Dysnatremia and 6-Month Functional Outcomes in Critically Ill Patients With Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.
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ABSTRACT: 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.
SUBMITTER: Cohen J
PROVIDER: S-EPMC8189636 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This study aims to investigate the characteristics of patients with mild aneurysmal and non-aneurysmal perimesencephalic and non-perimesencephalic subarachnoid hemorrhage (aSAH, pmSAH, npmSAH) with emphasis on admission biomarkers, clinical course, and outcome. A prospective cohort of 115 patients with aSAH (Hunt and Hess 1-3) and of 35 patients without aneurysms (16 pmSAH and 19 npmSAH) admitted between January 2014 and January 2020 was included. Demographic data, blood samples on admission, complications (hydrocephalus, shunt dependency, delayed cerebral ischemia DCI, DCI-related infarction, and mortality), and outcome after 6 months were analyzed. Demographic data was comparable between all groups except for age (aSAH 55 [48-65] vs. npmSAH 60 [56-68] vs. pmSAH 52 [42-60], p = 0.032) and loss of consciousness (33% vs. 0% vs. 0%, p = 0.0004). Admission biomarkers showed poorer renal function and highest glucose levels for npmSAH patients. Complication rate in npmSAH was high and comparable to that of aSAH patients (hydrocephalus, shunt dependency, DCI, DCI-related infarction, mortality), but nearly absent in patients with pmSAH. Favorable outcome after 6 months was seen in 92.9% of pmSAH, 83.3% of npmSAH, and 62.7% of aSAH (p = 0.0264). In this prospective cohort of SAH patients, npmSAH was associated with a complicated clinical course, comparable to that of patients with aSAH. In contrast, such complications were nearly absent in pmSAH patients, suggesting fundamental differences in the pathophysiology of patients with different types of non-aneurysmal hemorrhage. Our findings underline the importance for a precise terminology according the hemorrhage etiology as a basis for more vigilant management of npmSAH patients. NCT02142166, 05/20/2014, retrospectively registered.
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Project description:Aneurysmal subarachnoid hemorrhage (SAH) is a worldwide health burden with high fatality and permanent disability rates. The overall prognosis depends on the volume of the initial bleed, rebleeding, and degree of delayed cerebral ischemia (DCI). Cardiac manifestations and neurogenic pulmonary edema indicate the severity of SAH. The International Subarachnoid Aneurysm Trial (ISAT) reported a favorable neurological outcome with the endovascular coiling procedure compared with surgical clipping at the end of 1 year. The ISAT trial recruits were primarily neurologically good grade patients with smaller anterior circulation aneurysms, and therefore the results cannot be reliably extrapolated to larger aneurysms, posterior circulation aneurysms, patients presenting with complex aneurysm morphology, and poor neurological grades. The role of hypothermia is not proven to be neuroprotective according to a large randomized controlled trial, Intraoperative Hypothermia for Aneurysms Surgery Trial (IHAST II), which recruited patients with good neurological grades. Patients in this trial were subjected to slow cooling and inadequate cooling time and were rewarmed rapidly. This methodology would have reduced the beneficial effects of hypothermia. Adenosine is found to be beneficial for transient induced hypotension in 2 retrospective analyses, without increasing the risk for cardiac and neurological morbidity. The neurological benefit of pharmacological neuroprotection and neuromonitoring is not proven in patients undergoing clipping of aneurysms. DCI is an important cause of morbidity and mortality following SAH, and the pathophysiology is likely multifactorial and not yet understood. At present, oral nimodipine has an established role in the management of DCI, along with maintenance of euvolemia and induced hypertension. Following SAH, hypernatremia, although less common than hyponatremia, is a predictor of poor neurological outcome.
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Project description:BackgroudUsing electronic health data, we sought to identify clinical and physiological parameters that in combination predict neurologic outcomes after aneurysmal subarachnoid hemorrhage (aSAH).MethodsWe conducted a single-center retrospective cohort study of patients admitted with aSAH between 2011 and 2016. A set of 473 predictor variables was evaluated. Our outcome measure was discharge Glasgow Outcome Scale (GOS). For laboratory and physiological data, we computed the minimum, maximum, median, and variance for the first three admission days. We created a penalized logistic regression model to determine predictors of outcome and a multivariate multilevel prediction model to predict poor (GOS 1-2), intermediate (GOS 3), or good (GOS 4-5) outcomes.ResultsOne hundred and fifty-three patients met inclusion criteria; most were discharged with a GOS of 3. Multivariate analysis predictors of mortality (AUC 0.9198) included APACHE II score, Glasgow Come Scale (GCS), white blood cell (WBC) count, mean arterial pressure, variance of serum glucose, intracranial pressure (ICP), and serum sodium. Predictors of death/dependence versus independence (GOS 4-5)(AUC 0.9456) were levetiracetam, mechanical ventilation, WBC count, heart rate, ICP variance, GCS, APACHE II, and epileptiform discharges. The multiclass prediction model selected GCS, admission APACHE II, periodic discharges, lacosamide, and rebleeding as significant predictors; model performance exceeded 80% accuracy in predicting poor or good outcome and exceeded 70% accuracy for predicting intermediate outcome.ConclusionsVariance in early physiologic data can impact patient outcomes and may serve as targets for early goal-directed therapy. Electronically retrievable features such as ICP, glucose levels, and electroencephalography patterns should be considered in disease severity and risk stratification scores.
