Noninvasive Measurement of Cerebral Blood Flow and Blood Oxygenation Using Near-Infrared and Diffuse Correlation Spectroscopies in Critically Brain-Injured Adults

Background

This study assesses the utility of a hybrid optical instrument for noninvasive transcranial monitoring in the neurointensive care unit. The instrument is based on diffuse correlation spectroscopy (DCS) for measurement of cerebral blood flow (CBF), and near-infrared spectroscopy (NIRS) for measurement of oxy- and deoxy-hemoglobin concentration. DCS/NIRS measurements of CBF and oxygenation from frontal lobes are compared with concurrent xenon-enhanced computed tomography (XeCT) in patients during induced blood pressure changes and carbon dioxide arterial partial pressure variation.

Methods

Seven neurocritical care patients were included in the study. Relative CBF measured by DCS (rCBF_DCS), and changes in oxy-hemoglobin (ΔHbO₂), deoxy-hemoglobin (ΔHb), and total hemoglobin concentration (ΔTHC), measured by NIRS, were continuously monitored throughout XeCT during a baseline scan and a scan after intervention. CBF from XeCT regions-of-interest (ROIs) under the optical probes were used to calculate relative XeCT CBF (rCBF_XeCT) and were then compared to rCBF_DCS. Spearman’s rank coefficients were employed to test for associations between rCBF_DCS and rCBF_XeCT, as well as between rCBF from both modalities and NIRS parameters.

Results

rCBF_DCS and rCBF_XeCT showed good correlation (r _s = 0.73, P = 0.010) across the patient cohort. Moderate correlations between rCBF_DCS and ΔHbO₂/ΔTHC were also observed. Both NIRS and DCS distinguished the effects of xenon inhalation on CBF, which varied among the patients.

Conclusions

DCS measurements of CBF and NIRS measurements of tissue blood oxygenation were successfully obtained in neurocritical care patients. The potential for DCS to provide continuous, noninvasive bedside monitoring for the purpose of CBF management and individualized care is demonstrated.     

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 physiology in perinates with congenital hydrocephalus

Purpose

This study investigated changes in regional cerebral blood flow (rCBF), autoregulation (AR), and mean CO₂ reactivity (CO₂r) in nine neonates, who underwent cerebrospinal fluid (CSF) diversion for congenital hydrocephalus.

Methods

During shunt insertion, a thermal diffusion probe inserted adjacent to the ventricular catheter in the right parietal region recorded rCBF. Changes in rCBF, mean arterial pressure, intracranial pressure (ICP), and expired CO₂ tension were recorded before and after removing CSF.

Results

Mean baseline rCBF for the entire group was 19.5 mL/100 g/min (range 8.4–44.8), with a mean ICP of 9.9 mmHg (range 4–20). Following CSF removal, the rCBF increased significantly in two patients. Three patients demonstrated AR throughout their studies; one infant showed AR after CSF removal. One infant without AR during shunt insertion showed an increase in rCBF and AR during a revision 5 months later. Baseline CO₂r varied considerably but was greater than two in two patients and increased in three other children after CSF removal. Mean follow-up was 23.6 months. One child, with severe developmental delay, died. Death or severe delay was associated with the absence of AR and a negative CO₂r in three children. Normal or mild developmental delay was associated with AR and a neutral or positive CO₂r in five patients.

Conclusions

Baseline levels of rCBF were not associated with developmental prognosis. AR and a positive CO₂r were necessary but insufficient factors for normal development. The absence of AR and a negative CO₂r were associated with poor prognosis.     

Intra-hospital Transport of Brain-Injured Patients: A Prospective, Observational Study

Introduction

Discrepant data exist regarding the incidence and severity of clinical problems related to intra-hospital transport of brain-injured patients and no consensus exists whether modern-day intra-hospital transport represents a safe or potentially problematic environment for neurointensive care unit (NICU) patients.

Methods

We examined the incidence of clinical complications and physiological derangements that occurred in 160 neurologically injured patients (90 males, 70 females, mean age 57 ± 17 years) who underwent intra-hospital transport (288 cases, 237 scheduled, 51 unscheduled) for computed tomography scans.

