E. A. Schmidt

Intracranial hypertension: what additional information can be derived from ICP waveform after head injury?

SummaryObjective. Although intracranial hypertension is one of the important prognostic factors after head injury, increased intracranial pressure (ICP) may also be observed in patients with favourable outcome. We have studied whether the value of ICP monitoring can be augmented by indices describing cerebrovascular pressure-reactivity and pressure-volume compensatory reserve derived from ICP and arterial blood pressure (ABP) waveforms. Method. 96 patients with intracranial hypertension were studied retrospectively: 57 with fatal outcome and 39 with favourable outcome. ABP and ICP waveforms were recorded. Indices of cerebrovascular reactivity (PRx) and cerebrospinal compensatory reserve (RAP) were calculated as moving correlation coefficients between slow waves of ABP and ICP, and between slow waves of ICP pulse amplitude and mean ICP, respectively. The magnitude of ‘slow waves’ was derived using ICP low-pass spectral filtration. Results. The most significant difference was found in the magnitude of slow waves that was persistently higher in patients with a favourable outcome (p<0.00004). In patients who died ICP was significantly higher (p<0.0001) and cerebrovascular pressure-reactivity (described by PRx) was compromised (p<0.024). In the same patients, pressure-volume compensatory reserve showed a gradual deterioration over time with a sudden drop of RAP when ICP started to rise, suggesting an overlapping disruption of the vasomotor response. Conclusion. Indices derived from ICP waveform analysis can be helpful for the interpretation of progressive intracranial hypertension in patients after brain trauma.

Preliminary experience of the estimation of cerebral perfusion pressure using transcranial Doppler ultrasonography

OBJECTIVE The direct calculation of cerebral perfusion pressure (CPP) as the difference between mean arterial pressure and intracranial pressure (ICP) produces a number which does not always adequately describe conditions for brain perfusion. A non-invasive method of CPP measurement has previously been reported based on waveform analysis of blood flow velocity measured in the middle cerebral artery (MCA) by transcranial Doppler. This study describes the results of clinical tests of the prototype bilateral transcranial Doppler based apparatus for non-invasive CPP measurement (nCPP). METHODS Twenty five consecutive, paralysed, sedated, and ventilated patients with head injury were studied. Intracranial pressure (ICP) and arterial blood pressure (ABP) were monitored continuously. The left and right MCAs were insonated daily (108 measurements) using a purpose built transcranial Doppler monitor (Neuro QTM, Deltex Ltd, Chichester, UK) with software capable of the non-invasive estimation of CPP. Time averaged values of mean and diastolic flow velocities (FVm, FVd) and ABP were calculated. nCPP was then computed as: ABP×FVd/FVm+14. RESULTS The absolute difference between real CPP and nCPP (daily averages) was less than 10 mm Hg in 89% of measurements and less than 13 mm Hg in 92% of measurements. The 95% confidence range for predictors was no wider than ±12 mm Hg (n=25) for the CPP, varying from 70 to 95 mm Hg. The absolute value of side to side differences in nCPP was significantly greater (p<0.05) when CT based evidence of brain swelling was present and was also positively correlated (p<0.05) with mean ICP. CONCLUSION The device is of potential benefit for intermittent or continuous monitoring of brain perfusion pressure in situations where the direct measurement is not available or its reliability is in question.

Clinical assessment of cerebrospinal fluid dynamics in hydrocephalus. Guide to interpretation based on observational study.

Weerakkody RA, Czosnyka M, Schuhmann MU, Schmidt E, Keong N, Santarius T, Pickard JD, Czosnyka Z. Clinical assessment of cerebrospinal fluid dynamics in hydrocephalus. Guide to interpretation based on observational study. 
Acta Neurol Scand: 2011: 124: 85–98.
© 2011 John Wiley & Sons A/S.

Pressure-autoregulation, CO2 reactivity and asymmetry of haemodynamic parameters in patients with carotid artery stenotic disease. A clinical appraisal

