Relationship of Vascular Wall Tension and Autoregulation Following Traumatic Brain Injury

Background

The vascular wall tension (WT) of small cerebral vessels can be quantitatively estimated through the concept of critical closing pressure (CrCP), which denotes the lower limit of arterial blood pressure (ABP), below which small cerebral arterial vessels collapse and blood flow ceases. WT can be expressed as the difference between CrCP and intracranial pressure (ICP) and represent active vasomotor tone. In this study, we investigated the association of WT and CrCP with autoregulation and outcome of a large group of patients after traumatic brain injury (TBI).

Methods

We retrospectively analysed recordings of ABP, ICP and transcranial Doppler (TCD) blood flow velocity from 280 TBI patients (median age: 29 years; interquartile range: 20–43). CrCP and WT were calculated using the cerebrovascular impedance methodology. Autoregulation was assessed based on TCD-based indices, Mx and ARI.

Results

Low values of WT were found to be associated with an impaired autoregulatory capacity, signified by its correlation to FV-based indices Mx (R = ?0.138; p = 0.021) and ARI (R = 0.118; p = 0.048). No relationship could be established between CrCP and any of the autoregulatory indices. Neither CrCP nor WT was found to correlate with outcome.

Conclusions

Impaired autoregulation was found to be associated with a lower WT supporting the role of vasoparalysis in the loss of autoregulatory capacity. In contrast, no links between CrCP and autoregulation could be identified.     

A Continuous Correlation Between Intracranial Pressure and Cerebral Blood Flow Velocity Reflects Cerebral Autoregulation Impairment During Intracranial Pressure Plateau Waves

Background

In the healthy brain, small oscillations in intracranial pressure (ICP) occur synchronously with those in cerebral blood volume (CBV), cerebrovascular resistance, and consequently cerebral blood flow velocity (CBFV). Previous work has shown that the usual synchrony between ICP and CBFV is lost during intracranial hypertension. Moreover, a continuously computed measure of the ICP/CBFV association (Fix index) was a more sensitive predictor of outcome after traumatic brain injury (TBI) than a measure of autoregulation (Mx index). In the current study we computed Fix during ICP plateau waves, to observe its behavior during a defined period of cerebrovascular vasodilatation.

Methods

Twenty-nine recordings of arterial blood pressure (ABP), ICP, and CBFV taken during ICP plateau waves were obtained from the Addenbrooke’s hospital TBI database. Raw data was filtered prior to computing Mx and Fix according to previously published methods. Analyzed data was segmented into three phases (pre, peak, and post), and a median value of each parameter was stored for analysis.

Results

ICP increased from a median of 22–44 mmHg before falling to 19 mmHg. Both Mx and Fix responded to the increase in ICP, with Mx trending toward +1, while Fix trended toward ?1. Mx and Fix correlated significantly (Spearman’s R = ?0.89, p < 0.000001), however, Fix spanned a greater range than Mx. A plot of Mx and Fix against CPP showed a plateau (Mx) or trough (Fix) consistent with a zone of “optimal CPP”.

Conclusions

The Fix index can identify complete loss of cerebral autoregulation as the point at which the normally positive CBF/CBV correlation is reversed. Both CBF and CBV can be monitored noninvasively using near-infrared spectroscopy (NIRS), suggesting that a noninvasive method of monitoring autoregulation using only NIRS may be possible.     

Continuous Cerebral Blood Flow Autoregulation Monitoring in Patients Undergoing Liver Transplantation

Background

Clinical monitoring of cerebral blood flow (CBF) autoregulation in patients undergoing liver transplantation may provide a means for optimizing blood pressure to reduce the risk of brain injury. The purpose of this pilot project is to test the feasibility of autoregulation monitoring with transcranial Doppler (TCD) and near-infrared spectroscopy (NIRS) in patients undergoing liver transplantation and to assess changes that may occur perioperatively.

Methods

We performed a prospective observational study in 9 consecutive patients undergoing orthotopic liver transplantation. Patients were monitored with TCD and NIRS. A continuous Pearson??s correlation coefficient was calculated between mean arterial pressure (MAP) and CBF velocity and between MAP and NIRS data, rendering the variables mean velocity index (Mx) and cerebral oximetry index (COx), respectively. Both Mx and COx were averaged and compared during the dissection phase, anhepatic phase, first 30?min of reperfusion, and remaining reperfusion phase. Impaired autoregulation was defined as Mx????0.4.

Results

Autoregulation was impaired in one patient during all phases of surgery, in two patients during the anhepatic phase, and in one patient during reperfusion. Impaired autoregulation was associated with a MELD score?>15 (p?=?0.015) and postoperative seizures or stroke (p?p?=?0.0029). The relationship between COx and Mx remained when only patients with bilirubin?>1.2?mg/dL were evaluated (p?=?0.0419). There was no correlation between COx and baseline bilirubin (p?=?0.2562) but MELD score and COx were correlated (p?=?0.0458). Average COx was higher for patients with a MELD score?>15 (p?=?0.073) and for patients with a neurologic complication than for patients without neurologic complications (p?=?0.0245).

Conclusions

These results suggest that autoregulation is impaired in patients undergoing liver transplantation, even in the absence of acute, fulminant liver failure. Identification of patients at risk for neurologic complications after surgery may allow for prompt neuroprotective interventions, including directed pressure management.     

Cessation of Diastolic Cerebral Blood Flow Velocity: The Role of Critical Closing Pressure

Background

Reducing cerebral perfusion pressure (CPP) below the lower limit of autoregulation (LLA) causes cerebral blood flow (CBF) to become pressure passive. Further reductions in CPP can cause cessation of CBF during diastole. We hypothesized that zero diastolic flow velocity (FV) occurs when diastolic blood pressure becomes less than the critical closing pressure (CrCP).

Methods

We retrospectively analyzed studies of 34 rabbits with CPP below the LLA, induced with pharmacologic sympathectomy (N = 23) or cerebrospinal fluid infusion (N = 11). Basilar artery blood FV and cortical Laser Doppler Flow (LDF) were monitored. CrCP was trended using a model of cerebrovascular impedance. The diastolic closing margin (DCM) was monitored as the difference between diastolic blood pressure and CrCP. LDF was recorded for DCM values greater than and less than zero.

Results

Arterial hypotension caused a reduction of CrCP (p < 0.001), consistent with decreased wall tension (p < 0.001) and a drop in intracranial pressure (ICP; p = 0.004). Cerebrospinal infusion caused an increase of CrCP (p = 0.002) accounted for by increasing ICP (p < 0.001). The DCM was compromised by either arterial hypotension or intracranial hypertension (p < 0.001 for both). When the DCM reached zero, diastolic FV ceased for a short period during each heart cycle (R = 0.426, p < 0.001). CBF pressure passivity accelerated when DCM decreased below zero (from 1.51 ± 0.51 to 2.17 ± 1.17 % ΔLDF/ΔmmHg; mean ± SD; p = 0.010).

Conclusions

The disappearance of diastolic CBF below LLA can be explained by DCM reaching zero or negative values. Below this point the decrease in CBF accelerates with further decrements of CPP.     

Cerebrovascular Pressure Reactivity and Cerebral Oxygen Regulation After Severe Head Injury

Background

To investigate the relationship between cerebrovascular pressure reactivity and cerebral oxygen regulation after head injury.

Methods

Continuous monitoring of the partial pressure of brain tissue oxygen (P_brO₂), mean arterial blood pressure (MAP), and intracranial pressure (ICP) in 11 patients. The cerebrovascular pressure reactivity index (PRx) was calculated as the moving correlation coefficient between MAP and ICP. For assessment of the cerebral oxygen regulation system a brain tissue oxygen response (TOR) was calculated, where the response of P_brO₂ to an increase of the arterial oxygen through ventilation with 100 % oxygen for 15 min is tested. Arterial blood gas analysis was performed before and after changing ventilator settings.

Results

Arterial oxygen increased from 108 ± 6 mmHg to 494 ± 68 mmHg during ventilation with 100 % oxygen. P_brO₂ increased from 28 ± 7 mmHg to 78 ± 29 mmHg, resulting in a mean TOR of 0.48 ± 0.24. Mean PRx was 0.05 ± 0.22. The correlation between PRx and TOR was r = 0.69, P = 0.019. The correlation of PRx and TOR with the Glasgow outcome scale at 6 months was r = 0.47, P = 0.142; and r = ?0.33, P = 0.32, respectively.

Conclusions

The results suggest a strong link between cerebrovascular pressure reactivity and the brain’s ability to control for its extracellular oxygen content. Their simultaneous impairment indicates that their common actuating element for cerebral blood flow control, the cerebral resistance vessels, are equally impaired in their ability to regulate for MAP fluctuations and changes in brain oxygen.     

Critical Closing Pressure During Intracranial Pressure Plateau Waves

Background

Critical closing pressure (CCP) denotes a threshold of arterial blood pressure (ABP) below which brain vessels collapse and cerebral blood flow ceases. Theoretically, CCP is the sum of intracranial pressure (ICP) and arterial wall tension (WT). The aim of this study is to describe the behavior of CCP and WT during spontaneous increases of ICP, termed plateau waves, in order to quantify ischemic risk.

Methods

To calculate CCP, we used a recently introduced multi-parameter method (CCPm) which is based on the modulus of cerebrovascular impedance. CCP is derived from cerebral perfusion pressure, ABP, transcranial Doppler estimators of cerebrovascular resistance and compliance, and heart rate. Arterial WT was estimated as CCPm-ICP. The clinical data included recordings of ABP, ICP, and transcranial Doppler-based blood flow velocity from 38 events of ICP plateau waves, recorded in 20 patients after head injury.

Results

Overall, CCPm increased significantly from 51.89 ± 8.76 mmHg at baseline ICP to 63.31 ± 10.83 mmHg at the top of the plateau waves (mean ± SD; p < 0.001). Cerebral arterial WT decreased significantly during plateau waves by 34.3 % (p < 0.001), confirming their vasodilatatory origin. CCPm did not exhibit the non-physiologic negative values that have been seen with traditional methods for calculation, therefore rendered a more plausible estimation of CCP.

Conclusions

Rising CCP during plateau waves increases the probability of cerebral vascular collapse and zero flow when the difference: ABP–CCP (the “collapsing margin”) becomes zero or negative.     

Elevated resting heart rate and reduced orthostatic tolerance in obese humans

Background

Obesity is linked with numerous physiological impairments; however, its impact on orthostatic tolerance (OT) remains unknown. This study tested the hypothesis that OT is reduced in obese individuals, and that reduced heart rate (HR) reserve and impaired cerebral autoregulation contribute to impaired OT.

Methods

Eleven obese (8 females) and 22 non-obese (10 females) individuals were exposed to incremental lower body negative pressure (LBNP) to presyncope while HR, arterial blood pressure, and cerebral perfusion (middle cerebral artery blood velocity; MCA V _mean) were measured. OT was quantified with a cumulative stress index (CSI).

Results

OT was reduced in obese subjects, and there was an inverse relationship between body mass index (BMI) and OT (R = ?0.47). HR was higher at rest and during each level of LBNP completed by all subjects. Similar peak HR (HR_peak) during LBNP between obese and non-obese subjects resulted in obese having a higher %peak HR at rest and at each stage of LBNP compared. Relationships existed for BMI and resting %HR_peak (R = 0.45) and resting %HR_peak and CSI (R = ?0.52). Despite lower CSI in obese, MCA V _mean and indices of cerebral autoregulation were similar between groups at all time points.

Conclusions

These data suggest that OT is reduced in obese and a higher resting HR, but not impaired regulation of cerebral perfusion, may contribute to this reduction.     

Continuous Monitoring of Cerebrovascular Reactivity Using Pulse Waveform of Intracranial Pressure

Background

Guidelines for the management of traumatic brain injury (TBI) call for the development of accurate methods for assessment of the relationship between cerebral perfusion pressure (CPP) and cerebral autoregulation and to determine the influence of quantitative indices of pressure autoregulation on outcome. We investigated the relationship between slow fluctuations of arterial blood pressure (ABP) and intracranial pressure (ICP) pulse amplitude (an index called PAx) using a moving correlation technique to reflect the state of cerebral vasoreactivity and compared it to the index of pressure reactivity (PRx) as a moving correlation coefficient between averaged values of ABP and ICP.

