Cerebral perfusion pressure as a therapeutic target

Question 1 from the second paper of 2009 and Question 24 from the second paper of 2006 asked for a detailed discussion about the utility of using CPP as a therapeutic target. Unfortunately, the college model answer was very brief; it probably reflects some sort of minimal level of competence. An ideal synopsis of this issue is offered by LITFL. No resource improves on the brevity or clarity of their short note on this concept. If brevity and clarity are not your thing, then you should probably read this 2013 review article from the BJA, by Kirman and Smith, and the canonical "Guidelines for the management of severe traumatic brain injury" from the Brain Trauma Foundation.

In brief:

Advantages and Disadvantages of CPP-guided Therapy




From physiology

  • Only a surrogate for cerebral blood flow
  • As cereberal vascular resistance varies the measured CPP will remain the same.
  • The "optimal" CPP for an ideal CBF will differ in heterogenous brain apthology, as well as at different times and in different patients
  • CPP does not correlate very well with brain tissue oxygenation.

From pragmatism

  • Cheap and easy to monitor
  • The staff are familiar with it.
  • It can be monitored continuously.
  • On can react to changes more easily.
  • Augments clinical and radiological assessments of TBI
  • Probably better than MAP or ICP alone
  • It is unclear where to zero the transducer.
  • Even when guidelines for this are available, they are not being followed.
  • Even where the guidelines are being followed, it is unclear whether it makes any real positive difference.
  • When you zero the transducer at the foramen of Munro, you end up targeting an absurdly high blood pressure (when referenced at the heart according to normal practice) - this may have serious unintended consequences.

From authority

From evidence

  • There is no Class I evidence in support of this practice.
  • There is evidence that CPP-guided therapy can be harmful: ARDS tends to develop.
  • Mortality benefit mainly seen in one trial and is otherwise from retrospective cohort studies
In detail:

Relationship of blood pressure, intracranial pressure, cerebral perfusion and blood flow

Cerebral perfusion pressure is the driving pressure gradient which produces flow in the cerebral circulation against the resistance of cerebral vessels. Thus, it is the difference in mean cereberal arterial pressure and the mean cereral venous pressure. Because we can hardly measure the latter and we only guess at the former, a useful approximation is to subtract intracranial pressure (ICP) from the mean systemic arterial pressure (MAP). Thus, CPP = (MAP - ICP).

Cerebral perfusion pressure = MAP - (ICP or CVP, whichever is higher).

Cerebral blood flow = CPP / CVR (cerebral vascular resistance)

However, it is not a measure of cerebral blood flow. Flow is a very different property; cerebral blood flow is a function of both the pressure gradient and the resistance. Cerebral vascular resistance might change randomly and regionally, all without any change in systemic MAP. Not only that, but "flow" alone does not determine cereberal oxygenation - there are even more factors involved in this, such as the oxygen carrying capacity of red cells, the viscosity of the blood, etc etc...

Rationale for cerebral perfusion pressure monitoring

Why are we even interested in cerebral perfusion pressure?

  • ICP on its own is probably somewhat useless, given that it relates very indirectly to cerebral blood flow.
  • When cerebral autoregulation is impaired, the CPP correlates linearly with cerebral blood flow.
  • Thus, one can estimate that if one's cerebrovascular autoregulation is regionally impaired, with a CPP around 60mmHg one should have optimal blood flow both to the regions with impaired autoregulation and to the regions where it is preserved.
  • Thus, CPP rather than ICP should be the main parameter to guide therapy.
  • Targeting a CPP also forces one to actively manage hypotension, which has known negative associations in traumatic brain injury.

Evidence behind this rationale:

Advantages of cerebral perfusion pressure monitoring

There are some advantages of using CPP as a treatment target in traumatic brain injury. The brain-injured patient is unable to autoregulate their cerebral blood flow, and thus they rely on you to make sure that their cerebral arterial pressure remains reasonably high. Its easy enough to monitor it continuously if you have both an arterial line and an ICP monitor.

Arguments from convenience and safety

  • Cheap and easy to monitor, if the patient already has an arterial line and an ICP monitor.
  • Automatic algorithms perform the calculations for you.
  • It has been around for some decades, and the staff are familiar with it.
  • It can be monitored continuously.
  • Continuous monitoring allows one to observe severe fluctuations, and react to them
  • CPP monitoring does not negate clinical and radiological assessment of cerebral perfusion- rather, it augments them.

Arguments from authority

  • Endorsed by the Brain Trauma Foundation (target CPP 50-70 mmHg).
    • In their model answer to Question 1 from the second paper of 2009 the College makes a statement regarding there being no Class I evidence to suport the use of CPP-guided blood pressure management in traumatic brain injury. True, but the entire set of BTF guidelines only has one single piece of Class I evidence, which is "don't you ever use steroids". Thus, one cannot single out the CPP guidelines as somehow "baseless" on the grounds that no investigator has thus far dared to randomise a group of brain-injured patients to an experimental group in whom the CPP is totally unmanaged.
  • Endorsed by the Neuroanaesthesia Society of Great Britain and Ireland (NASGBI) and the Society of British Neurological Surgeons (SBNS) - see their position statement (apparently CPP monitoring "remains the standard of care", though the Societies acknowledge that "there has been recent controversy". This statement references the 2014 Kirkman and Smith article.

Arguments from pragmatic bedside concerns

  • If you can calculate the CPP, that means you are monitoring the ICP and the MAP.
  • Ergo, if you ignore the CPP, that means you think that either the MAP alone or the ICP alone are more important as therapeutic endpoints (contrary to internationally accepted guidelines). Or you would prefer to rely on something even more wacky and experimental. Sure, its an option. But what would the coroner say?
  • Thus, you should target the CPP while there is nothing better to target.

Arguments from evidence

  • A trial of CPP vs ICP-targeted management (Kumar et al, 2014) found a 20% difference in 90-day mortality in favour of the CPP-guided group (18.2% vs 38.2%);  however it must be mentioned that the study population were 110 children with meningitis, rather than TBI patients.

Disadvantages of cerebral perfusion pressure monitoring

Counter-arguments from theoretical physiology

  • CPP is only a surrogate for cerebral blood flow (CBF).
  • As cereberal vascular resistance varies (eg. with varying levels of vasoactive agents and sedatives, and with changes in respiration) the cerebral blood flow will also vary- but the measured CPP could remain the same. You simply wouldn't know.
  • With heterogeneous brain pathology, individual variations in cerebral vascular health, and hourly variations in the level of sedation, the "optimal" CPP for an ideal CBF will likely be very different in any given patient, at any given moment. Targeting a CPP tends to ignore the fact that no brain is uniformly injured, and that there are regions which are still able to autoregulate their bloodflow.
  • Brain oxygenation is really what we are interested in, but CPP does not correlate very well with the PbO2 (although when grouped with ICP it sort-of correlates with good perfusion, provided it is over 60mmHg)

Counter-aguments from the uselessness of guidelines

  • The recommendations for the use of CPP monitoring are by no means firm. The BTF only has Level II recommedations to make regarding keeping the CPP under 70, and Level III recommendations regarding keeping it above 50.
  • The site of transducer calibration should be at the level of the Foramen of Monro, as per NASGBI/SBNS guidelines - but according to a 2013 survey, everybody is ignoring this guideline and referencing the right atrium routinely.
    • This is worrying, because for patients with 50° head elevation, there is an 18mmHg CPP difference - which means that with a heart-referenced CPP of 60mmHg, the "true" CPP is around 42mmHg.
    • This is even more worrying, because the two papers (Changaris and Clifton) referenced by the Brain Trauma Foundation in support of their over-60mmHg CPP target both zeroed their transducers at the level of the heart. In fact, all the studies used by the BTF either used wildly different pressure reference levels, or simply failed to report their methodology. What was the true pressure at the tragus? Who knows.