Summary¶Objectives. Patients with carotid artery stenotic disease and poor cerebral haemodynamic reserve are in increased risk of stroke. Haemodynamic reserve can be estimated by measuring cerebrovascular reactivity induced by breathing CO2 and pressure-autoregulation by analyzing spontaneous slow fluctuation in arterial pressure and MCA blood flow velocity. We evaluated the relationship between clinical status, CO2 reactivity, pressure-autoregulation and other haemodynamic variables derived from Transcranial Doppler ultrasonography in patients with carotid artery disease.Methods. 38 patients were investigated. Arterial pressure and blood flow velocity were monitored during CO2 reactivity tests. Arterial pressure-corrected and non-corrected indices of CO2 reactivity were calculated to compare an influence of rise in arterial pressure during the test. The pressure-autoregulation index was calculated as correlation coefficient between slow waves in blood flow velocity and arterial pressure.Results. The increase in CO2 produced a consistent rise in arterial pressure and blood flow velocity and weakened the pressure autoregulation. The value of pressure-corrected CO2 reactivity was lower (p<0.0001) than the non-corrected one, indicating that the rise in arterial pressure during the test tends to over-estimate CO2 reactivity. The pressure-corrected reactivity was correlated with pressure autoregulation (r=−0.46; p<0.005). Both CO2 reactivity and pressure-autoregulation index correlated with a degree of carotid artery stenosis. Side-to-side difference of TCD pulsatility index demonstrated a close relationship with the asymmetry of stenosis (r=−0.61; p<0.0002) and symptoms (r=−0.49; p<0.003).Conclusions. When calculating CO2 reactivity in patients with carotid artery disease, changes in arterial pressure should be considered. Both CO2 reactivity and pressure-autoregulation describe the magnitude of haemodynamic deficit caused by stenosis, pulsatility index expresses the asymmetry of stenosis.

Intracranial baroreflex yielding an early Cushing response in human

The Cushing response is a pre-terminal sympatho-adrenal systemic response to very high ICP. Animal studies have demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response. Infusion studies are routine procedures to investigate, by infusing CSF space with saline, the cerebrospinal fluid (CSF) biophysics in patients suspected of hydrocephalus. Our study aims at assessing systemic and cerebral haemodynamic changes during moderate rise of ICP in human. Infusion studies were performed in 34 patients. This is a routine test perform in patients presenting with symptoms of NPH during their pre-shunting assessment. Arterial blood pressure (ABP) and cerebral blood flow velocity (FV) were non-invasively monitored with photoplethysmography and transcranial Doppler. The rise in ICP (8.2 +/- 5.1 mmHg to 25 +/- 8.3 mmHg) was followed by a significant rise in ABP (106.6 +/- 29.7 mmHg to 115.2 +/- 30.1 mmHg), drop in CPP (98.3 +/- 29 mmHg to 90.2 +/- 30.7 mmHg) and decrease in FV (55.6 +/- 17 cm/s to 51.1 +/- 16.3 cm/s). Increasing ICP did not alter heart rate (70.4 +/- 10.4/min to 70.3 +/- 9.1/min) but augmented the heart rate variance (0.046 +/- 0.058 to 0.067 +/- 0.075/min). In a population suspected of hydrocephalus, our study demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response, demonstrating an early Cushing response in human and a putative intracranial baroreflex.

Continuous assessment of cerebral autoregulation: clinical and laboratory experience.

The method for the continuous assessment of cerebral autoregulation using slow waves of MCA blood flow velocity (FV) and cerebral perfusion pressure (CPP) or arterial pressure (ABP) has been introduced seven years ago. We intend to review its clinical applications in various scenarios. Moving correlation coefficient (3-6 min window), named Mx, is calculated between low-pass filtered (0.05 Hz) signals of FV and CPP or ABP (when ICP is not measured directly). Data from ventilated 243 head injuries and 15 patients after poor grade subarachnoid haemorrhage, 38 patients with Carotid Artery stenosis, 35 patients with hydrocephalus and fourteen healthy volunteers is presented. Good agreement between the leg-cuff test and Mx has been confirmed in healthy volunteers (r = 0.81). Mx also correlated significantly with the static rate of autoregulation and transient hyperaemic response test. Autoregulation was disturbed (p < 0.021) by vasospasm after SAH and worse in patients with hydrocephalus in whom CSF circulation was normal (p < 0.02). In head injury, Mx indicated disturbed autoregulation with low CPP (< 55 mmHg) and too high CPP (> 95 mmHg). Mx strongly discriminated between patients with favourable and unfavourable outcome (p < 0.00002). This method can be used in many clinical scenarios for continuous monitoring of cerebral autoregulation, predicting outcome and optimising treatment strategies.

Continuous Assessment of Cerebral Autoregulation — Clinical Verification of the Method in Head Injured Patients

Previously, using transcranial Doppler ultrasonography, we investigated whether the hemodynamic response to spontaneous variations in cerebral perfusion pressure (CPP) provides reliable information about cerebral autoregulatory reserve. In the present study we have verified this method in 166 patients after head trauma. Waveforms of intracranial pressure (ICP), arterial pressure and transcranial Doppler flow velocity (FV) were captured daily over 0.5-2.0 hour periods. Time-averaged mean flow velocity (FV) and CPP were resolved. The correlation coefficient indices between FV and CPP (Mx) were calculated over 3 minutes epochs, and averaged for each investigation. An index of CBF (flow velocity diastolic to mean ratio) was calculated independently for each investigation. Mx depended on CPP (p < 0.0001) increasing to positive values when CPP decreased below 60 mm Hg. This threshold coincided with an averaged breakpoint for autoregulation, expressed by the index of CBF. Mx depended on outcome following head injury stronger than the Glasgow Coma Score on admission (ANOVA, F values 18 and 15 respectively; N = 166). In patients who died, cerebral autoregulation was disturbed during the first two days following injury. These results indicate an important role for the continuous monitoring of autoregulation following head trauma.

Asymmetry of critical closing pressure following head injury

Objective: Critical closing pressure (CCP) is the arterial pressure below which the vessels collapse. Hypothetically it is the sum of intracranial pressure (ICP) and vessel wall tension in the cerebral circulation. This study investigated transhemispherical asymmetry of CCP by studying its correlation with radiological findings on computed tomography (CT) scans in head injury patients. Method: ICP, arterial blood pressure, and middle cerebral artery blood flow velocity were recorded daily in 119 ventilated patients. Waveforms were processed to calculate CCP. CT scans were analysed according to a system based on the Marshall classification. Results: Left–right differences in CCP correlated with midline shift on the CT scan (r = 0.48; p<0.02). Asymmetry of CCP also corresponded with the side of the head lesion (p<0.007) and the side of the craniotomy where it was performed (p<0.006). Absolute CCP weakly correlated with brain swelling (r = −0.23; p<0.03) and arterial pressure (r = 0.21; p<0.02) but did not correlate with ICP. Cerebral perfusion pressure calculated as the difference between mean arterial pressure and CCP did not correlate with outcome, but “traditional” cerebral perfusion pressure (mean arterial pressure minus intracranial pressure) did. Conclusions: Critical closing pressure is disturbed by localised brain lesions. Its asymmetry corresponds to asymmetrical findings on CT scans. CCP seems to describe vascular resistance better than ICP.

Cerebrovascular effects of sodium nitroprusside in the anaesthetized baboon: a positron emission tomographic study

The effects of sodium nitroprusside (SNP), a potent hypotensive agent, on cerebral blood flow (CBF) have been extensively studied in clinical and experimental situations but the results remain controversial. Whereas its properties would predict a dilatation of cerebral blood vessels, most studies report either no change or a decrease in CBF. The aim of this study was to investigate the effects of SNP on CBF, cerebral blood volume (CBV), and cerebral oxygen metabolism (CMRO2), by means of positron emission tomography in the anaesthetized baboon. Measurements were performed during normotension (mean arterial pressure (MABP): 97±16 mm Hg) and repeated following SNP-induced hypotension (MABP: 44±9 mm Hg). Sodium nitroprusside led to an increase in CBF and CBV (+30% and +37%, respectively, P<0.05), whereas no change in CMRO2 was noted. Linear regression analysis of CBF values as a function of MABP confirmed that CBF increases when MABP is reduced by SNP. The comparison between these cerebrovascular changes and those found during trimetaphan-induced hypotension in our previously published studies further argues for a direct dilatatory effect of SNP on cerebral blood vessels.

Asymmetry of Cerebral Autoregulation Following Head Injury

OBJECTIVES To investigate asymmetry of cerebra autoregulation in head-injured patients with lateral brain contusions. METHODS Sixty five patients were admitted to Addenbrookes Hospital suffering from head injuries with mean Glasgow Coma Score 6 (range 3 to 10). The patients were paralyzed, sedated and ventilated to achieve mild hypocapnia. Intracranial pressure (ICP), arterial pressure (ABP) were monitored directly. The left and right Middle Cerebral Arteries were insonated daily and flow velocity (FV) was recorded. Correlation coefficients between slow waves in cerebral perfusion pressure (CPP) and FV were calculated for every 3 minute period. Positive value of Mx denotes a positive association between waves in FV and CPP, therefore deranged autoregulation. Zero or slightly negative value of Mx denotes a good autoregulatory capacity. In each patient all CT scans were reviewed to assess a dominant side of brain contusion and a level of brain compression. RESULTS The side-to-side difference in FV, pulsatility indices or critical closing pressures, did not correlate with the side of contusion or midline shift. In contrary, the side-to-side difference in Mx indices were significantly (p < 0.05) worse at a side of contusion and at the side of brain expansion in patients presenting with a midline shift (p < 0.05). Of those patients who died in hospital, significantly more presented within meaningful (ABS(Mx) > 0.2) asymmetry in cerebral autoregulation (40% versus 12%; p < 0.05). CONCLUSIONS Side-to-side difference in cerebral hemodynamic reserve of injured brain is a predictor of fatal outcome following head injury and correlates with the side of contusion or brain expansion.