Determinants of orthostatic cerebral oxygenation assessed using near-infrared spectroscopy.

BACKGROUND: To understand the relationship between blood pressure changes during standing up and clinical outcome, cerebral oxygenation needs to be measured, which may be performed using near-infrared spectroscopy (NIRS). However, the role of potential determinants of NIRS-derived orthostatic cerebral oxygenation, i.e., age, sex, type of postural change (i.e., standing up from sitting versus supine position), blood pressure (BP) and baroreflex sensitivity (BRS) is still unknown and needed to better interpret findings from studies using orthostatic NIRS measurements. METHODS: 34 younger (median age 25 years, inter quartile range (IQR) 22-45) and 31 older adults (median age 77 years, IQR 72-81) underwent BP, BRS and NIRS measurements during standing up from sitting and supine position. Linear regression models were used to assess the potential determinant role of age, sex, type of postural change, BP and BRS in orthostatic cerebral oxygenation drop and recovery. Orthostatic cerebral oxygenation test-retest reliability was assessed using intra class correlations. RESULTS: Younger age, male sex and standing up from supine compared to sitting position were positively associated with cerebral oxygenation drop; older age and standing up from sitting compared to supine position were associated with higher cerebral oxygenation recovery. Test-retest reliability was highest (ICC > 0.83) during standing up from supine position. CONCLUSION: Based on the findings of this study, age, sex and type of postural change are significant determinants of NIRS-derived orthostatic cerebral oxygenation and should be taken into account in the interpretation of NIRS measurements. In the design of new studies, standing up from supine position is preferable (higher reliability) over standing up from sitting position.

Feasibility of Diagnosing Initial Orthostatic Hypotension Using a Continuous Blood Pressure Device in Geriatric Rehabilitation Inpatients: RESORT.

BACKGROUND: Initial orthostatic hypotension (IOH) is highly prevalent in older adults and may interfere with the ability to regain function after acute hospitalization. IOH assessment requires a non-invasive, beat-to-beat continuous blood pressure device, which is not widely used in geriatric rehabilitation. Our aim was to test the feasibility of diagnosing IOH using a continuous blood pressure device in geriatric rehabilitation inpatients. METHODS: Geriatric rehabilitation inpatients of the REStORing Health of Acutely Unwell AdulTs (RESORT) cohort admitted to a tertiary hospital were randomly selected to undergo continuous blood pressure monitoring (Finapres) for 5 min in the supine position and 3 min of standing or sitting when unable to stand. Interventions to warm hands and adjusting the cuff pressure sizes were attempted if no signal was obtained or an error message occurred. RESULTS: Of 37 randomly selected inpatients, 29 {55.2% female; mean age 82.8 (standard deviation [SD]) 6.6 years} agreed to the continuous blood pressure measurement. Successful measurements were achieved in 20 out of 29 inpatients, two after hand warming. Patients with unsuccessful measurements were likely to be older (mean age 87.2 [SD] 4.4 years, p = 0.03), have cerebrovascular disease (p = 0.006), lower body mass index (p = 0.012), and a lower short physical performance battery score (p = 0.039). Eight out of 20 patients had IOH. CONCLUSION: The number of unsuccessful continuous blood pressure measurements was high in a population with high IOH prevalence despite multiple interventions to establish a signal. Future research should focus on improving the efficiency of continuous blood pressure devices in hospitalized patients with unsuccessful signals.

Orthostatic Blood Pressure Recovery Measured Using a Sphygmomanometer Is Not Associated with Physical Performance or Number of Falls in Geriatric Outpatients.

BACKGROUND: Orthostatic hypotension (OH) and impaired OH recovery derived from beat-to-beat blood pressure (BP) measurements are associated with detrimental clinical outcome, but the clinical relevance of OH recovery assessed using the widely available sphygmomanometer is still unclear. METHOD: 635 geriatric outpatients underwent comprehensive geriatric assessment, including orthostatic BP measurements using a sphygmomanometer, during supine rest and 1 and 3 min after standing up and assessment of physical performance (i.e., the timed up and go test and the Short Physical Performance Battery) and the number of falls in the past year. The association between BP recovery, defined as BP at 3 min minus BP at 1 min after standing up, with physical performance and falls was assessed using regression analyses, adjusting for age and sex, both in the entire cohort and after stratifying for the presence of OH at 1 min after standing up. RESULTS: BP recovery was not associated with physical performance or number of falls, neither in the entire cohort, nor in subpopulations with or without OH. CONCLUSION: The clinical relevance of BP recovery between 1 and 3 min after standing up could not be demonstrated. The results suggest that sphygmomanometer measurements have an inadequate time resolution to record the clinically relevant dynamics of orthostatic BP recovery.

