Aust. N.Z. .I. Med. (1978), 8, pp. 180-183 CASE REPORT

Compartmental Shift of Potassium-A Sympathomimetic Overdose D. J. McCleave",

Result of

P.J. Phillipst and A. E. Vedigf

From the intensive Care Unit, Royal Adelaide Hospital and the Institute of Medical and Veterinary Science, Adelaide

SUI'nmary: Compartmental shift of potassium -A result of sympathomimetic overdose. D. J. McCleave, P. J. Phillips and A. E. Vedig, Aust. N.Z. J. Med., 1978, 8, pp.180-183.

A 17-year-old youth was admitted with a serum potassium concentration of 1 . 8 m m o l / l after taking an overdose of pseudoephedrine and choline theophyllinate. Apart from tach ycardia, tach ypnoea and ankle clonus, examination was normal as was the initial electrocardiograph. The h ypokalaemia resolved, but there was an overall positive potassium balance of only 13 mmol. This suggests that the sympathomimetics pro voked a compartmental shift of potassium perhaps indirectly by inducing hyperglycaemia and hyperinsulinaemia, as well as directly. Other factors known to affect body potassium distribution were excluded. The fact that features commonly associated w i t h hypokalaemia could not be demonstrated may be explained by a normal body potassium content. Severe hypokalaemia caused by a compartmental shift occurs with large doses of sympathomimetics as well as in periodic paralysis.

In many clinical situations the serum potassium concentration is misleading since it is poorly correlated with the total body potassium content.' The extracellular fluid potassium concentration is regulated predominantly by movements of potassium between the intracellular and extracellular compartments under *Staff Specialist, Intensive Care Unit, Royal Adelaide Hospital. tClinical Bio-Chemist, Division of Clinical Chemistry, Institute of Medical and Veterinary Science, Adelaide, SA. $Senior Registrar, Intensive Care Unit, Royal Adelaide Hospital. Present position: Staff Specialist, lntensive Care Unit, Department of Anaesthesia and Intensive Care, Flinders Medical Centre, Bedford Park, SA. Correspondence: Dr. D. J. McCleave, Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA 5000 Accepted for publication: 14 November, 1977

the influence of insulin2 and aldo~terone.~ Compartmental shifts of potassium also occur with exercise and anoxia4; as part of a diurnal rhythm5 ; with hypokalaemic periodic paralysis6; as a property of P,-adrenergic stimulation' ; with disorders of acid base' and sodium metabolism'; and extracorporeal haemoperfusion.'O Other factors, including amiloride, triamterine' ', possibly spironolactone" and digitalis derivatives' ', interfere with such shifts. We report a case where an overdose with sympathomimetic drugs was associated with severe hypokalaemia which appeared to be caused by a compartmental shift of p0tassiu.m. Case Report Presentation

A 17-year-old youth was admitted six hours after attempting suicide by consuming an overdose of an unknown quantity of pseudoephedrine and choline theophyllinate prescribed for mild asthma. There was no significant past or family history and in particular none of gastrointestinal, renal, endocrine or muscle disorders. On admission he was anxious, restless and warm with a respiratory rate of 24 per minute, sinus tachycardia of 130 per minute, supine blood pressure of 135/70, and rectal temperature of 35.3"C. The patient was co-operative and orientated, both pupils were widely dilated and reactive to light, and reflexes were brisk with clonus being demonstrable in both ankles. There were no other abnormal clinical findings. The electrolyte profile at 0300 by Technicon Autoanalyser Model SMA 6/60 showed serum potassium and glucose concentrations of 1 ' 9 and 17.6 mmol/l respectively (Table 1). The chest X-ray was normal and the electrocardiograph showed minimal changes (Fig. 1). Pro y r e ss

With electrocardiograph monitoring in the Intensive Care Unit, 27 mmol of potassium chloride were infused over the next four hours and urine fluid losses were replaced. During the next 24 hours a further 234 mmol of potassium chloride was given with 2 .5 litres of fluid (1 5 litres of distilled water orally and 1 litre of 4", dextrose in 0.18 mg/100 ml saline intravenously). Thereafter the patient consumed distilled water and a ward diet duplicate portions of which were analysed. Throughout the admission, potassium balance was carefully monitored (Fig. 2). The biochemical findings during the patient's 60 hour stay in Intensive Care are shown (Table 1, Fig, 3). Six hours

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1978

181

SYMPATHOMIMETIC OVERDOSE A N D POTASSIUM

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1

u

.

8,

I

1

I

u

I, u

Y

n*Lf-> *I SERUM POT*SWM M C W O Y CONCENTRATTKIYS

-C

FIGURE 3. Changes in serum potassium and glucose concentrations.

FIGURE 1.

Electrocardiograph on admission

after admission rectal temperature and reflexes became normal and the blood pressure and respiratory rate became stable at 120/65 mmHg and 13 per minute respectively. The pupils remained dilated and the tachycardia persisted for 18 hours after admission. Subsequent progress was uneventful apart from the occurrence, 24 hours after admission, of generalized muscle pains which were precipitated by movement and not associated with tenderness or weakness. These abated over the next 36 hours. After 60 hours the patient was transferred to a general ward and discharged two days later. The patient has refused further investigation. +bl

+74

+?b

+34

+I3

I

I

’’

7,-

r

FIGURE 2.

since the plasma aldosterone concentration was normal on admission (120 pg/ml), the changes in acid base status were in the wrong direction, and there were only minor changes in the serum sodium concentration. However, hypokalaemia without potassium depletion could have been caused by a compartmental shift of potassium mediated by insulin and due to the drugs ingested. This is supported by the inverse changes of the serum glucose and potassium concentrations (Fig. 3). Both drugs may have contributed to the hyperglycaemia and hyperinsulinaemia. These could occur through an adrenergic-like action of pseudoephedrine on adenyl cyclase and choline theophyllinate’s inhibition of phosphodiesterase which would increase hepatic CAMP concentrations, activate phosphorylase a, inhibit glycogen synthesis and increase hepatic glucose release.16* The drugs may also have produced hyperglycaemia indirectly since 8-adrenergic stimuli are known to potentiate glucagon release.’ The resultant hyperglycaemia combined with direct adrenergic effects’ could have produced the marked insulin response (serum insulin 116 pU/ml) and thus a shift of potassium, phosphate and magnesium into the intracellular space. Pseudoephedrine poisoning is associated with hyperglycaemia2’ and the administration of the P,-adrenergic agonist salbutamol increases serum glucose and decreases serum potassium concentration.”, ” Alpha and beta adrenergic blockade seemed a rational therapy, but was not used in view of the patient’s general well being and past history of asthma. Many features commonly associated with h y p ~ k a l a e m i acould ~~ not be demonstrated

n

,*ow$,

~ Buwcrs I ~ I” 12 W

R RRlODS

Potassium balance in 12 hour periods

Discussion

Despite the marked hypokalaemia on admission the patient was not potassium depleted since during his 60 hour stay there was a net positive balance of potassium of only 13 mmol. The unmeasured body potassium fluxes were those of sweat and those from depletion of protein (3 mmol of potassium/g of n i t r ~ g e n ) ’and ~ glycogen (1 mmol of potassium/g of glycogen).” Recognised factors influencing potassium distribution could be excluded in this case

182

MCCLEAVE ET

AL.

VOL.8, NO. 2

TABLE 1 Biochemical data- All values are from serum specimens except lactate and blood gases (arterial blood) ~

Reference range (mmol/l) Sodium Potassium Chloride Bicarbonate Urea Glucose Calcium Phosphate Magnesium Lactate’

137-145 3.84.9 98-106 24-32 3.0-8.0 4.4-6.4 2.20-2.55 0.80-1.35 0.7-0.9 0.7-1.8

Insulin (pUjml)

