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Background: Hypertension induction (HTI) is often used for treating delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH); however, high‐quality studies on its efficacy are lacking. We studied immediate and 3−/6‐month clinical efficacy of HTI in aSAH patients with clinical DCI. Methods: A retrospective, multicenter, comparative, observational cohort study in aSAH patients with clinical deterioration due to DCI, admitted to three tertiary referral hospitals in the Netherlands from 2015 to 2019. Two hospitals used a strategy of HTI (HTI group) and one hospital had no such strategy (control group). We calculated adjusted relative risks (aRR) using Poisson regression analyses for the two primary (clinical improvement of DCI symptoms at days 1 and 5 after DCI onset) and secondary outcomes (DCI‐related cerebral infarction, in‐hospital mortality, and poor clinical outcome [modified Rankin Scale 4–6] assessed at 3 or 6 months), using the intention‐to‐treat principle. We also performed as‐treated and per‐protocol analyses. Results: The aRR for clinical improvement on day 1 after DCI in the HTI group was 1.63 (95% CI 1.17–2.27) and at day 5 after DCI 1.04 (95% CI 0.84–1.29). Secondary outcomes were comparable between the groups. The as‐treated and per‐protocol analyses yielded similar results. Conclusions: No clinical benefit of HTI is observed 5 days after DCI due to spontaneous reversal of DCI symptoms in patients treated without HTI. The 3−/6‐month clinical outcome was similar for both groups. Therefore, these data suggest that one may consider to not apply HTI in aSAH patients with clinical DCI. [ABSTRACT FROM AUTHOR]

Delayed cerebral ischemia (DCI) substantially contributes to disability and death in subarachnoid hemorrhage (SAH) patients; however, its pathophysiology is incompletely understood and diagnostic and therapeutic strategies are lacking. Biomarkers may help to elucidate the pathophysiology, optimize early diagnosis, or provide treatment targets. We systematically searched PubMed and Embase on October 13, 2021, for studies that evaluated at least one laboratory biomarker in patients with DCI, using the most up-to-date definition of DCI as proposed by a panel of experts in 2010. Quality of studies was assessed using the Newcastle-Ottawa Scale or Cochrane Collaboration's risk of bias assessment tool. Biomarkers of clinical and radiological DCI were analyzed separately. Results were meta-analyzed if possible, otherwise narratively reviewed. Biomarkers were classified as significant, inconclusive, or nonsignificant. We defined validated biomarkers as those with significant results in metaanalyses, or in at least two studies using similar methodologies within the same time interval after SAH. The search yielded 209 articles with 724 different biomarkers; 166 studies evaluated 646 biomarkers of clinical DCI, of which 141 were significant and 7 were validated biomarkers (haptoglobulin 2-1 and 2-2, ADAMTS13, vWF, NLR, P-selectin, F2-isoprostane); 78 studies evaluated 165 biomarkers of radiological DCI, of which 63 were significant and 1 was a validated biomarker (LPR). Hence, this review provides a selection of seven biomarkers of clinical DCI and one biomarker of radiological DCI as most promising biomarkers of DCI. Future research should focus on determining the exact predictive, diagnostic, and therapeutic potentials of these biomarkers. [ABSTRACT FROM AUTHOR]

Background: Our randomized clinical trial on induced hypertension in patients with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) was halted prematurely due to unexpected slow recruitment rates. This raised new questions regarding recruitment feasibility. As our trial can therefore be seen as a feasibility trial, we assessed the reasons for the slow recruitment, aiming to facilitate the design of future randomized trials in aSAH patients with DCI or other critically ill patient categories. Methods: Efficiency of recruitment and factors influencing recruitment were evaluated, based on the patient flow in the two centers that admitted most patients during the study period. We collected numbers of patients who were screened for eligibility, provided informed consent, and developed DCI and who eventually were randomized. Results: Of the 862 aSAH patients admitted in the two centers during the course of the trial, 479 (56%) were eligible for trial participation of whom 404 (84%) were asked for informed consent. Of these, 188 (47%) provided informed consent, of whom 50 (27%) developed DCI. Of these 50 patients, 12 (24%) could not be randomized due to a logistic problem or a contraindication for induced hypertension emerging at the time of randomization, and four (8%) were missed for randomization. Eventually, 34 patients were randomized and received intervention or control treatment. Conclusions: Enrolling patients in a randomized trial on a treatment strategy for DCI proved unfeasible: only 1 out of 25 admitted and 1 out of 14 eligible patients could eventually be randomized. These rates, caused by a large proportion of ineligible patients, a small proportion of patients providing informed consent, and a large proportion of patients with contraindications for treatment, can be used to make sample size calculations for future randomized trials in DCI or otherwise critically ill patients. Facilitating informed consent through improved provision of information on risks, possible benefits, and study procedures may result in improved enrolment. Trial registration: The original trial was prospectively registered with ClinicalTrials.gov (NCT01613235), date of registration 07-06-2012. [ABSTRACT FROM AUTHOR]

