Do acute stroke patients develop hypocapnia? A systematic review and meta-analysis.

PURPOSE: Carbon dioxide (CO2) is a potent cerebral vasomotor agent. Despite reduction in CO2 levels (hypocapnia) being described in several acute diseases, there is no clear data on baseline CO2 values in acute stroke. The aim of the study was to systematically assess CO2 levels in acute stroke. MATERIAL AND METHODS: Four online databases, Web of Science, MEDLINE, EMBASE and CENTRAL, were searched for articles that described either partial pressure of arterial CO2 (PaCO2) and end-tidal CO2 (EtCO2) in acute stroke. RESULTS: After screening, based on predefined inclusion and exclusion criteria, 20 studies were retained. There were 5 studies in intracerebral hemorrhage and 15 in ischemic stroke, totalling 660 stroke participants. Acute stroke was associated with a significant decrease in CO2 levels compared to controls. Cerebral haemodynamic studies using transcranial Doppler ultrasonography demonstrated a significant reduction in cerebral blood flow velocities and cerebral autoregulation in acute stroke patients. CONCLUSION: The evidence from this review suggests that acute stroke patients are significantly more likely than controls to be hypocapnic, supporting the value of routine CO2 assessment in the acute stroke setting. Further studies are required in order to evaluate the clinical impact of these findings

Cerebral autoregulation and response to intravenous thrombolysis for acute ischemic stroke

We hypothesized that knowledge of cerebral autoregulation (CA) status during recanalization therapies could guide further studies aimed at neuroprotection targeting penumbral tissue, especially in patients that do not respond to therapy. Thus, we assessed CA status of patients with acute ischemic stroke (AIS) during intravenous r-tPA therapy and associated CA with response to therapy. AIS patients eligible for intravenous r-tPA therapy were recruited. Cerebral blood flow velocities (transcranial Doppler) from middle cerebral artery and blood pressure (Finometer) were recorded to calculate the autoregulation index (ARI, as surrogate for CA). National Institute of Health Stroke Score was assessed and used to define responders to therapy (improvement of ≥ 4 points on NIHSS measured 24–48 h after therapy). CA was considered impaired if ARI < 4. In 38 patients studied, compared to responders, non-responders had significantly lower ARI values (affected hemisphere: 5.0 vs. 3.6; unaffected hemisphere: 5.4 vs. 4.4, p = 0.03) and more likely to have impaired CA (32% vs. 62%, p = 0.02) during thrombolysis. In conclusion, CA during thrombolysis was impaired in patients who did not respond to therapy. This variable should be investigated as a predictor of the response to therapy and to subsequent neurological outcome

Pooling data from different populations: should there be regional differences in cerebral haemodynamics?

BACKGROUND: Though genetic and environmental determinants of systemic haemodynamic have been reported, surprisingly little is known about their influences on cerebral haemodynamics. We assessed the potential geographical effect on cerebral haemodynamics by comparing the individual differences in cerebral blood flow velocity (CBFv), vasomotor tone (critical closing pressure- CrCP), vascular bed resistance (resistance-area product- RAP) and cerebral autoregulation (CA) mechanism on healthy subjects and acute ischaemic stroke (AIS) patients from two countries. METHODS: Participants were pooled from databases in Leicester, United Kingdom (LEI) and São Paulo, Brazil (SP) research centres. Stroke patients admitted within 48 h of ischaemic stroke onset, as well as age- and sex-matched controls were enrolled. Beat-to-beat blood pressure (BP) and bilateral mean CBFv were recorded during 5 min baseline. CrCP and RAP were calculated. CA was quantified using transfer function analysis (TFA) of spontaneous oscillations in arterial BP and mean CBFv, and the derived autoregulatory index (ARI). RESULTS: A total of 100 participants (50 LEI and 50 SP) were recruited. No geographical differences were found. Both LEI and SP AIS participants showed lower values of CA compared to controls. Moreover, the affected hemisphere presented lower resting CBFv and higher RAP compared to the unaffected hemisphere in both populations. CONCLUSIONS: Impairments of cerebral haemodynamics, demonstrated by several key parameters, was observed following AIS compared to controls irrespective of geographical region. These initial results should encourage further research on cerebral haemodynamic research with larger cohorts combining different populations

