Diagnosis and management of severe infections in infants and children: A review of experiences since the introduction of sulfonamide therapy

The Journal of Pediatrics VOL. 21

OCTOBER,19~2

No. 4

Original Communications D I A G N O S I S AND M A N A G E M E N T OF S E V E R E I N F E C T I O N S IN I N F A N T S AND C H I L D R E N : A R E V I E W OF E X P E R I E N C E S SINCE T H E I N T R O D U C T I O N OF S U L F O N A M I D E T H E R A P Y I. SEPSIS OF LATERAL SINUS PHLEBITIS

ALEXIS F. HART~rANN, M.D., DOROTHY WOLFF, PH.D., AND FRANCES LOVE, M.D. ST, Louis, Mo. HERE T from

can be little doubt that many of the remarkable recoveries infections since the introduction of sulfonamide drug therapy have been the direct results o~ such treatment. It is also becoming increasingly evident, however, that other factors such as early and accurate bacteriologic diagnosis, which may at an early stage of infection point clearly to the need of treatment other than ehemotherapyl effective correction of serious disturbances in water and electrolyte metabolism (particularly severe dehydration and acidosis) and maintenance of adequate nutrition in the broadest sense, both of which may require much skillful intravenous administration, serum therapy, and surgical procedures, m a y at times be of equal or of even greater importance. Because of these facts we are convinced that never before has there been a greater need for the fullest cooperation between the pediatrician, or internist, the surgeon, and the diagnostic laboratories; without it, the potentialities of chemotherapy may be largely unrealized, and, in fact, this most valuable measure may be so misused as to be largely discredited. Just prior to the availability of sulfonamide drugs, one of us (A. F . H . ) with Cone 1 reviewed the sixty cases of phlebitis of the lateral sinus encountered in the St. Louis Children's Hospital from 1920 through 1936. We expressed ourselves as "looking forward to the effects which might be obtained by the use of 'prontosil' and ' p r o n t y l i n ' ( s u l f a n i l a m i d e ) " feeling " t h a t these substances m a y prove to be of great value in controlling septicemia and the development of metastatic loci during the most dangerous preoperative and postoperative periods From the Departments of Pediatrics and Otolaryngology, Washington University School of Medicine, and the St. Louis Children's Hospital. 435

436

THE JOURNAL OF PEDIATRICS

o~ lateral sinus phlebitis." W e wish n o w to report on our experiences w i t h this serious condition over the past five years in m u c h the s a m e w a y as w e did in our p r e v i o u s c o m m u n i c a t i o n .

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REPORT OF RECOVERED CASES CASE 1 (Chart 1 and Table I ) . - - T h i s 3-year-old girl, A. It., developed pertussis eight weeks prior to admission and two weeks l a t e r complained of earache oa the r i g h t side. One week later there occurred spontaneous rupture of the right drum

HARTMANN ET AL.."

SEVERE INFECTIONS IN INFANTS AND CHILDREN

w i t h p u r u l e n t drainage. There were t h e n periods of i n t e r m i t t e n t drainage high f e v e r r a n g i n g up to 105 ~ F., a n d during the week j u s t before admission was v e r y i r r i t a b l e a n d vomited several times. On the d a y before admission r i g h t knee became swollen and painful. No c h e m o t h e r a p y was g i v e n during period.

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On admission on /rune 11, 1937, e x a m i n a t i o n revealed a f r e e l y d r a i n i n g r i g h t ear w i t h o b l i t e r a t i o n of all l a n d m a r k s on the drum. T h e r e was tenderness over the r i g h t mastoid a n d x-ray evidence of m a s t o i ~ t i s w i t h ' b r e a k d o w n of cell septa on t h a t side. The leucocyte count was 12,700 w i t h m o d e r a t e l e f t shift. The following m o r n i n g i t was t h o u g h t t h a t a thrombosed jugular vein could be palpated i n the neck; however, l u m b a r p u n c t u r e revealed a n e g a t i v e Tobey-Ayer test and essentially normal spinal fluid. Blood culture t a k e n 'on admission was reported on this day to be positive for hemolytic streptococci. C h e m o t h e r a p y w i t h sulfanilamide orally a n d subcutaneously was i n s t i t u t e d shortly a f t e r admission a n d was followed by a rapid i m p r o v e m e n t w i t h fall ]n t e m p e r a t u r e a f t e r a sharp rise on J u n e 12, Then a g a i n on J u n e 15 t h e r e was h i g h r e m i t t e n t fever, and at this time b i l a t e r a l papillcdema was noted. Blood cultures c o a t l n u e d to be positive for hemolytic streptococci. The Tobey-Ayer t e s t was repeated and f o u n d positive on the r i g h t side. Accordingly, on J u n e 16 a r i g h t mastoldectomy was performed b y Dr. Lee Wallace Dean, Jr., r e v e a l i n g bone necrosis and pus a n d an organizing t h r o m b u s in t h e l a t e r a l sinus. The j u g u l a r vein was t h e n ]igated in the neck. From the pus i n the sinus hemolytic streptococci were cultured. The t e m p e r a t u r e continued to be m o d e r a t e l y elevated and on 5une ]9 a probe was i n s e r t e d into the lateral sinus to secure b e t t e r drainage, following which the blood" culture a g a i n became positive a f t e r two successive n e g a t i v e cultures. The following d a y i t was a g a i n negative. Recovery t h e r e a f t e r was u n e v e n t f u l , a n d the knee i n v o l v e m e n t disappeared w i t h o u t local t r e a t m e n t . Throughout this illness, considerable supportive t r e a t m e n t in t h e form of f r e q u e n t whole blood t r a n s f u s i o n s was given. Cyanosis from m e t h e m o g l o b i n e m i a which developed w i t h i n t e n s i v e sulfanilamide t h e r a p y was controlled b y a d m i n i s t r a t i o n of methylene blue intravenously. CASE 2 (Chart 2 a n d Table I ) . - - T h i s 2-year-old boy, J. G., h a d spontaneous rupture of b o t h e a r d r u m s following a generalized upper r e s p i r a t o r y i n f e c t i o n five m o n t h s previously. I n t e r m i t t e n t pain and discharge s u b s e q u e n t l y were noted, Two weeks before e n t r y a t e n d e r swelling appeared in t h e neck on the l e f t side below the mastoid, a n d f e v e r a n d a w a t e r y d i a r r h e a developed. On the day before e n t r y on J u n e 28~ 1937~ he complained of pain on motion of the legs. Alt h o u g h t r e a t e d for t h e cervical adenitis, no c h e m o t h e r a p y was given prior to hospital entry. The i n i t i a l e x a m i n a t i o n revealed an acutely ill child w i t h cervical adenitis, swelling and tenderness of the r i g h t knee joint, a n d w i t h i n t a c t a n d r e t r a c t e d b u t gray a n d t h i c k e n e d drums. There were no e x t e r n a l signs of mastoiditis, b u t x-ray revealed poorly p n e u m a t i z e d mastoids, hazy on b o t h sides w i t h a t e n d e n c y toward a c u m i n a t l o n on the right. L u m b a r p u n c t u r e the following day showed the TobeyAyer t e s t to be questionably positive; on the second day following i t was f r a n k l y positive on the r i g h t side. The t e m p e r a t u r e for the first f e w days of hospital stay was septic in t y p e a n d blood cultures for the first three days were positive for hemolytic streptococci. A s p i r a t i o n of the r i g h t knee j o i n t yielded pus from which hemolytic streptococci grew. The leucocyte count on admission was 14,750 with only slight ]eft shift. Chemotherapy was i n s t i t u t e d w i t h oral doses of sulfanilamide, a n d t h e knee j o i n t was twice i r r i g a t e d w i t h a i p e r cent solution of sulfanilamlde. The j o i n t fluid was sterile a f t e r the first irrigation~ The t e m p e r a t u r e showed only slight response a n d on J u l y 3, the Sixth day of t r e a t m e n t , l e f t simple mastoidectomy was performed b y Dr. H a r r y L y m a u w i t h exposure and incision of the l a t e r a l sinus. A coalescent type o f mastoiditis was p r e s e n t w i t h a n organizing

438

THE ,JOURNAL OF PEDIATRICS

clot in t h e s i n u s f r o m w h i c h h e m o l y t i c s t r e p t o c o c c i w e r e c u l t u r e d . J u s t p r e c e d i n g t h e m a s t o i d e c t o m y t h e l e f t j u g u l a r v e i n w a s l i g a t e d in t h e n e c k , a n d a n a b s c e s s b e n e a t h t h e s t e r n o c l e i d o m a s t o i d m u s c l e d r a i n e d . T h e t e m p e r a t u r e r e m a i n e d elev a t e d s l i g h t l y .for t h e f o l l o w i n g two w e e k s , b u t w i t h t h e d i s c o n t i n u a n c e o f sulf a n i l a m i d e on J u l y 20, it c a m e to n o r m a l a n d r e m a i n e d so t h e r e a f t e r .

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S u p p o r t i v e t h e r a p y in t h i s c a s e c o n s i s t e d of w h o l e blood t r a n s f u s i o n s d a i l y duri n g t h e first f e w d a y s of t h e i l l n e s s a n d a d d i t i o n a l fluid a n d e l e c t r o l y t e i n t h e form of laetate-lginger's solution. CIkSE 3 ( C h a r t 3 a n d T a b l e I ) . - - M . l~IcO.~ w h o w a s 11. y e a r s old w h e n a d m i t t e d , h a d a h i s t o r y of r e p e a t e d a t t a c k s of o t i t i s m e d i a f r o n t i n f a n c y , w i t h i n t e r r a i t t e n t p a i n a n d d r a i n a g e f r o m e i t h e r or b o t h ears. O n J a n . 7, 1938, t h r e e w e e k s be'fore

tiARTiViANN .F.T AL. :

SEVERE 1NI,' ECTIONS iN INFANTS AND CkIILDREN

439

entry, he developed an acute generalized ~pper respiratory infection, and ou Jan. 11 the left eardrum ruptured spontaneo~sly. During this time he continued to h~ve a low-grade, nonseptic f e v e r and gradually became w e a k e r and m o r e listless. No chemotherapy was given prior to admission, t/[e was a d m i t t e d to the hospital from the o u t p a t i e n t cti~ie on Jan. 28.

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Initial examination revealed the following: No elevation of temperature when first taken; i n t a c t but dull, thick, and bulging i e f t eardrum; slight tenderness over the left mastoid; a f r a n k l y positive-Tobey-Ayer test on the l e f t ; positive blood culture for hemolytic streptococci; tellcoeyte count of ;10,400 w i t h slight l e f t shift;

440

THE JOURNAL

OF PEDIATRICS TABLE ~ULFONA~HDE-TREATED PATIENTS W I T H LATERAL PURULENT

CASE DATE OF NO.

