Ronald B. Easley

Continuous Monitoring of Cerebrovascular Pressure Reactivity After Traumatic Brain Injury in Children

OBJECTIVE: We hypothesized that pressure reactivity index (PRx) values indicating preserved cerebrovascular pressure autoregulation would be associated with survival in children with traumatic brain injury (TBI). This hypothesis was tested in a prospective, blinded, observational, pilot study. METHODS: Twenty-one children admitted between May 2006 and September 2008 with severe TBI necessitating invasive intracranial pressure monitoring were enrolled in this study. The PRx was continuously monitored as a moving, linear correlation coefficient between low-frequency waves of intracranial and arterial blood pressures. Positive values of PRx approaching 1 indicate impaired cerebrovascular pressure reactivity, whereas negative PRx values or values close to 0 indicate preserved cerebrovascular pressure reactivity. Survival was the primary outcome and was compared with the average PRx value obtained during the intracranial pressure-monitoring period. RESULTS: PRx was associated with survival in this cohort; survivors (N = 15) had a mean PRx ± SD of 0.08 ± 0.19, and nonsurvivors (N = 6) had a mean PRx of 0.69 ± 0.21 (P = .0009). In this sample, continuous PRx monitoring suggested impaired cerebrovascular pressure reactivity at low levels of cerebral perfusion pressure (CPP) and intact cerebrovascular pressure reactivity at higher levels of CPP. CONCLUSIONS: Intact cerebrovascular pressure reactivity quantified with the PRx is associated with survival after severe head trauma in children. The PRx is CPP dependent in children. The PRx may be useful for defining age-specific and possibly patient-specific optimal targets for CPP after TBI.

Relationship between cerebrovascular dysautoregulation and arterial blood pressure in the premature infant

Objective:To evaluate cerebrovascular autoregulation as a function of arterial blood pressure (ABP) in the critically ill, premature infant.Study Design:A prospective observational pilot study was conducted in two tertiary care Neonatal Intensive-Care Units. Premature infants (n=23, ⩽30 weeks estimated gestational age with invasive ABP monitoring) were enrolled and received routine care while undergoing continuous autoregulation monitoring, using the cerebral oximetry index (COx). The COx is a moving, linear correlation coefficient between cortical reflectance oximetry and ABP. COx values were stratified as a function of ABP for individual subject recordings and for the cohort.Result:The mean duration of autoregulation monitoring was 3.2 days (median: 2.97, range: 0.61–3.99). A total of 10 of 23 (43%) developed intraventricular hemorrhage and 1 of 23 (4%) developed periventricular leukomalacia by head ultrasound. No association was found between neurologic injury and percentage of the monitoring periods with autoregulation impairment (defined as COx>0.5). Lower ABP was associated with dysautoregulation (higher COx values, P<0.01). The percentage of time with impaired autoregulation was greater with lower ABP (P=0.013, Spearman r=0.51).Conclusion:All infants studied had periods with intact and periods with impaired cerebrovascular autoregulation, measured with the COx. Low ABP was associated with impaired autoregulation.

Cerebral blood flow and cerebrovascular autoregulation in a swine model of pediatric cardiac arrest and hypothermia.

