R espiration 25: 201-215 (1968)

The Cardio-Pulm onary L aboratory of the

Mary Imogene B assett H ospital, Cooperstown, N.Y.
(D irector: Jo h n C. M ithocfer, M. D.)

Indications for the U se o f Sodium Bicarbonate

in the T reatm ent o f Intractable Asthm a

J .C . M i t h o e f e r , W .F . P o r t e r 1 a n d M .S. K a r e t z k y 1

W e p re v io u sly re p o rte d t h a t w h en re s p ira to ry acidosis c o m p licates

s ta tu s a s th m a tic u s , th e c o rre c tio n o f acidem ia b y so d iu m b ic a rb o n a te
a d m in is tra tio n can b rin g a b o u t re la x a tio n of b ro n c h o sp a sm a n d re ­
s to re th e resp o n se to b ro n c h o d ila to r d ru g s [I]. W e h a v e now h a d f u r­
th e r ex p erien ce w hich h as s u b s ta n tia te d o u ro rig in a l o b se rv a tio n s a n d
b ro a d e n e d th e a p p lic a b ility o f th is fo rm o f th e ra p y . T h is p a p e r d e ­
scrib es its u se in six m ore cases a m o n g w hich w as a 12 -y ear-o ld child
w ho reco v ered fro m an episode o f s ta tu s a s th m a tic u s sev ere en o u g h
to p ro d u c e an a rte ria l p H o f 6.66, to o u r know ledge th e low est v a lu e
so fa r re c o rd e d in re s p ira to ry acidosis.
In th e p a tie n ts to b e p re s e n te d , a rte ria l blood sam p les w ere o b ­
ta in e d a t fre q u e n t in te rv a ls fro m an indw elling needle p la c e d in th e
b ra c h ia l a rte ry . T h e sam p les w ere a n aly zed fo r Pco 2, p H a n d P o 22*
T h e re s u lts o f re p re s e n ta tiv e a n a ly se s are show n in figures 1 -6 w hich
a re g ra p h ic a l r e p r e s e n ta tio n s o f th e H e n d e rs o n -H a s s c lb a le h e q u a tio n :

tt , , , H C O , (mEq/1)
p H = 6.1 + log ------------^ ----
.0301 PCO2 (m m H g)

T h e s h a d e d zone in d ic a te s th e n o rm a l v alu es. T h e b ro k e n lines o u t­

line th e kn o w n b o u n d a rie s fo r th e in vivo C 0 2 disso ciatio n c u rv e of
m a n [2 ]; t h a t is, th e c h an g e in b ic a rb o n a te co n c e n tra tio n a n d p H t h a t
w ill re s u lt o n ly from a c h an g e in p a rtia l pressu re o f c a rb o n d io x id e.

1 Research F ellows under N .I. H. T raining G rant 5T1-HE-5503-03. W ork supported

by N .I.H . G rant HE-09130-02.
2 Electrodes m anufactured by In stru m en tatio n Laboratory, Inc., W atertow n,
M assachusetts, USA.
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Respiration, Vol.25, No. 3 (1968) U

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202 Mith o efer et al. Indications for the Use of Sodium B icarbonate

F ig .l. Changes in arterial PCO21 P U and H C 03 during course of therapy.

C asel. B .W . (M IBH 58782). a 12-year-old girl who had suffered from asthm a since
the age of three years, was seen at the hospital in an acute asthm atic attack. She had
been treate d at home for one week w ith prednisone (10-25 mg per day), aminophylline
suppositories, isoproterenol spray and in term itten t injections of epinephrine. In the
preceding three hours she had received four subcutaneous injections, each of 0.2 mg
of epinephrine, 20 mg of phénobarbital by m outh on two occasions and 125 mg of
am inophylline by suppository. H er bronchospasm was n o t relieved and her condition
progressively deteriorated. W hen seen a t the hospital, she was unconscious, cyanotic
and had bilateral expiratory wheezes over both lung fields. H er arterial pH a t th a t
tim e was 6.66 (fig. 1, point 1). An endotracheal tube was inserted and she was paralyzed
w ith succinylcholine. An in term itten t positive pressure breathing apparatus3 capable
of delivering an inspiratory pressure of 50 cm of w ater was ineffective in expanding
her lungs and she was given m outh-to-m outh breathing while awaiting an anesthesia
machine which would deliver a higher inspiratory pressure. V entilation was then con­
trolled w ith this ap p aratu s by bim anual compression of a rubber bag a t pressures of
90 cm of w ater (70 mm Hg). She was given 22 m Eq of sodium bicarbonate4 in tra ­
venously and 5 m in later arterial Pcc>2 had fallen to 120 mm and th e pH had risen to
6.90 (point 2). 40 min later another 44 m E q of sodium bicarbonate was given and she
was again tried on the interm itten t positive pressure respirator. This again was not
effective (point 3) and she was reconnected to the anesthesia machine (point 4).
35 m in later another 44 m E q of sodium bicarbonate was given. 15 min later (after a
total of 110 m E q) the pH had risen to 7.27 and the Pcc>2 had fallen to 82 mm (point 5).
Associated w ith this change was a striking decrease in airw ay resistance felt by the
physician who was compressing the rubber bag. Chest expansion and breath sounds
increased in spite of a reduction in inspiratory pressure and she regained conscious­
ness. She was again tried on the in term itten t positive pressure respirator a t 50 cm of
w ater pressure and for the first time this pressure proved adequate in overcoming air­
way resistance (points 6 and 7). She was then given 0.2 mg of epinephrine sub-

