Anthony A Birch

Assessment of Autoregulation by Means of Periodic Changes in Blood Pressure

BACKGROUND AND PURPOSE The aim of this study was to test the hypothesis that the phase difference that occurs between an induced oscillation in blood pressure and the resultant oscillation in middle cerebral artery (MCA) flow velocity could reflect the competence of cerebral autoregulation. METHODS Fourteen volunteers performed 19 cycles of 10 seconds of squatting followed by 10 seconds of standing. Peak MCA velocity was measured with transcranial Doppler ultrasound, and blood pressure was measured with a servo-controlled finger plethysmograph held level with the head. Waveforms from each cycle were added to obtain averaged waveforms of arterial blood pressure and MCA velocity. These results were processed by Fourier analysis to extract the phase difference between the fundamental components of velocity and pressure. Each volunteer performed the exercise three times: first breathing normally, secondly hyperventilating (hypocapnia), and finally while breathing air containing 5% carbon dioxide (hypercapnia). Under these conditions the volunteers were expected to have normal, enhanced, and impaired auto-regulation, respectively. RESULTS The measurements made with normal breathing showed a phase lead of velocity ahead of pressure of 46 +/- 14 degrees (mean +/- SD). We noted a highly significant reduction in phase lead with hypercapnia (P < .00015) (Wilcoxon signed rank test, two-tailed) and a highly significant increase in phase lead with hypocapnia (P < .002). CONCLUSIONS The results support our hypothesis and may lead to a technique for assessing the competence of cerebral autoregulation.

Comparison of caffeine-induced changes in cerebral blood flow and middle cerebral artery blood velocity shows that caffeine reduces middle cerebral artery diameter.

Changes in cerebral blood flow (CBF) can be assessed directly with xenon clearance (XeC) or indirectly by measuring changes in middle cerebral artery blood velocity (Vmca) with transcranial Doppler (TCD). The aim of this study was to compare the changes in CBF and Vmca following caffeine ingestion. Nineteen patients (age 48-86, recovering from an acute stroke) and ten controls (age 52-85) were each studied twice. Bilateral measurements of CBF and Vmca were made before and after ingestion of 250 mg caffeine or matched placebo. The percentage change in CBF and Vmca after caffeine was calculated. Full results (CBF and Vmca) were obtained from 14 patients and 9 controls. There was no significant difference between patients and controls, so results were combined. Caffeine reduced CBF by 22% (95% confidence interval (CI) = 17% to 28%) and reduced Vmca by 13% (95% CI = 10% to 17%). The fall in Vmca was significantly less than that in CBF (p = 0.0016), showing that caffeine reduces mca diameter. Analysis based on Poiseuille flow in the arterioles suggests that caffeine reduced arteriole diameter by 5.9% (95% CI = 4.6% to 7.3%) and mca diameter by 4.3% (95% CI = 2.0% to 6.6%). TCD is being used as an alternative to XeC for assessing the effect of vasoconstrictors and vasodilators on CBF. This study has demonstrated that in mca diameter can be changed by the vasoactive agents, and that changes in Vmca do not necessarily reflect changes in CBF.

The repeatability of cerebral autoregulation assessment using sinusoidal lower body negative pressure

A forced periodic variation in blood pressure produces a similar variation in cerebral blood velocity. The amplitudes and phases of the pressure and velocity waveforms are indicative of the dynamic response of the cerebral autoregulation. The phase of the velocity leads the pressure; the greater the phase difference the faster the autoregulation response. Various techniques have been employed to oscillate arterial blood pressure but measurement reproducibility has been poor. The purpose of this study was to assess the reproducibility of phase measurements when sinusoidal lower body negative pressure is used to vary blood pressure. Five healthy volunteers were assessed at two vacuum levels on each of eight visits. For each measurement a 12 s sinusoidal cycle was maintained for 5 min. The Fourier components of blood pressure and the middle cerebral artery velocity were determined at the oscillation frequency. The phase of velocity consistently led the pressure. The mean phase difference was 42+/-13 degrees for the stronger vacuum and 36+/-42 degrees for the weaker vacuum. The variation given is the within-subjects standard deviation estimated from a one-way analysis of variance. Sinusoidal lower body negative pressure is a useful stimulus for investigating autoregulation; it has advantages over other methods. High vacuums show good reproducibility but are too uncomfortable for patient use.

Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania

Transcranial Doppler ultrasonography measures cerebral blood flow velocity (CBFv) of basal intracranial vessels and is used clinically to detect stroke risk in children with sickle cell anaemia (SCA). Co‐inheritance in SCA of alpha‐thalassaemia and glucose‐6‐phosphate dehydrogenase (G6PD) polymorphisms is reported to associate with high CBFv and/or risk of stroke. The effect of a common functional polymorphism of haptoglobin (HP) is unknown. We investigated the effect of co‐inheritance of these polymorphisms on CBFv in 601 stroke‐free Tanzanian SCA patients aged <24 years. Homozygosity for alpha‐thalassaemia 3·7 deletion was significantly associated with reduced mean CBFv compared to wild‐type (β‐coefficient −16·1 cm/s, P = 0·002) adjusted for age and survey year. Inheritance of 1 or 2 alpha‐thalassaemia deletions was associated with decreased risk of abnormally high CBFv, compared to published data from Kenyan healthy control children (Relative risk ratio [RRR] = 0·53 [95% confidence interval (CI):0·35–0·8] & RRR = 0·43 [95% CI:0·23–0·78]), and reduced risk of abnormally low CBFv for 1 deletion only (RRR = 0·38 [95% CI:0·17–0·83]). No effects were observed for G6PD or HP polymorphisms. This is the first report of the effects of co‐inheritance of common polymorphisms, including the HP polymorphism, on CBFv in SCA patients resident in Africa and confirms the importance of alpha‐thalassaemia in reducing risk of abnormal CBFv.

Dynamic cerebral autoregulation assessment using an ARX model: comparative study using step response and phase shift analysis

Middle cerebral arterial blood velocity (MCAv) response to spontaneous and manipulated changes of arterial blood pressure (ABP) was studied in eight subjects using a linear autoregressive with exogenous input (ARX) model. ABP and MCAv were measured non-invasively by photoplethysmograph and transcranial Doppler ultrasound, respectively. Data were recorded at rest (spontaneous changes in ABP) and during thigh cuff (step-wise changes) and lower body negative pressure (sinusoidal changes of 1/12 Hz) tests in both normocapnia and hypercapnia (5% CO2). Since autoregulation is modulated by CO2, respiratory CO2 was simultaneously monitored to allow comparison of cerebral autoregulation status with different CO2 levels. ABP and MCAv were fitted by ARX models and dynamic cerebral autoregulation was estimated by analysing both the step responses and phase shift at the 1/12 Hz of the corresponding ARX models. The ARX model consistently modelled the phase lead of MCAv to ABP and it showed that the phase shift at 1/12 Hz of ARX model is consistent with the real phase shift of the data (p=0.59). Strong linear relationships between pCO2 and gradient of the step response (r=-0.58, p<0.0001) and between pCO2 and phase shift (r=-0.76, p<0.0001) were observed, which suggests that cerebral autoregulation can be assessed by step response or phase shift analysis of the ARX model fitted to ABP and MCAv data with spontaneous changes.

Detection of Impaired Cerebral Autoregulation Improves by Increasing Arterial Blood Pressure Variability

Although the assessment of dynamic cerebral autoregulation (CA) based on measurements of spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CBF) is a convenient and much used method, there remains uncertainty about its reliability. We tested the effects of increasing ABP variability, provoked by a modification of the thigh cuff method, on the ability of the autoregulation index to discriminate between normal and impaired CA, using hypercapnia as a surrogate for dynamic CA impairment. In 30 healthy volunteers, ABP (Finapres) and CBF velocity (CBFV, transcranial Doppler) were recorded at rest and during 5% CO2 breathing, with and without pseudo-random sequence inflation and deflation of bilateral thigh cuffs. The application of thigh cuffs increased ABP and CBFV variabilities and was not associated with a distortion of the CBFV step response estimates for both normocapnic and hypercapnic conditions (P = 0.59 and P = 0.96, respectively). Sensitivity and specificity of CA impairment detection were improved with the thigh cuff method, with the area under the receiver–operator curve increasing from 0.746 to 0.859 (P = 0.031). We conclude that the new method is a safe, efficient, and appealing alternative to currently existing assessment methods for the investigation of the status of CA.

Do the Finapres? and Colin? radial artery tonometer measure the same blood pressure changes following deflation of thigh cuffs?

The objective of this work was to determine if systematic differences exist between blood pressure time series measured by two non-invasive techniques. Cerebral blood flow autoregulation is often measured while a change in blood pressure is induced by deflation of thigh cuffs. To interpret the result a continuous measurement of arterial blood pressure is required. The Finapres is a non-invasive blood pressure monitor that is often used when assessing autoregulation but there is uncertainty about its reliability. A more recent device, the Colin tonometer, uses radial artery tonometry, which may prove to be a more reliable non-invasive method of obtaining a blood pressure waveform. Twenty healthy volunteers were recruited; blood pressure trends following cuff deflation were measured simultaneously with a Finapres and a Colin tonometer. A significant difference was found between the blood pressure waveforms measured with the two devices. The most striking difference was a slower recovery time measured with the Finapres (Wilcoxon signed rank test P < 0.001). Peripheral vasoaction may be distorting the measurement of blood pressure by the Finapres. This would account for the difference that exists between the techniques. Comparison with a direct arterial line would confirm which non-invasive measurement is more accurate.

