Blood Pressure Variability and Outcome in Acute Ischemic and Hemorrhagic Stroke: A Post-Hoc Analysis of the HeadPoST Study

The Head Positioning in Acute Stroke Trial (HeadPoST) is a pragmatic, international, cluster crossover randomized trial of 11,093 patients with acute stroke assigned to a lying-flat (0o) or sitting-up (head elevated ≥30o) position. This post-hoc analysis aimed to determine the association between BPV and outcomes for patients from a wide range of international clinical settings and how the association was modified by randomized head position. BPV was defined according to standard criteria with the key parameter considered the coefficient of variation (CV) of systolic BP (SBP) over 24 hours. Outcome was ordinal 90-day modified Rankin Scale (mRS) score. The association was analyzed by ordinal, logistic regression, hierarchical, mixed models with fixed intervention (lying-flat vs. sitting-up), and fixed period, random cluster, and random cluster-period, effects. 9,156 (8,324 AIS and 817 ICH; mean age 68.1 years; 39.2% women) were included in the analysis. CV of SBP had a significant linear association with unfavorable shift of mRS at 90 days (adjusted odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02-1.11; P=0.01). There was no heterogeneity of the association by randomized head positioning. In addition, CV of diastolic BP (DBP) (1.08, 1.03-1.12; P=0.001) over 24 hours post stroke, was significantly associated with 3-month poor outcome. The association was more apparent in sitting-up position (1.12, 1.06-1.19) compared with lying-flat position (1.03, 0.98-1.09) (P interaction = 0.005). BPV was associated with adverse stroke outcome, the magnitude of the association was greater with sitting-up head positioning in terms of DBP variability

Highlighting the Potential Value of Capnography in Acute Stroke

I read with keen interest the comprehensive review by Long et al. regarding the value of capnography in the emergency department (ED) (1). This review provides a clear and concise summary of the breadth of applications of capnography in an ED setting and emphasises the key aspects of accurate interpretation of carbon dioxide (CO2) measurements

Dabigatran: Important Considerations in the Elderly

We read, with keen interest, the report by Dezman et al. regarding the severity of bleeding and mortality in trauma patients taking dabigatran (1). Stroke physicians frequently prescribe non-vitamin K antagonist oral anticoagulants (NOAC) like dabigatran for stroke prevention in the context of nonvalvular atrial fibrillation. Although the introduction of NOAC into clinical practice has been a major advance with reduction of monitoring requirement, there remains ongoing concern about the risk of bleeding and the absence of an antidote. The NOAC randomized controlled trials have uniformly reported clinically significant reductions in intracranial hemorrhage (ICH) risk, but not gastrointestinal hemorrhage (2)

Emerging evidence in the delivery of stroke thrombolysis

Intravenous Thrombolysis (IVT) significantly increases the chance of functional independence post-stroke, and an improved understanding of delivery has ensured better safety and clinical outcomes. Despite this, there remain several aspects of IVT delivery that are yet to be clarified including: the role of new thrombolytic agents; treatment strategies for stroke with unknown onset time, including wake-up stroke; and the role of an intensive peri-thrombolysis BP target. Tenecteplase is an emerging IVT agent that has preferential characteristics yet to be fully examined in larger studies of AIS patients or sub-groups including ‘wake-up’ stroke. We await the results of on-going trials to ensure continuing optimisation of IVT delivery

Latest developments in clinical stroke care

Stroke medicine has seen rapid developments in diagnosis and management, and consequently improved prognosis. Management of ischaemic stroke, in particular, has benefited from these advances. The approach to management has evolved from one of historical passivity to active intervention with time of the essence following stroke onset. The last decade has seen the comparative effectiveness of several pharmacological agents being tested, creating significant randomised controlled trial evidence to support the management of common clinical problems following acute stroke. While several of these interventions are widely available, some remain less accessible. This review will discuss the latest developments in clinical stroke medicine, based on a symposium presentation at the Royal College of Physicians of Edinburgh, and reference key randomised controlled trial evidence in an effort to provide a balanced perspective on our current understanding of acute ischaemic and haemorrhagic stroke

New Horizons for Stroke Medicine: Understanding the Value of Social Media

Social media (SM) has provided individuals and organizations with an openly accessible platform encouraging participation and engagement in different forms of media (blogs, photos, infographics, and videos). In the past decade, there has been an exponential increase in platforms supporting user-driven content all encouraging differing degrees of SM interaction. Despite the initial SM revolution being based on social interaction, increasingly medical professionals are harboring such streams of communication to further medical knowledge and develop professional networks. An example of a SM platform is Twitter, a well-established microblogging tool,1 which supports communities2 of medical professionals interacting regularly. Importantly, data support an increasing coverage of biomedical literature on Twitter (≈10% of all published literature).3 Stroke medicine is constantly evolving to adapt to new technologies, which have supported new therapies and new diagnostic tools. However, little is known about the benefit of new technologies to our ways of communicating. In this article, we discuss how stroke trainees in particular could benefit from using SM to communicate and improve their educational, professional, and academic development. Furthermore, we provide for the first time Twitter analytic data from an international stroke trainee-based meeting to demonstrate real-world value to trainees and importantly organizations

Evolving the Proposed HEMS Stroke Triaging Tool

Letter to the Editor - Evolving the Proposed HEMS Stroke Triaging Too

Sex differences in cerebral haemodynamics across the physiological range of PaCO2

