Management of Spontaneous Intracerebral Hemorrhage

Purpose of Review

We review the current evidence for medical and surgical treatments of spontaneous intracerebral hemorrhage (ICH).

Recent Findings

Therapy with hemostatic agents (e.g. factor VIIa and tranexamic acid) if started early after bleeding onset may reduce hematoma expansion, but their clinical effectiveness has not been shown. Rapid anticoagulation reversal with prothrombin concentrates (PCC) plus vitamin K is the first choice in vitamin K antagonist-related ICH. In ICH related to dabigatran, anticoagulation can be rapidly reversed with idarucizumab. PCC are recommended for ICH related to FXa inhibitors, whereas specific reversal agents are not yet approved. While awaiting ongoing trials studying minimally invasive approaches or hemicraniectomy, the role of surgery in ICH remains to be defined. Therapies targeting downstream molecular cascades in order to prevent secondary neuronal damage are promising, but the complexity and multi-phased nature of ICH pathophysiology is challenging. Finally, in addition to blood pressure control, antithrombotic prevention after ICH has to consider the risk of recurrent bleeding as well as the risk of ischemic events.

Summary

Treatment of acute ICH remains challenging, and many promising interventions for acute ICH await further evidence from trials.

     

Impact of Recent Studies for the Treatment of Intracerebral Hemorrhage

Purpose of Review

The present review will cover most recent and important studies on acute treatment of intracerebral hemorrhage (ICH).

Recent Findings

Overly pessimistic prognostication in ICH may deny meaningful recovery achieved by specialized neurocritical care. Hematoma enlargement represents the most important target of acute ICH care, which is reduced by aggressive blood pressure management (targeting a systolic blood pressure of 140 mmHg) and appropriate hemostatic treatment especially in anticoagulation-associated ICH (INR reversal using prothrombin complex concentrates, eventually idarucizumab, andexanet, or tranexamic acid). Surgical treatment strategies involving fibrinolytics either used for direct hematoma lysis or used for intraventricular clot removal with/without additional lumbar drainage show great promise. Further novel treatment strategies are underway and need validation or evaluation strongly warranting well-designed future ICH research.

Summary

Several randomized and large-sized observational studies have considerably expanded the field and the evidence on how to treat acute ICH patients. Yet, the one breakthrough intervention to improve functional outcome is still missing, though various treatment concepts possibly interacting with one another have been evaluated and such treatment bundle may improve patients’ outcome.

     

Cerebral small vessel disease burden and functional and radiographic outcomes in intracerebral hemorrhage

Objective

To examine the effect of individual cerebral small vessel disease (CSVD) markers and cumulative CSVD burden on functional independence, ambulation and hematoma expansion in spontaneous intracerebral hemorrhage (ICH).

Methods

Retrospective analysis of prospectively collected data from an observational study of consecutive patients with spontaneous ICH, brain MRI within 1 month from ictus, premorbid modified Rankin Scale (mRS) score?≤?2, available imaging data and 90-day functional status in a tertiary academic center. Functional outcomes included 90-day functional independence (mRS?≤?2) and independent ambulation; radiographic outcome was hematoma expansion (>?12.5 ml absolute or >?33% relative increase in ICH volume). We identified the presence and burden of individual CSVD markers (cerebral microbleeds (CMBs), enlarged perivascular spaces, lacunes, white matter hyperintensities) and composite CSVD burden score and explored their association with outcomes of interest in multivariable models adjusting for well-established confounders.

Results

111 patients were included, 65% lobar ICH, with a median volume 20.8 ml. 43 (38.7%) achieved functional independence and 71 (64%) independent ambulation. In multivariable adjusted models, there was higher total CSVD burden (OR 0.61, 95% CI 0.37–0.96, p?=?0.03) and CMBs presence (OR 0.32, 95% CI 0.1–0.88, p?=?0.04) remained independently inversely associated with functional independence. Individual CSVD markers or total CSVD score had no significant relation with ambulation and ICH expansion. Larger ICH volume and deep ICH location were the major determinants of lack of independent ambulation.

Conclusions

Our findings suggest that in ICH patients without previous functional dependence, total CSVD burden and particularly presence of CMBs significantly affect functional recovery. The latter is a novel finding and merits further exploration.

