Prompt closure versus gradual weaning of external ventricular drainage for hydrocephalus following aneurysmal subarachnoid haemorrhage: Protocol for the DRAIN randomised clinical trial

Background: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening disease caused by rupture of an intracranial aneurysm. A common complication following aSAH is hydrocephalus, for which placement of an external ventricular drain (EVD) is an important first-line treatment. Once the patient is clinically stable, the EVD is either removed or replaced by a ventriculoperitoneal shunt. The optimal strategy for cessation of EVD treatment is, however, unknown. Gradual weaning may increase the risk of EVD-related infection, whereas prompt closure carries a risk of acute hydrocephalus and redundant shunt implantations. We designed a randomised clinical trial comparing the two commonly used strategies for cessation of EVD treatment in patients with aSAH. Methods: DRAIN is an international multi-centre randomised clinical trial with a parallel group design comparing gradual weaning versus prompt closure of EVD treatment in patients with aSAH. Participants are randomised to either gradual weaning which comprises a multi-step increase of resistance over days, or prompt closure of the EVD. The primary outcome is a composite outcome of VP-shunt implantation, all-cause mortality, or ventriculostomy-related infection. Secondary outcomes are serious adverse events excluding mortality, functional outcome (modified Rankin scale), health-related quality of life (EQ-5D) and Fatigue Severity Scale (FSS). Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, type I error 5%, power 80%), 122 patients are needed in each intervention group. Outcome assessment for the primary outcome, statistical analyses and conclusion drawing will be blinded

The effect of baseline pressure errors on an intracranial pressure-derived index: results of a prospective observational study

Background In order to characterize the intracranial pressure-volume reserve capacity, the correlation coefficient (R) between the ICP wave amplitude (A) and the mean ICP level (P), the RAP index, has been used to improve the diagnostic value of ICP monitoring. Baseline pressure errors (BPEs), caused by spontaneous shifts or drifts in baseline pressure, cause erroneous readings of mean ICP. Consequently, BPEs could also affect ICP indices such as the RAP where in the mean ICP is incorporated. Methods A prospective, observational study was carried out on patients with aneurysmal subarachnoid hemorrhage (aSAH) undergoing ICP monitoring as part of their surveillance. Via the same burr hole in the scull, two separate ICP sensors were placed close to each other. For each consecutive 6-sec time window, the dynamic mean ICP wave amplitude (MWA; measure of the amplitude of the single pressure waves) and the static mean ICP, were computed. The RAP index was computed as the Pearson correlation coefficient between the MWA and the mean ICP for 40 6-sec time windows, i.e. every subsequent 4-min period (method 1). We compared this approach with a method of calculating RAP using a 4-min moving window updated every 6 seconds (method 2). Results The study included 16 aSAH patients. We compared 43,653 4-min RAP observations of signals 1 and 2 (method 1), and 1,727,000 6-sec RAP observations (method 2). The two methods of calculating RAP produced similar results. Differences in RAP ≥0.4 in at least 7% of observations were seen in 5/16 (31%) patients. Moreover, the combination of a RAP of ≥0.6 in one signal and 0.2 was significantly associated with the frequency of BPEs (5 mmHg ≤ BPE <10 mmHg). Conclusions Simultaneous monitoring from two separate, close-by ICP sensors reveals significant differences in RAP that correspond to the occurrence of BPEs. As differences in RAP are of magnitudes that may alter patient management, we do not advocate the use of RAP in the management of neurosurgical patients

Timelines and rebleeds in patients admitted into neurosurgical care for aneurysmal subarachnoid haemorrhage