3 B ennett R espirator U n it P.R . 1, B ennett R espiration Products, Santa Monica,

California, USA.
4 Sodium B icarbonate 3.75 g (44.6 m E q) in 50 ml. A bbott Laboratories, N orth
Chicago, Illinois, USA.
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 in the T reatm en t of In tractab le A sthm a 203

cutaneously and her bronchospasm appeared to respond favorably. Three hours after
the last dose of bicarbonate (point 8), th e plasm a bicarbonate concentration had
fallen, resulting in a pH of 7.24. Consequently, another 44 mF.q of sodium bicarbonate
was given intravenously and the pH rose to 7.40 (point 9). She continued to receive
epinephrine in doses of 0.2 mg every 15 m in, each time apparently associated w ith a
decrease in bronchospasm. The inspiratory pressure of the positive pressure respirator
had been reduced in stages during the previous four hours and by 12 noon, six hours
after the initial arterial blood study, adequate ventilation was m aintained a t an
inspiratory pressure of 15 cm of w ater (point 10). Five hours after the last dose of
bicarbonate, th e endotracheal tu b e was removed and she breathed spontaneously,
the pH and PCO2 having returned to norm al (point 11). She rem ained alert and cheerful
w ithout signs of damage to the central nervous system.

T h is ch ild reco v ered fro m a n a tta c k o f a s th m a c o m p lic a te d b y

re s p ira to ry acidosis o f su ch s e v e rity as to h av e low ered a rte ria l p H
to 6.66. H e r seru m la c tic acid c o n c e n tra tio n a t th is tim e w as n o rm a l
(1.3 m E q/1). T h e case illu s tra te s t h a t airw a y re sista n c e can be so high
as to p re v e n t a d e q u a te v e n tila tio n b y m ech an ical m ean s even a t
d a n g e ro u sly h ig h in s p ira to ry p re ssu re s. W hen acid em ia w as co r­
re c te d b y so d iu m b ic a rb o n a te in fu sio n , b ro n ch o sp asm w as reliev ed
a n d a d e q u a te artificial v e n tila tio n a t low er in s p ira to ry p re ssu re s w as
p o ssib le.
Case 2. B. E ., a 42-year-old woman (MIBH 14473), was brought to th e emergency
room w ith severe asthm a which sta rte d the night before and failed to respond to sub­
cutaneously injected epinephrine given a t her home 30 min before. On exam ination
she was comatose and cyanotic w ith labored respirations and had loud expiratory
wheezes over both lung fields. Oxygen was given by mask and an arterial blood showed
a pH of 7.16, P c 02 84 mm and P o 2 128 mm (fig. 2, point 1). Oxygen th erapy did not
appear to depress her ventilation and she continued to struggle violently to breathe.
Sodium bicarbonate (88 m E q i.v . in 5 m in) was given and she became slightly more
responsive; her bronchospasm decreased som ewhat and she was switched from oxygen

Fig. 2. Changes in arterial Pcc>2 >p H and I1C03 during course of therapy.
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204 Mith o efer e t al. Indications for th e Use of Sodium Bicarbonate

breathing to a 32 % V enturi mask5 (point 2). She was given 0.3 mg of epinephrine i. v.
w ithout response a t which tim e her arterial blood was 7.22 (point 3). Another 88 mEq
of sodium bicarbonate was given which brought th e pH to 7.31 (point 4). V entilatory
m inute volume was measured at this time and found to be 7.3 1/min. Oxygen therapy
was sw itched to a 28% V enturi mask. Aminophylline (250 mg) was given intraven­
ously which produced considerable im provem ent in her bronchospasm; measured
ventilatory volum e a t this tim e was 8 .1 1/min, arterial p H rising to 7.33 and P c 02 de­
creasing to 53 mm (point 5). Two-tenths mg of epinephrine was then given which
resulted in significant decrease in her bronchospasm and she had regained conscious­
ness. A fter two more epinephrine injections (0.2 mg) at 15-min intervals, her arterial
pH was 7.42 and PcOa 52 (point 6); ventilatory volume was 9.9 1/min. She continued
to respond to epinephrine; 75 m in la te r the pH was 7.45, P c 02 43 mm and broncho­
spasm had disappeared.

I n th is case, th e e le v a tio n in p H fro m 7.16 to 7.22 d id n o t re sto re

re sp o n siv e n e ss to ep in e p h rin e b u t w hen i t w as f u r th e r in c re a se d to
7.31 b y a d d itio n a l b ic a rb o n a te , b ro n ch o sp asm resp o n d ed to b o th
a m in o p h y llin e a n d ep in e p h rin e . In th is case (as in cases 3 a n d 6), th e
use o f a rtific ia l re s p ira tio n w as a v o id ed b y co rrectio n o f acidem ia.
Case 3. R .S . (M IB II 15426), a 59-year-old m an, was adm itted for the second time
w ith acute bronchial asthm a (an account of his first admission has been previously
reported) [1], Following his first hospital admission, he had no sym ptom s of asthm a.
A pproxim ately one hour prior to admission, w ithout w arning, he developed severe
bronchospasm. W hen seen in the emergency room, he was severely dyspneic and
cyanotic. One hour later, after he failed to respond to frequent doses of epinephrine
(total 1.2 mg i.m .) and aminophylline (500 mg i.v .), his cyanosis increased and he
became unresponsive. He was receiving oxygen by mask b u t it had not apparently
depressed his respiration and he continued to exert strong ventilatory effort against
a high airw ay resistance. A t this tim e his arterial pH was 6.92 and Pco 2 150 mm (fig. 3,
point 1). He was given 88 inEq of sodium bicarbonate intravenously over a five-
m inute period. H is bronchospasm im m ediately decreased and he regained conscious-

Fig. 3. Changes in arterial PCO2, pH and IIC 0 3 during course of therapy.

5 V entim ask m anufactured by Oxygenaire L td., London, W .l, England.

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 in the T reatm en t of In tractab le A sthm a 205

ness. Following this, his bronchospasm appeared for the first time to respond slightly
to epinephrine and aminophy lline. One hour after the first dose of sodium bicarbonate,
his pH was 7.14 and Pcoj 87 mm (point 2). A t th a t time he was given another 88 m E q
intravenously again w ith an im m ediate im provem ent in bronchospasm and m ental
status. One hour later arterial pH had risen to 7.27 and PCO2 had fallen to 70 mm
(point 3). An additional 45 m E q of sodium bicarbonate given at th a t tim e b rought his
pH to 7.40 and Pcc>2 to 53 mm (point 4) 15 m in after injection. A t this tim e, the
bronchospasm was nearly gone an d the p a tie n t was asking to go home. Six hours later,
w ithout furth er therapy, pH was 7.56 and PCO2 43 (point 5), indicating m oderate m eta­
bolic alkalosis, the result of bicarbonate adm inistrat ion, b u t norm al PcOs- By the next
day, the excess bicarbonate had been excreted, pH was 7.45 and Pcc>2 45 mm. He did
well in the hospital w ithout recurrence of his asthm a and was discharged after one
week w ith no specific etiology having been found.

T h is case illu s tra te s th e re lie f o f b ro n ch o sp asm b y co rrectio n of

a c id e m ia , p re s u m a b ly th ro u g h th e re sto ra tio n of resp o n siv en ess to
b ro n c h o d ila to rs . I t f u r th e r illu s tra te s t h a t w ith th is fo rm o f th e ra p y
th e use o f a rtific ia l re sp ira tio n can in som e cases be av o id ed (see also
cases 2 a n d 6). I n re tro s p e c t, we th in k t h a t sodium b ic a rb o n a te sh o u ld
h a v e b een given a t m ore f re q u e n t in te rv a ls earlier a n d its effect m o n i­
to re d b y m o re fre q u e n t m e a s u re m e n ts o f a rte ria l p H a n d Pco 2 -
Case 4. L.C. (M IBH 55313), a 67-year-old woman, was adm itted to the hospital
w ith congestive h eart failure, th e first sym ptom s of which had started three m onths
before. During th e previous nine years, she had had seven hospital admissions for
chronic bronchitis and asthm a. She had evidence of congestive h eart failure m ani­
fested by cardiac enlargem ent, dyspnea, tachycardia and moist rales at b o th lung
bases. She was started on a program of digitalis and diuretics and on the third hospital
day after a 2 kg weight loss she suddenly became confused, lethargic and cyanotic.
E xpiratory wheezes were heard over b o th lung fields and her dyspnea had become
more intense. H er serum electrolytes were norm al except for a slight elevation in
potassium concentration. She was given in term itten t positive pressure breathing
through an endotracheal tube and 30 min later her arterial oxygen tension was 92 mm,
pH 7.19, PCO2 82 mm, and she had lost consciousness (fig. 4, point 1). The airw ay re-

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Fig.4. Changes in arterial Pco 2 <p H and H C 0 3 during course of therapy.

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206 Mith o efer et al. Indications for the Use of Sodium Bicarbonate

sistance could n o t be adequately overcome by the respirator and she was given 88 m Eq
of sodium bicarbonate intravenously over a five-minute period. Bronchospasm was
im m ediately decreased and 30 min later pH had risen to 7.31, Pcos 65 mm, P 02 98 ram
and she had regained consciousness (point 2). 30 min later 45 m E q of sodium bicar­
bonate was given, again followed by im provem ent (point 3). Two hours later the
bronchospasm had completely disappeared (point 4). The endotracheal tube was re­
moved the following day and she appeared to be convalescing satisfactorily. W ithout
having developed fu rth er bronchospasm or evidence of cardiac failure, she died sud­
denly three days after the episode described above. I t was the clinical impression th a t
she had suffered a massive pulm onary embolus b u t permission for an autopsy was
not granted.
T h is case (as in cases 1 a n d 5) illu s tra te s th e use of sodium b ic a r­
b o n a te in c o n ju n c tio n w ith artificial re sp ira tio n w hen a irw ay re sist­
ance is to o h ig h to p e rm it a d e q u a te v e n tila tio n b y th e use of a resp i­
r a to r alone. I t also illu s tra te s t h a t , w h en n ecessary , sodium b ic a r­
b o n a te c a n b e a d m in is te re d in larg e doses (133 m E q ) to a p a tie n t in
co n g estiv e h e a r t fa ilu re w ith o u t in d u c in g f u rth e r fa ilu re or p u lm o n ­
a ry ed em a. In th is p a tie n t, b ro n c h o sp asm w as reliev ed b y th e use of
so d iu m b ic a rb o n a te alo n e w ith o u t ep in ep h rin e or o th e r b roncho-
d ila to r d ru g s.
Case 5. C. H. (M IB II106310), a 69-ycar-old man with a 30-year history of bronchial
asthm a, was adm itted to the hospital in an acute asthm atic attack which had been
precipitated by a respiratory tract infection. His illness was complicated by mild con­
gestive h eart failure resulting from arteriosclerotic h eart disease. He was treated with
aminophylline by suppository (250 mg) and three subcutaneous injections of epine­
phrine (0.2 mg each) and oxygen by in term itten t positive pressure breathing, but his
bronchospasm continued and he developed rapid atrial fibrillation w ith left bundle
branch block. A t this time, his arterial pH was 7.09, PCO2 190 m m , Po-> 77 mm (fig. 5,
point 1). Sodium bicarbonate (176 m Eq) was given intravenously over a five-minute
period and his bronchospasm im mediately lessened. 45 min late r his pH had risen to
7.22, PcojSS mm, P o j 115 nnn (point 2). An additional 88 m E q of sodium bicarbonate

Fig. 5. Changes in arterial PCO2, pH and IIC 0 3 during course of therapy.

