Monitoring of cerebrovascular pressure reactivity in children may predict neurologic outcome after hypoxic-ischemic brain injury.

OBJECTIVES: Impaired cerebral blood flow is a first-line reason of ischemic-hypoxic brain injury in children. The principal goal of intensive care management is to detect and prevent further cerebral blood flow deficits. This can be achieved by actively managing cerebral perfusion pressure (CPP) using input from cerebrovascular autoregulation (CAR). The main objective of the current study was to investigate CAR after cardiac arrest in children. METHODS: Nineteen consecutive children younger than 18 years after cardiopulmonary resuscitation, in whom intracranial pressure (ICP) was continuously measured, were included. Blood pressure and ICP were continuously monitored via ICM + software and actively managed using the pressure reactivity index (PRx) to achieve and maintain an optimal CPP. Outcome was scored using the extended Glasgow outcome scale (eGOS) at discharge and 6 months. RESULTS: Eight children died in hospital. At 6 months, further 4 children had an unfavorable (eGOS1-4) and 7 a favorable (eGOS5-8) outcome. Over the entire monitoring period, we found an elevated ICP (24.5 vs 7.4 mmHg), a lower CPP (50.3 vs 66.2 mmHg) and a higher PRx (0.24 vs - 0.01), indicating impaired CAR, in patients with unfavorable outcome. The dose of impaired autoregulation was significantly higher in unfavorable outcome (54.6 vs 29.3%). Analyzing only the first 72 h after cardiac arrest, ICP ≥ 10 mmHg and PRx > 0.2 correlated to unfavorable outcome. CONCLUSIONS: Significant doses of impaired CAR within 72 h after resuscitation are associated with unfavorable outcome. The inability to restore autoregulation despite active attempts to do so as well as an elevated ICP may serve as a bad prognostic sign indicating a severe initial hypoxic-ischemic brain injury.

Effects of hypertonic saline on intracranial pressure and cerebral autoregulation in pediatric traumatic brain injury.

OBJECTIVE: Hypertonic saline (HTS) is commonly used in children to lower intracranial pressure (ICP) after severe traumatic brain injury (sTBI). While ICP and cerebral perfusion pressure (CPP) correlate moderately to TBI outcome, indices of cerebrovascular autoregulation enhance the correlation of neuromonitoring data to neurological outcome. In this study, the authors sought to investigate the effect of HTS administration on ICP, CPP, and autoregulation in pediatric patients with sTBI. METHODS: Twenty-eight pediatric patients with sTBI who were intubated and sedated were included. Blood pressure and ICP were actively managed according to the autoregulation index PRx (pressure relativity index to determine and maintain an optimal CPP [CPPopt]). In cases in which ICP was continuously > 20 mm Hg despite all other measures to decrease it, an infusion of 3% HTS was administered. The monitoring data of the first 6 hours after HTS administration were analyzed. The Glasgow Outcome Scale (GOS) score at the 3-month follow-up was used as the primary outcome measure, and patients were dichotomized into favorable (GOS score 4 or 5) and unfavorable (GOS score 1-3) groups. RESULTS: The mean dose of HTS was 40 ml 3% NaCl. No significant difference in ICP and PRx was seen between groups at the HTS administration. ICP was lowered significantly in all children, with the effect lasting as long as 6 hours. The lowering of ICP was significantly greater and longer in children with a favorable outcome (p < 0.001); only this group showed significant improvement of autoregulatory capacity (p = 0.048). A newly established HTS response index clearly separated the outcome groups. CONCLUSIONS: HTS significantly lowered ICP in all children after sTBI. This effect was significantly greater and longer-lasting in children with a favorable outcome. Moreover, HTS administration restored disturbed autoregulation only in the favorable outcome group. This highlights the role of a "rescuable" autoregulation regarding outcome, which might be a possible indicator of injury severity. The effect of HTS on autoregulation and other possible mechanisms should be further investigated.

Impaired Autoregulation Following Resuscitation Correlates with Outcome in Pediatric Patients: A Pilot Study.