Abstract Background Mortality and morbidity of aneurysmal subarachnoid haemorrhage (aSAH) remain high, and prognosis is influenced by multiple non-modifiable factors such as aSAH severity. By analysing the chronology of aSAH management, we aim at identifying modifiable factors with emphasis on the occurrence of rebleeds in a setting with 24/7 surgical and endovascular availability of aneurysm repair and routine administration of tranexamic acid. Methods Retrospective analysis of institutional quality registry data of aSAH cases admitted into neurosurgical care during the time period 01 January 2013–31 December 2017. We registered time and mode of aneurysm repair, haemorrhage patterns, course of treatment, mortality and functional outcome. Rebleeding was scored along the entire timeline from ictus to discharge from the primary stay. Results We included 544 patients (368, 67.6% female), aged 58 ± 14 years (range 1–95 years). Aneurysm repair was performed in 486/544 (89.3%) patients at median 7.4 h after arrival and within 3, 6, 12 and 24 h in 26.8%, 44.7%, 73.0% and 96.1%, respectively. There were circadian variations in time to repair and in rebleeds. Rebleeding prior to aneurysm repair occurred in 9.7% and increased with aSAH severity and often in conjunction with patient relocations or interventions. Rebleeds occurred more often during surgical repair outside regular working hours, whereas rebleeds after repair (1.8%) were linked to endovascular repair. Conclusions The risk of rebleed is imminent throughout the entire timeline of aSAH management even with ultra-early aneurysm repair. Several modifiable factors can be linked to the occurrence of rebleeds and they should be identified and optimised within neurosurgical departments

The effect of tracheotomy on drug consumption in patients with acute aneurysmal subarachnoid hemorrhage: an observational study

Background Patients with aneurysmal subarachnoid hemorrhage (aSAH) are common in intensive care units (ICU). In patients with aSAH, sedation is used as a neuroprotective measure in order to secure adequate cerebral perfusion pressure (CPP). Compared with the use of an endotracheal tube, a tracheotomy has the advantage of securing the airway at a much lower level of distress, and aSAH patients can often be awakened more rapidly. Little is known about the impact of tracheotomy on the consumption of sedative/analgesic and vasoactive drugs and the maintenance of CPP within defined limits in aSAH patients. Methods We conducted an observational study of aSAH patients who underwent percutaneous tracheotomy. A prospective registry of patient data was supplemented with retrospective retrievals from medical records. Sedative, analgesic and vasoactive drug doses were registered for 3 days prior to and after percutaneous tracheotomy, respectively. Blood pressure, CPP, and the mode of mechanical ventilation were registered 24 h prior to and after tracheotomy. Results Between January 2001 and June 2009, 902 aSAH patients were admitted to our hospital; 74 (8%) were deeply comatose/dying upon arrival. The ruptured aneurysm was repaired in 828 patients (surgical repair 50%) and percutaneous tracheotomy was performed 182 times in 178 patients (59 men and 119 women). This subpopulation (178 of 828 patients) was significantly older (56 vs. 53 years) and presented with a more severe Hunt & Hess grade (p < 0.001). Percutaneous tracheotomy caused a marked decline in mean daily consumption of the analgesics/sedatives fentanyl, midazolam, and propofol, as well as the vasoactive drugs noradrenaline and dopamine. These declines were statistically and clinically significant. The mean CPP was 76 mmHg (SD 8.6) the day before and 79 mmHg (SD 9.6) 24 h after percutaneous tracheotomy. After percutaneous tracheotomy, mechanical ventilatory support could be reduced to a patient-controlled ventilatory support mode in a significant number of patients (p < 0.001). Conclusions Percutaneous tracheotomy in aSAH patients is a swift procedure with low risk that is associated with a significant decline in the consumption of sedative/analgesic and vasoactive drugs while clinical surveillance parameters remain stable or improve

Survival and outcome in patients with aneurysmal subarachnoid hemorrhage in Glasgow coma score 3–5

Background Outcome of early, aggressive management of aneurysmal subarachnoid hemorrhage (aSAH) in patients with Hunt and Hess grade V is hitherto limited, and we therefore present our results. Methods Retrospective study analyzing the medical data of 228 aSAH patients in Glasgow Coma Score 3–5 admitted to our hospital during the years 2002–2012. Background and treatment variables were registered. Outcome was evaluated after 3 and 12 months. Results We intended to treat 176 (77.2%) patients, but only 146 went on to aneurysm repair. Of 52 patients managed conservatively, 27 had abolished cerebral circulation around arrival and 25 were deemed unsalvageable. One-year overall mortality was 65.8% and most (84.7%) of the fatalities occurred within 30 days. One-year mortality was higher in patients > 70 years. Without aneurysm repair, mortality was 100%. After 1 year, 21.9% of all patients lived independently and 4.8% lived permanently in an institution. Outcome in the 78 survivors (34.2%) was favorable in 64.1% in terms of modified Rankin Scale score 0–2, and 85.9% of survivors were able to live at home. Return to work was low for all 228 patients with 14.0% of those employed prior to the hemorrhage having returned to paid work, and respectively, 26.3% in the subgroup of survivors. Conclusions Even with aggressive, early treatment, 1-year mortality is high in comatose aSAH patients with 65.8%. A substantial portion of the survivors have a favorable outcome at 1 year (64.1%, corresponding to 21.9% of all patients admitted) and 85.9% of the survivors could live at home alone or aided

