The objective of the study was to assess the long-term self-reported health status and quality of... more The objective of the study was to assess the long-term self-reported health status and quality of life (QoL) of patients following an aneurysmal subarachnoid haemorrhage (ASAH) using a self-completed questionnaire booklet. A two-cohort study. A regional tertiary neurosurgical centre. 2 cohorts of patients with ASAH treated between 1998 and 2008 and followed up at approximately 1 year. Routine care. A range of standardised scales included: AKC Short Sentences Test, the Barthel Index, the Self-Report Dysexecutive Questionnaire, the Everyday Memory Questionnaire, Stroke Symptom Checklist, Wimbledon Self-Report Scale, Modified Rankin Score (MRS) and a new Stroke-QoL. The data from summated scales were fit to the Rasch measurement model to validate the summed score. 214 patients (48%) returned the questionnaires; the majority (76%) had a World Federation of Neurosurgeons grade of 1 or 2. The most frequent aneurysm type was that of the anterior communicating artery (28%) with approximatel...
The traditional axiom that vasospasm induced reduction of blood flow leads to poor tissue oxygena... more The traditional axiom that vasospasm induced reduction of blood flow leads to poor tissue oxygenation and ischaemic cellular injury culminating in delayed neurological deficits has been challenged and the efficacy of triple H therapy in reversal of the above is debated. In this study we assess cerebral physiology before and during onset of DIND and with application of triple H therapy with real time neuro-monitoring tools. Patients with Fisher grade 3/4/3 + 4/rebleed were consented. Probes for measuring rCBF, pTiO2, and Microdialysis parameters - glucose, glycerol, lactate, and pyruvate were inserted at time of coiling/clipping. Subsequent monitoring was done in HDU/ITU setting. Return of parameters to baseline was regarded as effective triple H therapy. Study is ongoing and the current paper presents our experience with first five patients. The results suggest safety and feasibility of multimodal monitoring in clinical setting to establish an understanding of relationship between c...
Delayed ischemic neurologic deficit (DIND) is a serious and poorly understood complication of ane... more Delayed ischemic neurologic deficit (DIND) is a serious and poorly understood complication of aneurysmal subarachnoid hemorrhage. Although advances in treatment have improved prognosis for these patients, long-term clinical outcomes remain disappointing. Historically, angiographic vasospasm was thought to result in a DIND, although an increasing body of evidence suggests that this is an oversimplification, because interventions that have effectively targeted angiographic vasospasm have not improved outcome. Consequently, the relationship between angiographic vasospasm and neurologic outcome may be associative rather than causative. Although our understanding of the underlying molecular processes and pathophysiology is improving, responsible mediators or pathways have yet to be identified. The aim of this review is to summarize the key historical events that have helped shape our understanding of the pathophysiology of this phenomenon (microcirculation, autoregulation, microthrombosi...
Successful critical care management of patients with aneurysmal subarachnoid hemorrhage requires ... more Successful critical care management of patients with aneurysmal subarachnoid hemorrhage requires a thorough understanding of the disease and its complications and a familiarity with modern multimodality neuromonitoring technology. This article reviews the natural history of aneurysmal subarachnoid hemorrhage and strategies for disease management in the acute setting. Available tools for monitoring brain function are discussed.
The outcome of patients with aneurysmal subarachnoid hemorrhage (SAH) has improved slowly over th... more The outcome of patients with aneurysmal subarachnoid hemorrhage (SAH) has improved slowly over the past 25 years. This improvement may be due to early aneurysm repair by endovascular or open means, use of nimodipine, and better critical care management. Despite this improvement, mortality remains at about 40%, and many survivors have permanent neurologic, cognitive, and neuropsychologic deficits. Randomized clinical trials have tested pharmacologic therapies, but few have been successful. There are numerous explanations for the failure of these trials, including ineffective interventions, inadequate sample size, treatment side effects, and insensitive or inappropriate outcome measures. Outcome often is evaluated on a good-bad dichotomous scale that was developed for traumatic brain injury 40 years ago. To address these issues, we established the Subarachnoid Hemorrhage International Trialists (SAHIT) data repository. The primary aim of the SAHIT data repository is to provide a uniqu...
Outcome of patients with aneurysmal subarachnoid hemorrhage (SAH) has improved over the last deca... more Outcome of patients with aneurysmal subarachnoid hemorrhage (SAH) has improved over the last decades. Yet, case fatality remains nearly 40% and survivors often have permanent neurological, cognitive and/or behavioural sequelae. Other than nimodipine drug or clinical trials have not consistently improved outcome. We formed a collaboration of SAH investigators to create a resource for prognostic analysis and for studies aimed at optimizing the design and analysis of phase 3 trials in aneurysmal SAH. We identified investigators with data from randomized, clinical trials of patients with aneurysmal SAH or prospectively collected single- or multicentre databases of aneurysmal SAH patients. Data are being collected and proposals to use the data and to design future phase 3 clinical trials are being discussed. This paper reviews some issues discussed at the first meeting of the SAH international trialists (SAHIT) repository meeting. Investigators contributed or have agreed to contribute da...