Counter-arguments from pragmatic bedside concerns

  • To maintain a CPP of 60mmHg at the Foramen of Monro with an ICP of 20mmHg, one must maintain a heart-reference-level MAP of 98mmHg, which would probably correspond to an SBP of around 150-170mmHg. This is not a benign blood pressure. In one's desperate bid to protect the brain, one may inadvertantly flood the patient with fluid and cause pulmonary oedema, or exacerbate existing neurogenic pulmonary oedema.
  • Thus, therapy to maintain CPP can be harmful.
  • Specifically, the monitoring of CPP requires the monitoring of ICP, which requires a hole to be drilled in your head, with all the inconvenience thereof.
  • Even with an ICP monitor and an arterial line, you are making measurements which are subject to error, and then you are amplifying that error by calculating a derived parameter from them.

Counter-arguments from hard evidence

  • There is no Class I data to support the use of CPP monitoring in TBI.
  • Specifically, there is no well-designed trial comparing CPP to another validated therapeutic goal in the setting of adult TBI.
  • There is evidence that mindless pursuit of the CPP can be harmful: ARDS tends to develop.


Oh's Intensive Care manual

Chapter 52   (pp. 580)  Cerebral  protection by Victoria  Heaviside  and  Michelle  Hayes

Harper, A. MURRAY. "Autoregulation of cerebral blood flow: influence of the arterial blood pressure on the blood flow through the cerebral cortex." Journal of neurology, neurosurgery, and psychiatry 29.5 (1966): 398.

Phillips, Stephen J., and Jack P. Whisnant. "Hypertension and the brain."Archives of internal medicine 152.5 (1992): 938-945.

Paulson, O. B., S. Strandgaard, and L. Edvinsson. "Cerebral autoregulation." Cerebrovascular and brain metabolism reviews 2.2 (1989): 161-192.

Busija, David W., and Donald D. Heistad. Factors involved in the physiological regulation of the cerebral circulation. Springer Berlin Heidelberg, 1984.

Immink, Rogier V., et al. "Impaired cerebral autoregulation in patients with malignant hypertension." Circulation 110.15 (2004): 2241-2245.

Mankovsky, B. N., et al. "Impairment of cerebral autoregulation in diabetic patients with cardiovascular autonomic neuropathy and orthostatic hypotension." Diabetic medicine 20.2 (2003): 119-126.

Strauss, Gitte Irene, et al. "Cerebral autoregulation in patients with end-stage liver disease." European journal of gastroenterology & hepatology 12.7 (2000): 767-771.

Taccone, Fabio Silvio, et al. "Cerebral autoregulation is influenced by carbon dioxide levels in patients with septic shock." Neurocritical care 12.1 (2010): 35-42.

SYMON, LINDSAY, K. Held, and N. W. C. Dorsch. "A study of regional autoregulation in the cerebral circulation to increased perfusion pressure in normocapnia and hypercapnia." Stroke 4.2 (1973): 139-147.

Eames, P. J., et al. "Dynamic cerebral autoregulation and beat to beat blood pressure control are impaired in acute ischaemic stroke." Journal of Neurology, Neurosurgery & Psychiatry 72.4 (2002): 467-472.

Golding, Elke M., Claudia S. Robertson, and Robert M. Bryan. "The consequences of traumatic brain injury on cerebral blood flow and autoregulation: a review." Clinical and experimental hypertension 21.4 (1999): 299-332.

Schaafsma, A., et al. "Cerebral perfusion and metabolism in resuscitated patients with severe post-hypoxic encephalopathy." Journal of the neurological sciences 210.1 (2003): 23-30.

Symon, L., et al. "Effect of supratentorial space-occupying lesions on regional intracranial pressure and local cerebral blood flow: an experimental study in baboons." Journal of Neurology, Neurosurgery & Psychiatry 37.6 (1974): 617-626.

Møller, Kirsten, et al. "Dependency of cerebral blood flow on mean arterial pressure in patients with acute bacterial meningitis." Critical care medicine 28.4 (2000): 1027-1032.

Tang, Sung-Chun, et al. "Impaired cerebral autoregulation in a case of severe acute encephalitis." Journal of the Formosan Medical Association 106.2 (2007): S7-S12.

Eriksson, Evert A., et al. "Cerebral perfusion pressure and intracranial pressure are not surrogates for brain tissue oxygenation in traumatic brain injury."Clinical Neurophysiology 123.6 (2012): 1255-1260.

Kumar, Ramesh, et al. "Randomized Controlled Trial Comparing Cerebral Perfusion Pressure–Targeted Therapy Versus Intracranial Pressure–Targeted Therapy for Raised Intracranial Pressure due to Acute CNS Infections in Children*." Critical care medicine 42.8 (2014): 1775-1787.

Kirkman, M. A., and M. Smith. "Intracranial pressure monitoring, cerebral perfusion pressure estimation, and ICP/CPP-guided therapy: a standard of care or optional extra after brain injury?." British journal of anaesthesia (2013): aet418.

Nordström, Carl-Henrik, et al. "Assessment of the lower limit for cerebral perfusion pressure in severe head injuries by bedside monitoring of regional energy metabolism." Anesthesiology 98.4 (2003): 809-814.

Clifton, Guy L., et al. "Fluid thresholds and outcome from severe brain injury*."Critical care medicine 30.4 (2002): 739-745.

Balestreri, Marcella, et al. "Impact of intracranial pressure and cerebral perfusion pressure on severe disability and mortality after head injury."Neurocritical care 4.1 (2006): 8-13.

Juul, Niels, et al. "Intracranial hypertension and cerebral perfusion pressure: influence on neurological deterioration and outcome in severe head injury*."Journal of neurosurgery 92.1 (2000): 1-6.

Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons. "Guidelines for the management of severe traumatic brain injury." J Neurotrauma 2007;24(Suppl. 1):S1-106.

Kosty, Jennifer A., et al. "A Comparison of Clinical and Research Practices in Measuring Cerebral Perfusion Pressure: A Literature Review and Practitioner Survey." Anesthesia & Analgesia 117.3 (2013): 694-698.

CHANGARIS, DAVID G., et al. "Correlation of cerebral perfusion pressure and Glasgow Coma Scale to outcome." Journal of Trauma and Acute Care Surgery27.9 (1987): 1007-1013.

Al-Rawi, P. G., et al. "Multiparameter brain tissue monitoring--correlation between parameters and identification of CPP thresholds." Zentralblatt Fur Neurochirurgie 61.2 (1999): 74-79.

Rao, Vidar, et al. "Confusion with cerebral perfusion pressure in a literature review of current guidelines and survey of clinical practise." Scand J Trauma Resusc Emerg Med 21.1 (2013): 78.

Tisdall, Martin M., and Martin Smith. "Cerebral microdialysis: research technique or clinical tool." British journal of anaesthesia 97.1 (2006): 18-25.

Zweifel, Christian, et al. "Continuous monitoring of cerebrovascular pressure reactivity in patients with head injury." Neurosurgical focus 25.4 (2008): E2.

Contant, Charles F., et al. "Adult respiratory distress syndrome: a complication of induced hypertension after severe head injury." Journal of neurosurgery 95.4 (2001): 560-568.

Kirkman, M. A., and M. Smith. "Intracranial pressure monitoring, cerebral perfusion pressure estimation, and ICP/CPP-guided therapy: a standard of care or optional extra after brain injury?." British journal of anaesthesia 112.1 (2013): 35-46.

Livesay, Sarah L., et al. "Challenges of Cerebral Perfusion Pressure Measurement." Journal of Neuroscience Nursing49.6 (2017): 372-376.