Although hypokalemia has been reported after cardiac arrest and successful resuscitation, experimental data indicate that potassium is released from cells during ischemia. The purpose of this investigation was to study serum potassium concentration ([K+]) during closed chest cardiopulmonary resuscitation (CC-CPR) in humans. Twenty-two patients presenting to the emergency department (ED) in cardiopulmonary arrest had simultaneous measurement of central venous and arterial [K+] and blood gases during CC-CPR utilizing current advanced cardiac life support protocols and a pneumatic chest compressor and ventilator. Mean arterial and central venous [K+] were 5.0 +/- 1.3 and 5.6 +/- 2.9 mEq/L, respectively, (p greater than .05) with 7 patients having [K+] of greater than 6 mEq/L. Significant hyperkalemia does occur in some patients during cardiac arrest and CC-CPR. Because poor tissue perfusion during CC-CPR impairs exchange between the interstitial and intravascular compartments, increases in interstitial [K+] would be expected to be even greater. Interstitial hyperkalemia may play a role in the genesis of wide complex electromechanical dissociation (EMD) seen after prolonged cardiac arrest. Since calcium has long been known to be beneficial in the treatment of hyperkalemia-induced dysrhythmias, the success of calcium chloride in treating wide complex EMD may be on the basis of this phenomenon.