Infusão de noradrenalina aumenta o débito urinário de crianças
                        recebendo drogas sedoanalgésicas

Piva, Jefferson; Alquati, Tamila; Garcia, Pedro Celiny; Fiori, Humberto; Einloft, Paulo; Bruno, Francisco

doi:10.1590/1806-9282.60.03.008

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Original Articles • Rev. Assoc. Med. Bras. 60 (3) • May-Jun 2014 • https://doi.org/10.1590/1806-9282.60.03.008 linkcopiar

Infusão de noradrenalina aumenta o débito urinário de crianças recebendo drogas sedoanalgésicas

Autoria SCIMAGO INSTITUTIONS RANKINGS

Objetivo: avaliar os efeitos da infusão de noradrenalina (NA) em crianças submetidas a ventilação mecânica (VM) requerendo infusão contínua de sedoanalgesia.

Métodos: estudo duplo cego, randomizado e placebo controlado envolvendo crianças de 1 mês a 12 anos, admitidas em uma UTI pediátrica brasileira com a expectativa de necessidade de VM e sedoanalgesia por, no mínimo, 5 dias. As crianças foram randomizadas a receber infusão de NA (0,15 mcg/kg/min) ou solução salina, iniciadas nas primeiras 24 horas de VM e mantidas por 72 horas. Comparamos as variáveis hemodinâmicas, oferta hídrica, função renal e débito urinário entre os dois grupos.

Resultados: 40 crianças foram alocadas aos grupos NA e placebo, sem diferenças nas características basais, achados laboratoriais, escore PRISM II, tempo de VM ou mortalidade. A infusão média de NA foi 0,143 mcg/kg/min. O grupo NA apresentou maior débito urinário (p = 0,016) e aumento constante da pressão arterial média quando comparado aos níveis basais (p = 0,043). Não se observou diferenças nas demais variáveis hemodinâmicas, reposição hídrica ou no uso de furosemida.

Conclusão: infusão precoce de NA em crianças submetidas a VM em uso sedoanalgesia promove aumento na pressão arterial média e aumento da diurese. Esses efeitos são atribuídos à reversão da vasoplegia induzida pelas drogas sedativas e analgésicas.

vasopressor; vasoplegia; choque; sedativo; débito urinário

		All children (n = 40)	Norepinephrine (n = 20)	Placebo (n = 20)	P
Age (month)		3.5 (1-111)	3 (1-70)	6 (2-111)	0.100
Weight (kg)		6.45 (3.1-36)	5.6 (3.1-20)	7.05 (3.9 -36)	0.076
Male gender, n (%)		27 (67.5)	16 (80)	11 (55)	0.177
PRISM II score		9 (4-27)	10 (4-23)	9 (4-27)	0.461
Length of PICU stay (days)		14 (5-107)	14 (7-107)	13.5 (5-28)	0.489
Length of MV (days)		9 (4-22)	9 (4-21)	9.5 (4-22)	0.946
Admitted from
	Emergency department	15	10	5	0.102
	Pediatric/surgical ward	25	10	15	0.102
Main reason for MV
	Sepsis	5	4	1	0.319
	AVB/asthma	25	13	12
	Pneumonia	6	2	4
	Other	4	1	3
Extubation failure, n (%)		4 (10%)	3 (15%)	1 (5%)	0.605
Early PICU mortality, n (%)		2 (5%)	1 (5%)	1 (5%)	1.000
Late PICU mortality, n (%)		4 (10%)	1 (5%)	3 (15%)	0.605

