Transient Hyperemic Response Test Research Articles

Autoregulation Disturbance Events Correlate with History of Loss of Consciousness in Mild Traumatic Brain Injury Patients

Abstract Introduction: Cerebral autoregulation disturbance may compromise cerebral blood flow, thereby increasing the risk of hypoperfusion, which increases the risk of loss of consciousness (LOC). Transient hyperemic response test (THRT) using transcranial Doppler (TCD) can be used to assess cerebral autoregulation disturbance. The goal of this study was to assess the relationship between impaired cerebral autoregulation assessed using TCD and a history of LOC in patients with a mild head injury. Patients and Methods: This study was a comparative analytic study with unpaired data and cross-sectional design that involved 73 people divided into two groups. Group A (36 subjects) consists of mild brain injury patients with a history of LOC, and Group B (37 subjects) consists of mild brain injury patients without a history of LOC. THRT was assessed using TCD by identifying the absence (negative result) in flow velocity increase upon applying pressure on ipsilateral carotid artery. We employed the chi-square and logistic regression tests to assess any correlation between variables. A value of P < 0.05 was considered significant. Results: Approximately 93% of subjects who experienced LOC also showed negative THRT results. We found a statistically significant relationship (P < 0.001) between the history of LOC and THRT. In the logistic regression test, we found that age, gender, and hematocrit were not statistically related to negative THRT results. Conclusion: There is a statistically significant relationship between cerebral autoregulation disturbance and decreased consciousness event in mild head injury patients.

Effect of dexmedetomidine on dynamic cerebral autoregulation and carbon dioxide reactivity during sevoflurane anesthesia in healthy patients.

BackgroundThere are conflicting opinions on the effect of dexmedetomidine on cerebral autoregulation. This study assessed its effect on dynamic cerebral autoregulation (dCA) using a transcranial Doppler (TCD).MethodsThirty American Society of Anesthesiologists physical status I and II patients between 18 and 60 years, who underwent lumbar spine surgery, received infusions of dexmedetomidine (Group D) or normal saline (Group C), followed by anesthesia with propofol and fentanyl, and maintenance with oxygen, nitrous oxide and sevoflurane. After five minutes of normocapnic ventilation and stable bispectral index value (BIS) of 40–50, the right middle cerebral artery flow velocity (MCAFV) was recorded with TCD. The transient hyperemic response (THR) test was performed by compressing the right common carotid artery for 5–7 seconds. The lungs were hyperventilated to test carbon dioxide (CO2) reactivity. Hemodynamic parameters, arterial CO2 tension, pulse oximetry (SpO2), MCAFV and BIS were measured before and after hyperventilation. Dexmedetomidine infusion was discontinued ten minutes before skin-closure. Time to recovery and extubation, modified Aldrete score, and emergence agitation were recorded.ResultsDemographic parameters, durations of surgery and anesthesia, THR ratio (Group D: 1.26 ± 0.11 vs. Group C: 1.23 ± 0.04; P = 0.357), relative CO2 reactivity (Group D: 1.19 ± 0.34 %/mmHg vs. Group C: 1.23 ± 0.25 %/mmHg; P = 0.547), blood pressure, SpO2, BIS, MCAFV, time to recovery, time to extubation and modified Aldrete scores were comparable.ConclusionsDexmedetomidine administration does not impair dCA and CO2 reactivity in patients undergoing spine surgery under sevoflurane anesthesia.

Early Transcranial Doppler Evaluation of Cerebral Autoregulation Independently Predicts Functional Outcome After Aneurysmal Subarachnoid Hemorrhage.

