Use of Antiepileptic Drugs in Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: Controversy exists in antiepileptic drug (AED) prophylaxis prescribing in patients with aneurysmal subarachnoid hemorrhage (SAH). We undertook the Use of Antiepileptic Drugs in Aneurysmal Subarachnoid Hemorrhage (ALIBI) study to identify factors associated with prescribing practices. METHODS: A retrospective chart review of all consecutive patients requiring Level 1 care with aneurysmal SAH admitted between 2012 and 2014 to the intensive care unit at Toronto Western Hospital, Ontario, Canada, was conducted. Data were collected on clinical and imaging characteristics. Primary and secondary outcomes were AED prophylaxis and clinical seizure activity during hospitalization. Data were compared using chi-square or Mann-Whitney U-tests. Those variables found to be significant, or trending toward significance, on univariate analysis were fitted to multivariate regression. RESULTS: Sixty-eight patients were included. Mean age was 62 ± 12.2, and 42.6% of patients were male. Of these, 21 patients (30.9%) received AED prophylactically, while 18 (26.5%) had reported seizures at some point during hospitalization. Female gender and presence of midline shift (MLS) were significantly associated or approached significance with AED prophylaxis in univariate analysis (p = 0.036 and p = 0.062, respectively). In multivariate analysis, only MLS was an independent predictor (odds ratio 5.09, p = 0.04). CONCLUSION: The presence of MLS was an independent predictor of seizure activity in patients with aneurysmal SAH. AED prophylaxis prescribing patterns seemed arbitrary and was not informed by identifiable clinical factors or true risk factors for seizure. A current lack of evidence guiding AED prescribing practice highlights the need for larger studies in this patient population.

Utiliser des médicaments antiépileptiques dans des cas d'hémorragie sous-arachnoïdienne anévrismale. Introduction: Dans les cas de patients victimes d'hémorragie sous-arachnoïdienne anévrismale, il faut savoir qu'un traitement prophylactique au moyen de médicaments antiépileptiques demeure controversé. Dans cette étude, nous avons donc entrepris d'identifier les facteurs associés aux pratiques de prescription de ces médicaments lorsque survient ce type d'hémorragie. Méthodes: Pour ce faire, nous avons passé en revue les dossiers de tous les patients vus consécutivement et ayant nécessité, après avoir été admis entre 2012 et 2014 à l'unité des soins intensifs du Toronto Western Hospital (Ontario, Canada), des soins de niveau 1 à la suite d'une hémorragie sous-arachnoïdienne anévrismale. Nous avons collecté nos données en nous basant sur des aspects cliniques et sur d'autres aspects liés à des examens d'IRM. Notre principal résultat mesuré a été l'efficacité d'un traitement prophylactique au moyen de médicaments antiépileptiques; dans un deuxième temps, nous avons aussi cherché à mesurer l'activité convulsive clinique en cours d'hospitalisation. Nous avons ensuite comparé nos données en utilisant les tests du X2 ou de U Mann-Whitney. Les variables apparues significatives ou tendant à être significatives dans le cadre d'une analyse univariée ont été ajustées pour une régression multivariée. Résultats: 68 patients ont été inclus dans cette étude. Leur âge moyen était de 62 ± 12,2; 42,6% d'entre eux étaient des hommes. De ce nombre, 21 patients (30,9%) ont alors suivi un traitement prophylactique au moyen de médicaments antiépileptiques tandis que 18 (26,5%) ont fait état de crises convulsives à un moment ou un autre de leur séjour à l'hôpital. Dans le cadre d'une analyse univariée, le fait d'être une femme et la présence d'une déviation de la ligne médiane (midline shift) ont été par ailleurs nettement associés ou en grande partie associés à un traitement prophylactique au moyen de médicaments antiépileptiques (respectivement p = 0,036 et p = 0,062). Dans le cadre d'une analyse multivariée, seule la déviation de la ligne médiane s'est avérée un facteur prédicteur indépendant (rapport des cotes de 5,09; P = 0,04). Conclusion: La présence de déviation de la ligne médiane constitue un facteur prédictif indépendant d'activité convulsive chez des patients victimes d'hémorragie sous-arachnoïdienne anévrismale. De plus, les tendances en matière de prescription de médicaments antiépileptiques apparaissent arbitraires et ne reposent pas sur des facteurs cliniques identifiables ou sur de véritables facteurs de risque liés aux convulsions. Le manque actuel de preuves pouvant orienter les pratiques de prescription de ces médicaments met en lumière la nécessité d'effectuer de plus amples études au sein de cette population de patients.

A multicentre observational study of the use of antiseizure medication in patients with aneurysmal subarachnoid haemorrhage in the PROMOTE-SAH study.

Our objective was to describe antiseizure medication (ASM) prescription patterns, and associations between ASM use and death and disability outcomes in patients with aneurysmal subarachnoid haemorrhage (aSAH) admitted to ICU. This was a multi-centre prospective observational study. The study took place in eleven ICUs across Australia and New Zealand. Data was collected from 1 April 2017 to 1 October 2018. Three hundred and fifty-seven adult patients with aSAH were enrolled. The primary outcome was to describe patterns of ASM prescription. The secondary outcome of interest was death or disability (modified Rankin Scale (mRS) score ≥ 4) at six months, and its association with ASM therapy, and relevant clinical subgroups. Forty percent of patients received an ASM and the most commonly used agent was levetiracetam. The median length of ASM administration was eight days (IQR 4.5-12.5). A number of patients with prehospital seizures did not receive ASM therapy (14/55, 2725%). There was a tendency towards ASM prescription with both higher radiological and clinical grade aSAH. There was no significant association between death or disability at six month (mRS ≥ 4) and ASM vs No ASM prescription. Testing for an interaction effect between ASM administration and WFNS grade suggested inferior outcomes with ASM use in lower aSAH grades (p = 0.04). In conclusion, the prescription of ASM for aSAH in Australia is variable across and within sites, with the majority of patients not receiving ASM chemoprophylaxis. We demonstrated no significant association between death or disability at six months and the use of ASM. There may be an association with poorer outcomes in patients with lower grade aSAH. This finding requires further exploration.