		All children (n = 40)	Norepinephrine (n = 20)	Placebo (n = 20)	p
HR (bpm)		148.8 ± 22.2	151.8 ± 16.7	145.7 ± 26.7	0.397 ⁺ + Values with normal distribution were expressed through mean+ SD and compared using the Student t test;
RR (bpm)		36.1 ± 12.8	35.4 ± 10.7	36.7 ± 14.8	0.752 ⁺ + Values with normal distribution were expressed through mean+ SD and compared using the Student t test;
Systolic blood pressure (mmHg)		104.5 ± 10.7	102 ± 11.4	107.1 ± 9.7	0.139 ⁺ + Values with normal distribution were expressed through mean+ SD and compared using the Student t test;
Diastolic blood pressure (mmHg)		52.3 ± 8.2	52.4 ± 8.1	52.2 ± 8.6	0.955 ⁺ + Values with normal distribution were expressed through mean+ SD and compared using the Student t test;
Mean arterial pressure (mmHg)		73.2 ± 9.4	71.3 ± 9.2	75.1 ± 9.4	0.200 ⁺ + Values with normal distribution were expressed through mean+ SD and compared using the Student t test;
Urine output (mL/kg/h)		3.9 ± 2.6	4.3 ± 2.9	3.5 ± 2.2	0.316 ⁺ + Values with normal distribution were expressed through mean+ SD and compared using the Student t test;
Maintenance fluid (mL/kg/d)		101 ± 19.3	106.2 ± 19.7	95.7 ± 18	0.086 ⁺ + Values with normal distribution were expressed through mean+ SD and compared using the Student t test;
IV Fluid bolus (mL/kg/d)
	N (%)	34 (85%)	19 (95%)	15 (75%)
	Median	21 (0-202.4)	29.1 (0-202.4)	16.0 (0-115.4)	0.291 ^* * Values with asymmetrical distribution were expressed through median (range) and compare using the U Mann-Whitney test
Vasopressor score
	Median	5 (0-55)	5 (0-55)	0 (0-25)	0.16 ^* * Values with asymmetrical distribution were expressed through median (range) and compare using the U Mann-Whitney test
Sedatives
	Morphine (mg/kg/d)	0.48 (0-1.56)	0.51 (0-1.56)	0.44 (0-1.44)	0.725 ^* * Values with asymmetrical distribution were expressed through median (range) and compare using the U Mann-Whitney test
Diazepam (mg/kg/d)		6.3 (1.1-19.6)	6.5 (2-17.2)	4.4 (1.1-19.6)	0.57 ^* * Values with asymmetrical distribution were expressed through median (range) and compare using the U Mann-Whitney test
IV Beta2 agonist n (%)		11 (27.5%)	3 (15%)	8 (40%)	0.156 ^# # Percentage values were compared using the Chi Square test or the Exact Fischer test
Blood acid base
	pH	7.33 ± 0.16	7.32 ± 0.17	7.33 ± 0.16	0.885 ⁺ + Values with normal distribution were expressed through mean+ SD and compared using the Student t test;
	HCO₃-	19.4 ± 5.3	17.9 ± 4.8	20.9 ± 5.4	0.067 ⁺ + Values with normal distribution were expressed through mean+ SD and compared using the Student t test;
Hemoglobin		9.9 ± 1.9	9.8 ± 2.2	9.9 ± 1.7	0.981 ⁺ + Values with normal distribution were expressed through mean+ SD and compared using the Student t test;
Sodium		136.4 ± 4.7	136.1 ± 5.4	136.6 ± 4.1	0.719 ⁺ + Values with normal distribution were expressed through mean+ SD and compared using the Student t test;
Potassium		4.4 ± 0.7	4.4 ± 0.8	4.4 ± 0.7	0.933 ⁺ + Values with normal distribution were expressed through mean+ SD and compared using the Student t test;