Cerebral autoregulation (CA) impairment after aneurysmal subarachnoid hemorrhage (SAH) has been associated with delayed cerebral ischemia and an unfavorable outcome. We investigated whether the early transient hyperemic response test (THRT), a transcranial Doppler (TCD)-based CA evaluation method, can predict functional outcome 6months after aneurysmal SAH. This is a prospective observational study of all aneurysmal SAH patients consecutively admitted to a single center between January 2016 and February 2017. CA was evaluated within 72h of hemorrhage by THRT, which describes the changes in cerebral blood flow velocity after a brief compression of the ipsilateral common carotid artery. CA was considered to be preserved when an increase ≥ 9% of baseline systolic velocity was present. According to the modified Rankin Scale (mRS: 4-6), the primary outcome was unfavorable 6months after hemorrhage. Secondary outcomes included cerebral infarction, vasospasm on TCD, and an unfavorable outcome at hospital discharge. Forty patients were included (mean age = 54 ± 12years, 70% females). CA was impaired in 19 patients (47.5%) and preserved in 21 (52.5%). Impaired CA patients were older (59 ± 13 vs. 50 ± 9, p = 0.012), showed worse neurological conditions (Hunt&Hess 4 or 5-47.4% vs. 9.5%, p = 0.012), and clinical initial condition (APACHE II physiological score-12 [5.57-13] vs. 3.5 [3-5], p = 0.001). Fourteen patients in the impaired CA group and one patient in the preserved CA group progressed to an unfavorable outcome (73.7% vs. 4.7%, p = 0.0001). The impaired CA group more frequently developed cerebral infarction than the preserved CA group (36.8% vs. 0%, p = 0.003, respectively). After multivariate analysis, impaired CA (OR 5.15 95% CI 1.43-51.99, p = 0.033) and the APACHE II physiological score (OR 1.67, 95% CI 1.01-2.76, p = 0.046) were independently associated with an unfavorable outcome. Early CA impairment detected by TCD and admission APACHE II physiological score independently predicted an unfavorable outcome after SAH.

Early abnormal transient hyperemic response test can predict delayed ischemic neurologic deficit in subarachnoid hemorrhage

BackgroundEarly detection of vasospasm is crucial to prevent significant delayed ischemic neurological deficit post subarachnoid hemorrhage. The standard methods of detection, including cerebral angiogram and computed tomography are invasive and not safe to be repeated, as is very often indicated clinically. Transient hyperemic response test has been previously used to predict autoregulation failure in traumatic brain injury and subarachnoid hemorrhage.AimsWe investigate the usability of transient hyperemic response test as a predictor of clinical vasospasm in a cohort of patients with aneurismal subarachnoid hemorrhage.MethodsA retrospective review of all THRT examinations done between January 2011 and July 2012 conducted at Montreal Neurological Institute and Hospital and the Montreal General Hospital. Patients diagnosed with aSAH in which the THRT was performed within the first 24–48 h of admission were included in the study. Two-dimensional transcranial Doppler images were obtained and velocities were recorded. A positive response was one in which the velocity was increased by more than 9% of the baseline systolic velocity, indicating an intact cerebral autoregulation. Lindegaard ratio > 3 is considered abnormal and in the context of elevated systolic velocity of the MCA, is highly suggestive of DIND.ResultsFifteen patients met the inclusion criteria. A total of 6 patients developed clinical and radiological vasospasm. Out of these 6 patients, 5 (83%) had an abnormal THRT in the initial TCD assessment (p = 0.0406). We found that abnormal transient hyperemic response test readings are predictive of subsequent vasospasm development.ConclusionsThe results of this small retrospective study support the notion that transient hyperemic response test has predictive value in vasospasm development and may prove useful in patient monitoring and successful clinical management.

Pressure Autoregulation Measurement Techniques in Adult Traumatic Brain Injury, Part I: A Scoping Review of Intermittent/Semi-Intermittent Methods.

The purpose of this study was to perform a systematic, scoping review of commonly described intermittent/semi-intermittent autoregulation measurement techniques in adult traumatic brain injury (TBI). Nine separate systematic reviews were conducted for each intermittent technique: computed tomographic perfusion (CTP)/Xenon-CT (Xe-CT), positron emission tomography (PET), magnetic resonance imaging (MRI), arteriovenous difference in oxygen (AVDO2) technique, thigh cuff deflation technique (TCDT), transient hyperemic response test (THRT), orthostatic hypotension test (OHT), mean flow index (Mx), and transfer function autoregulation index (TF-ARI). MEDLINE®, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to December 2016), and reference lists of relevant articles were searched. A two tier filter of references was conducted. The total number of articles utilizing each of the nine searched techniques for intermittent/semi-intermittent autoregulation techniques in adult TBI were: CTP/Xe-CT (10), PET (6), MRI (0), AVDO2 (10), ARI-based TCDT (9), THRT (6), OHT (3), Mx (17), and TF-ARI (6). The premise behind all of the intermittent techniques is manipulation of systemic blood pressure/blood volume via either chemical (such as vasopressors) or mechanical (such as thigh cuffs or carotid compression) means. Exceptionally, Mx and TF-ARI are based on spontaneous fluctuations of cerebral perfusion pressure (CPP) or mean arterial pressure (MAP). The method for assessing the cerebral circulation during these manipulations varies, with both imaging-based techniques and TCD utilized. Despite the limited literature for intermittent/semi-intermittent techniques in adult TBI (minus Mx), it is important to acknowledge the availability of such tests. They have provided fundamental insight into human autoregulatory capacity, leading to the development of continuous and more commonly applied techniques in the intensive care unit (ICU). Numerous methods of intermittent/semi-intermittent pressure autoregulation assessment in adult TBI exist, including: CTP/Xe-CT, PET, AVDO2 technique, TCDT-based ARI, THRT, OHT, Mx, and TF-ARI. MRI-based techniques in adult TBI are yet to be described, with the main focus of MRI techniques on metabolic-based cerebrovascular reactivity (CVR) and not pressure-based autoregulation.

