Maternal Risk Modeling in Critical Care-Development of a Multivariable Risk Prediction Model for Death and Prolonged Intensive Care.

OBJECTIVES: We aimed to develop and validate an accurate risk prediction model for both mortality and a combined outcome of mortality and morbidity for maternal admissions to critical care. DESIGN: We used data from a high-quality prospectively collected national database, supported with literature review and expert opinion. We tested univariable associations between each risk factor and outcome. We then developed two separate multivariable logistic regression models for the outcomes of acute hospital mortality and death or prolonged ICU length of stay. We validated two parsimonious risk prediction models specific for a maternal population. SETTING: The Intensive Care National Audit and Research Centre Case Mix Programme is the national clinical audit for adult critical care in England, Wales, and Northern Ireland. PATIENTS: All female admissions to adult general critical care units, for the period January 1, 2007-December 31, 2016, 16-50 years old, and admitted either while pregnant or within 42 days of delivery-a cohort of 15,480 women. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We aimed to develop and validate an accurate risk prediction model for both mortality and a combined outcome of mortality and morbidity for maternal admissions to critical care. For the primary outcome of acute hospital mortality, our parsimonious risk model consisting of eight variables had an area under the receiver operating characteristic of 0.96 (95% CI, 0.91-1.00); these variables are commonly available for all maternal admissions. For the secondary composite outcome of death or ICU length of stay greater than 48 hours, the risk model consisting of 17 variables had an area under the receiver operating characteristic of 0.80 (95% CI, 0.78-0.83). CONCLUSIONS: We developed risk prediction models specific to the maternal critical care population. The models compare favorably against general adult ICU risk prediction models in current use within this population.

Compartmentalisation of the inflammatory response following aneurysmal subarachnoid haemorrhage.

INTRODUCTION: There is some evidence to suggest that a systemic and central nervous system (CNS) inflammatory response occurs following aneurysmal subarachnoid haemorrhage (aSAH) which may be related to the pathophysiology of early brain injury and delayed ischaemic neurological deficit (DIND). The aim of this study was to measure inflammatory mediator levels in plasma and cerebrospinal fluid (CSF) in the days following aSAH and to determine their association with aSAH, DIND and clinical outcome. MATERIAL AND METHODS: Plasma and CSF samples were obtained prospectively from patients with aSAH on days 1-3, 5, 7 and 9 and profiled for interleukin (IL)-1α, IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-15, IL-17, IL-18, macrophage chemotactic protein (MCP)-1, vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF)-α. Plasma and CSF samples from non-aSAH patients undergoing spinal anaesthesia were used as controls. RESULTS: The CSF levels of all cytokines investigated except for IL-1α were significantly higher in aSAH compared to controls in the first seven days of ictus. CSF levels of IL-1α (p = 0.014), IL-18 (p = 0.016), IL-6 (p = 0.0006) and IL-8 (p = 0.006) showed significant increases in the days following aSAH. Conversely IL-17 demonstrated a decrease. In particular, IL-4 was higher in the CSF of patients who had DIND at all time-points (p = 0.032). Plasma IL-6 and IL-8 levels were higher, and IL-1α levels lower, than controls at most time-points. All mediators demonstrated persistent elevation in the CSF compared to plasma apart from IL-1α and IL-18 which followed the opposite trend. Day 3 plasma IL-6 levels predicted poor outcome at six months (Exp(B) 1.12 1.03-1.22, P = 0.012), although this association was lost in the second analysis incorporating Fisher grade, WFNS grade and age. CONCLUSION: The post aSAH inflammatory response peaks on days 5-7 post ictus and remains largely compartmentalised within the CNS. IL-4 may have a particular association with DIND although its precise role in the pathophysiology of the disorder remains unclear. IL-6 predicted poor outcome but not independently of clinical grade, suggesting that it may be a surrogate marker of early brain injury.

Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage: a prospective, randomized, controlled trial (LUMAS).