ADM.

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a n d x - r a y e v i d e n c e o f m a s t o i d i t i s on t h e l e f t side w i t h q u e s t i o n a b l e s i g n s o f l e f t p e t r o s i t i s also. T h e s p i n a l fluid w a s s t e r i l e w i t h 16 cells p e r cubic m i l l i m e t e r . T r e a t m e n t w a s i n s t i t u t e d w i t h oral s u l f a n i l a m i d e i n a m o u n t s a v e r a g i n g 0.2 Gm. p e r k i l o g r a m p e r d a y , on w h i c h dose blood c o n c e n t r a t i o n s r a n g i n g f r o m 5 to ] 5 m g . p e r 100 c.c. were o b t a i n e d . T h e t e m p e r a t u r e w a s n e v e r s e p t i c i n n a t u r % b u t w i t h t h e h i s t o r y a n d f i n d i n g s in k e e p i n g w i t h m a s t o i d i t i s a n d l a t e r a l s i n u s p h l e b i t i s a n d b e c a u s e of p o s i t i v e blood c u l t u r e in t h e a b s e n c e o f o t h e r w i s e a d e q u a t e c a u s e , l e f t m a s t o i d e c t o m y w i t h ] i g a t i o n of t h e l e f t j u g u l a r v e i n w a s p e r f o r m e d on J a n . 31, t h e f o u r t h d a y of t r e a t m e n t , b y Dr. R o b e r t V o t a w . S c l e r o s i n g o f t h e m a s t o i d cortex w i t h p y o g e n i c n l e m b r a n e l i n i n g t h e cells w a s f o u n d , a n d in a d d i t i o n t h e r e w a s p u s w i t h i n t h e l u m e n of a t h r o m b o s e d l a t e r a l s i n u s . H e m o l y t i c s t r e p t o c o c c i were c u l t u r e d f r o m t h e m a s t o i d , b u t t h e p u s f r o m t h e s i n u s p r o v e d sterile. T h e r e were no f u r t h e r p o s i t i v e blood c u l t u r e s a f t e r t h e o n e on t h e first day. A s in t h e two p r e c e d i n g cases, f r e q u e n t w h o l e blood t r a n s f u s i o n s w e r e g i v e n to m a i n t a i n r e d cells a n d h e m o g l o b i n . M e t h y l e n e b l u e w a s a d m i n i s t e r e d to c o n t r o l t h e r a t h e r c o n s i d e r a b l e c y a n o s i s f r o m m e t h e m o g l o b i n e m i a , w h i c h s o m e t i m e s a m o u n t e d to as m u c h as 20 p e r c e n t o f t h e t o t a l p i g m e n t . R e c o v e r y w a s u n e v e n t f u l a n d c h e m o t h e r a p y w a s d i s c o n t i n u e d on t h e t e n t h d a y . CASE 4 ( C h a r t 4 a n d T a b l e I ) . - - J . M., a g e d 5 years, became a c u t e l y ill with scarlet f e v e r on F e b . 4, 1938. R a s h a n d h i g h f e v e r p e r s i s t e d f o r t h r e e d a y s . T h e l a t t e r t h e n s u b s i d e d s o m e w h a t , b u t n o t to n o r m a l , a n d on Feb. 12, a l e f t m y r i n g o t -

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HARTMANN ET AL. :

SEVERE INFECTIONS IN INFANTS AND CHILDREN

441

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omy was performed. No drainage was obtained; m y r l n g o t o m y was repeated on Feb. 16, w i t h a flow of pus this time. P u r u l e n t drainage continued up to the time of e n t r y on Feb. 17. On the day just previous to admission 1.~33 Gin. of sulfanilamide was given orally. The initial examination revealed a moderately ill child w i t h tonsillitis, cervical adenitis~ and tenderness over the l e f t mastoid. The l e f t ear was draining pus through a a adequate incision. X-ray showed cloudiness but w i t h apparently intact trabeculae o f the l e f t mastoid. Leucocytosis of 35,000 w i t h a slight l e f t s h i f t was present. All blood cultures were negative, but cultures of ear and t h r o a t showed hemolytic streptococci. I n spite of chemotherapy w i t h oral sulfanilamide in doses of 0.2 Gin. per kilogram per day~ marked elevation of t e m p e r a t u r e persisted. This was thought to be due to the cervical adenitls for a period of nine days. Then since the t e m p e r a t u r e became more septic in type and signs of mastoid involvem e n t persisted, l e f t mastoidcctomy was d e c i d e d n p o n . A t the time of operation on March 3, w i t h the p a t i e n t under anesthesia, a lumbar puncture w a s made and the Tobey-Ayer test was found to be f r a n k l y positive. L e f t simple mastoidectomy w i t h ligatlon of the jugular vein in the neck was t h e n p e r f o r m e d b y Dr. A. B. Potter. A n t r a l and tip cell necrosis and considerable granulation tissue were found, but the small portion of exposed lateral sinus appeared normal and was not; incised. 1Yo cultures were made. The temperature followlng operation fell promptly and was normal in f o r t y - e i g h t hours and remalned so w h e n chemotherapy was dlscontinued. X rays repeated on Feb. 15, 1938, were interpreted as showing petrositis on the left.

442

THE JOURNAL OF ]?EDIATRICS

CASE 5 (Chart 5 and Table I ) . - - T h i s ~-year-old boy, C. S., had a history of earaches following measles two months previously. He became ill with a rash, fever, and sore t h r o a t diagnosed as scarlet fever eleven days before e n t r y to the hospital. Three days later, eight days prior to admission, bilatera] cervical swellings ap-

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peared. P a i n recurred in the left ear, and the next day there was spontaneous rupture of the ]eft eardrum with subsequent purulent drainage. The child had n e i t h e r eaten nor t a k e n fluSds well during the illness and was having difficulty with b r e a t h i n g and swallowing. Some sulfonamide chemotherapy may have been given.

IKARTIVIANN ET AL. :

443

SEVERE INFECTIONS IN INFANTS AND CHILDREN

O n a d m i s s i o n on F e b . 17~ 1938~ e x a m i n a t i o n r e v e a l e d a n a c u t e l y ill b o y w h o w a s listless a n d showed ~ a r k e d loss of hea.ring. T h e r e w-as typical p o s t s c a r l e t d e s q u a m a t i o n o~ t h e s k i n , m o d e r a t e d e h y d r a t i o n , b i l a t e r a l c e r v i c a l adenitis~ a n d p u s dra~ining f r o m a l a r g e per:~oration of t h e l e f t d r u m . T h e t e m p e r a t u r e on adm i s s i o n .was v e r y h i g l ~ a n d t h e c h i l d a p p e a r e d v e r y toxic. T h e l e u c o c y t e c o u n t

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w a s 19,100 With m o d e r a t e l e f t s h i f t . toiditis with density about the canals strueture~ m o r e m a r k e d on t h e r i g h t : on t h e r i g h t . Blood c u l t u r e s were all

X - r a y s h o w e d e v i d e n c e of b i l a t e r a l mason e i t h e r side a n d p o o r l y defined cellular T h e r e w a s also q u e s t i o n a b l e p a p i l l ' e d e m a n e g a t i v e . T h e T o b e y - A y e r t e s t w a s per-

444

THE JOURNAL OF PEDIATRICS

formed twice, on Feb. 18 and 19, and was f r a n k l y positive on each occasion. The t e m p e r a t u r e for the next two days was high and septic in type. On Feb. 19, the t h i r d day of t r e a t m e n t , ligation of the ]eft jugular vein in the neck and ]eft m a s t o i d e c t o m y w i t h ~ncision of the lateral sinus were performed b y Dr. A. J. Cone. A t operation necrotic pericarotid, groove ~nd tip cells, and an organizing f

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clot in the lateral sinus were found. Both mastoid and lateral sinus cultures were positive f o r hemolytic streptococci. Chemotherapy was begun on the day of admission w i t h oral and subcutaneous sulfanilamide in amounts averaging 0.2 Gin. per kilogram per day. T h e postoperative course w a s uneventful with rapid subsidence of the fever. The w o u n d was irrigated three times with a i per cent solution of sulfanilamide in R i n g e r ' s solution w i t h v e r y rapid healing. Considerable ~supportive t r e a t m e n t was necessary especially for the first few days. This

I-IARTMANN ET AL. :

SEVERE INFECTIONS IN INFANTS AND CHILDREN

~5

was in the f o r m of f r e q u e n t whole blood transfusions and l a c t a t e - R i u g e r ' s solution. Cyanosis was controlled by t h e admi~dstration of methylene blue administered both orally and intravenously. CASE 6 (Chart 6, Table I).--~YL W., 8 years old, had dexelopcd earache three weeks previous to admission. Five days later the ]eft drum ruptured spontaneously, and two days a f t e r t h a t the right drum was incised. She was t r e a t e d for ten days in the o u t p a t i e n t clinic without chemotherapy. Drainage from both ears ceased seven days prior to hospital entry, b~t the ]eft ear drained again for a short while t h r e e or four days later. She also had complained of severe headache and dizziness and had appeared drowsy to her parents. On the initial examination on Feb. 19, 1938, b o t h eardrums were found dull, thickened, and retracted, but intact. She was complaining of headache and there was a stiff neck. The leucocyte count was 15,000 w i t h slight left shift, and the spinal fluid contained 410 "cells per cubic millimeter, b u t no organisms were seen. The initial blood culture was positive for hemolytic streptococci, but the spinal fluid culture was sterile. The Tobey-Ayer t e s t was negative. X-rays showed bilateral cloudiness of the mastoids with possible erosion of cellular structure on the left and some haziness of the petrous apex on the right side. Simple left mastoidectomy was done on Feb. 23 b y Dr. Robert Votaw, revealing some mastoid cells containing pyogenic membrane, necrotic cells and dural plate, and some grayness of the wall of the lateral sinus. The l a t t e r did not appear thrombosed and was not incised. No cultures were made. P o s t o p e r a t i v e l y there was no elevation of t e m p e r a t u r e and blood cultures remained negative. Oh Feb. 26 a right simple mastoidectomy was done, revealing soft bone and a few cells containing pyogenic m e m b r a n e and a similar discoloration of the sinus wall. The child was t r e a t e d during this period with oral sulfanilamide and f r e q u e n t whole blood transfusions. CASE 7 (Chart 7 and Table I ) . - - T h i s 7-year-old girl, L. S., had a generalized upper respiratory infection two weeks before admission. Two days later she complained of earache. Bilateral myringotomy Was done, and pus was obtained from the right ear. At this time only bloody fluid was obtained f r o m the l e f t ear, but five days l a t e r it also began to discharge pus. Two days l a t e r she b e g a n to complain of pain and tenderness behind the right ear which lasted two or three days. On the same day a rash appeared over the body which was suggestive of scarlet fever. Sulfanilamide was given in the amount of 2.6 Gm. on April 25, I938, and for the n e x t two days there was no elevation of temperature. On the n i g h t before e n t r y to the hospital, the temperature suddenly rose to 105 ~ F., affd she was adm i t t e d the n e x t day , April 29. The initial examination showed all acutely iI1~ p r o s t r a t e d child with high fever, There was an erythematous rash over the body which was fading, and her throat and tongue were compatible with a diagnosis of scarlet fever. Bilateral purulent otitis media w i t h o u t external signs of mastoiditis was present. The leucocyte count was 12,000 w i t h a definite left shift. X-ray findings of hazy cellular structure and poorly defined trabeculae on the right pointed to a mastoiditis on t h a t side. The initial and two subsequent blood cultures were positive for hemolytic streptococci. A Tobey-Ayer t e s t a t t e m p t e d on the following morning was suggestively positive on the ]eft but not conclusive because of failure of the p a t i e n t to cooperate. This was repeated the next day under e t h e r anesthesia and revealed a complete block on the l e f t side. Chemotherapy was begun shortly a f t e r admission w i t h orally administered sulfanilamide w i t h o u t favorable response as the t e m p e r a t u r e remained markedly