The “Time” to Timely Predict Ischemic Deficit After Subarachnoid Hemorrhage

Cerebral vasospasm still represents the leading cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Nevertheless, ischemic deficits due to cerebral vasospasm are—at least in part—preventable. We know that vasospasm affects primarily patients with a major rupture resulting in an initial poor clinical condition, but it remains difficult to accurately and timely predict who, among patients with SAH, will develop symptomatic vasospasm and eventually a cerebral infact or infarcts. The only way to avoid possible disastrous delays in recognizing a decrease of cerebral perfusion is the continuous analysis of state of cerebral hemodynamics. We have some instruments to do this, some with detailed probing into brain physiology, but one simple tool—the transcranial Doppler Ultrasound (TCD)—developed about 3 decades ago [1], still remains the only system to monitor cerebral vasospasm: The expert operator knows that precious information on the status of cerebral hemodynamics is hidden in the indistinct noise produced by the TCD during vasospasm. Sometime, this is when the sound of TCD looses its unpleasant noisy character and becomes ‘‘musical’’, as a consequence of regular vibration of a spastic segment of an artery [1]. Spectral analysis of ultrasound echoes provides different quantitative measures, the most obvious of which is the velocity of blood flow. The quantification of the flow velocity (FV) can detect vasospasm, but this is insufficient for predicting its course and clinical relevance. In fact, an increase of the flow velocities over 120 cm/s can be recorded in more than 70% of patients with aneurysmal SAH, while the incidence of ‘‘clinical’’ vasospasm averages 30% half of whom will develop a stroke [2]. Therefore many TCD findings have been used in an attempt to predict outcome after SAH [3]. For example, an average rise in FV of more than 20 cm/s/day between day 3-7 after SAH, a rapid early rise of FV (more than 25%/ day), a mean maximal absolute rise in FV in the middle or anterior cerebral arteries of 65 ± 5 cm/s over a 24-h period, and a higher Lindegaard ratio (6 ± 0.3) have been noted in patients who develop a delayed ischemic deficit. Increased pulsatility index and poor cerebrovascular reactivity to acetazolamide have also been associated with incipient cerebral ischemia and poor prognosis. The loss of cerebrovascular reserve leads also to an impairment of cerebral autoregulation. Its determination—using the transient hyperemic response test—can distinguish patients who are at risk of developing neurological symptoms [4]. This latter observation was done by the group of the University of Cambridge, UK. In this issue of Neurocritical Care, this leading group in the study of cerebral hemodynamics presents a novel hemodynamic index, the ‘‘time constant’’ of cerebral arterial bed. The time constant describes how fast the cerebral arterial bed, distal to the point of TCD insonation, is filled with blood after cardiac contraction. The authors continuously and simultaneously recorded FV and arterial blood pressure and used a relatively simple mathematical model to decode information hidden in the spectral display of the TCD. Indeed, the spectrum of the TCD reflects the flow velocities of each single blood cell moving into the brain arteries. The spectral distribution of different velocities is therefore expression of the arterial blood pressure during the different phases of the cardiac cycle, the section of the arteries of the cranial base, the resistance of the whole system to the downstreaming and blood outflow. A. Conti (&) F. Tomasello Department of Neurosurgery, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy e-mail: alfredo.conti@unime.it

Factors affecting the transient hyperaemic response test of the cerebral autoregulation

The transient compression of the internal carotid artery (ICA) results in dilatation of cerebral arterioles by effect of autoregulation. In the THR test, the increase in middle cerebral artery (MCA) blood flow immediately after release of transient compression of the ICA is measured, which is proportional to cerebral autoregulation. The aim of the study was to determine the significance of several factors of the test - blood flow inertia (acceleration), dimensions (length and radius) of ICA, patency of the Circle of Willis (WC), and asynchrony between release of ICA compression and arterial pressure pulsations (phase shift).

Transient hyperaemic response to assess skin vascular reactivity: effects of heat and iontophoresed norepinephrine

Forearm skin vascular reactivity may be assessed using a transient hyperaemic response (THR) after 20 s of brachial artery compression. THR has been manipulated by iontophoresis of vasodilators, but not vasoconstrictors, possibly because of low baseline blood flow. The effects of vasoconstrictors on vascular reactivity of pre-dilated blood vessels are unknown. We have investigated this using locally applied heat to vasodilate the skin microcirculation before iontophoresis of norepinephrine. Active and control laser Doppler probes measured forearm skin blood flow-flux. Three THR tests were performed before and after heating skin for 5 min, and then after iontophoresis of norepinephrine 0.1%. Iontophoresis was pulsed using 45 s periods of 75 microA and 0 current over 10 min. Three temperatures were used: unheated skin, skin at 35 degrees C, and skin at 42 degrees C. Baseline flow-flux was measured for 60 s before each set of THR tests. THR ratio (THRR) was calculated by comparing baseline flow-flux immediately before arterial compression (F1) with the maximum after release (F2): THRR=F2/F1. The average values of each group of THRR results, and baseline data, were compared using the Kruskal-Wallis test. Iontophoresis of norepinephrine caused significant decreases in flow-flux (P<0.005). Unheated skin and skin heated to 35 degrees C showed significant decreases in THRR after norepinephrine. THRR was abolished by heating to 42 degrees C and partially restored by iontophoresis of norepinephrine. Iontophoresed norepinephrine causes vasoconstriction, and it partially restores vascular reactivity in the heat-induced vasodilated skin. This may be of benefit when norepinephrine is used in clinical situations.

The relationship between the intracranial pressure–volume index and cerebral autoregulation

The pressure-volume index (PVI) can be used to assess the cerebrospinal fluid dynamics and intracranial elastance in critically ill brain injured patients. The dependency of PVI on the state of cerebral autoregulation within the physiologic range of cerebral perfusion pressure (CPP) can be described by mathematical models that account for changes in cerebral blood volume during PVI testing. This relationship has never been verified clinically using direct PVI measurement and independent cerebral autoregulation assessment. PVI and cerebral autoregulation were prospectively assessed in a cohort of 19 comatose patients admitted to an academic intensive care unit in Brescia, Italy. None. PVI was measured injecting a fixed volume of 2 ml of 0.9% sodium chloride solution into the cerebral ventricles through an intraventricular catheter. Cerebral autoregulation was assessed using transcranial Doppler transient hyperaemic response (THR) test. Fifty-nine PVI assessments and 59 THR tests were performed. Mean PVI was 20.0 (SD 10.2) millilitres in sessions when autoregulation was intact (THR test >or=1.1) and 31.6 (8.8) millilitres in sessions with defective autoregulation (THR test <1.1) (DeltaPVI = 11.7 ml, 95% CI = 4.7-19.3 ml; P = 0.002). Intracranial pressure, CPP and brain CT findings were not significantly different between the measurements with intact and disturbed autoregulation. Cerebral autoregulation status can affect PVI estimation despite a normal CPP. PVI measurement may overestimate the tolerance of the intracranial system to volume loads in patients with disturbed cerebral autoregulation.

