Pulmonary edema and blood volume after aneurysmal subarachnoid hemorrhage: a prospective observational study

Introduction  

Pulmonary edema (PED) is a severe complication after aneurysmal subarachnoid hemorrhage (SAH). PED is often treated with diuretics and a reduction in fluid intake, but this may cause intravascular volume depletion, which is associated with secondary ischemia after SAH. We prospectively studied intravascular volume in SAH patients with and without PED.     

Endothelin-receptor antagonists for aneurysmal subarachnoid hemorrhage: an updated meta-analysis of randomized controlled trials

Introduction

The previous meta-analysis on the use of endothelin-receptor antagonists (ETRAs) to treat aneurysmal subarachnoid hemorrhage (SAH) has become outdated due to recently published phase 3 clinical trials. An up-to-date meta-analysis is needed to provide the best available evidence for the efficacy of ETRAs for aneurysmal SAH.

Methods

We performed a systematic review and meta-analysis of published randomized controlled trials that investigate efficacy of ETRAs in patients with aneurysmal SAH. Mortality, unfavorable outcome, delayed ischemic neurological deficit (DIND), delayed cerebral infarction (DCI), angiographic vasospasm and adverse events were analyzed. Meta-analysis was performed in terms of the risk ratio (RR) and 95% confidence interval (CI).

Results

Five eligible studies were reviewed and analyzed, involving 2,595 patients. The pooled RRs of mortality and unfavorable outcome after SAH were 1.03 (95% CI = 0.77 to 1.36) and 1.07 (95% CI = 0.93 to 1.22), respectively. The pooled RRs were 0.87 (95% CI = 0.74 to 1.03) for DCI, 0.77 (95% CI = 0.66 to 0.90) for DIND, and 0.66 (95% CI = 0.57 to 0.77) for angiographic vasospasm. There were significant increases in lung complications (RR = 1.80, 95% CI = 1.55 to 2.09), hypotension (RR = 2.42, 95% CI = 1.78 to 3.29) and anemia (RR = 1.47, 95% CI = 1.19 to 1.83) in patients administered ETRAs.

Conclusion

There is no evidence that ETRAs could benefit clinical outcome in patients with SAH. Owing to the increased adverse events, further clinical trials of ETRAs in SAH patients should be more carefully formulated and designed. The present results also suggest that DCI may be a better outcome measure than vasospasm and DIND in SAH clinical trials and observational studies.     

Cerebral microdialysis for detection of bacterial meningitis in aneurysmal subarachnoid hemorrhage patients: a cohort study

Introduction  

Bacterial meningitis (BM) is a severe complication in patients with aneurysmal subarachnoid haemorrhage (SAH). Clinical signs of meningitis are often masked by SAH-related symptoms, and routine cerebrospinal fluid (CSF) analysis fails to indicate BM. Microdialysis (MD) is a technique for monitoring cerebral metabolism in patients with SAH. A cohort study was performed to investigate the value of MD for the diagnosis of BM.     

Red blood cell transfusion in patients with subarachnoid hemorrhage: a multidisciplinary North American survey

Introduction  

Anemia is associated with poor outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH). It remains unclear whether this association can be modified with more aggressive use of red blood cell (RBC) transfusions. The degree to which restrictive thresholds have been adopted in neurocritical care patients remains unknown.     

Comparison of sufentanil with sufentanil plus magnesium sulphate for sedation in the intensive care unit using bispectral index

Introduction  

In intensive care unit patients we assessed, using bispectral index (BIS) monitoring, whether the addition of magnesium sulphate infusion could decrease the sufentanil infusion required to maintain sedation.     

Insulin-related decrease in cerebral glucose despite normoglycemia in aneurysmal subarachnoid hemorrhage

Introduction  

Hyperglycaemia following aneurysmal subarachnoid hemorrhage (SAH) is associated with complications and impaired neurological recovery. The aim of this study was to determine the effect of insulin treatment for glucose control on cerebral metabolism in SAH patients.     