Objective:Knowledge remains limited regarding cerebral blood flow autoregulation after cardiac arrest and during postresuscitation hypothermia. We determined the relationship of cerebral blood flow to cerebral perfusion pressure in a swine model of pediatric hypoxic-asphyxic cardiac arrest during normothermia and hypothermia and tested novel measures of autoregulation derived from near-infrared spectroscopy. Design:Prospective, balanced animal study. Setting:Basic physiology laboratory at an academic institution. Subjects:Eighty-four neonatal swine. Interventions:Piglets underwent hypoxic-asphyxic cardiac arrest or sham surgery and recovered for 2 hrs with normothermia followed by 4 hrs of either moderate hypothermia or normothermia. In half of the groups, blood pressure was slowly decreased through inflation of a balloon catheter in the inferior vena cava to identify the lower limit of cerebral autoregulation at 6 hrs postresuscitation. In the remaining groups, blood pressure was gradually increased by inflation of a balloon catheter in the aorta to determine the autoregulatory response to hypertension. Measures of autoregulation obtained from standard laser-Doppler flowmetry and indices derived from near-infrared spectroscopy were compared. Measurements and Main Results:Laser-Doppler flux was lower in postarrest animals compared to sham-operated controls during the 2-hr normothermic period after resuscitation. During the subsequent 4-hr recovery, hypothermia decreased laser-Doppler flux in both the sham surgery and postarrest groups. Autoregulation was intact during hypertension in all groups. With arterial hypotension, postarrest, hypothermic piglets had a significant decrease in the perfusion pressure lower limit of autoregulation compared to postarrest, normothermic piglets. The near-infrared spectroscopy-derived measures of autoregulation accurately detected loss of autoregulation during hypotension. Conclusions:In a pediatric model of cardiac arrest and resuscitation, delayed induction of hypothermia decreased cerebral perfusion and decreased the lower limit of autoregulation. Metrics derived from noninvasive near-infrared spectroscopy accurately identified the lower limit of autoregulation during normothermia and hypothermia in piglets resuscitated from arrest.

The lower limit of cerebral blood flow autoregulation is increased with elevated intracranial pressure.

BACKGROUND: The cerebral perfusion pressure that denotes the lower limit of cerebral blood flow autoregulation (LLA) is generally considered to be equivalent for reductions in arterial blood pressure (ABP) or increases in intracranial pressure (ICP). However, the effect of decreasing ABP at different levels of ICP has not been well studied. Our objective in the present study was to determine if the LLA during arterial hypotension was invariant with ICP. METHODS: Using continuous ventricular fluid infusion, anesthetized piglets were assigned to 1 of 3 groups: naïve ICP (n = 10), moderately elevated ICP (20 mm Hg; n = 11), or severely elevated ICP (40 mm Hg; n = 9). Gradual hypotension was induced by inflation of a balloon catheter in the inferior vena cava. The LLA was determined by monitoring cortical laser-Doppler flux. RESULTS: The naïve ICP group had an average CPP at the LLA (LLACPP) of 29.8 mm Hg (95% CI: 26.5–33.0 mm Hg). However, the moderately elevated ICP group had a mean LLACPP of 37.6 mm Hg (95% CI: 32.0–43.2 mm Hg), and the severely elevated ICP group had a mean LLACPP of 51.4 mm Hg (95% CI: 41.2–61.7 mm Hg). The LLA significantly differed among groups, and the increase in LLA correlated with the increase in ICP. CONCLUSIONS: In this atraumatic, elevated ICP model in piglets, the LLA had a positive correlation with ICP, which suggests that compensating for an acute increase in ICP with an equal increase in ABP may not be sufficient to prevent cerebral ischemia.

A pilot study of cerebrovascular reactivity autoregulation after pediatric cardiac arrest

AIM Improved survival after cardiac arrest has placed greater emphasis on neurologic resuscitation. The purpose of this pilot study was to evaluate the relationship between cerebrovascular autoregulation and neurologic outcomes after pediatric cardiac arrest. METHODS Children resuscitated from cardiac arrest had autoregulation monitoring during the first 72h after return of circulation with an index derived from near-infrared spectroscopy in a pilot study. The range of mean arterial blood pressure (MAP) with optimal vasoreactivity (MAPOPT) was identified. The area under the curve (AUC) of the time spent with MAP below MAPOPT and MAP deviation below MAPOPT was calculated. Neurologic outcome measures included placement of a new tracheostomy or gastrostomy, death from a primary neurologic etiology (brain death or withdrawal of support for neurologic futility), and change in the Pediatric Cerebral Performance Category score (ΔPCPC). RESULTS Thirty-six children were monitored. Among children who did not require extracorporeal membrane oxygenation (ECMO), children who received a tracheostomy/gastrostomy had greater AUC during the second 24h after resuscitation than those who did not (P=0.04; n=19). Children without ECMO who died from a neurologic etiology had greater AUC during the first 48h than did those who lived or died from cardiovascular failure (P=0.04; n=19). AUC below MAPOPT was not associated with ΔPCPC when children with or without ECMO were analyzed separately. CONCLUSIONS Deviation from the blood pressure with optimal autoregulatory vasoreactivity may predict poor neurologic outcomes after pediatric cardiac arrest. This experimental autoregulation monitoring technique may help individualize blood pressure management goals after resuscitation.

