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Objective: To describe the effects of balanced solution use on the short-term outcomes of patients with traumatic brain injury enrolled in BaSICS trial. Methods: Patients were randomized to receive either 0.9% saline or balanced solution during their intensive care unit stay. The primary endpoint was 90-day mortality, and the secondary outcomes were days alive and free of intensive care unit stay at 28 days. The primary endpoint was assessed using Bayesian logistic regression. The secondary endpoint was assessed using a Bayesian zero-inflated beta binomial regression. Results: We included 483 patients (236 in the 0.9% saline arm and 247 in the balanced solution arm). A total of 338 patients (70%) with a Glasgow coma scale score ≤ 12 were enrolled. The overall probability that balanced solutions were associated with higher 90-day mortality was 0.98 (OR 1.48; 95%CrI 1.04 - 2.09); this mortality increment was particularly noticeable in patients with a Glasgow coma scale score below 6 at enrollment (probability of harm of 0.99). Balanced solutions were associated with -1.64 days alive and free of intensive care unit at 28 days (95%CrI -3.32 - 0.00) with a probability of harm of 0.97. Conclusion: There was a high probability that balanced solutions were associated with high 90-day mortality and fewer days alive and free of intensive care units at 28 days.

Rationale: Coated devices may reduce biofilm formation and reduce the occurrence of device-related infections in critically ill patients. A bundle of coated devices (an endotracheal tube [ETT], central venous catheter [CVC], and urinary catheter [UC]) simultaneously inserted may optimize benefits of coated devices in patients with the most severe illness. Objectives: To assess the feasibility of a randomized controlled trial on simultaneous insertion of gold/silver/palladium-coated devices versus uncoated devices in severely ill patients, which required sequential insertion of all three devices (an ETT, CVC, and UC) for support in the intensive care unit (ICU). Methods: This was a multicenter randomized controlled pilot trial. Patients who required simultaneous insertion of an ETT, CVC, and UC were randomized to treatment with coated versus uncoated devices, which were used as necessary for up to 28 days. The primary endpoint was feasibility, defined as the trial being able to enroll enough participants to have the sample size necessary for its secondary primary endpoint (estimating sepsis incidence in this population) in less than 1 year and for estimating the number of admitted patients who require simultaneous insertion of all three devices. Secondary endpoints included the incidence of sepsis and device-associated infections (ventilator-associated pneumonia, catheter-related bloodstream infection, and catheter-related urinary-tract infection) within each group as well as the number of days alive and free of antibiotics during the ICU stay. All events were adjudicated. Results: One hundred and three patients (48 in the coated-device group and 55 in the uncoated-device group) were included in the perprotocol analysis. The inclusion period was 8 months. There were 13 septic events in each group (26 in total), with an approximate incidence of sepsis of 32.3 (95% credible interval [CrI], 22.4-44.9) per 100 patient-days. The overall incidences of ventilator-associated pneumonia, catheter-related urinary-tract infection, and catheterrelated bloodstream infection were 15.2 (95% CrI, 7.8-26.4), 6.3 (95% CrI, 2.4-13.7), and 7.9 (95% CrI, 3.6-15.1) per 1,000 patient-days, and incidence rates were not statistically different between groups. Patients in the coated-device group had more days alive and free of antibiotics in the ICU (28.97 d vs. 19.62 d per 100 patient-days; mean ratio, 1.48; 95% CrI, 1.16-1.89). Conclusions: Use of a bundle of coated devices as the initial treatment for of severely ill patients is feasible. Coated devices may be associated with more days alive and free of antibiotics. Clinical trial registered with www.clinicaltrials.gov (NCT 03868241).

Summary Background The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19. Methods We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278. Findings 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94–1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups. Interpretation In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19. Funding COALITION COVID-19 Brazil and EMS.

Importance Slower intravenous fluid infusion rates could reduce the formation of tissue edema and organ dysfunction in critically ill patients; however, there are no data to support different infusion rates during fluid challenges for important outcomes such as mortality. Objective To determine the effect of a slower infusion rate vs control infusion rate on 90-day survival in patients in the intensive care unit (ICU). Design, Setting, and Participants Unblinded randomized factorial clinical trial in 75 ICUs in Brazil, involving 11 052 patients requiring at least 1 fluid challenge and with 1 risk factor for worse outcomes were randomized from May 29, 2017, to March 2, 2020. Follow-up was concluded on October 29, 2020. Patients were randomized to 2 different infusion rates (reported in this article) and 2 different fluid types (balanced fluids or saline, reported separately). Interventions Patients were randomized to receive fluid challenges at 2 different infusion rates; 5538 to the slower rate (333 mL/h) and 5514 to the control group (999 mL/h). Patients were also randomized to receive balanced solution or 0.9% saline using a factorial design. Main Outcomes and Measures The primary end point was 90-day survival. Results Of all randomized patients, 10 520 (95.2%) were analyzed (mean age, 61.1 years [SD, 17.0 years]; 44.2% were women) after excluding duplicates and consent withdrawals. Patients assigned to the slower rate received a mean of 1162 mL on the first day vs 1252 mL for the control group. By day 90, 1406 of 5276 patients (26.6%) in the slower rate group had died vs 1414 of 5244 (27.0%) in the control group (adjusted hazard ratio, 1.03; 95% CI, 0.96-1.11;P = .46). There was no significant interaction between fluid type and infusion rate (P = .98). Conclusions and Relevance Among patients in the intensive care unit requiring fluid challenges, infusing at a slower rate compared with a faster rate did not reduce 90-day mortality. These findings do not support the use of a slower infusion rate. Trial Registration ClinicalTrials.gov Identifier:NCT02875873