     

Defining the Optimal Midline Shift Threshold to Predict Poor Outcome in Patients with Supratentorial Spontaneous Intracerebral Hemorrhage

Background

Midline shift (MLS) has been associated with unfavorable outcome in patients with intracerebral hemorrhage (ICH). However, the optimal criteria to define the MLS measurements that indicate future outcome in ICH patients are absent, and the quantitative threshold of MLS that differentiates favorable and poor clinical outcome should be further explored.

Methods

We enrolled patients with ICH who underwent admission computed tomography (CT) within 6 h after onset of symptoms. We assessed MLS at several locations, including the pineal gland, septum pellucidum, and cerebral falx. MLS(max) was defined as the maximum midline shift among these locations. Functional outcomes were assessed with the Modified Rankin Scale (mRS) at 3 months. We performed multivariate logistic regression analysis to investigate the MLS locations for predicting poor outcome. ROC curve analysis was used to establish whether MLS values were predictive of 90-day poor outcome.

Results

In 199 patients with ICH, 78 (39.2%) patients had poor functional outcome at 3-month follow-up. Pineal gland shift, septum pellucidum shift, cerebral falx shift, and MLS(max) all showed a significant difference between poor outcome and favorable outcome (p < 0.001). After adjustment for age, baseline Glasgow Coma Scale score, ICH location, time to initial CT, baseline ICH volume, and intraventricular hemorrhage, the MLS(max) was independently associated with poor outcome (p = 0.032). MLS(max) > 4 mm (our proposed optimal threshold) was more likely to have poorer outcomes than those without (p < 0.001).

Conclusions

MLS(max) can be a good independent predictor of clinical outcome, and MLS(max) > 4 mm is an optimal threshold associated with poor outcome in patients with ICH.

     

The apoE-mimetic Peptide,COG1410, Improves Functional Recovery in a Murine Model of Intracerebral Hemorrhage

Background

Apolipoprotein E has previously been demonstrated to modulate acute brain injury responses, and administration of COG1410, an apoE-mimetic peptide derived from the receptor-binding region of apoE, improves outcome in preclinical models of acute neurological injury. In the current study, we sought to establish the optimal dose and timing of peptide administration associated with improved functional outcome in a murine model of intracerebral hemorrhage (ICH).

Methods

Ten to twelve-week-old C57/BL6 male mice were injured by collagenase-induced ICH and randomly selected to receive either vehicle or one of four doses of COG1410 (0.5, 1, 2, or 4 mg/kg) via tail vein injection at 30 min after injury and then daily for 5 days. The injured mice were euthanized at various time points to assess inflammatory mediators, cerebral edema, and hematoma volume. Over the first 5 days following injury, vestibulomotor function was tested via Rotorod (RR) latency. After an optimal dose was demonstrated, a final cohort of animals was injured with ICH and randomly assigned to receive the first dose of COG1410 or vehicle at increasingly longer treatment initiation times after injury. The mice were then assessed for functional deficit via RR testing over the first 5 days following injury.

Results

The mice receiving 2 mg/kg of COG1410 after injury demonstrated reduced functional deficit, decreased brain concentrations of inflammatory proteins, and less cerebral edema, although hematoma volume did not vary. The improved RR performance was maintained when peptide administration was delayed for up to 2 h after ICH.

Conclusions

COG1410 administered at a dose of 2 mg/kg within 2 h after injury improves functional recovery in a murine model of ICH.

     

Influence of Bleeding Pattern on Ischemic Lesions After Spontaneous Hypertensive Intracerebral Hemorrhage with Intraventricular Hemorrhage

Background

Concomitant acute ischemic lesions are detected in up to a quarter of patients with spontaneous intracerebral hemorrhage (ICH). Influence of bleeding pattern and intraventricular hemorrhage (IVH) on risk of ischemic lesions has not been investigated.

Methods

Retrospective study of all 500 patients enrolled in the CLEAR III randomized controlled trial of thrombolytic removal of obstructive IVH using external ventricular drainage. The primary outcome measure was radiologically confirmed ischemic lesions, as reported by the Safety Event Committee and confirmed by two neurologists. We assessed predictors of ischemic lesions including analysis of bleeding patterns (ICH, IVH and subarachnoid hemorrhage) on computed tomography scans (CT). Secondary outcomes were blinded assessment of mortality and modified Rankin scale (mRS) at 30 and 180 days.