Cerebral autoregulation assessed by near-infrared spectroscopy: validation using transcranial Doppler in patients with controlled hypertension, cognitive impairment and controls.

PURPOSE: Cerebral autoregulation (CA) aims to attenuate the effects of blood pressure variation on cerebral blood flow. This study assessed the criterion validity of CA derived from near-infrared spectroscopy (NIRS) as an alternative for Transcranial Doppler (TCD). METHODS: Measurements of continuous blood pressure (BP), oxygenated hemoglobin (O2Hb) using NIRS and cerebral blood flow velocity (CBFV) using TCD (gold standard) were performed in 82 controls, 27 patients with hypertension and 94 cognitively impaired patients during supine rest (all individuals) and repeated sit to stand transitions (cognitively impaired patients). The BP-CBFV and BP-O2Hb transfer function phase shifts (TFφ) were computed as CA measures. Spearman correlations (ρ) and Bland Altman limits of agreement (BAloa) between NIRS- and TCD-derived CA measures were computed. BAloa separation < 50° was considered a high absolute agreement. RESULTS: NIRS- and TCD-derived CA estimates were significantly correlated during supine rest (ρ = 0.22-0.30, N = 111-120) and repeated sit-to-stand transitions (ρ = 0.46-0.61, N = 19-32). BAloa separation ranged between 87° and 112° (supine rest) and 65°-77° (repeated sit to stand transitions). CONCLUSION: Criterion validity of NIRS-derived CA measures allows for comparison between groups but was insufficient for clinical application in individuals.

Orthostatic blood pressure recovery associates with physical performance, frailty and number of falls in geriatric outpatients.

OBJECTIVE: Blood pressure (BP) recovery after orthostatic hypotension might be important to prevent cerebral hypoperfusion episodes in older adults, and be related to better clinical outcome. The objective was to study the relationship between BP recovery and clinical outcome, that is physical and cognitive performance, frailty and falls, in geriatric outpatients. METHODS: One hundred and sixty-eight geriatric outpatients underwent continuous (beat-to-beat) BP measurements during standing up, and a comprehensive geriatric assessment, including assessment of physical performance (chair stand test), cognitive performance (Mini Mental State Examination), frailty (Fried criteria) and falls in the previous year. BP recovery was evaluated at 15-30, 30-60, 60-120 and 120-180 s after standing up and defined as mean SBP and DBP in the respective time intervals minus baseline BP. Associations with clinical outcome were assessed using linear (physical and cognitive performance and frailty) and logistic (falls) regression, adjusting for age, sex, baseline BP and initial BP drop. RESULTS: SBP recovery was associated with frailty (30-60 s interval; ß = 0.013, P = 0.02) and falls (30-60 s interval; odds ratio = 1.024, P = 0.02). DBP recovery was associated with physical performance (30-60 s interval; ß = 0.215, P = 0.01), frailty (30-60 s interval; ß = 0.028, P = 0.02) and falls (30-60 s interval; odds ratio = 1.039, P = 0.04). Neither SBP nor DBP recovery was associated with cognitive performance. CONCLUSION: DBP recovery was particularly associated with clinical outcome in geriatric outpatients, suggesting BP recovery to be of clinical interest.

Pulse transit time as a proxy for vasoconstriction in younger and older adults.

OBJECTIVES: Changes of vasoconstriction may be measured non-invasively using pulse transit time. This study assessed the sensitivity, test-retest reliability and validity of pulse transit time during vasoconstriction provocation and active standing, and the predictive value of pulse transit time for blood pressure drop. METHODS: Fifty-five younger (age < 65 years) and 31 older adults (age > 70 years) underwent electrocardiography, wrist and finger photoplethysmography and continuous blood pressure and total peripheral resistance measurements during vasoconstriction provocation using a cold pressor test (21 younger adults), or active stand tests (all other participants). Pulse transit time was defined as the time lag between the electrocardiography R-peak and the peak in the photoplethysmography first derivative; sensitivity as a significant decrease relative to baseline; test-retest reliability as the intra class correlation between different repeats of the same test; validity as the association between peripheral resistance and pulse transit time; predictive value as the association between supine resting pulse transit time and mean arterial pressure drop during active standing. RESULTS: Finger pulse transit time was sensitive and reliable (ICC 0.2-0.8) during vasoconstriction provocation, but wrist pulse transit time was poorly reliable (ICC 0-0.5); only finger pulse transit time was sensitive to and reliable (ICC 0.4-0.8) during active standing in both younger and older adults. Finger pulse transit time was not associated with total peripheral resistance. Supine resting pulse transit time had predictive value for blood pressure drop during active standing in older adults (ß -0.16; p 0.025). CONCLUSIONS: Pulse transit time was sensitive to and reliable during vasoconstriction provocation and active standing, but did not significantly differ between younger and older adults. Pulse transit time could not be demonstrated to particularly reflect vasoconstriction, but it had predictive value for blood pressure drop during active standing.

Blood Pressure Drop Rate After Standing Up Is Associated With Frailty and Number of Falls in Geriatric Outpatients.

Background The relationship between orthostatic hypotension and clinical outcome in older adults is poorly understood. Blood pressure drop rate (ie, speed of blood pressure drop) may particularly reflect the imposed challenge to the baroreflex and the associated clinical outcome (ie, frailty and number of falls). This study aimed to compare orthostatic blood pressure drop rate and drop magnitude with regard to their association with frailty and number of falls. Methods and Results Blood pressure was measured continuously during a standardized active stand task in 168 patients (mean age 81.4±7.0; 55.4% female) who visited a geriatric outpatient clinic for cognitive or mobility problems. The association of orthostatic blood pressure drop rate, blood pressure drop magnitude, and baroreflex sensitivity (ie, increase in heart rate divided by systolic blood pressure drop magnitude) with frailty (Fried criteria and 4 frailty markers) and self-reported number of falls was assessed using linear regression models, adjusting for age and sex. Systolic blood pressure drop rate had the strongest association with frailty according to the 4 frailty markers (ß 0.30; 95% CI, 0.11-0.49; P=0.003) and number of falls (ß 1.09; 95% CI, 0.19-1.20; P=0.018); diastolic blood pressure drop magnitude was most strongly associated with frailty according to the Fried criteria (ß 0.37; 95% CI, 0.15-0.60; P<0.001). Baroreflex sensitivity was associated with neither frailty nor number of falls. Conclusions Orthostatic blood pressure drop rate was associated with frailty and falls and may reflect the challenge to the baroreflex rather than drop magnitude.

Multimodal Monitoring of Cardiovascular Responses to Postural Changes.

BACKGROUND: In the poorly understood relationship between orthostatic hypotension and falls, next to blood pressure (BP), baroreflex sensitivity (BRS) and cerebral autoregulation (CAR) may be key measures. The posture- and movement dependency of orthostatic hypotension requires continuous and unobtrusive monitoring. This may be possible using simultaneous photoplethysmography (PPG), electrocardiography (ECG), and near-infrared spectroscopy (NIRS) signal recordings, from which pulse wave velocity (PWV; potentially useful for BP estimation), BRS and CAR can be derived. The PPG, NIRS and PWV signal correlation with BP and BRS/CAR reliability and validity need to be addressed. METHODS: In 34 healthy adults (mean age 25 years, inter quartile range 22-45; 10 female), wrist and finger PPG, ECG, bifrontal NIRS (oxygenated and deoxygenated hemoglobin) and continuous BP were recorded during sit to stand and supine to stand movements. Sixteen participants performed slow and rapid supine to stand movements; eighteen other participants performed a 1-min squat movement. Pulse wave velocity (PWV) was defined as the inverse of the ECG R-peak to PPG pulse delay; PPG, NIRS and PWV signal correlation with BP as their Pearson correlations with mean arterial pressure (MAP) within 30 s after the postural changes; BRS as inter beat interval drop divided by systolic BP (SBP) drop during the postural changes; CAR as oxygenated hemoglobin drop divided by MAP drop. BRS and CAR were separately computed using measured and estimated (linear regression) BP. BRS/CAR reliability was defined by the intra class correlation between repeats of the same postural change; validity as the Pearson correlation between BRS/CAR values based on measured and estimated BP. RESULTS: The highest correlation with MAP was found for finger PPG and oxygenated hemoglobin, ranging from 0.75-0.79 (sit to stand), 0.66-0.88 (supine to stand), and 0.82-0.94 (1-min squat). BRS and CAR reliability was highest during the different supine to stand movements, ranging from 0.17 - 0.49 (BRS) and 0.42-0.75 (CAR); validity was highest during rapid supine to stand movements, 0.54 and 0.79 respectively. CONCLUSION: PPG-ECG-NIRS recordings showed high correlation with BP and enabled computation of reliable and valid BRS and CAR estimates, suggesting their potential for continuous unobtrusive monitoring of orthostatic hypotension key measures.