Cerebral autoregulation (CA) impairment after aneurysmal subarachnoid hemorrhage (SAH) has been associated with delayed cerebral ischemia and an unfavorable outcome. We investigated whether the early transient hyperemic response test (THRT), a transcranial Doppler (TCD)-based CA evaluation method, can predict functional outcome 6 months after aneurysmal SAH. This is a prospective observational study of all aneurysmal SAH patients consecutively admitted to a single center between January 2016 and February 2017. CA was evaluated within 72 h of hemorrhage by THRT, which describes the changes in cerebral blood flow velocity after a brief compression of the ipsilateral common carotid artery. CA was considered to be preserved when an increase ≥ 9% of baseline systolic velocity was present. According to the modified Rankin Scale (mRS: 4–6), the primary outcome was unfavorable 6 months after hemorrhage. Secondary outcomes included cerebral infarction, vasospasm on TCD, and an unfavorable outcome at hospital discharge. Forty patients were included (mean age = 54 ± 12 years, 70% females). CA was impaired in 19 patients (47.5%) and preserved in 21 (52.5%). Impaired CA patients were older (59 ± 13 vs. 50 ± 9, p = 0.012), showed worse neurological conditions (Hunt&Hess 4 or 5–47.4% vs. 9.5%, p = 0.012), and clinical initial condition (APACHE II physiological score—12 [5.57–13] vs. 3.5 [3–5], p = 0.001). Fourteen patients in the impaired CA group and one patient in the preserved CA group progressed to an unfavorable outcome (73.7% vs. 4.7%, p = 0.0001). The impaired CA group more frequently developed cerebral infarction than the preserved CA group (36.8% vs. 0%, p = 0.003, respectively). After multivariate analysis, impaired CA (OR 5.15 95% CI 1.43–51.99, p = 0.033) and the APACHE II physiological score (OR 1.67, 95% CI 1.01–2.76, p = 0.046) were independently associated with an unfavorable outcome. Early CA impairment detected by TCD and admission APACHE II physiological score independently predicted an unfavorable outcome after SAH.

Importance Intravenous fluids are used for almost all intensive care unit (ICU) patients. Clinical and laboratory studies have questioned whether specific fluid types result in improved outcomes, including mortality and acute kidney injury. Objective To determine the effect of a balanced solution vs saline solution (0.9% sodium chloride) on 90-day survival in critically ill patients. Design, Setting, and Participants Double-blind, factorial, randomized clinical trial conducted at 75 ICUs in Brazil. Patients who were admitted to the ICU with at least 1 risk factor for worse outcomes, who required at least 1 fluid expansion, and who were expected to remain in the ICU for more than 24 hours were randomized between May 29, 2017, and March 2, 2020; follow-up concluded on October 29, 2020. Patients were randomized to 2 different fluid types (a balanced solution vs saline solution reported in this article) and 2 different infusion rates (reported separately). Interventions Patients were randomly assigned 1:1 to receive either a balanced solution (n = 5522) or 0.9% saline solution (n = 5530) for all intravenous fluids. Main Outcomes and Measures The primary outcome was 90-day survival. Results Among 11 052 patients who were randomized, 10 520 (95.2%) were available for the analysis (mean age, 61.1 [SD, 17] years; 44.2% were women). There was no significant interaction between the 2 interventions (fluid type and infusion speed;P = .98). Planned surgical admissions represented 48.4% of all patients. Of all the patients, 60.6% had hypotension or vasopressor use and 44.3% required mechanical ventilation at enrollment. Patients in both groups received a median of 1.5 L of fluid during the first day after enrollment. By day 90, 1381 of 5230 patients (26.4%) assigned to a balanced solution died vs 1439 of 5290 patients (27.2%) assigned to saline solution (adjusted hazard ratio, 0.97 [95% CI, 0.90-1.05];P = .47). There were no unexpected treatment-related severe adverse events in either group. Conclusion and Relevance Among critically ill patients requiring fluid challenges, use of a balanced solution compared with 0.9% saline solution did not significantly reduce 90-day mortality. The findings do not support the use of this balanced solution. Trial Registration ClinicalTrials.gov Identifier:NCT02875873

Background: Many randomized controlled trials (RCT) have assessed new treatments in subarachnoid hemorrhage (SAH), yet most show no treatment efficacy. One explanation is the statistical analysis of the primary endpoint was not as efficient as possible. We reanalyzed SAH RCTs with various statistical tests to determine whether the statistical method affects RCT primary outcome.Methods: Individual patient data for the primary outcome (Glasgow outcome scale [GOS]) of two SAH RCTs were analyzed using 15 statistical methods. For tests requiring outcome dichotomization, multiple cut-points in the 5-level GOS were assessed. Next, a synthetic dataset generated using random sampling with replacement from ten SAH RCTs was assessed using the same statistical tests. A Friedman test (two-way non-parametric analysis of variance) determined which tests produced the highest average absolute Z-values. The number of times each test reported significance of pResults: Bootstrapping with replacement produced the best-ranking results, followed by three χ2-tests: one differentiating excellent (GOS=5) from good (GOS=4), poor (GOS=2-3), or dead (GOS=1) outcomes; one differentiating favorable (GOS=4-5) from poor or dead outcomes; and one differentiating favorable (GOS=4-5) from unfavorable outcomes. Each of these reported statistical significance for both RCTs, as did the following ranked tests, respectively: Wilcoxon median test, Student’s t-test, ordinal logistic regression, median test, and a chi-square dichotomizing excellent (GOS≥4) and inferior outcomes. Statistical significance for one or neither RCT was reported by two Cochrane-Armitage tests and two logistic regressions with alternate versions of bucketing, the Kolmogorov-Smirnov test and chi-square test differentiating surviving from dead patients. The synthetic dataset returned similar results, with the same nine most and six least efficient tests.Conclusions: Bootstrapping produced the most efficient results but is time-and resource-intensive. Chi-square tests grouping outcomes into dichotomous or multiple buckets are also efficient, and their ease of use and popularity make them appropriate candidates for statistical analysis in future SAH RCTs.

Respiratory complications are common in patients with acute brain injury and represent a significant challenge from both a respiratory and a neurological perspective. Commonly used ventilatory and non-ventilatory strategies may affect cerebral perfusion and oxygen delivery. The concomitant use of brain and general critical care ultrasound techniques aimed at monitoring cerebral perfusion and cardiorespiratory parameters at the bedside may offer a significant benefit in delivering both lung- and neuroprotective approaches in patients with complex ventilatory needs and deranged cerebrovascular physiology. In this chapter we discuss potential applications of ultrasonography for the management of patients with severe respiratory failure. Although appealing and physiologically sound, the use of ultrasound is currently supported by limited evidence and more data are needed to support its routine use in clinical practice.

OBJECTIVETreatment of wide-necked intracranial aneurysms is associated with higher recanalization and complication rates; however, the most commonly used methods are not specifically designed to work in bifurcation lesions. To address these issues, the authors describe the evolution in the design and use of the eCLIPs (Endovascular Clip System) device, a novel hybrid stent-like assist device with flow diverter properties that was first described in 2008.METHODSA registry was established covering 13 international centers at which patients were treated with the second-generation eCLIPs device. Aneurysm morphology and rupture status, device neck coverage, coil retention, and procedural and late morbidity and mortality were recorded. For those patients who had undergone successful implantation more than 6 months earlier, the final imaging and clinical follow-up results and need for re-treatment were recorded.RESULTSThirty-three patients were treated between June 2013 and September 2015. Twenty-five (76%) patients had successful placement of an eCLIPs device; 23 (92%) of these 25 patients had complete data. Eight cases of nondeployment occurred during the 1st year of use, consistent with a learning curve; no failures of deployment occurred thereafter. Two periprocedural transient ischemic attacks and 2 asymptomatic thrombotic events occurred. Twenty-one (91%) of 23 patients underwent follow-up at an average of 8 months (range 3–18 months); 9 (42.9%) of these 21 patients demonstrated an improvement in Raymond grade at follow-up; no cases of worsening Raymond grade were recorded, and 17 (81.0%) patients sustained a modified Raymond-Roy Classification class of I or II angiographic result at follow-up. Two delayed ruptures were recorded, both in previously coiled, symptomatic giant aneurysms where the device was used as a part of a salvage strategy.CONCLUSIONSThe second-generation eCLIPs device is a viable treatment option for bifurcation aneurysms. The aneurysm occlusion rates in this initial clinical series are comparable to the initial experience with other bifurcation support devices.

Additional file 1: Supplemental Table 1. The GHOST-CAP mnemonic with reasonable target values for each component and when specific invasive monitoring systems could help individualize the targets.

Background: Poor-grade subarachnoid hemorrhage (SAH) has been associated with a high case fatality, either in the acute phase or in the later stages. The exact causes of death in these patients are unknown. Methods: We performed a retrospective study of all consecutive patients with SAH with World Federation of Neurosurgical Societies grade IV or V on admission from 2009 to 2013 at 2 tertiary referral centers in Amsterdam, the Netherlands, and Toronto, Ontario, Canada, who had died during their hospital stay. Results: Of 357 patients, 152 (43%) had died. Of these 152 patients, 87 (24%) had not undergone aneurysm treatment. The median interval to death was 3 days (interquartile range, 1–12 days) after initial hemorrhage. The major cause of death in both centers was withdrawal of life support (107 patients [71%]; 74 of 94 [79%] in Amsterdam and 33 of 58 [58%] in Toronto; P < 0.01), followed by brain death in 23 (15%; 16 of 58 [28%] in Amsterdam vs. 7 of 94 [7%] in Toronto; P < 0.01). The remaining causes of death represented

