Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH) study: a protocol for an experimental interventional study

Jatinder S Minhas, Ronney B Panerai, Thompson G Robinson, Jatinder S Minhas, Ronney B Panerai, Thompson G Robinson

Abstract

Introduction: Cerebral autoregulation (CA) is impaired in a multitude of neurological conditions. Increasingly, clinical studies are correlating the nature of this impairment with prognostic markers. In acute intracerebral haemorrhage (ICH), impairment of CA has been associated with worsening clinical outcomes including poorer Glasgow Coma Score and larger haematoma volume. Hypocapnia has been shown to improve CA despite concerns over hypoperfusion and consequent ischaemic risks, and it is therefore hypothesised that hypocapnia (via hyperventilation) in acute ICH may improve CA and consequently clinical outcome. BREATHE-ICH is a CA-targeted interventional study in acute ICH utilising a simple bedside hyperventilatory manoeuvre.

Methods and analysis: Patients with acute ICH within 48 hours of onset will be included. The experimental set-up measures cerebral blood flow (cerebral blood velocity, transcranial Doppler), blood pressure (Finometer) and end tidal carbon dioxide (capnography) at baseline, and in response to hypocapnia (-5 mm and -10 mm Hg below baseline) achieved via a 90 s hyperventilatory manoeuvre. Autoregulation is evaluated with transfer function analysis and autoregulatory index calculations. Important classical endpoints associated with this before and after interventional study include death and disability at 14 days and the proportion of recruited individuals able to comply with the full measurement protocol.

Ethics and dissemination: A favourable opinion was granted by the East Midlands-Nottingham 1 Research Ethics Committee (17/EM/0283). It is anticipated that the results of this study will be presented at national and international meetings, with reports being published in journals during late 2018.

Trial registration number: NCT03324321.

Keywords: hypertension; neurological injury; neuroradiology; physiology; stroke.

Conflict of interest statement

Competing interests: None declared.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
Bedside physiological measurement set-up for BREATHE-ICH study: (A) capnograph; (B) cerebral blood velocity waveforms from Dopplerbox (V.10.5.1 software) dedicated laptop; (C) Finometer; (D) PHYSIDAS data acquisition system; (E) DWL Dopplerbox; (F) Korg Metronome.

