Electrocardiographic manifestations of severe hyperkalemia

Severe hyperkalemia is a hazardous condition that warrants urgent intervention. In critically ill patients, the electrocardiogram (ECG) can be the most immediately available diagnostic tool in identifying patients with potentially lethal hyperkalemia. Peaking of the T waves, the most widely appreciated ECG sign, is actually rarely a manifestation of life-threatening hyperkalemia. In this review, we provide several clinical-electrocardiographic manifestations that can help identify those patients with hyperkalemia who require prompt intervention.     

Life-threatening hyperkalemia in severe heart failure

The therapeutic course of patients with severe heart failure can be complicated by disturbances in potassium homeostasis. Although hypokalemia in more prevalent, hyperkalemia may occur. Among 730 consecutive patients admitted to the hospital because of heart failure, nine episodes of acute, life-threatening hyperkalemia (mean serum potassium level: 7.2 +/- 0.5 mEq/L) were diagnosed in six patients (0.8%) with severe chronic heart failure during maintenance oral potassium therapy and exacerbation of heart failure and/or after additional oral doses had been administered for correction of hypokalemia. Of nine hyperkalemic episodes observed, one was fatal, seven episodes were successfully treated, and one resolved spontaneously. Only one patient was receiving an angiotensin-converting enzyme inhibitor. An awareness of this complication and the clinical setting in which it is likely to occur could lead to earlier recognition and successful management.     

Mineralocorticoid unresponsiveness with severe neonatal hyponatremia and hyperkalemia

An infant with severe neonatal hyponatremia and hyperkalemia is described. Although marked elevations of urinary 17-hydroxycorticosteroids suggested an 18-dehydrogenase aldosterone biosynthetic defect, the infant proved to have mineralocorticoid unresponsiveness, or pseudohypoaldosteronism. Dietary sodium supplementation and ion exchange resin administration resulted in normalization of serum electrolytes and urinary 17-hydroxycorticosteroids. ACTH infusion produced natriuresis, suggesting the need for additional sodium supplementation during the stress of illness, with a resultant increase in ACTH secretion. Determinations of the relative amounts of urinary 18-hydroxy and aldosterone metabolites appear necessary for early definitive diagnosis of the disorder.     

Drug-induced hyperkalemia

After reviewing the available data on drug-induced hyperkalemia, we conclude that the situation has not improved since Lawson quantitatively documented the substantial risks of potassium chloride over a decade ago (90). As discussed, the risk of developing hyperkalemia in hospital remains at least at the range of 1 to 2% and can reach 10%, depending on the definition used (Table 2). Potassium chloride supplements and potassium-sparing diuretics remain the major culprits but they have been joined by a host of new actors, e.g., salt substitutes, beta-blockers, converting enzyme inhibitors, nonsteroidal antiinflammatory agents, and heparin, among others. Readily identifiable risk factors (other than drugs) for developing hyperkalemia are well-known but seem to be consistently ignored, even in teaching hospitals. The presence of diabetes mellitus, renal insufficiency, hypoaldosteronism, and age greater than 60 years results in a substantial increase in the risk of hyperkalemia from the use of any of the drugs we have reviewed. If prevention of hyperkalemia is the goal, as it should be, the current widespread and indiscriminate use of potassium supplements and potassium-sparing diuretics will need to end. We remain intrigued by Burchell's prescient pronouncement of over a decade ago that "more lives have been lost than saved by potassium therapy" (28).     

Heparin-induced hyperkalemia

An 85-year-old lady with type 2 diabetes mellitus of 32 years duration with peripheral neuropathy was admitted under the vascular surgeons with extensive gangrene of her lower limb. She was on insulin for the last 7 years. Initial investigations showed normal serum electrolytes. She was started on antibiotics and unfractionated heparin, and her electrolytes showed hyperkalemia, which persisted on active treatment. Her short synacthen test showed good response, renin was normal with low aldosterone, urinary pH, sodium, potassium and osmolality was normal. On stopping heparin serum, potassium became normal. On restarting heparin (low molecular weight) during a suspected episode of pulmonary embolism, she developed hyperkalemia and heparin was stopped. Her potassium and aldosterone became normal on discontinuation of heparin. She developed hyperkalemia with both unfractionated and low molecular weight heparin.     

Heparin-induced hyperkalemia

Heparin sodium is routinely used in the prophylaxis against deep venous thrombosis in medical and surgical patients. While most physicians are aware of heparin-induced thrombocytopenia and skin necrosis, the association of heparin and hyperkalemia is less well recognized. We present four cases in which the use of heparin was associated with hyperkalemia and discuss the pathophysiology. Our findings suggest that hyperkalemia can develop with the use of low-dose heparin, within seven days of initiating heparin therapy, and that patients with diabetes mellitus or chronic renal insufficiency are especially predisposed to this complication.     

Pentamidine-induced acute pancreatitis in a patient with AIDS.

We report pentamidine-induced acute pancreatitis in a patient with the acquired immunodeficiency syndrome (AIDS). The course of this pancreatitis was prolonged but favorable. Pentamidine was detected in serum as late as one month after discontinuation of therapy. The special pharmacokinetics of this drug may account for the potential severity of pentamidine-induced acute pancreatitis.     

Pentamidine-induced beta cell toxicity is not preventable by high glucose

The incidence of beta cell damage attributable to pentamidine treatment of pneumocystis pneumonia is increasing in frequency because of the AIDS epidemic. We carried out in vitro studies in perfused rat islets using insulin secretion as an index of beta cell damage to study the effects of pentamidine and to test whether glucose can prevent toxicity in this physiologic model. Isolated islets were cultured for 16-18 hours of static incubation, in a culture medium containing 100 mg/dl glucose, with or without pentamidine (10(-6) M, a therapeutic concentration). Islets were then perfused with media containing 60 mg/dl followed by 300 mg/dl glucose concentrations to study the insulin secretory response. Incubation of islets with pentamidine was associated with subsequent basal hypersecretion of insulin (0.40 +/- 0.05 microU/islet .5 minute vs. 0.18 +/- 0.04 microU/islet .5 minute, p less than .005), and an insulin secretory response to glucose which was completely abolished (0.05 +/- 0.04 microU/islet .5 minute versus 1.12 +/- 0.02 microU/islet .5 minute, p less than .005). To determine whether glucose may protect against the effects of pentamidine, islets were then exposed to high glucose concentrations during simultaneous incubation with pentamidine. Coincubation with high glucose did not prevent these insulin secretory defects. A more extended culture of pentamidine-treated islets in the absence of pentamidine and at a glucose concentration of 100 mg/dl did not result in any recovery of insulin secretion. We conclude that pentamidine-induced beta cell damage is irreversible, not preventable by incubation with high glucose concentrations, and may therefore result from a mechanism different to that of alloxan.