Effects of xenon and hypothermia on cerebrovascular pressure reactivity in newborn global hypoxic-ischemic pig model

Authors: Chakkarapani E, Dingley J, Aquilina K, Osredkar D, Liu X, Thoresen M.

Autoregulation of cerebral perfusion is impaired in hypoxic-ischemic encephalopathy. We investigated whether cerebrovascular pressure reactivity (PRx), an element of cerebral autoregulation that is calculated as a moving correlation coefficient between averages of intracranial and mean arterial blood pressure (MABP) with values between -1 and +1, is impaired during and after a hypoxic-ischemic insult (HI) in newborn pigs. Associations between end-tidal CO2, seizures, neuropathology, and PRx were investigated. The effect of hypothermia (HT) and Xenon (Xe) on PRx was studied. Pigs were randomized to Sham, and after HI to normothermia (NT), HT, Xe or xenon hypothermia (XeHT). We defined PRx >0.2 as peak and negative PRx as preserved. Neuropathology scores after 72 hours of survival was grouped as 'severe' or 'mild.' Secondary PRx peak during recovery, predictive of severe neuropathology and associated with insult severity (P=0.05), was delayed in HT (11.5 hours) than in NT (6.5 hours) groups. Seizures were associated with impaired PRx in NT pigs (P=0.0002), but not in the HT/XeHT pigs. PRx was preserved during normocapnia and impaired during hypocapnia. Xenon abolished the secondary PRx peak, increased (mean (95% confidence interval (CI)) MABP (6.5 (3.8, 9.4) mm Hg) and cerebral perfusion pressure (5.9 (2.9, 8.9) mm Hg) and preserved the PRx (regression coefficient, -0.098 (95% CI (-0.18, -0.01)), independent of the insult severity.Journal of Cerebral Blood Flow & Metabolism advance online publication, 31 July 2013; doi:10.1038/jcbfm.2013.123.

Lessons from the Intracranial Pressure Monitoring-Trial in TBI patients

Authors: Sarrafzadeh AS, Smoll NR, Unterberg AW.

BACKGROUND: Monitoring of intracranial pressure (ICP) has been used for decades in patients with severe traumatic brain injury (TBI) and is recommended in the Guidelines of the Brain Trauma Foundation. It is the standard of care in most industrialized countries.
METHODS: Chesnut et al. have now performed the first randomized trial of ICP monitoring in patients with severe TBI. Patients were randomly assigned to one of two specific protocols - ICP monitoring (n=157) or imaging and clinical exam (n=167). The study was conducted in Latin America, where ICP-monitoring is not the standard of care in most hospitals.
RESULTS: Six months after injury, patients groups had similar scores on functional status and cognition and similar cumulative mortality. Patients who underwent ICP monitoring had a significantly lower intensity of brain-specific treatment and received fewer treatments for intracranial hypertension.
CONCLUSION: The benefit of this study is that ICP-monitoring - and more advanced multimodal monitoring allows a tailored treatment avoiding an overtherapy of drugs with unfavorable side effects. For low income countries, the results of this trial are encouraging, though efforts should be done to further improve after ICU-care and outcome. However, we guard against the use of this data to reform European and North American treatment guidelines. The authors have proven that neurosurgery can be studied in an elegant fashion. Thanks to their team of neurosurgeons and neurointensivists, the outcome of TBI-patients will continue to improve, driven by clinical practice guidelines.

Association of MRI findings and visual outcome in idiopathic intracranial hypertension

Authors: Saindane AM, Bruce BB, Riggeal BD, Newman NJ, Biousse V.

OBJECTIVE. Patients with idiopathic intracranial hypertension (IIH) have elevated intracranial pressure (ICP) without an identifiable cause. The clinical course is variable, resulting in irreversible vision loss in some and a benign course in others. Although MRI findings have been described in IIH, their association with visual outcome has not been evaluated to date. MATERIALS AND METHODS. Forty-six patients with IIH underwent funduscopic evaluation, visual field testing, lumbar puncture with opening pressure (OP) measurement, and MRI. Patients were stratified into the following groups by visual outcome: group 1, no vision loss (n = 28); group 2, some vision loss (n = 10); and group 3, severe vision loss (n = 8). MRI findings in the orbits, pituitary gland, and optic canals and the frequency of skull base cephaloceles and of transverse sinus (TS) stenosis were assessed by a reviewer blinded to the patients' visual outcome. Demographic, clinical, and MRI findings were evaluated for association with visual outcome. RESULTS. Patients in group 3 (worst visual outcome) were significantly younger (p = 0.03) and had higher OP (p = 0.04) than patients in the other groups. There were no significant differences in sex, race, or body mass index. Despite worse visual outcomes and sometimes fulminant vision loss, there were no differences in the frequency of orbital MRI findings or TS stenosis, optic canal diameter, and pituitary appearance among the three groups. Group 3 had significantly lower cephalocele frequency than the other groups (p = 0.04). CONCLUSION. Although MRI findings may suggest elevated ICP and the diagnosis of IIH, they are not predictive of visual outcome in patients with IIH.