Results

Our findings indicate that (1) at least one significant complication (predominantly hemodynamic) occurred in over one-third (36 %) of all transports (p = n.s scheduled vs. unscheduled) necessitating the deployment of interventions designed to treat changes in arterial pressure (2) despite the presence of trained medical personnel and availability of specialized equipment, intra-cranial pressure was not adequately monitored during transports (especially in patients with intra-cranial hypertension prior to transport) (3) intra-hospital transfer was associated with minor but statistically significant clinical changes, including a reduction in arterial partial pressure of oxygen ( $ {\text{Pa}}_{{{\text{O}}_{ 2} }} $ )/inspired oxygen fraction ( $ {\text{Fi}}_{{{\text{O}}_{ 2} }} $ ) (only in the scheduled transport population), decreased arterial lactate levels (scheduled transport population), lowered body temperature (scheduled transport population), and increased arterial partial pressure of carbon dioxide ( $ {\text{Pa}}_{{{\text{CO}}_{ 2} }} $ ) (scheduled transport population).

Conclusions

Intra-hospital transport of brain-injured NICU patients may present some hazards even if performed by skilled personnel with specialized equipment. In Trauma Centers such as ours, an improvement in the frequency of neuromonitoring [intra-cranial pressure (ICP) and end-tidal CO₂ ( $ {\text{ET}}_{{{\text{CO}}_{ 2} }} $ )] during transport is recommended.     

Impact of Methamphetamine on Regional Metabolism and Cerebral Blood Flow After Traumatic Brain Injury

Background

Substance abuse is a frequent comorbid condition among patients with traumatic brain injury (TBI), but little is known about its potential additive or interactive effects on tissue injury or recovery from TBI. This study aims to evaluate changes in regional metabolism and cerebral perfusion in subjects who used methamphetamine (METH) prior to sustaining a TBI. We hypothesized that METH use would decrease pericontusional cerebral perfusion and markers of neuronal metabolism, in TBI patients compared to those without METH use.

Methods

This is a single center prospective observational study. Adults with moderate and severe TBI were included. MRI scanning was performed on a 3 Tesla scanner. MP-RAGE and FLAIR sequences as well as Metabolite spectra of NAA and lactate in pericontusional and contralateral voxels identified on the MP-RAGE scans. A spiral-based FAIR sequence was used for the acquisition of cerebral blood flow (CBF) maps. Regional CBF images were analyzed using ImageJ open source software. Pericontusional and contralateral CBF, NAA, and lactate were assessed in the entire cohort and in the METH and non-METH groups.

Results

Seventeen subjects completed the MR studies. Analysis of entire cohort: pericontusional NAA concentrations (5.81 ± 2.0 mM/kg) were 12 % lower compared to the contralateral NAA (6.98 ± 1.2 mM/kg; p = 0.03). Lactate concentrations and CBF were not significantly different between the two regions; however, regional CBF was equally reduced in the two regions. Subgroup analysis: 41 % of subjects tested positive for METH. The mean age, Glasgow Coma Scale, and time to scan did not differ between groups. The two subject groups also had similar regional NAA and lactate. Pericontusional CBF was 60 % lower in the METH users than the non-users, p = 0.04; contralateral CBF did not differ between the groups.

Conclusion

This small study demonstrates that tissue metabolism is regionally heterogeneous after TBI and pericontusional perfusion was significantly reduced in the METH subgroup.     

Imidafenacin on bladder and cognitive function in neurologic OAB patients

Objective

To explore imidafenacin’s effects on bladder and cognitive function in neurologic overactive bladder (OAB) patients.

Methods

Sixty-two subjects (25 men, 37 women; mean age 70 years (25–86) with OAB due to neurologic diseases) were enrolled in the study. We conducted a urinary symptom survey and cognitive tests (MMSE, FAB, ADAS-cog) in all patients. We performed urodynamics in 35 patients and measured real-time near-infrared spectroscopy (NIRS)-urodynamics in eight patients before and after the administration of imidafenacin, an anticholinergic agent, for 3 months at 0.2 mg/day.

Results

Imidafenacin significantly ameliorated urinary urgency, nighttime urinary frequency, and quality of life index (p < 0.05). Three cognitive measures did not change significantly. Urodynamics showed increased bladder capacity (p < 0.05) but detrusor overactivity did not change significantly. NIRS showed that the subtraction of oxyhemoglobin between the start of filling and the first sensation increased in the bilateral prefrontal area but without statistical significance.

Conclusions

Imidafenacin ameliorated bladder sensation without cognitive worsening, with a trend of prefrontal activation. Regarding cognitive function, imidafenacin is safely used in OAB patients due to neurologic diseases.

Synopsis

In order to explore imidafenacin (anticholinergic agent)’s effects on bladder and brain function, we performed urinary questionnaire, cognitive tests, urodynamics and near-infrared spectroscopy (selected cases) in 62 overactive bladder (OAB) patients due to various neurologic diseases. As a result, imidafenacin ameliorated bladder sensation without cognitive worsening, with a trend of prefrontal activation. Imidafenacin seems safe in treating OAB patients due to neurologic diseases.     

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.     

First Clinical Experience with Intranasal Cooling for Hyperthermia in Brain-Injured Patients

Introduction

Hyperthermia is common in brain-injured patients and associated with a worse outcome. As brain rather than body temperature reduction, theoretically, is the most important in cerebral protection, there is logic in targeting cooling at the brain. Selective brain cooling can, in theory, be obtained by cooling the skull or by heat loss from the upper airways. In this preliminary safety and efficacy study, we report clinical data from brain-injured patients who because of hyperthermia were treated with intranasal cooling.

Methods

Nine intubated brain-injured patients with hyperthermia were treated using a prototype intranasal balloon system perfused with cold saline. Temperature in the cerebrum, esophagus, and bladder was monitored together with intracranial pressure.

Results

In only two of nine patients, normothermia was reached in the esophagus and in only four of nine patients it was reached in the bladder. When normothermia was reached, the time to normothermia was delayed. In the brain, normothermia was reached in two of five patients after approximately 72 h. Median temperature curves from the first 72 h of cooling showed that normothermia was not reached in any of the three compartments. The temperature in the brain and bladder were on average 0.6 and 0.5 °C higher than in the esophagus. ICP increased with increasing brain temperature. We found no signs of clinical important injury to the nasal mucosa from the cold saline or pressure in the balloons.

Conclusion

In brain-injured patients with hyperthermia, cooling with a prototype intranasal balloon system was clinically inadequate as the effect was delayed and not brain selective.     

Cerebral oxygenation and hemodynamic measurements during craniosynostosis surgery with near-infrared spectroscopy

Introduction

Focal pressure-related changes in brain perfusion and metabolism are discussed in single-suture craniosynostosis and brachycephalic cases (bicoronal synostosis). Raised intracranial pressure levels could be measured in some cases. In order to find possible loco-regional brain tissue changes during plastic surgery, we investigated oxygenation and perfusion parameters using non-invasive near-infrared spectroscopy (NIRS) probes.

Methods

Twenty-two consecutively operated cases (mean age 7 months) with single-suture craniosynostosis were prospectively investigated using a NIRS probe (LEA^©, O2C, white light 500–800 nm, laser NIR). Measurements for oxygen saturation (SO₂), relative quantity of hemoglobin (rHb), blood flow, and blood flow velocity of the bilateral frontal, temporal, and parietal cortices were taken transosseously (prior to decompression) and epidurally directly after decompression as well as 15 and 30 min after decompression and before closure.

Results

Twenty-two patients with scaphocephaly (11), trigonocephaly (6), anterior plagiocephaly (3), and brachycephaly (2) were investigated. SO₂ was improving in all patient subgroups, showing the highest levels in the fronto-temporal region; rHb improved in scaphocephalic, trigonocephalic, and brachycephalic children. Again, the highest values were found not only in the temporal but also in the frontal region and in brachycephalic patients also in the parietal cortex.

Conclusion

These preliminary results of a new technology for brain tissue oxygenation and blood flow measurements suggest a regional compromise of cortical metabolism and circulation in patients with craniosynostosis.     

A Prospective, Observational Clinical Trial of Fever Reduction to Reduce Systemic Oxygen Consumption in the Setting of Acute Brain Injury

Introduction

Fever after acute brain injury appears to be a detrimental factor, associated with impaired neurological outcomes. This study assessed physiological changes in systemic oxygen consumption (VO2) during cutaneous cooling after severe brain injury.

Methods

This prospective, observational, clinical study evaluated ten, critically ill, brain-injured patients requiring mechanical ventilation with a core body temperature of greater or equal to 38°C. Febrile patients failing to defervesce after acetaminophen underwent indirect calorimetry for a 1-hour baseline period followed by a 4 h cooling period. The Arctic Sun® Temperature Management System (Medivance®) directed core temperature to a goal of 36°C.

Results

The patients had a mean age of 32 years (95% CI 23, 40), Glasgow Coma Scale of 6 (95% CI 5,7), and APACHE 2 score of 19 (95% CI 15, 22), with 8 of 10 patients suffering traumatic brain injuries. The baseline 1-h core temperature was significantly reduced from 38.6°± 0.9 to 36.3°± 1.2°C (P < 0.0001) over 4 h. Two cohorts were identified based upon the presence or absence of shivering. Within the non-shivering cohort, systemic VO2 was significantly reduced from 415 ± 123 to 308 ± 115 ml/min (?27 ± 18%) (P < 0.05). In contrast, those with shivering showed no significant reduction in VO2, despite significantly decreasing core temperature. The overall percentage change of VCO2 correlated with VO2 (r ² = 0.91).

Conclusion

Fever reduction in acute brain injury appears to significantly reduce systemic VO2, but is highly dependent on shivering control.     

QTc-Prolongation in Posterior Circulation Stroke

Background and Purpose

To evaluate the relationship between infarct location and QTc-prolongation in patients with posterior circulation strokes.

Methods

Admission electrocardiograms (ECG) of 131 patients among a prospective sample of 407 consecutive adult patients in the New England Medical Center Posterior Circulation Registry were retrospectively analyzed. The QT interval (ms) was measured and corrected using Bazett’s formula (QTc_Bazett) as well as linear regression functions (QTc_Linear). QTc_Bazett > 440 ms and QTc_Linear ≥ 450 ms for men (≥460 ms for women) were considered prolonged. Multivariable linear and logistic regression analyses were used to identify independent predictors of the QTc.

Results

Overall, 34 % of patients had a prolonged QTc_Bazett and 7 % had a prolonged QTc_Linear noted on the admission ECG. There was a significant association between temporal lobe infarction and QTc_Bazett and QTc_Linear (p < 0.001 for both) in multivariable linear regression analyses adjusting for demographics, ECG parameters, and preadmission medication use. In multivariable logistic regression analysis, temporal lobe infarction emerged as an independent predictor of prolonged QTc_Bazett (p = 0.009) and QTc_Linear (p = 0.008), respectively. Sensitivity analyses excluding patients with transient ischemic attack yielded similar results. Exploratory analyses indicated that patients with temporal lobe infarction had worse functional 30-day outcomes in multivariable logistic regression (p = 0.022). However, there was no significant association between QTc and 30-day functional outcome.

Conclusions

QTc-prolongation is common after posterior circulation stroke and associated with temporal lobe infarction. Prospective studies are needed to confirm these preliminary findings and to examine potential long-term consequences.     

The Physiologic Effects of Indomethacin Test on CPP and ICP in Severe Traumatic Brain Injury (sTBI)

Background

Refractory intracranial hypertension (RICH) is associated with high mortality in severe traumatic brain injury (sTBI). Indomethacin (INDO) can decrease intracranial cerebral pressure (ICP) improving cerebral pressure perfusion (CPP). Our aim was to determine modifications in ICP and CPP following INDO in RICH secondary to sTBI.

Methods

INDO was administered in a loading dose (0.8 mg/kg/15 min), followed by continuous 2-h infusion period (0.5 mg/kg/h). Clinical outcome was assessed at 30 days according to Glasgow Outcome Scale (GOS). Differences in ICP and CPP values were assessed using repeated-measures ANOVA. Receiver operating characteristic curve (AUC) was used for discrimination in predicting 30-day survival and good functional outcome (GOS 4 or 5). Analysis of INDO safety profile was also conducted.

Results

Thirty-two patients were included. Median GCS score was 6 (interquartile range: 4–7). The most frequent CT finding was the evacuated mass lesion (EML) according to Marshall classification (28.1 %). Mortality rate was 34.4 %. Within 15 min of INDO infusion, ICP decreased (Δ%: ?54.6 %; P < 0.0001), CPP increased (Δ%: +44.0 %; P < 0.0001), and the remaining was stable during the entire infusion period. Patients with good outcome (n = 12) showed a greater increase of CPP during INDO test (P = 0.028). CPP response to INDO test discriminated moderately well surviving patients (AUC = 0.751; P = 0.0098) and those with good functional recovery (AUC = 0.763; P = 0.0035) from those who died and from those with worse functional outcome, respectively. No adverse events were observed.

Conclusions

INDO appears effective in reducing ICP and improving CPP in RICH. INDO test could be a useful tool in identifying RICH patients with favorable outcome. Future studies are needed.     

Regional cerebral blood flow during auditory recall in 47 subjects exposed to assaultive and non–assaultive trauma and developing or not posttraumatic stress disorder

Objective

Psychological trauma leads to posttraumatic stress disorder (PTSD) in susceptible subjects. The aim of this study was to investigate the differences in regional cerebral blood flow (rCBF) between two groups of subjects exposed to different types of traumatic stressor either developing or not developing PTSD.

Methods

Twenty subjects developing (S) and 27 not developing (NS) PTSD after being exposed to either earlier person–under–the–train accident (NA) or being assaulted in the underground environment (A) were included in the study. ^99mTc–HMPAO SPECT was performed and the uptake in 29 regions of the brain (VOIs), bilaterally, was assessed. rCBF distribution was compared, using analysis of variance (ANOVA), between groups (S/NS) and type (A/NA) during a situation involving an auditory evoked re–experiencing of the traumatic event. Discriminant analysis was applied to test the concordance between clinical diagnosis and SPECT findings.

Results

In the general analyses significant differences were found between groups and types and there was a significant hemisphere × type interaction. S showed higher CBF than NS and so did A as compared to NA, particularly in the right hemisphere. Discriminant analysis correctly classified 66% of cases (p < 0001) in testing S/NS and 72% (p < 0001) in testing NA/A.

Conclusions

Under recall of their traumatic experience we found higher relative CBF distribution values in S as compared to NS. CBF was higher in the right hemisphere and particularly in assaulted subjects. These findings underscore the role upon trauma recall of both the right hemisphere and the nature of the stressing event.     

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.     

Therapeutic Hypothermia Reduces Middle Cerebral Artery Flow Velocity in Patients with Severe Aneurysmal Subarachnoid Hemorrhage

Background

Transcranial Doppler (TCD) is widely used to detect and follow up cerebral vasospasm after subarachnoid hemorrhage (SAH). Therapeutic hypothermia might influence blood flow velocities assessed by TCD. The aim of the study was to evaluate the effect of hypothermia on Doppler blood flow velocity after SAH.

Methods

In 20 patients treated with hypothermia (33°) due to refractory intracranial hypertension or delayed cerebral ischemia (DCI), mean flow velocity of the middle cerebral artery (MFV_MCA) was assessed by TCD. Thirteen patients were treated with combined hypothermia and barbiturate coma and seven with hypothermia alone. MFV_MCA was obtained within 24 h before and after induction of hypothermia as well as before and after rewarming.

Results

Hypothermia was induced on average 5 days after SAH (range 1–12) and maintained for 144 h (range 29–270). After hypothermia induction, MFV_MCA decreased from 113.7 ± 49.0 to 93.8 ± 44.7 cm/s (p = 0.001). The decrease was independent of SAH-related complications and barbiturate coma. MFV_MCA further decreased by 28.2 cm/s between early and late hypothermia (p < 0.001). This second decrease was observed in patients with DCI (p < 0.001), but not in patients with intracranial hypertension (p = 0.715). Compared to late hypothermia, MFV_MCA remained unchanged after rewarming (65.6 ± 32.1 vs 70.3 ± 36.8 cm/s; p = 0.219). However, patients treated with hypothermia alone showed an increase in MFV_MCA after rewarming (p = 0.016).

Conclusion

Therapeutic hypothermia after SAH decreases Doppler blood flow velocity in both intracranial hypertension and DCI cases. The results can be the effect of hypothermia-related mechanisms or resolving cerebral vasospasm during prolonged hypothermia.     

Response of Brain Oxygen to Therapy Correlates with Long-Term Outcome After Subarachnoid Hemorrhage

Background

Brain oxygen (P_btO₂) monitoring can help guide care of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients. The relationship between P_btO₂-directed therapy and long-term outcome is unclear. We hypothesized that responsiveness to P_btO₂-directed interventions is associated with outcome.

Methods

Seventy-six aSAH patients who underwent P_btO₂ monitoring were included. Long-term outcome [Glasgow Outcome Score-Extended (GOS-E) and modified Rankin Scale (mRS)] was ascertained using the social security death database and structured telephone interviews. Univariate and multivariate regression were used to identify variables that correlated with outcome.

Results

Data from 64 patients were analyzed (12 were lost to follow-up). There were 530 episodes of compromised P_btO₂ (<20 mmHg) during a total of 7,174 h of monitor time treated with 1,052 interventions. Forty-two patients (66 %) survived to discharge. Median follow-up was 8.5 months (range 0.1–87). At most recent follow-up 35 (55 %) patients were alive, and 28 (44 %) had a favorable outcome (mRS ≤3). In multivariate ordinal regression analysis, only age and response to P_btO₂-directed intervention correlated significantly with outcome. Increased age was associated with worse outcome (coeff. 0.8, 95 % CI 0.3–1.3, p = 0.003), and response to P_btO₂-directed intervention was associated with improved outcome (coeff. ?2.12, 95 % CI ?4.0 to ?0.26, p = 0.03). Patients with favorable outcomes had a 70 % mean rate of response to P_btO₂-directed interventions whereas patients with poor outcomes had a 45 % response rate (p = 0.005).

Conclusions

Response to P_btO₂-directed intervention is associated with improved long-term functional outcome in aSAH patients.     

Noninvasive optical measures of CBV,StO2, CBF index,and rCMRO2 in human premature neonates' brains in the first six weeks of life

With the causes of perinatal brain injuries still unclear and the probable role of hemodynamic instability in their etiology, bedside monitoring of neonatal cerebral hemodynamics with standard values as a function of age are needed. In this study, we combined quantitative frequency domain near infrared spectroscopy (FD‐NIRS) measures of cerebral tissue oxygenation (StO₂) and cerebral blood volume (CBV) with diffusion correlation spectroscopy (DCS) measures of a cerebral blood flow index (CBF_ix) to test the validity of the CBV‐CBF relationship in premature neonates and to estimate cerebral metabolic rate of oxygen (rCMRO₂) with or without the CBF_ix measurement. We measured 11 premature neonates (28–34 weeks gestational age) without known neurological issues, once a week from one to six weeks of age. In nine patients, cerebral blood velocities from the middle cerebral artery were collected by transcranial Doppler (TCD) and compared with DCS values. Results show a steady decrease in StO₂ during the first six weeks of life while CBV remains stable, and a steady increase in CBF_ix. rCMRO₂ estimated from FD‐NIRS remains constant but shows wide interindividual variability. rCMRO₂ calculated from FD‐NIRS and DCS combined increased by 40% during the first six weeks of life with reduced interindividual variability. TCD and DCS values are positively correlated. In conclusion, FD‐NIRS combined with DCS offers a safe and quantitative bedside method to assess CBV, StO₂, CBF, and rCMRO₂ in the premature brain, facilitating individual follow‐up and comparison among patients. A stable CBV‐CBF relationship may not be valid for premature neonates. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Admission oxygenation and ventilation parameters associated with discharge survival in severe pediatric traumatic brain injury

