Research Article: Influence of mild-moderate hypocapnia on intracranial pressure slow waves activity in TBI

Date Published: December 16, 2019

Publisher: Springer Vienna

Author(s): Erta Beqiri, Marek Czosnyka, Afroditi D. Lalou, Frederick A. Zeiler, Marta Fedriga, Luzius A. Steiner, Arturo Chieregato, Peter Smielewski.


In traumatic brain injury (TBI) the patterns of intracranial pressure (ICP) waveforms may reflect pathological processes that ultimately lead to unfavorable outcome. In particular, ICP slow waves (sw) (0.005–0.05 Hz) magnitude and complexity have been shown to have positive association with favorable outcome. Mild-moderate hypocapnia is currently used for short periods to treat critical elevations in ICP. Our goals were to assess changes in the ICP sw activity occurring following sudden onset of mild-moderate hypocapnia and to examine the relationship between changes in ICP sw activity and other physiological variables during the hypocapnic challenge.

ICP, arterial blood pressure (ABP), and bilateral middle cerebral artery blood flow velocity (FV), were prospectively collected in 29 adult severe TBI patients requiring ICP monitoring and mechanical ventilation in whom a minute volume ventilation increase (15–20% increase in respiratory minute volume) was performed as part of a clinical CO2-reactivity test. The time series were first treated using FFT filter (pass-band set to 0.005–0.05 Hz). Power spectral density analysis was performed. We calculated the following: mean value, standard deviation, variance and coefficient of variation in the time domain; total power and frequency centroid in the frequency domain; cerebrospinal compliance (Ci) and compensatory reserve index (RAP).

Hypocapnia led to a decrease in power and increase in frequency centroid and entropy of slow waves in ICP and FV (not ABP). In a multiple linear regression model, RAP at the baseline was the strongest predictor for the decrease in the power of ICP slow waves (p < 0.001). In severe TBI patients, a sudden mild-moderate hypocapnia induces a decrease in mean ICP and FV, but also in slow waves power of both signals. At the same time, it increases their higher frequency content and their morphological complexity. The difference in power of the ICP slow waves between the baseline and the hypocapnia period depends on the baseline cerebrospinal compensatory reserve as measured by RAP.

Partial Text

In traumatic brain injury (TBI) the mean value of intracranial pressure (ICP) might not be sufficient to help fully interpret the clinical status of the patient, while ICP waveforms contain information about the nature of the cerebrospinal circulation pathophysiology. ICP waveform can be decomposed into the following components defined in the frequency domain: the pulse waveform (which fundamental harmonic component frequency equals the heart rate), the respiratory waveform (related to the frequency of the respiratory cycle, 8–20 cycles/minute) and the “Slow waves” [7] which were previously defined in the Lundberg thesis as B waves with “frequency 0.5–2/min with amplitude from discernibility to 20 mmHg” [24] and which definition was modified and adjusted in the latest years. Slow waves can be defined as oscillations in cerebral pressures and cerebral blood flow of duration longer than those of the respiratory origin with a spectral representation within the frequency limits defined roughly as 0.005–0.05 Hz [7]. Analysis of slow waves in ICP could provide information about cerebral blood flow (CBF) autoregulation [36], brain compliance [27, 24] and brainstem activity [37, 22, 15]. Moreover, various parameters derived from slow waves, in particular higher magnitude [2] and higher complexity [23], were shown to be associated with outcome after TBI.

We present a retrospective analysis of waveform recordings of ICP, ABP, and bilateral MCA blood flow velocity (left – FVl, and right – FVr), prospectively collected during CO2-reactivity studies in adult (age > 16 years) severe TBI patients requiring ICP monitoring and mechanical ventilation admitted in the Neurocritical Care Unit (NCCU) at Addenbrooke’s Hospital, Cambridge, from March 2001 to February 2002. Reaching back to digital recordings from past studies was motivated by new findings regarding slow ICP waves and the role of autoregulation assessment [21, 3].

