Statistics from Altmetric.com
Czosnyka et al 1recently published a study investigating the clinical significance of critical closing pressure (CCP) estimates in patients with head injury. I see problems both with the theoretical foundation of their CCP concept and with the interpretation of their results.
Firstly, the physiological meaning of both formulae of CCP presented (CCP1 and CCP2, respectively) is questionable. The implication of both presented equations is that the instantaneous value of cerebral blood flow velocity (FV(t)) at a given moment t is equal to arterial blood pressure at the given time (ABP(t)) minus CCP divided by cerebrovascular resistance (CVR):
FV(t) = (ABP(t)−CCP)/CVR (1)
At the time of systolic and diastolic pressure values (ABPs, ABPd), respectively, it follows that systolic and diastolic FV (FVs, FVd) should be equal to (ABPs−CCP)/CVR and (ABPd−CCP)/CVR, respectively. However, it is a well known fact that the vascular resistance valid for the static pressure/flow connection (CVR0, concerning mean pressures and flows) is different from and is in general much higher than resistances determining dynamic pressure/flow relations (CVR1) as in the case of pulsatile pressures.2 Therefore, equation 1 cannot be applied to describe dynamic flow. This can best be illustrated using the frequency domain approach (ABP=mean pressure; FV=mean flow velocity; A1=amplitude of the pulsatile pressure wave; F1=amplitude of the pulsatile flow wave):
Inserting equations 2 and 3 into the frequency domain equation for CCP2 of the authors
=ABP(1−CVR1/CVR0)+CVR1/ CVR0×CCP (5)
Obviously, CCP2 is only in the case of CVR1=CVR0 equal to CCP. Under the more realistic assumption that CVR1 is equal to about half of CVR0 it follows for CCP2:
With decreasing CVR1/CVR0 ratios, CCP2 becomes more and more dependent on ABP and independent of CCP. In any case, without exact knowledge of the CVR1/CVR0 ratio, equation 4 is useless for a valid CCP calculation.
The second criticism concerns the correlation of the calculated CCP2 values with mean ABP found by the authors (r=0.5; p<0.05). According to the original idea of Burton,3 CCP represents a certain mean ABP value below which small vessels begin to collapse. CCP should, therefore, be a constant value independent of the actual ABP. On the other hand, this significant correlation can be explained by our equation 5, again indicating the missing physiological basis of the CCP concept of the authors.
Thirdly, it seems doubtful that CCP could be estimated using pressure and flow values from ABP ranges clearly above CCP and flow values clearly above zero flow, respectively. As long as small vessels do not collapse (ABP>CCP) it is not possible to decide whether their actual wall tension is determined more by transmural pressure or by active vasoconstriction. However, the relative contribution of both effects is critical for the limit of CCP.
Finally, I would be interested in the authors' explanation of negative diastolic flow values as seen in Doppler spectra of arteries with a high vascular resistance (peripheral arteries, middle cerebral artery during strong hypocapnea). In the case of ABPd<CCP and a small vessel collapse according to the model of the authors, CVR should increase towards ∞ and FVd towards zero (equation 1). Negative flow values could, consequently, not occur.
I suggest that the relation between pulsatile pressure and flow should be better described using the concept of different static and dynamic resistances (CVR0 and CVR1). The driving pressure of the mean FV is more accurately given by cerebral perfusion pressure (CPP=ABP-ICP) than by ABP-CCP. Therefore, equation 2 changes to
and equation 5 to
CCP2=ABP(1−CVR1/CVR0)+CVR1/ CVR0×ICP (7)
Equation 7 explains well the positive correlations found between CCP2 and ABP and between CCP2 and ICP, respectively, without assuming a connection between CCP2 and Burton's concept of “critical closing pressure”.3
Czosnyka et al reply:
We thank Diehl very much for the interesting letter provoking some mathematical considerations about cerebral haemodynamics.
We need to emphasise that our primary intention1-1 was to investigate Burton's hypothesis in patients with head injury1-2 that critical closing pressure (CCP) may be represented by a sum of intracranial pressure (ICP) and the tension in the arterial walls:
CCP=ICP+active tension of arterial walls
Aaslid1-3 proposed the mathematical formula taken for calculations:
(where ABP and FV are mean values of arterial pressure and MCA flow velocity, ABPs and FVs are systolic values, ABPpp and FVpp are peak to peak amplitudes ). A graphical interpretation of this formula has been given in1-1 in fig 1. CCP1 is an x intercept point of linear regression between subsequent systolic and diastolic values recorded within 6 second intervals of flow velocity (along y axis) and arterial pressure (along x axis).
In fact, the formula proposed by Michel et al 1-4 is very similar. The only difference is that instead of the original waveforms of FV and ABP, first (fundamental) harmonic components were taken for the same graphical construction—that is:
In our paper1-1 we confirmed empirically that both CCP1 and CCP2 produced the same values in a group of patients after head injury, therefore the mathematical consideration of Diehl (equations 1–5) must contain an error!
First of all we cannot see how equation (1) from Diehl's letter can be derived from any of our formulae. Everyone who has tried to plot momentary values from ABP pulse waveform against momentary values of FV waveform knows that it never plots a straight line (as equation (1) implies). In between two “clouds” of systolic and diastolic values of ABP and FV waveforms (fig 1 in1-1) one can rather see an ellipsoidal shape which is very seldom regular enough to be approximated by a straight section. Therefore, equation (1) in Diehl's letter is not correct. In fact, CVR is a frequency dependent variable (represents vascular impedance) and if a linear theory can be applied, division in (1) should be substituted by a convolution with an inverse of Fourier transform of “cerebrovascular admitance”.
Definition of CVR0 as FV/(ABP-CCP) is completely artificial and lacks a physiological basis. It is rather taken from the geometrical interpretation of figure 1 in1-1. In our material equivalent of parameter CVR0 (as defined by Diehl) is 1.007 (SD 031) and CVR1 0.972 (SD 0.29), the difference between them was not statistically significant. Therefore, the suggestion that the CVR1/CVR0 ratio is 0.5 is not correct. Real CVR0 should be calculated as (ABP−ICP)/FV. We fully agree that equation (5) proposed by Diehl is “useless for valid CCP calculation”. We have not used it and have never suggested anyone could do so.
The second criticism was that our CCP positively correlated with ABP.
It should not be a surprise. When ABP decreases, vasodilatation occurs and arterial wall tension decreases. Therefore presuming ICP was constant, CCP should decrease. A rather weak (though significant) correlation suggests that not all of our patients were pressure reactive or ICP was not always constant.
The final issue concerning negative flow velocity is a trap Diehl has prepared for himself. We never suggested that any factor interpretable as cerebrovascular resistance (CVR0 or CVR1) should be involved in the concept of critical closing pressure. From the definition, closure is a strongly non-linear phenomenon, therefore applying linear theory here is very risky. How risky—we can see from Diehl's letter. Cerebrovascular resistance certainly never increases to infinity, only after death.
We fully agree with the considerations regarding equations (6) and (7). CCP can be understood as a combination of ABP and ICP with coefficients describing properties of the cerebrovascular bed. Whether it simplifies our knowledge—we personally find it doubtful.
Finally, we are truly obliged to Diehl for an opportunity to have this interesting discussion.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.