Intravenous magnesium therapy in adult patients with an aneurysmal subarachnoid haemorrhage: A systematic review and meta-analysis

BackgroundThe value of magnesium for the prevention of cerebral arterial vasospasm in patients with aneurysmal subarachnoid haemorrhage (SAH) is debatable. We performed a systematic review to collate the available evidence to evaluate the effects of intravenous magnesium for the prevention of cerebral arterial vasospasm.Materials and methodsAn electronic search of MEDLINE (Ovid), ProQuest, CINAHL and the Cochrane Database of Systematic Reviews was undertaken up to 1st October 2012 for randomised controlled trials (RCTs) of intravenous magnesium for the prevention of vasospasm in adult patients with aneurysmal SAH. Primary outcome measures were risk of vasospasm, functional outcomes and mortality. Results are presented as risk ratios (RR) and 95% confidence intervals (CI).ResultsNine of 38 trials were included in this review. Not all trials could be combined for analyses due to differences in reported outcomes and outcome definitions. Of the trials that could be combined we found a statistically significant reduction on the incidence of vasospasm with magnesium (RR 0.83; 95% CI 0.71, 0.98; P = 0.03). No statistical difference for the last reported favourable functional outcome (RR 1.00; 95% CI 0.96, 1.05; P = 0.84); or mortality (RR 0.95; 95% CI 0.77, 1.18; P = 0.67) between magnesium treated and standard care/control groups was found.ConclusionWe identified a benefit in the role of magnesium to reduce the incidence of cerebral vasospasm in patients with an aneurysmal SAH. However no benefit was found regarding improved favourable functional outcome or a reduction of mortality.     

Cerebrolysin for the Treatment of Aneurysmal Subarachnoid Hemorrhage in Adults: A Retrospective Chart Review

Introduction

Cerebrolysin is a neuroprotective drug used in the treatment of acute ischemic stroke. To our knowledge, this drug has never been evaluated in patients with aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to evaluate the effect of Cerebrolysin in patients with aneurysmal SAH.

Methods

Aneurysmal SAH patients who had their aneurysm obliterated at our institution from 2007 to 2016 were retrospectively studied. Patients received Cerebrolysin treatment or standard care only (control group). Subgroup analyses were performed according to Hunt and Hess grade (good grade?≤?2, N?=?216; poor grade?≥?3, N?=?246) and treatment procedure (clip or coil).

Results

In good-grade patients (N?=?216), clinical outcomes and mortality did not differ significantly between the control and Cerebrolysin groups. In poor-grade patients (N?=?246), the mortality rate was significantly lower in the Cerebrolysin group (8.7%) than in the control group (25.4%, p?=?0.006). In patients who received microsurgical clipping (N?=?328), the mortality rate was significantly lower in the Cerebrolysin group (7.3%) than in the control group (18.5%, p?=?0.016).

Conclusion

Cerebrolysin injection during the acute period of SAH appeared to reduce the mortality rate, especially in poor-grade patients. This study suggests the potential of Cerebrolysin for treating aneurysmal SAH. Further studies are needed to confirm our results.

     

Non-invasive assessment of vasospasm following aneurysmal SAH using C-arm FDCT parenchymal blood volume measurement in the neuro-interventional suite: Technical feasibility

Introduction

Cerebral vasospasm is the leading cause of morbidity and mortality in patients with aneurysmal subarachnoid haemorrhage (SAH) surviving the initial ictus. Commonly used techniques for vasospasm assessment are digital subtraction angiography and transcranial Doppler sonography. These techniques can reliably identify only the major vessel spasm and fail to estimate its haemodynamic significance. To overcome these issues and to enable comprehensive non-invasive assessment of vasospasm inside the interventional suite, a novel protocol involving measurement of parenchymal blood volume (PBV) using C-arm flat detector computed tomography (FDCT) was implemented.

Materials and methods

Patients from the neuro-intensive treatment unit (ITU) with suspected vasospasm following aneurysmal SAH were scanned with a biplane C-arm angiography system using an intravenous contrast injection protocol. The PBV maps were generated using prototype software. Contemporaneous clinically indicated MR scan including the diffusion- and perfusion-weighted sequences was performed. C-arm PBV maps were compared against the MR perfusion maps.

Results

Distribution of haemodynamic impairment on C-arm PBV maps closely matched the pattern of abnormality on MR perfusion maps. On visual comparison between the two techniques, the extent of abnormality indicated PBV to be both cerebral blood flow and cerebral blood volume weighted.

Conclusion

C-arm FDCT PBV measurements allow an objective assessment of the severity and localisation of cerebral hypoperfusion resulting from vasospasm. The technique has proved feasible and useful in very sick patients after aneurysmal SAH. The promise shown in this early study indicates that it deserves further evaluation both for post-SAH vasospasm and in other relevant clinical settings.     