Integrative assessment of cerebral blood regulation in COPD patients

Cerebrovascular responses were compared between COPD and non-COPD participants. The association between COPD severity and cognitive function was also investigated. Cerebral blood velocity in the middle cerebral artery, blood pressure, and end-tidal CO2 were recorded at rest, followed by a brain activation paradigm, and an inhaled gas mixture (5% CO2) to assess cerebral autoregulation (CA), neurovascular coupling (NVC) and cerebrovascular reactivity to carbon dioxide (CVRCO2), respectively. Pulmonary function, blood gas analysis (COPD) and cognitive function (MoCA test) were also performed. No difference in baseline (systemic and cerebral parameters) and CA was found between 20 severe COPD and 21 non-COPD. Reduced NVC and CVRCO2 test were found in the COPD group. Lower pulmonary function was positively correlated with CA, NVC and CVRCO2 in COPD patients. Cognitive impairment (MoCA<26) was associated with lower NVC responses (COPD and non-COPD) and lower pulmonary function (COPD). Both mechanisms, CVRCO2 and NVC, were lower in COPD patients. Moreover, disease severity and cognitive impaired were associated with worse cerebrovascular regulation

Dynamic cerebral autoregulation: A marker of post-operative delirium?

OBJECTIVE: We investigated the potential association of cerebral autoregulation (CA) with postoperative delirium (PD), a common complication of cardiac surgery with cardiopulmonary bypass (CPB). METHODS: In patients undergoing coronary artery bypass graft (CABG) surgery with CPB, cerebral blood flow velocity (CBFV) and blood pressure (BP) were continuously recorded during 5-min preoperatively (T1), after 24 h (T2), and 7 days after procedure (T3). Prospective multivariate logistic regression analysis was performed to determine the independent risk factors of PD. Autoregulation index (ARI) was calculated from the CBFV response to a step change in BP derived by transfer function analysis. RESULTS: In 67 patients, mean age 64.3 ± 9.5 years, CA was depressed at T2 as shown by values of ARI (3.9 ± 1.7), compared to T1 (5.6 ± 1.7) and T3 (5.5 ± 1.8) (p < 0.001). Impaired CA was found in 37 (55%) patients at T2 and in 7 patients (20%) at T3. Lower ARI at T1 and T2 were predictors of PD (p = 0.003). CONCLUSION: Dynamic CA was impaired after CABG surgery with CPB and was a significant independent risk factor of PD. SIGNIFICANCE: Assessment of CA before and after surgery could have considerable potential for early identification of patients at risk of PD, thus reducing poor outcomes and length of stay

Cerebral blood flow autoregulation in ischemic heart failure

Patients with ischemic heart failure (iHF) have a high risk of neurological complications such as cognitive impairment and stroke. We hypothesized that iHF patients have a higher incidence of impaired dynamic cerebral autoregulation (dCA). Adult patients with iHF and healthy volunteers were included. Cerebral blood flow velocity (CBFV, transcranial Doppler, middle cerebral artery), end-tidal CO2(capnography), and arterial blood pressure (Finometer) were continuously recorded supine for 5 min at rest. Autoregulation index (ARI) was estimated from the CBFV step response derived by transfer function analysis using standard template curves. Fifty-two iHF patients and 54 age-, gender-, and BP-matched healthy volunteers were studied. Echocardiogram ejection fraction was 40 (20-45) % in iHF group. iHF patients compared with control subjects had reduced end-tidal CO2(34.1 ± 3.7 vs. 38.3 ± 4.0 mmHg, P < 0.001) and lower ARI values (5.1 ± 1.6 vs. 5.9 ± 1.0, P = 0.012). ARI <4, suggestive of impaired CA, was more common in iHF patients (28.8 vs. 7.4%, P = 0.004). These results confirm that iHF patients are more likely to have impaired dCA compared with age-matched controls. The relationship between impaired dCA and neurological complications in iHF patients deserves further investigation

Reproducibility of dynamic cerebral autoregulation parameters: a multi-centre, multi-method study

OBJECTIVE: Different methods to calculate dynamic cerebral autoregulation (dCA) parameters are available. However, most of these methods demonstrate poor reproducibility that limit their reliability for clinical use. Inter-centre differences in study protocols, modelling approaches and default parameter settings have all led to a lack of standardisation and comparability between studies. We evaluated reproducibility of dCA parameters by assessing systematic errors in surrogate data resulting from different modelling techniques. APPROACH: Fourteen centres analysed 22 datasets consisting of two repeated physiological blood pressure measurements with surrogate cerebral blood flow velocity signals, generated using Tiecks curves (autoregulation index, ARI 0-9) and added noise. For reproducibility, dCA methods were grouped in three broad categories: 1. Transfer function analysis (TFA)-like output; 2. ARI-like output; 3. Correlation coefficient-like output. For all methods, reproducibility was determined by one-way intraclass correlation coefficient analysis (ICC). MAIN RESULTS: For TFA-like methods the mean (SD; [range]) ICC gain was 0.71 (0.10; [0.49-0.86]) and 0.80 (0.17; [0.36-0.94]) for VLF and LF (p  =  0.003) respectively. For phase, ICC values were 0.53 (0.21; [0.09-0.80]) for VLF, and 0.92 (0.13; [0.44-1.00]) for LF (p  <  0.001). Finally, ICC for ARI-like methods was equal to 0.84 (0.19; [0.41-0.94]), and for correlation-like methods, ICC was 0.21 (0.21; [0.056-0.35]). SIGNIFICANCE: When applied to realistic surrogate data, free from the additional exogenous influences of physiological variability on cerebral blood flow, most methods of dCA modelling showed ICC values considerably higher than what has been reported for physiological data. This finding suggests that the poor reproducibility reported by previous studies may be mainly due to the inherent physiological variability of cerebral blood flow regulatory mechanisms rather than related to (stationary) random noise and the signal analysis methods