Sensitivity and reliability of cerebral oxygenation responses to postural changes measured with near-infrared spectroscopy.

PURPOSE: Cerebral oxygenation as measured by near-infrared spectroscopy (NIRS) might be useful to discriminate between physiological and pathological responses after standing up in individuals with orthostatic hypotension. This study addressed the physiological sensitivity of the cerebral oxygenation responses as measured by NIRS to different types and speeds of postural changes in healthy adults and assessed the reliability of these responses. METHODS: Cerebral oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb) and tissue saturation index (TSI) were measured bilaterally on the forehead of 15 healthy individuals (12 male, age range 18-27) using NIRS. Participants performed three repeats of sit to stand, and slow and rapid supine to stand movements. Responses were defined as the difference between mean, minimum and maximum O2Hb, HHb and TSI values after standing up and baseline. Test-retest, interobserver and intersensor reliabilities were addressed using intraclass correlation coefficients (ICCs). RESULTS: The minimum O2Hb response was most sensitive to postural changes and showed significant differences (- 4.09 µmol/L, p < 0.001) between standing up from sitting and supine position, but not between standing up at different speeds (- 0.31 µmol/L, p = 0.70). The minimum O2Hb response was the most reliable parameter (ICC > 0.6). CONCLUSIONS: In healthy individuals, NIRS-based cerebral oxygenation parameters are sensitive to postural change and discriminate between standing up from supine and sitting position with minimum O2Hb response as the most sensitive and reliable parameter. The results underpin the potential value for future clinical use of NIRS in individuals with orthostatic hypotension.

Orthostatic Hypotension and Falls in Older Adults: A Systematic Review and Meta-analysis.

OBJECTIVES: Orthostatic hypotension is a potential risk factor for falls in older adults, but existing evidence on this relationship is inconclusive. This study addresses the association between orthostatic hypotension and falls. DESIGN: Systematic review and meta-analysis of the cross-sectional and longitudinal studies assessing the association between orthostatic hypotension and falls, as preregistered in the PROSPERO database (CRD42017060134). SETTING AND PARTICIPANTS: A literature search was performed on February 20, 2017, in MEDLINE (from 1946), PubMed (from 1966), and EMBASE (from 1947) using the terms orthostatic hypotension, postural hypotension, and falls. References of included studies were screened for other eligible studies. Study selection was performed independently by 2 reviewers using the following inclusion criteria: published in English; mean/median age of the population ≥65 years; blood pressure measurement before and after postural change; and assessment of the association of orthostatic hypotension with falls. The following studies were excluded: conference abstracts, case reports, reviews, and editorials. Data extraction was performed independently by 2 reviewers. MEASURES: Unadjusted odds ratios of the association between orthostatic hypotension and falls were used for pooling using a random effects model. Studies were rated as high, moderate, or low quality using the Newcastle-Ottawa Scale. RESULTS: Out of 5646 studies, 63 studies (51,800 individuals) were included in the systematic review and 50 studies (49,164 individuals) in the meta-analysis. Out of 63 studies, 39 were cross-sectional and 24 were longitudinal. Orthostatic hypotension was positively associated with falls (odds ratio 1.73, 95% confidence interval 1.50-1.99). The result was independent of study population, study design, study quality, orthostatic hypotension definition, and blood pressure measurement method. CONCLUSIONS AND IMPLICATIONS: Orthostatic hypotension is significantly positively associated with falls in older adults, underpinning the clinical relevance to test for an orthostatic blood pressure drop and highlighting the need to investigate orthostatic hypotension treatment to potentially reduce falls.

