The main goal of this study was to investigate the causes of pediatric hypertensive crisis and the efficacy of drugs used to control it. We found that cancer and renal disease were the two common causes of hypertensive crisis as described in other studies [14, 15]. Our study also exhibited that there was no difference between nicardipine and labetalol in the treatment of hypertensive crisis, which differed from the result of an adult study that showed nicardipine to be more efficacious within 30 minutes than labetalol in patients with renal dysfunction [16]. However, Thomas et al. also reported no significant difference of efficacy between nicardipine and labetalol in infants and small children with a hypertensive crisis [17]. Particularly, we tried to compare the hypertensive emergency with hypertensive urgency in children.
Although hypertension is usually regarded as a disease of adulthood, with a prevalence of 30 % [18], it can also affect children and adolescents, traditionally with a prevalence of 1 %–2 %. However, recent studies have suggested that it has increased to over 3 %, with a much higher prevalence of 4.5 % in children with obesity [3, 19]. Severe childhood hypertension is associated with adulthood morbidity and mortality as a long-standing elevated blood pressure [14]. Ninety-day mortality rates were reported to be 11 % in patients who were hospitalized and treated in emergency circumstances [20]. These serious situations are related to acute end-organ damage and require immediate, controlled blood pressure reduction, and close observation. Without proper treatment, the 1-year mortality rate of hypertensive emergencies increases to 90 % [10]. However, there is no formal standard of treatment for severely elevated blood pressure in such emergency circumstances in children and adolescents with renal disease. Therefore, this study serves to demonstrate an optimal treatment option for hypertensive crisis patients with renal dysfunction, with results indicating that antihypertensive therapy should be tailored to each patient.
Nicardipine hydrochloride, approved by the Food and Drug Administration in December 1988, belongs to the class of dihydropyridine calcium channel blockers used to treat vascular disorders including high blood pressure, Raynaud’s phenomenon, and chronic stable angina [13], whereas labetalol is a mixed adrenergic antagonist that blocks α1-receptor and nonselective β receptor with an α:β blocking ratio of 1:7 [21]. The action mechanism of nicardipine and its clinical effects closely resemble those of nifedipine and the other dihydropyridines, such as felodipine and amlodipine; however, nicardipine is more selective for cerebral and coronary blood vessels [13]. Moreover, nicardipine does not intrinsically reduce myocardial contractility and has a longer half-life than nifedipine, as labetalol causes a decrease in systemic arterial blood pressure and systemic vascular resistance without a substantial reduction in resting heart rate, cardiac output, or stroke volume, apparently due to its combined α- and β-adrenergic blocking activity [22, 23].
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure declared that arterial blood pressure must be decreased by no more than 10 %–25 % during the first hour of treatment [24]. Both nicardipine and labetalol were found to decrease SBP by 14.6 % and 11.9 % within 1 hour in our study, respectively. DBP also decreased to 15.7 % of the initial DBP within 1 hour in nicardipine-treated patients, whereas patients with labetalol treatment had 14.2 % elevated blood pressure within 1 hour. These findings were thought to be generally caused by the fact that appropriate titration, redosing, and monitoring of labetalol were not easy in a busy emergency room, suggesting that more aggressive dosing of labetalol might be required for blood pressure response in patients with hypertensive emergency.
There is concern that iatrogenic effects such as hypotension and bradycardia can occur when using nicardipine and labetalol. Rapid blood pressure declines in nicardipine and labetalol patients were not observed, possibly owing to physician understanding and acknowledgment. In fact, reported adverse events including drowsiness, weakness, hyperkalemia, and drug eruption were uncommon in our study due to the short period of treatment. Both medications are metabolized by the liver; therefore, patients with renal impairment may be treated without profound complications.
We were not able to draw firm conclusions with regard to the comparative efficacy and safety of nicardipine vs. labetalol in children and adolescents with hypertensive crisis. As the data were insufficient for measuring long-term outcomes in patients experiencing hypertensive crises, further research is necessary in the near future. There is a possibility that some with hypertensive emergency may not have been ultimately diagnosed with acute end-organ damage due to a low SBP under 180 mmHg or a DBP under 120 mmHg. In the treatment of such patients without hypertensive emergency, oral antihypertensive medication may have been a reasonable option. It can be very challenging to collect data on children and adolescents with true hypertensive emergencies. Thus, the study population may not represent the patients to whom nicardipine and labetalol would most likely be prescribed. Additionally, ethnic differences between Asian, African, and Caucasian populations should be taken into account.