Researchers and other stakeholders continue to express concern about the failure of randomized cl... more Researchers and other stakeholders continue to express concern about the failure of randomized clinical trials (RCT) in subarachnoid hemorrhage (SAH) to show efficacy of new treatments. Pooled data may be particularly useful to generate hypotheses about causes of poor outcomes and reasons for failure of RCT in SAH, and strategies to improve them. Investigators conducting SAH research collaborated to share data with the intent to develop a large repository of pooled individual patient data for exploratory analysis and testing of new hypotheses relevant to improved trial design and analysis in SAH. This repository currently contains information on 11,443 SAH patients from 14 clinical databases, of which 9 are datasets of recent RCTs and 5 are datasets of prospective observational studies and hospital registries. Most patients were managed in the last 15Â years. Data validation and quality checks have been conducted and are satisfactory. Data is available on demographic, clinical, neuro...
Clinical prediction models can enhance clinical decision-making and research. However, available ... more Clinical prediction models can enhance clinical decision-making and research. However, available prediction models in aneurysmal subarachnoid hemorrhage (aSAH) are rarely used. We evaluated the methodological validity of SAH prediction models and the relevance of the main predictors to identify potentially reliable models and to guide future attempts at model development. We searched the EMBASE, MEDLINE, and Web of Science databases from January 1995 to June 2012 to identify studies that reported clinical prediction models for mortality and functional outcome in aSAH. Validated methods were used to minimize bias. Eleven studies were identified; 3 developed models from datasets of phase 3 clinical trials, the others from single hospital records. The median patient sample size was 340 (interquartile range 149-733). The main predictors used were age (n = 8), Fisher grade (n = 6), World Federation of Neurological Surgeons grade (n = 5), aneurysm size (n = 5), and Hunt and Hess grade (n = 3). Age was consistently dichotomized. Potential predictors were prescreened by univariate analysis in 36 % of studies. Only one study was penalized for model optimism. Details about model development were often insufficiently described and no published studies provided external validation. While clinical prediction models for aSAH use a few simple predictors, there are substantial methodological problems with the models and none have had external validation. This precludes the use of existing models for clinical or research purposes. We recommend further studies to develop and validate reliable clinical prediction models for aSAH.
To evaluate and compare the safety and efficacy of cisatracurium (51W89) and atracurium administe... more To evaluate and compare the safety and efficacy of cisatracurium (51W89) and atracurium administered by continuous infusion to critically ill patients requiring neuromuscular blocking agents to facilitate mechanical ventilation. Open, randomized, multicenter study of patients receiving cisatracurium or atracurium infusion to facilitate mechanical ventilation. Five university teaching hospital intensive care units in the United Kingdom. Sixty-one adult patients requiring neuromuscular blocking agents to facilitate mechanical ventilation. Bolus doses followed by continuous infusions of cisatracurium or atracurium were administered. Onset, maintenance, and recovery of neuromuscular blockade were measured, using transcutaneous ulnar nerve stimulation and an accelerometer. Forty patients received cisatracurium (mean duration 48.1 +/- 4.2 [SEM] hrs), and 21 patients received atracurium (mean duration 46.1 +/- 5.8 hrs). The infusion rate for patients receiving cisatracurium was 3.1 +/- 0.2 microg/kg/min, and for patients receiving atracurium 10.4 +/- 0.9 microg/kg/min. There were no significant differences in mean times to 70% recovery of Train-of-Four ratio (cisatracurium 60 mins, atracurium 57 mins), although there was considerable interpatient variation (20 to 175 mins with cisatracurium vs. 35 to 85 mins with atracurium). One patient who received cisatracurium exhibited intermittent bronchospasm during and after the study period. Cisatracurium, an isomer of atracurium, appears to be a suitable agent for providing muscle relaxation in critically ill patients.
Cerebral Vasospasm: Neurovascular Events After Subarachnoid Hemorrhage, 2012
Patients recovered from subarachnoid hemorrhage can be assessed for neuropsychological dysfunctio... more Patients recovered from subarachnoid hemorrhage can be assessed for neuropsychological dysfunction using postal questionnaires. We assessed 214 patients using various tests of memory, mood and strategic thinking. Patients in good outcome categories (modified Rankin Scale [mRS] 0-1) nevertheless exhibited mood disorder (28%), memory deficit and executive dysfunction (20%). Return to work (49%) was most influenced by previous employment status, Rankin scale and mood.