References

    1. Aaslid R, Lindegaard KF, Sorteberg W, et al. . Cerebral autoregulation dynamics in humans. Stroke 1989;20:45–52. 10.1161/01.STR.20.1.45
    1. Patel N, Panerai RB, Haunton V, et al. . The Leicester cerebral haemodynamics database: normative values and the influence of age and sex. Physiol Meas 2016;37:1485–98. 10.1088/0967-3334/37/9/1485
    1. Tiecks FP, Lam AM, Aaslid R, et al. . Comparison of static and dynamic cerebral autoregulation measurements. Stroke 1995;26:1014–9. 10.1161/01.STR.26.6.1014
    1. Reinhard M, Neunhoeffer F, Gerds TA, et al. . Secondary decline of cerebral autoregulation is associated with worse outcome after intracerebral hemorrhage. Intensive Care Med 2010;36:264–71. 10.1007/s00134-009-1698-7
    1. Nakagawa K, Serrador JM, LaRose SL, et al. . Dynamic cerebral autoregulation after intracerebral hemorrhage: A case-control study. BMC Neurol 2011;11:108,2377–11. 10.1186/1471-2377-11-108
    1. Oeinck M, Neunhoeffer F, Buttler KJ, et al. . Dynamic cerebral autoregulation in acute intracerebral hemorrhage. Stroke 2013;44:2722–8. 10.1161/STROKEAHA.113.001913
    1. Ma H, Guo ZN, Liu J, et al. . Temporal Course of Dynamic Cerebral Autoregulation in Patients With Intracerebral Hemorrhage. Stroke 2016;47:674–81. 10.1161/STROKEAHA.115.011453
    1. Ma H, Guo ZN, Sun X, et al. . Hematoma volume is a predictive factor of disturbed autoregulation after spontaneous intracerebral hemorrhage. J Neurol Sci 2017;382:96–100. 10.1016/j.jns.2017.09.035
    1. van Asch CJ, Luitse MJ, Rinkel GJ, et al. . Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol 2010;9:167–76. 10.1016/S1474-4422(09)70340-0
    1. Anderson CS, Heeley E, Huang Y, et al. . Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med 2013;368:2355–65. 10.1056/NEJMoa1214609
    1. Neumann JO, Chambers IR, Citerio G, et al. . The use of hyperventilation therapy after traumatic brain injury in Europe: an analysis of the BrainIT database. Intensive Care Med 2008;34:1676–82. 10.1007/s00134-008-1123-7
    1. Laffey JG, Hypocapnia KBP. N Engl J Med 2002;347:43–53.
    1. Brian JE. Carbon dioxide and the cerebral circulation. Anesthesiology 1998;88:1365–86.
    1. Muizelaar JP, Marmarou A, Ward JD, et al. . Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg 1991;75:731–9. 10.3171/jns.1991.75.5.0731
    1. Meng L, Gelb AW. Regulation of cerebral autoregulation by carbon dioxide. Anesthesiology 2015;122:196–205. 10.1097/ALN.0000000000000506
    1. Ma X, Willumsen L, Hauerberg J, et al. . Effects of graded hyperventilation on cerebral blood flow autoregulation in experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab 2000;20:718–25. 10.1097/00004647-200004000-00009
    1. Strauss GI. The effect of hyperventilation upon cerebral blood flow and metabolism in patients with fulminant hepatic failure. Dan Med Bull 2007;54:99–111.
    1. McCulloch TJ, Boesel TW, Lam AM. The effect of hypocapnia on the autoregulation of cerebral blood flow during administration of isoflurane. Anesth Analg 2005;100:1463–7. 10.1213/01.ANE.0000148623.06596.7E
    1. Møller K, Høgh P, Larsen FS, et al. . Regional cerebral blood flow during hyperventilation in patients with acute bacterial meningitis. Clin Physiol 2000;20:399–410. 10.1046/j.1365-2281.2000.00276.x
    1. Paulson OB, Strandgaard S, Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev 1990;2:161–92.
    1. Panerai RB. Assessment of cerebral pressure autoregulation in humans--a review of measurement methods. Physiol Meas 1998;19:305–38. 10.1088/0967-3334/19/3/001
    1. Manning L, Hirakawa Y, Arima H, et al. . Blood pressure variability and outcome after acute intracerebral haemorrhage: a post-hoc analysis of INTERACT2, a randomised controlled trial. Lancet Neurol 2014;13:364–73. 10.1016/S1474-4422(14)70018-3
    1. Brodie FG, Atkins ER, Robinson TG, et al. . Reliability of dynamic cerebral autoregulation measurement using spontaneous fluctuations in blood pressure. Clin Sci 2009;116:513–20. 10.1042/CS20080236
    1. Menon DK, Coles JP, Gupta AK, et al. . Diffusion limited oxygen delivery following head injury. Crit Care Med 2004;32:1384–90. 10.1097/01.CCM.0000127777.16609.08
    1. Huttner HB, Steiner T, Hartmann M, et al. . Comparison of ABC/2 estimation technique to computer-assisted planimetric analysis in warfarin-related intracerebral parenchymal hemorrhage. Stroke 2006;37:404–8. 10.1161/01.STR.0000198806.67472.5c
    1. Claassen JA, Meel-van den Abeelen AS, Simpson DM, et al. . Transfer function analysis of dynamic cerebral autoregulation: A white paper from the International Cerebral Autoregulation Research Network. J Cereb Blood Flow Metab 2016;36:665–80. 10.1177/0271678X15626425
    1. Minhas JS, Robinson T, Panerai R. PaCO2 measurement in cerebral haemodynamics: face mask or nasal cannulae? Physiol Meas 2017;38:N101–N106. 10.1088/1361-6579/aa6f9f
    1. Coverdale NS, Gati JS, Opalevych O, et al. . Cerebral blood flow velocity underestimates cerebral blood flow during modest hypercapnia and hypocapnia. J Appl Physiol 2014;117:1090–6. 10.1152/japplphysiol.00285.2014

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren