Population characteristics

Seventy-four patients who received 102 fenoldopam infusions were included in the study. The population characteristics are presented in Table 1. Patients’ median age was 10 years (IQR 4–15 years) and 60% were male. Thirty-eight patients presented a previous kidney transplantation, and 20 patients were affected by a primary kidney disease. Eighty percent of patients had a pre-existing diagnosis of CKD, while 20% presented with AKI. In patients with CKD, 11 had an eGFR > 90 ml/min/1.73 m2, 2 had an eGFR between 60–89 ml/min/1.73 m2, 3 had an eGFR between 30–59 ml/min/1.73 m2, 5 had an eGFR between 15–29 ml/min/1.73 m2, and 53 (72%) patients exhibited kidney failure.

Table 1 Population characteristics at the start of fenoldopam infusion

Among patients with acute kidney dysfunction, 47% had stage I, 13% stage II and 40% stage III AKI. The etiology of AKI and CKD diseases are reported separately in Table 1.

Most of the patients (72%) were already receiving antihypertensive medications before their hospital admission. Within this group, 15% were treated with a single medication, 5% with two medications, and in 52% of patients more than two different antihypertensive drugs were prescribed, which were continued during fenoldopam infusion, unless needed for fasting. Forty-one percent of patients were treated with CNI. Eighty-three percent of patients experienced a systolic hypertensive crisis, while 17% had an isolated diastolic hypertensive crisis and 36% of patients exhibited both SBP and DBP that exceeded the 95th percentile by 30 mmHg for their age, height, and sex.

Fenoldopam infusion characteristics

Fenoldopam infusions were initiated for treating hypertensive urgencies in 86% of cases, and emergencies in 14% of cases (Table 2). Among hypertensive emergencies, neurological involvement was the most common presentation, affecting 65% of cases, while cardiac (7%), ocular (14%), and external bleeding (14%) were less frequent. Four out of the 9 patients with neurological involvement during a hypertensive emergency were also treated with anti-seizure medications. Following resolution of the epileptic crisis, all patients required continuation of the fenoldopam therapy due to persistent BP elevation, with one patient exceeding the 95th percentile for age, height, and sex, and the remaining three exceeding the 95th percentile by an additional 30 mmHg.

Table 2 Fenoldopam infusion characteristics and efficacy

Furthermore, at the onset of the infusion, 43% of cases presented with fluid overload which was treated in all cases with loop diuretics or hemodialysis in patients refractory to diuretics. The median duration of the fenoldopam infusion was 115 h (IQR 76–302 h). The median starting dose was 0.3 mcg/kg/min (IQR 0.2–0.5 mcg/kg/min) and the median maximum dose was 0.6 mcg/kg/min (IQR 0.4–1.4 mcg/kg/min). In 8 cases, the infusion duration was less than 24 h.

Fenoldopam efficacy

Fenoldopam was associated with a BP reduction (MAP, SBP and DBP) in all cases after 8 h of treatment, but in 87% of patients the MAP drop pressure after 8 h was higher than 25% of calculated drop pressure (Table 2). Normalization of MAP under the 95th percentile occurred in 26% and 35% of patients at 24 and 48 h, respectively. The median dose administered at these three time points was 0.3 mcg/kg/min (IQR 0.2–0.5 mg/kg/min), 0.4 mcg/kg/min (IQR 0.2–0.8 mg/kg/min) and 0.5 mcg/kg/min (IQR 0.3–1.0 mg/kg/min), respectively. MAP was normal in 77% of cases at the end of infusion.

MAP resulted in lower than the 95th percentile + 30 mmHg in 88% of cases at 8 h, 91% at 24 h, and 94% at 48 h. All hypertensive emergencies presented a resolution of symptoms within 8 h after the start of fenoldopam infusion. Neurological symptoms secondary to hypertension developed in only two cases during fenoldopam infusion (2%). No difference in terms of dose administered was observed in the first 8 h between hypertensive urgency and emergency (median fenoldopam dose of 0.3 (IQR 0.2–0.4) and 0.4 mcg/kg/min (IQR 0.2–0.5), respectively; p = 0.40).

In 14% of patients, fenoldopam was the only drug used to treat hypertension, 19% received one additional anti-hypertensive drug, and the remaining 67% were treated with two or more additional anti-hypertensive drugs. In 7 cases, a surgical treatment for hypertension resolution, such as kidney artery stenting or nephrectomy was required.

A maximal median dose of 0.8 mcg/kg/min (IQR 0.6–1.7 mcg/kg/min) of fenoldopam was administered in cases who required a surgical correction of hypertension, while the ones reaching a MAP less or higher than 95th percentile at the end of infusion received a maximal median dose of 0.7 (IQR 0.4–1.4 mcg/kg/min) and 0.35 mcg/kg/min (IQR 0.2–1.0 mcg/kg/min; p = 0.070), respectively (Fig. 1).

Fig. 1

Differences in maximal dose of fenoldopam administered for patients with a mean arterial pressure > 95th percentile, < 95th percentile and who required a surgical correction of hypertension at the end of infusion

The median duration of fenoldopam infusion to achieve BP normalization at the end of the infusion was 150 h (IQR 75–257 h). This duration did not significantly differ from that of patients who did not achieve BP normalization (median 144 h, IQR 90–300 h, p = 0.75), nor did it differ significantly from the time to surgical resolution of hypertensive crisis (median 346 h, IQR 137–515 h, p = 0.2). The percentage of patients who achieved BP normalization over time is presented in Fig. 2.

Fig. 2

Percentage of patients who achieved BP normalization over time

Comparison between patients with or without BP drop > 25% at 8 h

Differences in fenoldopam dosages between patients having a BP reduction (SBP, DBP, MAP) exceeding or not the 25% of calculated drop after 8 h of infusion are presented in Table 3. Distribution of cases showing a MAP reduction exceeding or falling under the 25% of the target BP after 8 h of treatment, according to the administered fenoldopam dose, is presented in Fig. 3. Cases with a MAP reduction < 25% of calculated drop pressure received a lower median fenoldopam dose (0.2 mcg/kg/min; IQR 0.1–0.2) than patients having a MAP reduction > 25% of calculated drop pressure (0.4 mcg/kg/min; IQR 0.2–0.6; p = 0.002). The same results were obtained considering SBP and DBP (Fig. 4). A median fenoldopam dose not exceeding 0.2 mcg/kg/min at 8 h was associated with an acceptable reduction of MAP in 38% of cases. Conversely, higher dosages resulted in a MAP decrease exceeding 25% of the calculated target in 91% of patients (p < 0.001).

Table 3 Mean fenoldopam doses at 8, 24 and 48 h of infusion according to our study outcome measuresFig. 3

Distribution of cases that had a MAP reduction above or less than 25% of BP target according to fenoldopam dose after 8 h of treatment

Fig. 4

Differences in dose of fenoldopam administered for obtaining a DBP (left), SBP (right) and MAP (down) reduction exceeding or falling under the 25% of the target BP after 8 h. SBP: systolic blood pressure, DBP: dyastolic blood pressure, MAP: mean arterial pressure

Comparison between patients with or without BP < 95th at 24 and 48 h

Considering MAP normalization at 24 and 48 h of treatment, there were no differences in median fenoldopam doses between responders and non-responders (responders at 24 h 0.35 mcg/kg/min [IQR 0.2–0.5] vs. non-responders 0.4 mcg/kg/min [IQR 0.2–0.8], p = 0.150; responders at 48 h 0.5 mcg/kg/min [IQR 0.3–0.8] vs. non-responders 0.5 mcg/kg/min [IQR 0.3–1.1], p = 0.260). In multivariate analysis, no predictors of response to fenoldopam infusion were identified. The trend of both SBP and DBP SDS over time demonstrated a significant drop during the first 8 h of infusion, followed by a slower and progressive BP reduction until the end of infusion (Fig. 5).

Fig. 5

Standard deviation scores in systolic and diastolic blood pressure over time during the first 48 h of treatment with fenoldopam

Fenoldopam safety

Hypotension developed in 6% of fenoldopam infusions after a median time of 164 h (IQR 36–418). Median fenoldopam doses were not significantly different in patients who experienced or not hypotension (0.8 mcg/kg/min IQR 0.5–0.95 in hypotension group vs. 0.7 mcg/kg/min IQR 0.4–1.4, p = 0.420). The administration of additional drugs also did not differ significantly between these two groups (p = 0.62), as reported in Table 4.

Table 4 Distribution of additional hypotensive drugs in cases that presented or not hypotension

None of the patients with a MAP drop higher than 25% of calculated MAP reduction after 8 h of infusion presented symptoms of hypotension. Detailed drop of calculated MAP after 8 h was as follows: 46% of patients presented a reduction of 25–30%, 28% of cases of 30–35% and the remaining 13% presented a drop of 35–40%. Hypokalemia occurred in 13% of cases, 5% of patients presented nausea and 3% headache. No further adverse events were identified.