible to arrhythmias. Dramaticfalls in mean systemic arterial pressure of up to50 mmHg have been noted and this could provedangerous.

In view of all these findings, I feel that adrenaline-a time-honoured therapy-should be discon-tinued.

(b) Aminophylline. We found that the intravenousinjection of 500 mg of aminophylline producedchanges in the Pao2 similar to those produced byadrenaline. Nausea and sickness were noted in theoccasional patient but there were no arrhythmias.The differentiation of left ventricular failure fromasthma in the elderly patient can be difficult; even tothe experienced, and it is in this situation thataminophylline is particularly useful. Suppositories(one or two) at night are also effective. The oral doserequired to produce relief provokes severe gastricirritation and vomiting. In a situation where thework of breathing is greatly increased (McIlroy &Marshall, 1956) any decrease produced by relievingairways obstruction is valuable.

Other oral 'bronchodilators' such as isoprenalineand ephedrine are not particularly helpful in theacute situation.

3. Corticosteroids and/or ACTHAs many patients will have been on long-term

corticosteroid therapy it seems more rational to givecorticosteroids rather than ACTH. The dosageusually used is 60-100 mg of prednisone during thefirst 24 hr and adjusting it thereafter according toclinical progress. Some workers favour hydro-cortisone given intravenously, 50-100 mg every 6 hr,and it is often useful to give 100 mg intravenously atthe start of therapy with oral prednisone. Grant(1966) favours much higher initial doses of cortico-steroids. Others have found ACTH 40 units, every4-6 hr given intramuscularly, or 60 units in 1 litreof fluid given intravenously over 6 hr, followed byintramuscular therapy, to be useful. Althoughcorticosteroids and ACTH take many hours or daysto produce any effect, it is likely that they play animportant part in therapy. As loss of potassium mayoccur with large doses of steroids and ACTH, watchmust be kept on the serum potassium level andsupplements given orally if necessary. Scribner,Freemont-Smith & Burnell (1955) have also shownthat overall potassium depletion exists when acidosisis present, even though the serum level may benormal.

4. AntibioticsIdeally sputum should be cultured and therapy

instituted accordingly, but in the situation of statusasthmaticus this approach is impossible. Unless theprecipitating factor is obviously allergic or psycho-logical, it is wise to give a bactericidal antibiotic such

as penicillin and streptomycin or ampicillin. Threepatients given terramycin with high dosage ofcorticosteroids developed severe pneumonia from ahospital penicillin-resistant staphylococcus, whereasno other patient on bactericidal drugs did. This, ofcourse, is a clinical impression and as such has to beinterpreted cautiously. It is worth noting that sputumcontaining large numbers of eosinophil cells may beyellow.

5. Fluid replacementDehydration is often overlooked. When one takes

into account the poor fluid intake because of severedyspnoea, the excessive loss during respiration andoften increased loss through the skin of a feverishpatient, then there is more than sufficient cause forthe dehydration. Close check should be made onthe urinary output and the intake adjusted accord-ingly. It may be necessary to give intravenous fluids-preferably 5% dextrose, rather than saline, eventhough I do not believe congestive cardiac failureoccurs in asthma uncomplicated by chronic bron-chitis or bronchiectasis. Transient right ventricularstrain may be noted on the electrocardiogram. Inview of the marked tachycardia which is usuallypresent, it is prudent to give fluid slowly at a rate of1 litre every 6 hr, and make every effort to get thepatient to take fluid by mouth. I used to be taughtthat a nurse should never walk past a patient withpneumonia without making him take a drink andthis should apply equally to a patient in statusasthmaticus.