Background: Literature is inconclusive regarding the association between antiplatelet agents use and outcome after aneurysmal subarachnoid hemorrhage. Aims: To investigate the association between clinical outcome and prehemorrhage use in aneurysmal subarachnoid hemorrhage patients as well as the impact of thrombocyte transfusion on rebleed and clinical outcome. Methods: Data were collected from prospective databases of two European tertiary reference centers for aneurysmal subarachnoid hemorrhage patients. Patients were divided into "antiplatelet-user" and "non-user" according to the use of acetylsalicylic acid prior to the hemorrhage. Primary outcome was poor clinical outcome at six months (Glasgow Outcome Scale score 1–3). Secondary outcomes were in-hospital mortality and impact of thrombocyte transfusion. Results: Of the 1033 patients, 161 (15.6%) were antiplatelet users. The antiplatelet users were older with higher incidence of cardiovascular risk factors. Antiplatelet use was associated with poor outcome and in-hospital mortality. After correction for age, sex, World Federation of Neurosurgical Societies score, infarction and heart disorder, pre-hemorrhage acetylsalicylic acid use was only associated with poor clinical outcome at six months (adjusted OR 1.80, 95% CI 1.08–3.02). Thrombocyte transfusion was not associated with a reduction in rebleed or poor clinical outcome. Conclusion: In this multicenter study, the prehemorrhage acetylsalicylic acid use in aneurysmal subarachnoid hemorrhage patients was independently associated with poor clinical outcome at six months. Thrombocyte transfusion was not associated with the rebleed rate or poor clinical outcome at six months. [ABSTRACT FROM AUTHOR]

Background Patients with World Federation of Neurosurgical Societies (WFNS) grade V subarachnoid hemorrhage (SAH) mostly have a poor outcome. Correct identification of patients who might benefit from treatment remains challenging. We investigated which disease-related characteristics, present at admission, could identify patients with chance of good outcome. Methods In total, 146 consecutive patients with WFNS grade V SAH (2002–2013) were included. Demographic and disease-related characteristics were compared between patients with a good outcome (Glasgow Outcome Scale 4 and 5) and a poor outcome (Glasgow Outcome Scale 1-3). Subgroups were made of patients with aneurysm treatment according to outcome; 1) good outcome; 2) poor outcome, with optimal general treatment; and 3) poor outcome, general treatment discontinued. Results In total, 34 of the 146 patients had a good outcome (36% of all treated patients); 16 (47%) of these presented with a Glasgow Coma Scale score of 3, versus 65 (58%) of patients with a poor outcome (P = 0.33). Eleven (33%) patients in the good outcome group presented with pupillary abnormalities; 4 (12%) even had bilaterally fixed and dilated pupils, versus 49 (46%) in patients with a poor outcome (P < 0.01). In 51 patients, the aneurysm was not treated; all died. Conclusions More than one third of all treated patients with WFNS grade V SAH had a good outcome. All patients in whom the aneurysm was not treated died. Reliable identification of patients who will reach good outcome, on the basis of symptoms on admission, seems impossible, as these symptoms are not discriminating enough. Highlights • More than one third of patients with aggressively treated WFNS grade V SAH reach a good outcome. • Almost one half of the WFNS grade V patients with a good outcome present with a GCS 3. • Twelve percent of the patients with a good outcome presented with bilateral fixed and dilated pupils. • Reliable identification of patients who will reach a good outcome is challenging. [ABSTRACT FROM AUTHOR]

Purpose: Decompressive craniectomy (DC) has been proposed as lifesaving treatment in aneurysmal subarachnoid haemorrhage (aSAH) patients with elevated intracranial pressure (ICP). However, data is sparse and controversy exists whether the underlying cause of elevated ICP influences neurological outcome. The purpose of this study is to clarify the role of the underlying cause of elevated ICP on outcome after DC. Materials and methods: We retrospectively studied the one-year neurological outcome in a single-centre cohort to identify predictors of favourable (Glasgow Outcome Scale (GOS) 4-5) and unfavourable (GOS 1-3) outcome. Additionally, available individual patient data in the literature was reviewed with a special emphasis on the underlying reason for DC. Results: From 2006-2015, 53 consecutive aSAH patients underwent DC. Nine (17%) achieved favourable, 44 (83%) unfavourable outcome (31 patients died). One fourth of the patients undergoing DC for hematoma or (hematoma-related) oedema survived favourably (increasing to 46% for patients aged <51 years), versus none of the patients undergoing DC for secondary infarction. Analysis of individual data of 105 literature patients showed a similar trend, although overall outcome was much better: half of the patients undergoing DC for hematoma/oedema regained independence, versus less than one-fourth of patients undergoing DC for secondary infarction. Conclusions: DC in aSAH patients is associated with high rates of unfavourable outcome and mortality, but hematoma or oedema as underlying reason for DC is associated with better outcome profiles compared to secondary infarction. Future observational cohort studies are needed to further explore the different outcome profiles among subpopulations of aSAH patients requiring DC. [ABSTRACT FROM AUTHOR]