The effects of induced hypertension (IH) on cerebral perfusion after subarachnoid hemorrhage (SAH) are unclear. The objectives of this investigation are to: (1) determine whether there are differences in cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) measured with computed tomography perfusion (CTP) before and after IH; (2) evaluate differences in the presence of infarction and clinical outcome between patients with and without IH.We performed a retrospective cohort analysis of 25 aneurysmal SAH patients. IH was initiated as per the standard institutional protocol when patients showed clinical symptoms of delayed cerebral ischemia (DCI). Differences in CBF, CBV, and MTT between early (72 h after aneurysm rupture) and late (7-10 days after aneurysm rupture) CTP were quantified in patients with (n = 13) and without IH (n = 12). Outcome measures included cerebral infarction and clinical outcome at 3 months.Early MTT was significantly greater in the IH group compared to the no-IH group. There was no difference in early or late CBV or CBF between the two groups. In patients that received IH, there was a significant decrease in MTT between the early (7.0 ± 1.2 s) and late scans (5.8 ± 1.6 s; p = 0.005). There was no difference in the incidence of infarction (5/13 vs. 2/11) or poor outcome (3/11 vs. 6/13) between the IH and no-IH groups, respectively (p 0.05).Elevated MTT is a significant factor for the development of DCI in patients eventually requiring IH therapy and is improved by IH treatment. Therapies to prevent DCI and improve clinical outcome may need to be initiated earlier, when cerebral perfusion abnormalities are first identified.

ObjectiveThe recent guidelines on management of aneurysmal subarachnoid hemorrhage (aSAH) advise pharmacological thromboprophylaxis (PTP) after aneurysm obliteration. However, no study has addressed the safety of PTP in the aSAH population. Therefore, the aim of this study was to assess the safety of early PTP after aSAH.MethodsRetrospective cohort of aSAH patients admitted between January 2012 and June 2013 in a single high-volume aSAH center. Traumatic SAH and perimesencephalic hemorrhage patients were excluded. Patients were grouped according to PTP timing: early PTP group (PTP within 24 hours of aneurysm treatment), and delayed PTP group (PTP started > 24 hours).ResultsA total of 174 SAH patients (mean age 56.3±12.5 years) were admitted during the study period. Thirty-nine patients (22%) did not receive PTP, whereas 135 patients (78%) received PTP after aneurysm treatment or negative angiography. Among the patients who received PTP, 65 (48%) had an external ventricular drain. Twenty-eight patients (21%) received early PTP, and 107 (79%) received delayed PTP. No patient in the early treatment group and three patients in the delayed PTP group developed an intracerebral hemorrhagic complication. Two required neurosurgical intervention and one died. These three patients were on concomitant PTP and dual antiplatelet therapy.ConclusionsThe initiation of PTP within 24 hours may be safe after the treatment of a ruptured aneurysm or in angiogram-negative SAH patients with diffuse aneurysmal hemorrhage pattern. We suggest caution with concomitant use of PTP and dual antiplatelet agents, because it possibly increases the risk for intracerebral hemorrhage.

Background Elevated catecholamine levels might be associated with unfavorable outcome after traumatic brain injury (TBI). We investigated the association between catecholamine levels in the first 24 h post-trauma and functional outcome in patients with isolated moderate-to-severe TBI. Methods A cohort of 174 patients who sustained isolated blunt TBI was prospectively enrolled from three Level-1 Trauma Centers. Epinephrine (Epi) and norepinephrine (NE) concentrations were measured at admission (baseline), 6, 12 and 24 h post-injury. Outcome was assessed at 6 months by the extended Glasgow Outcome Scale (GOSE) score. Fractional polynomial plots and logistic regression models (fixed and random effects) were used to study the association between catecholamine levels and outcome. Effect size was reported as the odds ratio (OR) associated with one logarithmic change in catecholamine level. Results At 6 months, 109 patients (62.6%) had an unfavorable outcome (GOSE 5–8 vs. 1–4), including 51 deaths (29.3%). Higher admission levels of Epi were associated with a higher risk of unfavorable outcome (OR, 2.04, 95% CI: 1.31–3.18, p = 0.002) and mortality (OR, 2.86, 95% CI: 1.62–5.01, p = 0.001). Higher admission levels of NE were associated with higher risk of unfavorable outcome (OR, 1.59, 95% CI: 1.07–2.35, p = 0.022) but not mortality (OR, 1.45, 95% CI: 0.98–2.17, p = 0.07). There was no relationship between the changes in Epi levels over time and mortality or unfavorable outcome. Changes in NE levels with time were statistically associated with a higher risk of mortality, but the changes had no relation to unfavorable outcome. Conclusions Elevated circulating catecholamines, especially Epi levels on hospital admission, are independently associated with functional outcome and mortality after isolated moderate-to-severe TBI. Electronic supplementary material The online version of this article (doi:10.1186/s13054-017-1620-6) contains supplementary material, which is available to authorized users.

OBJECTIVEPatients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) (World Federation of Neurosurgical Societies Grade IV or V) are often considered for decompressive craniectomy (DC) as a rescue therapy for refractory intracranial hypertension. The authors performed a systematic review and meta-analysis to assess the impact of DC on functional outcome and death in patients after poor-grade aSAH.METHODSA systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles were identified through the Ovid Medline, Embase, Web of Science, and Cochrane Library databases from inception to October 2015. Only studies dedicated to patients with poor-grade aSAH were included. Primary outcomes were death and functional outcome assessed at any time period. Patients were grouped as having a favorable outcome (modified Rankin Scale [mRS] Scores 1–3, Glasgow Outcome Scale [GOS] Scores 4 and 5, extended Glasgow Outcome Scale [GOSE] Scores 5–8) or unfavorable outcome (mRS Scores 4–6, GOS Scores 1–3, GOSE Scores 1–4). Pooled estimates of event rates and odds ratios with 95% confidence intervals were calculated using the random-effects model.RESULTSFifteen studies encompassing 407 patients were included in the meta-analysis (all observational cohorts). The pooled event rate for poor outcome across all studies was 61.2% (95% CI 52%–69%) and for death was 27.8% (95% CI 21%–35%) at a median of 12 months after aSAH. Primary (or early) DC resulted in a lower overall event rate for unfavorable outcome than secondary (or delayed) DC (47.5% [95% CI 31%–64%] vs 74.4% [95% CI 43%–91%], respectively). Among studies with comparison groups, there was a trend toward a reduced mortality rate 1–3 months after discharge among patients who underwent DC (OR 0.58 [95% CI 0.27–1.25]; p = 0.168). However, this trend was not sustained at the 1-year follow-up (OR 1.09 [95% CI 0.55–2.13]; p = 0.79).CONCLUSIONSResults of this study summarize the best evidence available in the literature for DC in patients with poor-grade aSAH. DC is associated with high rates of unfavorable outcome and death. Because of the lack of robust control groups in a majority of the studies, the effect of DC on functional outcomes versus that of other interventions for refractory intracranial hypertension is still unknown. A randomized trial is needed.

There are a range of opinions on the benefits and thresholds for the transfusion of red blood cells in critically ill patients with traumatic brain injury (TBI) and an urgent need to understand the neurophysiologic effects. The aim of this study was to examine the influence of red blood cell transfusions on cerebral tissue oxygenation (SctO2) in critically ill TBI patients. This prospective observational study enrolled consecutive TBI patients with anemia requiring transfusion. Cerebral tissue oxygen saturation (SctO2) was measured noninvasively with bilateral frontal scalp probes using near-infrared spectroscopy (NIRS) technology. Data were collected at baseline and for 24 h after transfusion. The primary outcome was the applicability of a four-wavelength near-infrared spectrometer to monitor SctO2 changes during a transfusion. Secondary outcomes included the correlation of SctO2 with other relevant physiological variables, the dependence of SctO2 on baseline hemoglobin and transfusion, and the effect of red blood cell transfusion on fractional tissue oxygen extraction. We enrolled 24 patients with severe TBI, of which five patients (21 %) were excluded due to poor SctO2 signal quality from large subdural hematomas and bifrontal decompressive craniectomies. Twenty transfusions were monitored in 19 patients. The mean pre- and post-transfusion hemoglobin concentrations were significantly different [74 g/L (SD 8 g/L) and 84 g/L (SD 9 g/L), respectively; p value

Background Traumatic brain injury (TBI) is a heterogeneous syndrome with a broad range of outcome. We developed a simple model for long-term outcome prognostication after severe TBI. Methods Secondary data analysis of a large multicenter randomized trial. Patients were grouped according to 6-month extended Glasgow outcome scale (eGOS): poor-outcome (eGOS ≤ 4; severe disability or death) and acceptable outcome (eGOS > 4; no or moderate disability). A prediction decision tree was built using binary recursive partitioning to predict poor or acceptable 6-month outcome. Comparison to two previously published and validated models was made. Results The decision tree included the predictors of head Abbreviated Injury Scale (AIS) severity, the Marshall computed tomography score, and pupillary reactivity. All patients with a head AIS severity of 5 were predicted to have a poor outcome. In patients with head AIS severity

Background: Acute coagulopathy after traumatic brain injury (TBI) involves a complex multifactorial hemostatic response that is poorly characterized. Objectives: To examine early posttraumatic alterations in coagulofibrinolytic, endothelial, and inflammatory blood biomarkers in relation to sympathetic nervous system (SNS) activation and 6-month patient outcomes, using multivariate partial least-squares (PLS) analysis. Patients and Methods: A multicenter observational study of 159 adult isolated TBI patients admitted to the emergency department at an urban level I trauma center, was performed. Plasma concentrations of 6 coagulofibrinolytic, 10 vascular endothelial, 19 inflammatory, and 2 catecholamine biomarkers were measured by immunoassay on admission and 24 h postinjury. Neurological outcome at 6 months was assessed using the Extended Glasgow Outcome Scale. PLS-discriminant analysis was used to identify salient biomarker contributions to unfavorable outcome, whereas PLS regression analysis was used to evaluate the covariance between SNS correlates (catecholamines) and biomarkers of coagulopathy, endotheliopathy, and inflammation. Results: Biomarker profiles in patients with an unfavorable outcome displayed procoagulation, hyperfibrinolysis, glycocalyx and endothelial damage, vasculature activation, and inflammation. A strong covariant relationship was evident between catecholamines and biomarkers of coagulopathy, endotheliopathy, and inflammation at both admission and 24 h postinjury. Conclusions: Biomarkers of coagulopathy and endotheliopathy are associated with poor outcome after TBI. Catecholamine levels were highly correlated with endotheliopathy and coagulopathy markers within the first 24 h after injury. Further research is warranted to characterize the pathogenic role of SNS-mediated hemostatic alterations in isolated TBI.