Nurses' prediction of volume status after aneurysmal subarachnoid haemorrhage: a prospective cohort study

Introduction  

Patients who have suffered aneurysmal subarachnoid haemorrhage (SAH) often have derangements in blood volume, contributing to poor outcome. To guide fluid management, regular assessments of volume status must be conducted. We studied the ability of nursing staff to predict hypovolaemia or hypervolaemia, based on their interpretation of available haemodynamic data.     

Dose evaluation for long-term magnesium treatment in aneurysmal subarachnoid haemorrhage

BACKGROUND: Magnesium is a neuroprotective agent that might prevent or reverse delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage (SAH). We are presently running a randomized, placebo-controlled, double blind trial with magnesium sulphate (64 mmol/day intravenously). We studied whether this treatment regime resulted in our target serum magnesium levels of 1.0-2.0 mmol/L. METHODS: Magnesium sulphate was administered intravenously as soon as possible after admission and continued until 14 days after occlusion of the aneurysm. Serum magnesium measurements were done at baseline and at least every 2 days during administration of trial medication. For comparison we used the serum magnesium levels of the placebo-treated patients. RESULTS: Magnesium therapy was begun in 94 patients. The mean magnesium level in the treatment period was 1.47 +/- 0.32 mmol/L. In 81 patients serum magnesium stayed within target levels during the entire treatment period. One patient had a serum magnesium level below 1.0 mmol/L (0.91 mmol/L) in a single measurement and 10 patients had serum magnesium levels above 2.0 mmol/L at one or more measurements. In six patients magnesium therapy was discontinued: in three because of nausea, headache, or both in combination with serum magnesium levels above 2.0 mmol/L and in the other three because of hypotension, phlebitis and renal failure. CONCLUSIONS: With an intravenous dosage schedule of 64 mmol magnesium sulphate a day, serum magnesium levels of 1.0-2.0 mmol/L can easily be maintained without severe side effects for an extended period in a vast majority of patients with SAH.     

Comparison of nebulised magnesium sulphate and salbutamol combined with salbutamol alone in the treatment of acute bronchial asthma: a randomised study

Objective

To test the hypothesis that combined administration of multiple doses of nebulised salbutamol and magnesium sulphate provides additional benefit compared with salbutamol alone in adult patients with acute asthma.

Design

Randomised, double blind, prospective study.

Methods

A total of 100 patients presenting to an emergency department with an acute attack of bronchial asthma were randomised to two groups: nebulisation with a combination of salbutamol and magnesium sulphate (group A) and nebulisation with salbutamol only (group B). Both groups received nebulisation thrice at intervals of 20 minutes. Salbutamol and magnesium sulphate were administered in doses of 0.5 mg and 500 mg, respectively, and the solutions were made isotonic to plasma osmolality. Pulse rate, blood pressure, and peak expiratory flow rate (PEFR) were measured at baseline and at 15, 60, 75, and 120 minutes. Serum magnesium levels and blood gases were measured at 0 and 120 minutes in both groups.

Results

All patients had either acute severe or life threatening asthma. The baseline characteristics were comparable in the two groups. Both groups showed significant rise in PEFR at all time intervals, however, there was no significant difference between the groups in rise in PEFR at any time point. Serum magnesium levels remained within normal limits, and there was no difference in requirement of additional medication during the study or hospital admission rates in both groups. No significant side effects were noted.

Conclusion

This study suggests that there is no therapeutic benefit of adding magnesium sulphate to salbutamol nebulisation in the treatment of patients with acute severe or life threatening asthma.     

Effect of different components of triple-H therapy on cerebral perfusion in patients with aneurysmal subarachnoid haemorrhage: a systematic review

Introduction  

Triple-H therapy and its separate components (hypervolemia, hemodilution, and hypertension) aim to increase cerebral perfusion in subarachnoid haemorrhage (SAH) patients with delayed cerebral ischemia. We systematically reviewed the literature on the effect of triple-H components on cerebral perfusion in SAH patients.     

Nutritional support and brain tissue glucose metabolism in poor-grade SAH: a retrospective observational study

Introduction

We sought to determine the effect of nutritional support and insulin infusion therapy on serum and brain glucose levels and cerebral metabolic crisis after aneurysmal subarachnoid hemorrhage (SAH).