Intra-aortic balloon counterpulsation: augmentation of cerebral blood flow after aneurysmal subarachnoid haemorrhage.

Abstract Objective. To measure cerebral blood flow before and after intra-aortic balloon counterpulsation (IABC) in patients at high risk of developing delayed cerebral ischaemia after aneurysm surgery following subarachnoid haemorrhage. Methods. Six prospectively selected patients at high risk of developing delayed ischaemia had elective IABC after clipping of their cerebral aneurysm(s). The IAB inflates in early diastole and deflates at the end of diastole to increase cardiac perfusion and decrease afterload. This results in enhanced cardiac efficiency. It also augments cerebral blood flow (CBF). Results. We demonstrated a significant increase in the mean hemispheric CBF from the preoperative (preIABC) value of 35.6 mls/100 g/min to 50.9±12.3 mls/100 g/min (p=0.0042) as a result of balloon augmentation. Each patient developed a neurological deficit as a result of delayed cerebral ischaemia. These were reversed in 5 patients with increased CBF. There were minimal balloon related complications. Conclusion. IABC consistently enhanced CBF in these patients and resulted in stable cardiovascular parameters. This represents a possible new technique in the management of cerebral ischaemia following subarachnoid haemorrhage and needs further assessment to ascertain its role.

A new mathematical model of dynamic cerebral autoregulation based on a flow dependent feedback mechanism

A new mathematical model representing dynamic cerebral autoregulation as a flow dependent feedback mechanism is presented. Two modelling parameters are introduced, lambda, the rate of restoration, and tau, a time delay. Velocity profiles are found for a general arterial blood pressure, allowing the model to be applied to any experiment that uses changes in arterial blood pressure to assess dynamic cerebral autoregulation. Two such techniques, thigh cuffs and a lower body negative pressure box, which produce step changes and oscillatory variations in arterial blood pressure respectively, are investigated. Results derived using the mathematical model are compared with data from the two experiments. The comparisons yield similar estimates for lambda and tau, suggesting these parameters are independent of the pressure change stimulus and depend only on the main features of the dynamic cerebral autoregulation process. The modelling also indicates that for imposed oscillatory variations in arterial blood pressure a small phase difference between pressure and velocity waveforms does not necessarily imply impaired autoregulation. It is shown that the ratio between the variation in maximum velocity and pressure variation can be used, along with the phase difference, to indicate the nature of the autoregulatory response.

A Randomized Controlled Trial of Prophylactic Intra-aortic Balloon Counterpulsation in High-Risk Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— To assess whether prophylactic postoperative intraaortic balloon counterpulsation (IABC) reduces the risk of poor outcome because of vasospasm following aneurysmal subarachnoid haemorrhage relative to conventional hypervolemic therapy (HT). Methods— This was a single-center, parallel group randomized controlled trial. Patients suffering a subarachnoid hemorrhage at high risk of vasospasm were eligible. Patients were randomly allocated to receive prophylactic IABC (n=35) or HT (n=36). The primary end point was Glasgow Outcome and SF-36 scores assessed at 6 months by a blinded and independent observer and analyzed by intention to treat. Secondary analysis of physiological parameters was by treatment performed. Results— Twenty-seven patients in each arm had a good outcome (P=0.55). There was no statistical difference in mean SF-36 score (t=0.39, P=0.70). There were no long-term complications secondary to IABC. There were no differences in preload (pulmonary artery wedge pressure, P=0.97) or afterload (mean arterial pressure, P=0.97). IABC was associated with a lower cardiac output (P=0.002) and higher systemic vascular resistance (P=0.005), although for both groups mean cardiac output was >6 L/min. Cerebral blood flow was not different between groups: HT=41.5 (SD 7.2), IABP=44.9 (SD 8.6) mL/100 g/min (P=0.14). Conclusions— In this study, prophylactic IABC did not improve perfusion indices or confer any clinical benefit following subarachnoid haemorrhage in patients with normal cardiac function. The study was small, however, and cannot be extrapolated to patients with cardiac failure and medically refractory symptomatic cerebral vasospasm. Clinical Trial Registration— This trial was not registered because enrolment began prior to July 1, 2005.