Aneurysmal subarachnoid haemorrhage is a neurological syndrome with complex systemic complications. The rupture of an intracranial aneurysm leads to the acute extravasation of arterial blood under high pressure into the subarachnoid space and often into the brain parenchyma and ventricles. The haemorrhage triggers a cascade of complex events, which ultimately can result in early brain injury, delayed cerebral ischaemia, and systemic complications. Although patients with poor-grade subarachnoid haemorrhage (World Federation of Neurosurgical Societies 4 and 5) are at higher risk of early brain injury, delayed cerebral ischaemia, and systemic complications, the early and aggressive treatment of this patient population has decreased overall mortality from more than 50 % to 35 % in the last four decades. These management strategies include (1) transfer to a high-volume centre, (2) neurological and systemic support in a dedicated neurological intensive care unit, (3) early aneurysm repair, (4) use of multimodal neuromonitoring, (5) control of intracranial pressure and the optimisation of cerebral oxygen delivery, (6) prevention and treatment of medical complications, and (7) prevention, monitoring, and aggressive treatment of delayed cerebral ischaemia. The aim of this article is to provide a summary of critical care management strategies applied to the subarachnoid haemorrhage population, especially for patients in poor neurological condition, on the basis of the modern concepts of early brain injury and delayed cerebral ischaemia.

Contains fulltext : 172587.pdf (Publisher’s version ) (Closed access) BACKGROUND AND PURPOSE: Poor-grade subarachnoid hemorrhage (SAH) (World Federation of Neurosurgical Societies grade 4 and 5) is associated with high mortality rates and unfavorable functional outcomes. We report a single-center cohort of poor-grade SAH patients, combined with a systematic review of studies reporting functional outcome in the poor-grade SAH population. METHODS: Data on a cohort of poor-grade SAH patients treated between 2009 and 2013 were retrospectively collected and combined with a systematic review (from inception to November 2015; PubMed, Embase). Two reviewers assessed the studies independently based on predefined inclusion criteria: consecutive poor-grade SAH, functional outcome measured at least 3 months after hemorrhage, and the report of patients who died before aneurysm treatment. RESULTS: The search yielded 329 publications, and 23 met our inclusion criteria with 2713 subjects enrolled from 1977 to 2014 in 10 countries (including 179 poor-grade patients from our cohort). Mortality rate was 60 % (1683 patients), of which 806 (29 %) died before and 877 (31 %) died after aneurysm treatment, respectively. Treatment was undertaken in 1775 patients (1775/2826-63 %): 1347 by surgical clipping (1347/1775-76 %) and 428 (428/1775-24 %) by endovascular methods. Outcome was favorable in 794 patients (28 %) and unfavorable in 1867 (66 %). When the studies were grouped into decades, favorable outcome increased from 13 % in the late 1970s to early 1980s to 35 % in the late 1980s to early 1990s, and remained unchanged thereafter. CONCLUSION: Although mortality remains high in poor-grade SAH patients, a favorable functional outcome can be achieved in approximately one-third of patients. The development of new diagnostic methods and implementation of therapeutic approaches were probably responsible for the decrease in mortality and improvement in the functional outcome from 1970 to the 1990s. The plateau in functional outcome seen thereafter might be explained by the treatment of sicker and older patients and by the lack of new therapeutic interventions specific for SAH.

Background and Purpose— Patients are classically at risk of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage. We validated a grading scale—the VASOGRADE—for prediction of DCI. Methods— We used data of 3 phase II randomized clinical trials and a single hospital series to assess the relationship between the VASOGRADE and DCI. The VASOGRADE derived from previously published risk charts and consists of 3 categories: VASOGRADE-Green (modified Fisher scale 1 or 2 and World Federation of Neurosurgical Societies scale [WFNS] 1 or 2); VASOGRADE-Yellow (modified Fisher 3 or 4 and WFNS 1–3); and VASOGRADE-Red (WFNS 4 or 5, irrespective of modified Fisher grade). The relation between the VASOGRADE and DCI was assessed by logistic regression models. The predictive accuracy of the VASOGRADE was assessed by receiver operating characteristics curve and calibration plots. Results— In a cohort of 746 patients, the VASOGRADE significantly predicted DCI ( P Conclusions— The VASOGRADE results validated previously published risk charts in a large and diverse sample of subarachnoid hemorrhage patients, which allows DCI risk stratification on presentation after subarachnoid hemorrhage. It could help to select patients at high risk of DCI, as well as standardize treatment protocols and research studies.

Patients with aneurysmal subarachnoid hemorrhage are at high risk of complications, including rebleeding, delayed cerebral ischemia, cerebral infarction, and death. This review presents a practical approach for managing this condition and its complications.

Objective - To develop and validate a set of practical prediction tools that reliably estimate the outcome of subarachnoid haemorrhage from ruptured intracranial aneurysms (SAH).Design - Cohort study with logistic regression analysis to combine predictors and treatment modality.Setting - Subarachnoid Haemorrhage International Trialists' (SAHIT) data repository, including randomised clinical trials, prospective observational studies, and hospital registries.Participants - Researchers collaborated to pool datasets of prospective observational studies, hospital registries, and randomised clinical trials of SAH from multiple geographical regions to develop and validate clinical prediction models.Main outcome measure - Predicted risk of mortality or functional outcome at three months according to score on the Glasgow outcome scale.Results - Clinical prediction models were developed with individual patient data from 10 936 patients and validated with data from 3355 patients after development of the model. In the validation cohort, a core model including patient age, premorbid hypertension, and neurological grade on admission to predict risk of functional outcome had good discrimination, with an area under the receiver operator characteristics curve (AUC) of 0.80 (95% confidence interval 0.78 to 0.82). When the core model was extended to a "neuroimaging model," with inclusion of clot volume, aneurysm size, and location, the AUC improved to 0.81 (0.79 to 0.84). A full model that extended the neuroimaging model by including treatment modality had AUC of 0.81 (0.79 to 0.83). Discrimination was lower for a similar set of models to predict risk of mortality (AUC for full model 0.76, 0.69 to 0.82). All models showed satisfactory calibration in the validation cohort.Conclusion - The prediction models reliably estimate the outcome of patients who were managed in various settings for ruptured intracranial aneurysms that caused subarachnoid haemorrhage. The predictor items are readily derived at hospital admission. The web based SAHIT prognostic calculator (http://sahitscore.com) and the related app could be adjunctive tools to support management of patients.