Results

Ischemic lesions occurred in 23 (4.6%) during first 30 days after ICH. Independent risk factors associated with ischemic lesions in logistic regression models adjusted for confounders were higher IVH volume (p = 0.004) and persistent subarachnoid hemorrhage on CT scan (p = 0.03). Patients with initial IVH volume ≥ 15 ml had five times the odds of concomitant ischemic lesions compared to IVH volume < 15 ml. Patients with ischemic lesions had significantly higher odds of death at 1 and 6 months (but not poor outcome; mRS 4–6) compared to patients without concurrent ischemic lesions.

Conclusions

Occurrence of ischemic lesions in the acute phase of IVH is not uncommon and is significantly associated with increased early and late mortality. Extra-parenchymal blood (larger IVH and visible subarachnoid hemorrhage) is a strong predictor for development of concomitant ischemic lesions after ICH.

     

National Institutes of Health Stroke Scale in patients with primary intracerebral hemorrhage

Background

The National Institutes of Health Stroke Scale (NIHSS) is able to predict mortality and functional outcome in patients with ischemic stroke. Its role in primary intracerebral hemorrhage (ICH) is not clear. The objective of our study was to investigate whether NIHSS is a reliable instrument of clinical monitoring and correlates with mortality and functional outcome in ICH.

Methods

One hundred fifty-six consecutive subjects with primary ICH were included. We evaluated NIHSS at admission. The functional state after a 30-day and a 3-month-long follow-up was assessed by the modified Rankin Scale (mRS). Spearman’s rank correlation coefficient analysis was used for statistics. Sensitivity, specificity, positive predictive value, negative predictive value, global accuracy, and ROC curve were computed using the median score 7 as NIHSS cutoff and the score 4 as mRS cutoff.

Results

Median NIHSS score at admission was 7 (16–4); the mean (± SD) was 10.82 (±?8.27). Thirty-two patients (20.5%) died within 30 days and other 22 (14.1%) within 3 months. The median mRS score at 3 months was 4 (6–1); the mean (± SD) was 3.38 (±?2.42). We found a statistically significant correlation between initial NIHSS score and mRS score after 30 days (0.74) and 3 months (0.66, p?<?0.01). Sensitivity was 93.5 and 92.2%, specificity 82.3 and 69.6%, and GA 87.8 and 80.8%, respectively, at 1 and 3 months. The 1- and 3-month ROC curves comparing initial NIHSS and mRS showed a fitted area as 0.914 and 0.833, respectively.

Conclusions

NIHSS is a reliable tool of clinical monitoring and correlates with 30-day and 3-month mortality and functional outcome in subjects with ICH.

     

Seizures Among Long-Term Survivors of Conservatively Treated ICH Patients: Incidence,Risk Factors,and Impact on Functional Outcome

Background

Seizures are a common complication after intracerebral hemorrhage (ICH) but there is a substantial lack of information on the long-term incidence in ICH survivors and whether post-ICH seizures affect functional long-term outcome.

Methods

Over a five-year period 464 consecutive patients with spontaneous ICH were analyzed. Focussing on 1-year ICH survivors, clinical, and radiological parameters were retrieved from institutional prospective databases. The occurrence of seizures was categorized as early (≤7 days) or late (>7 days). Functional outcome was assessed by mailed questionnaires and telephone interviews, and was categorized into good vs. poor (mRS: 0–2 vs. 3–5) and favorable vs. unfavorable (mRS: 0–3 vs. 4–5). Multivariate regression models were calculated to investigate risk factors associated with post-ICH seizures including an a priori defined subgroup analysis of lobar ICH patients.

Results

Among 203 long-term ICH survivors, 19.7 % developed seizures of which 55 % occurred late. Factors associated with seizures were lobar location (OR 8.10; 95 % CI 3.04–21.59; p < 0.001), sepsis (OR 4.59; 95 % CI 1.20–17.53; p = 0.026), and history of alcohol abuse (OR 3.36; 95 % CI 1.25–9.06; p = 0.017). Subgroup analysis of lobar ICH patients revealed history of alcohol abuse as the only independent predictor of post-ICH seizures (OR 5.22; 95 % CI 1.25–21.78; p = 0.024). Functional long-term outcome among survivors was slightly worse in patients with post-ICH seizures (p = 0.059). In multivariate regression modeling for prediction of poor outcome, the parameter “post-ICH seizures” again reached a statistical trend (p = 0.065), and established parameters such as age, GCS, and hemorrhage volume were independently related to poor outcome.