446

THE JOURNAL OF PEI)IATRICS

elevated a~d the blood cultures positive. On 1V[ay ] the third day of t r e a t m e n t a ]igation of the left jugular vein in the neck w i t h l e f t simple mastoideetomy and incisio~ of the lateral sinus was performed b y Dr. A. B. Potter. Pyogenic mere. brane, soft trabeeulae, and a gray lateral sinus were found. No cultures were made. P o s t o p e r a t i v e l y the temperature remained markedly elevated w i t h little improvement in the p a t i e n t ' s condition. On May 7 the temperature rose to over <

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41 ~ C., and another positive blood culture was obtaiued. On the following day a righ t simple mastoideetomy w a s performed, revealing necrosis and pus of the mastoid cells but a normal lateral sinus. The t e m p e r a t u r e the~ fell promptly ~o normal in forty-elght hours and remained so throughout the remainder of her hospital stay. F r e q u e n t whole blood transfusions, parenteral ituid, and clec,trolyte were given as supportive therapy. Some of the sulfanilamide during the postoperative course was incorpoorated~with subcutaneously administered lactate-Ringer!s solution. Considerable m e t h y l e n e blue was given orally and intravenously to eontrql the methemoglobinemia.

I-iAR'PMANN ET AL. :

SEVZP~I INFEtYI!IONS IN INFANTS AND CttlLDtlEN

447

I t should be noted in t h i s case t h a t there were local collcctions of pus in both m a s t o i d s which n e e e s s l t a t e d s u r g i c a l d r a i n a g e before s u l f a n i l a m i d e was completely effective in controlling the infection. Thls is c o n s i s t e n t With all t h a t we now k n o w about t h e i n e f f e c t i v e n e s s of c h e m o t h e r a p y in s t e r i l i z i n g collections of f r a n k pus.

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CASE 8 ( C h a r t 8 a n d Table I ) . - - T M s 7-year-old b a y s D. M , h a d a generaIized upper r e s p i r a t o r y i n f e c t i o n live weeks before hospital admission. This h a d app a r e n t l y cleared, b u t he a p p e a r e d listless a n d later was o b s e r v e d to hold his head to t h e r i g h t side a n d complain of a ligtle stiffness of his neck. Ten days before e n t r y ,he b e g a n to h a v e an i r r e g u l a r s h i g h and septic t y p e of t e m p e r a t u r e w i t h

c6 x: 9

~4~

THE JOURNAL 0F PEDIATRICS

rise on one occasion to 106.5 ~ F. He complained of pain in the ear only once, at the onset of fever, but not again. L a t e r questioning elicited a history o f a disCharging ear four years previously a n d two subsequent attacks of earache, in September and December, ]938, each lasting several days. The initial examination on Jan. 3, 1939, revealed i n t a c t eardrums, b u t w i t h the r i g h t one red, thick, and bulging. The t e m p e r a t u r e was quite high, being 39 ~ C. No resistance to motion of the neck was found, b u t there was some pain on ext r e m e flexion. X-ray evidence pointed to mastoiditis on the right side with acumination of the cells at the tip and relatively poor cellular development. On Jan. 5, during the night his temperature rose rapidly to 107.5 ~ F. but fell below normal by morning. Lumbar puncture done a t this time revealed a positive Tobey-Ayer test on the right. The blood culture and the culture of the pus aspirated from the ear on Jan. 6 were positive for hemolytic streptococci. The spinal fluid contained 14 lymphoaytes and was sterile. T r e a t m e n t was begun with sodium sulfapyridine per rectum in amounts totaling 0.2 Gin. per kilogram per day. On Jan. 7, the fourth day of t r e a t m e n t , the r i g h t jugular vein was ligated in the neck and right mastoideetomy was performed w i t h incision of the lateral sinus b y Dr. H. M. Smit. The vein was found completely thrombosed and suppurating at one point, and there was necrosis of the mastoid cells. Hemolytic streptoeocM were cultured from the lateral sluus pus. The temperature subsided following operation but not to normal. The mastoid wound healed rapidly, and the persisting low-grade t e m p e r a t u r e w a s t h o u g h t due to i n f e c t e d maxillary sinuses which were present. Treatment was changed f r o m rectal sodium sulfapyridine to orM sulfanilamide on the t e n t h day of treatment. General supportive t r e a t m e n t was administered w i t h whole blood transfusions, dextrose, and subcutaneous l a c t a t e - R i n g e r ' s solution. W i t h chemotherapy entirely in the form of sulfapyridine, only a slight degree of methemoglobinemia, amounting to about 3 per cent of the total pigment, developed, and it was not necessary to employ methylene blue therapy. Before he l e f t the hospital, his maxillary a n t r a were irrigated, and tonsillectomy and adenoidectomy were performed. He was discharged in excellent condition. CASE 9 (Chart 9 and Table I ) . - - A . M., ]0 years old on admission, had a history of otitis media for sixteen days, beginning w i t h severe paln in the right ear on Feb. 27, 1939, with m y r i n g o t o m y two days later. Discharge was profuse f r o m the draining ear, but it had decreased somewhat in amount just before entry. However, eleven days prior to hospital admission, she began to have repeated chills associated w i t h high f e v e r once or twice daily. The temperature was irregular and septic in type, ranging from 98 to 106 ~ F. H i s t o r y also r e v e a l e d float three years previously there was spontaneous p e r f o r a t i o n of the r i g h t ear followed b y a discharge for two weeks. She had also complained of pain in the right ankle and t h i g h f o r about one week. Sulfanilamide in amounts of about 2 Gin. daily was s t a r t e d four days before admission. The i n i t i a l hospital examination revealed an acutely ill child w i t h a temperature of 39 ~ C. The right drum was i n t a c t b u t thickened and scarred, and there were no external signs of mastoiditis. X~ray examination showed cloudiness of the mastoid ou the right side. A Tobey-Ayer t e s t done on the second day was not eonc]uslve but did not show as high a rise on the right as on the ]eft. The leucocyte count was 10,600 w i t h slight l e f t shif% and the initial blood ~ulture was positive for hemolytic streptococci. The spinal fluid findings were essentially normal. On March 16, the t h i r d day of t r e a t m e n t , the r i g h t jugular vein was llgated in the neck by Dr. H. M. Smit and followed b y right mastoidectomy and incision of the lateral sinus. There was necrosis and pus in the mastoid cells,

I-IARTIVIANlq ]~T A L , :

SEVERE INFECTIONS

IN

INFANTS

AND

CHILDREN

~9

and the lateral sinus was gray in appearance and coatalned aa organizing thrombus. The pus from the mastoid was sterile on cultur% b u t s the lateral sinus hemo]ytic streptococci were cultured. The temperature ~ell to normal in four days and remulned so e~cept for a few d~ys of low-grade elevation ~ust bes discharge, not associated w~th any significant physical findings.

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Chemotherapy in this case consisted of oral doses of su]fapyridine on which blood concentrations f r o m 10 to 16 rag. per 100 c.c. were obtained. F r e q u e n t small whole blood transfusions were also given and small amounts of methylene blue f o r mild cyanosis due to methemoglobinemia. CASE 10 (Chart 10 and Table I ) . - - T h i s boy, 1~. C., 11 years old on admission, had a history of f r e q u e n t colds accompanied b y sore t h r o a t s for many years. In

450

THE

August~ 1938~ there for a few days and from the ears with two weeks before

JOURNAL

OF

PEDIATRICS

occurred a spontaneous rupture of both drums~ which drained then healed. Subsequently, there was intermittent drainage each fresh respiratory infection. On Nfay 15~ 1939~ which was hospital entry~ he complained of pain in the left ear and

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d e v e l o p e d h i g h f e v e r . A f e w d a y s ] a t e r s o m e d i s c h a r g e w a s n o t e d f r o m t h a t side~ a n d p a i n in t h e e a r b e c a m e q u i t e s e v e r e . T h e t e m p e r a t u r e c o n t i n u e d to be i r r e g u l a r l y elevated a n d h i g h e r in the evening. No c h e m o t h e r a p y }vas given, d u r i n g tile illness. Oll a d m i s s i o n on M a y 29 e x a m i n a t i o n r e v e a l e d a n a c u t e l y ill c h i l d w i t h a t e m p e r a t u r e of 40 ~ C.~ intact eardrums but with the left d~'um gray and tliiek~ and

HARTMANN ET AL. :

