Use and Effect of Vasopressors after Pediatric Traumatic Brain Injury

Abstract

Background: Vasopressors are commonly used to increase mean arterial blood pressure (MAP) and cerebral perfusion pressure (CPP) after traumatic brain injury (TBI), but there are few data comparing vasopressor effectiveness after pediatric TBI. Objective: To determine which vasopressor is most effective at increasing MAP and CPP in children with moderate-to-severe TBI. Methods: After institutional review board approval, we performed a retrospective cohort study of children 0–17 years old admitted to a level 1 trauma center (Harborview Medical Center, Seattle, Wash., USA) between 2002 and 2007 with moderate-to-severe TBI who received a vasopressor to increase blood pressure. Baseline demographic and physiologic characteristics and hourly physiologic monitoring for 3 h after having started a vasopressor were abstracted. We evaluated differences in MAP and CPP at 3 h after initiation of therapy between phenylephrine, dopamine and norepinephrine among patients who did not require a second vasopressor during this time. Multivariate linear regression was used to adjust for age, gender, injury severity score and baseline MAP or CPP and to cluster by subject. Results: Eighty-two patients contributed data to the entire dataset. The most common initial medication was phenylephrine for 47 (57%). Patients receiving phenylephrine and norepinephrine tended to be older than those receiving dopamine and epinephrine. Thirteen (16%) of the patients received a second vasopressor during the first 3 h of treatment and were thus not included in the regression analyses; these patients received more fluid resuscitation and exhibited higher in-hospital mortality (77 vs. 32%; p = 0.004) compared to patients receiving a single vasopressor. The norepinephrine group exhibited a 5 mm Hg higher MAP (95% CI: –4 to 13; p = 0.31) and a 12 mm Hg higher CPP (95% CI: –2 to 26; p = 0.10) than the phenylephrine group, and a 5 mm Hg higher MAP (95% CI: –4 to 15; p = 0.27) and a 10 mm Hg higher CPP (95% CI: –5 to 25; p = 0.18) than the dopamine group. However, in post hoc analysis, after adjusting for time to start of vasopressor, hypertonic saline and pentobarbital, the effect on MAP was lost, but the CPP was 8 mm Hg higher (95% CI: –10 to 25; p = 0.39) than in the phenylephrine group, and 5 mm Hg higher (95% CI: –14 to 24; p = 0.59) than in the dopamine group. Conclusions: Vasopressor use varied by age. While there was no statistically significant difference in MAP or CPP between vasopressor groups, norepinephrine was associated with a clinically relevant higher CPP and lower intracranial pressure at 3 h after start of vasopressor therapy compared to the other vasopressors examined.

Retracted:Norepinephrine Protects Cerebral Autoregulation and Reduces Hippocampal Necrosis after Traumatic Brain Injury via Blockade of ERK MAPK and IL-6 in Juvenile Pigs

“…27 The results of that study were remarkably similar to that observed with NE; Phe and NE prevented impairment of autoregulation in the newborn female via blockade of ERK MAPK upregulation, but these same agents did not do so in newborn males where it augmented ERK MAPK upregulation. 17,19 In the present study, we observed that NE prevented impairment of autoregulation in juvenile male and female pigs due to blockade of ERK MAPK upregulation, indicating that for this vasoactive agent outcome is dependent on both age and sex.…”

“…7 Cerebral autoregulation is impaired to a greater extent in newborn compared with juvenile pigs, which parallels that observed clinically. 4,8 Current 2012 Pediatric Guidelines recommend maintaining CPP above 40 mm Hg in children and adolescents with severe TBI, noting that an age-related continuum for the optimal CPP is between 40 and 65 mm Hg. 9,10 Maintaining CPP within these levels is often managed by use of vasoactive agents to increase CPP and optimize CBF.…”

Blood-brain barrier and cerebral blood flow: Age differences in hemorrhagic stroke

“…[27][28][29] Here, we analyzed the e®ects of adrenaline on cerebral venous circulation in newborn and adult rats in normal state and after stroke development. Our results showed that adrenaline caused the constrictor e®ect on the sagittal sinus in healthy animals without any age di®erences.…”

“…25 Adrenaline caused vasoconstriction of cerebral vessels in healthy rats but did not induce any changes in the CBF in rats with intracranial hemorrhages, probably due to decrease in the BBB permeability. 13 Here, we proposed adrenaline test as additional indirect method to the study of BBB permeability as well as to determine e®ectiveness of adrenaline as a main course in therapy of stroke [27][28][29] in neonates and adults.…”

The Experimental Study of Stress-Related Pathological Changes in Cerebral Venous Blood Flow in Newborn Rats Assessed by Doct

“…30 Notice, there is limited information regarding the age particularities of adrenergic control of cerebral circulation. 26,30 There are a lot of techniques providing CBF imaging. The most accepted are positron emission tomography (PET), 31,32 magnetic resonance imaging (MRI) (including functional MRI), 33À36 Doppler ultrasound and near-infrared spectroscopy (NIRS).…”