Twenty-nine adult (median age 39 years, 5 females) severe TBI patients (mean GCS 6 ± 3) were included. Figure 2 shows a typical example of the time trends of the recorded signals and Fig. 3 shows an example of the trend of the calculated slow waves component and the PSD chart during the baseline and the hypocapnia period, where mean pCO2 dropped from 5.10 ± 0.36 kPa to 4.39 ± 0.35 kPa, p < 0.001. Statistical comparisons of baseline versus hypocapnic period values are given in Table 1. Correlations between changes in ICP slow wave pattern and other physiological variables are presented in Table 2.Fig. 2Example of the time trends of the recorded signals. Sampling frequency = 30 Hz. The gaps in the charts are due to the manual removal of artifacts such as arterial line flush, ICP transients, or FV disturbed signals. ABP, arterial blood pressure; ICP, intracranial pressure; FVl, flow velocity left; FVr, flow velocity rightFig. 3Time trend of the calculated ICP slow wave component and the PSD chart during the baseline and the hypocapnia period. ICP time series is presented as resampled to 1 Hz. ICP_sw shows the trend of the slow wave component of intracranial pressure as obtained by applying the FFT band-pass filter. Power spectral density analysis is shown (periodogram method using Hanning window) for the specific frequency range, for the two selected periods (baseline and hypocapnia). The correspondent power and centroid are shown in the spectral statistics table. ICP, intracranial pressure; ICP_sw, intracranial pressure slow waves time series; PSD, power spectral densityTable 1Mean values and SD of the studied parameters at the baseline and during hypocapnia. When the changes between baseline and hypocapnia are significant, the direction of the change is highlighted. p values of univariate analysis are quoted uncorrected for multiple comparisonVariableBaselineHypocapniaChangep valueMeanSDMeanSDFrequency domainPower of sw (mmHg2)ICP1.041.820.270.49↘0.006*ABP2.954.141.901.400.177FVl16.0220.4810.9013.66↘0.049*FVr16.8821.699.4811.67↘0.005*Centroid of sw (Hz)ICP0.0200.0060.0230.005↗< 0.001*ABP0.0160.0050.0200.006↗< 0.001*FVl0.0230.0060.0270.004↗< 0.001*FVr0.0220.0060.0260.005↗< 0.001*Time domain, swEntropy of swICP0.500.110.560.06↗< 0.001*ABP0.440.110.510.10↗< 0.001*FVl0.550.070.580.05↗< 0.001*FVr0.540.090.580.07↗< 0.001*Time domain, time seriesTime series (mmHg)ICP16.656.7013.036.35↘< 0.001*ABP96.458.9898.8311.650.100FVl77.6735.6565.5729.72↘< 0.001*FVr78.1426.8261.6517.50↘< 0.001*Coefficient of variationICP0.↘0.006*ABP14.9413.2917.1032.210.700FVl37.1036.2939.3771.750.825FVr40.8941.6537.8372.340.869Time domain, derivate indexesCoherence ICP-FVl0.780.190.780.190.951Coherence ICP-FVr0.760.210.760.190.401Ci_l (cm3/mmHg)2.151.413.082.38↗0.006*Ci_r (cm3/mmHg)2.361.633.072.69↗0.008*RAP0.510.340.410.34↘0.026*sw slow waves, ICP intracranial pressure, ABP arterial blood pressure, FVl flow velocity left, FVr flow velocity right, Ci_l compliance of cerebrospinal space left, Ci_r compliance of cerebrospinal fluid right, RAP compensatory reserve index* denotes statistically significant findingTable 2Correlations between changes in ICP slow waves pattern and other physiological variables. The analysis is performed both for the changes between baseline and hypocapnia, and for the hypocapnic absolute values. The p values were not adjusted for multiple comparisonsVariablesrpICP-FV(baseline–hypocapnia)∆PICP; ∆PFVl0.150.44∆PICP; ∆PFVr0.330.08∆CICP; ∆CFVl0.270.17∆CICP; ∆CFVr0.300.12∆EICP; ∆EFVl0.380.04∆EICP; ∆EFVr0.320.09ICP-FV(during hypocapnia)PICP; PFVl0.050.80PICP; PFVr0.060.74CICP; CFVl0.210.27CICP; CFVr0.400.03EICP; EFVl0.140.46EICP; EFVr0.310.10ICP-Ci(during hypocapnia)PICP; Cil− 0.110.58PICP; Cir− 0.140.47ICP-Ci(baseline–hypocapnia)∆PICP; ∆Cil0.150.42∆PICP; ∆Cir0.140.48ICP-RAP∆PICP; ∆RAP0.580.001∆PICP; RAPb0.71< 0.001FV-RAP∆PFVl; ∆RAP0.260.18∆PFVr; ∆RAP0.500.007∆ absolute delta value calculated as baseline–hypocapnia, P power of the slow waves, E entropy of the slow waves, C centroid of the slow waves, ICP intracranial pressure, FVl flow velocity left, FVr flow velocity right, Cil cerebrospinal compliance on the left side, Cir cerebrospinal compliance on the right side, RAP compensatory reserve index, RAPb compensatory reserve at the baseline In this study, we intended to scrutinize the behavior of the slow waves of ICP during short hypocapnia tests in TBI patients and to relate it to the other relevant physiological variables. In this retrospective study, only 29 patients were investigated and the patient heterogeneity as well as the injury pattern heterogeneity was not taken into account. Further studies with a larger cohort of patients will be needed to validate these preliminary findings. We found that in severe TBI patients, a sudden mild to moderate hypocapnia induces a decrease in ICP and FV slow wave power. It also increases their higher frequency content and their morphological complexity (entropy). The difference in power of the ICP slow waves between the baseline and the hypocapnia period depends on the baseline compensatory reserve, as expressed by RAP index.   Source: