The Values of Cerebrovascular Pressure Reactivity and Brain Tissue Oxygen Pressure Reactivity in Experimental Anhepatic Liver Failure

Background

We investigated in a porcine model of anhepatic acute liver failure (ALF), the value of two parameters describing cerebrovascular autoregulatory capacity, pressure reactivity index (PRx) and brain tissue oxygen pressure reactivity (ORx), regarding their power to predict the development of intracranial hypertension.

Methods

In six pigs, hepatectomy was performed. Only one animal was sham operated. All animals received neuromonitoring including arterial blood pressure, intracranial pressure (ICP), and brain tissue partial oxygen pressure (P_brO₂). The average time of neuromonitoring was 31.0 h. Cerebral perfusion pressures (CPP), cerebrovascular pressure reactivity index (PRx) and brain tissue oxygen reactivity index (ORx) were calculated.

Results

Perioperative disturbance of AR improved within 4 h after surgery. From 6 to 16 h post hepatectomy, ICP did slowly increase by 4 mmHg from baseline; CPP remained stable around 40 mmHg. PRx and ORx, however, indicated in this period a progressive loss of AR, reflected in a decrease of P_brO₂ despite unchanged CPP. Beyond 16 h, ICP rose quickly. At CPP levels below 35 mmHg, P_brO₂ fell to ischemic levels.

Conclusions

The loss of cerebrovascular autoregulatory capacity, indicated by a rise of PRx and ORx precedes the final crisis of uncontrollable intracranial hypertension in this animal model by hours. During this phase cerebral blood flow, as reflected in tissue oxygenation, deteriorates despite unchanged CPP. Monitoring of AR during ALF therefore seems to carry the power to identify a risk for development of critical CBF and intracranial hypertension.

     

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.     

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.     

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.     

Further Controversies About Brain Tissue Oxygenation Pressure-Reactivity After Traumatic Brain Injury

Background

Continuous monitoring of cerebral autoregulation is considered clinically useful due to its ability to warn against brain ischemic insults, which may translate to a relationship with adverse outcome. It is typically performed using the pressure reactivity index (PRx) based on mean arterial pressure and intracranial pressure. A new ORx index based on brain tissue oxygenation and cerebral perfusion pressure (CPP) has been proposed that similarly allows for evaluation of cerebrovascular reactivity. Conflicting results exist concerning its clinical utility.

Methods

Retrospective analysis was performed in 85 patients with traumatic brain injury (TBI). ORx was calculated using three time windows of 5, 20, and 60 min. Correlation coefficients and individual “optimal CPP” (CPP_opt) were calculated using both PRx and ORx, and relation to patient outcome investigated.

Results

Correlation coefficients for all comparisons between PRx and ORx indicated poor association between these indices (range from ?0.04 to 0.07). PRx was significantly lower in patients with good outcome (p = 0.01), while none of the ORx indices proved to be significantly different in the two outcome groups. Higher mortality related to average CPP < CPP_opt was found regardless of which index was used to calculate CPP_opt.

Conclusion

In the TBI setting, ORx does not appear to correlate with vascular pressure reactivity as assessed with PRx. Its potential use for individualizing CPP thresholds remains unclear.

     

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.     

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.     

Temporal changes in cerebral tissue oxygenation with cerebrovascular pressure reactivity in severe traumatic brain injury

Objective

To investigate the temporal relationship between cerebrovascular pressure reactivity and brain tissue oxygenation in patients with severe head injury.

Methods

In 40 patients, brain tissue oxygenation and intracranial pressure were monitored. Time‐averaged values for intracranial pressure (ICP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP) and brain tissue oxygenation (PtiO₂) were computed. The pressure reactivity index (PRx) was calculated. The mean values of the variables were obtained at the 6‐h and 72‐h post‐injury time points, and the difference between the two time points for each of the variables was denoted as delta (δ).

Results

Of the 40 patients, 32 were survivors and 8 were non‐survivors. Statistically significant differences were present between these two groups with regard to δMAP (p = 0.013), ICP at 6 h (p = 0.027), CPP at 72 h (p = 0.018), δCPP (p = 0.033), PRx at 6 h (p = 0.029), PRx at 72 h (p = 0.002), PtiO₂ at 72 h (p<0.0005) and δPtiO₂ (p = 0.023) values, reflecting an improvement with time in survivors and a deterioration with time in non‐survivors. In non‐survivors, the magnitude of change in PtiO₂ and CPP with time correlated in a negative linear fashion (p = 0.042 and 0.029, respectively) with the change in PRx with time, whereas no such relationship was seen in survivors.

Conclusion

The severity of brain tissue oxygenation derangement correlates with increasing cerebrovascular dysautoregulation in patients succumbing to severe head injury, supporting the utility of PRx as a monitoring variable and the rationale for a target‐driven approach to head injury management.Cerebral ischaemia is a critical contributory factor to secondary brain injury after trauma. In the presence of an unstable cerebral perfusion pressure (CPP), the autoregulatory cerebrovascular reactivity attempts to maintain an adequate cerebral blood flow. Increasing CPP may result in raised or lowered intracranial pressure (ICP), depending on whether cerebral autoregulation is preserved. Rosner et al¹ have described how increases in CPP within the autoregulatory range lead to compensatory vasoconstriction to maintain a stable cerebral blood flow. In so doing, cerebral blood volume and thus ICP levels fall. However, outside of these autoregulatory limits, a pressure‐passive scenario exists where increases in CPP lead to vasodilatation and a rise in ICP. Investigators have defined an index comparing arterial blood pressure (ABP) and ICP to quantify this relationship between CPP and ICP, known as the pressure reactivity index (PRx).^2,3 If a rise in ABP (and hence CPP) leads to a parallel increase in ICP, a good correlation exists, and the PRx is positive. However, in the face of intact cerebral autoregulatory capacity, vasoconstriction in the face of rising CPP leads to a drop in ICP, and hence PRx approaches zero or takes a negative value. Measurement of PRx could thus form the basis for target‐driven management, as ABP can be manipulated.Clinical studies on patients with head injury have shown the feasibility of continuous monitoring of local brain tissue oxygenation (PtiO₂) as a variable for cerebral oxygenation.^4,5,6 Despite the limitations of such a local method of measurement, PtiO₂ indicates global cerebral oxygenation when the monitoring is carried out in a relatively uninjured part of the brain.⁶ The presence of autoregulation disturbance could conceivably lead to disturbance in oxygen tension in the tissue of interest by virtue of blood flow metabolism uncoupling as PtiO₂ reflects the net balance between oxygen supply and demand at the tissue level.⁷We hypothesised that a worsening PRx indicative of increasing dysautoregulation during the temporal course of monitoring is related to mortality, and this may arise from specific patterns of change in various physiological variables including PtiO₂.     

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.

     

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.     

Reduced Brain/Serum Glucose Ratios Predict Cerebral Metabolic Distress and Mortality After Severe Brain Injury

Background

The brain is dependent on glucose to meet its energy demands. We sought to evaluate the potential importance of impaired glucose transport by assessing the relationship between brain/serum glucose ratios, cerebral metabolic distress, and mortality after severe brain injury.

Methods

We studied 46 consecutive comatose patients with subarachnoid or intracerebral hemorrhage, traumatic brain injury, or cardiac arrest who underwent cerebral microdialysis and intracranial pressure monitoring. Continuous insulin infusion was used to maintain target serum glucose levels of 80–120 mg/dL (4.4–6.7 mmol/L). General linear models of logistic function utilizing generalized estimating equations were used to relate predictors of cerebral metabolic distress (defined as a lactate/pyruvate ratio [LPR] ≥ 40) and mortality.

Results

A total of 5,187 neuromonitoring hours over 300 days were analyzed. Mean serum glucose was 133 mg/dL (7.4 mmol/L). The median brain/serum glucose ratio, calculated hourly, was substantially lower (0.12) than the expected normal ratio of 0.40 (brain 2.0 and serum 5.0 mmol/L). In addition to low cerebral perfusion pressure (P = 0.05) and baseline Glasgow Coma Scale score (P < 0.0001), brain/serum glucose ratios below the median of 0.12 were independently associated with an increased risk of metabolic distress (adjusted OR = 1.4 [1.2–1.7], P < 0.001). Low brain/serum glucose ratios were also independently associated with in-hospital mortality (adjusted OR = 6.7 [1.2–38.9], P < 0.03) in addition to Glasgow Coma Scale scores (P = 0.029).

Conclusions

Reduced brain/serum glucose ratios, consistent with impaired glucose transport across the blood brain barrier, are associated with cerebral metabolic distress and increased mortality after severe brain injury.     

The Neurological Wake-up Test Does not Alter Cerebral Energy Metabolism and Oxygenation in Patients with Severe Traumatic Brain Injury

Background

The neurological wake-up test (NWT) is used to monitor the level of consciousness in patients with traumatic brain injury (TBI). However, it requires interruption of sedation and may elicit a stress response. We evaluated the effects of the NWT using cerebral microdialysis (MD), brain tissue oxygenation (Pb_tiO₂), jugular venous oxygen saturation (SjvO₂), and/or arterial-venous difference (AVD) for glucose, lactate, and oxygen in patients with severe TBI.

Methods

Seventeen intubated TBI patients (age 16–74 years) were sedated using continuous propofol infusion. All patients received intracranial pressure (ICP) and cerebral perfusion pressure (CPP) monitoring in addition to MD, Pb_tiO₂ and/or SjvO₂. Up to 10 days post-injury, ICP, CPP, Pb_tiO₂ (51 NWTs), MD (49 NWTs), and/or SjvO₂ (18 NWTs) levels during propofol sedation (baseline) and NWT were compared. MD was evaluated at a flow rate of 1.0 μL/min (28 NWTs) or the routine 0.3 μL/min rate (21 NWTs).

Results

The NWT increased ICP and CPP levels (p < 0.05). Compared to baseline, interstitial levels of glucose, lactate, pyruvate, glutamate, glycerol, and the lactate/pyruvate ratio were unaltered by the NWT. Pathological SjvO₂ (<50 % or >71 %; n = 2 NWTs) and Pb_tiO₂ (<10 mmHg; n = 3 NWTs) values were rare at baseline and did not change following NWT. Finally, the NWT did not alter the AVD of glucose, lactate, or oxygen.

Conclusions

The NWT-induced stress response resulted in increased ICP and CPP levels although it did not negatively alter focal neurochemistry or cerebral oxygenation in TBI patients.     

Does Prone Positioning Increase Intracranial Pressure? A Retrospective Analysis of Patients with Acute Brain Injury and Acute Respiratory Failure

Purpose

The objective of our trial was to obtain more comprehensive data on the risks and benefits of kinetic therapy in intensive care patients with intracerebral pathology.

Methods

Standardized data of prone positioning in our NeuroIntensive Care Unit were collected from 2007 onward. A post hoc analysis of all available data was undertaken, with special consideration given to values of intracranial pressure (ICP), cerebral perfusion pressure (CPP) and oxygenation in correlation to prone (PP), or supine positioning (SP) of patients. Cases were considered eligible if kinetic therapy and ICP were documented. Prone positioning was performed in a 135° position for 8 h per treatment unit.

Results

A total of 115 patients treated with prone positioning from 2007 to 2013 were identified in our medical records. Of these, 29 patients received ICP monitoring. Overall, 119 treatment units of prone positioning with a mean duration of 2.5 days per patient were performed. The mean baseline ICP in SP was 9.5 ± 5.9 mmHg and was increased significantly during PP (p < 0.0001). There was no significant difference between CPP in SP (82 ± 14.5 mmHg) compared to PP (p > 0.05). ICP values >20 mmHg occurred more often during PP than SP (p < 0.0001) and were associated with significantly more episodes of decreased CPP <70 mmHg (p < 0.0022). The mean paO₂/FiO₂ ratio (P/F ratio) was increased significantly in prone positioning of patients (p < 0.0001).

Conclusions

The analyzed data allow a more precise understanding of changes in ICP and oxygenation during prone positioning in patients with acute brain injury and almost normal baseline ICP. Our study shows a moderate, yet significant elevation of ICP during prone positioning. However, the achieved increase of oxygenation by far exceeded the changes in ICP. It is evident that continuous monitoring of cerebral pressure is required in this patient group.     

Induced Normothermia Attenuates Intracranial Hypertension and Reduces Fever Burden after Severe Traumatic Brain Injury

Introduction

Hyperthermia following a severe traumatic brain injury (TBI) is common, potentiates secondary injury, and worsens neurological outcome. Conventional fever treatment is often ineffective. An induced normothermia protocol, utilizing intravascular cooling, was used to assess the impact on fever incidence and intracranial pressure (ICP) in patients with severe TBI.

Methods

A comparative cohort study of 21 adult patients with severe TBI (GCS ≤ 8) treated with induced normothermia [36–36.5°C rectal probe setting; intravascular cooling catheter (CoolLine^®, Alsius Corporation, Irvine, CA)] were matched by age, gender, and severity of injury to 21 historical control severe TBI patients treated with conventional fever control methods. ICP was measured via an external ventricular catheter and time duration for ICP > 25 mmHg was calculated for the initial 72-h monitoring period. Non-parametric rank tests were performed.

Results

Mean (±SD) or median [range] demographics did not differ between groups [total N = 42 (6 female, 36 male, age 36.4 ± 14.8 years and initial GCS 7 [3–8], median and range]. Fever burden in the first 3 days (time >38°C) in the induced normothermia versus control group was significantly less at 1.6% versus 10.6%, respectively (P = 0.03). Mean ICP for patients with induced normothermia versus control was 12.74 ± 4.0 and 16.37 ± 6.9 mmHg, respectively. Furthermore, percentage of time with ICP > 25 mmHg was significantly less in the induced normothermia group (P = 0.03).

Conclusion

Induced normothermia (fever prophylaxis via intravascular cooling catheter) is effective in reducing fever burden and may offer a means to attenuate secondary injury, as evidenced by a reduction in the intracranial hypertension burden.     

Fluid Responsiveness and Brain Tissue Oxygen Augmentation After Subarachnoid Hemorrhage

Background

The objective of this study was to investigate the relationship between cardiac index (CI) response to a fluid challenge and changes in brain tissue oxygen pressure (PbtO₂) in patients with subarachnoid hemorrhage (SAH).

Methods

Prospective observational study was conducted in a neurological intensive care unit of a university hospital. Fifty-seven fluid challenges were administered to ten consecutive comatose SAH patients that underwent multimodality monitoring of CI, intracranial pressure (ICP), and PbtO₂, according to a standardized fluid management protocol.

Results

The relationship between CI and PbtO₂ was analyzed with logistic regression utilizing generalized estimating equations. Of the 57 fluid boluses analyzed, 27 (47 %) resulted in a ≥ 10 % increase in CI. Median absolute (+5.8 vs. +1.3 mmHg) and percent (20.7 vs. 3.5 %) changes in PbtO₂ were greater in CI responders than in non-responders within 30 min after the end of the fluid bolus infusion. In a multivariable model, a CI response was independently associated with PbtO₂ response (adjusted odds ratio 21.5, 95 % CI 1.4–324, P = 0.03) after adjusting for mean arterial pressure change and end-tidal CO₂. Stroke volume variation showed a good ability to predict CI and PbtO₂ response with areas under the ROC curve of 0.86 and 0.81 with the best cut-off values of 9 % for both responses.

Conclusion

Bolus fluid resuscitation resulting in augmentation of CI can improve cerebral oxygenation after SAH.     

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.     

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.

     

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.     

Intraoperative secondary insults during extracranial surgery in children with traumatic brain injury

Purpose

Data on intraoperative secondary insults in pediatric traumatic brain injury (TBI) are limited.

Methods

We examined intraoperative secondary insults during extracranial surgery in children with moderate-severe TBI and polytrauma and their association with postoperative head computed tomography (CT) scans, intracranial pressure (ICP), and therapeutic intensity level (TIL) scores 24 h after surgery. After IRB approval, we reviewed the records of children <18 years with a Glasgow Coma Scale score <13 who underwent extracranial surgery within 72 h of TBI. Definitions of secondary insults were as follows: systemic hypotension (SBP <70?+?2?×?age or 90 mmHg), cerebral hypotension (cerebral perfusion pressure <40 mmHg), intracranial hypertension (ICP >20 mmHg), hypoxia (oxygen saturation <90 %), hypercarbia (end-tidal CO₂ >45 mmHg), hypocarbia (end-tidal CO₂ <30 mmHg without hypotension and in the absence of intracranial hypertension), hyperglycemia (blood glucose >200 mg/dL), hyperthermia (temperature >38 °C), and hypothermia (temperature <35 °C).

Results

Data from 50 surgeries in 42 patients (median age 15.5 years, 25 males) revealed systemic hypotension during 78 %, hypocarbia during 46 %, and hypercarbia during 25 % surgeries. Intracranial hypertension occurred in 64 % and cerebral hypotension in 18 % surgeries with ICP monitoring (11/50). Hyperglycemia occurred during 17 % of the 29 surgeries with glucose monitoring. Cerebral hypotension and hypoxia were associated with postoperative intracranial hypertension (p?=?0.02 and 0.03, respectively). We did not observe an association between intraoperative secondary insults and postoperative worsening of head CT scan or TIL score.

Conclusions

Intraoperative secondary insults were common during extracranial surgery in pediatric TBI. Intraoperative cerebral hypotension and hypoxia were associated with postoperative intracranial hypertension. Strategies to prevent secondary insults during extracranial surgery in TBI are needed.