Mortality Risk After Acute Severe Hyperkalemia

Patients with comorbidities such as chronic kidney disease or congestive heart failure commonly experience hyperkalemia. Severe hyperkalemia is associated with increased risk of adverse clinical events including ventricular arrhythmias and sudden cardiac death. Previous studies have focused on the prognostic implications of chronic hyperkalemia. However, according to José Luis Gorriz, MD, and colleagues there are few data available on the long-term clinical consequences following an episode of severe hyperkalemia.

The study was designed to examine the association between the trajectory of potassium  measurements in patients with acute hyperkalemia and long-term all-cause mortality. Results were reported online in Nephrology Dialysis Transplantation [doi:10.1093/ndt/gfab003]

The retrospective observational study included patients with acute severe hyperkalemia, defined as potassium >6 mEq/L, without hemolysis. Eligible study patients presented to the emergency department (ED) of Doctor Peset University Hospital in Valencia, Spain, from January 2016 to March 2017. Comprehensive state-of-the-art regression models that can accommodate time-dependent exposure modeling were used to assess the multivariable-adjusted association of serum potassium with mortality.

During a median follow-up period of 17.3 months, there were 172 episodes of acute hyperkalemia in 160 patients in the ED. Mean age of the patients was 77 years, 47% were >80 years of age, 59% had non-dialysis CKD (estimated glomerular filtration rate, <60 mL/min/1.73 m²), and 27.3% did not have renal dysfunction. Among the patients with CKD, the underlying cause of kidney disease was nephroangiosclerosis (28%), diabetic kidney disease (25%), interstitial disease (7%), glomerulonephritis (8%), polycystic kidney disease (3%), and other/unknown cause (29%).

Mean potassium level at presentation was 6.6 mEq/L; 76.7% of patients had potassium level between 6 and 7 mEq/L. Approximately one-quarter (23.3%) of the hyperkalemia episodes were life-threatening (potassium >7 mEq/L). Mean potassium level in the last measurement prior to the acute hyperkalemia episode was 4.8 mEq/L. Of the 160 patients, 72.7% (n=125) were hospitalized.

Most of the patients (84.3%) had one to four comorbidities, and 7.5% had more than four comorbidities. The most common comorbidities were CKD (71.2%), diabetes (56.9%), and hypertension (56.9%), followed by coronary heart disease (36.3%), congestive heart failure (35%), and cerebrovascular disease (12.5%).

In 107 episodes (67.7% of patients with electrocardiogram [ECG] reports in electronic health records), there were ECG alterations; of those, 44.9% presented at least one ECG alteration, primarily peaked T waves. Thirty-six percent of the patients were on chronic treatment with renin-angiotensin-aldosterone system inhibitors (RAASi), 28.5% were being treated with mineral receptor antagonists, and 53.4% received both treatments.

Only seven patients (4.1%) were receiving potassium-binding resins prior to the acute hyperkalemia episode; of those, three were receiving hemodialysis. Patients with better renal function were more likely to be treated with RAASi, loop-diuretics, and potassium-sparing diuretics.

Treatments for hyperkalemia received in the ED were dextrose fluid plus insulin (43%), intravenous (IV) loop diuretics (28.5%), inhaled salbutamol (26.7%), oral calcium polystyrene sulphonate (25%), IV sodium bicarbonate (25%), IV calcium gluconate (16.32%), hemodialysis (10.5%), and calcium polystyrene sulphonate enema (8.1%). Of the patients treated with hemodialysis, 61% had CKD stage 5 and were receiving dialysis prior to the acute hyperkalemia episode.

Potassium was measured at six time points: (1) prior to the severe hyperkalemia episode; (2) at the time of the episode; (3) at the time of discharge; (4) 30 days following discharge; (5) between 30 and 90 days following discharge; and (6) later than 90 days following discharge. The rates of hyperkalemia were higher in the ED and decreased throughout successive visits. Of the 786 potassium measurements at the different time points, 57.3% (n=451) were <5.5 mEq/L, 10.2% (n=80) were 5.5-6 mEq/L, 26.2% (n=206) were 6-7 mEq/L, and 6.4% (n=50) were >7 mEq/L.

Among the patients who were monitored during follow-up, 39.5% had recurrences of hyperkalemia (potassium >5.5mEq/L); 16% of those patients had one recurrence, 13.6% had two recurrences, and 9.9% had three recurrences. The recurrences occurred within the first month after discharge in 22.8%, between 30 and 60 days after discharge in 26.3%, and later than 90 days after discharge in 17.2% of patients with recurrences.

At the end of the median follow-up of 17.3 months, 42.5% (n=68) of the patients had died. Most of them died due to cardiovascular events (47.2%) or infection (23.5%). Other causes of death were liver-gastrointestinal (11.8%), malignancies (16.2%), and other (1.5%). Mean survival was 18 months; survival at 3, 6, 12, 18, and 24 months was 73%, 66%, 63%, 60%, and 55%, respectively.

Multivariate Cox proportional hazards models of death demonstrated that age, low serum sodium levels, absence of RAASi treatment before the episode of acute hyperkalemia, presence of ventricular tachycardia, and lack of routine laboratory follow-up after discharge were independent factors related to increased risk of mortality. For each year of age, the risk of mortality increased by 3%, RAASi treatment was associated with a 67% reduction in mortality risk, the presence of ventricular tachycardia was associated with a 12-fold increase in mortality risk, the performance of analytics at follow-up was associated with a 75% reduction in mortality risk, and each decrease of 1 mEq/L in serum sodium levels was related to an increase in the risk of death by 0.08%.

Previous potassium levels during an acute severe hyperkalemia episode were not predictors of mortality. Conversely, the post-discharge longitudinal trajectories of potassium were able to predict all-cause mortality (overall P=.0015). The effect of transitioning from hyperkalemia to normokalemia (potassium >5.5 mEq/L to potassium ≤5.5 mEq/L) following the acute episode was significant, and was inversely associated with the risk of mortality.

The researchers cited some limitations to the study findings, including the retrospective design that resulted in missing relevant clinical information, and the single-center design that possibly limits the generalizability of the findings to other centers.

In conclusion, the authors said, “Potassium levels prior to a severe hyperkalemia event do not predict mortality. Conversely, following an episode of acute severe hyperkalemia, serial kinetic of potassium trajectories predict the risk of death. Further evidence is needed to confirm these findings and clarify the optimal long-term management of these patients.”

Takeaway Points

1. Results of a retrospective observational study to assess the long-term trajectory of potassium and the risk of mortality in patients with acute severe hyperkalemia (potassium >6 mEq/L).
2. Following an episode of severe hyperkalemia, recurrent hyperkalemia was a frequent finding, particularly in the 6 months following discharge.
3. Post-discharge longitudinal trajectories of potassium were predictors of all-cause mortality. The effect of transitioning from hyperkalemia to normokalemia after the acute episode was significant, and inversely associated with mortality risk.