Dynamic Cerebral Autoregulation Reproducibility Is Affected by Physiological Variability

Parameters describing dynamic cerebral autoregulation (DCA) have limited reproducibility. In an international, multi-center study, we evaluated the influence of multiple analytical methods on the reproducibility of DCA. Fourteen participating centers analyzed repeated measurements from 75 healthy subjects, consisting of 5 min of spontaneous fluctuations in blood pressure and cerebral blood flow velocity signals, based on their usual methods of analysis. DCA methods were grouped into three broad categories, depending on output types: (1) transfer function analysis (TFA); (2) autoregulation index (ARI); and (3) correlation coefficient. Only TFA gain in the low frequency (LF) band showed good reproducibility in approximately half of the estimates of gain, defined as an intraclass correlation coefficient (ICC) of >0.6. None of the other DCA metrics had good reproducibility. For TFA-like and ARI-like methods, ICCs were lower than values obtained with surrogate data (p < 0.05). For TFA-like methods, ICCs were lower for the very LF band (gain 0.38 ± 0.057, phase 0.17 ± 0.13) than for LF band (gain 0.59 ± 0.078, phase 0.39 ± 0.11, p ≤ 0.001 for both gain and phase). For ARI-like methods, the mean ICC was 0.30 ± 0.12 and for the correlation methods 0.24 ± 0.23. Based on comparisons with ICC estimates obtained from surrogate data, we conclude that physiological variability or non-stationarity is likely to be the main reason for the poor reproducibility of DCA parameters

Assessment of dynamic cerebral autoregulation in humans: Is reproducibility dependent on blood pressure variability?

We tested the influence of blood pressure variability on the reproducibility of dynamic cerebral autoregulation (DCA) estimates. Data were analyzed from the 2nd CARNet bootstrap initiative, where mean arterial blood pressure (MABP), cerebral blood flow velocity (CBFV) and end tidal CO2 were measured twice in 75 healthy subjects. DCA was analyzed by 14 different centers with a variety of different analysis methods. Intraclass Correlation (ICC) values increased significantly when subjects with low power spectral density MABP (PSD-MABP) values were removed from the analysis for all gain, phase and autoregulation index (ARI) parameters. Gain in the low frequency band (LF) had the highest ICC, followed by phase LF and gain in the very low frequency band. No significant differences were found between analysis methods for gain parameters, but for phase and ARI parameters, significant differences between the analysis methods were found. Alternatively, the Spearman-Brown prediction formula indicated that prolongation of the measurement duration up to 35 minutes may be needed to achieve good reproducibility for some DCA parameters. We conclude that poor DCA reproducibility (ICC 0.6) values when cases with low PSD-MABP are removed, and probably also when measurement duration is increased

Assessment of dynamic cerebral autoregulation in humans: Is reproducibility dependent on blood pressure variability?

We tested the influence of blood pressure variability on the reproducibility of dynamic cerebral autoregulation (DCA) estimates. Data were analyzed from the 2nd CARNet bootstrap initiative, where mean arterial blood pressure (MABP), cerebral blood flow velocity (CBFV) and end tidal CO2 were measured twice in 75 healthy subjects. DCA was analyzed by 14 different centers with a variety of different analysis methods. Intraclass Correlation (ICC) values increased significantly when subjects with low power spectral density MABP (PSD-MABP) values were removed from the analysis for all gain, phase and autoregulation index (ARI) parameters. Gain in the low frequency band (LF) had the highest ICC, followed by phase LF and gain in the very low frequency band. No significant differences were found between analysis methods for gain parameters, but for phase and ARI parameters, significant differences between the analysis methods were found. Alternatively, the Spearman-Brown prediction formula indicated that prolongation of the measurement duration up to 35 minutes may be needed to achieve good reproducibility for some DCA parameters. We conclude that poor DCA reproducibility (ICC 0.6) values when cases with low PSD-MABP are removed, and probably also when measurement duration is increased