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Project description:BackgroundAneurysmal subarachnoid hemorrhage (aSAH) is an important indication for intensive care unit admission and may lead to significant morbidity and mortality. We assessed the ability of C-terminal proarginine vasopressin (CT-proAVP) to predict disease outcome, mortality, and delayed cerebral ischemia (DCI) in critically ill patients with aSAH compared with the World Federation of Neurological Surgeons (WFNS) score and Acute Physiological and Chronic Health Evaluation IV (APACHE IV) model.MethodsC-terminal proarginine vasopressin was collected on admission in this single-center, prospective, observational cohort study. The primary aim was to investigate the relationship between CT-proAVP and poor functional outcome at 1 year (Glasgow Outcome Scale score 1-3) in a multivariable logistic regression model adjusted for WFNS and APACHE IV scores. Secondary aims were mortality and DCI. The multivariable logistic regression model for DCI was also adjusted for the modified Fisher scale.ResultsIn 100 patients, the median CT-proAVP level was 24.9 pmol/L (interquartile range 11.5-53.8); 45 patients had a poor 1-year functional outcome, 19 patients died within 30 days, 25 patients died within 1 year, and DCI occurred in 28 patients. Receiver operating characteristics curves revealed high accuracy for CT-proAVP to identify patients with poor 1-year functional outcome (area under the curve [AUC] 0.84, 95% confidence interval [CI] 0.77-0.92, p < 0.001), 30-day mortality (AUC 0.84, 95% CI 0.76-0.93, p < 0.001), and 1-year mortality (AUC 0.79, 95% CI 0.69-0.89, p < 0.001). CT-proAVP had a low AUC for identifying patients with DCI (AUC 0.67, 95% CI 0.55-0.79, p 0.008). CT-proAVP ≥ 24.9 pmo/L proved to be a significant predictor for poor 1-year functional outcome (odds ratio [OR] 8.04, 95% CI 2.97-21.75, p < 0.001), and CT-proAVP ≥ 29.1 pmol/L and ≥ 27.7 pmol/L were significant predictors for 30-day and 1-year mortality (OR 9.31, 95% CI 1.55-56.07, p 0.015 and OR 5.15, 95% CI 1.48-17.93, p 0.010) in multivariable models with WFNS and APACHE IV scores. CT-proAVP ≥ 29.5 pmol/L was not a significant predictor for DCI in a multivariable model adjusted for the modified Fisher scale (p = 0.061).ConclusionsC-terminal proarginine vasopressin was able to predict poor functional outcome and mortality in critically ill patients with aSAH. Its prognostic ability to predict DCI was low.Trial registrationNederlands Trial Register: NTR4118.
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Project description:BackgroundNimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH). Guidelines recommend that all patients should receive a fixed-dose nimodipine for 21 days. However, studies reported variability of nimodipine concentrations in aSAH. It is not clear if reduced systemic exposure contributes to worsening outcomes. The aim of this study was to compare nimodipine systemic exposure in those who experienced poor outcomes to those who experienced favorable outcomes.MethodsThis was a pilot prospective observational study in 30 adult patients admitted to the University of Alberta Hospital with aSAH. Data were collected from the electronic health records following enrollment. Blood samples were collected around one nimodipine 60 mg dose at a steady state, and nimodipine [total, (+)-R and (-)-S enantiomers] plasma concentrations were determined. The poor outcome was defined as a modified Rankin Scale (mRS) score at 90 days of 3-6, while the favorable outcome was an mRS score of 0-2. The correlation between nimodipine concentrations and percent changes in mean arterial pressure (MAP) before and after nimodipine administration was also determined. Furthermore, covariates potentially associated with nimodipine exposure were explored.ResultsIn total, 20 (69%) participants had favorable outcomes and 9 (31%) had poor outcomes. Following the exclusion of those with delayed presentation (>96 h from aSAH onset), among those presented with the World Federation of Neurological Surgeons (WFNS) grade 3-5, nimodipine median (interquartile range) area under the concentration time curve (AUC0-3h) in those with favorable outcomes were 4-fold higher than in those with poor outcomes [136 (52-192) vs. 33 (23-39) ng.h/mL, respectively, value of p = 0.2]. On the other hand, among those presented with WFNS grade 1-2, nimodipine AUC0-3h in those with favorable outcomes were significantly lower than in those with poor outcomes [30 (28-36) vs. 172 (117-308) ng.h/mL, respectively, value of p = 0.03)]. (+)-R-nimodipine AUC0-3h in those who did not develop vasospasm were 4-fold significantly higher than those who had vasospasm (value of p = 0.047). (-)-S-nimodipine was significantly correlated with percentage MAP reduction. Similar results were obtained when the whole cohort was analyzed.ConclusionThe study was the first to investigate the potential association between nimodipine exposure following oral dosing and outcomes. In addition, it suggests differential effects of nimodipine enantiomers, shedding light on the potential utility of nimodipine enantiomers. Larger studies are needed.