Transcranial Doppler ultrasonography in intensive care

Transcranial Doppler is an innovative, flexible, accessible tool for the bedside monitoring of static and dynamic cerebral flow and treatment response. Introduced by Rune Aaslid in 1982, it has become indispensable in clinical practice. The main obstacle to ultrasound penetration of the skull is bone. Low frequencies, 1-2 MHz, reduce the attenuation of the ultrasound wave caused by bone. Transcranial Doppler also provides the advantage of acoustic windows representing specific points of the skull where the bone is thin enough to allow ultrasounds to penetrate. There are four acoustic windows: transtemporal, transorbital, suboccipital and retromandibular. The identification of each intracranial vessel is based on the following elements: (a) velocity and direction; (b) depth of signal capture; (c) possibility of following the vessel its whole length; (d) spatial relationship with other vessels; and (e) response to homolateral and contralateral carotid compression. The main fields of clinical application of transcranial Doppler are assessment of vasospasm, detection of stenosis of the intracranial arteries, evaluation of cerebrovascular autoregulation, non-invasive estimation of intracranial pressure, measure of effective downstream pressure and assessment of brain death. Mean flow velocity is directly proportional to flow and inversely proportional to the section of the vessel. Any circumstance that leads to a variation of one of these factors can thus affect mean velocity. The main pathological condition affecting flow velocity is the vasospasm. Vasospasm is a frequent complication of subarachnoid haemorrhage, it often remains clinically silent and the factors that make it symptomatic are largely unknown. Threshold velocities above which vasospasm comes into place are well defined as regards the median cerebral artery, while there is no consensus for the other vessels. Nevertheless, an increase in velocity alone is not sufficient to arrive at a diagnosis of vasospasm; a condition of hyperaemia also presents with an increase in flow velocity. The Lindegaard Index has therefore been introduced, which is defined by the ratio between the mean flow velocity in the median cerebral artery and the mean flow velocity in the internal carotid artery. Criteria for diagnosis of a stenosis >50% of an intracranial vessel with transcranial Doppler include: (a) segmentary acceleration of flow velocity; (b) drop in velocity below the stenotic segment; (c) asymmetry; and (d) circumscribed flow disturbances (turbulence and musical murmur). The transcranial Doppler enables us to assess both components of self-regulation. The static component is measured by observing changes in flow velocity caused by pharmacologically induced episodes of hypertension and hypotension. The dynamic component of autoregulation can be measured using a method devised by Aaslid known as the 'cuff test'. A very effective and safe device for measuring cerebral autoregulation is the transient hyperaemic response test. This test is based on the compensatory vasodilatation of the arterioles, which occurs after brief compression of the common carotid. Csonyka proposed the following formula based on clinical observation for the calculation of cerebral perfusion pressure: CPP = MAP x FVd/FVm + 14. Brain death is defined as the irreversible cessation of all functions of the whole brain. The clinical criteria are usually considered sufficient to establish a diagnosis of brain death; however, they might not be sufficient in patients who have been on sedatives or when there are ethical or legal controversies. Many authors have demonstrated the existence of a transcranial Doppler pattern, which is typical of brain death.

Assessment of cerebral autoregulation with the Transient Hyperemic Response test. Comparison with CO2 Reactivity in head-injury patients

Assessment of cerebral autoregulation with the Transient Hyperemic Response test. Comparison with CO2 Reactivity in head-injury patients

Effects of acute treatment with statins on cerebral autoregulation in patients after aneurysmal subarachnoid hemorrhage

The authors previously have demonstrated that acute treatment with pravastatin after aneurysmal subarachnoid hemorrhage (SAH) can ameliorate vasospasm-related delayed ischemic neurological deficits (DINDs). In the current study, they test the hypothesis that these effects are associated with improvement in indices describing autoregulation of cerebral blood flow. In this double-blind study, 80 patients between the ages of 18 and 84 years who had aneurysmal SAH were randomized equally to receive either 40 mg of oral pravastatin or placebo once daily for up to 14 days (medication was started 1.8 x 1.3 days after ictus). Autoregulation was measured using a daily transient hyperemic response test (THRT) on transcranial Doppler ultrasonography (800 measurements in 80 patients), and data were compared between the pravastatin and placebo groups and between patients with or without vasospasm, DINDs, or unfavorable outcome. Measurement of autoregulation also was performed using the pressure-reactivity index, a moving correlation coefficient between mean arterial and intracranial pressures (Days 0-5, 132 measurements in 32 patients). There was no difference in baseline autoregulation indices between the trial groups. The members of the pravastatin group not only had a shorter duration of impaired autoregulation but also had stronger transient hyperemic response ratios (THRRs) bilaterally. A negative correlation existed between the mean flow velocity in the middle cerebral artery and THRRs. Onset of DINDs occurred when bilateral autoregulation failed. On Days 3, 4, and 5, the pressure-reactivity index correlated significantly with ipsilateral impaired autoregulation. The neuroprotective effects of acute treatment with pravastatin following aneurysmal SAH are associated with enhancement of autoregulation. A routine and daily assessment of cerebral autoregulation by using the THRT may help identify patients at high risk of DINDs.

