Blood Pressure Management in Early Aneurysmal Subarachnoid Hemorrhage: A National Cross-Sectional Survey of Canadian Intensivists and Cerebrovascular Neurosurgeons.

BACKGROUND: In aneurysmal subarachnoid hemorrhage (aSAH), rebleeding of the culprit aneurysm is associated with significant morbidity and mortality. Blood pressure reduction to specific target levels, with the goal of preventing rebleeding, has been a mainstay of care prior to definitively securing the aneurysm. Clinical practice guidelines have recently changed and no longer recommend specific blood pressure targets. This survey aims to identify the reported practice patterns and beliefs regarding blood pressure management during the early phase of aSAH. METHODS: We conducted a self-administered, Web-based survey of critical care physicians and cerebrovascular neurosurgeons practicing in Canada. The questionnaire contained 21 items, including 3 case-based scenarios to elicit blood pressure target selection, both before and after aneurysm securing. RESULTS: In the presecured period, systolic blood pressures of 160 mm Hg (50% [144 of 287]) and 140 mm Hg (42% [120 of 287]) were the most frequently selected upper-limit targets. In the postsecured period, a systolic blood pressure of 180 mm Hg (32% [93 of 287]) was the most frequently selected upper-limit target, but there was a wide distribution of targets selected across all three cases ranging from 100 to > 200 mm Hg. A mean arterial pressure of 65 mm Hg was the most common lower-limit target in both the presecured and postsecured periods. There was little change in blood pressure targets with increasing clinical severity. Predictors of higher or lower blood pressure target selection and barriers to implementation of the desired target were identified. CONCLUSIONS: During the presecured period, nearly half of the reported upper-limit blood pressure targets are lower than previous guideline recommendations. These targets remain consistent despite increasing clinical severity and could potentially exacerbate cerebral ischemia and negatively impact clinical outcomes. In the postsecured period, there is wide variation in the reported blood pressure targets. A clinical trial is urgently needed to guide decision-making.

Anemia and Red Blood Cell Transfusion in Aneurysmal Subarachnoid Hemorrhage.

Anemia is very common in aneurysmal subarachnoid hemorrhage (aSAH), with approximately half of the aSAH patient population developing moderate anemia during their hospital stay. The available evidence (both physiologic and clinical) generally supports an association of anemia with unfavorable outcomes. Although aSAH shares a number of common mechanisms of secondary insult with other forms of acute brain injury, aSAH also has specific features that make it unique: an early phase (in which early brain injury predominates) and a delayed phase (in which delayed cerebral ischemia and vasospasm predominate). The effects of both anemia and transfusion are potentially variable between these phases, which may have unique considerations and possibly different risk-benefit profiles. Data on transfusion in this population are almost exclusively limited to observational studies, which suffer from significant heterogeneity and risk of bias. Overall, the results are conflicting, with the balance of the studies suggesting that transfusion is associated with unfavorable outcomes. The transfusion targets that are well established in other critically ill populations should not be automatically applied to patients with aSAH because of the unique disease characteristics of this population and the limited representation of aSAH in the clinical trials that established these targets. There are two upcoming clinical trials evaluating transfusion in aSAH that should help clarify specific transfusion targets. Until then, it is reasonable to base transfusion decisions on the current guidelines and use an individualized approach incorporating physiologic and clinical data when available.

Impact of an emergency department opioid prescribing guideline on emergency physician behaviour and incidence of overdose in the Saskatoon Health Region: a retrospective pre-post implementation analysis.