Early brain injury (EBI) can occur within 72 h of aneurysmal subarachnoid hemorrhage (aSAH). The objective of this study was to determine if there are differences in early CTP parameters (72 h) with respect to delayed cerebral ischemia (DCI), cerebral infarction, and functional outcome.We performed a prospective cohort study of aSAH patients admitted to a single tertiary care center. MTT, CBF and blood-brain barrier permeability (PS) were quantified with CTP within 72 h of aneurysm rupture. Primary outcomes were functional outcome by the Modified Rankin Scale (mRS) at 3 months and cerebral infarction. Secondary outcome was the development of DCI. Differences between early CTP parameters were determined with respect to primary and secondary outcomes.Fifty aSAH patients were included in the final analysis. MTT was significantly higher in patients who developed DCI (6.7 ± 1.2 vs 5.9 ± 1.0; p = 0.03) and cerebral infarction (7.0 ± 1.2 vs 5.9 ± 0.9; p = 0.007); however, no difference in MTT was found between patients with and without a poor outcome (mRS 2). Early CBF and PS did not differ with respect to functional outcome, DCI, and cerebral infarction.Elevated MTT within 72 h of aneurysm rupture is associated with DCI and cerebral infarction but not with long-term functional outcome. Blood-brain barrier permeability, as assessed by CT perfusion, was not associated with DCI or worse outcome in this cohort.

BACKGROUND: Up to 83% of aneurysmal subarachnoid hemorrhage (aSAH) survivors experience cognitive deficits - particularly in the domain of executive functioning, which encompasses skills necessary for everyday functioning. The neural correlates of these deficits have not yet been investigated. Resting-state functional magnetic resonance imaging (rs-fMRI) is an imaging technique to investigate functional connectivity between brain regions at rest - that is, without the use of a stimulation task. Spontaneous neural activity at rest is an intrinsic property of healthy brains and can be disrupted by various pathologies. In rs-fMRI, deviations from the norm (increases or decreases) are abnormalities indicative of the existence of impairments. HYPOTHESIS: We hypothesized that aSAH patients will exhibit altered resting-state functional connectivity within frontal brain networks that would map onto impaired performance on tests of executive functioning relative to matched healthy controls. METHODS: 14 aSAH patients and 11 healthy controls matched on age, education and gender were included. To differentiate between patients with good and poor cognitive outcome, a composite Executive Function score was generated using the z-scores of executive tests, and patients with negative composites were then classified as ‘Impaired’ for further analyses. RESULTS: The Impaired group scored significantly worse than both Controls and Unimpaired patients on 10 measures of executive functioning. Resting-state connectivity between the right dorsolateral prefrontal cortex (DLPFC) and the left superior frontal gyrus (SFG) was significantly increased in the ‘Impaired’ patients and this connection covaried significantly with composite executive scores. Increased connectivity between the left DLPFC and right precuneus was seen in the impaired patients relative to controls, covarying significantly with reduced mood scores. CONCLUSIONS: The aberrant connection between the right DLPFC and left SFG may underlie executive impairments after aSAH. This imaging modality could be explored as a potential diagnostic tool to identify cognitive impairment in aSAH patients and direct them to appropriate rehabilitation programs for improved cognitive outcomes.

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening stroke that can be treated with endovascular coiling. Coiling can be associated with microemboli, although the extent to which they are due to aSAH versus the coiling procedure has seldom been investigated. We investigated the implications of these microemboli on clinical outcome. Hypothesis: We hypothesized that the presence, number, location and volume of microemboli would correlate with clinical outcome. Methods: We retrospectively analyzed diffusion-weighted imaging (DWI) scans and apparent diffusion coefficient maps obtained within 7 days of aneurysm rupture in 140 patients. We analyzed the DWI scans of 80 patients with unruptured intracranial aneurysms (UIA) who underwent coiling at our institution as a control group. We assessed the presence and location of microemboli, quantified their volume and number, and correlated these factors with clinical variables and intervention details. Results: The aSAH and UIA groups did not differ in the presence of microemboli. The location of the lesions significantly correlated with the aneurysm location (p Conclusions: Microemboli commonly occur in coiled aSAH patients and have implications on clinical outcome. They are secondary to the coiling procedure and were not increased by presence of aSAH. Catheter-induced microemboli may initiate an early ischemic burden that contributes to angiographic vasospasm and cerebral infarction. That left-sided microemboli contribute to angiographic vasospasm is consistent with prior studies suggesting a left-sided approach significantly contributes to procedure-related microembolism. This suggests that improvements in endovascular practices are required to lower the risk of ischemic damage, especially when employing a left-sided approach.