Conclusions

Post-ICH seizures among long-term ICH survivors are common and may contribute to unfavorable functional outcome. Especially lobar ICH patients with a history of alcohol abuse are at risk to develop post-ICH seizures. Therefore, this subgroup may represent a target population for a prophylactic anticonvulsive treatment approach, preferably investigated in a prospective randomized trial.

     

Intensive Care Unit Admission for Patients in the INTERACT2 ICH Blood Pressure Treatment Trial: Characteristics,Predictors, and Outcomes

Background

Wide variation exists in criteria for accessing intensive care unit (ICU) facilities for managing patients with critical illnesses such as acute intracerebral hemorrhage (ICH). We aimed to determine the predictors of admission, length of stay, and outcome for ICU among participants of the main Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2).

Methods

INTERACT2 was an international, open, blinded endpoint, randomized controlled trial of 2839 ICH patients (<6 h) and elevated systolic blood pressure (SBP) allocated to receive intensive (target SBP <140 mmHg within 1 h) or guideline-recommended (target SBP <180 mmHg) BP-lowering treatment. The primary outcome was death or major disability, defined by modified Rankin scale scores 3–6 at 90 days. Logistic regression and propensity score analyses were used to determine independent associations.

Main Results

Predictors of ICU admission included younger age, recruitment in China, prior ischemic/undetermined stroke, high SBP, severe stroke [National Institute of Health stroke scale (NIHSS) score ≥15], large ICH volume (≥15 mL), intraventricular hemorrhage (IVH) extension, early neurological deterioration, intubation and surgery. Determinants of prolonged ICU stay (≥5 days) were prior antihypertensive use, NIHSS ≥15, large ICH volume, lobar ICH location, IVH, early neurological deterioration, intubation and surgery. ICU admission was associated with higher-risk major disability at 90-day assessment compared to those without ICU admission.

Conclusions

This study presents prognostic variables for ICU management and outcome of ICH patients included in a large international cohort. These data may assist in the selection and counseling of patients and families concerning ICU admission.

     

Comparison of CT black hole sign and other CT features in predicting hematoma expansion in patients with ICH

Background and purpose

The hematoma expansion (HE) is an important risk factor for early neurological deterioration and poor prognosis. In this study, we aimed to compare the black hole sign with other computed tomography (CT) features to predict the HE and the outcome in patients with intracerebral hemorrhage (ICH).

Methods

Patients were enrolled within 12 h after stroke attack in the emergency department of Henan Provincial People’s Hospital between January 2012 and June 2016. The clinical characters and CT features including the initial CT and the follow-up CT within 48 h were recorded. The outcome was assessed by using the modified Rankin Scale on discharge. Logistic regression analyses were used to investigate whether the factors were the independent predictor of HE and the outcome in patients with ICH. The sensitivity, specificity, positive predictive value, and negative predictive of CT features in predicting HE were calculated.

Results

A total of 185 ICH patients were enrolled, including 70 (37.8%) patients in HE group and 115 (62.2%) patients in non-HE group. There were significant difference in the initial hematoma volume, irregular shape, and CT black hole sign (P?=?0.013, 0.006 and P?<?0.001) between the two groups. While irregular shape and CT black hole sign were independent predictors for HE, the sensitivity and specificity were 71.45 and 54.78, 51.4 and 81.7%, respectively. Multivariable analysis identified CT black hole sign (P?=?0.108) and initial intraventricular hemorrhage expansion (P?=?0.214) were not the independent predictors of poor outcome.

Conclusion

CT black hole sign presented the best predictive accuracy of predicting HE in patients with ICH compared to other CT features. However, it was not an independent predictor of poor outcome.