Drug reaction with eosinophilia and systemic symptoms syndrome secondary to acetazolamide associated with markedly elevated procalcitonin.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an important cause of multi-organ dysfunction and can mimic other disorders including sepsis. We describe a patient presenting with septic shock and accompanying high procalcitonin. Although initially treated empirically with antibiotics, the emergence of eosinophilia during the admission lead to a revised diagnosis of DRESS syndrome, presumed secondary to acetazolamide. This case highlights the importance of regular clinical assessment and re-evaluation is key in identifying emerging features such as eosinophilia, rash and organ dysfunction, which can secure the diagnosis. Furthermore, the case also highlights that acetazolamide may be a rare cause of DRESS syndrome.

Dysnatremia and 6-Month Functional Outcomes in Critically Ill Patients With Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.

OBJECTIVES: To investigate the association between plasma sodium concentrations and 6-month neurologic outcome in critically ill patients with aneurysmal subarachnoid hemorrhage. DESIGN: Prospective cohort study. SETTING: Eleven ICUs in Australia and New Zealand. PARTICIPANTS: Three-hundred fifty-six aneurysmal subarachnoid hemorrhage patients admitted to ICU between March 2016 and June 2018. The exposure variable was daily measured plasma sodium. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six-month neurologic outcome as measured by the modified Rankin Scale. A poor outcome was defined as a modified Rankin Scale greater than or equal to 4. The mean age was 57 years (± 12.6 yr), 68% were female, and 32% (n = 113) had a poor outcome. In multivariable analysis, including age, illness severity, and process of care measures as covariates, higher mean sodium concentrations (odds ratio, 1.17; 95% CI, 1.05-1.29), and greater overall variability-as measured by the sd (odds ratio, 1.53; 95% CI, 1.17-1.99)-were associated with a greater likelihood of a poor outcome. Multivariable generalized additive modeling demonstrated, specifically, that a high initial sodium concentration, followed by a gradual decline from day 3 onwards, was also associated with a poor outcome. Finally, greater variability in sodium concentrations was associated with a longer ICU and hospital length of stay: mean ICU length of stay ratio (1.13; 95% CI, 1.07-1.20) and mean hospital length of stay ratio (1.08; 95% CI, 1.01-1.15). CONCLUSIONS: In critically ill aneurysmal subarachnoid hemorrhage patients, higher mean sodium concentrations and greater variability were associated with worse neurologic outcomes at 6 months, despite adjustment for known confounders. Interventional studies would be required to demonstrate a causal relationship.

MyD88 signaling controls autoimmune myocarditis induction.

BACKGROUND: Experimental autoimmune myocarditis (EAM) is a CD4+ T-cell-mediated mouse model of postviral cardiomyopathy. Activation of interleukin-1 type 1 and Toll-like receptors that share the common downstream adaptor molecule MyD88 is required for disease induction. The specific role of MyD88 in myocarditis, however, is not known. METHODS AND RESULTS: In contrast to control littermates, MyD88(-/-) mice were protected from myocarditis after immunization with alpha-myosin heavy chain-derived peptide (MyHC-alpha) and complete Freund's adjuvant. Disease resistance of MyD88(-/-) mice resulted from impaired expansion of heart-specific CD4+ T cells after immunization. Intrinsic defects of MyD88(-/-) CD4+ T cells were excluded. In contrast, MyD88(-/-) but not MyD88(+/+) primary antigen presenting dendritic cells (DCs) were defective in their capacity to prime CD4+ T cells. This defect mainly resulted from the inability of MyD88(-/-) DCs to release tumor necrosis factor-alpha. The critical role of MyD88 signaling in DCs in the peripheral lymphatic compartments was finally proven by repetitive injection of activated, MyHC-alpha-loaded MyD88(+/+) DCs that fully restored T-cell expansion and myocarditis in MyD88(-/-) mice. CONCLUSIONS: Autoimmune myocarditis induction depends on MyD88 signaling in self-antigen presenting cells in the peripheral compartments. We conclude that MyD88 might become a target for prevention of heart-specific autoimmunity and cardiomyopathy.

Critical care management of aneurysmal subarachnoid haemorrhage in Australia and New Zealand: what are we doing, and where to from here?

Patients with an aneurysmal subarachnoid haemorrhage (SAH) frequently require admission to the intensive care unit. There, a variety of therapeutic strategies are initiated, in addition to definitive procedures aimed at securing the aneurysm. Despite a substantial investment in caring for these patients, outcomes for this group remain poor. Although the severity of the initial bleed is crucial in this context, many patients undergo further deterioration in the ICU. Delayed cerebral ischaemia is a significant cause of longterm morbidity and mortality after SAH. There are limited data supporting much of the critical care provided to patients with SAH in the ICU, leading to substantial institutional and practitioner variation in treatment. Whether this influences patient outcomes is unknown, although it represents a major knowledge gap in neurocritical practice in Australia and New Zealand.