The ontogeny of cerebrovascular pressure autoregulation in premature infants

Objective:To quantify cerebrovascular autoregulation as a function of gestational age (GA) and across the phases of the cardiac cycle.Study design:The present study is a hypothesis-generating re-analysis of previously published data. Premature infants (n=179) with a GA range of 23 to 33 weeks were monitored with umbilical artery catheters and transcranial Doppler insonation of the middle cerebral artery for 1-h sessions over the first week of life. Autoregulation was quantified by three methods, as a moving correlation coefficient between: (1) systolic arterial blood pressure (ABP) and systolic cerebral blood flow (CBF) velocity (Sx); (2) mean ABP and mean CBF velocity (Mx); and (3) diastolic ABP and diastolic CBF velocity (Dx). Comparisons of individual and cohort cerebrovascular pressure autoregulation were made across GA for each aspect of the cardiac cycle.Results:Systolic, mean and diastolic ABP increased with GA (r=0.3, 0.4 and 0.4; P<0.0001). Systolic CBF velocity was pressure-passive in infants with the lowest GA, and Sx decreased with advancing GA (r=−0.3; P<0.001), indicating increased capacity for cerebral autoregulation during systole during development. By contrast, Dx was elevated, indicating dysautoregulation, in all subjects and showed minimal change with advancing GA (r=−0.06; P=0.05). Multivariate analysis confirmed that both GA (P<0.001) and ‘effective cerebral perfusion pressure’ (ABP minus critical closing pressure (CrCP); P<0.01) were associated with Sx.Conclusion:Premature infants have low and usually pressure-passive diastolic CBF velocity. By contrast, the regulation of systolic CBF velocity by pressure autoregulation developed in this cohort between 23 and 33 weeks GA. Elevated effective cerebral perfusion pressure derived from the CrCP was associated with dysautoregulation.

The Upper Limit of Cerebral Blood Flow Autoregulation Is Decreased With Elevations in Intracranial Pressure

BACKGROUND The upper limit of cerebrovascular pressure autoregulation (ULA) is inadequately characterized. OBJECTIVE To delineate the ULA in an infant swine model. METHODS Neonatal piglets with sham surgery (n = 9), interventricular fluid infusion (INF) (n = 10), controlled cortical impact (CCI) (n = 10), or CCI + INF (n = 11) had intracranial pressure monitoring and bilateral cortical laser-Doppler flowmetry recordings during arterial hypertension to lethality using an aortic balloon catheter. An increase of red cell flux as a function of cerebral perfusion pressure was determined by piecewise linear regression, and static rates of autoregulation were determined above and below this inflection. The ULA was rendered as the first instance of an upward deflection of Doppler flux causing a static rate of autoregulation decrease greater than 0.5. RESULTS ULA was identified in 55% of piglets after sham surgery, 70% after INF, 70% after CCI, and 91% after CCI with INF (P = .36). When identified, the median (interquartile range) ULA was as follows: sham group, 102 mm Hg (97-109 mm Hg); INF group, 75 mm Hg (52-84 mm Hg); CCI group, 81 mm Hg (69-101 mm Hg); and CCI + INF group, 61 mm Hg (52-57 mm Hg) (P = .01). In post hoc analysis, both groups with interventricular INF had significantly lower ULA than that observed in the sham group. CONCLUSION Neonatal piglets without intracranial pathology tolerated acute hypertension with minimal perturbation of cerebral blood flow. Piglets with acutely increased intracranial pressure with or without trauma demonstrated loss of autoregulation when subjected to arterial hypertension.

Static autoregulation is intact early after severe unilateral brain injury in a neonatal Swine model.