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Project description:Aneurysmal subarachnoid hemorrhage (aSAH) is one of the most severe neurological disorders, with a high mortality rate and severe disabling functional sequelae. Systemic inflammation following hemorrhagic stroke may play an important role in mediating intracranial and extracranial tissue damage. Previous studies showed that various systemic inflammatory biomarkers might be useful in predicting clinical outcomes. Anti-inflammatory treatment might be a promising therapeutic approach for improving the prognosis of patients with aSAH. This review summarizes the complicated interactions between the nervous system and the immune system.
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Project description:OBJECTIVE:The aim of the study was to assess the relation between cerebrovascular function early after aneurysmal subarachnoid hemorrhage onset and functional and rehabilitation outcomes. DESIGN:Observational cohort study of subarachnoid hemorrhage patients (n = 133) admitted to rehabilitation (n = 49), discharged home (n = 52), or died before discharge (n = 10). We obtained hemodynamic markers of cerebral autoregulatory function from blood flow velocities in the middle cerebral artery and arterial pressure waveforms, recorded daily on days 2-4 after symptom onset, and functional independence measure (FIM) scores and FIM efficiency for those admitted to acute rehabilitation. RESULTS:Compared to those discharged home, the range of pressures within which autoregulation is effective was lower in patients admitted to rehabilitation (4.6 [0.2] vs. 3.9 [0.2] mm Hg) and those who died (2.7 [0.4], P = 0.04). For those admitted to rehabilitation, autoregulatory range and the ability of cerebrovasculature to increase flow were related to discharge FIM score (R = 0.33 and 0.43, P < 0.01) and efficiency (R = 0.33 and 0.47 P < 0.01). The latter marker, along with subarachnoid hemorrhage severity and admission FIM, explained 84% and 69% of the variability in discharge FIM score and efficiency, respectively, even after accounting for age. CONCLUSIONS:Early cerebrovascular function is a major contributor to functional outcomes after subarachnoid hemorrhage and may represent a modifiable target to develop therapeutic approaches. TO CLAIM CME CREDITS:Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Define cerebral autoregulation; (2) Explain the importance of the integrity of cerebral autoregulation for longer-term functional and rehabilitation outcomes after aneurysmal subarachnoid hemorrhage; and (3) Theorize why treatment strategies that may be effective in reducing large-vessel vasospasms after an aneurysmal subarachnoid hemorrhage might not always translate into improved functional outcomes. LEVEL:Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
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Project description:Objective: Systemic inflammation after subarachnoid hemorrhage (SAH) is implicated in delayed cerebral ischemia (DCI) and adverse clinical outcomes. We hypothesize that early changes in peripheral leukocytes will be associated with outcomes after SAH. Methods: SAH patients admitted between January 2009 and December 2016 were enrolled into a prospective observational study and were assessed for Hunt Hess Scale (HHS) at admission, DCI, and modified Ranked Scale (mRS) at discharge. Total white blood cell (WBC) counts and each component of the differential cell count were determined on the day of admission (day 0) to 8 days after bleed (day 8). Global cerebral edema (GCE) was assessed on admission CT, and presence of any infection was determined. Statistical tests included student's t-test, Chi-square test, and multivariate logistic regression (MLR) models. Results: A total of 451 subjects were analyzed. Total WBCs and neutrophils decreased initially reaching a minimum at day 4-5 after SAH. Monocyte count increased gradually after SAH and peaked between day 6-8, while basophils and lymphocytes decreased initially from day 0 to 1 and steadily increased thereafter. Neutrophil to lymphocyte ratio (NLR) reached a peak on day 1 and decreased thereafter. WBCs, neutrophils, monocytes, and NLR were higher in patients with DCI and poor functional outcomes. WBCs, neutrophils, and NLR were higher in subjects who developed infections. In MLR models, neutrophils and monocytes were associated with DCI and worse functional outcomes, while NLR was only associated with worse functional outcomes. Occurrence of infection was associated with poor outcome. Neutrophils and NLR were associated with infection, while monocytes were not. Monocytes were higher in males, and ROC curve analysis revealed improved ability of monocytes to predict DCI and poor functional outcomes in male subjects. Conclusions: Monocytosis was associated with DCI and poor functional outcomes after SAH. The association between neutrophils and NLR and infection may impact outcomes. Early elevation in monocytes had an improved ability to predict DCI and poor functional outcomes in males, which was independent of the occurrence of infection.
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