Methods

We used a retrospective observational cohort study of 50 mechanically ventilated poor-grade (Hunt-Hess 4 or 5) aneurysmal SAH patients who underwent brain microdialysis monitoring for an average of 109 hours. Enteral nutrition was started within 72 hours of admission whenever feasible. Intensive insulin therapy was used to maintain serum glucose levels between 5.5 and 7.8 mmol/l. Serum glucose, insulin and caloric intake from enteral tube feeds, dextrose and propofol were recorded hourly. Cerebral metabolic distress was defined as a lactate to pyruvate ratio (LPR) > 40. Time-series data were analyzed using a general linear model extended by generalized estimation equations (GEE).

Results

Daily mean caloric intake received was 13.8 ± 6.9 cal/kg and mean serum glucose was 7.9 ± 1 mmol/l. A total of 32% of hourly recordings indicated a state of metabolic distress and < 1% indicated a state of critical brain hypoglycemia (< 0.2 mmol/l). Calories received from enteral tube feeds were associated with higher serum glucose concentrations (Wald = 6.07, P = 0.048), more insulin administered (Wald = 108, P < 0.001), higher body mass index (Wald = 213.47, P < 0.001), and lower body temperature (Wald = 4.1, P = 0.043). Enteral feeding (Wald = 1.743, P = 0.418) was not related to brain glucose concentrations after accounting for serum glucose concentrations (Wald = 67.41, P < 0.001). In the presence of metabolic distress, increased insulin administration was associated with a relative reduction of interstitial brain glucose concentrations (Wald = 8.26, P = 0.017), independent of serum glucose levels.

Conclusions

In the presence of metabolic distress, insulin administration is associated with reductions in brain glucose concentration that are independent of serum glucose levels. Further study is needed to understand how nutritional support and insulin administration can be optimized to minimize secondary injury after subarachnoid hemorrhage.     

Effects of acute hypermagnesaemia on intracellular calcium concentration and adrenergic activity

The effects of acute hypermagnesaemia on intracellular free calcium and adrenergic activity were investigated in six normotensive volunteers given intravenous magnesium sulphate for 3 h. The free calcium concentration in platelets decreased after the first hour of infusion (P less than 0.05), but did not remain significantly depressed after 2 and 3 h of continued infusion. Plasma noradrenaline increased during the infusion (P less than 0.05), with no change in plasma adrenaline. The results demonstrate that the effects of intravenous magnesium sulphate on free intracellular calcium and plasma catecholamines are similar to those described with calcium antagonists.     

Subarachnoid Hemorrhage in Type 1 Diabetes: A prospective cohort study of 4,083 patients with diabetes

OBJECTIVE

To estimate for the first time the incidence of subarachnoid hemorrhage (SAH) in type 1 diabetes.

RESEARCH DESIGN AND METHODS

Using the nationwide Finnish Diabetic Nephropathy (FinnDiane) Study cohort of 4,083 patients with type 1 diabetes (mean age of 37.4 ± 11.8 years at enrollment), we analyzed the incidence of first-ever SAH events.

RESULTS

During the follow-up time of 36,680 person-years (median 9.4 years), 15 patients with type 1 diabetes experienced an aneurysmal or nonaneurysmal SAH, and thus the crude incidence of SAH was 40.9 (95% CI 22.9–67.4) per 100,000 person-years. One patient had a verified aneurysmal SAH, and four patients died suddenly of an SAH, which was most likely caused by an aneurysm. SAHs in 10 out of 15 patients were classified as nonaneurysmal SAH, and thus the crude incidence of nonaneurysmal SAH was 27.3 (13.1–50.1) per 100,000 person-years. None of the nonaneurysmal SAHs were fatal. In univariate analysis, current smokers had a hazard ratio of 4.82 (95% CI 1.31–17.81) for nonaneurysmal SAH.