6. SedationThere is no known sedative which can be guaran-

teed not to produce respiratory depression. However,many of the patients are physically exhausted andhave not slept for several nights. In this situationand when the Paco2 is low or normal, sedation withpromazine 50-100 mg intramuscularly, or amylo-barbitone sodium 100-200 mg orally, may ensure amuch-needed rest. In certain cases where the Paco2is raised and monitoring facilities are available, I feelsedation is permissible. Such patients are agitatedand make increased metabolic demands on anoxygen supply which is already precarious. Underthese circumstances a calculated risk is justifiableprovided close watch is kept and respiratory stimu-lants and/or assisted ventilation instituted ifnecessary.Opium alkaloids, of which morphia is commonly

used, cause release of histamine (Nasmyth &Stewart, 1950) as well as respiratory depression andshould never be used.

7. Other measuresIt is not surprising that a large number of remedies

have been tried in a situation which may be resistantto conventional therapy.

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230 Harry A. Rees

(a) Humidification with steam may be helpful,particularly in children who are in an oxygen tent.The bronchial mucosa is dry and water vapour maywell help to rehydrate it.

(b) Bronchial lavage has its supporters, includingMarchand & Van Hasselt (1966), but- I find itdifficult to imagine how anything less than anAtlantic storm could loosen the tenacious plugswhich obstruct the bronchioles.

(c) Tracheostomy with aspiration of plugs hasoccasionally proved useful (Hugh-Jones, 1958) butagain the problem of accessibility of the plugs exists.

(d) Inhalation of adrenaline or isoprenaline usinga Collinson's apparatus or Wright's nebulizer aresometimes used. These drugs may also be ad-ministered under positive pressure using a Bennett orBird ventilator.

(e) Clinical experience with the new mucolyticagent acetyl-cysteine (Airbron) has proved encourag-ing but its efficacy has yet to be proved.

(f) General anaesthesia has its advocates (Tausig,Papper & Barach, 1952) and more recently rectalether described in 1931 by Maytum has been againput forward as effective therapy.

(g) I feel that hypnotherapy is impracticable andmight even be dangerous.

Summary1. The mortality from asthma appears to be rising

again, after falling in the late 1950s. Many workersascribed this fall to the use of long-term cortico-steroid therapy. It may well be that factors, otherthan decreased effectiveness of long-term steroidtherapy, are responsible for the present increase.

2. The management of status asthmaticus may bedivided into: (a) prevention, and (b) therapy of theacute attack.

(a) It should be possible using large doses ofsteroid therapy to prevent status asthmaticus alto-gether but only at the expense of serious side-effects. However, the careful use of small doses ofsteroids on a long-term basis (i.e. longer than3 months) can significantly reduce the incidence ofstatus asthmaticus.Should an attack not respond to 24 hr of intensive

therapy at home, then hospital admission is advis-able, as it is felt that some of the deaths that occur athome are preventable.

(b) The treatment of the acute attack is discussedin the light of the experience gained in monitoringsystemic arterial gas tensions and pH during theacute episode and for the ensuing days. Hypoxaemiawas invariably present and often severe. Paco2 waslow or normal in most of the patients, but in thefew patients in whom it was raised it was a graveprognostic sign. The pH was also low in thesepatients.

We found to our immense surprise that adrenalineand aminophylline did not produce any substantialchange in the Pao2 levels. Evidence is put forwardthat adrenaline is best avoided and aminophyllineused as a 'bronchodilator', although its effects werenot dramatic.As well as giving large doses of steroids attention

must be paid to the maintenance of fluid balance,and antibiotics used where necessary. Sedation inselected cases is probably both beneficial andjustifiable.Above all else, the most important life-saving

therapy is the administration of oxygen, bearing inmind that hypoxaemia often persists for weeks.The patient should be kept in hospital, under sur-veillance, for 3 weeks after the acute episode andoxygen administered if indicated.

AcknowledgmentsThe work on arterial blood gases was carried out in the

University Department of Medicine (Professor K. W.Donald) with the financial support of the Asthma ResearchCouncil.

It is a pleasure to acknowledge the help of Dr J. S. Millar,Medical Research Council Scholar, and of the physiciansof the Royal Infirmary and City Hospital, Edinburgh, whoallowed me to study their patients.

ReferencesBROOM, B. (1961) Adrenaline and status asthmaticus. Lancet,

ii, 1174.CAMPBELL, E.J.M. & HOWELL, J.B.L. (1962) Rebreathingmethod for measurement of mixed venous Pco2. Brit.med. J. ii, 630.

CURRAN, W.S., OSER, J.F., LONGFIELD, A.N., BRODERICK,E.G. & CULVAHOUSE, B.M. (1966) Glomectomy forsevere bronchial asthma. Amer. Rev. resp. Dis. 93, 84.

DERBES, V.J. & ENGELHARDT, H.T. (1946) The Treatment ofBronchial Asthma, p. 24. Philadelphia.

FELDMAN, R. (1962) Recognition and treatment of potentiallyfatal asthma. Ann. intern. Med. 57, 29.

GRANT, I.W.B. (1966) Treatment of status asthmaticus.Lancet, i, 363.

HARRISON, E.M. & GALLOON, S. (1965) Venous blood as analternative to arterial blood for the measurement ofcarbon dioxide tensions. Brit. J. Anaesth. 37, 13.

HUGH-JONES, P. (1958) Oligopnoea. Proc. roy. Soc. Med.51, 104.

LOCKETT, M.F. (1965) Dangerous effects of Isoprenaline inmyocardial failure. Lancet, ii, 104.

MCILROY, M.B. & MARSHALL, R. (1956) The mechanicalproperties of the lungs in asthma. Clin. Sci. 15, 345.

MAHER-LOUGHNAN, G.P., MACDONALD, N., MASON, A.A.& FRY, L. (1962) Controlled trial of hypnosis in thesymptomatic treatment of asthma. Brit. med. J. ii, 371.

MARCHAND, P. & VAN HASSELT, H. (1966) Last-resorttreatment of status asthmaticus. Lancet, i, 227.

MAYTUM, C.K. (1931) Bronchial asthma: Relief of pro-longed attack by colonic administration of ether. Med.Clin. N. Amer. 15, 201.

MITHOEFER, J.C., RUNSER, R.H. & KARETZKY, M.S. (1965)The use of sodium bicarbonate in the treatment of acutebronchial asthma. New Engl. J. Med. 272, 1200.

NASMYTH, P.A. & STEWART, H.C. (1950) The release ofhistamine by opium alkaloids. J. Physiol. (Lond.), 111, 19P.

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RECTOR, F.C., JR, SELDEN, D.W., ROBERTS, A.D., JR &SMITH, J.S. (1960) The role of plasma carbon dioxidetension and carbonic anhydrase activity in the renalabsorption of bicarbonate. J. clin. Invest. 39, 1706.

REES, H.A., MILLAR, J.S. & DONALD, K.W. (1967) Theassessment of therapy in status asthmaticus. (In pre-paration).

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SCRIBNER, B.H., FREEMONT-SMITH, K. & BURNELL, J.M.(1955) The effect of acute respiratory acidosis on theinternal equilibrium of potassium. J. clin. Invest. 34,1276.

TAUSIG, D., PAPPER, E.M. & BARACH, A.L. (1952) Con-tributions of anesthesiology to the management of patientswith asthma. N. Y. State J. Med. 52, 1893.

TROMP, S.W. (1964) Difference in thermoregulation efficiencyand meteortropic behaviour between asthmatic, bronchiticand normal subjects. Trans. Wld Asthma Conf., ChestHeart Ass., pp. 27-33.

WALTON, C.H.A., PENNER, D.W. & WILT, J.C. (1951)Sudden death from asthma. Canad. med. Ass. J. 64, 95.

WHELAN, R.F. & YOUNG, I.M. (1953) Effects of adrenalineand noradrenaline infusions on respiration in man.Brit. J. Pharmacol. 8, 98.

WILLIAMs, D.A. (1953) Deaths from asthma in England andWales. Thorax, 8, 137.