	Basal	1	2	3	4	p
Heart rate (bpm)
NE-group	152±17	146±22	143±18	141±17	136±19	^* NE-group= children receiving norepinephrine infusion; Vasopressor Score=[dopamine + dobutamine + (epinephrine X 100) + (norepinephrine X 100) + (milrinone X 10)]. a-The vasopressor score was calculated without considering the infused solution (placebo or norepinephrine). It was used to compare impact of both solutions in the hemodynamic response. The continuous variables were expressed as mean and SD, being compared through the Anova one way and by the area under the curve (Auc). The asymmetrical variables were expressed as median with the respective range, being through the Anova log rank and by the area under the curve (Auc) 0.421
Placebo-group	146±27	142±29	136±29	137±27	134±24
Fluid (mL/kg/day)
NE-group	106±20	106±19	112±28	115±24	120±23	^* NE-group= children receiving norepinephrine infusion; Vasopressor Score=[dopamine + dobutamine + (epinephrine X 100) + (norepinephrine X 100) + (milrinone X 10)]. a-The vasopressor score was calculated without considering the infused solution (placebo or norepinephrine). It was used to compare impact of both solutions in the hemodynamic response. The continuous variables were expressed as mean and SD, being compared through the Anova one way and by the area under the curve (Auc). The asymmetrical variables were expressed as median with the respective range, being through the Anova log rank and by the area under the curve (Auc) 0.444
Placebo-group	96±18	96±23	101±26	97±21	112±30
IV Bolus (mL/kg/day)
NE-group	29(0-202)	10(0-66)	10(0-51)	0(0-24)	0(0-38)	^* NE-group= children receiving norepinephrine infusion; Vasopressor Score=[dopamine + dobutamine + (epinephrine X 100) + (norepinephrine X 100) + (milrinone X 10)]. a-The vasopressor score was calculated without considering the infused solution (placebo or norepinephrine). It was used to compare impact of both solutions in the hemodynamic response. The continuous variables were expressed as mean and SD, being compared through the Anova one way and by the area under the curve (Auc). The asymmetrical variables were expressed as median with the respective range, being through the Anova log rank and by the area under the curve (Auc) 0.699
Placebo-group	16(0-115)	7.5(0-63)	0(0-42)	0(0-115)	9(0-115)
Vasopressor score ^a NE-group= children receiving norepinephrine infusion; Vasopressor Score=[dopamine + dobutamine + (epinephrine X 100) + (norepinephrine X 100) + (milrinone X 10)]. a-The vasopressor score was calculated without considering the infused solution (placebo or norepinephrine). It was used to compare impact of both solutions in the hemodynamic response. The continuous variables were expressed as mean and SD, being compared through the Anova one way and by the area under the curve (Auc). The asymmetrical variables were expressed as median with the respective range, being through the Anova log rank and by the area under the curve (Auc)
NE-group	5(5-55)	6.25(0-73)	10(0-51)	9.9(0-45)	8.9(0-115)	^* NE-group= children receiving norepinephrine infusion; Vasopressor Score=[dopamine + dobutamine + (epinephrine X 100) + (norepinephrine X 100) + (milrinone X 10)]. a-The vasopressor score was calculated without considering the infused solution (placebo or norepinephrine). It was used to compare impact of both solutions in the hemodynamic response. The continuous variables were expressed as mean and SD, being compared through the Anova one way and by the area under the curve (Auc). The asymmetrical variables were expressed as median with the respective range, being through the Anova log rank and by the area under the curve (Auc) 0.888
Placebo-group	0(0-25)	8.75(0-60)	11(0-75)	8.75(0-135)	8.75(0-115)
Urine output (mL/kg/hr)
NE-group	4.3±2.9	4.7±1.7	5.1±1.7	4.9±1.5	4.5±1.2	^* NE-group= children receiving norepinephrine infusion; Vasopressor Score=[dopamine + dobutamine + (epinephrine X 100) + (norepinephrine X 100) + (milrinone X 10)]. a-The vasopressor score was calculated without considering the infused solution (placebo or norepinephrine). It was used to compare impact of both solutions in the hemodynamic response. The continuous variables were expressed as mean and SD, being compared through the Anova one way and by the area under the curve (Auc). The asymmetrical variables were expressed as median with the respective range, being through the Anova log rank and by the area under the curve (Auc) 0.016
Placebo-group	3.5±2.2	3.9±1.6	3.8±1.0	4.1±1.5	4.5±1.5
Furosemide (mg/kg/day)
NE-group	0(0-2.5)	0.25(0-2.3)	1(0-4.2)	0.5(0-4.2)	0.7(0-4.5)	^* NE-group= children receiving norepinephrine infusion; Vasopressor Score=[dopamine + dobutamine + (epinephrine X 100) + (norepinephrine X 100) + (milrinone X 10)]. a-The vasopressor score was calculated without considering the infused solution (placebo or norepinephrine). It was used to compare impact of both solutions in the hemodynamic response. The continuous variables were expressed as mean and SD, being compared through the Anova one way and by the area under the curve (Auc). The asymmetrical variables were expressed as median with the respective range, being through the Anova log rank and by the area under the curve (Auc) 0.616
Placebo-group	0(0-2.6)	1(0-3.2)	1.1(0-6.0)	0.9(0-4.3)	0.5(0-4.2)
Diazepam (mg/kg/day)
NE-group	6.5±3.6	7.3±2.6	7.1±3.6	6.1±3.5	4.9±3.2	^* NE-group= children receiving norepinephrine infusion; Vasopressor Score=[dopamine + dobutamine + (epinephrine X 100) + (norepinephrine X 100) + (milrinone X 10)]. a-The vasopressor score was calculated without considering the infused solution (placebo or norepinephrine). It was used to compare impact of both solutions in the hemodynamic response. The continuous variables were expressed as mean and SD, being compared through the Anova one way and by the area under the curve (Auc). The asymmetrical variables were expressed as median with the respective range, being through the Anova log rank and by the area under the curve (Auc) 0.091
Placebo-group	6.9±5.9	8.9±4.0	8.9±4.2	9±4.5	7.1±4.5
Morphine (mg/kg/day)
NE-group	0.5±0.4	0.8±0.4	0.8±0.5	0.7±0.4	0.6±0.4	^* NE-group= children receiving norepinephrine infusion; Vasopressor Score=[dopamine + dobutamine + (epinephrine X 100) + (norepinephrine X 100) + (milrinone X 10)]. a-The vasopressor score was calculated without considering the infused solution (placebo or norepinephrine). It was used to compare impact of both solutions in the hemodynamic response. The continuous variables were expressed as mean and SD, being compared through the Anova one way and by the area under the curve (Auc). The asymmetrical variables were expressed as median with the respective range, being through the Anova log rank and by the area under the curve (Auc) 0.188
Placebo-group	0.5±0.4	1±0.6	1.1±0.8	1±0.8	0.8±1

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[1] AVB = acute viral bronchiolitis; Early PICU mortality = death occurring within the first week of Pediatric Intensive Care Unit (PICU); Late PICU mortality = Death occurring after one week of admission to the PICU. The continuous variables were expressed as a median with the respective range, being compared using the Mann-Whitney U test. The categorical variables were expressed as absolute number and the respective percentage being compared using the Chi Square test or Exact Fischer test.