SEVFRE INFECTIONS IN INFANTS AND CHILDREN

451

questionable tenderness over the left mastoid. The leucocyte count was 14,400 without left shift. B~ood culture taken on admission was pQsitive for helnolytic streptococci. The x-rays showed marked increase in density about the canals on both sides and aeumination of cells plus destruction of trabeculae od the left. A Tobey-Ayer t e s t on the m o r n i n g of May 30 was frankly positive on the left. The temperature continued septic in type, and on 5fay 31 the l e f t jugular vein was ]igated in the neck, and simple left mastoideetomy w i t h incision of the lateral sinus was performed b y Dr. I-L IV[. Smit. No t ~ s or necrotic tissue was found, but there was granulation tissue in the mastoid antrum. The lateral sint~s wall was thick and g r a y but compressible in the p a r t uncovered in the temporal bone; the thrombosis was t h o u g h t to be below the knee of the sinus. The vein was not incised. The t e m p e r a t u r e subsided somewhat during the n e x t two days but later again became elevated w i t h daily spikes. Chemotherapy Was b e g n n on the day of admission w i t h oral sulfapyridine and conlinued through the n i n t h day. Soon a f t e r the drug was discontinued, the temperature rose higher and showed greater variation. On 3/Iay 10, the t h i r t e e n t h day of t r e a t m e n t , ~here was a sharp rise in ' t e m p e r a t u r e , and a n o t h e r blood culture positive for hemolytic streptococci was obtained. Accordingly, chemotherapy was resumed w i t h oral doses of sulfanilamide and continued f o r the next seven days, the temperature falling promptly to normal and remaining so t h e r e a f t e r . On J u n e 19 an eye examination revealed two diopters papilledema of both optic discs. The eyegrounds had previous]y been negative except for some fullness of the veins. There were~ however, no other abnormal neurol0gie findings, and the papilledema subsided w i t h i n a f e w days and did not recur. The physical condition at the time of discharge on July 6, 1939~ was excellent except for x-ray evidence of ethmoiditis on the left and bilateral sphenoiditis. CASE 11 (Chart 11 and Table I ) . - - T h i s 7-year-old boy, J. ~I.~ developed a generalized acute upper respiratory infection on Feb. 11, 1910, which included bilateral otitis media. J u s t two ~days later meningeal symptoms began and admission to the hospital occurred on, the t h i r d day of meningitis, Feb. 15, 1940. The initial examlnation revealed a yery seriously and acutely ill boy with spinal fluid liter~ ally teeming w i t h streptococci, proved later on culture to be l~emolytie. Cell count of this initial tap was only 380. The Tobey-Ayer t e s t was already positive on t h e right side i and the blood culture proved also to be positive on the day of admission. T r e a t m e n t was s t a r t e d with a single dose of sodium sulfamethylthlazole followed b y sutfamethylthiazole given orally. From the second through the f o u r t e e n t h day of sulfonamide t r e a t m e n t both sulfamethylthiazole and sulfanilamide w e r e admi~fistered, the total dosage averaging a b o u t 0.4 Gm. per kilogram of body weight per day. The temperature fell steadily a f t e r the beginning of t r e a t m e n t , and the boy showed gradual improvement. While organisms could not be seen in the spinal fluid on the second day and t h e r e a f t e r , t h e y continued to grow on culture for the first six days, a f t e r which the spinal fluid continued to be sterile. As in p r e v i o u s cases of a similar nature, immediately a f t e r t r e a t m e n t t h e spinal fluid cell count rose a s t h e number of organisms diminished, and then fell. On the seventh day of sulfonamide t r e a t m e n t , a f t e r the blood culture had ~een sterile, for five days, and on the first day of sterile spinal fluid, ligation of the right internal jugular vein was made, and9 then a right simple mastoidectomy was performed w i t h exposure and inelsion of the laterM sinus. 1Kastold cells everywhere were found involved, granulations Spread over the knee of the lateral Slnus, ~i~d~ where exposed, the dura was found red and thickened. The temperature then si0wlY r e t u r n e d % w a r d normal. The spinal fl~uid continued to show some i n c r e a s e in Cell count but remained without organisms to be seen and was always sterile, findings possibly to be explained by some remaining pocket of

~52

THE JOURNAL OF I~EDIATI4ICS

infectiom Strabismus and dilated pupils were the o~ly neurologic findings suggestive of continued central nervous system involvement. As in previous cases, there was need for considerable supportive treatment, especially early in the course of the infection, and f o r about t h i r t e e n days fluid was given b y the continuous intravenous ~njection method consisting of dextrose

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HARThIA~NN ET AL. :

SEVERE INFECTIONS IN INFA1NTS AND CHILDREN

453

peni~ was noted, the blood count dropping f r o m 23,500 on Feb. 16 to 6,40(} on Feb. 19. The dosage of the drug~ however, was not reduced, and on Feb. 21 the count doubled. On April 6 the tonsils and adenoids were removed, and on April 17 the child was t r a n s f e r r e d to Ridge l%rm, our country convalescent department, to complete his recovery. He was finally discharged f r o m the hospital on June 19, 1940, completely rec6vered except for u dilated and fixed r i g h t pupil.

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CASE 12 (Chart 12 and Table I ) . - - T h i s ll-year-old boy, 1~. D., had an earache on the l e f t side on April 18, 1940, not accompanied b y any generalized respiratory infection. Two days later the left drum ruptured spontaneously w i t h a small amount of discharge. There was only a little elevation of temperature the next day w h e n the ear was f u r t h e r opened by a physician. There was then no change until the n i g h t before admission, at which time he suddenly had a chili and developed a t e m p e r a t u r e of 103 ~ F. No chemotherapy had been given.

4~

THE JOURNAl, OF I'EDIATRICS

On admission~ ~r 9, 1940, e x a m i n a t i o n r e v e a l e d a ~noderately a c u t e l y ill child w i t h a t e m p e r a t u r e of 40 ~ The e a r d r u m s Were i n t a c t b u t t h e l e f t drum was full a n d red. The leucocyte count w a s 14,050 w i t h a s l i g h t l e f t shift. The x - r a y s showed d e s t r u c t i o n of t h e m a s t o i d cells on b o t h sides a n d an increase in d e n s i t y a b o u t the canal on t h e l e f t side. A T o b e y - A y e r t e s t done s h o r t l y a f t e r

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e n t r y showed a positive t e s t on the l e f t side. Blood culture m a d e on iVIay 9 w a s positive f o r hemolytic streptococci, a n d h e m o l y t i c streptococci were c u l t u r e d f r o m the ears. T r e a t m e n t w a s b e g u n w i t h s u l f a n i l a m i d e g i v e n s u b c u t a n e o u s l y , a n d on the f o l l o w i n g day~ ~/[ay ]0, l i g a t i o n of the l e f t j u g u l a r vein in the n e c k a n d left m a s t o i d e e t o m y were p e r f o r m e d w i t h incision of t h e l e f t l a t e r a l sinus b y Dr; A. J. Cone. H e m o r r h a g i c , s o f t b o n e ' w a s f o u n d in t h e mastoid. The operation was b r o u g h t rapidly to a close because of the critical condition of the patient." I n add{tion to c h e m o t h e r a p y , supportive t r e a t m e n t in t h e form of whole blood transfusions, d e x t r o s e in 10 per cent solntion~ a n d l a c t a t e - R i n g e r ' s solution was given.

[IARTMANN ET AL. :

SEVERE INFECTIONS IN INFANTS AND CHILDREN

~55

D u r i n g t h e o p e r a t i o n i t w a s n e e e s s a r y to a d m i n i s t e r i n t r a v e n o u s fluid, o x y g e n , and eoramine. The sulfanilamide given for the next three days was mainly i n c o r p o r a t e d in t h e s u b c u t a n e o u s fluids. ? ' o l l o w i n g o p e r a t i o n t h e t e m p e r a t u r e s u b s i d e d to n o r m a l w i t h i n six d a y s , a n d chemotherapy was discontinued. H o w e v e r , on lV[ay 22, t h e f o u r t e e n t h d a y of t r e a t m e n t , t h e t e m p e r a t u r e w a s a g a i n e l e v a t e d a n d d u r i n g t h e n e x t f e w d a y s rose g r a d u a l l y u n t i l 1V[ay 28~ a t w h i c h t i m e t h e r e w a s a s h a r p rise to 39.5 ~ C. Chemot h e r a p y w a s r e s u m e d w i t h oral d o s e s of sulfanil'a~mide~ wi~h, h o w e v e r , l i t t l e effect on t h e t e m p e r a t u r e . O n f f u n e 4 a p r o b e w a s i n s e r t e d i n t o t h e l a t e r a l sirius a n d pus obtained. T h e t e m p e r a t u r e t h e n r e m a i n e d p r a c t i c a l l y n o r m a l u n t i l t h e end of t h e h o s p i t a l s t a y . H e w a s d i s c h a r g e d on J u n e 12 in good c o n d i t i o n . CASE 13 ( C h a r t 13 a n d Table I).~--This 9-year old girl, J. R , c o m p l a i n e d of eara c h e on X~Iay 28, 1939. On J u n e 5 s h e b e g a n to h a v e a l o w - g r a d e f e v e r , a n d t h e f o l l o w i n g d a y t h e r i g h t d r u m r u p t u r e d s p o n t a n e o u s l y a n d b e g a n to d r a i n . I n a n o t h e r hospita]~ x - r a y s a n d a blood c u l t u r e w e r e takeu~ a b l o o d t r a n s f u s i o n w a s given~ a n d site w a s g i v e n s u l f a n i l a m i d e ~ t h e e x a c t a m o u n t n o t b e i n g k n o w n . D r u g t h e r a p y w a s d i s c o n t i n u e d on J u n e 12 a n d r e s u m e d on J u n e 17 b e c a u s e of c o n t i n u e d t e m p e r a t u r e e l e v a t i o n . T h e e a r h a d c e a s e d d r a i n i n g b y J u n e 17, b u t t h e t e m p e r a t u r e w a s s h o w i n g m a r k e d f l u c t u a t i o n w i t h r i s e s g o i n g to 105 ~ F. on J u n e 18. She w a s a d m i t t e d to t h e h o s p i t a l here on J u n e 19 w i t h a t e m p e r a t u r e of 38.5 ~ C., a n d a p p e a r i n g a c u t e l y ill, t o x i c a n d c y a n o t i c . T h e r i g h t e a r d r u m w h i c h w a s i n t a c t w a s , h o w e v e r , t h i c k a n d red; t h e r e w a s t e n d e r n e s s o v e r t h e r i g h t m a s t o i d . T h e r e w a s p a p i l l e d e m a o f b o t h discs a n d h e m o r r h a g e s o f t h e r e t i n a e . T h e leuc o c y t e c o u n t w a s o n l y 6,800 b u t w i t h a m a r k e d l e f t s h i f t . A T o b e y - A y e r t e s t p e r f o r m e d on t h e s a m e d a y w a s p o s i t i v e on t h e r i g h t side. C h e m o t h e r a p y w a s g i v e n as orally" a d m i n i s t e r e d s u l f a n i l a m i d e . On J u n e 20 t h e r i g h t j u g u l a r v e i n w a s t i e d off i n t h e n e c k b y Dr. R o b e r t V o t a w , a n d r i g h t m a s t o i d e c t o m y w a s done with incision o f t h e l a t e r a l s i n u s . P u s a n d g r a n u l a t i o n t i s s u e w e r e f o u n d in t h e m a s t o i d cells, a n d in t h e l a t e r a l s i n u s a w h i t e t h r o m b n s w a s f o u n d . No o r g a n i s m s were c u l t u r e d f r o n t t h e o p e r a t i o n site or f r o m t h e blood, a n d t h e n a t u r e o f t h e causative organism remained unknown. I t is p o s s i b l e t h a t ~he c o n s i d e r a b l e a m o u n t of c h e m o t h e r a p y w h i c h t h e p a t i e n t h a d r e c e i v e d h a d s t e r i l i z e d t h e infect i o n b y t h e t i m e of o p e r a t i o n . T h i s f u r t h e r e m p h a s i z e s t h a t w h i l e s u r g i c a l t r e a t m e n t o f s u c h a c o n d i t i o n is n e c e s s a r y , c h e m o t h e r a p y g i v e s a n a d d e d m a r g i n of s a f e t y b y c o n t r o l l i n g t h e i n f e c t i o n in l a r g e p a r t . R e c o v e r y f o l l o w i n g t h e operal i o n w a s v e r y s a t i s f a c t o r y w i t h r e t u r n o f t h e t e m p e r a t u r e to n o r m a l on t h e s i x t h postoperative day. S u p p o r t i v e t r e a t m e n t in t h e f o r m of w h o l e blood t r a n s f u s i o n s and d e x t r o s e a n d l a c t a t e - R i n g e r ' s s o l u t i o n s w a s g i v e n , as in t h e p r e c e d i n g cases. T h e e y a n o s i s f r o m m e t h e m o g ] o b i n e m i a s o m e t i m e s b e c a m e i n t e n s e b u t w a s s u c c e s s f u l l y cont r o l l e d b y m e t h y l e n e b l u e g i v e n orally. CASE 14 ( C h a r t 14 a n d T a b l e I).--'vV. B., 4 y e a r s old, entered with a h i s t o r y of r e p e a t e d p r e v i o u s a t t a c k s of t o n s i l l i t i s a n d e a r a c h e w i t h o u t d r a i n a g e . On April 29, 1938, he b e g a n to c o m p l a i n o f p a i n in t h e l e f t ear. H e w a s g i v e n t r e a t m e n t Iocally w i t h o u t c h e m o t h e r a p y f o r s e v e r a l d a y s , a n d on M a y 7 t h e l e f t d r u m r u p t u r e d s p o n t a n e o u s l y . O n M a y ]0 t h e r e w a s a s u d d e n chill a n d a rise in temp e r a t u r e to 106 ~ F. H e b e c a m e d r o w s y a n d c o m p l a i n e d of solne s t i f f n e s s of his neck. On e n t r y to t h e h o s p i t M on X a y 11 t h e i n i t i a l e x a m i n a t i o n r e v e a l e d an a c u t e l y ill c h i l d w i t h p t o s i s of t h e l e f t eyelid, m i l d p a p i l l e d e m a of b o t h discs, l a t e r a l n y s t a g m u s on looking to left, s u p p u r a t i v e otitis m e d i a on t h e left, a n d a