In children with a traumatic brain injury, the duration of autoregulation impairment correlates with the neurological outcome. This pilot study explored whether a similar relation exists in nontraumatic hypoxic-ischemic brain injury following resuscitation.We investigated 11 children after resuscitation. Blood pressure and intracranial pressure (ICP) were monitored with ICM+ software and actively managed to maintain optimal cerebral perfusion pressure (CPP), using the pressure reactivity index (PRx). Outcomes were scored according to the Glasgow Outcome Scale.Three children died within 24 h. Three survivors had an unfavorable outcome and five had a favorable outcome. In the first 72 h, ICP and CPP values did not differ between, or predict, children with favorable or unfavorable outcomes. The duration of a PRx value ≥0.2 was significantly greater in children with an unfavorable outcome. A PRx value ≤0 was associated with a favorable outcome in all except one child. Children with an unfavorable outcome had areas of ischemic brain tissue on magnetic resonance imaging.The duration of poor autoregulation within the first 72 h is associated with an unfavorable outcome. Prognostic signs for insult severity are initially poor autoregulation plus inability to restore autoregulation despite active attempts to do so. Limited ischemia, especially in the basal ganglia, cannot be detected by ICP-based monitoring of autoregulation and may still result in an unfavorable outcome despite good global autoregulation.

Survey of the management of perioperative bridging of anticoagulation and antiplatelet therapy in neurosurgery.

BACKGROUND: A growing number of patients on anticoagulation or antiplatelet therapy (APT) are planned for elective surgery. The management of perioperative anticoagulation and APT is challenging because it must balance the risk of thromboembolism and bleeding, and specific recommendations for the management of bridging in neurosurgical patients are lacking. We surveyed German neurosurgical centers about their management of perioperative bridging of anticoagulation and APT to provide an overview of the current bridging policy. METHOD: From April to August 2016, all German neurosurgical departments were invited to participate in the survey. We used SurveyMonkey to compose ten questions and to conduct the survey, and we defined three different approaches for the perioperative management of patients on a preexisting medication: medication will be discontinued (A) with perioperative "bridging" and (B) without perioperative bridging, or (C) medication will be continued perioperatively. RESULTS: Out of 141 respondents, 84 (60%) partially and 77 (55%) fully completed the questionnaire. No defined policy for the perioperative management of anticoagulation and APT was established in 60.7% (51/84) of participating centers. The perioperative management of anticoagulation and APT varied widely among different centers in all items of the questionnaire; for example, in the group of patients at high risk for thromboembolism, acetylsalicylic acid was discontinued in 22%, bridged in 35%, and continued in 35% of centers. CONCLUSIONS: There is significant uncertainty regarding the management of perioperative bridging of anticoagulation and APT in neurosurgery because of a lack of prospective and limited retrospective data.

ICP Monitoring by Open Extraventricular Drainage: Common Practice but Not Suitable for Advanced Neuromonitoring and Prone to False Negativity.

OBJECTIVE: A drawback in the use of an external ventricular drain (EVD) originates in the fact that draining cerebrospinal fluid (CSF) (open system) and intracranial pressure (ICP) monitoring can be done at the same time but is considered to be unreliable regarding the ICP trace. Furthermore, with the more widespread use of autoregulation monitoring using blood pressure and ICP signals, the question arises of whether an ICP signal from an open EVD can be used for this purpose. Using an EVD system with an integrated parenchymal ICP probe we compared the different traces of an ICP signal and their derived parameters under opened and closed CSF drainage. METHODS: Twenty patients with either subarachnoid or intraventricular hemorrhage and indication for ventriculostomy plus ICP monitoring received an EVD in combination with an air-pouch-based ICP probe. ICP was monitored via an open ventricular catheter (ICP_evd) and ICP probe (ICP_probe) simultaneously. Neuromonitoring data (ICP, arterial blood pressure, cerebral perfusion pressure, pressure reactivity index (PRx)) were recorded by ICM+ software for the time of ICU intensive care treatment. Routinely (at least every 4 h) ICP was recorded with a closed CSF drainage system for at least 15 min. ICP, ICP amplitude, and the autoregulation parameters (PRx_probe, PRx_evd) were evaluated for every episode with closed CSF drainage and during the 3 h prior with an open drainage system. RESULTS: One hundred and forty-four episodes with open/closed drainage were evaluated. During open drainage, overall mean ICP_evd levels were nonsignificantly different from those of ICP_probe, with 9.8 + 3.3 versus 8.2 + 3.2 mmHg, respectively. Limits of agreement ranged between 5.2 and -8.3 mmHg. However, 51 increases of ICP >20 mmHg with a duration of 3-30 min were missed by ICP_evd, and in 101 episodes the difference between ICPs was greater than 10 mmHg. After closure of the EVD, ICP increased moderately using both methods. Mean PRx_evd was significantly higher (falsely indicating impaired autoregulation) and more subjected to fluctuations than PRx_probe. CONCLUSION: The general practice of draining CSF and monitoring ICP via a (usually open) EVD plus frequently performed catheter closure for ICP reading is feasible for assessment of overall ICP trends. However, it does have clinically relevant drawbacks, namely, a significant amount of undetected increases in ICP above thresholds, and continuous assessment of cerebrovascular autoregulation is less reliable. In conclusion, all patients who need CSF drainage plus ICP monitoring due to the severity of their brain insult need either an EVD with integrated ICP probe or an EVD line plus a separate ICP probe.

