Anaemia and its treatment in neurologically critically ill patients: being reasonable is easy without prospective trials

Most healthy humans have a haemoglobin concentration of 12 to 15 g/dL and most intensivists now transfuse packed red blood cells for haemoglobin <7 g/dL. Higher haemoglobin is associated with improved intermediate and clinical outcomes after subarachnoid hemorrhage (from ruptured brain aneurysm) or neurotrauma. An observational study in a recent issue shows that higher haemoglobin was associated with better functional outcomes in patients with spontaneous intracerebral haemorrhage; few patients received a packed red blood cell transfusion, so it is not known if that treatment is better than the disease. The mechanism of anaemia's purported impact on outcome is unclear, although altered metabolism in brain tissue that is sensitive to reduced oxygen delivery is plausible. These data may intensify the differences of opinion between intensivists: whether neurologic patients are better served by higher haemoglobin and potentially by more packed red blood cell transfusion, or simply need to be studied more in prospective clinical trials, remains unclear

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

Abstract 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. Methods We performed a survey of North American academic neurointensivists, vascular neurosurgeons and multidisciplinary intensivists who regularly care for patients with SAH to determine hemoglobin (Hb) concentrations which commonly trigger a decision to initiate transfusion. We also assessed minimum and maximum acceptable Hb goals in the context of a clinical trial and how decision-making is influenced by advanced neurological monitoring, clinician characteristics and patient-specific factors. Results The survey was sent to 531 clinicians, of whom 282 (53%) responded. In a hypothetical patient with high-grade SAH (WFNS 4), the mean Hb concentration at which clinicians administered RBCs was 8.19 g/dL (95% CI, 8.07 to 8.30 g/dL). Transfusion practices were comparatively more restrictive in patients with low-grade SAH (mean Hb 7.85 g/dL (95% CI, 7.73 to 7.97 g/dL)) (P < 0.0001) and more liberal in patients with delayed cerebral ischemia (DCI) (mean Hb 8.58 g/dL (95% CI, 8.45 to 8.72 g/dL)) (P < 0.0001). In each setting, there was a broad range of opinions. The majority of respondents expressed a willingness to study a restrictive threshold of ≤8 g/dL (92%) and a liberal goal of ≥10 g/dl (75%); in both cases, the preferred transfusion thresholds were significantly higher for patients with DCI (P < 0.0001). Neurosurgeons expressed higher minimum Hb goals than intensivists, especially for patients with high-grade SAH (β = 0.46, P = 0.003), and were more likely to administer two rather than one unit of RBCs (56% vs. 19%; P < 0.0001). Institutional use of transfusion protocols was associated with more restrictive practices. More senior clinicians preferred higher Hb goals in the context of a clinical trial. Respondents were more likely to transfuse patients with brain tissue oxygen tension values <15 mmHg and lactate-to-pyruvate ratios >40. Conclusions There is widespread variation in the use of RBC transfusions in SAH patients. Practices are heavily influenced by the specific dynamic clinical characteristics of patients and may be further modified by clinician specialty and seniority, the use of protocols and advanced neurological monitoring

A Human Depression Circuit Derived From Focal Brain Lesions

Background: Focal brain lesions can lend insight into the causal neuroanatomical substrate of depression in the human brain. However, studies of lesion location have led to inconsistent results.Methods: Five independent datasets with different lesion etiologies and measures of postlesion depression were collated (N = 461). Each 3-dimensional lesion location was mapped to a common brain atlas. We used voxel lesion symptom mapping to test for associations between depression and lesion locations. Next, we computed the network of regions functionally connected to each lesion location using a large normative connectome dataset (N = 1000). We used these lesion network maps to test for associations between depression and connected brain circuits. Reproducibility was assessed using a rigorous leave-one-dataset-out validation. Finally, we tested whether lesion locations associated with depression fell within the same circuit as brain stimulation sites that were effective for improving poststroke depression.Results: Lesion locations associated with depression were highly heterogeneous, and no single brain region was consistently implicated. However, these same lesion locations mapped to a connected brain circuit, centered on the left dorsolateral prefrontal cortex. Results were robust to leave-one-dataset-out cross-validation. Finally, our depression circuit derived from brain lesions aligned with brain stimulation sites that were effective for improving poststroke depression.Conclusions: Lesion locations associated with depression fail to map to a specific brain region but do map to a specific brain circuit. This circuit may have prognostic utility in identifying patients at risk for poststroke depression and therapeutic utility in refining brain stimulation targets.</p

Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care : a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data

Blood Pressure Medication and Acute Kidney Injury After Intracerebral Haemorrhage: An Analysis of the ATACH-II Trial

Background Acute blood pressure (BP) reduction is standard of care after acute intracerebral haemorrhage (ICH). More acute BP reduction is associated with acute kidney injury (AKI). It is not known if the choice of antihypertensive medications affects the risk of AKI.Methods We analysed data from the ATACH-II clinical trial. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. We analysed antihypertensive medication from two sources. The first was a case report form that specified the use of labetalol, diltiazem, urapidil or other. We tested the hypothesis that the secondary medication was associated with AKI with χ2 test. Second, we tested the hypotheses the dosage of diltiazem was associated with AKI using Mann-Whitney U test.Results AKI occurred in 109 of 1000 patients (10.9%). A higher proportion of patients with AKI received diltiazem after nicardipine (12 (29%) vs 21 (12%), p=0.03). The 95%ile (90%–99% ile) of administered diltiazem was 18 (0–130) mg in patients with AKI vs 0 (0–30) mg in patients without AKI (p=0.002). There was no apparent confounding by indication for diltiazem use.Conclusions The use of diltiazem, and more diltiazem, was associated with AKI in patients with acute ICH

Blood pressure medication and acute kidney injury after intracerebral haemorrhage: an analysis of the ATACH-II trial

Background Acute blood pressure (BP) reduction is standard of care after acute intracerebral haemorrhage (ICH). More acute BP reduction is associated with acute kidney injury (AKI). It is not known if the choice of antihypertensive medications affects the risk of AKI.Methods We analysed data from the ATACH-II clinical trial. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. We analysed antihypertensive medication from two sources. The first was a case report form that specified the use of labetalol, diltiazem, urapidil or other. We tested the hypothesis that the secondary medication was associated with AKI with χ2 test. Second, we tested the hypotheses the dosage of diltiazem was associated with AKI using Mann-Whitney U test.Results AKI occurred in 109 of 1000 patients (10.9%). A higher proportion of patients with AKI received diltiazem after nicardipine (12 (29%) vs 21 (12%), p=0.03). The 95%ile (90%–99% ile) of administered diltiazem was 18 (0–130) mg in patients with AKI vs 0 (0–30) mg in patients without AKI (p=0.002). There was no apparent confounding by indication for diltiazem use.Conclusions The use of diltiazem, and more diltiazem, was associated with AKI in patients with acute ICH

The Story of Intracerebral Hemorrhage: From Recalcitrant to Treatable Disease

This invited special report is based on an award presentation at the World Stroke Organization/European Stroke Organization Conference in November of 2020 outlining progress in the acute management of intracerebral hemorrhage (ICH) over the past 35 years. ICH is the second most common and the deadliest type of stroke for which there is no scientifically proven medical or surgical treatment. Prospective studies from the 1990s onward have demonstrated that most growth of spontaneous ICH occurs within the first 2 to 3 hours and that growth of ICH and resulting volumes of ICH and intraventricular hemorrhage are modifiable factors that can improve outcome. Trials focusing on early treatment of elevated blood pressure have suggested a target systolic blood pressure of 140 mm Hg, but none of the trials were positive by their primary end point. Hemostatic agents to decrease bleeding in spontaneous ICH have included desmopressin, tranexamic acid, and rFVIIa (recombinant factor VIIa) without clear benefit, and platelet infusions which were associated with harm. Hemostatic agents delivered within the first several hours have the greatest impact on growth of ICH and potentially on outcome. No large Phase III surgical ICH trial has been positive by primary end point, but pooled analyses suggest that earlier ICH removal is more likely to be beneficial. Recent trials emphasize maximization of clot removal and minimizing brain injury from the surgical approach. The future of ICH therapy must focus on delivery of medical and surgical therapies as soon as possible if we are to improve outcomes