(-)-OSU6162 in the treatment of fatigue and other sequelae after aneurysmal subarachnoid hemorrhage: a double-blind, randomized, placebo-controlled study

OBJECTIVE Fatigue after aneurysmal subarachnoid hemorrhage (aSAH) is common and usually long-lasting, and it has a considerable negative impact on health-related quality of life (HRQOL), social functioning, and the ability to return to work (RTW). No effective treatment exists. The dopaminergic regulator (−)-OSU6162 has shown promising results regarding the mitigation of fatigue in various neurological diseases, and therefore the authors aimed to investigate the efficacy of (−)-OSU6162 in alleviating fatigue and other sequelae after aSAH. METHODS A double-blind, randomized, placebo-controlled, single-center trial was performed in which 96 participants with post-aSAH fatigue were administered 30–60 mg/day of (−)-OSU6162 or placebo over a period of 12 weeks. Efficacy was assessed using the Fatigue Severity Scale (FSS), the Mental Fatigue Scale (MFS), the Beck Anxiety Inventory (BAI), the Beck Depression Inventory II (BDI-II), the SF-36 questionnaire, and a neuropsychological test battery. Assessments were performed at baseline, after 1, 4, 8, and 12 weeks of treatment, and at follow-up, 8 weeks after treatment. RESULTS The 96 participants with post-aSAH fatigue were randomized to treatment with (−)-OSU6162 (n = 49) or placebo (n = 47). The FSS, MFS, and BDI scores improved significantly in both groups after 12 weeks of treatment, whereas the BAI scores improved in the placebo group only. HRQOL improved significantly in the SF-36 domain “Vitality” in both groups. Neuropsychological test performances were within the normal range at baseline and not affected by treatment. The FSS score was distinctly improved in patients with complete RTW upon treatment with (−)-OSU6162. Concomitant use of antidepressants improved the efficacy of (−)-OSU6162 on the FSS score at week 1 beyond the placebo response, and correspondingly the use of beta- or calcium-channel blockers improved the (−)-OSU6162 efficacy beyond the placebo response in MFS scores at week 4 of treatment. There was a significant correlation between improvement in FSS, BAI, and BDI scores and the plasma concentration of (−)-OSU6162 at the dose of 60 mg/day. No serious adverse events were attributable to the treatment, but dizziness was reported more often in the (−)-OSU6162 group. CONCLUSIONS Fatigue and other sequelae after aSAH were similarly alleviated by treatment with (−)-OSU6162 and placebo. (−)-OSU6162 improved fatigue, as measured with the FSS score, significantly in patients with complete RTW. There seemed to be synergetic effects of (−)-OSU6162 and medications interfering with dopaminergic pathways that should be explored further. The strong placebo response may be exploited in developing nonpharmacological treatment programs for post-aSAH fatigue

Fatigue after aneurysmal subarachnoid hemorrhage: Clinical characteristics and associated factors in patients with good outcome

Fatigue after aneurysmal subarachnoid hemorrhage (post-aSAH fatigue) is a frequent, often long-lasting, but still poorly studied sequel. The aim of the present study was to characterize the nature of post-aSAH fatigue with an itemized analysis of the Fatigue Severity Scale (FSS) and Mental Fatigue Scale (MFS). We further wanted to assess the association of fatigue with other commonly observed problems after aSAH: mood disorders, cognitive problems, health-related quality of life (HRQoL), weight gain, and return to work (RTW). Ninety-six good outcome aSAH patients with fatigue completed questionnaires measuring fatigue, depression, anxiety, and HRQoL. All patients underwent a physical and neurological examination. Cognitive functioning was assessed with a neuropsychological test battery. We also registered prior history of fatigue and mood disorders as well as occupational status and RTW. The patients experienced fatigue as being among their three most disabling symptoms and when characterizing their fatigue they emphasized the questionnaire items “low motivation,” “mental fatigue,” and “sensitivity to stress.” Fatigue due to exercise was their least bothersome aspect of fatigue and weight gain was associated with depressive symptoms rather than the severity of fatigue. Although there was a strong association between fatigue and mood disorders, especially for depression, the overlap was incomplete. Post-aSAH fatigue related to reduced HRQoL. RTW was remarkably low with only 10.3% of patients returning to their previous workload. Fatigue was not related to cognitive functioning or neurological status. Although there was a strong association between fatigue and depression, the incomplete overlap supports the notion of these two being distinct constructs. Moreover, post-aSAH fatigue can exist without significant neurological or cognitive impairments, but is related to reduced HRQoL and contributes to the low rate of RTW