Chronic overdrainage syndrome: pathophysiological insights based on ICP analysis: a case-based review.

INTRODUCTION: Chronic overdrainage affects shunted patients producing a variety of symptoms that may be misdiagnosed. The best known symptoms are so-called shunt-related headaches. There is mounting evidence that changes in cerebrospinal venous system dynamics are a key factor to the pathophysiology of chronic overdrainage syndrome. CLINICAL PRESENTATION: We report the case of a 29-year-old woman with a shunt since the postnatal period suffering from chronic but the most severe intermittent headache attacks, despite an open shunt and with unchanged ventricular width during attacks. Intracranial pressure (ICP) recordings were performed during headache attacks and thereafter. DIAGNOSIS AND MANAGMENT: Massively increased ICPs, a continuous B wave "storm," and severely compromised intracranial compliance despite an open shunt were found, a scenario that was always self-limiting with the resolution of symptoms after several hours. When mobilized to the upright position, her ICPs dropped to - 17 mm Hg, proving shunt overdrainage. OUTCOME AND CONCLUSIONS: Symptomatology can only be explained by sudden venous entrapment following chronic venous distention as a result of chronic overdrainage. Subsequent therapeutic management with an overdrainage preventing shunt and satisfying clinical outcome with complete ceasing of headache attacks adds insight into the pathophysiology of chronic overdrainage syndrome.

Time spent with impaired autoregulation is linked with outcome in severe infant/paediatric traumatic brain injury.

BACKGROUND: It could be shown in traumatic brain injury (TBI) in adults that the functional status of cerebrovascular autoregulation (AR), determined by the pressure reactivity index (PRx), correlates to and even predicts outcome. We investigated PRx, cerebral perfusion pressure (CPP) and intracranial pressure (ICP) and their correlation to outcome in severe infant and paediatric TBI. METHODS: Seventeen patients (range, 1 day to 14 years) with severe TBI (median GCS at presentation, 4) underwent long-term computerised ICP and mean arterial pressure (MAP) monitoring using dedicated software to determine CPP and PRx and optimal CPP (CPP level where PRx shows best autoregulation) continuously. Outcome was determined at discharge and at follow-up using the Glasgow Outcome Scale. RESULTS: Favourable outcome was reached in eight patients, unfavourable outcome in seven patients. Two patients died. Nine patients underwent decompressive craniectomy to control ICP during Intensive Care Unit treatment. When dichotomised to outcome, no significant difference was found for overall ICP, CPP and PRx. The time with severely impaired AR (PRx >0.2) was significantly longer for patients with unfavourable outcome (64 h vs 6 h, p = 0.001). Continuously impaired AR of ≥24 h and age <1 year was associated to unfavourable outcome. Children with favourable outcome spent the entire monitoring time at or above the optimal CPP. CONCLUSIONS: Integrity of AR has a similar role for outcome after TBI in the paediatric population as in adults. The amount of time spent with deranged AR seems to be associated with outcome; a factor especially critical for infant patients. The results of this preliminary study need to be validated in the future.

Effect of Intra-Arterial and Intravenous Nimodipine Therapy of Cerebral Vasospasm After Subarachnoid Hemorrhage on Cerebrovascular Reactivity and Oxygenation.