BACKGROUND: Deaths related to opioid overdoses are increasing in North America, with the emergency department being identified as a potential contributor toward this epidemic. Our goal was to determine whether a departmental guideline for the prescribing of restricted medications resulted in a reduction in opioids prescribed in a Canadian setting, with a secondary objective of determining the impact on local overdose frequency. METHODS: We conducted a retrospective analysis of the prescribing habits of emergency department physicians in 3 hospitals in the Saskatoon Health Region, Saskatchewan, before (Nov. 1, 2015, to Apr. 30, 2016) and after (Nov. 1, 2016, to Apr. 30, 2017) implementation of a guideline in September 2016 for the prescribing of restricted medications. We quantified opioids prescribed per hour worked and per patient seen. We performed Student paired 2-tailed t tests for both individual drug formulations and the combined total morphine equivalents. RESULTS: Thirty-two emergency department physicians were included. We found a decrease of 31.1% in opioids prescribed, from 10.36 morphine milligram equivalents (MME) per patient seen to 7.14 MME per patient seen (absolute change -3.22 MME, 95% confidence interval -4.81 to -1.63 MME). Over the same period, we found no change in prehospital naloxone use and a modest increase in the amount of naloxone dispensed by emergency department pharmacies. There was no decrease in the number of overdoses after guideline implementation. INTERPRETATION: Implementation of a guideline for the prescribing of restricted medications in a Canadian emergency department setting was associated with a decrease in the quantity of opioids prescribed but not in the number of overdoses. This finding suggests that the emergency department is unlikely the source of opioids used in acute overdose, although emergency department opioid prescriptions cannot be ruled out as a risk factor for opioid use disorder.

CpG stimulation of precursor B-lineage acute lymphoblastic leukemia induces a distinct change in costimulatory molecule expression and shifts allogeneic T cells toward a Th1 response.

Immunostimulatory DNA containing unmethylated cytosine-phosphate-guanosine (CpG) induces the development of T helper 1 (Th1) immune responses. The response of B cells to CpG stimulation involves increased proliferation, cytokine production, and costimulatory molecule expression. Similar effects have been observed following CpG stimulation of a variety of malignant B cells. Pediatric precursor B acute lymphoblastic leukemia (B-ALL) cells express low levels of costimulatory molecules and are generally poor stimulators of T-cell responses. In this study, we evaluated the impact of CpG stimulation on precursor B-ALL cell lines and pediatric patient-derived samples. The ability to respond to CpG oligodeoxynucleotides was determined by the level of Toll-like receptor 9 (TLR9) expression. In contrast to both nonleukemic B-cell precursors and mature B cells, the response of precursor B-ALL cells was characterized by increased CD40 expression but only small changes in CD86 levels and no induction of CD80 expression. CpG stimulation of ALL blasts produced increased levels of interleukin-6 (IL-6), IL-8, and IL-10 but no detectable IL-12p70 and led to a skewing of allogeneic T cells, with enhanced interferon gamma (IFN-gamma) production and reduced secretion of IL-5. These results demonstrate the functional relevance of CpG stimulation of precursor B-ALL cells and provide a rational basis for study of these agents for use in treatment of this disease.

Altered patterns of T cell cytokine production induced by relapsed pre-B ALL cells.

Relapse of pediatric acute lymphoblastic leukemia (ALL) remains a significant clinical problem. The graft-versus-leukemia (GVL) effect after hematopoietic stem cell transplantation indicates that immune mechanisms may play a role in the control of ALL blasts. In this study, we analyzed primary diagnostic and relapsed pre-B ALL samples for the surface expression of several molecules implicated in immune responses and for the induction of allogeneic T cell responses. There were no significant differences in the expression of CD11a, CD40, CD80 and CD86 or MHC classes I and II molecules between the diagnostic and relapsed samples. We found no significant differences in the overall ability of diagnostic and relapsed pre-B ALL samples to induce T cell proliferation and cytokine production. However, in the case of T cell responses induced by diagnostic ALL samples, there was excellent correlation between proliferation and production of all cytokines analyzed. In the case of relapsed samples, the only correlation obtained was with IL-5. This observation indicates that the nature of the immune response generated by relapsed ALL cells in an allogeneic setting differs from that obtained with diagnostic samples, suggests a biasing towards a Th2 response may contribute to the evasion of effective immune responses by relapsed ALL.