CONCLUSIONS

The incidence of nonaneurysmal SAH is high among patients with type 1 diabetes. Our findings suggest that nonaneurysmal SAH is a distinct new microvascular complication in type 1 diabetes.Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular event, which is usually caused by a rupture of a cerebrovascular aneurysm. These aneurysms are mostly found in relatively large-caliber (≥1 mm) vessels and can often be considered as macrovascular lesions. The overall incidence of SAH has been reported to be 10.3 per 100,000 person-years (1), even though the variation in incidence between countries is substantial (1). Notably, the population-based incidence of SAH is 35 per 100,000 person-years in the adult (≥25 years of age) Finnish population (2). The incidence of nonaneurysmal SAH is globally unknown, but it is commonly believed that 5–15% of all SAHs are of nonaneurysmal origin. Prospective, long-term, population-based SAH risk factor studies suggest that smoking (2–4), high blood pressure (2–4), age (2,3), and female sex (2,4) are the most important risk factors for SAH, whereas diabetes (both types 1 and 2) does not appear to be associated with an increased risk of SAH (2,3).An increased risk of cardiovascular disease is well recognized in people with diabetes. There are, however, very few studies on the risk of cerebrovascular disease in type 1 diabetes since most studies have focused on type 2 diabetes alone or together with type 1 diabetes. Cerebrovascular mortality in the 20–39-year age-group of people with type 1 diabetes is increased five- to sevenfold in comparison with the general population but accounts only for 15% of all cardiovascular deaths (5). Of the cerebrovascular deaths in patients with type 1 diabetes, 23% are due to hemorrhagic strokes (5). However, the incidence of SAH in type 1 diabetes is unknown.By knowing the incidence of SAH in type 1 diabetes, the overall risk of stroke in patients with type 1 diabetes could be estimated more accurately. Moreover, comprehensive prospective patient cohorts that are susceptible to cerebrovascular events may provide new knowledge of the risk factors for SAH. In this prospective cohort study of 4,083 patients with type 1 diabetes, we aimed to determine the incidence and characteristics of SAH.     

Interferon-β attenuates lung inflammation following experimental subarachnoid hemorrhage

Introduction  

Aneurysmal subarachnoid hemorrhage (SAH) affects relatively young people and carries a poor prognosis with a case fatality rate of 35%. One of the major systemic complications associated with SAH is acute lung injury (ALI) which occurs in up to one-third of the patients and is associated with poor outcome. ALI in SAH may be predisposed by neurogenic pulmonary edema (NPE) and inflammatory mediators. The objective of this study was to assess the immunomodulatory effects of interferon-β (IFN-β) on inflammatory mediators in the lung after experimental SAH.     

Magnesium sulfate for aneurysmal subarachnoid hemorrhage: the end of the road or more trials?

Delayed cerebral ischemia (DCI) is a feared complication and an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). In the current study, Wong and colleagues performed a systematic review and meta-analysis of randomized controlled trials that investigated the efficacy of magnesium sulfate in patients with aneurysmal SAH. Outcome measures were DCI, cerebral infarction, and functional outcome 3 and 6 months after SAH. Magnesium sulfate decreased the rate of cerebral infarction, but not of DCI or poor functional outcome. Regarding outcome, a beneficial effect of magnesium sulfate on outcome can not be ruled out because of sample size limitations. Even if this meta-analysis had shown an effect on outcome, the question remains which treatment protocol should be applied in daily practice, since the administration of magnesium sulfate differed between most included studies. The present meta-analysis also underlines the importance of defining clinically relevant endpoints in SAH trials. Clinical deterioration due to DCI is more subject to inter-observer bias compared to cerebral infarction, which represents the ultimate outcome of the ischemic event. The Magnesium in Aneurysmal Subarachnoid Hemorrhage-II (MASH-II: ISRCTN68742385) phase III clinical trial nears completion. It aims to include 1,200 patients, and its results are urgently awaited.     

Impact of intravenous magnesium infusion rate during ambulatory replacements on serum magnesium concentrations after allogeneic stem cell transplant

Purpose

For an outpatient cancer center to operate efficiently, optimizing the use of chair time is essential. Allogeneic hematopoietic cell transplant (allo-HCT) recipients are seen frequently in this setting after hospital discharge and regularly for several months thereafter. Aggressive electrolyte replacement is commonly required in these patients, primarily due to renal wasting with calcineurin inhibitor use. Frequent intravenous (IV) magnesium repletion, requiring several hours of infusion time, is often needed in these patients to adequately manage their magnesium deficiencies. The purpose of this study is to explore the impact of extending the infusion rate of intravenous magnesium sulfate on the frequency and degree of IV magnesium replacements required in allo-HCT recipients.

Methods

We conducted a retrospective study to compare two cohorts of patients administered IV magnesium sulfate at a rate of 4 g/1 h versus 4 g/2 h.

Results

A total of 103 continuous patients were assessed in two groups as cohort 1 at the 4 g/1 h rate and cohort 2 at the 4 g/2 h rate. Cohort 1 required less IV magnesium per outpatient visit (median 2.2 vs. 2.9 g/visit, P?=?0.0211) and less total IV magnesium replacement through day +100 (median 68 vs. 85 g, P?=?0.0479) than cohort 2.

Conclusion

These data suggest that there is no apparent benefit of prolonging magnesium infusion from 1 to 2 h in our outpatient allo-HCT population.