Confusion with cerebral perfusion pressure in a literature review of current guidelines and survey of clinical practise

Maintaining an adequate cerebral perfusion pressure (CPP) is crucial in patients with traumatic brain injury (TBI). CPP is defined as the difference between the mean arterial pressure (MAP) and the intracranial pressure (ICP). Aggressive attempts to keep the CPP above 70 mmHg have been reported to be detrimental[1, 2], as have CPP levels below 50 mmHg[3]. International guidelines by the Brain Trauma Foundation[4] therefore propose that target CPP should be somewhere between 50 to 70 mmHg, but due to the weaknesses in the existing literature, the optimal CPP after traumatic brain injury is still not settled.

Curiously, how to measure MAP and consequently also CPP in the first place, has not been given much attention. Since most patients with TBI are managed with head elevation, the level of zero calibration of the arterial blood pressure will affect the MAP, and hence CPP levels, significantly. Simple trigonometry reveals that in a person with 30 degrees elevation head and 30 cm distance between heart and the head, the difference in measured MAP/CPP levels will be 11 mmHg depending on if the blood pressure transducer is calibrated in the heart or head level (Figure 1).

The aim of this study was to review the literature that the CPP guidelines are based upon, regarding calibration of the blood pressure transducer for measuring MAP and CPP. We also performed a survey of clinical practice with respect to MAP, CPP and head elevation in European centres treating TBI patients.

The Brain Trauma Foundation has published recommendations regarding CPP thresholds. As evidence for the present recommendation, a total of 11 studies are listed, of which 6 are classified as new, i.e. published between the years 2000 – 2005. These 11 publications were obtained in full text and reviewed carefully to see if there were any details in the text regarding how the MAP was measured, and even more importantly, at what level the arterial line was calibrated. If this information was not revealed in the publications, we contacted the corresponding author by e-mail and/or mail. Evidence levels and grades of recommendations were assessed according to the classification from Oxford Centre for Evidence-Based Medicine. We have not attempted to do a systematic literature search and review of the available literature not included in the Brain Trauma Foundations guidelines.

A short questionnaire was sent to European centres treating patients with TBI. The survey was conducted by using an Internet-based survey tool (SurveyMonkey Inc., Palo Alto, CA, USA, (http://​www.​surveymonkey.​com)). In February 2013 a short questionnaire (Table 1) was sent by e-mail to the head of 309 European neurosurgical centres treating patients with brain injuries. The e-mail addresses were obtained by contacting the national neurosurgical societies in each respective country. A reminder e-mail was sent to all non-responders after 1 week and 4 weeks, before the survey was closed after 8 weeks. All answers were managed anonymously.

The statistical analysis and graphs were performed using IBM Statistical Package for the Social Sciences (SPSS) V.21. A Pearson Chi-square test was used to investigate the relationship between desired CPP-thresholds and level of arterial line calibration.

Measurements of and interventions to obtain optimal CPP is a cornerstone in neuro-intensive care. However, routines on how to measure MAP will affect observed CPP levels profoundly. Unfortunately, we find that studies behind the recommended CPP thresholds often do not elaborate on how MAP and CPP are measured. Additionally, methods of MAP and CPP measurements vary considerably in the studies where this information was available. The only level II evidence study cited in respect to CPP in the TBI guidelines measured MAP and ICP at the same level[2]. This randomised study from 1999 compared an ICP-targeted protocol and a CPP-targeted protocol and reports that the risk of cerebral ischemia was 2.4-fold greater with the ICP-targeted protocol, but that the risk of ARDS was a 5-fold greater with a CPP-targeted protocol. Median CPP levels were >70 mmHg in both protocols, but somewhat lower in the ICP-targeted group. This single study is the basis for the level II recommendation against CPP > 70 mmHg in the Brain Trauma foundation guidelines. In addition to resting on limited evidence from few studies, the recommended CPP target values can be questioned since there is no consensus on how to measure CPP in the first place. Indeed, our small survey among neurosurgical departments further demonstrates that clinical practice is highly variable, both in terms on how to measure CPP and when to intervene.

A limitation of the study was the low response rate in the survey, but it was somewhat as expected when comparing to other internet based surveys[13]. This raises some caution against the interpretation of the distribution of responses within each category. Nevertheless, the 58 respondents give a clear answer of that practices vary between neurosurgical centres related to the measurement of CPP and treatment of TBI patients. As it is very unlikely that only centres with a varied practice answered the survey, a higher response rate would not change the fact that there are different routines. The principles of validity and reliability are fundamental cornerstones of all scientific and clinical measures. While the low number of studies and the low evidence level published limit the validity of CPP when it comes to the clinical implication (e.g. target values), the diversity in how CPP is measured both in the literature and in clinical practice greatly limits the reliability. A shortness in both reliability and validity is clearly problematic for any measure.

In conclusion, the methods for CPP measurements in studies used for development of TBI guidelines are often not reported. Studies that report how CPP is obtained use various methods. Clinical practice related to the measurement and treatment of CPP varies between neurosurgical centres. Until a consensus is reached on how to measure CPP, confusion will prevail.