2-12 7.35-7.45 35-45

PH* PCO,* (mmHg)

~~~~

Time after admission (hours) 0

3

6

140 139 142 1.9 1.8 2.3 106 105 109 15 15 14 5.0 4.5 5.5 17-6 2 5 . 2 2 8 . 4 2.65 0.25 0.65 6

9

12

18

21

140 139 139 2.7 3.5 5.2 111 109 105 13 17 20 4 . 0 10.0 5.0 1 8 . 8 10.6 8.4 2.55 2 . 6 5 0 . 4 0 1 .0 0.90 8

116 96 45 7.33 7.33 7.50 28 28 27

24

30

33

39

42

54

137 139 138 138 136 138 6.5 5.6 5.0 4.3 4.2 4.2 106 105 104 103 103 102 19 19 20 21 24 26 6 . 0 , 5.5 5.0 5.0 5.5 6.0 6.6 5.4 6.4 5.6 6.0 4.0 2.80 2.60 1.15 1.35 0.85 0.85 1 .o 7.46 29

7.46 38

7.46 1.49 38 35

*Arterial blood.

in our patient. Serum creatinine concentration was normal (0.09 mmol/l) and while renal concentrating and acidifying ability and phosphate handling could not be tested in the acute situation, there was no evidence of a proximal tubular disorder since the amino acid excretion showed only a slight excess of lysine and urinary protein excretion was normal. Apart from the muscle pains which occurred when the hypokalaemia was resolving there was no clinical evidence of neuro-muscular disturbance. Serum creatine kinase activity was normal (1 10 U/litre) and myoglobin was not detected in the urine. The absence of electrocardiographic changes may be explained by the t a ~ h y c a r d i abut ~ ~may reflect a normal total body pota~sium.’~ Obviously, nitrogen utilization and glucose tolerance could not be investigated in this complex situation but there was a marked insulin response to the hyperglycaemia. Other biochemical and clinical features are of interest. The acid base status six hours after admission reflected a respiratory alkalosis (presumably due to stimulation of the respiratory centre by pseudoephedrine and a xanthine derivativei6*17) with a metabolic acidosis accounted for by an elevated arterial blood lactate concentration (presumably due to increased glycolysis secondary to hyperglycaemia and adrenergic effects on blood vessels26). Hypophosphataemia may reflect the effects of hyperglycaemia and insulinaemia and hypo-

capnea.” The initially low body temperature is explained by clinically evident skin vasodilatation due to the drugs. Hypokalaemia of the degree which occurred in this patient has not, to our knowledge, been described as being due to a compartmental shift, except in hypokalaemic periodic paralysis. The absence of classically described features of hypokalaemia may reflect the normal body potassium content. The case shows that the serum potassium concentration can be a grossly misleading indicator of the total body potassium content. Acknowledgements

The authors express their appreciation to Dr. R. C. Angove for permission to study the patient who was under his care in the Royal Adelaide Hospital, to Mr. M. Howley for technical assistance, and to Dr. A. Pollard of the Adelaide Children’s Hospital for the amino-acid analysis. References 1. SCRIBNER, El. H. and BURNELL, 1. M. (1956): Interpretation of the serum potassium concentration. Melobollsm 5, 468. 2. SANTEUSAN!~, F., FALOONA, G. R., KNOCHEL, J. P. and UNGAR,R. H. (1973): Evidence for a role of endogenous insulin and glucagon in the regulation of potassium homeostasis, 3. Lob. din. Med. 81, 809. N. G . and BERKELEY, P. (1968): An extra3. A ~E X A N D EE.RA,, , LEVINSKY, renal mechanism of potassium adaptation, 1.clin. Invesr. 47, 740. 4. DANOWSKI, T. S. and ELKINGTON, J . R. (1951): Exchanges of potassium related to organs and systems, Phormocol. Rev. 3, 42. 5 . ANDRES,R., CADER,G., GOLDMAN, P. and ZIERLER, K. L. (1957): Net potassium movement between muscle and plasma in man in the basal state and during the night, 3. clin. Invest. 36, 723. 