456

THE JOURNAL OF PEDIATRICS

t e m p e r a t u r e of 38.6 ~ C. There were no e x t e r n a l signs of m a s t o i d i t i s , b u t there w a s t e n d e r n e s s along the l e f t mandible, a n d x - r a y revealed g r e a t l y obscured cellular s t r u c t u r e on t h e l e f t side. The r i g h t side also showed some cloudiness. T h e leucocyte count w a s 25,400 w i t h m o d e r a t e l e f t s h i f t . A Tobey-Ayer t e s t done on t h e d a y of a d m i s s i o n was q u e s t i o n a b l y p o s i t i v e on the l e f t side. The temperat u r e c o n t i n u e d to be h i g h a n d to show large d a i l y fluctuations. The i n i t i a l blood c u l t u r e w a s positive f o r Streptococcus ~iriclans. The patient was placed on chemotherapy, sulfanilamide given orally, a n d on M a y 13 a l e f t m a s t o i d e c t o m y w i t h

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ligation of the l e f t j u g u l a r vein in the neck and incision of the lateral sinus was done b y Dr. R o b e r t Votaw. There was considerable bone p a t h o l o g y in t h e m a s t o i d a n d a g r a y a n d t h i c k e n e d b u t compressible l a t e r a l sinus. The v e i n w a s not incised. No c u l t u r e s were m a d e f r o m either m a s t o i d or l a t e r a l sinus. The posto p e r a t i v e course w a s s t o r m y w i t h h i g h septic t e m p e r a t u r e f o r eleven d a y s a n d t h e n subsidence to a low-grade elevation f o r t h e n e x t two weeks. However, as

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the general condition improved markedly in the l a t t e r period and blood cultures remained negative, chemotherapy was discontinued on J u n e 8. The temperature then fell to normal and remained so. As in all oLher cases, the general care o~ the p a t i e n t included whole blood transfusions and nmintenunce of proper fluid and electrolyte balanco. He was discharged on J u n e 13, 1939, in good condition except for a large d e f e c t over the mastoid due to the operative+wound.

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C~SE 15 (Chart 15 and Table I ) . - - T h i s glrl, M. 1~[., was 2 years old on admission to the hospital. She had been well untll three weeks previously when she compla]aed of pain in the right e~r. Th~s was relieved at the time b y local therapy. One week prior to e n t r y she became f r e t f u l and again complained of pain in the

458

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ear, and three days before entry the right eardrum ruptured spont~neously and drained. On this same day a swelling began to appear behind the right ear. She was admitted to the hospital on Jan. 29, 1940, with a normal temperature but with signs of acute suppurative otitls media and a subperiosteal abscess on tile right side. She was given no chemotherapy, and two days l a t e r a right mastoideetomy was performed by Dr. Lee Wallace Dean, Jr., and there was found a coalescent type of mastoiditis from which the pncumoeoeeus type I I I was cultured. The dura and Jateral sinus were not exposed. The postoperative course was une v e n t f u l f o r the first week, but then there developed a high septic type of temperature w i t h large daily fluctuations. Acute otitis media was discovered on the left side, and myringotomy was done on that side on l~eb. 16. After two more days of high spiking temperature, on the recommendation of the D e p a r t m e n t of Pediatrics, chemotherapy was begun on Peb. 19 with orally administered su]famethylthiazole, and on Feb. 20 a second mastoldeetomy on the right was done w i t h incision of the lateral sinus by Dr. Guerdan IIardy. A t this operation a residual layer of i n f e c t e d cells overlying the lateral sinus was found, and the sinus itself was discolored. Cultures made at this time were sterile, but a biopsy revealed lateral sinus phlebitis. The temperature had fallen promptly to ~ormal before the operation with the institution of chemotherapy and remained so until lVIareh 4, the drug having been discontinued on Feb. 29. The~. following att e m p t e d closure of the wound, there was again elevation of temperature which was due to the development of cervical adeni-As. Chemotherapy was resumed with sulfamethylthiazole ou t h a t day and was continued until March i8~ which was five days a f t e r the regaining of a normal t e m p e r a t u r e on :Yfareh 13. Blood concentrations of betwee~ 5 and 10 mg. per 100 e.e. were obtained with su]famethylthiazole administered b y mouth. A Tobey-Ayer test was performed just before the second mastoidectomy but was negative. Blood cultures t a k e n at this time from the right internal jugular vein and l e f t femoral vein simultaneously were both sterile. Following the second course of chemotherapy the improvement was rapid, and she was discharged on March 19, 19407 in good condition. CASE 16 (Chart 16 and Table I ) . - - T h i s 7-year-old girl, D. tI., first developed otitis media when 4 months of age. The l e f t ear seemed chiefly involved, and each w i n t e r there would be reeurrenees of pain and purulent drainage. About a month before admission she again com)lained of severe pain in her left ear and developed f e v e r which persisted and was r e m i t t e n t in type. Two weeks later v e r y severe frontal headache began and persisted, aud a week before admission projectile vomiting, marked drowsiness, f r e q u e n t shrill cry, a turning of her head and eyes to the right, and nystagmus developed and persisted. On admission on Feb. 22, 1940, all of the above-mentioned symptoms and signs were verified~ and in addition there was noted severe dehydration, emaciation, and anemia. The left ear canal was filled with foul pus, discharging through multiple perforations in a g r e a t l y thickened drum. There were no external signs o f mastoiditis. The r i g h t drum was also thick and gray, with a small d W perforation anteriorly. There was a slight, but definite, left facial paralysis. The original impression of Dr. A l f r e d Schwartz, who a d m i t t e d her, was t h a t she had left mastoiditis with probably a left eerebellar abscess, localized meningitis and possibly lateral sinus thrombosis, all of which later were found to be present. A diagnostic lumbar puncture revealed ground-glass appearing fluid containing approximately 1j0O0 cells but proving to be sterile on culture. The Tobey-Ayer test was f r a n k l y positive on the left. Dehydration was quickly relieved by fluid administration, and chemotherapy was started with i n t r a v e n o u s l y administered sodium sulfamethylthiazole. X-ray revealed complete obliteration of the eellular structures

HARTMANN ET AL. :

SEVERE INFECTIONS I N INFANTS AND CHILDREN

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460

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There was an area about the size of a dime where the bone overlying the sinus was gone. ]~o normal-looking dura or sinus could be found, and in clearing out T r o u t m a n ' s triangle, a hole through the dura was encountered, through which about two ounces of foul greenish pus gushed. Bacillus proteus was cultured from 9

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the mastoid pus and Bacillus aerogenes from the brain abscess. Following this operation and with continued sulfamethylthiazole administration and supportive therapy~ gradual improvement followed. Some mental obtuseness and abnormal behavior continued, however, and on Ziarch 14 bilateral papilledema was noted. Daily lumbar punctures were t h e n made w i t h diminution and then complete disappearance of the papilledema. Chemotherapy was discontinued on March 22. Shortly a f t e r w a r d headache and papi]ledema recurred, and because of these findings and the persistence of some increase in spinal fluid cell count~ a re-

HARTMANN ET AL. :