     

Impact of Perihemorrhagic Edema on Short-Term Outcome After Intracerebral Hemorrhage

Background

Intracerebral hemorrhage (ICH) is a devastating disease with ICH volume being the main predictor of poor outcome. The prognostic role of perihemorrhagic edema (PHE) is still unclear; however, available data are mainly derived from analyses during the first days after symptom onset. As PHE growth may continue up to 14 days after ICH, we evaluated PHE over a longer period of time and investigated its impact on short-term clinical outcome.

Methods

In this monocentric retrospective cohort study, patients with spontaneous supratentorial ICH were identified from our institutional data base. Different time points of CT scans were merged to time clusters for better comparison (day 1, 2–3, 4–6, 7–9, 10–12). Absolute volumes of ICH and PHE were obtained using a validated semiautomatic volumetric algorithm. Clinical outcome at discharge was assessed using the modified Rankin Scale (0–3 = favorable, 4–6 = poor).

Results

220 patients (83 with favorable, 137 with poor outcome) were included in the final analysis. Mean ICH volume on admission was 22.8 [standard deviation (SD) 24.6] cm³. Mean absolute PHE volume on admission was 22.5 (SD 20.8) cm³ and increased to a mean peak volume of 38.1 (SD 31.4) cm³ during 6.7 (SD 4.1) days on average. Besides GCS on admission, functional status before ICH, peak hematoma volume, lobar localization and fever burden, and high peak PHE volume predicted poor outcome at discharge [OR 0.977 (95 % CI 0.957–0.998)] in the multivariable analysis.

Conclusions

PHE may have a negative impact on short-term functional outcome after ICH and therefore represent a possible treatment target.

     

TURN Score Predicts 24-Hour Cerebral Edema After IV Thrombolysis

Background and Purpose

Cerebral edema is associated with poor outcome after IV thrombolysis. We recently described the TURN score (Thrombolysis risk Using mRS and NIHSS), a predictor of severe outcome after IV thrombolysis. Our purpose was to evaluate its ability to predict 24-h cerebral edema.

Methods

We retrospectively analyzed data from 303 patients who received IV rt-PA during the NINDS rt-PA trial. Measures of brain swelling included edema, mass effect and midline shift assessed at baseline, at 24 h and new onset at 24 h. Outcome was assessed using intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), 90-day severe outcome, and 90-day mortality. Statistical associations were assessed by logistic regression reporting odds ratios (OR) and by areas under the receiver operating characteristic curves (AUROC).

Results

Baseline brain swelling did not predict poor outcome; however, 24-h brain swelling predicted ICH (OR 5.69, P < 0.001), sICH (OR 9.50, P = 0.01), 90-day severe outcome (OR 7.10, P < 0.001), and 90-day mortality (OR 5.65, P = 0.01). Similar results were seen for new brain swelling at 24 h. TURN predicted 24-hour brain swelling (OR 2.5, P < 0.001; AUROC 0.69, 95 % CI 0.63–0.75) and new brain swelling at 24 h (OR 2.1, P < 0.001; AUROC 0.67, 95 % CI 0.61–0.73).

Conclusions

Cerebral edema at 24 h is associated with poor outcome and 90-day mortality. TURN predicts ischemic stroke patients who will develop 24-h cerebral edema after IV thrombolysis.

     

Prophylactic Anticonvulsants in Intracerebral Hemorrhage

Background and Purpose

Prophylactic anticonvulsants are routinely prescribed in the acute setting for intracerebral hemorrhage (ICH) patients, but some studies have reported an association with worse outcomes. We sought to characterize the prevalence and predictors of prophylactic anticonvulsant administration after ICH as well as guideline adherence. We also sought to determine whether prophylactic anticonvulsants were independently associated with poor outcome.

Methods

We performed a retrospective study of primary ICH in our two academic centers. We used a propensity matching approach to make treated and non-treated groups comparable. We conducted multiple logistic regression analysis to identify independent predictors of prophylactic anticonvulsant initiation and its association with poor outcome as measured by modified Rankin score.