The Effect of Sevoflurane on Cerebral Autoregulation in Young Children as Assessed by the Transient Hyperemic Response

The transient hyperemic response (THR) test is a simple, noninvasive technique to evaluate cerebral autoregulation using transcranial Doppler. It has not yet been used in studies involving children. In this study we evaluated this response in children undergoing general anesthesia using sevoflurane. Twenty ASA physical status I children undergoing elective urological surgery sequentially received sevoflurane at 0.5, 1.0, and 1.5 MAC in a randomized order. Analgesia was solely provided by caudal anesthesia. The right middle cerebral artery flow velocities before (F1), during (F2), and after (F3) a 10-s ipsilateral carotid artery compression were recorded. The THR ratios (THRR) (+/- sd) for 0.5 MAC, 1.0 MAC, and 1.5 MAC were 1.24 +/- 0.11, 1.16 +/- 0.09, and 1.13 +/- 0.07, respectively. The THRR was significantly different between 0.5 MAC versus 1.0 and 1.5 MAC, respectively (P < 0.05). However, no difference was detected between 1.0 and 1.5 MAC. A THRR of more than 1.09 has previously been accepted as the lower limit of a positive response. The results in this study suggest that THR is affected by sevoflurane in a dose-dependent fashion but is maintained at up to 1.5 MAC. This suggests cerebral autoregulation is preserved in children anesthetized with up to 1.5 MAC sevoflurane.

Cerebral haemodynamics in patients with chronic renal failure: effects of haemodialysis

We measured middle cerebral artery (MCA) flow velocity (FV), dynamic pressure autoregulation, and carbon dioxide reactivity (CRCO(2)) in patients with chronic renal failure before and after haemodialysis using transcranial Doppler ultrasonography. Twelve patients on long-term haemodialysis were recruited. MCA FV was measured continuously. The transient hyperaemic response test was used to assess cerebral autoregulation, and per cent change in FV per kPa change in end-tidal carbon dioxide was calculated to assess CRCO(2). All measurements were recorded before and after haemodialysis. MCA FV (mean [sd]) decreased from 57 (10) cm s(-1) before to 46 (13) cm s(-1) after haemodialysis (P<0.01). The transient hyperaemic response ratio (THRR) was (mean [sd]) 1.29 (0.13) before haemodialysis and did not change significantly following haemodialysis (1.36 [0.10]). CRCO(2) was 21.7 (8.3)% kPa(-1) before haemodialysis and remained unchanged afterwards (20.9 [3.8]% kPa(-1)). Values in normal subjects for MCA FV, THRR and CRCO(2) are 56 (12) cm s(-1), 1.26 (0.13) and 22 (6)% kPa(-1), respectively. MCA FV decreases significantly after haemodialysis. Dynamic pressure autoregulation and CRCO(2) remain normal in patients with chronic renal failure, and are not altered significantly by haemodialysis.

Effects of ephedrine, dobutamine and dopexamine on cerebral haemodynamics: transcranial Doppler studies in healthy volunteers

Sympathomimetic drugs are assumed to have no direct effects on cerebral haemodynamics on the basis of animal experiments; there is little evidence of their direct effects in humans. This study aimed to address this issue. The effects of ephedrine, dobutamine, and dopexamine on cerebral autoregulation, cerebral vascular reactivity to carbon dioxide, estimated cerebral perfusion pressure, and zero flow pressure (ZPF) were studied in 10 healthy volunteers using transcranial Doppler ultrasound. The strength of autoregulation was measured using the transient hyperaemic response test. The reactivity to carbon dioxide was measured as the change in middle cerebral artery flow velocity with a step change in end-tidal carbon dioxide. For the estimated cerebral perfusion pressure and the ZFP, established formulae were used which utilized instantaneous values of arterial pressure and middle cerebral artery flow velocity. Measurements were made at baseline and after i.v. infusion of the study drug to an endpoint of 25% increase in mean arterial pressure (MAP) (ephedrine, dobutamine) or cardiac index (dopexamine). There was no significant change in the strength of autoregulation (from (mean (SD)) 1.07 (0.16) to 1.07 (0.18); from 1.07 (0.16) to 1.03 (0.19); from 1.04 (0.12) to 1.04 (0.25)), reactivity to carbon dioxide (from 40% (8) to 36 (10); from 37 (12) to 37 (11); from 45 (12) to 43 (11)) with ephedrine, dobutamine, or dopexamine, respectively. Despite a clinically significant increase in MAP with ephedrine and dobutamine and a clinically significant increase in cardiac index with dopexamine, the estimated cerebral perfusion pressure did not change significantly (from 81 (38) to 60 (16) mm Hg with ephedrine; from 67 (22) to 63 (11) mm Hg with dobutamine; from 87 (27) to 79 (17) mm Hg with dopexamine). The ZFP increased significantly with ephedrine (from 29 (10) to 44 (11) mm Hg) and dobutamine (from 35 (14) to 43 (10) mm Hg) but not dopexamine (from 3 (23) to 11 (22) mm Hg). Sympathomimetic agents do not significantly change cerebrovascular homeostasis as assessed by the transient hyperaemic response test, reactivity to carbon dioxide and estimated cerebral perfusion pressure.