OBJECTIVE: Cerebral blood flow (CBF) is influenced by changes in arterial CO2 (PaCO2). Recently, cerebral haemodynamic parameters were demonstrated to follow a four parameter logistic curve offering simultaneous assessment of dCA and CO2 vasoreactivity. However, the effects of sex on cerebral haemodynamics have yet to be described over a wide range of PaCO2. APPROACH: CBF velocity (CBFV, transcranial Doppler), blood pressure (BP, Finometer) and end-tidal CO2 (EtCO2, capnography) were measured in healthy volunteers at baseline, and in response to hypo- (-5 mmHg and  -10 mmHg below baseline) and hypercapnia (5% and 8% CO2), applied in random order. MAIN RESULTS: Forty-five subjects (19 male, 26 female, mean age 37.5 years) showed significant differences between males and females in CBFV (50.9  ±  10.4 versus 61.5  ±  12.3 cm · s-1, p  =  0.004), EtCO2 (39.2  ±  2.8 versus 36.9  ±  3.0 mmHg, p  =  0.005), RAP (1.16  ±  0.23 versus 0.94  ±  0.40 mmHg cm · s-1, p  =  0.005) and systolic BP (125.2  ±  8.0 versus 114.6  ±  12.4 mmHg, p  =  0.0372), respectively. Significant differences between sexes were observed in the four logistic parameters: y min, y max, k (exponential coefficient) and x (EtCO2 level) across the haemodynamic variables. Significant differences included the CBFV-EtCO2 and ARI-EtCO2 relationship; ARImin (p  =  0.036) and CBFVmax (p  =  0.001), respectively. Furthermore, significant differences were observed for both CrCPmin (p  =  0.045) and CrCPmax (p  =  0.005) and RAPmin (p  <  0.001) and RAPmax (p  <  0.001). SIGNIFICANCE: This is the first study to examine sex individually within the context of a multi-level CO2 protocol. The demonstration that the logistic curve parameters are influenced by sex, highlights the need to take into account sex differences between participants in both physiological and clinical studies

Inter-subject analysis of transfer function coherence in studies of dynamic cerebral autoregulation

Objective: The gain and phase of the arterial blood pressure (BP)-cerebral blood flow velocity (CBFV) relationship, assessed by transfer function analysis (TFA), are widely used dynamic cerebral autoregulation (CA) metrics, but their reliability depend on the statistical significance of the magnitude squared coherence (MSC) function. We tested a new approach, based on inter-subject data, to estimate the confidence limits of MSC. Approach: Five minute beat-to-beat time series of mean arterial BP (MAP, Finometer) and CBFV (transcranial Doppler) were used for intra-subject (MAP and CBFV from same subject) and inter-subject (BP and CBFV swapped between subjects) estimates of MSC. The 95% confidence limit of MSC was obtained by non-parametric methods for the cases of single frequency harmonics in the range [0.02-0.50 Hz], and also from the mean value of all possible frequency intervals in this range. Main results: Intra-subject estimates of MSC were obtained from 100 healthy subjects (48 female, age range: 21-82 years old) allowing calculation of 9,900 inter-subject estimates, with 95% confidence limits in excellent agreement with classical values derived from surrogate random data. Confidence limits of MSC, derived from mean values, decreased asymptotically to around 0.16 with the increasing number of harmonics averaged. Significance: Replacing estimates of MSC at a single frequency harmonic by the mean calculated over the range [0.02-0.30 Hz] could lead to more robust studies of dynamic CA with greater acceptance of recordings, an important consideration in clinical studies where measurements tend to be more susceptible to noise and artefacts.

Different strategies to initiate and maintain hyperventilation: their effect on continuous estimates of dynamic cerebral autoregulation

OBJECTIVE: Capnography is a key monitoring intervention in several neurologically vulnerable clinical states. Cerebral autoregulation (CA) describes the ability of the cerebrovascular system to maintain a near constant cerebral blood flow throughout fluctuations in systemic arterial blood pressure, with the partial pressure of arterial carbon dioxide known to directly influence CA. Previous work has demonstrated dysautoregulation lasting around 30 s prior to the anticipated augmentation of hyperventilation-associated hypocapnia. In order assess to potential benefit of hypocapnic interventions in an acute stroke setting, minimisation of dysregulation is paramount. APPROACH: Hyperventilation strategies to induce and maintain hypocapnia were performed in 61 healthy participants, effects on temporal estimates of dynamic cerebral autoregulation (autoregulation index, ARI) were assessed to validate the most effective strategy for inducing and maintaining hypocapnia. MAIN RESULTS: The extent of initial decrease was significantly smaller in the continuous metronome strategy compared to the delayed metronome and voluntary strategies (▵ARI 0.33  ±  1.18, 2.80  ±  3.33 and 3.69  ±  2.79 respectively, p   <  0.017). SIGNIFICANCE: The use of a continuous metronome to induce hypocapnia rather than the sudden inception of an auditory stimulus appears to reduce the initial decrease in autoregulatory capacity seen in previous studies. Dysautoregulation can be minimised by continuous metronome use during hyperventilation-induced hypocapnia. This advancement in understanding of the behaviour of CA during hypocapnia permits safer delivery of CA targeted interventions, particularly in neurologically vulnerable patient populations