Purpose

Current Brain Trauma Foundation guidelines recommend avoiding hypoxemia after severe pediatric traumatic brain injury (TBI). Yet, recent studies on optimum admission oxygenation and ventilation parameters associated with discharge survival in pediatric TBI are lacking.

Materials and methods

After IRB approval, a retrospective study involving pediatric patients ages ≤14 years with severe TBI (head Abbreviated Injury Scale (AIS) score of ≥3, Glasgow Coma Scale score of ≤8 on admission) admitted to Harborview Medical Center (level 1 pediatric trauma center), Seattle, WA, during 2003 to 2007 was performed. Admission demographics, clinical data, and laboratory characteristics were abstracted. Hypoxemia was defined as PaO₂?<?60 mmHg, hypocarbia was defined as PaCO₂?≤?35 mmHg, and hypercarbia was defined as PaCO₂?≥?46 mmHg.

Results

One hundred ninety-four patients met inclusion criteria of which 162 (83.5 %) patients survived. Admission hypoxemia occurred in nine (5.6 %) patients who survived and eight (25 %) patients who died (p?<?0.001). Children with admission PaCO₂ between 36 and 45 mmHg had greater discharge survival compared with those with both admission hypocarbia (PaCO₂?≤?35 mmHg) and hypercarbia (PaCO₂?≥?46 mmHg). Admission PaO₂ 301–500 mmHg (adjusted odds ratio (AOR), 8.02 (95 % confidence interval (CI), 1.73–37.10); p?=?0.008) and admission PaCO₂?=?36–45 mmHg (AOR, 5.47 (95 % CI, 1.30–23.07); p?=?0.02) were independently associated with discharge survival.

Conclusions

Discharge survival after severe pediatric TBI was associated with admission PaO₂ 301–500 mmHg and PaCO₂?=?36–45 mmHg. Admission hypocarbia and hypercarbia were each associated with increased discharge mortality.     

The Prognostic Value of Brain Extracellular Fluid Nitric Oxide Metabolites After Traumatic Brain Injury

Background

Nitric oxide (NO) is a compound with both protective and damaging effects on neurons. Quantification of NO metabolites in humans is limited by sample contamination with blood. In vivo cerebral microdialysis may offer an alternative approach as sampling of extracellular fluid (ECF) adjacent to neurons becomes possible. We investigate the prognostic value of brain ECF NO metabolites in patients with traumatic brain injury (TBI).

Methods

A prospective case cohort of 195 ECF samples collected from 11 cases over 4 days following TBI was collected. Nitrate and nitrite concentrations ([NO _x ]) were quantified using a vanadium-based colorimetric assay.

Results

Early ECF [NO _x ] (<48 h post TBI) were significantly higher in non-survivors (median 59.2 μmol/l, n = 7) compared to survivors (23.3 μmol/l, n = 4) (P = 0.04). Late (48–96 h) ECF [NO _x ] remained higher in non-survivors (47.9 μmol/l) compared to survivors (23.0 μmol/l) but this was not significant (P = 0.29). Receiver operator characteristic analysis shows an optimized cutoff level for ECF [NO _x ] of 26.5 μmol/l measured <48 h post TBI for predicting non-survival (sensitivity 100%, specificity 75%).

Conclusion

Early ECF NO _x concentrations are of prognostic value after TBI. ECF NO _x may be a useful biomarker for treatment trials targeted at nitric oxide metabolism.     

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.