Effects of magnesium sulphate on cerebral haemodynamics in healthy volunteers: a transcranial Doppler study

Magnesium is increasingly being considered as a neuroprotective agent. We aimed to study its effects on middle cerebral artery blood flow velocity (V(mca)), cerebral autoregulation and cerebral vascular reactivity to carbon dioxide (CRCO(2)) in healthy volunteers. Fifteen healthy volunteers were recruited. Using transcranial Doppler ultrasonography, V(mca) was recorded continuously. The strength of autoregulation was assessed by the transient hyperaemic response test, and the CRCO(2) was measured by assessing changes in V(mca) to the induced changes in end-tidal carbon dioxide. I.V. infusion of magnesium sulphate was then started (loading dose of 16 mmol followed by an infusion at the rate of 2.7 mmol h(-1)) for 45 min. The cerebral haemodynamic variables were measured again near the end of the infusion of magnesium sulphate. Total serum magnesium levels were doubled by the infusion regimen. However, there were no significant changes in V(mca), strength of autoregulation, or CRCO(2). Five of the volunteers reported marked nausea and two developed significant hypotension during the loading dose. Infusion of magnesium sulphate, in a dose that doubles its concentration in plasma, does not affect V(mca), strength of autoregulation or CRCO(2) in healthy volunteers. However, it can be associated with nausea and hypotension.

Transient hyperaemic response to assess vascular reactivity of skin: effect of locally iontophoresed acetylcholine, bradykinin, epinephrine and phenylephrine

Recently, the transient hyperaemic response (THR) to brief compression (20 s) of the brachial artery has been described as a way to assess vascular reactivity of the forearm skin. We studied the effects of locally iontophoresed vasoactive agents on this response in 20 male volunteers. An iontophoresis chamber attached to the anterior forearm permitted simultaneous administration of drugs by iontophoresis and measurement of skin blood flow-flux by laser Doppler probe. Three THR tests were performed before and after iontophoresis by compressing the brachial artery with digital pressure for 20 s and then releasing. The following were iontophoresed: saline 0.9% (iontophoresis vehicle control), acetylcholine, bradykinin, epinephrine and phenylephrine. The THR ratio (THRR) was calculated as F2/F1 where F1 was baseline blood flow-flux immediately before compression and F2 was peak blood flow-flux after release. When compared with saline 0.9%, acetylcholine and bradykinin increased median F1 from 9.2 (range 5.2-23.8) to 22.1 (8.7-61.5) and from 4.8 (3.0-23.2) to 15.0 (2.5-31.8), respectively, and reduced THRR from 1.26 (1.07-2.2) to 0.99 (0.93-1.04) and from 1.63 (1.06-2.58) to 1.09 (0.93-1.19), respectively. Epinephrine, but not phenylephrine, caused a significant reduction in F1 from 9.2 (5.2-23.8) to 4.0 (1.5-22.3). Neither epinephrine nor phenylephrine had significant effect on THRR. Iontophoresed acetylcholine and bradykinin significantly increase the flow-flux and impair THR in forearm skin, further validating the concept that THR represents true vasodilatation during arterial occlusion. In addition, iontophoresis of vasoconstrictors does not appear to have any consistent effect.

Continuous assessment of cerebral autoregulation: clinical and laboratory experience.

The method for the continuous assessment of cerebral autoregulation using slow waves of MCA blood flow velocity (FV) and cerebral perfusion pressure (CPP) or arterial pressure (ABP) has been introduced seven years ago. We intend to review its clinical applications in various scenarios. Moving correlation coefficient (3-6 min window), named Mx, is calculated between low-pass filtered (0.05 Hz) signals of FV and CPP or ABP (when ICP is not measured directly). Data from ventilated 243 head injuries and 15 patients after poor grade subarachnoid haemorrhage, 38 patients with Carotid Artery stenosis, 35 patients with hydrocephalus and fourteen healthy volunteers is presented. Good agreement between the leg-cuff test and Mx has been confirmed in healthy volunteers (r = 0.81). Mx also correlated significantly with the static rate of autoregulation and transient hyperaemic response test. Autoregulation was disturbed (p < 0.021) by vasospasm after SAH and worse in patients with hydrocephalus in whom CSF circulation was normal (p < 0.02). In head injury, Mx indicated disturbed autoregulation with low CPP (< 55 mmHg) and too high CPP (> 95 mmHg). Mx strongly discriminated between patients with favourable and unfavourable outcome (p < 0.00002). This method can be used in many clinical scenarios for continuous monitoring of cerebral autoregulation, predicting outcome and optimising treatment strategies.