Methods

A retrospective analysis of prospective 327 TBI patients (admitted on neurocritical care unit of a university hospital in the period 2003?C2009) with continuous ABP and ICP monitoring.

Results

PAx was worse in patients who died compared to those who survived (?0.04?±?0.15 vs. ?0.16?±?0.15, ??²?=?28, p?2?=?6, p?=?0.01).

Conclusions

PAx is a new modified index of cerebrovascular reactivity which performs equally well as established PRx in long-term monitoring in severe TBI patients, but importantly is potentially more robust at lower values of ICP. In view of establishing an autoregulation-oriented CPP therapy, continuous determination of PAx is feasible but its value has to be evaluated in a prospective controlled trail.     

Non-invasive Monitoring of Dynamic Cerebrovascular Autoregulation Using Near Infrared Spectroscopy and the Finometer Photoplethysmograph

Background

Near infrared spectroscopy (NIRS) enables continuous monitoring of dynamic cerebrovascular autoregulation, but this methodology relies on invasive blood pressure monitoring (iABP). We evaluated the agreement between a NIRS based autoregulation index calculated from invasive blood pressure monitoring, and an entirely non-invasively derived autoregulation index from continuous non-invasive blood pressure monitoring (nABP) using the Finometer photoplethysmograph.

Methods

Autoregulation was calculated as the moving correlation coefficient between iABP and rSO₂ (iTOx) or nABP and rSO₂ (nTOx). The blood pressure range where autoregulation is optimal was also determined for invasive (iABP_OPT) and non-invasive blood pressure measurements (nABP_OPT).

Results

102 simultaneous bilateral measurements of iTOx and nTOx were performed in 19 patients (median 2 per patient, range 1–9) with different acute pathologies (sepsis, cardiac arrest, head injury, stroke). Average iTOx was 0.01 ± 0.13 and nTOx was 0.01 ± 0.11. The correlation between iTOx and nTOx was r = 0.87, p < 0.001, 95 % agreement ± 0.12, bias = 0.005. The interhemispheric asymmetry of autoregulation was similarly assessed with iTOx and nTOx (r = 0.81, p < 0.001). Correlation between iABP_OPT and nABP_OPT was r = 0.47, p = 0.003, 95 % agreement ± 32.1 mmHg, bias = 5.8 mmHg. Coherence in the low frequency spectrum between iABP and nABP was 0.86 ± 0.08 and gain was 1.32 ± 0.77.

Conclusions

The results suggest that dynamic cerebrovascular autoregulation can be continuously assessed entirely non-invasively using nTOx. This allows for autoregulation assessment using spontaneous blood pressure fluctuations in conditions where iABP is not routinely monitored. The nABP_OPT might deviate from iABP_OPT, likely because of discordance between absolute nABP and iABP readings.

     

Monitoring cerebral autoregulation after head injury. Which component of transcranial Doppler flow velocity is optimal?

Background

Cerebral autoregulation assessed using transcranial Doppler (TCD) mean flow velocity (FV) in response to various physiological challenges is predictive of outcome after traumatic brain injury (TBI). Systolic and diastolic FV have been explored in other diseases. This study aims to evaluate the systolic, mean and diastolic FV for monitoring autoregulation and predicting outcome after TBI.

Methods

300 head-injured patients with blood pressure (ABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), and FV recordings were studied. Autoregulation was calculated as a correlation of slow changes in diastolic, mean and systolic components of FV with CPP (Dx, Mx, Sx, respectively) and ABP (Dxa, Mxa, Sxa, respectively) from 30 consecutive 10?s averaged values. The relationship with age, severity of injury, and dichotomized 6?months outcome was examined.

Results

Association with outcome was significant for Mx and Sx. For favorable/unfavorable and death/survival outcomes Sx showed the strongest association (F?=?20.11; P?=?0.00001 and F?=?13.10; P?=?0.0003, respectively). Similarly, indices derived from ABP demonstrated the highest discriminatory value when systolic FV was used (F?=?12.49; P?=?0.0005 and F?=?5.32; P?=?0.02, respectively). Indices derived from diastolic FV demonstrated significant differences (when calculated using CPP) only when comparing between fatal and non-fatal outcome.