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 in the T reatm en t of In tractab le A sthm a 207

was then given followed by epinephrine (0.2 mg i. v.). This im m ediately resulted in a
decrease in bronchospasm and a fu rth er fall in P co2 to 70 mm (point 3). 88 m E q of
sodium bicarbonate and 0.2 mg of epinephrine were again given intravenously w ith
fu rth er prom pt im provem ent in bronchospasm . One hour later there was fu rth er
clinical im provem ent (point 4). W ithout fu rth er treatm ent, he continued to im prove
and three hours later pH was 7.44, Pco2 48 and P o 2 395 mm (point 5); this m oderate
m etabolic alkalosis resulting from bicarbonate adm inistration was subsequently cor­
rected spontaneously and pH retu rn ed to 7.43 and PcOa to 44. The rem ainder of his
hospital course was uncomplicated.

T h is case (as in cases 1 a n d 4) illu s tra te s th e relief o f b ro n c h o sp a sm

b y so d iu m b ic a rb o n a te a d m in is tra tio n in a p a tie n t w hose a irw a y
re sista n c e w as to o high to be a d e q u a te ly overcom e b y a rtificial v e n ­
tila tio n alone. T h e in itia l in je c tio n o f b ic a rb o n a te p ro d u c e d som e d e ­
c rease in b ro n c h o sp a sm w ith o u t f u r th e r e p in ep h rin e a d m in is tra tio n ;
b u t th e seco n d a d m in is tra tio n , w h ich w as given in c o m b in a tio n w ith
a dose of e p in e p h rin e to w h ich he h a d p re v io u sly b e e n re fra c to ry ,
re s u lte d in a m uch g re a te r fall in a irw a y resistan ce. As in cases 4 a n d
6, th is p a tie n t also h a d a sso c ia te d co n g estiv e h e a rt fa ilu re w hich w as
n o t a d v e rse ly affected b y a to ta l dose of 352 m E q o f so d iu m b ic a r­
b o n a te .

Case 6. B. S. (M IBH 87130), an 85-year-old m an, was adm itted in an acute asth­
m atic attack . His past history included frequent mild attacks of asthm a, chronic
bronchitis, em physema, arteriosclerotic h eart disease and congestive h e a rt failure. On
admission he was dyspneic an d cyanotic. There were bilateral expiratory wheezes
w ithout signs of pulm onary edema. He was treated with digitoxin, hydrocortisone
(100 mg i.v .), am inophylline (250 mg i.v .) and oxygen by mask. Two and one-half
hours later, his arterial pH was 7.12, P c 02 80, Po2 69 mm Hg (fig. 6, p o in t 1). Over the
n ext half hour he received two intravenous injections of 250 mg of am inophylline
w ith no im provem ent and he became more cyanotic and appeared m oribund. His
arterial pH , Pco2 and Po2 were unchanged (point 2). He was then given 0.2 mg of

Fig. 6. Changes in arterial P co 2 >p H and H C 0 3 during course of therapy.

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208 Mith o efer et al. Indications for the Use of Sodium B icarbonate

epinephrine i.v . w ith some im provem ent in his bronchospasm, b u t he remained

stuporous and there was slight depression of plasma bicarbonate concentration (point
3).The arterial blood 15 min later showed fu rth er fall in P co j w ith a l’o 2 of 56 (point 4),
b u t there was no im provem ent in his m ental statu s and a fall in plasma bicarbonate
concentration suggested the development of metabolic acidosis (plasma lactate was
3.6 mEq/1). T hroughout this phase, his blood pressure was unobtainable and the
metabolic acidosis was thought to be the result of hypoxia from circulatory failure. He
was then given sodium bicarbonate (88 m Eq i. v. over a five-minute period). The arte­
rial blood im m ediately following injection (point 5) showed both a rise in pH and Pco2
due to the injected bicarbonate. 2 min later (point 6), the p atien t suddenly became
alert and his bronchospasm was dram atically relieved. A rterial bloods 7 and 8 were
draw n at 15 and 30 min following the injection of bicarbonate and showed progressive
im provem ent w ith o u t additional therapy. His course in the hospital was th a t of con­
tinued im provem ent.

T h is case illu s tra te s th a t in som e p a tie n ts b ro n c h o sp a sm responds

to e p in e p h rin e in sp ite o f an a rte ria l p H as low as 7.12. In th is case,
a fall in p la s m a b ic a rb o n a te a n d a la c ta te c o n c e n tra tio n o f 3.6 m Eq/1
in d ic a te d th e d e v e lo p m e n t o f m e ta b o lic acidosis c o m p licatin g re sp i­
r a to r y acid o sis as a resu lt o f c irc u la to ry failu re. B ro n ch o sp asm a n d
th e p a tie n t’s m e n ta l s ta tu s w ere s u b se q u e n tly im m e d ia te ly im p ro v ed
b y th e c o rre c tio n o f a cid em ia b y b ic a rb o n a te in je c tio n w ith o u t f u r­
th e r e p in e p h rin e a d m in is tra tio n . As in cases 4 a n d 5, sodium b ic a r­
b o n a te (88 m E q ) w as given to a p a tie n t in co n g estiv e h e a rt failu re
w ith o u t ill effect.

D iscussion
In o u r e x p e rie n c e, th e m o st im p o r ta n t a p p ro a c h to th e tr e a tm e n t of
a c u te b ro n c h ia l a s th m a is b y sy s te m a tic , re p e a te d e v a lu a tio n s of th e
re su lts of th e r a p y a t sh o rt in te rv a ls o f tim e. T h e ra p y sh o u ld s ta r t w ith
sim p le c o n v e n tio n a l m easu res su ch as b ro n c h o d ila to r d ru g s a n d th e
re su lts o f th e ir use sh o u ld be e v a lu a te d a t 15 to 30-m in in te rv a ls. I f
s a tis fa c to ry p ro g re ss is n o t m ad e c o n tin u o u sly , th e n th e tr e a tm e n t
m u s t be in te n sifie d . M ost im p o rta n tly , th is a p p ro a c h m u st be sy ste m ­
a tic a n d th e in te rv a ls o f e v a lu a tio n reaso n ab ly s h o rt, co m m e n su ra te
w ith th e o n se t o f a c tio n of th e a g e n ts in use. U p to a p o in t, sim ple
clinical e v a lu a tio n c a n suffice; b u t b e y o n d it, if sa tisfa c to ry th e r a ­
p e u tic p ro g re ss is n o t b e in g m ad e, th e serial d e te rm in a tio n o f a rte ria l
p H , P C02 a n d P o 2 offers an o b je c tiv e m eans o f d e te rm in in g pro g ress
a n d d e te c tin g th e e a rly d e v e lo p m e n t o f re s p ira to ry acidosis.
M any cases o f a c u te b ro n c h ia l a s th m a are re fra c to ry to c o n v e n tio n ­
al th e r a p y w ith b ro n c h o d ila to rs in th e absence o f acid em ia. Som e, in
fa c t, re s u lt in itia lly in re s p ira to ry alk alosis. C learly, a t th is stag e o f an
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 in the T reatm en t o f In tractab le A sthm a 209