SEVERE INFECTIONS IN INFANTS AND CHILDREN

461

exploration of t h e mastoid was done on )/[arch 30. Some tissue t h o u g h t to be sinus, which was yellow and softer t h a n the surrounding dura, was removed and found to be necrotic b r a i n tissue. Two days later, because of increase i n spinal fluid cell count to approximately 2,000, chemotherapy was resumed, this time w i t h sulfapyrldine. Althougl~ the spinal fluid a g a i n proved to b e sterile and the cell count a g a i n dropped, t h e p a t i e n t became more and more stuporous and w i t h increasing papilledema a n d soon h a d to be g i v e n fluid b y the continuous intravenous i n j e c t i o n method. Some eerebellar he~.'iation developed, and f r e q u e n t l u m b a r p u n c t u r e s were again made to reduce pressure. On A p r i l 17 a pneumoencepha]ogram showed m a r k e d i n t e r n a l hydrocephalus. D a i l y l u m b a r punctures were continued and on M a y 21 d i a t h e r m y was used to reduce t h e herniation, and g r a d u a l l y the wound could be closed. The p a t i e n t was d i s c h a r g e d from t h e hosp i t a l on J u l y 5 and r e t u n f e d to school the n e x t fall, a n d w h e n examined on Oct. 29, 1940, seemed p e r f e c t l y well. CASE 17 (Chart 17 and Table I ) . - - T h i s 6-year-old glrl, R. 1~I. P., became ill on Sept. 4, 1940, w i t h w h a t was p r o b a b l y acute b a c i l l a r y dysentery. She was v e r y ill w i t h this i n f e c t i o n which was complicated b y the development of a generalized upper r e s p i r a t o r y i n f e c t i o n on Sept. 23. Three days l a t e r the l e f t eardrum ruptured spontaneously. She coughed considerably, ate v e r y poorly, continued to have diarrhea, lost much w e i g h t and strength, and finally became stuporous. During the t w e n t y - f o u r hours prior to admission on Oct. 3, she received 3 Gin. of su]fathiazole. On admission she was f o u n d to be stuporous, dehydrated, acidotic, severely malnourished, and anemic, with cheilitis, stomatitis, tonsillitis, pansiffusitis, bilateral p u r u l e n t otitis media, b i l a t e r a l mastoiditis of the coalescent type, bronchopneumonia, a n d large subcutaneous abscesses. The l a t t e r c o n t a i n e d staphylococcus pus a n d originated a t the sites of subcutaneous fluid g i v e n more t h a n a week before admission to the hospital. The acidosis a n d d e h y d r a t i o n were immediately relieved by a d m i n i s t r a t i o n of ~ 5/L* sodium r-lactate a n d l a c t a t e - R i n g e r ' s and dextrose solutions~ a n d the anemia b y whole c i t r a t e d blood transfusions. Chemot h e r a p y was s t a r t e d i m m e d i a t e l y w i t h sulfathlazole in a dosage of slightly more t h a n 0.25 Gm. p e r kilogram p e r t w e n t y - f o u r hours. On Oct. 8, the sixth day of sulfonamide t h e r a p y , t h e Tobey-Ayer t e s t was f o u n d positive on t h e ]eft, and on the following d a y the l e f t j u g u l a r vein was ligated in the neck b y Dr. A. J. Cone, a left simple m a s t o l d e c t o m y performed, w i t h necrotic pus-tilled cells b e i n g found, and the lateral sinus which was found discolored was incised. Bacillus proteus grew from the mastoid culture. Sulfapyridine was t h e n s u b s t i t u t e d for sulfathiazole a f t e r considerable postoperative t e m p e r a t u r e rise, following which the temperature fell almost to normal. On Oct. 16, the f o u r t e e n t h day of sulfonamide treatment, a r i g h t simple mastoideetomy was done, cells b e i n g f o u n d necrotic b u t sterile on culture. A f t e r this the t e m p e r a t u r e remained n o r m a l a n d the p a t i e n t g r a d u a l l y improved w i t h the aid of repeated a d m i n i s t r a t i o n of whole e i t r a t e d blood a n d of dextrose a n d l a c t a t e - R i n g e r ' s solution, a n d v i t a m i n s , especially of the B complex. On Oct. 18 a severe convulsion occurred w h i c h b e g a n on the left side a n d spread to the right. The following day a right-sided hemiparesis was noted which s u b s e q u e n t l y gradually improved. On Dec. 19 pus was aspirated from b o t h m a x i l l a r y a n t r a , and the sinuses l a t e r were ~rrigated b y way o2 treatm e n t u n t i l the w a s h i n g s r e t u r n e d clear. On Feb. 2, 1941, a severe convulsion occurred which began on the right side and later spread to the ]eft. The spinal fluid a t t h a t time was normal. Au electroencephalogram made a m o n t h l a t e r suggested a lesion in the l e f t tempero-occipital region. Convulsions recurred a t a p p r o x i m a t e l y b i w e e k l y intervals. On 1Y~arch 13, a pncumoencephalogram *Molar.

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s h o w e d c h a n g e s s u g g e s t i v e of a d e g e n e r a t i v e lesion in the p o s t e r i o r p a r t of the l e f t c e r e b r a l h e m i s p h e r e . At no time w a s definite p a p i l l e d e m a noted. CASE 18 (Chart 18 and Table I ) . - - T h i s 25-month old girl, G. E., when 9 m o n t h s of age, developed otitis media in one ear, which one was not remembered b y the m o t h e r , w i t h d r a i n a g e l a s t i n g f o r t h r e e m o n t h s . F i v e days b e f o r e a d m i s s i o n to b.

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the h o s p i t a l she developed p a i n in h e r l e f t ear, a n d two days l a t e r s p o n t a n e o u s r u p t u r e of t h e l e f t d r u m occurred. The f o l l o w i n g d a y some s w e l l i n g b e h i n d the ear w a s noted, a n d the t e m p e r a t u r e r e a c h e d 104 ~ P. On a d m i s s i o n oi1 Nov. 26, 1937, p u r u l e n t otitis m e d i a on the l e f t w a s f o u n d , c u l t u r e f r o m the p u s s h o w i n g S t a p h y l o c o c c u s auzeus. There were also tenderness and swelling over the mastoid.

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SEVERE INFECTIONS IN INFANTS AND CHILDREN

463

On x-ray the cellular structures were found hazy. On Nov. 28, mastoidectomy was done by Dr. L. W. Dean, Jr., and pus under pressure was noted in the ceils, the culture of which showed a large gram-positive coccus, and a sing]e colony of a green streptococcus. The sinus plate seemed normal and was ]eft. The next day a catheterized specimen of urine contained a few ]eucoc2~tes but contained Bacillus coli and Staph. au~'eus on culture. Sulfanilamide therapy was begun at this time. No i m p r o v e m e n t followed the operation or the institution of chemotherapy. On Nov. 30 signs of pneumonia were noted in tl~:h right ldwer lobe. Some cervical adenitis developed. The Tobey~Ayer tests continued to be negative w i t h normal spinal fluid findings. Otitis media developed on the right side, and on Dec. 7 myringotomy revealed pus from which gn unidentified pneumoeoccus was growu. Oa Dee. 9 the left mastoid was reopened, the sinus plate removed, aud the sinus fonnd white, thickened, and covered with a thick pyogenie m e m b r a n e from the bulb to the knee. I t was still compressible. The jugular vein was then ligated :in the neck, and t h e n the lateral sinus was incised through the worst looldng portion. The picture of sepsis continued, and on Dec. 10 a swelling of the soft tissue of the r i g h t thigh was noted which, the following day, was seen to contain gas on x-ray examination. Twenty cubic centimeters of polyvalent gas gangrene antitoxin were t h e n given intramuscularly. On Dec. 13 the thigh was drained, and a large abscess pocket was found extending alosg the femur. From this pus, Dr. Louis Juliane]le isolated an anaerobic hemolytic streptococcus, an unidentified gram-negative gas-producing bacillus, and a nomnannite f e r m e n t i n g staphylococcus. Death occurred on Dee. 15, on which day a staphylococcus was grown from the blood, the first positive blood culture. At autopsy ~ hemolytic Staph. a ~ ' s u s was grown from the heart~s blood, mastoid and thigh. A thrombus was found in the lower branch of the right pulmonary artery with infarction of the right lower lobe. Embolic abscesses were seen in both kidneys. Permission was not granted for examination of the brain. CASE 19 (Chart 19 and TaMe I ) . - - T h ] s 7-year old boy, g. I., developed pain in his ]eft ear on Dec. 7, :[937, during the course of an upper respiratory infection. The earache had barely subsided when, on Dee. 13, he developed measles. On Dec. 19, a f t e r recurrence of pain, the l e f t drum ruptured spontaneously. Ite was adm i t t e d to the hospital the following day where it was noted t h a t , in addition to purulent otitis media, there was cellulitis with much edema involving the face, neck, and scalp surrounding the affected ear. There was also evidence of acute pansinusitis. Cultures from the draining ear~ from the scalp infection, from the nasopharynx, and from the blood showed a streptococcus, which at first produced greenish colonies w i t h but slight hemolysis. L a t e r t h e organism from the blood and f r o m the lateral sinus seemed more typically a fl hemolytic streptococcus. On Dee. 22 signs of pneumonitis developed in the right lower lobe, and the scalp infection was drained. X-ray of the mastoid showed hazy, poorly defined trabeculae on the l e f t ; of the sinuses, complete opacity of the maxillary antra; and of the chest, questionable early bronchopnenmonia. Despite drainage of the scalp infection, sulfanilamide administration, transfusions, and fluid administrations, the picture of sepsis continued and the blood cultures remained positive. On Dec. 26 the Tobey-Ayer test was found f r a n k l y positive on the left, and bilateral papilledema w i t h retinal hemorrhages was noted. The n e x t day the left internal jugular vein was ligated by Dr. Arthur iV[. Alden at the usual site in the neck. I t seemed normal. 3s was then done, and a coalescent type of mastoiditis was found. The lateral sinus was throrabosed over a considerable length and was incised until free bleeding was obtMned posteriorIy. No improvement followed this operation despite continued sulfanilamide administration and supportive t h e r a p y in the form of blood ~ransfuslons, dextrose and l a c t a t e - R i n g e r ' s

~c6~

~I~HE JOURNAL OF I'EDIATRICS

administration, and methylene blue, which was f r e q u e n t l y necessary to control methemogIobinemia. Blood cultures continued to be positive. On Jan. ], 1938, ulceration of the helix of the right auricle was noted, and the next day an abscess formed over the sacrum. A t this time purulent drainage was also noted coming f r o m the neck wound where the jugular vein was ligated. Central nervous system symptoms, including bilateral ankle c]onus, K e r ~ i g ' s signs, and nuchal r~gidity, lateral nystagmus, and diplopia t h e n developed and prompted diagnostic lumbar

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puncture. The spinal fluid was found normal, however. Prontosil was then administered in addition to sulfanilamide, but no improvement followed. On Jan. 6 the neck was reopened and the jugular vein, t o g e t h e r w i t h some enlarged glands, was excised from the point of ligation to the angle of the jaw. A small undrained pocket of pus was f o u n d at the site of the ]igation. A f t e r this the p a t i e n t did even less well; the mastoid and neck wounds continued to drain profusely, and

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SEVERE INFECTIONS IN INFANTS AND CI-IILDREN

465

n u m e r o u s skin ulcers a p p e a r e d which showed no t e n d e n c y to heal. Swelling of t h e l e f t shoulder r e g l o a developed w i t h dilated superficial veins. L a t e r edema of the whole l e f t u p p e r e x t r e m i t y w a s noted~ a n d v e n o u s o b s t r u c t i o n was suspected. Considerable b l e e d i n g t h e n occurred, p a r t i c u l a r l y f r o m tile neck wound. Signs of p u l m o n a r y i n v o l v e m e n t continued, a n d on J a n . 26, s h o r t l y before death, thoracentesis yielded some 200 e.e. of dark, t h i n fluid f r o m w h i c h h e m o l y t i c streptococci grew. T h e s u l f a n i l a m i d e c o n t e n t of t h i s fluid was 40 rag. per 100 e.c. The s p i n a l fluid at t h i s t i m e was x a n t h o c h r o m i e but~:'~eontaine8 only 13 cells per cubic millimeter. On J a n . 20 1 c.e. of c i t r a t e d blood, c u l t u r e d i m m e d i a t e l y , showed 1,100 colonies. One-tenth of a cubic centimeter a f t e r twenty-four h o u r s ' incubation showed too m a n y colonies to count. On J a n . 26 the blood as d r a w n showed 2,900 colonies per cubic c e n t i m e t e r , a n d a f t e r t w e n t y - f o u r h o u r s ' i n c u b a t i o n , 2,400,000, despite a s u l f a n i l a m i d e c o n c e n t r a t i o n of 66.3 rag. per 100 c.e. At p o s t - m o r t e m Dr. It. 3s f o u n d (1) e x t e n s i o n of t h e infection of tt~e l e f t j u g u l a r v e i n into t h e a x i l l a r y vein, w i t h an occluding t h r o m b u s t h e r e ; (2) a n abscess of t h e r i g h t lower lobe of the lung, w i t h fibrinous p l e u r i s y a n d bronchop n e u m o n i a of t h e r e m a i n d e r oti the lower lobe and of t h e middle lobe; (3) localized m e n i n g i t i s over t h e inferior s u r f a c e of the l e f t t e m p o r a l lobe, w i t h a d j a c e n t osteomyelitis of t h e t e m p o r a l bone; (4) n u m e r o u s s u b c u t a n e o u s abscesses; a n d (5) p u r u l e n t a r t h r i t i s of the l e f t s t e r n o c l a v i c u l a r a n d shoulder joints. F r o m the h e a r t ' s blood grew a s l i g h t l y h e m o l y t i c streptococcus. Temporal bone s t u d i e s m a d e b y one of us (D. W.) revealed the following: A mile] otitis m e d i a and m a s t o i d i t i s were f o u n d in t h e r i g h t ear upon microscoplc p o s t - m o r t e m e x a m i n a t i o n . A n a n a t o m i c v a r i a t i o n w a s observed in t h a t the mMleo-lncudal j o i n t a n d dr~m m e m b r a n e were r e l a t i v e l y inferior]y placed. I n the l e f t ear, w h i c h w a s the one operated upon, the surgical w o u n d was clean and f r e e f r o m pus. A v e r y delicate e m p y e m i c m e m b r a n e lined it and filled in the r e m a i n i n g p n e u m a t i c cells, t h e a d i t u s ad a n t r u m , and t h e posterior h a l f of the middle ear cavity. Malleo-ineudal joint lay embedded in this m e m b r a n e as did the posterior erus of t h e stapes. The h y p o t y m p a n i c cells were filled w i t h it. Alt h o u g h p r a c t i c a l l y no p u s cells were seen, it was e v i d e n t t h a t a~ active osteitis was still in progress at the time of death. The bony trabeeulae a t the upper level of t h e m a s t o i d were a b n o r m a l l y i r r e g u l a r in contour and n e w bo~le was b e i n g lald down. The bone b o r d e r i n g the cranial e a v l t y h a d j a g g e d edges in m a n y places. I n the region of the j u g u l a r bulb the bone h a d a m o t h - e a t e n appearance, and multiple fistulous p a t h s led toward the fossa in which a well-organized thrombus lay. The i n n e r ears on b o t h sides exhibited atrophle organs of Corti and v e s t i b u l a r e n d - o r g a n s of the t y p e of d e g e n e r a t i o n u s u a l l y seen in eachexia. I t is believed t h a t t h e chemical n a t u r e of the e n d o l y m p h becomes so a l t e r e d t h a t the end-organs p r a c t i c a l l y go into solution, b u t there is never a n y evidence of f r a g m e n t a t i o n of cells as in a u t o l y t i e d e g e n e r a t i o n . DISCUSSION

I. I n c i d e n c e . ~ A s in our previous cases, boys o u t n u m b e r e d tile girls, and the period of highest incidence was f r o m 5 to 9 years of age. The absence of cases in 1941 coincides with a marked reduction in the ineidence of operated mastoids, which in t u r n seems p r o b a b l y due to the more w i d e s p r e a d use of sulfonamide d r u g s in the t r e a t m e n t of acute u p p e r r e s p i r a t o r y infections, and especially otitis media.

466

THE

J O U R N A L OF P E D I A T R I C S

H. Etiology.---As in all previous studies of the etiology of lateral sinus phlebitis, the hemolytic streptococcus was b y f a r the most frequently encountered organism, as m a y be noted f r o m Table I. There are a number of possible routes of extension to the lateral sinus f r o m an infection in the temporal bone. As Ruskin has said, " T h e t e m p o r a l bone lies in a venous b e d . " The superior lateral sinus borders the medial angle of the bone, following along the attachment of the tentorium. I t connects the cavernous sinus with the u p p e r e~td of the sigmoid sinus. The inferior petrosal descends f r o m the cavernous sinus t h r o u g h D o r e l l o ' s canal (in which also lies the sixth nerve) to join the j u g u l a r bulb. The cavernous sinus is f u r t h e r linked with the jugular bulb b y the tortuous pericarotid venous plexus. A n y one or all of these venous channels are subject to vascular and direct extension from the ears. Fig. 1 illustrates vividly direct extension to the sigmoid sinus from infected mastoid cells in a ease of pneumococcus t y p e I I I infection. The p a t i e n t was hospitalized before sulfonamide drugs were developed. Following a simple mastoidectomy the patient suffered with headache for nine weeks. A t this time a second mastoidectomy was done. Postm o r t e m examination of serial sections of the temporal bone showed that the routes of extension i n t r a c r a n i a l w a r d were multiple. Not only this extension to the sinus occurred, but a p u r u l e n t labyrinthitis was present, angle cells showed erosion intraeranialward, and infection f r o m the E u s t a c h i a n tube had eroded into the carotid sheath. Fig. 2 illustrates a pathologic dehiscence into the j u g u l a r bulb region t h r o u g h the floor of the middle ear cavity. This was in a ease of Streptococcus he,~olyticus in a 4-year-old child. I-Iere again multiple routes of extension were present. Fig: 3 illustrates a thrombus in the pericarotid venous plexus. I n addition to this, abscesses f r o m the submucosa of the Eustachian tube were draining into the m a r r o w of the petrous apex. Pathologic routes similar to these could be traced microscopically in twelve cases studied post mortem by one of us (D. W.). F i v e of these were adults. All were postoperative patients except two. The extension oecurred at the operative site in five of the ten operated eases. A t operation the sinus a p p e a r e d normal in this region in three eases. Ligation of the j u g u l a r was done in three cases. The organisms found in these cases of lateral sinus thrombosis varied. F o u r were Streptococcus hemolyticus, three were pneumoeoeeus I I I , two were Bacillus influenzae, and three staphylocoecus. III. Diagnosis.~As in our previous eases, involvement of the sinus oeeurred within the first two months of otitis media in the great m a j o r i t y of eases (fifteen of nineteen). Of eonsiderable assistance in diagnosis was the fact that in nine eases p u r u l e n t otitis media was unilateral, and in only two instances bilateral. I n eight instanees both

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e a r d r u m s were f o u n d intact when first examined; in the m a j o r i t y of these, however, tile history of previous purulent drainage pointed correctly to the more seriously involved side. I n three eases tile subperiosteal t y p e of mastoiditis was present on the side of the phlebitis, and in twelve other eases, despite the absence of external evidence of mastoiditis, the x - r a y indicated correctly the presence of mastoiditis on at least one side. I n three eases there were neither external signs nor

:Fig. 1 . - - A d u l t m a l e , 37 y e a r s o f a g e . Vertical section through the mastoid of a pneumococeus type III otitis and meningitis. Note the direct extension from infected mastoid ceils to the thrombosed sigmoid sinus, lYIultiple r o u t e s o f e x t e n s i o n w e r e present in this case. Two mastoid operations were performed. The patient was hosp i t a l i z e d i n 1931 p r i o r t o t h e t i m e o f c h e m o t h e r a p y .

clear-cut x - r a y evidence of mastoiditis on either side, and in five eases it was eventually determined that the sinus was involved on the side opposite to that at first suspected f r o m the ear history and findings and the x-rays of the mastoids. I n these eases the Tobey-Ayer test was the d e t e r m i n i n g f a c t o r in the m a k i n g of the correct diagnosis. In fifteen of the nineteen eases this test was positive when first made, and in two other eases it beeame positive after an initial negative response. I n the other two cases it remained persistently negative,

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]~ig. 2.--2~ vertical section through the right temporal bone in a case of streptococcus otitis media and meningitis. Note the pathologic dehiscence from the floor of the infected middle ear cavity into the jugular fossa. This 4-year-old boy was sick only ten days. Multiple abscesses were found throughout the petrosa, even in the tensor tympani muscle.