Conclusions

Systolic flow indices (Sx and Sxa) demonstrated a stronger association with outcome than the mean flow indices (Mx and Mxa), irrespective of whether CPP or ABP was used for calculation.     

Acute Effect of Intravenous Sildenafil on Cerebral Blood Flow in Patients with Vasospasm After Subarachnoid Hemorrhage

Background

The phosphodiesterase-5 inhibitor sildenafil has been shown to attenuate delayed cerebral ischemia (DCI) and improve neurologic function in experimental subarachnoid hemorrhage (SAH). We recently demonstrated that it could improve cerebral vasospasm (CVS) in humans after SAH. However, successful therapies for DCI must also restore cerebral blood flow (CBF) and/or autoregulatory capacity. In this study, we tested the effects of sildenafil on CBF in SAH patients at-risk for DCI.

Methods

Six subjects with angiographically confirmed CVS received 30-mg of intravenous sildenafil (mean 9 ± 2 days after aneurysmal SAH). Each underwent ¹⁵O-PET imaging to measure global and regional CBF at baseline and post-sildenafil.

Results

Mean arterial pressure declined by 10 mm Hg on average post-sildenafil (8 %, p = 0.01), while ICP was unchanged. There was no change in global CBF (mean 34.5 ± 7 ml/100g/min at baseline vs. 33.9 ± 8.0 ml/100g/min post-sildenafil, p = 0.84). The proportion of brain regions with low CBF (<25 ml/100g/min) was also unchanged after sildenafil infusion.

Conclusions

Infusion of sildenafil does not lead to a change in global or regional perfusion despite a significant reduction in cerebral perfusion pressure. While this could reflect the ineffectiveness of sildenafil-induced proximal vasodilatation to alter brain perfusion, it also suggests that cerebral autoregulatory function was preserved in this group. Future studies should assess whether sildenafil can restore or enhance autoregulation after SAH.

     

Sympathetic withdrawal is associated with hypotension after hepatic reperfusion

Objective

Post-reperfusion syndrome (PRS), severe hypotension after graft reperfusion during liver transplantation, is an adverse clinical event associated with poorer patient outcomes. The purpose of this study was to determine whether alterations in autonomic control in liver transplant recipients prior to graft reperfusion are associated with the subsequent development of PRS.

Methods

Heart rate variability (HRV), systolic arterial blood pressure (SBP) variability, and baroreflex sensitivity of 218 liver transplant recipients were evaluated using 5 min of ECG and arterial blood pressure signals 10 min before graft reperfusion along with other clinical parameters. Logistic regression analyses were performed to assess predictors of PRS occurrence.

Results

Seventy-seven patients (35 %) developed PRS while 141 did not. There were significant differences in SBP (110 ± 16 vs. 119 ± 16 mmHg, P < 0.001) and the ratio of low frequency power to high frequency power (LF/HF) of HRV (1.0 ± 1.4 vs. 2.1 ± 3.7, P = 0.003) between the PRS group and No-PRS group. In multivariate logistic regression analysis, predictors were LF/HF (odds ratio 0.817, P = 0.028) and SBP (odds ratio 0.966, P < 0.001).

Interpretation

Low LF/HF and SBP measured before hepatic graft reperfusion were significantly correlated with subsequent PRS occurrence, suggesting that sympathovagal imbalance and depressed SBP may be key factors predisposing to reperfusion-related severe hypotension in liver transplant recipients.     

Should the Neurointensive Care Management of Traumatic Brain Injury Patients be Individualized According to Autoregulation Status and Injury Subtype?

Introduction

The status of autoregulation is an important prognostic factor in traumatic brain injury (TBI), and is important to consider in the management of TBI patients. Pressure reactivity index (PRx) is a measure of autoregulation that has been thoroughly studied, but little is known about its variation in different subtypes of TBI. In this study, we examined the impact of PRx and cerebral perfusion pressure (CPP) on outcome in different TBI subtypes.

Methods

107 patients were retrospectively studied. Data on PRx, CPP, and outcome were collected from our database. The first CT scan was classified according to the Marshall classification system. Patients were assigned to “diffuse” (Marshall class: diffuse-1, diffuse-2, and diffuse-3) or “focal” (Marshall class: diffuse-4, evacuated mass lesion, and non-evacuated mass lesion) groups. 2 × 2 tables were constructed calculating the proportions of favorable/unfavorable outcome at different combinations of PRx and CPP.

Results

Low PRx was significantly associated with favorable outcome in the combined group (p = 0.002) and the diffuse group (p = 0.04), but not in the focal group (p = 0.06). In the focal group higher CPP values were associated with worse outcome (p = 0.02). In diffuse injury patients with disturbed autoregulation (PRx >0.1), CPP >70 mmHg was associated with better outcome (p = 0.03).

Conclusion

TBI patients with diffuse injury may differ from those with mass lesions. In the latter higher levels of CPP may be harmful, possibly due to BBB disruption. In TBI patients with diffuse injury and disturbed autoregulation higher levels of CPP may be beneficial.     

Cerebral vasoreactivity: impact of heat stress and lower body negative pressure

Objective

Cerebrovascular reactivity represents the capacity of the cerebral circulation to raise blood flow in the face of increased demand, and may be reduced in some clinical and physiological conditions. We tested the hypothesis that the hypercapnia-induced increase in cerebral perfusion is attenuated during heat stress (HS) compared to normothermia (NT), and this response is further reduced during the combined challenges of HS and lower body negative pressure (LBNP).

Methods

Ten healthy individuals (9 men) undertook rebreathing-induced hypercapnia during NT, HS, and HS + 20 mmHg LBNP (HS_LBNP), while cerebral perfusion was indexed from middle cerebral artery blood velocity (MCA V _mean). Cerebrovascular responses were calculated from the slope of the change in MCA V _mean and cerebral vascular conductance (CVCi) relative to the increase in end tidal carbon dioxide ( \( {\text{PET}}_{{{\text{CO}}_{ 2} }} \) ) during rebreathing.

Results

MCA V _mean was similar in HS (55 ± 19 cm s^?1) and HS_LBNP (52 ± 16 cm s^?1), and both values were reduced relative to NT (66 ± 20 cm s^?1), yet the rise in MCA V _mean per Torr increase in \( {\text{PET}}_{{{\text{CO}}_{ 2} }} \) during rebreathing was similar in each condition (NT: 2.5 ± 0.6 cm s^?1 Torr^?1; HS: 2.4 ± 0.8 cm s^?1 Torr^?1; HS_LBNP: 2.1 ± 1.1 cm s^?1 Torr^?1). Likewise, the rate of increase in CVCi was not different between conditions (NT: 2.1 ± 0.65 cm s^?1 mmHg^?1100 Torr^?1; HS: 2.4 ± 0.8 cm s^?1 mmHg^?1 100 Torr^?1; HS_LBNP: 2.0 ± 1.0 cm s^?1 mmHg^?1 100 Torr^?1).

Interpretations

These data indicate that cerebrovascular reactivity is not compromised during whole-body heat stress alone or when combined with mild orthostatic stress relative to normothermic conditions.     

Pressures,Flow, and Brain Oxygenation During Plateau Waves of Intracranial Pressure

Background

Plateau waves are common in traumatic brain injury. They constitute abrupt increases of intracranial pressure (ICP) above 40 mmHg associated with a decrease in cerebral perfusion pressure (CPP). The aim of this study was to describe plateau waves characteristics with multimodal brain monitoring in head injured patients admitted in neurocritical care.

Methods

Prospective observational study in 18 multiple trauma patients with head injury admitted to Neurocritical Care Unit of Hospital Sao Joao in Porto. Multimodal systemic and brain monitoring of primary variables [heart rate, arterial blood pressure, ICP, CPP, pulse amplitude, end tidal CO₂, brain temperature, brain tissue oxygenation pressure, cerebral oximetry (CO) with transcutaneous near-infrared spectroscopy and cerebral blood flow (CBF)] and secondary variables related to cerebral compensatory reserve and cerebrovascular reactivity were supported by dedicated software ICM+ (www.neurosurg.cam.ac.uk/icmplus). The compiled data were analyzed in patients who developed plateau waves.

Results

In this study we identified 59 plateau waves that occurred in 44 % of the patients (8/18). During plateau waves CBF, cerebrovascular resistance, CO, and brain tissue oxygenation decreased. The duration and magnitude of plateau waves were greater in patients with working cerebrovascular reactivity. After the end of plateau wave, a hyperemic response was recorded in 64 % of cases with increase in CBF and brain oxygenation. The magnitude of hyperemia was associated with better autoregulation status and low oxygenation levels at baseline.

Conclusions

Multimodal brain monitoring facilitates identification and understanding of intrinsic vascular brain phenomenon, such as plateau waves, and may help the adequate management of acute head injury at bed side.     

ICP Versus Laser Doppler Cerebrovascular Reactivity Indices to Assess Brain Autoregulatory Capacity

Background

To explore the relationship between various autoregulatory indices in order to determine which approximate small vessel/microvascular (MV) autoregulatory capacity most accurately.

Methods

Utilizing a retrospective cohort of traumatic brain injury patients (N = 41) with: transcranial Doppler (TCD), intracranial pressure (ICP) and cortical laser Doppler flowmetry (LDF), we calculated various continuous indices of autoregulation and cerebrovascular responsiveness: A. ICP derived [pressure reactivity index (PRx)—correlation between ICP and mean arterial pressure (MAP), PAx—correlation between pulse amplitude of ICP (AMP) and MAP, RAC—correlation between AMP and cerebral perfusion pressure (CPP)], B. TCD derived (Mx—correlation between mean flow velocity (FVm) and CPP, Mx_a—correlation between FVm and MAP, Sx—correlation between systolic flow velocity (FVs) and CPP, Sx_a—correlation between FVs and MAP, Dx—correlation between diastolic flow index (FVd) and CPP, Dx_a—correlation between FVd and MAP], and LDF derived (Lx—correlation between LDF cerebral blood flow [CBF] and CPP, Lx_a—correlation between LDF-CBF and MAP). We assessed the relationship between these indices via Pearson correlation, Friedman test, principal component analysis (PCA), agglomerative hierarchal clustering (AHC), and k-means cluster analysis (KMCA).

Results

LDF-based autoregulatory index (Lx) was most associated with TCD-based Mx/Mx_a and Dx/Dx_a across Pearson correlation, PCA, AHC, and KMCA. Lx was only remotely associated with ICP-based indices (PRx, PAx, RAC). TCD-based Sx/Sx_a was more closely associated with ICP-derived PRx, PAx and RAC. This indicates that vascular-derived indices of autoregulatory capacity (i.e., TCD and LDF based) covary, with Sx/Sx_a being the exception, whereas indices of cerebrovascular reactivity derived from pulsatile CBV (i.e., ICP indices) appear to not be closely related to those of vascular origin.

Conclusions

Transcranial Doppler Mx is the most closely associated with LDF-based Lx/Lx_a. Both Sx/Sx-a and the ICP-derived indices appear to be dissociated with LDF-based cerebrovascular reactivity, leaving Mx/Mx-a as a better surrogate for the assessment of cortical small vessel/MV cerebrovascular reactivity. Sx/Sx_a cocluster/covary with ICP-derived indices, as seen in our previous work.

     

Effect of Early Physiotherapy on Intracranial Pressure and Cerebral Perfusion Pressure

Background

Physiotherapy plays an important role in the therapy of patients with acute cerebral diseases. Studies concerning the effects of physiotherapy on intracerebral pressure (ICP) and cerebral perfusion pressure (CPP) are, however, rare.

Methods

An observational study was performed on critically ill patients who were receiving ICP measurements and who were treated with passive range of motion (PROM) on our neuro-intensive care unit. ICP, CPP, mean arterial pressure (MAP) and heart rate were recorded continuously every minute, beginning 15 min before, during (26 min) and 15 min after treatment with PROM. Patients with mean ICP <15 mmHg (Group 1) and patients with mean ICP ≥15 mmHg (Group 2) before physiotherapy were analyzed separately.