a tta c k , som e cause o th e r th a n a cid em ia is responsible fo r th e lack of

re sp o n se to tr e a tm e n t. If, h o w ev er, b ro n ch o sp asm is sev ere an d if it
c o n tin u e s fo r a long e n o u g h tim e , p rog ressiv e a lv eo lar h y p o v e n tila ­
tio n a n d in c re a se d C 0 2 p ro d u c tio n w ill e v e n tu a lly le a d to re s p ira to ry
acidosis. I t is a t th is s ta g e t h a t th e co n d itio n o f th e p a tie n t becom es
c ritic a l a n d a t th is sta g e a re la tio n s h ip ap p ears to e x ist b e tw e e n a c i­
dosis a n d th e resp o n se to th e r a p y , c o rrectio n of acidem ia re su ltin g in
a p r o m p t re v e rsa l of th e clin ical co u rse [1 ,3 ,4 ,5 ] .
A cidosis is kn o w n to h a v e a d e p re s sa n t effect u p o n b o th c o n tra c tile
a n d re la x a tio n responses to e p in e p h rin e [3, 6] th ro u g h a d ire c t h y d ro ­
gen ion effect [7]. T his h a s been p o s tu la te d as th e m ech an ism re sp o n ­
sible fo r th e re fra c to rin e ss to e p in e p h rin e in a d v a n c e d sta g e s o f s ta tu s
a s th m a tic u s a n d for th e re la x a tio n o f b ro n ch o sp asm w hich follow s
th e c o rre c tio n o f acid em ia [1, 3]. T h is is a reaso n ab le e x p la n a tio n for
th e re s u lts in m o st o f o u r cases (cases 1, 2, 3, 5, 6), b u t a d ire c t effect
o f acidosis on th e to n e o f b ro n c h ia l sm o o th m uscle, in d e p e n d e n t of
d e p ressio n o f e p in e p h rin e re sp o n se , c a n n o t be ru le d o u t. Such a m e c h ­
a n ism is su g g e ste d b y th e re sp o n se o f case 4 w here b ro n c h o sp a sm
w as reliev ed b y th e co rre c tio n o f acid em ia alone, w ith o u t th e a d m in ­
is tr a tio n o f ep in e p h rin e or o th e r b ro n c h o d ila to rs. O ne c a n n o t b e c e r­
ta in , h o w e v e r, t h a t in th is case b ro n c h o sp a sm w as n o t reliev ed follow ­
in g th e c o rrectio n of acid em ia b y re sto ra tio n of resp o n siv en ess to
en d o g en o u s ep in ep h rin e.
T h e d eg ree of a cid em ia a t w h ich th e ra p e u tic response b ecom es a t ­
te n u a te d , b y w h a te v e r m e c h a n ism , a p p ears to v a ry a m o n g in d iv id ­
u a ls. Case 2 in o u r p re v io u s p u b lic a tio n [1] w as re fra c to ry to e p in e ­
p h rin e w h en th e p H w as 7.24 w hile case 6 in th e p re s e n t series show ed
a slig h t b u t defin ite d ecrease in b ro n ch o sp asm in response to ep in e­
p h rin e w hen th e p H w as 7.12.
V e n tila tio n w as m e a su re d d ire c tly only in case 2 ; b u t in d ire c t
e v id e n c e fo r an in crease in a lv e o la r v e n tila tio n , re su ltin g fro m b ic a r­
b o n a te th e r a p y , is seen in th e c h a n g e s in a rte ria l Pco 2 w hich follow its
a d m in is tra tio n . T h e re is an im m e d ia te rise in Pco2 (case 6) follow ing
b ic a rb o n a te infusion as b ic a rb o n a te ion com bines w ith h y d ro g e n ions
to fo rm c a rb o n ic acid, w h ich th e n d issociates to C 0 2 a n d w a te r:

H C O s + H + = H 2C 0 2 = C 0 2 + h 2o

T h e C O , fo rm e d is d eliv ered to th e lu n g w here its ra te o f o u tp u t is

a fu n c tio n o f alv eo lar v e n tila tio n . I f v e n tila tio n w ere n o t in creased ,
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a r te r ia l Pco2 w ould re m a in e le v a te d . T h is is show n in fig. 7 w h ich p lo ts

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pH no
7.44 [HCOJ -53.8
mEq/l
100
733 37.4
7.31 33.6
90

80
18.9
»-62 nr£q NaHCO, Time-min
5 10 15 20 25 30

Fig. 7. Changes in arterial PcOî, pH and IIC 0 3 following intravenous N aIIC 0 3 in dogs
w ith m echanically induced hypoventilation. The ventilation was held constant
throughout.