Introduction: It is well established that cognitive and functional impairments persist despite good clinical outcomes in patients who suffer aneurysmal subarachnoid hemorrhage (aSAH). The impact of these impairments on real-world tasks such as driving a motor vehicle is currently unclear. This study aimed to investigate driving ability of aSAH patients using a driving simulator. We hypothesized that patients would exhibit more driving errors during the most cognitively demanding aspects, particularly while executing left turns at busy intersections, where the driver must quickly integrate many complex and dynamic visual stimuli to make a rapid decision and turn safely. Methods: Nine functionally independent aSAH patients (>3 months post-ictus) and nine healthy control participants matched for age (patients: 58±13; controls: 59±14, p > 0.05) completed two driving scenarios (STISIM). The total number of errors committed and errors associated with intersections were compared between groups. Errors included collisions, speeding, centerline crossings, road edge excursions, stop signs missed and traffic light tickets. Results: The mean number of total errors did not differ between the patient and control groups (28 versus 22, p > 0.05); however, patients committed a greater number of hazardous errors, including collisions (2.4 versus 0.1, p < 0.05) and road edge excursions (3.7 versus 0.3, p < 0.01), than controls. Total errors at intersection turns were greater for patients (7.7 versus 3.2, p < 0.05). When stratified by type of turn, patients experienced more errors than controls during left turns (1.6 versus 0.2, p < 0.01) and left turns with oncoming traffic (2.3 versus 0.8, p < 0.05) but not during right turns (3.8 versus 2.2, p > 0.05). Conclusion: Our results suggest probable driving impairment in some aSAH patients during more difficult aspects of driving, such as making left turns at a busy intersection, which is where most real-world accidents occur. This analysis was limited by a small sample, and further research should explore the clinical and cognitive correlates of driving ability in a large sample of aSAH patients.

Background: Venous thrombo-embolism (VTE) is common in patients admitted to intensive care units. The incidence of VTE in patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) varies from 1.5 to 18%, depending on the series and the screening strategy. There is limited data addressing the role of chemical prophylaxis in the aSAH population. Our institutional guidelines suggest VTE prophylaxis with sequential compression pneumatic devices prior to securing a ruptured intracranial aneurysm. Unfractionated heparin (UFH) at a dose of 5,000 IU (SC every 12 h) is considered after the aneurysm has been secured for 24 hours. Methods: We retrospectively reviewed data from all aSAH patients admitted to a 19-bed high volume aSAH ICU, between January 2013 and June 2013. Results: Fifty-two patients with aSAH (mean age 58.6, range 28-93) were admitted during the study period. In total, 61 aneurysms were found, 46 ruptured, and additional 10 incidentally discovered aneurysm. 72.1% of aSAH patients received UFH after aneurysm treatment. In the 26.9% of patients UFH was withheld; these patients had either unsecured aneurysms or withdrawal of life-sustaining treatments. Of the patients who received UFH 48.7% received the medication at 24h after aneurysm treatment, 33.5% within 72h; and in 15.4% heparin was started beyond 72h after aneurysm treatment. The mean time from aneurysm treatment to initiation of VTE prophylaxis was 2.1 days. Of those patients who received UFH, 22 patients (58%) had an External Ventricular Drain. Endovascular treatment was the main modality as compared to surgical clipping (61.5 vs 15.4%). 6 patients (11.5%) received prophylactic dose of UFH and dual antiplatelets therapy (aspirin and clopidogrel). 1 patient (2%) who was on UFH had a major cerebral hemorrhagic complication and died, however, this patient was also on aspirin and clopidogrel. 8 patients (21%) were investigated for clinical suspicion of VTE; 1 patient (2%) on UFH had a pulmonary embolism. Conclusion: The use of subcutaneous UFH for VTE prophylaxis after 24h of aneurysm treatment is feasible, safe, and effective in an aSAH population. Caution should be taken in patients receiving subcutaneous UFH and antiplatelet agents, in whom the risk of intra-cerebral bleeding is higher.

Neuroimaging is a key element in the management of patients suffering from subarachnoid haemorrhage (SAH). In this article, we review the current literature to provide a summary of the existing neuroimaging methods available in clinical practice. Noncontrast computed tomography is highly sensitive in detecting subarachnoid blood, especially within 6 hours of haemorrhage. However, lumbar puncture should follow a negative noncontrast computed tomography scan in patients with symptoms suspicious of SAH. Computed tomography angiography is slowly replacing digital subtraction angiography as the first-line technique for the diagnosis and treatment planning of cerebral aneurysms, but digital subtraction angiography is still required in patients with diffuse SAH and negative initial computed tomography angiography. Delayed cerebral ischaemia is a common and serious complication after SAH. The modern concept of delayed cerebral ischaemia monitoring is shifting from modalities that measure vessel diameter to techniques focusing on brain perfusion. Lastly, evolving modalities applied to assess cerebral physiological, functional and cognitive sequelae after SAH, such as functional magnetic resonance imaging or positron emission tomography, are discussed. These new techniques may have the advantage over structural modalities due to their ability to assess brain physiology and function in real time. However, their use remains mainly experimental and the literature supporting their practice is still scarce. Electronic supplementary material The online version of this article (doi:10.1186/s13054-014-0557-2) contains supplementary material, which is available to authorized users.