The objective of the study was to assess the long-term self-reported health status and quality of... more The objective of the study was to assess the long-term self-reported health status and quality of life (QoL) of patients following an aneurysmal subarachnoid haemorrhage (ASAH) using a self-completed questionnaire booklet. A two-cohort study. A regional tertiary neurosurgical centre. 2 cohorts of patients with ASAH treated between 1998 and 2008 and followed up at approximately 1 year. Routine care. A range of standardised scales included: AKC Short Sentences Test, the Barthel Index, the Self-Report Dysexecutive Questionnaire, the Everyday Memory Questionnaire, Stroke Symptom Checklist, Wimbledon Self-Report Scale, Modified Rankin Score (MRS) and a new Stroke-QoL. The data from summated scales were fit to the Rasch measurement model to validate the summed score. 214 patients (48%) returned the questionnaires; the majority (76%) had a World Federation of Neurosurgeons grade of 1 or 2. The most frequent aneurysm type was that of the anterior communicating artery (28%) with approximatel...
The traditional axiom that vasospasm induced reduction of blood flow leads to poor tissue oxygena... more The traditional axiom that vasospasm induced reduction of blood flow leads to poor tissue oxygenation and ischaemic cellular injury culminating in delayed neurological deficits has been challenged and the efficacy of triple H therapy in reversal of the above is debated. In this study we assess cerebral physiology before and during onset of DIND and with application of triple H therapy with real time neuro-monitoring tools. Patients with Fisher grade 3/4/3 + 4/rebleed were consented. Probes for measuring rCBF, pTiO2, and Microdialysis parameters - glucose, glycerol, lactate, and pyruvate were inserted at time of coiling/clipping. Subsequent monitoring was done in HDU/ITU setting. Return of parameters to baseline was regarded as effective triple H therapy. Study is ongoing and the current paper presents our experience with first five patients. The results suggest safety and feasibility of multimodal monitoring in clinical setting to establish an understanding of relationship between c...
Delayed ischemic neurologic deficit (DIND) is a serious and poorly understood complication of ane... more Delayed ischemic neurologic deficit (DIND) is a serious and poorly understood complication of aneurysmal subarachnoid hemorrhage. Although advances in treatment have improved prognosis for these patients, long-term clinical outcomes remain disappointing. Historically, angiographic vasospasm was thought to result in a DIND, although an increasing body of evidence suggests that this is an oversimplification, because interventions that have effectively targeted angiographic vasospasm have not improved outcome. Consequently, the relationship between angiographic vasospasm and neurologic outcome may be associative rather than causative. Although our understanding of the underlying molecular processes and pathophysiology is improving, responsible mediators or pathways have yet to be identified. The aim of this review is to summarize the key historical events that have helped shape our understanding of the pathophysiology of this phenomenon (microcirculation, autoregulation, microthrombosi...
Successful critical care management of patients with aneurysmal subarachnoid hemorrhage requires ... more Successful critical care management of patients with aneurysmal subarachnoid hemorrhage requires a thorough understanding of the disease and its complications and a familiarity with modern multimodality neuromonitoring technology. This article reviews the natural history of aneurysmal subarachnoid hemorrhage and strategies for disease management in the acute setting. Available tools for monitoring brain function are discussed.
The outcome of patients with aneurysmal subarachnoid hemorrhage (SAH) has improved slowly over th... more The outcome of patients with aneurysmal subarachnoid hemorrhage (SAH) has improved slowly over the past 25 years. This improvement may be due to early aneurysm repair by endovascular or open means, use of nimodipine, and better critical care management. Despite this improvement, mortality remains at about 40%, and many survivors have permanent neurologic, cognitive, and neuropsychologic deficits. Randomized clinical trials have tested pharmacologic therapies, but few have been successful. There are numerous explanations for the failure of these trials, including ineffective interventions, inadequate sample size, treatment side effects, and insensitive or inappropriate outcome measures. Outcome often is evaluated on a good-bad dichotomous scale that was developed for traumatic brain injury 40 years ago. To address these issues, we established the Subarachnoid Hemorrhage International Trialists (SAHIT) data repository. The primary aim of the SAHIT data repository is to provide a uniqu...
Outcome of patients with aneurysmal subarachnoid hemorrhage (SAH) has improved over the last deca... more Outcome of patients with aneurysmal subarachnoid hemorrhage (SAH) has improved over the last decades. Yet, case fatality remains nearly 40% and survivors often have permanent neurological, cognitive and/or behavioural sequelae. Other than nimodipine drug or clinical trials have not consistently improved outcome. We formed a collaboration of SAH investigators to create a resource for prognostic analysis and for studies aimed at optimizing the design and analysis of phase 3 trials in aneurysmal SAH. We identified investigators with data from randomized, clinical trials of patients with aneurysmal SAH or prospectively collected single- or multicentre databases of aneurysmal SAH patients. Data are being collected and proposals to use the data and to design future phase 3 clinical trials are being discussed. This paper reviews some issues discussed at the first meeting of the SAH international trialists (SAHIT) repository meeting. Investigators contributed or have agreed to contribute da...