Orthostatic hypotension and physical functioning in older adults: A systematic review and meta-analysis.

BACKGROUND: Orthostatic hypotension (OH) may negatively affect physical functioning and aggravate morbidities, but existing evidence is contradictory. METHODS: MEDLINE (from 1946), PubMed (from 1966) and EMBASE databases (from 1947) were systematically searched for studies on the association of OH and physical functioning in older adults, categorized as: balance, gait characteristics, walking speed, Timed Up and Go time, handgrip strength (HGS), physical frailty, exercise tolerance, physical activity, activities of daily living (ADL), and performance on the Hoehn and Yahr scale (HY) and Unified Parkinson's Disease Rating Scale (UPDRS). Study quality was assessed using the Newcastle Ottawa Scale. RESULTS: Forty-two studies were included in the systematic review (29,421 individuals) and 29 studies in the meta-analyses (23,879 individuals). Sixteen out of 42 studies reported a significant association of OH with worse physical functioning. Meta-analysis showed a significant association of OH with impaired balance, ADL performance and HY/UPDRS III performance, but not with gait characteristics, mobility, walking speed, TUG, HGS, physical frailty, exercise tolerance, physical activity and UPDRS II performance. CONCLUSIONS: OH was associated with impaired balance, ADL performance and HY/UPDRS III performance, but not with other physical functioning categories. The results suggest that OH interventions could potentially improve some aspects of physical functioning.

Rapid Systolic Blood Pressure Changes After Standing Up Associate With Impaired Physical Performance in Geriatric Outpatients.

Background Orthostatic hypotension is a prevalent condition in older adults and is associated with impaired physical performance and falls. The ability of older adults to compensate for rapid changes in systolic blood pressure ( SBP ; ie, SBP decline rate and SBP variability) may be important for physical performance. This study investigates the association of rapid SBP changes after standing up with physical performance. Methods and Results Consecutive patients who visited the Center of Geriatrics Amsterdam in 2014 and 2015 were included. The following SBP parameters were computed in 2 intervals (0-15 and 15-180 seconds) after standing up: steepness of steepest SBP decline; ratio of standing/supine SBP variability; and magnitude of largest SBP decline. Physical performance was assessed using the following measures: chair stand time, timed up and go time, walking speed, handgrip strength, and tandem stance performance. A total of 109 patients (45% men; age, mean, 81.7 years [ standard deviation , 7.0 years]) were included. Steepness of steepest SBP decline (0-15 seconds) was associated with slower chair stand time ( P<0.001), timed up and go time ( P=0.022), and walking speed ( P=0.024). Ratio of standing/supine SBP variability (0-15 seconds) was associated with slower chair stand time ( P=0.005). Magnitude of largest SBP decline was not associated with physical performance. Conclusions SBP parameters reflecting rapid SBP changes were more strongly associated with physical performance compared with SBP decline magnitude in geriatric outpatients. These results support the hypothesis of an inadequate cerebral autoregulation during rapid SBP changes and advocate the use of continuous blood pressure measurements.

Beamforming applied to surface EEG improves ripple visibility.

OBJECTIVE: Surface EEG can show epileptiform ripples in people with focal epilepsy, but identification is impeded by the low signal-to-noise ratio of the electrode recordings. We used beamformer-based virtual electrodes to improve ripple identification. METHODS: We analyzed ten minutes of interictal EEG of nine patients with refractory focal epilepsy. EEGs with more than 60 channels and 20 spikes were included. We computed ∼79 virtual electrodes using a scalar beamformer and marked ripples (80-250 Hz) co-occurring with spikes in physical and virtual electrodes. Ripple numbers in physical and virtual electrodes were compared, and sensitivity and specificity of ripples for the region of interest (ROI; based on clinical information) were determined. RESULTS: Five patients had ripples in the physical electrodes and eight in the virtual electrodes, with more ripples in virtual than in physical electrodes (101 vs. 57, p = .007). Ripples in virtual electrodes predicted the ROI better than physical electrodes (AUC 0.65 vs. 0.56, p = .03). CONCLUSIONS: Beamforming increased ripple visibility in surface EEG. Virtual ripples predicted the ROI better than physical ripples, although sensitivity was still poor. SIGNIFICANCE: Beamforming can facilitate ripple identification in EEG. Ripple localization needs to be improved to enable its use for presurgical evaluation in people with epilepsy.