Cerebral haemodynamics in pregnancy and pre-eclampsia as assessed by transcranial Doppler ultrasonography

Altered cerebral circulation, as reported during normal pregnancy, and in patients with pre-eclampsia, can be associated with changes in cerebral vascular reactivity and/or cerebral autoregulation. The aim of our study was to perform a comparative assessment of cerebral haemodynamics, including vascular reactivity and autoregulation, in pre-eclamptic patients, healthy pregnant women, and healthy non-pregnant women. Thirty patients with pre-eclampsia were recruited. Age- and height-matched healthy pregnant (n=30) and non-pregnant control (n=30) groups were also recruited. Monitoring included transcranial Doppler ultrasonography, end-tidal carbon dioxide and non-invasive arterial pressure measurement. Cerebral autoregulation was assessed by performing the transient hyperaemic response (THR) test. The cerebrovascular reactivity to carbon dioxide (CRCO(2)) was assessed by measuring middle cerebral artery blood flow velocity (MCAFV) after induced changes in end-tidal carbon dioxide. Estimated cerebral perfusion pressure (eCPP) and critical closing pressure (CrCP) were calculated using established formulae. Statistical analysis included ANOVA with Tukey's pairwise comparisons. Mean arterial pressure (MAP) was increased in pre-eclampsia (P<0.05). Mean MCAFV was lower in healthy pregnancy (P<0.05), but in pre-eclampsia it was similar to the non- pregnant group. When compared with the non-pregnant group, mean eCPP was higher in the healthy pregnant and pre-eclamptic groups (P<0.05). There were no meaningful differences in cerebral autoregulation or CRCO(2). Healthy pregnancy increases eCPP, presumably by decreasing CrCP. In pre-eclampsia, eCPP is maintained at the same level as in healthy pregnancy despite an increased MAP. Pre-eclampsia has no significant effect on cerebral autoregulation or CRCO(2).

Cerebral haemodynamics in pregnancy and pre-eclampsia as assessed by transcranial Doppler ultrasonography

Altered cerebral circulation, as reported during normal pregnancy, and in patients with pre-eclampsia, can be associated with changes in cerebral vascular reactivity and/or cerebral autoregulation. The aim of our study was to perform a comparative assessment of cerebral haemodynamics, including vascular reactivity and autoregulation, in pre-eclamptic patients, healthy pregnant women, and healthy non-pregnant women.Thirty patients with pre-eclampsia were recruited. Age- and height-matched healthy pregnant (n=30) and non-pregnant control (n=30) groups were also recruited. Monitoring included transcranial Doppler ultrasonography, end-tidal carbon dioxide and non-invasive arterial pressure measurement. Cerebral autoregulation was assessed by performing the transient hyperaemic response (THR) test. The cerebrovascular reactivity to carbon dioxide (CRCO(2)) was assessed by measuring middle cerebral artery blood flow velocity (MCAFV) after induced changes in end-tidal carbon dioxide. Estimated cerebral perfusion pressure (eCPP) and critical closing pressure (CrCP) were calculated using established formulae. Statistical analysis included ANOVA with Tukey's pairwise comparisons.Mean arterial pressure (MAP) was increased in pre-eclampsia (P<0.05). Mean MCAFV was lower in healthy pregnancy (P<0.05), but in pre-eclampsia it was similar to the non- pregnant group. When compared with the non-pregnant group, mean eCPP was higher in the healthy pregnant and pre-eclamptic groups (P<0.05). There were no meaningful differences in cerebral autoregulation or CRCO(2).Healthy pregnancy increases eCPP, presumably by decreasing CrCP. In pre-eclampsia, eCPP is maintained at the same level as in healthy pregnancy despite an increased MAP. Pre-eclampsia has no significant effect on cerebral autoregulation or CRCO(2).