BACKGROUND: For the treatment and prevention of delayed cerebral ischemia after subarachnoid hemorrhage, the vasodilating agent nimodipine (NDP) is widely employed. This study investigates the effect of NDP on cerebrovascular autoregulation, assessed by pressure reactivity index (PRx), and brain tissue oxygenation (pbrO2) when given continuously intravenously as an intra-arterial bolus or during continuous intra-arterial therapy. METHODS: Computerized continuous neuromonitoring data (intracranial pressure, mean arterial pressure, cerebral perfusion pressure [CPP], pbrO2, PRx) of 105 patients with aneurysmal SAH were retrospectively evaluated. The effect of NDP on all parameters was compared when applied intra-arterially for the treatment of severe macrovasospasm leading to perfusion deficits as either bolus treatment (n = 111 in 37 patients) or continuous infusion (n = 20 patients) to patients without or with only mild macrovasospasm who received either intravenous NDP or no NDP at all. RESULTS: Compared with patients without treatment, the intravenous application of NDP was associated with a significantly higher PRx. Autoregulation was strongly and long lastingly affected (high PRx) in continuous intra-arterial NDP infusion, accompanied by a sustained improvement of pbrO2. Intra-arterial bolus NDP application resulted as well in a significant increase of pbrO2 and PRx; the induced effect, however, was transient and subsided within 6 hours. Intracranial pressure, mean arterial pressure, and CPP were not affected during the monitoring period. CONCLUSION: The pharmacologically induced alteration of the cerebrovascular autoregulation by NDP correlates with changes of pbrO2 and indicates a beneficial effect on cerebral blood flow if CPP is maintained. This effect is limited to a few hours after bolus treatment and milder for intravenous compared with intra-arterial application.

State of Cerebrovascular Autoregulation Correlates with Outcome in Severe Infant/Pediatric Traumatic Brain Injury.

OBJECTIVE: It could be shown in adults with severe traumatic brain injury (TBI) that the functional status of cerebrovascular autoregulation (AR), determined by the pressure reactivity index (PRx), correlates with and even predicts outcome. We investigated PRx and its correlation with outcome in infant and pediatric TBI. Methods Ten patients (median age 2.8 years, range 1 day to 14 years) with severe TBI (Glasgow Coma Scale score <9 at presentation) underwent long-term computerized intracranial pressure (ICP) and mean arterial pressure (MAP) monitoring using dedicated software for continuous determination of cerebral perfusion pressure (CPP) and PRx. Outcome was determined at discharge and at follow-up at 6 months using the Glasgow Outcome Scale (GOS) score. RESULTS: Median monitoring time was 182 h (range 22-355 h). Seven patients underwent decompressive craniectomy to control ICP during treatment in the intensive care unit. Favorable outcome (GOS 4 and 5) was reached in 4 patients, an unfavorable outcome (GOS 1-3) in 6 patients. When dichotomized to outcome, no correlation was found with ICP and CPP, but median PRx correlated well with outcome (r = -0.79, p = 0.006) and tended to be lower for GOS 4 and 5 (-0.04) than for GOS 1-3 (0.32; p = 0.067). CONCLUSION: The integrity of AR seems to play the same fundamental role after TBI in the pediatric population as in adults and should be determined routinely. It carries an important prognostic value. PRx seems to be an ideal candidate parameter to guide treatment in the sense of optimizing CPP, aiming at improvement of cerebrovascular autoregulation (CPPopt concept).