th e ch an g es in Pco 2, p H a n d b ic a rb o n a te c o n c e n tra tio n a g a in st tim e

follow ing th e in je c tio n of 62 m E q of so d iu m b ic a rb o n a te in a n e s th e t­
ized dogs b ein g a rtific ia lly v e n tila te d a t a fixed level. M ean v alu es
are sh o w n fro m th re e a n im a ls b re a th in g room a ir w ho w ere a n e s th e t­
ized w ith p e n to b a r b ita l, th e n p a ra ly z e d w ith su ccin y lch o lin e. A l­
v e o la r h y p o v e n tila tio n w as in d u c e d b y d ecreasin g th e a m p litu d e of
th e re s p ir a to r u n til an a rte ria l Pco 2 o f 77 m m w as e sta b lish e d d u rin g
th e c o n tro l p e rio d . T h is v e n tila tio n w as m a in ta in e d th ro u g h o u t. I m ­
m e d ia te ly fo llo w in g b ic a rb o n a te in je c tio n , th e Pco 2 rose to 107 m m ,
th e n fell a t a p ro g ressiv ely d ecreasin g ra te . I t w as still ab ove th e co n ­
tro l level a fte r 30 m in . A t no tim e d id th e P m >2 fall below th e co n tro l
v a lu e . T h is re s u lt, w hen th e v e n tila tio n does n o t in crease in associa­
tio n w ith b ic a rb o n a te in je c tio n , is to be co m p ared to th e p ro m p t fall
in P CO2 w h ic h follow s its a d m in is tra tio n in s ta tu s a sth m a tic u s.
I n a s th m a , w h ere a irw a y re sista n c e is g re a t en o u g h to p re v e n t a d e ­
q u a te v e n tila tio n in sp ite o f v ig o ro u s re s p ira to ry effort, th e rise in
a lv e o la r v e n tila tio n w hich follow s b ic a rb o n a te in je c tio n im plies a d e ­
crease in a irw a y re sista n c e — an im p lic a tio n c o n siste n t w ith ob serv ed
ch an g e in a u s c u lta to r y findings.
In n o rm a l s u b je c ts a n d in p a tie n ts w ith ch ro n ic p u lm o n a ry disease
a n d c o m p e n sa te d re s p ira to ry acidosis, th e im m e d ia te effect of i n t r a ­
v e n o u s b ic a rb o n a te a d m in is tra tio n is an in crease in a lv eo lar v e n tila ­
tio n in a sso c ia tio n w ith a rise in P cû2 - H ere, th e in creased Pco 2 ac ts as
a v e n tila to r y stim u lu s in sp ite of a rise in p H . T h is resu lts, w ith in
5 m in a fte r in je c tio n , in an o u tp u t b y th e lungs o f a p p ro x im a te ly 11 %
of th e C 0 2 a d m in is te re d as b ic a rb o n a te . 30 m in a fte r in je c tio n , th e P c o 2
is a b o u t 2 m m h ig h e r th a n b efo re in je c tio n in n o rm a l su b je c ts, b u t is
a t th e c o n tro l lev el in p a tie n ts w ith ch ro n ic p u lm o n a ry disease [8 ,9 ].
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M ech an ical v e n tila tio n b y th e u se o f a re sp ira to r h as an e sta b lish e d

v a lu e in th e tr e a tm e n t of s ta tu s a s th m a tic u s [4, 10, 11]. W e h av e
fo u n d , h o w ev er, th a t its use c a n o fte n be av o id ed if acid em ia is
p r o m p tly c o rre c te d b y so d iu m b ic a rb o n a te a d m in is tra tio n (cases 2,
3, 6). O ne o f th e d ifficu lties in th e use of re sp ira to rs, in th e tr e a tm e n t
o f a c u te b ro n c h ia l a s th m a , is t h a t o fte n th e a irw ay re sista n c e is so
g re a t t h a t d a n g e ro u sly h ig h in sp ire d pressu res are re q u ire d to p ro ­
d u ce ev en in a d e q u a te a lv e o la r v e n tila tio n (70 m in o f H g in case 1).
U n d e r th e se c irc u m sta n c es, th e c o rrectio n o f acid em ia b y so d iu m
b ic a rb o n a te serves to low er a irw a y re sistan ce a n d allow a d e q u a te v e n ­
tila tio n a t safe levels of in s p ira to ry p re ssu re . W h en we use a re s p ira to r
in th e tr e a tm e n t o f s ta tu s a s th m a tic u s , we v e n tila te b y w a y o f a
cuffed e n d o tra c h e a l tu b e . W e h a v e n e v e r fo u n d it n ecessary to use a
tra c h e o s to m y .
In o u r o rig in al c o m m u n ic a tio n on th is su b ject,w e c a u tio n e d a g a in st
th e a d m in is tra tio n of so d iu m b ic a rb o n a te to p a tie n ts w ith c ard iac
fa ilu re , th ro u g h m ista k in g b ro n c h ia l a sth m a for c a rd ia c a s th m a .
Since th e n , we h a v e given larg e doses o f sodium b ic a rb o n a te to th re e
p a tie n ts w ith co n g estiv e fa ilu re e x istin g in asso ciatio n w ith a c u te
b ro n c h ia l a s th m a w ith o u t d e le te rio u s ca rd io v a sc u lar effects (352 in E q
in case 5). F u rth e rm o re , so d iu m b ic a rb o n a te has re c e n tly been su c ­
cessfully used in th e tr e a tm e n t o f a cid em ia asso ciated w ith a c u te p u l­
m o n a ry e d em a [12]. F o r th e se re a so n s, we now h av e no h e sita n c y in
usin g it w hen o th erw ise in d ic a te d in p a tie n ts w ith b ro n c h ia l a s th m a
a sso c ia te d w ith c ard iac failu re.
W e h a v e h a d no ex p erien ce w ith alk alin izin g a g e n ts o th e r th a n
N a I I C 0 3 in th e c o rre c tio n o f a c id e m ia in b ro n ch ial a s th m a . W e are in
a g re e m e n t w ith criticism s w hich h a v e been d ire c te d a t th e use of
T H A M (tris -h y d ro x y m e th y l-a m in o m e th a n e ) a n d so d iu m la c ta te [13,
14] a n d find no in d ic a tio n fo r th e ir use in place of sodium b ic a rb o n a te .
P a tie n ts w ith a c u te b ro n c h ia l a s th m a an d severe b ro n c h o sp a sm
stru g g le to b re a th e a g a in s t a h ig h a irw a y resistan ce. T h e r e s u lta n t
a lv e o la r h y p o v e n tila tio n c o m b in e d w ith an a b n o rm a l d is trib u tio n b e ­
tw een v e n tila tio n a n d p e rfu sio n [15] resu lts in th e e v e n tu a l d e v e lo p ­
m e n t of sev ere h y p o x ia as w ell as a n e le v a tio n in a lv eo lar a n d a rte ria l
Pco 2 - I f su ch p a tie n ts are n o t g iv en su p p le m e n ta ry o x y g en to b re a th e ,
as w ith all p a tie n ts in r e s p ira to ry fa ilu re, a rise in alv e o la r P o >2 to
a b o u t 80 m m will so d isp lace o x y g en from th e a lv eo lar gas as to p ro ­
d u c e f a ta l h y p o x ia . T h e a d m in is tra tio n o f oxygen in th is s itu a tio n
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p re v e n ts f a ta l h y p o x ia w ith o u t n e c e ssarily d ep ressin g v e n tila tio n as

