Cerebral hypoperfusion in neurocritical care. Ready for a TCD-guided therapy

Dear Editor,

we read with very interest the excellent paper from Melo et al. [1], and we strongly agree that Transcranial Doppler (TCD) is not only a monitoring device, but a tool for guiding therapy in case of neurological deterioration. Indeed, growing evidence suggests that TCD:

• Allows for an estimate of the absolute value of the cerebral perfusion pressure (CPP), both when either intracranial hypertension or arterial hypotension are present [2]. Some formulas are frequently used for this purpose [3].

• Can estimate the adequacy of CPP through the analysis of waveform parameters [Pulsatility index (PI), Diastolic velocity (Vdia), Mean velocity (Vmean)] [4, 5]. Regardless of the absolute value, the presence of a PI greater than 1.3 together with a Vdia less than 20 cm/sec is associated with insufficient CPP [6]. Even if these criteria are not accurate, since affected from several confounding factors, they could be useful to target absolute values of CPP bedside.

• Allows for the evaluation of static cerebral autoregulation, providing not only qualitative information, but also giving us the possibility to determine the patient’s position within the Lassen curve [7]. In fact, in the ascending part of the curve before the plateau, TCD will show hypoperfusion parameters, and an increase in systemic arterial pressure will be associated with an increase in velocities, indicating an absence of autoregulation. During the plateau of the curve, autoregulation will be present, and TCD will show small or no changes in velocities, in response to changes in systemic arterial pressure. In the ascending part of the curve after the plateau, autoregulation will be absent, and TCD will show hyperemic parameters.

TCD to identify the cause of hypoperfusion

As the authors interestingly state, TCD findings should not be interpreted in isolation, but integrated with systemic hemodynamic assessment. In their clinical vignette, TCD was suggestive of cerebral hypoperfusion. After ruling out hypovolemia, they chose to increase systemic arterial pressure, which normalized TCD cerebral perfusion data.

This is consistent with several evidence that showed that normalization of Vdia and PI is feasible in a TCD-guided resuscitation strategy in traumatic and non-traumatic comatose patients, and could be associated with a better prognosis [4, 8, 9]. Ract observed that a TCD guided strategy corrected brain hypoperfusion on admission in ICU in 9 severe head injured patients on 11, and was associated with a better GOS at three months ((3 vs. 1 p < 0.006) [4]. Similar results were obtained on 19 comatose patients by Tamagnone et al., who observed that increasing Mean Arterial Pressure (MAP) with fluids and norepinephrine, a TCD pattern of brain hypoperfusion was corrected in 68% of cases [8]. Tazarourte et al. observed that mortality was 100% in patients for whom the TCD could not be corrected during early phase of care [9].

Furthermore, hypoperfusion on TCD could be secondary not only to arterial hypotension, but also to high intracranial pressure (ICP). In these cases, ruling out intracranial hypertension could be an important and necessary information for optimizing treatment. To this aim, by integrating TCD data with systemic blood pressure parameters, some authors used the Czosnyka formula, achieving good accuracy in ruling out intracranial hypertension [3]. According with this formula, CPP can be estimated as eCPP= (MAP * Vdia/Vmean) + 14. Subsequently, ICP can be calculated as eICP = MAP-eCPP. If compared with other formulas, such as Bellner equation, it has the advantage of putting together TCD waveform and systemic pressure, obtaining a more accurate evaluation of ICP [10]. In Impressit-2 study, Rasulo et al. found a low concordance correlation between global values of eICP and ICP, but an high discriminant accuracy of eICP in excluding intracranial hypertension (Negative Predicted Value (NPV) 91.3% if ICP > 20 mmHg; NPV 95.6% if ICP > 22 mmHg; NPV 98.6% if ICP > 25 mmHg) [3].

In our opinion, using Czosnyka method, TCD has the potential not only to identify hypoperfusion as the authors focused on, but also to understand its cause. This approach can be a useful adjunct when invasive ICP monitoring is not possible.

Hypoperfusion or Intracranial hypertension?

On the other side, a normal TCD waveform does not in itself rule out intracranial hypertension [2]. In fact, TCD can give us an estimate of CPP, which may be normal in cases of intracranial hypertension associated with arterial hypertension. Therefore, the presence of a normal PI and a normal Vdia is not sufficient to exclude high ICP, but must be associated with an assessment of systemic blood pressure. Czosnyka method should be used in this setting [3]. This point is in contrast with one of the recent recommendations of the B-ICONIC Consensus, which suggests considering threshold values of PI lower than 1.3 and of Vdia higher than 20 cm/sec for excluding high ICP [6].

Taking these considerations into account, the clinical vignette deserves further comment. Indeed, the normalization of TCD hypoperfusion indices through an increase in arterial pressure indicates the achievement of eCPP associated with improved cerebral perfusion, but does not completely rule out a high ICP. This is true, in particular if MAP is higher than normal. Even in this case, the use of the Czosnyka method can be useful.

Hypoperfusion with normal CPP

Interestingly, the authors underline the limits of PI, and correctly state that a high PI could be the effect of increased arterial pulsatility (such as in hyperdynamic state, or in case of increased compliance during arterial hypotension) or an increase of distal resistances [11]. Nevertheless, an increased PI together with low Vdia is suggestive of cerebral hypoperfusion regardless of the cause that induced it. In particular, hypocapnia is a frequent cause of TCD pattern of hypoperfusion, even if CPP is normal. In contrast with authors, we think that PI can reflect a true reduction in cerebral perfusion in hypocapnia, and a low CO₂ should be ruled out before manipulating CPP.

We congratulate the authors on their excellent review of the physiological principles underlying the use of TCD and its practical applications. We believe that a wider diffusion of Czosnyka method, that put together TCD waveform and arterial pressure, could have an important diagnostic role in the correct interpretation of TCD data. We are convinced that despite its several limitations in diagnosis of brain hypoperfusion, TCD will be able to provide important information when included within a structured algorithm for the diagnosis and treatment of patients with acute neurological deterioration [12].

Author contributions

All authors contributed to the conception, preparation of the original draft and revision for important intellectual content. All authors approved the final version of the manuscript.

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Competing interests

The authors declare no competing interests.