Long-Term, Continuous Intra-Arterial Nimodipine Treatment of Severe Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Secondary vasospasm and disturbances in cerebrovascular autoregulation are associated with the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. An intra-arterial application of nimodipine has been shown to increase the vessel diameter, although this effect is transient. The feasibility of long-term, continuous, intra-arterial nimodipine treatment and its effects on macrovasospasm, autoregulation parameters, and outcome were evaluated in patients with refractory severe macrovasospasm. METHODS: Ten patients were included with refractory macrovasospasm despite bolus nimodipine application (n = 4) or with primary severe vasospasm (n = 6). The patients were assessed with continuous multimodal neuromonitoring (mean arterial pressure, intraceranial pressure, cerebral perfusion pressure, brain tissue oxygen tension probe), daily transcranial Doppler examinations, and computed tomography angiography/perfusion. Autoregulation indices, the pressure reactivity index, and oxygen reactivity index were calculated. Indwelling microcatheters were placed in the extracranial internal carotid arteries and 0.4 mg nimodipine was continuously infused at 50 mL/hour. RESULTS: The duration of continuous, intra-arterial nimodipine ranged from 9 to 15 days. During treatment intracranial pressure remained stable, transcranial Doppler flow velocity decreased, and brain tissue oxygen tension improved by 37%. Macrovasospasm, as assessed via computed tomography angiography, had improved (n = 5) or disappeared (n = 5) at the end of treatment. Cerebrovascular autoregulation according to the pressure reactivity index and oxygen reactivity index significantly worsened during treatment. All patients showed a favorable outcome (median Glasgow Outcome Scale 5) at 3 months. CONCLUSIONS: In well-selected patients with prolonged severe macrovasospasm, continuous intra-arterial nimodipine treatment can be applied as a rescue therapy with relative safety for more than 2 weeks to prevent secondary cerebral ischemia. The induced impairment of cerebrovascular autoregulation during treatment seems to have no negative effects.

Impact of anesthesia on pathophysiology and mortality following subarachnoid hemorrhage in rats.

BACKGROUND: Anesthesia is indispensable for in vivo research but has the intrinsic potential to alter study results. The aim of the current study was to investigate the impact of three common anesthesia protocols on physiological parameters and outcome following the most common experimental model for subarachnoid hemorrhage (SAH), endovascular perforation. METHODS: Sprague-Dawley rats (n = 38) were randomly assigned to (1) chloral hydrate, (2) isoflurane or (3) midazolam/medetomidine/fentanyl (MMF) anesthesia. Arterial blood gases, intracranial pressure (ICP), mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), and regional cerebral blood flow (rCBF) were monitored before and for 3 hours after SAH. Brain water content, mortality and rate of secondary bleeding were also evaluated. RESULTS: Under baseline conditions isoflurane anesthesia resulted in deterioration of respiratory parameters (arterial pCO2 and pO2) and increased brain water content. After SAH, isoflurane and chloral hydrate were associated with reduced MAP, incomplete recovery of post-hemorrhagic rCBF (23 ± 13% and 87 ± 18% of baseline, respectively) and a high anesthesia-related mortality (17 and 50%, respectively). Anesthesia with MMF provided stable hemodynamics (MAP between 100-110 mmHg), high post-hemorrhagic rCBF values, and a high rate of re-bleedings (> 50%), a phenomenon often observed after SAH in humans. CONCLUSION: Based on these findings we recommend anesthesia with MMF for the endovascular perforation model of SAH.

Vasopressin V(1a) receptors mediate posthemorrhagic systemic hypertension thereby determining rebleeding rate and outcome after experimental subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Arginine vasopressin V(1) receptors have been suggested to be involved in the pathophysiology of acute brain injury. Therefore, we aimed to determine the role of arginine vasopressin V(1) receptors after experimental subarachnoid hemorrhage (SAH). METHODS: Sprague-Dawley rats subjected to SAH by endovascular puncture received either vehicle or a V(1) receptor antagonist intravenously from 1 minute before until 3 hours after SAH. Intracranial pressure, cerebral blood flow, and mean arterial blood pressure were monitored until 60 minutes after SAH. Brain water content was quantified 24 hours after SAH and neurological function and mortality were assessed daily for 7 days after hemorrhage. RESULTS: In control rats, SAH induced high intracranial pressure, a brief increase in plasma arginine vasopressin, a subsequent increase in systemic blood pressure (Cushing response), a high rebleeding rate (30%), severe neurological deficits, and a 7-day mortality rate of 50%. V(1) receptor antagonist-treated animals exhibited a far less pronounced Cushing response, a less severe increase of intracranial pressure, did not exhibit rebleedings, had less severe brain edema formation and neurological deficits, and a mortality rate of only 20% (all P<0.05 versus vehicle). CONCLUSIONS: Inhibition of arginine vasopressin V(1a) receptors reduces the severity of SAH and prevents rebleedings by blunting the posthemorrhagic hypertonic response (Cushing reflex), thereby reducing mortality and secondary brain damage after experimental SAH. Because the severity of the initial bleeding and rebleedings are major factors contributing to an unfavorable outcome after SAH, inhibition of V(1a) receptors may represent a novel strategy to treat SAH.