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it so o fte n does in ch ro n ic p u lm o n a ry em p h y sem a. F o r th is reason,

p a tie n ts w ith b ro n c h ia l a s th m a m a y develop v e ry severe re s p ira to ry
acidosis (p H 6.66 in case 1) as lo n g as th e y are able to su rv iv e b y th e
p re v e n tio n o f fa ta l h y p o x ia th ro u g h oxygen th e ra p y . I t m u st n o t be
assu m e d t h a t th e ir sev ere re s p ira to ry acidosis is necessarily a m a n i­
fe s ta tio n o f v e n tila to r y d epression b y oxygen th e ra p y , as it m a y be in
p a tie n ts w ith p u lm o n a ry em p h y se m a. In our exp erien ce, m o st p a ­
tie n ts w ith b ro n c h ia l a s th m a w hen given high in sp ire d oxygen c o n ­
c e n tra tio n s c o n tin u e to e x e rt m a x im a l v e n tila to ry effort as long as a ir­
w ay re sista n c e is hig h , even th o u g h h y p o x ia is c o rre c ted b y oxygen a d ­
m in is tra tio n . T h is p ro b lem h as h een discussed in d e ta il elsew here [16].
O n th e b a sis o f o u r ex p erien ce to d a te , we m ak e th e follow ing re ­
c o m m e n d a tio n s fo r th e tr e a tm e n t of a c u te b ro n ch ial a sth m a w h ich is
re fra c to ry to c o n v e n tio n a l b ro n c lio d ila to r a n d ste ro id th e ra p y :
1. A n in d w ellin g needle sh o u ld be p la c e d in th e b ra c h ia l a rte ry an d
left in p la c e u n til th e a tta c k is ov er. A n a rte ria l b lo o d sam p le sh o u ld be
d ra w n im m e d ia te ly a n d a n a ly z e d fo r Pco2 a n d p H a n d , if possible, P o 2.
2. I f sig n ific a n t re s p ira to ry acidosis is p re s e n t, a 0.9M so lu tio n of
so d iu m b ic a rb o n a te sh o u ld be a d m in iste re d in tra v e n o u s ly o v er a tw o
to fiv e -m in u te p e rio d in a dose o f a p p ro x im a te ly 1.5 m E q /k g of b o d y
w eig h t.
3. 10 to 15 m in follow ing th is in je c tio n , an a rte ria l blood an aly sis
sh o u ld be re p e a te d a n d b ic a rb o n a te a d m in iste re d a t 15-inin in te rv a ls
u n til th e p H is n o rm a l or b ro n c h o sp a sm is relieved.
4. W h ile c o rre c tio n of acid em ia is u n d e r w ay , e p in ep h rin e sh o u ld
be a d m in is te re d in tra v e n o u s ly in re p e a te d doses (0.2 to 0.3 m g). A
d ecrease in b ro n c h o sp a sm in resp o n se to ep in ep h rin e m ay be a n tic i­
p a te d as th e p H a p p ro a c h e s n o rm al.
5. I f c o rre c tio n o f acid em ia is accom plished e a rly , th e use o f a r ti­
ficial v e n tila tio n b y re s p ira to r h as, in o u r exp erien ce, been u n n e c e s­
s a ry . If, h o w ev er, it becom es n ecessary or is a lre a d y in p ro g ress, th e
c o rre c tio n o f a c id e m ia will decrease a irw a y re sistan ce a n d allow a m ore
a d e q u a te v e n tila tio n b y th e re s p ira to r a t low er in s p ira to ry pressu res.
6. T h e c o ex isten ce o f cong estiv e h e a rt failu re w ith a c u te b ro n c h ia l
a s th m a n e e d n o t be co n sid ered a c o n tra in d ic a tio n to sodium b ic a r­
b o n a te a d m in is tra tio n in th e doses reco m m en d ed .
7. I f it is n o t p ossible to m easu re a rte ria l p H a n d Pco2, th e n in a
p a tie n t w ith sev ere b ro n c h ia l a s th m a w ho is re fra c to ry to c o n v e n tio n ­
al th e r a p y a n d show s clinical m a n ife sta tio n s o f re sp ira to ry acidosis,
w e w o u ld re c o m m e n d t h a t so d iu m b ic a rb o n a te b e a d m in iste re d in th e
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dose o f 1.5 m E q /k g , o v er 5-m in p e rio d s, a t 15-m in in te rv a ls , u n til re ­

sp o n siv en ess to b ro n c h o d ila to r d ru g s h as been resto red .