]~Tig. Fig. 2. ence of tion in

3.--A section through the apex of the same streptococcus Here an infected thrombus is seen in the pericarotid venous blood in the internal carotid arterylgives evidence of some the arterial system.

case illustrated in plexus. The presvascular obstruc-

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E T AD. :

SEVERE I N F E C T I O N S

IN INFANTS

AND CHILDREN

~(J9

Anatomically the human lateral sinuses are subject to variations in size and course. Whether these variations are related to racial differences is not known. Statistics compiled in E u r o p e and in this count r y v a r y considerably. All agree that the right lateral sinus is more frequently larger than the left. W h e t h e r this bears any relationship to the greater f r e q u e n c y of otitis reported iK~the right ear is not known. Rudinger ~ (quoted from Piersol) found t h a t bilateral symmetry occurred in 3 per cent of his cases; tile left lateral'sinus was larger in 27 per cent of the eases, and the right lateral sinus was larger in 70 per cent of the cases. These statistics come f r o m central Europe. Woodhall ~ studied 100 eases at autopsy in Baltimore. He found bilateral symmetry in 48 per cent of the eases; the left lateral sinus was larger in 13 per cent of the cases; the right lateral sinus was larger in 39 per cent of the eases. Observations were made at fifty-nine autopsies in the Washington University Medical School by one of us (D. W.). I n this group, fifty-four belonged to the white race; five were Negroes. There were forty-two male and seventeen female individuals. Both races and both sexes felt in each classified group and with no demonstrable significance of distribution. Bilateral s y m m e t r y was obseryed in 27.1 per cent of the eases; the right lateral sinus was larger in 54.2 per cent of the eases, and the left was larger in 18.7 p e r cent of the eases. Numerous anomalies of the lateral sinuses have been reported in the literature. ~-~2 A v e r y large mastoid emissary vein m a y be present, e a r r y i n g most or all of the blood outside of t h e skull before it reaches the sigmoid portion of the lateral sinus. The blood front the horizontal portion may pass over the tegmen of the petrosa as a persistent petrosquamosal sinus and empty through the f o r a m e n spurium (normally present only in the young infant). (This f o r a m e n is f0und in adult monkeys and carries about one-third of the blood from the horizontal portion of the lateral sinus.) The blood m a y eontiIme more anteriorly and pass out of the skull through the foralaen spinosum. WoodhalP found anomalies of sufficient degree to alter readings in the Queekenstedt (Tobey-Ayer) test in 4 per c e n t of the cases. F o u r anomalies reported of congenital lack of a l a t e r a l sinus all occurred on the right side. This is interesting in view of t h e fact that the left lateral sinus is more f r e q u e n t l y smaller. Ersner a n d Myers stressed the necessity for x-rays of the jugular bulb regionr The importance especially of ruling out p n e u m o n i a as a cause for symptoms suspected of being due to lateral sinus involvement is well illustrated in Cases 20 and 21 (Charts 20 a n d 21) as is also the remarkable effect which sulfonamide treatment has o n the pneumonie proeess. Recently we had difficulty for a few days i n ruling out lateral sinus thrombosis in an i n f a n t 20 months of age w i t h a history of previous purulent otitis media, who later developed a n unexplained septic type of fever and on whom. a Tobey-Ayer test was f o u n d positive on the left

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side. A f t e r some forty-eight hours of incubation the blood culture grew out a Vi. strain of typhoid bacilli, and the course subsequently was typical of that of typhoid fever in an infant.

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HART1V[ANN

ET

AL. :

SEVERE

INFECTIONS

IN

INFANTS

AND

471

CHILDREN

it should certainly be repeated (under anesthesia if necessary), and all of the possible reasons for false-positive and false-negative results should be carefully considered. Even after such precautions are taken, one should expect occasionally both to fail to find thrombosis and to over-

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look its presence, especially if it is an incomplete or mural thrombus. W i t h the protection that snlfonamide chemotherapy affords, it would seem wiser to risk the former error rather than leave an infected vein undrained.

~72

THE JOURNAL OF PEDIATRICS

I n ten eases the initial blood culture was positive, in two more subsequent eultures became positive, while in the remaining seven eases cultures were negative, single cultures in two instances, and repeated cultures in two others; in one case there were three persistently negative cultures, and in the two others, four. The failure to find in every instance the classical signs of lateral sinus thrombosis, (1) external evidence of coalescent mastoiditis, (2) complete venous block on one side only, and (3) persistent baeteremia, which would make the recognition and localization of lateral sinus involvement easy, is not, in our opinion, to be a t t r i b u t e d to any great extent to a so-railed " m a s k i n g " effect of sulfonamides. We emphasized the eommonness of " m a s k e d " mastoiditis in our previous paper, arid in our present series, of the three eases without external evidence of mastoiditis and without eiear-eut x-ray findings, two patients (Cases 2 and 11) had not had previous chemotherapy, and in Case 7 the d r u g administered had been so small in amount and so shortly before admission as to be of doubtful significance f r o m this point of view. I n Cases 4, 5, 9, and 18, receiving chemotherapy in much the same manner, there was no unusual " m a s k i n g . " I f we all would but accept and remember the teachings of L . W . Dean, Sr., t h a t " e v e r y ease of otitis media is potentially a ease of mastoiditis, and every ease of mastoiditis is potentially a ease of lateral sinus phlebitis and one cannot always be certain of what m a y or m a y not be in a mastoid without operative inspection," made long before the discovery of the value of sulfonamide drugs, we would not r e g a r d too seriously a n y possible " m a s k i n g " effect of sulfonamide chemotherapy and would learn to diagnose types of mastoid involvement other t h a n the coalescent subperiosteal variety. IV. Pathologic Findings (At Operation or Post MortemO.--As in our previous eases, the pathologic changes in the mastoid varied f r o m the acute hemorrhagic type to the sclerotic not only in different subjects but in different parts of the same mastoid. I t should specially be noted t h a t f r o m the ten mastoids specifically cultured at the time of operation, organisms were recovered f r o m seven, despite usually sufficient chemot h e r a p y to abolish baeteremia. Much the same variation as previously noted in sinus pathology was also found, a n d f r o m eight cultures, organisms were grown in five, only two being associated with p o s i t i v e mastoid cultures. A similar situation was noted in the two fatal eases (18 and 19). Of the nine cases without positive cultures f r o m mastoid or sinus, no cultures were made in four, while in three others only one of the two sites was cultured. The persistence of viable organisms in the u n d r a i n e d necrotic mastoid cells and in the thrombosed sinus is in m a r k e d contrast to the r a p i d i t y with which baeteremia was abolished a f t e r institution of chemotherapy. I n the twelve eases with positive blood cultures, baeteremia was abolished preoperatively in all instances but two (Cases 7 and 19). I n another

HARTMANN

E T AL. :

SEVERE I N F E C T I O N S I N I N F A N T S A N D C t I I L D R E N

473

patient (Case 9) operated on the third day of chemotherapy, the blood culture became positive immediately following operatibn but was negative again the following day. I n ' t h e patient in Case 11 the spinal fluid had also become sterile before operation, as was true in all of our operated eases of hemolytic streptococcal meningitis, to be reported later. V. Clinical Courses Of Operated Cases a~d Results.--In our previous patients receiving no sulfonamide drug, the gro~s mortality rate was twenty-one of sixty, or 35 per cent, and with the exelusion of the unoperated eases and those moribund at the time of operation , it was 27.8 per cent. There was also a high incidence of metastatic infection not associated with a fatal outcome. In the present series of sulfonamide treated eases, there were two deaths and seventeen recoveries, a mortality rate of 10.5 per cent. ~" One of the fatalities (Case 18) was a mixed infeetion with gas gangrene, all the organisms involved apparently being unaffeeted by the one drug, sulfanilamide, then available. In the other fatality (Case 19) the streptococcal infection followed shortly after measles, and the patient apparently had unusually little resistance to it. Extension of the infected t h r o m b u s in the internal jugular vein continued to descend into the axillary vein and led to a persistent and very heavy blood stream infection. V e r y high concentrations of sulfanilamide (46 rag. per 100 e.c.) failed to sterilize the blood stream or to prevent continued multiplication or organisms in drawn blood. On the other hand, all the other cases had what was noted in twentytwo, or approximately only o~e-third, of the sixty earlier cases, namely, uneomplicated, quick, or only slightly delayed postoperative recoveries from the septic manifestations. Among them were one ease of generalized hemolytic streptococcal meningitis, one ease of sterile meningitis, one brain abscess which drained quite satisfactorily through the mastoid wound, two eases of arthritis (one definitely p u r u l e n t ) , and three cases of pneumonitis. Those patients showing slightly protracted courses (Cases 4, 7, 10, 12 and 15) were given either considerably less drug than we would now administer or had the drug administration discontinued too soon. SUMMARY The

addition

of sulfonamide

AND

CONCLUSIONS

chemotherapy

to the management

of

sepsis f r o m lateral sinus phlebitis during' the past five years has greatly *Since this paper was written, another patient was successfully treated with sulfadiazine, mastoidectomy, jugular vein ligation, and sinus incision. This girl, 3 i/~ years old, had bilateral purulent otitis media of two weeks' duration. No sulfonamide therapy had been given. She was found extremely septic on admission, with marked dehydration, anemia, enlargement of the liver and spleen, and blood culture positive for hemolytic streptococci. ]Both eardrums had sloughed away. There were no definite external signs of mastoiditis, but in association with cervical adenitis on the right side, there was purulent drainage through the external auditory canal with considerable hemorrhage. The x-rays indicated bilateral mastoid involvement, nlore on the right than the left. The Tobey-Ayer test was positive on the right. At operation, frank pus, without blood, was found in a white, compressible right lateral sinus, from which hemolytic streptococci were cultured.

474

WnE JOURNAL OF PEDIATRICS

improved treatment and has reduced the previous mortality rate of 28 to 35 per cent to approximately 10 per cent. Because of this, it should be added to the usual pre- and postoperative supportive measures, and, when properly administered and used in conjunction with proper ,)perative measures, should (1) quickly abolish bacteremia, (2) prevent metastatic infection, (3) prevent postoperative spread of infection, (4) and help to reduce practically to zero mortality ~rom hemolytic streptococcal lateral sinus phlcbitis. REFERENCES 1. /-Iartmann~ A. l~., and Cone~ A . J . : South. ~VL J. 30: 487~ t937. 2. Riidinger: Quoted from Piersol's Human Anatomy, Philadelphia, 1930, J. B. Lippineott Co, p. 869. 3. Woodhall, B.: Arch. Surg. 33: 297~ 1936. 4. Woodhall~/3, and Seeds, A.: Arch. Surg. 33: 867~ 1936. 5. Ersner, ~ . S , and Myers, D.: Laryngoscope 4:3: 800~ 1933. 6. Furstenberg~ A.: Laryngoscope 50: 950~ 1940. 7. Furstenberg, A.: Tr. Am. Acad. Ophth. & Otolaryng., p. 424, 1937. 8. Hildlng~ A.: Arch. 0tolaryng. 26: 143, 1937. 9. Itoople, G.D.: Ann. OtoL Rhin. & Laryng. 45: 1019~ 1930. 10. Laff, H.: Arch. Otolaryng. 11: 151~ 1930. 11. Williams, It. L , Jr.: Arch. OtoIaryng. 12: 339, 1930. 12. Williams, It. L , and I-Iallberg, O.: Arch. Oto]aryng. 33: 78, 1941.