Non-invasive intracranial pressure estimation by orbital subarachnoid space measurement: the Beijing intracranial and intraocular pressure (iCOP) study

Authors: Xie X, Zhang X, Fu J, Wang H, Jonas JB, Peng X, Tian G, Xian J, Ritch R, Li L, Kang Z, Zhang S, Yang D, Wang N.

INTRODUCTION: The orbital subarachnoid space surrounding the optic nerve is continuous with the circulation system for cerebrospinal fluid (CSF) and can be visualized using magnetic resonance imaging (MRI). We hypothesized that the orbital subarachnoid space width (OSASW) is correlated with and can serve as a surrogate for intracranial pressure (ICP). Our aim was to develop a method for a non-invasive measurement of the intracranial CSF-pressure (CSF-P) based upon MRI-assisted OSASW.

Patterns of Retinal Hemorrhage Associated With Increased Intracranial Pressure in Children

Authors: Binenbaum G, Rogers DL, Forbes BJ, Levin AV, Clark SA, Christian CW, Liu GT, Avery R.

OBJECTIVE:Raised intracranial pressure (ICP) has been proposed as an isolated cause of retinal hemorrhages (RHs) in children with suspected traumatic head injury. We examined the incidence and patterns of RHs associated with increased ICP in children without trauma, measured by lumbar puncture (LP).METHODS:Children undergoing LP as part of their routine clinical care were studied prospectively at the Children's Hospital of Philadelphia and retrospectively at Nationwide Children's Hospital. Inclusion criteria were absence of trauma, LP opening pressure (OP) ≥20 cm of water (cm H2O), and a dilated fundus examination by an ophthalmologist or neuro-ophthalmologist.RESULTS:One hundred children were studied (mean age: 12 years; range: 3-17 years). Mean OP was 35 cm H2O (range: 20-56 cm H2O); 68 (68%) children had OP >28 cm H2O. The most frequent etiology was idiopathic intracranial hypertension (70%). Seventy-four children had papilledema. Sixteen children had RH: 8 had superficial intraretinal peripapillary RH adjacent to a swollen optic disc, and 8 had only splinter hemorrhages directly on a swollen disc. All had significantly elevated OP (mean: 42 cm H2O).CONCLUSIONS:Only a small proportion of children with nontraumatic elevated ICP have RHs. When present, RHs are associated with markedly elevated OP, intraretinal, and invariably located adjacent to a swollen optic disc. This peripapillary pattern is distinct from the multilayered, widespread pattern of RH in abusive head trauma. When RHs are numerous, multilayered, or not near a swollen optic disc (eg, elsewhere in the posterior pole or in the retinal periphery), increased ICP alone is unlikely to be the cause.

Microvascular shunts in the pathogenesis of high intracranial pressure

Authors: Nemoto EM, Bragin D, Stippler M, Pappu S, Kraynik J, Berlin T, Yonas H.

Hyperemia in the infarcted brain has been -suggested for years by "red veins" reported by neurosurgeons, shunt peaks in radioactive blood flow clearance curves, and quantitative cerebral blood flow using stable xenon CT. Histological characterization of infarcted brain revealed capillary rarefaction with prominent microvascular shunts (MVS). Despite abundant histological evidence, the presence of cerebrovascular shunts have been largely ignored, perhaps because of a lack of physiological evidence demonstrating the transition from capillary flow to MVS flow. Our studies have shown that high intracranial pressure induces a transition from capillary to microvascular shunt flow resulting in cerebral hypoperfusion, tissue hypoxia and brain edema, which could be delayed by increasing cerebral perfusion pressure. The transition from capillary to microvascular shunt flow provides for the first time a physiological basis for evaluating the optimal cerebral perfusion pressure with increased intracranial pressure. It also provides a physiological basis for evaluating the effectiveness of various drugs and therapies in reducing intracranial pressure and the development of brain edema and tissue hypoxia after brain injury and ischemia. In summary, the clear-cut demonstration of the transition from capillary to MVS flow provides an important method for evaluating various therapies for the treatment of brain edema and loss of autoregulation.

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