EMERGENCY CASE REPORT

Alcoholic Ketoacidosis in a Pregnant Woman

John R. Lumpkin, MD Frank J. Baker, II, MD

Jacek B. Franaszek, MD Chicago, Illinois

A case of alcoholic ketoacidosis in a 23-year-old chronic alcoholic, gravada V, para IV, is reported. Symptoms were constant, severe, nonradiating pain with crampy exacerbations, anorexia, nausea and vomiting. The patient had a tender and irritable full-term uterus. She was treated inhospital with vigorous fluid therapy and 5% dextrose in normal saline, sodium bicarbonate, glucose and insulin and showed improvement overnight. Alcoholic ketoacidosis has not been reported in pregnant women. Metabolic derangements combine to pro- duce ketoacidosis more readily in the pregnant alcoholic. Differentiation of al- coholic ketoacidosis and diabetic ketoacidosis is important since treatment var- ies. For alcoholic ketoacidosis, treatment is vigorous rehydration with dextrose-saline while diabetic ketoacidosis usually requires multiple therapeutic modalities. Lumpkin JR, Baker FJ II, Franaszek JB: Alcohol ic ketoacidosis in a pregnant woman. JACEP 8:21-23, January, 1979. ketoacidosis, alcoholism, pregnancy; pregnancy, alcoholic ketoacidosis.

INTRODUCTION

The complicat ions of alcoholism are well known, but l i t t le has been wr i t t en about the problems of alcoholism in pregnancy. Recent ar t ic les have presented a number of cases of the fetal alcohol syndrome ~,~ and others have discussed the effects of ma te rna l malnu t r i t ion , common in alcoholics, on the fetus and fetal development.3, 4 There have also been reports of ma te rna l morbid i ty associated with t r a u m a dur ing intoxicat ion. 5

Wi th the e luc ida t ion of me tabo l i c p rob lems in alcoholics has come an awareness of the i r cl inical d iagnosis and t rea tment . One specific complicat ion recent ly repor ted is alcoholic ketoacidosis2 -9 We presen t a documented case of alcoholic ketoacidosis in a p regnan t woman. We have not found a s imi la r case repor ted in the l i te ra ture .

CASE REPORT

A 23-year-old woman, g r a va da V, pa r a IV, in her 38th week of gestat ion, came to the emergency d e p a r t m e n t complain ing of lower back and abdominal pain tha t began the previous evening after she fell a shor t distance. The non- r ad ia t ing pa in was cons tant and severe, wi th crampy exacerbat ions occurring every five to t en minu tes and l as t ing three to four minutes . There were no exacerba t ing or amel io ra t ing factors. The pa t i en t complained of two days of anorexia , nausea and vomit ing. She denied d iar rhea , constipat ion, hematemes i s or melena. There was u r i na ry frequency bu t no dysur ia , urgency, hematur ia ,

From the Division of Emergency Medicine, University of Chicago Hospitals and Clinics, Chicago, illinois.

Address for reprints: John R. Lumpkin, MD, University of Chicago Hospitals and Clinics, 950 East 59th Street - - Box #448, Chicago, Illinois 60637.

8:1 (January) 1979 JACEP 21/35

n o c t u r i a , p o l y d i p s i a , or v a g i n a l b leeding or discharge.

The pa t i en t was not known to be a diabet ic but t hough t t ha t an uncle h a d d i a b e t e s . She a d m i t t e d to chron ic a lcohol a b u s e w i t h h e a v y e t h a n o l c o n s u m p t i o n d u r i n g the week p r i o r to h e r admiss ion . She had stopped d r i n k i n g the day before the fal l because of nausea . Dur ing a hospi ta l iza t ion th ree yea r s ago, she had been told t h a t she had cirrhosis. The p a t i e n t ' s only med ic ines were p rena ta l v i t amins and iron.

On p h y s i c a l e x a m i n a t i o n , the p a t i e n t w a s we l l d e v e l o p e d , we l l nou r i shed b u t l e tha rg ic , appea r ing older t h a n he r s t a t ed age of 23. A dis t inct ive odor of acetone was pres- en t on h e r b r e a t h . Blood p re s su re was 150/90 m m Hg. There was no or- thos ta t ic change. Her pulse rate was 96 /minu te , t e m p e r a t u r e was 37 C (98.6 F). Respi ra t ions were 40/min- ute and K u s s m a u l in character . The lungs were clear and the cardiovas- cu lar sys tem appeared normal. There was t enderness in the lumbar para - sp inous muscles , bu t t he re was no v e r t e b r a l or c o s t o v e r t e b r a l a n g l e tenderness . The abdomen was ovoid, n o n t e n d e r , w i t h n o r m a l bowe l sounds, and no hepa tosp lenomegaly was p r e s e n t . She h a d a f u l l - t e r m u te rus tha t was t ende r and i r r i table . The fetal h e a r t r a te was 130/minute. The cervix was closed and noneffaced on pe lv i c e x a m i n a t i o n . The ex- t remi t ies were free of edema and the neu ro log i ca l e x a m i n a t i o n r e v e a l e d diffuse hyperref lexia .

D e x t r o s t i x r e a d i n g was 90 rag/100 ml. Ar t e r i a l blood gases re- vea led a pO2 of 117 mm Hg; pCO~, 14 m m Hg, a n d pH, 7.15. U r i n a l y s i s showed 4+ ke tones but was negat ive for protein and glucose. Other perti- n e n t l a b o r a t o r y v a l u e s i n c l u d e d s e r u m g l u c o s e , 78 mg/100 ml; sodium, 136 mEq/ l i t e r ; po tas s ium, 4.8 m E q / l i t e r ; ch lo r ide , 102 mEq/ l i ter; b icarbonate , 5; blood u rea ni- t r ogen (BUN), 5 mg/100 ml; crea- t in ine level, 1.9; to ta l b i l i rubin , 1.4 mg/100 ml; se rum glutamic oxaloace- t ic t r a n s a m i n a s e (SGOT), 100 IU, and se rum g lu tamic pyruvic t rans- aminase (SGPT), 70 IU. Serum lac- t a te was 2 mEq/l i ter ; serum acetone, 4 + , and s e r u m a lcoho l zero. The complete blood cell count (CBC) was: whi te blood cell count (WBC) 10.4, r e d b lood ce l l c o u n t (RBC) 4.66, hemog lob in (Hgb) 14.9, hema toc r i t (Hct) 44.4. F lu id t he r apy wi th lac- t a ted Ringer ' s was star ted.

The eva lua t ion of the labora tory da ta revea led an anion gap of 33 and

a r t e r i a l blood gases compat ible wi th a metabol ic acidosis. The f inding of b o t h u r i n a r y a n d s e r u m a c e t o n e leads to the diagnosis of ketoacidosis. The combina t ion of ke toacidos is in the presence of a no rma l serum glu- cose in a pa t i en t wi th the his tory of h e a v y e t h a n o l i n t a k e m a k e s t h e d iagnosis alcohol ketoacidosis.

The pa t i en t was then admi t t ed by the obs te t r i ca l serv ice and was t r ea ted wi th vigorous fluid the rapy of 5% dextrose in normal saline wi th 20 mEq po tass ium chloride (KC1) per l i ter , a to ta l of 200 mEq of sodium bicarbonate and two separa te doses of 5 uni ts of r e gu l a r insulin.

By the following morning, blood gases and e lec t ro ly tes were wi th in normal l imits , her Kussmau l respi- r a t ions ceased, and the u t e r i n e ir- r i t ab i l i t y subsided. When the pa t i en t was s u b s e q u e n t l y d e l i v e r e d by c a e s a r i a n sec t ion , t he i n f a n t had p h y s i c a l f i n d i n g s c o n s i s t e n t w i t h fetal alcohol syndrome. 1,2

DISCUSSION Alcoholic ketoacidosis , a c l inical

en t i ty recen t ly ident i f ied and stud- ied, is seen f requent ly in our emer- gency depa r tmen t . As has been re- p o r t e d p r e v i o u s l y , 6-s i t occurs in chronic alcoholics who have had a re- cent large alcohol intake. Al though i t does occu r m o r e f r e q u e n t l y in w o m e n t h a n in m e n , s a l c o h o l i c ke toac idos i s h a s not been r epor t ed p r e v i o u s l y in p r e g n a n t w o m e n . Other ac idemias seen in pregnancy i n c l u d e d i a b e t i c k e t o a c i d o s i s , 1°,11 s t a r v a t i o n k e t o s i s , 12-14 and l ac t i c acidosis. 15 Al l have de t r imen ta l ef- fects on fetal survival . 16,~7

Normal ly , the body's in i t i a l re- sponse to fas t ing is to continue to use i ts glucose and glycogen stores. Fast- ing leads to increased levels of the h u m a n g rowth hormone, g lucagon, a n d e p i n e p h r i n e . These r e s p o n s e s promote glycolysis , gluconeogenesis a n d l i p o l y s i s . In t i m e , g l y c o g e n stores are deple ted and l ipids become the ma jo r metabo l ic pa thway . The shift to l ipolysis is responsible ibr the p r o d u c t i o n of t h e k e t o s i s s een in starvation.~S, TM The conversion from pr imary ca rbohydra te metabo l i sm to l ipid metabol i sm takes , on the aver- age, th ree to four days.

P r e g n a n t w o m e n e x h i b i t in- c reased c a r b o h y d r a t e use r e su l t i ng in ea r l i e r glycogen deplet ion and a s h i f t to l i p o l y s i s as t he p r i m a r y m e t a b o l i c p a t h w a y . 12,~3 The fe tus u se s g lucose as i t s sole source of energy34 This d~ain on carbohydra te stores has been t e rmed ~accelerated

s t a r v a t i o n ''13 and r e su l t s in lower f a s t i ng glucose leve ls in p r e g n a n t women . B e c a u s e of t he d e c r e a s e d glucose level , t h e r e is a ref lex in- crease in l ipolyt ic hormones, includ- ing glucagon, g rowth hormone and cortisol.

H u m a n chor ionic somato t rop in is produced in increas ing quant i t ies as the conceptus matures . Somato. t ropin wil l also increase t rans ien t ly in the f a s t ing or ma l nou r i shed pa- t ient . 12 H u m a n chorionic somatotro. p in is an i n s u l i n a n t a g o n i s t and s t i m u l a t e s lypo lys i s and gluconeo. genesis .12,2o

E t h a n o l a n d p r e g n a n c y have s imi la r effects on carbohydrate , lipid and pro te in metabol ism. The inhibi- t o r y e f fec t s of a l coho l on hepa t i c gluconeogenesis coupled with the de. p le ted hepa t ic glycogen stores seen in t h e c h r o n i c m a l n o u r i s h e d al- coholic combine to favor l ipolysis as the p r ima ry metabol ic pa thway. In addit ion, alcohol favors the produc- t ion of ke toacids by in ter fer ing with the product ion of n icot inamide-ade- n ine-dinucleot ide phosphate (NADP), shunt ing acetyl -CoA from the Krebs cycle in to the fo rma t ion of ketone bodies, p r imar i l y be ta hydroxy buty- ra te , r a the r t han acetoacetate. 2~,~2

We can logical ly assume tha t the me tabo l i c d e r a n g e m e n t s discussed above combine to produce ketoacido- sis more r ead i ly in the p regnan t al- coholic. It is i n t r igu ing tha t , while the ketogenic changes of pregnancy l ead to an i n c r e a s e d inc idence of diabet ic ketoacidosis, to our knowl- edge the re have been no previously r epo r t ed cases of ke toac idos is in a p r egnan t alcoholic. In our case, al- coholic ketoacidosis may have been u n m a s k e d by the severe l iver dis- e ase.

T h e o c c u r r e n c e of a lcohol ic ketoacidosis mus t be recognized and d i f f e r e n t i a t e d f rom d i a b e t i c keto- acidosis, s ince t r e a t m e n t is different. E a r l y de tec t ion and t r e a t m e n t are impor t an t in order to intercede in a process po ten t i a l ly damaging to the fetus. An e x a m i n a t i o n of the urine for both sugar and ketones wil l give t h e f i r s t c lue in a p a t i e n t with K u s s m a u l resp i ra t ions and acetone on the brea th . Ur ine tha t contains large amoun t of ketones but is nega t ive for glucose, in an alcoholic pa- t i e n t , is s u g g e s t i v e of a l coho l i c ketoacidosis. De te rmina t ions of arte- r i a l blood gases and blood glucose will confirm the diagnosis.

Alcoholic ketoacidosis is t reated w i t h v i g o r o u s r e h y d r a t i o n us ing dext rose-sa l ine solutions. It usually

36/22 JACEP 8:1 (January) 1979

resolves wi thou t other the rapeu t ic raodalities.7, s Potassium levels mus t be m a i n t a i n e d w i t h r e h y d r a t i o n . Small amounts of alkal i may be indi- cated in a few cases, s

A l t h o u g h i n s u l i n t h e r a p y has been t r i e d / it is unnecessary since the pr imary defect is hepatic and not related to i n s u l i n deficiency. Wi th fluid therapy alone, most symptoms and e l e c t r o l y t c i n b a l a n c e resolve within 12 to 48 hours.6, 7

In contrast , diabetic ketoacidosis usually requires mult iple therapeu- tic modal i t i es for successful t rea t - ment. The priori ty of t r e a tmen t in diabetic ketoacidosis is the use of fluids to t r ea t shock and dehydra- tion, and bicarbonate to t reat acido- sis. I n s u l i n and po tas s ium supple- ments are of crit ical importance to the pat ient ' s recovery.

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2. Ferrier PE, Nocod I, Ferrier S: Fetal alcohol syndrome. Lancet 2:1496, 1973.

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4. Churchill JA, Moghissi KS, Evans TN,

et al: Relationships of maternal amino acid blood levels to fetal development. Obstet Gynecol 121:456-459, 1975.

5. Jewett JF: Committee on maternal welfare. Alcoholism and ruptured uterus. N Engl J Med 294:335-336, 1976.

6. Isselbacher KJ: Metabolic effects of al- cohol. N Engl J Med 296:612-616, 1977.

7. Jenkin DW, Eckel RE, Crain JW: Al- coholic ketoacidosis. JAMA 217:177-183, 1971. 8. Levy L, Duga J, Girgis M, et al: Ketoacidosis associated with alcoholism in nondiabetic subjects. Ann Intern Med 78:213-219, 1973.

9. Peterson G: Alcoholism and ketoacido- sis. Ann Intern Med 78:983, 1973.

10. Tyson JE: Obstetrical management of the pregnant diabetic. Med Clin North Am 55:961-973, 1971.

11. Tyson JE, Felig P: Medical aspects of diabetes in pregnancy and the diabeto- genic effects of oral contraceptives. IVied Clin North Am 55:947-959, 1975.

12. Tyson JE, Austin KL, Farinholr JW: Prolonged nut r i t iona l deprivation in pregnancy: changes in human chorionic somatotropin and growth hormone secre- tion. Am J Obstet Gynecol 109:1080-1082, 1971.

13, Bleicher SJ, O'Sullivan JB, Freinkel N: Carbohydrate metabolism in preg- nancy. N Engl J Med 121:866-872, 1974.

14. Felig P, Lynch V: Starvation in human pregnancy: hypoglycemia, hypoin-

sulinemia, and hyperketonemia. Science 170:990-992, 1970.

15. Ott A, Hayes J, Pollin J: Severe lactic acidosis associated with intravenous al- cohol for premature labor, Obstet G ynecol 48:362-364, 1976.

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18. Felig P, Marliss E, Owen Ok, et al: Blood glucose and gluconeogenesis in fasting man. Arch Intern Med 123:293- 298, 1969.

19. Ruderman NB, Toews CJ, Shafrir E: Role of free fatty acids in glucose homeo- stasis. Arch Intern Med 123:299-313, 1969.

20. Grumbach MM, Kaplan SL, Sciarra JJ, et al: Chronic growth hormone- prolactin: secretion, disposition, biologic activity in man and postulated function as the "growth hormone" of the second half of pregnancy. Ann N Y Acad Sci 148:501-531, 1968.

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