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Discussion to the paper by H. A. Rees

GRANT. I share Dr Rees' impression, not yet con-firmed by statistics, that there has been an increase inmortality from bronchial asthma during 1965 and 1966.My own experience suggests that a high proportion ofrecent deaths took place in patients' homes, or in transitto hospital. When patients reach hospital alive, statusasthmaticus can usually be controlled by massive dosesof corticosteroids, without recourse to more elaboratemeasures. Up-to-date and detailed information aboutdeaths from asthma are urgently required, particularlyin respect of those occurring outside hospital. I suspectthat many of these deaths result from delay on thepart of the patient or the relatives in summoning medicalassistance, and from errors of judgment on the part ofthe general practitioner in not administering largeenough doses of corticosteroid and in not expeditingthe patient's admission to hospital. These factors cannotaccount for an increase in the death-rate from bronchialasthma, if this has in fact occurred. I doubt the credibilityof Dr Rees' suggestion that the nature of the disease haschanged, and put forward the view that individualpatients receiving long-term treatment with corticoster-oids may have become relatively resistant to theseagents, with the result that whenever they 'escape'from control, they tend to deteriorate more rapidlythan untreated patients, unless the dose is promptlyand massively increased.With regard to the management of status asthmaticus

in general practice, I consider that if a patient does notshow a distinct improvement within 6 hr, admission tohospital is imperative. I feel that in certain cases even adelay of this duration may be dangerous. Cortico-steroids do not begin to exert any useful effect for about8 hr. During this critical period a patient may continueto deteriorate, and therapeutic measures other thancorticosteroids may then have a decisive influence onthe outcome. In most instances oxygen therapy, adequatehydration and the frequent administration of an iso-prenaline aerosol by intermittent positive-pressureventilation (IPPV) via a facemask, using a patient-triggered ventilator (Bird or Bennett), are sufficient to tidethe patient over this dangerous phase, and it is rarelynecessary to resort to oro-tracheal intubation and full-scale IPPV. Facilities for this procedure should, however,be readily available in every unit undertaking the treat-ment of status asthmaticus, as they may be urgently

required for the resuscitation of patients admitted inextremis, and for those who continue to deteriorateafter admission. I agree with Dr Rees that a Paco2 ofmore than 50 mmHg is an absolute indication for startingartificial ventilation, but consider that in gravely ex-hausted patients there may be a case for embarking onthis treatment even when the Paco2 is normal or onlyslightly increased. One of the great benefits of artificialventilation is that it allows the patient to be deeplysedated without risk, and this in itself may tip the scalesin his favour.

I accept the view of Dr Rees that adrenaline, whetheradministered subcutaneously or intravenously, has noplace in the treatment of status asthmaticus. The experi-mental evidence that adrenaline, particularly whencombined with isoprenaline, could induce ventricularfibrillation, may not necessarily be applicable to humansubjects, but as adrenaline is in practice seldom effectivein status -asthmaticus, there would seem to be no realjustification for using it. I believe that aminophyllineadministered intravenously is in a slightly differentcategory. Unlike adrenaline it does not produce cardiacarrhythmias and although, as Dr Rees has shown, itmay not increase the Pao2, it may in some cases producepartial relief of airways obstruction, and a consequentreduction in the work of breathing. In this respect,however, neither adrenaline nor aminophylline is aseffective as an isoprenaline aerosol administered byIPPV.AMBIAVAGAR. Two points made in the preceding paper

are worth amplifying. In describing deaths from asthma,it was stated that a sudden death due to cardiac arrest,sometimes preceded by a period of hypotension, wascharacteristic of this disease. These deaths, which allauthorities agree are usually unexpected, occur during aperiod of gradual suffocation-and asthma is perhapsthe only known circumstance where gradual suffocationoccurs. The incongruity of this point, sudden unexpectedcardiac death during a period of gradual suffocationled us to investigate the cardiovascular abnormalitiespresent during asthma. Clinical signs and electro-cardiograms show that acute right ventricular strainoccurs and cardiac catheterization showed severalabnormalities.

Fig. Al is a composite trace of the cyclical intrapleuratpressure changes during asthma of this severity, the

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