6. ZIERLER, K. L. and ANDRES,R. (1957): Movement of potassium into skeletal muscle during spontaneous attack in familial periodic paralysis, 3. clln. Invest. 36, 730. 1. WANG,P. and CLAUSEN, T. (1976): Treatment of attacks in hyperkalaemic familial periodic paralysis by inhalation of salbutamol, Loncet 1, 221. 8. BURNELL,J . M., VILLAMIL, M. F., UYENO,B. T. and SCRIBNER, B. H. (1956): The effect in humans of extracellular pH change on the relationship between serum potassium concentration and intracellular potassium, 1. din. Invest. 35, 935. 9. MORENO, M., MURPHY,C., GOLDSMITH, C. and MORAN, H. (1969): Increase in serum potassium resulting from the administration of hypertonic mannitol and other solutions, 3. Lob. clin. Med. 73, 291.

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10. Y OK OW M A , M..FUKIKURA, 1.. YOKOYAMA, K. and SAKAKIBARA, S. (1972):

Transient hypopotassemia and ECG changes following hernodilution perfusion. Arch. Surg. 104, 640. 1 I . SACHS, J. R. and WELT,L. G. (1968): Concentration dependence of active potassium transport in the human red cell in the presence of inhibitors, J. elin. Invest. 47, 949. R. T. and BEHRLE, F. C. (1961): Use of spironolactone in renal 12. MANNING, edema-effectiveness and association with hyperkalemia, J . Amer. med. Ass. 176, 97. 13. ASTRUP,I. (1974): The effect of hypokalaemia and of digoxin therapy on red cell sodium and potassium content. Some clinical aspects. Scand. J. din. Lab. Invest. 33, 11. 14. GAMBLE, J. L., Ross, G. S. and TISDALL, F. F. (1923): Metabolism of fixed base during fasting, J. biol. Chem. 57, 633. IS. FENN.W. 0. (19391: The deoosition of ootassium and ohosohate . . with glycogen in rat live&. 3. bio/.'Chem. 128, i97. 16. INNES. I. R. and NICKERSON, M. (1970): Chapter 14 in: The Pharmacological Basis of Therapeutics, Goodman, L. S . and Gilman, A,, Macmillan, New York, p. 478. I. M. (1970): Chapter 19, ibid., 358. 17. RITCHIE, 18. GERICH,I. E., LORENZI,M.,TSALIKIAN, E. and KARAM, J. H. (1976): Studies on the mechanism of epinephrine induced hyperglycemia in man, Diabeles 25, 65.

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19. MASSARA,F., FASSIO, F., CAWNNI,F. and MOLINUTTI,G. M. (1975): Salbutamol-induced increase in plasma insulin in man, Horm. Mefab. Res. 1 , 94. 20. JARRETT, P. E. M. (1966): Franol poisoning, h n c e t ii, 1190. 21. LEITCH,A. G., CLANCY, L. J., COSTELLO, J. F. and FLENLEY,D. C. (1976): Effect of intravenous infusion of salbutamol on ventilatory response to carbon dioxide and hypoxia and on heart rate and plasma potassium in normal man, Brit. med. J. 1, 365. 22. JoNes, P. L., PHILLIPS, P.I., CHAPMAN, M.G., VEOIG,A. E. and EDWARDS, J. B. (1977): The metabolic effects of salbutamol, Proc. Endoc. SOC.Aust. 20, 49. 23. LINDEMAN, R. D.(1976): Hypokalemia,causes,consequencesandcorrection, Amer. J . Med. Sci. 212, 5 . 24. S u u w t c z , B. (1967): Relationship between electrocardiogram and elcctrolytes, Amer. Heart J. 73, 814. W. B., LZVINE, H. D. and RELMAN, A. S. (1954): The electro25. SCHWARTZ, cardiogram in potassium depletion: its relation t o the total potassium deficit and the serum concentration, Amer. J. Med. 16, 395. 26. KOLENDORF, K. and MOLLER,B. B. (1974): Lactic acidosis in epinephrine poisoning, A d a med. scand. 1%. 4-55. 27. KNOCHEL, I. P. (1977): The pathophysiology and clinical characteristics of severe hypophosphataemia, Arch. intern. Med. 131, 203.

Compartmental shift of potassium--a result of sympathomimetic overdose.

Aust. N.Z. .I. Med. (1978), 8, pp. 180-183 CASE REPORT Compartmental Shift of Potassium-A Sympathomimetic Overdose D. J. McCleave", Result of P.J...
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