Impact of smoking on course and outcome of aneurysmal subarachnoid hemorrhage

Abstract Background While the smoking-related risk of experiencing an aneurysmal subarachnoid hemorrhage (aSAH) is well established, it remains unclear whether smoking has an unexpected “protective effect” in aSAH, or if smokers are more at risk for complications and poor outcomes. Methods Prospective, observational study investigating the course and outcome of aSAH in patients admitted during the years 2011 and 2012. Smoking status at admittance, demographic, medical, and radiological variables were registered along with management, complications, and outcome at 1 year in terms of mortality, modified Rankin score, and Glasgow outcome score extended. We compared current smokers with nonsmokers on group level and by paired analysis matched by aSAH severity, age, and severity of vasospasm. Results We included 237 patients, thereof 138 current smokers (58.2%). Seventy-four smoker/nonsmoker pairs were matched. Smokers presented more often in poor clinical grade, had less subarachnoid blood, and were younger than nonsmokers. Ruptured aneurysms were larger, and multiple aneurysms more common in smokers. Severe multi-vessel vasospasm was less frequent in smokers, whereas all other complications occurred at similar rates. Mortality at 30 days was lower in smokers and functional outcome was similar in smokers and nonsmokers. Poor clinical grade, age, cerebral infarction, and vertebrobasilar aneurysms were independent predictors of 1-year mortality and of poor functional outcome. Serious comorbidity was a predictor of 1-year mortality. Smoking did not predict mortality or poor functional outcome. Conclusions Notwithstanding clinically more severe aSAH, smokers developed less frequently severe vasospasm and had better outcome than expected. The risk for complications after aSAH is not increased in smokers

Effect of early mobilization and rehabilitation on complications in aneurysmal subarachnoid hemorrhage

OBJECTIVE: Early rehabilitation is effective in an array of acute neurological disorders but it is not established as part of treatment guidelines after aneurysmal subarachnoid hemorrhage (aSAH). This may in part be due to the fear of aggravating the development of cerebral vasospasm, which is the most feared complication of aSAH. The aim of this study was to evaluate the effect of early rehabilitation and mobilization on complications during the acute phase and within 90 days after aSAH. METHODS: This was a prospective, interventional study that included patients with aSAH at the neuro-intermediate ward after aneurysm repair. The control group received standard treatment, whereas the early rehab group underwent early rehabilitation and mobilization in addition to standard treatment. Clinical and radiological characteristics of patients with aSAH, progression in mobilization, and treatment variables were registered. The frequency and severity of cerebral vasospasm, cerebral infarction acquired in conjunction with the aSAH, and acute and chronic hydrocephalus, as well as pulmonary and thromboembolic complications, were compared between the 2 groups. RESULTS: Clinical and radiological characteristics of patients with aSAH were similar between the groups. The early rehab group was mobilized beginning on the first day after aneurysm repair. The significantly quicker and higher degree of mobilization in the early rehab group did not increase complications. Clinical cerebral vasospasm was not as frequent in the early rehab group and it also tended to be less severe. Each step of mobilization achieved during the first 4 days after aneurysm repair reduced the risk of severe vasospasm by 30%. Acute and chronic hydrocephalus were similar in both groups, but there was a tendency toward earlier shunt implantation among patients in the control group. Pulmonary infections, thromboembolic events, and death before discharge or within 90 days after the ictus were similar between the 2 groups. CONCLUSIONS: Early rehabilitation of patients after aSAH is safe and feasible. The earlier and higher degree of mobilization does not increase neurosurgical complications. Rather, the frequency and severity of cerebral vasospasm following aSAH are alleviated and are not aggravated by early rehabilitation. © 2017 American Association of Neurological Surgeon