BACKGROUND AND PURPOSE: A single-center prospective randomized controlled trial has been conducted to determine if lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage reduces the prevalence of delayed ischemic neurological deficit and improves clinical outcome. METHODS: Patients with World Federation of Neurological Surgeons Grade 1 to 3 aneurysmal subarachnoid hemorrhage and modified Fisher Grades 2, 3, 4, and 3+4 were randomized to either the study group of standard therapy plus insertion of a lumbar drain or the control group of standard therapy alone. The primary outcome measure was the prevalence of delayed ischemic neurological deficit. RESULTS: Two hundred ten patients with aneurysmal subarachnoid hemorrhage (166 female, 44 male; median age, 54 years; interquartile range, 45-62 years) were recruited into the control (n=105) and study (n=105) groups of the trial. World Federation of Neurological Surgeons grade was: 1 (n=139), 2 (n=60), and 3 (n=11); Fisher grade was: 2 (n=87), 3 (n=85), and 4 (n=38). The prevalence of delayed ischemic neurological deficit was 35.2% and 21.0% in the control and study groups, respectively (P=0.021). The prevalence of a modified Rankin Scale score of 4, 5, or 6 at Day 10 and 6 months, respectively, was 62.5% and 18.6% in the control group and 44.8% and 19.8% in the study group (P=0.009 and 0.83, respectively). CONCLUSIONS: Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage has been shown to reduce the prevalence of delayed ischemic neurological deficit and improve early clinical outcome but failed to improve outcome at 6 months after aneurysmal subarachnoid hemorrhage. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00842049.

Self-perceived health status following aneurysmal subarachnoid haemorrhage: a cohort study.

OBJECTIVE: 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. DESIGN: A two-cohort study. SETTING: A regional tertiary neurosurgical centre. PARTICIPANTS: 2 cohorts of patients with ASAH treated between 1998 and 2008 and followed up at approximately 1 year. INTERVENTIONS: Routine care. PRIMARY AND SECONDARY OUTCOMES: 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. RESULTS: 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 approximately 90% of aneurysms of the anterior circulation. Of those previously in full or part-time employment, 48.9% were unemployed at follow-up. All summated scales satisfied the Rasch measurement model requirements, such that their summed scores were a sufficient statistic. Given this, one-third of patients were noted to have a significant mood disorder and 25% had significant dysexecutive function. Patients with an MRS of 3, 4 or 5 had significantly worse scores on most outcome measures, but a significant minority of those with a score of zero had failed to return to work and displayed significant mood disorder. CONCLUSIONS: A range of self-reported cognitive and physical deficits have been highlighted in a cohort of patients with ASAH. While the MRS has been shown to provide a reasonable indication of outcome, in routine clinical follow-up it requires supplementation by instruments assessing dysexecutive function, memory and mood.

A review of delayed ischemic neurologic deficit following aneurysmal subarachnoid hemorrhage: historical overview, current treatment, and pathophysiology.

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, microthrombosis, inflammation, apoptosis, spreading depolarization, oxidative stress) and to present the evidence underlying current treatment strategies (hemodynamic therapy, oral nimodipine, endovascular therapy, statins, cerebrospinal fluid drainage, thrombolysis, magnesium) and the translational and clinical research investigating DIND.

A comparison of the outcome of aneurysmal subarachnoid haemorrhage before and after the introduction of an endovascular service.

There has been a rapid change from predominantly surgical to endovascular treatment of ruptured intracranial aneurysms giving the opportunity to assess change in patient outcome during this transition. We identified and followed 139 patients with subarachnoid haemorrhage (SAH) treated in the year prior to (group 1) and following (group 2) the introduction of an endovascular service in a retrospective, cross-sectional study. A total of 78.7% of patients in group 1 underwent surgical treatment, 10.7% underwent endovascular treatment and 10.7% received no treatment, whereas patients in group 2 received 29.7%, 65.7% and 4.7%, respectively. MRS scores were obtained in 91% of patients in group 1 and in 89% of patients in group 2. A total of 30.7% and 24.0% of patients had a poor outcome in groups 1 and 2 respectively (p=0.34). The overall change in the management of ruptured cerebral aneurysms in the post-International Subarachnoid Aneurysm Trial (ISAT) era has not significantly changed cross-sectional outcome, although absolute differences appear to reflect difference in outcome noted in the ISAT.