S u m m a ry
W h en s ta tu s a s th m a tic u s is re fra c to ry to b ro n c h o d ila to rs a n d has
re s u lte d in re s p ira to ry acid o sis, th e co rrectio n o f acid em ia b y th e in ­
tra v e n o u s a d m in is tra tio n of so d iu m b ic a rb o n a te relieves b ro n c h o -
sp a sm and re sto re s resp o n siv en ess to ep in ep h rin e. F re q u e n c y o f a d ­
m in is tra tio n sh o u ld be d e te rm in e d b y re p e a te d a n aly sis o f a rte ria l
p H a n d P co2 * T h e re c o m m e n d e d sin gle dose is 1.5 m E q /k g i.v .
S ix cases a re p re s e n te d illu s tr a tin g th is , am ong th e m a 12-year-old
ch ild w ho, b y th is th e r a p y , re c o v e red from an a tta c k o f a s th m a w hich
h a d lo w ered h e r a rte ria l p H to 6.66.
B y th is a p p ro a c h , th e use o f m e c h an ical v e n tila tio n can o fte n be
a v o id e d . W h en artificial v e n tila tio n is used, c o rre c tio n of acid em ia
lo w ers a irw a y re sista n c e a n d allow s m ore effective v e n tila tio n a t lo w ­
er, a n d safer, in s p ira to ry p re ssu re s. T h e coexistence o f co n g estiv e
h e a r t fa ilu re does n o t a p p e a r to b e a c o n tra in d ic a tio n to th is th e ra p y .

Z u sa m m en fa ssu n g
W en n A sth m a b ro n c h ia le d e r B e h an d lu n g von B ro n c h o d ila ta to re n
w id e rs te h t u n d A tem azid o se z u r F o lge h a t, e rle ic h te rt die V e rb e s­
se ru n g d e r B lu tü b e rs ä u e ru n g d u rc h in tra v e n ö se V e ra b re ich u n g v o n
N a triu m b ik a r b o n a t den B ro n c h o sp a sm u s un d ste llt die R e a k tio n s ­
fä h ig k e it a u f E p in e p h rin w ied er h e r. D ie H äu fig k eit d e r V e ra b re i­
c h u n g so llte d u rc h w ie d e rh o lte U n te rsu c h u n g des a rte rie lle n p H -
W e rte s u n d des Pcoa b e s tim m t w e rd en . Die em p fo h len e E in zeld o sis
is t 1,5 m E q /k g i.v.
E s w erd en sechs F älle v o rg e s te llt, die dies v e ra n sc h a u lich e n , u n te r
ih n e n ein 12jäh rig es M ädchen, d a s a u fg ru n d dieser T h e ra p ie v o n ei­
n e m A s th m a a n fa ll genas, d e r sein en a rte rie llen p H -W e rt a u f 6,66 g e­
s e n k t h a tte .
D u rc h diese A n n ä h e ru n g k a n n die V erw en d u n g m ech an isch er V e n ­
tila tio n h äu fig v e rm ie d e n w e rd e n . W en n die k ü n stlic h e V e n tila tio n
b e n u tz t w ird , s e n k t die V e rb e sse ru n g der B lu tü b e rs ä u e ru n g den
A te m w eg sw id e rsta n d u n d e rla u b t eine w irk sam ere V e n tila tio n bei
n ie d rig e re n u n d sich ereren in s p ira to risc h e n D rucken. D as gleichzeitige
V o rh a n d e n se in eines k o n g e stiv e n H erzfeh lers sch ein t keine K o n tr a ­
in d ik a tio n zu dieser T h e ra p ie zu sein.
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R ésum é
L o rsq u e l’é t a t de m al a s th m a tiq u e e s t ré fra c ta ire a u x b ro n c h o ­
d ila ta te u r s e t q u ’u n e acidose re s p ira to ire est a p p a ru e , la co rrectio n
de celle-ci p a r l’a d m in is tra tio n in tra -v e in e u se de b ic a rb o n a te fa it
ré g re sse r le b ro n c h o sp a sm e e t r é ta b lit la sen sib ilité à l’a d rén alin e. La
fré q u e n c e d ’a d m in is tra tio n d o it ê tre d é te rm in é e p a r l’an aly se ré p é ­
té e d u p H e t de la pco 2- L a dose re c o m m an d ée p a r in je c tio n est de
1,5 m E q /k g i.v .
Ceci e s t illu stré p a r la p ré s e n ta tio n de six cas, p a rm i lesquels un
e n fa n t de 12 an s, q u i, grâce à ce tr a ite m e n t, est so rti d ’une crise
d ’a s tb m e , o ù le p H s’é ta it ab aissé à 6,66.
P a r ce m o y e n , on p e u t so u v e n t é v ite r une v e n tila tio n m écanique.
L o rsq u ’on a reco u rs à la re sp ira tio n artificielle, la co rrectio n de l’ac i­
dose d im in u e la ré sista n c e au p assag e de l’air e t p e rm e t une v e n tila ­
tio n p lu s efficace à des p ressions in sp ira to ire s p lu s basses e t plus sûres.
L ’in su ffisan ce c a rd ia q u e ne sem ble p as ê tre une c o n tre -in d ic a tio n à
c e tte th é ra p e u tiq u e .

References
1. M it h o e f e r , J.C . ; R u n s e r , R . I I . and K a r e t z k y , M. S. : The use of sodium b i­
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A uthor«’ address: Jo h n C. Mithoefer, M .D .; W illiam F. P o rter, M .D.; Monroe S. K aretz k y , M .D., T h e M ary
Imogone B assett H ospital, C ardio-Pulm onary L ab o rato ry , Cooperstown, N ew Y ork 13326
(USA)

A ddendum
A fter this paper had been set in type, th e publication by U l m e r et al. appeared in
this journal (34: 338; 1967). In principle, th e authors come to sim ilar conclusions.
They show th a t, ap art from chemical influences, neurom uscular factors are also in­
volved in the connection between C 02 and respiration dealt w ith in their investi­
gations.

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