In the management of aneurysmal subarachnoid hemorrhage (aSAH), aneurysm treatment as early as feasible is mandatory to minimize the risk of a rebleed and may thus improve outcome. We assessed the different time intervals from the first symptoms of aSAH to start of aneurysm treatment in an effort to identify which factors contribute mostly to a delay in time to treatment. In 278 aSAH patients, time intervals between the different steps from initial hemorrhage to aneurysm treatment were retrospectively reviewed, and delaying factors were determined. Half of the patients presented to a hospital within 115 min (IQR 60-431). The median (IQR) interval from hemorrhage to diagnosis was 169 min (96-513), and from diagnosis to treatment 1,057 min (416-1,428), or 17.6 h. Aneurysm treatment started within 24 h in 76 % of treated patients. Independent factors predicting delay to treatment were primary presentation at a referring hospital and admission to the treatment center later in the day. Delay in treatment was not independently related to poor outcome. The interval to aneurysm treatment might be improved upon by immediate and direct transport to the treatment center combined with optimization of in-hospital logistics, following the 'time-is-brain' concept so successfully adopted in the treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

From a pathophysiological point of view, early neurosurgical treatment seems essential to prevent secondary brain injury and has been stated as the "time-is-brain" concept. However, the question immediately rises: "Is there an optimal time window for acute intracranial neurosurgical interventions?" In neurosurgery, treatment modality has been studied far more extensively than timing to surgery ("time-to-surgery"). The majority of acute intracranial neurosurgical interventions are carried out for traumatic brain injury and hemorrhagic or ischemic stroke. Current guidelines for traumatic brain injury, spontaneous intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage, and middle cerebral artery infarction are reviewed and lessons learned from the randomized controlled trials mentioned are discussed. In acute intracranial neurosurgical interventions, "delayed consent" procedures could play an important role for this field of research. Whether there is an optimal time window for acute intracranial neurosurgical interventions seems difficult to be answered with randomized controlled trials referred to in the current guidelines. Observational designs, such as comparative effectiveness research, and special statistical techniques, may provide a better understanding in the optimal "time-to-surgery." [ABSTRACT FROM AUTHOR]

Objective Since 2009, we have performed skin augmentation using a Gore-Tex patch as a last-resort measure to reduce intracranial pressure (ICP) in uncontrollable brain swelling during decompressive craniectomy (DC). Here, we report our experience and outcome in a consecutive series of patients undergoing DC with skin augmentation (DC+S). Methods In 2009–2015, a prospective database was created registering all patients who underwent DC+S when ICP increased >25 mm Hg while approximating the skin edges after DC (or when closing the skin was impossible because of uncontrollable brain swelling in patients without an ICP monitoring catheter). Patients' baseline characteristics and 1-year outcome were compared with patients undergoing DC without the need of skin augmentation in the same time frame. Outcome according to the Glasgow Outcome Scale (GOS) was dichotomized into favorable (GOS score 4–5) and unfavorable (GOS 1–3). Results Of a total of 180 consecutive patients with DC, 20 (11%) underwent DC+S. Four (20%) survived favorably, 2 (10%) unfavorably, and 14 (70%) died (compared with 36%, 22%, and 42%, respectively, in patients with standard DC). Four of 7 patients in whom DC+S was performed ≥24 hours after injury or at second surgery survived favorably, versus none of the 13 patients in whom DC+S was performed <24 hours after injury and at first surgery. Two of 10 patients surviving the first week after DC+S had a skinplasty-related infection. Conclusions Decompressive craniectomy with skin augmentation may be used as a last-resort measure in cases of severe brain swelling despite DC. Highlights • Brain swelling after decompressive craniectomy may hamper skin closure. • Skin augmentation may be used as a last-resort measure in severe brain swelling. • A favorable outcome is possible when primary skin closure is not possible. [ABSTRACT FROM AUTHOR]