Researchers and other stakeholders continue to express concern about the failure of randomized cl... more Researchers and other stakeholders continue to express concern about the failure of randomized clinical trials (RCT) in subarachnoid hemorrhage (SAH) to show efficacy of new treatments. Pooled data may be particularly useful to generate hypotheses about causes of poor outcomes and reasons for failure of RCT in SAH, and strategies to improve them. Investigators conducting SAH research collaborated to share data with the intent to develop a large repository of pooled individual patient data for exploratory analysis and testing of new hypotheses relevant to improved trial design and analysis in SAH. This repository currently contains information on 11,443 SAH patients from 14 clinical databases, of which 9 are datasets of recent RCTs and 5 are datasets of prospective observational studies and hospital registries. Most patients were managed in the last 15Â years. Data validation and quality checks have been conducted and are satisfactory. Data is available on demographic, clinical, neuro...
Clinical prediction models can enhance clinical decision-making and research. However, available ... more Clinical prediction models can enhance clinical decision-making and research. However, available prediction models in aneurysmal subarachnoid hemorrhage (aSAH) are rarely used. We evaluated the methodological validity of SAH prediction models and the relevance of the main predictors to identify potentially reliable models and to guide future attempts at model development. We searched the EMBASE, MEDLINE, and Web of Science databases from January 1995 to June 2012 to identify studies that reported clinical prediction models for mortality and functional outcome in aSAH. Validated methods were used to minimize bias. Eleven studies were identified; 3 developed models from datasets of phase 3 clinical trials, the others from single hospital records. The median patient sample size was 340 (interquartile range 149-733). The main predictors used were age (n = 8), Fisher grade (n = 6), World Federation of Neurological Surgeons grade (n = 5), aneurysm size (n = 5), and Hunt and Hess grade (n = 3). Age was consistently dichotomized. Potential predictors were prescreened by univariate analysis in 36 % of studies. Only one study was penalized for model optimism. Details about model development were often insufficiently described and no published studies provided external validation. While clinical prediction models for aSAH use a few simple predictors, there are substantial methodological problems with the models and none have had external validation. This precludes the use of existing models for clinical or research purposes. We recommend further studies to develop and validate reliable clinical prediction models for aSAH.
To evaluate and compare the safety and efficacy of cisatracurium (51W89) and atracurium administe... more To evaluate and compare the safety and efficacy of cisatracurium (51W89) and atracurium administered by continuous infusion to critically ill patients requiring neuromuscular blocking agents to facilitate mechanical ventilation. Open, randomized, multicenter study of patients receiving cisatracurium or atracurium infusion to facilitate mechanical ventilation. Five university teaching hospital intensive care units in the United Kingdom. Sixty-one adult patients requiring neuromuscular blocking agents to facilitate mechanical ventilation. Bolus doses followed by continuous infusions of cisatracurium or atracurium were administered. Onset, maintenance, and recovery of neuromuscular blockade were measured, using transcutaneous ulnar nerve stimulation and an accelerometer. Forty patients received cisatracurium (mean duration 48.1 +/- 4.2 [SEM] hrs), and 21 patients received atracurium (mean duration 46.1 +/- 5.8 hrs). The infusion rate for patients receiving cisatracurium was 3.1 +/- 0.2 microg/kg/min, and for patients receiving atracurium 10.4 +/- 0.9 microg/kg/min. There were no significant differences in mean times to 70% recovery of Train-of-Four ratio (cisatracurium 60 mins, atracurium 57 mins), although there was considerable interpatient variation (20 to 175 mins with cisatracurium vs. 35 to 85 mins with atracurium). One patient who received cisatracurium exhibited intermittent bronchospasm during and after the study period. Cisatracurium, an isomer of atracurium, appears to be a suitable agent for providing muscle relaxation in critically ill patients.
Cerebral Vasospasm: Neurovascular Events After Subarachnoid Hemorrhage, 2012
Patients recovered from subarachnoid hemorrhage can be assessed for neuropsychological dysfunctio... more Patients recovered from subarachnoid hemorrhage can be assessed for neuropsychological dysfunction using postal questionnaires. We assessed 214 patients using various tests of memory, mood and strategic thinking. Patients in good outcome categories (modified Rankin Scale [mRS] 0-1) nevertheless exhibited mood disorder (28%), memory deficit and executive dysfunction (20%). Return to work (49%) was most influenced by previous employment status, Rankin scale and mood.
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