Results

Overall there were 84 patients (f:m = 1:1) with 298 treatments units, 224 in Group 1 and 74 in Group 2, respectively. Mean ICP before treatment was 11.5 ± 5.1 mmHg, with a significant decrease of 1 mmHg during therapy (p = 2.0e–10). This was also true for Group 1 (baseline ICP 9.4 ± 3.7 mmHg, decrease of 0.7 mmHg, p = 3.8e–6) and Group 2 (baseline ICP 18.1 ± 2.7 mmHg, decrease of 2 mmHg, p = 3.7e–6). However, a persistent ICP reduction after therapy was seen only in Group 2. There were no significant differences between mean CPP and MAP comparing ICP before and after PROM in all groups. No adverse side effects of PROM were observed.

Conclusions

Physiotherapy with PROM can be used safely in patients with acute neurological diseases, even if ICP is elevated before therapy.     

Continuous Optical Monitoring of Cerebral Hemodynamics During Head-of-Bed Manipulation in Brain-Injured Adults

Introduction

Head-of-bed manipulation is commonly performed in the neurocritical care unit to optimize cerebral blood flow (CBF), but its effects on CBF are rarely measured. This pilot study employs a novel, non-invasive instrument combining two techniques, diffuse correlation spectroscopy (DCS) for measurement of CBF and near-infrared spectroscopy (NIRS) for measurement of cerebral oxy- and deoxy-hemoglobin concentrations, to monitor patients during head-of-bed lowering.

Methods

Ten brain-injured patients and ten control subjects were monitored continuously with DCS and NIRS while the head-of-bed was positioned first at 30° and then at 0°. Relative CBF (rCBF) and concurrent changes in oxy- (ΔHbO₂), deoxy- (ΔHb), and total-hemoglobin concentrations (ΔTHC) from left/right frontal cortices were monitored for 5 min at each position. Patient and control response differences were assessed.

Results

rCBF, ΔHbO₂, and ΔTHC responses to head lowering differed significantly between brain-injured patients and healthy controls (P < 0.02). For patients, rCBF changes were heterogeneous, with no net change observed in the group average (0.3 ± 28.2 %, P = 0.938). rCBF increased in controls (18.6 ± 9.4 %, P < 0.001). ΔHbO₂, ΔHb, and ΔTHC increased with head lowering in both groups, but to a larger degree in brain-injured patients. rCBF correlated moderately with changes in cerebral perfusion pressure (R = 0.40, P < 0.001), but not intracranial pressure.

Conclusion

DCS/NIRS detected differences in CBF and oxygenation responses of brain-injured patients versus controls during head-of-bed manipulation. This pilot study supports the feasibility of continuous bedside measurement of cerebrovascular hemodynamics with DCS/NIRS and provides the rationale for further investigation in larger cohorts.     

Treadmill gait training improves baroreflex sensitivity in Parkinson’s disease

Background

Partial weight supported treadmill gait training (PWSTT) is widely used in rehabilitation of gait in patient with Parkinson’s Diseases (PD). However, its effect on blood pressure variability (BPV) and baroreflex sensitivity (BRS) in PD has not been studied.

Aim

To evaluate the effect of conventional and treadmill gait training on BPV components and BRS.

Methods

Sixty patients with idiopathic PD were randomized into three groups. Twenty patients in control group were on only stable medication, 20 patients in conventional gait training (CGT) group (Stable medication with CGT) and 20 patients in PWSTT group (Stable medication with 20 % PWSTT). The CGT and PWSTT sessions were given for 30 min per day, 4 days per week, for 4 weeks (16 sessions). Groups were evaluated in their best ‘ON’ states. The beat-to-beat finger blood pressure (BP) was recorded for 10 min using a Finometer instrument (Finapres Medical Systems, The Netherlands). BPV and BRS results were derived from artifact-free 5-min segments using Nevrocard software.

Results

BRS showed a significant group with time interaction (F = 6.930; p = 0.003). Post-hoc analysis revealed that PWSTT group showed significant improvement in BRS (p < 0.001) after 4 weeks of training. No significant differences found in BPV parameters; systolic BP, diastolic BP, co-variance of systolic BP and low frequency component of systolic BP.

Conclusions

Four weeks of PWSTT significantly improves BRS in patients with PD. It can be considered as a non-invasive method of influencing BRS for prevention of orthostatic BP fall in patients with PD.