BACKGROUND Autoregulation is impaired by traumatic brain injury. Cerebral blood flow disturbances are spatially heterogeneous, but autoregulation is often reported as a global metric. OBJECTIVE We tested lateralization of autoregulatory responses in the neonatal piglet brain during hypotension early after unilateral injury. METHODS Neonatal piglets (5-7 days old) had controlled cortical impact (severe, n = 12; moderate, n = 13; sham, n = 13) and recovery for 6 hours. The lower limit of autoregulation (LLA) and static rate of autoregulation (SRoR) were determined for each subject and compared among groups and between the ipsilateral and contralateral hemispheres. RESULTS The LLA was not increased by injury (sham, 34 mm Hg [29-39 mm Hg]; moderate injury, 37 mm Hg [33-41 mm Hg]; severe injury, 35 mm Hg [32-38 mm Hg]; P = .93, mean [95% confidence interval]). SRoR, when measured ipsilateral to injury and above the LLA, showed intact autoregulation and was not lower than SRoR in uninjured subjects (sham, 0.82 [0.53-1.1]; moderate injury, 1.0 [0.60-1.5]; severe, 0.91 [0.33-1.5]; P = .44). The average hemispheric LLA difference was 2.7 mm Hg, (95% limits of agreement, -7.5 to 7.0; bias, -0.25; Spearman r = 0.73; P < .0001). Ipsilateral and contralateral SRoR measurements also showed correlation in the injured groups (Spearman r = 0.85, P < .0001). CONCLUSION LLA was not increased by controlled cortical impact, nor did SRoR measurements demonstrate ineffective autoregulation when cerebral perfusion pressure was greater than and within 10 mm Hg of the LLA. Cerebral perfusion pressure optimization, indicated by autoregulation measurements, was significantly similar in the 2 hemispheres despite severe unilateral injury.

Alteration in the lower limit of autoregulation with elevations in cephalic venous pressure

Abstract Objectives: Recent studies suggest that elevated intracranial pressure (ICP), created by hydrocephalus, can alter the lower limit of cerebrovascular autoregulation (LLA). Our objective in the present study was to determine if ICP elevation from cerebral venous outflow obstruction would result in comparable alterations in the LLA. Methods: Anesthetized juvenile pigs were assigned to one of two groups: naïve ICP (n  =  15) or high ICP (>20 mmHg; n  =  20). To elevate ICP through venous obstruction, a modified 5F esophageal balloon catheter was inserted via the right external jugular vein into the superior vena cava (SVC) and inflated to maintain an ICP of >20 mmHg. To calculate the LLA, gradual hypotension was induced by continuous hemorrhage from a catheter in the femoral vein. The LLA was determined by monitoring cortical laser Doppler flux (LDF). Results: The naïve and high ICP groups had LLAs of 45 mmHg (95% CI: 41–49 mmHg) and 71 mmHg (95% CI: 66–77 mmHg) respectively by LDF. The LLA was significantly different between the two groups and correlated significantly with ICP. Discussion: Elevated ICP from cephalic venous engorgement leads to an increase in the LLA. These findings suggest that pathologic processes resulting in cephalic venous outflow obstruction and intracranial venous congestion can acutely elevate ICP and may place the brain at risk for impaired cerebrovascular autoregulation.

Ontogeny of cerebrovascular critical closing pressure

Background:Premature infants are at risk of vascular neurologic insults. Hypotension and hypertension are considered injurious, but neither condition is defined with consensus. Cerebrovascular critical closing pressure (CrCP) is the arterial blood pressure (ABP) at which cerebral blood flow (CBF) ceases. CrCP may serve to define subject-specific low or high ABP. Our objective was to determine the ontogeny of CrCP.Methods:Premature infants (n = 179) with gestational age (GA) from 23–31 wk had recordings of ABP and middle cerebral artery flow velocity twice daily for 3 d and then daily for the duration of the first week of life. All infants received mechanical ventilation. CrCP was calculated using an impedance-model derivation with Doppler-based estimations of cerebrovascular resistance and compliance. The association between GA and CrCP was determined in a multivariate analysis.Results:The median (interquartile range) CrCP for the cohort was 22 mm Hg (19–25 mm Hg). CrCP increased significantly with GA (r = 0.6; slope = 1.4 mm Hg/wk gestation), an association that persisted with multivariate analysis (P < 0.0001).Conclusion:CrCP increased significantly from 23 to 31 wk gestation. The low CrCP observed in very premature infants may explain their ability to tolerate low ABP without global cerebral infarct or hemorrhage.