Results

We identified 610 patients with primary ICH, of whom 98 were started on prophylactic anticonvulsants. Levetiracetam (97%) was most commonly prescribed. Age (OR 0.97, 95% CI 0.95–0.99, p < .001), lobar location (OR 2.94, 95% CI 1.76–4.91, p < .001), higher initial National Institutes of Health Stroke Scale (NIHSS) score (OR 2.31, 95% CI 1.40–3.79, p = .001), craniotomy (OR 3.06, 95% CI 1.51–6.20, p = .002), and prior ICH (OR 2.36, 95% CI 1.10–5.07, p = .028) were independently associated with prophylactic anticonvulsant initiation. Prophylactic anticonvulsant use was not associated with worse functional outcome [modified Rankin score (mRS) 4–6] at hospital discharge or with increased case-fatality. There was no difference in prescribing patterns after 2010 guideline publication.

Discussion

Levetiracetam was routinely prescribed following ICH and was not associated with worse outcomes. Future investigations should examine the effect of prophylactic levetiracetam on cost and neuropsychological outcomes as well as the role of continuous EEG in identifying subclinical seizures.

     

CT Angiography Spot Sign,Hematoma Expansion,and Outcome in Primary Pontine Intracerebral Hemorrhage

Background and Purpose

The computed tomography angiography (CTA) spot sign is a validated predictor of hematoma expansion and poor outcome in supratentorial intracerebral hemorrhage (ICH), but patients with brainstem ICH have typically been excluded from the analyses. We investigated the frequency of spot sign and its relationship with hematoma expansion and outcome in patients with primary pontine hemorrhage (PPH).

Methods

We performed a retrospective analysis of PPH cases obtained from a prospectively collected cohort of consecutive ICH patients who underwent CTA. CTA first-pass readings for spot sign presence were analyzed by two trained readers. Baseline and follow-up hematoma volumes on non-contrast CT scans were assessed by semi-automated computer-assisted volumetric analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive and negative likelihood ratio, and accuracy of spot sign for prediction of in-hospital mortality were calculated.

Results

49 subjects met the inclusion criteria of whom 11 (22.4 %) showed a spot sign. In-hospital mortality was higher in spot sign-positive versus spot sign-negative subjects (90.9 vs 47.4 %, p = 0.020). Spot sign showed excellent specificity (95 %) and PPV (91 %) in predicting in-hospital mortality. Absolute hematoma growth, defined as parenchymal and intraventricular hematoma expansion of any amount, was significantly higher in spot sign-positive versus spot sign-negative subjects (13.72 ± 20.93 vs 3.76 ± 8.55 mL, p = 0.045).

Conclusions

As with supratentorial ICH, the CTA spot sign is a common finding and is associated with higher risk of hematoma expansion and mortality in PPH. This marker may assist clinicians in prognostic stratification.

     

Lymphopenia,Infectious Complications,and Outcome in Spontaneous Intracerebral Hemorrhage

Background

Lymphopenia is increasingly recognized as a consequence of acute illness and may predispose to infections. We investigated whether admission lymphopenia (AL) is associated with increased risk of infectious complications and poor outcome in patients with spontaneous intracerebral hemorrhage (ICH).

Methods

We retrospectively analyzed a prospectively collected cohort of ICH patients ascertained between 1994 and 2015. We identified subjects with lymphocyte count obtained within 24 h from onset, and AL was defined as lymphocyte count <1000/μL. Infectious complications were assessed through retrospective chart review. Association between AL, infections, and mortality was investigated using multivariable logistic regression.

Results

Of the 2014 patients meeting inclusion criteria, 548 (27.2%) had AL and 605 (30.0%) developed an infectious complication. Case-fatality at 90 days was 36.9%. Patients with AL had larger hematoma volumes, higher frequency of intraventricular hemorrhage, and lower Glasgow Coma Scale score on presentation (all p < 0.001). AL was independently associated with increased risk of pneumonia [odds ratio (OR) 1.97, 95% confidence interval (CI) 1.50–2.58, p < 0.001] and multiple infections (OR 1.84, 95% CI 1.24–2.71, p = 0.003). AL was also an independent predictor of 90-day mortality (OR 1.55, 95% CI 1.18–2.04, p = 0.002) after adjusting for confounders.

Conclusions

AL is common in ICH patients and independently associated with increased risk of infectious complications and poor outcome. Further studies will be needed to determine whether prophylactic antibiotics in ICH patients with AL can improve outcome.

     

Factors Considered by Clinicians when Prognosticating Intracerebral Hemorrhage Outcomes

Background

The early subjective clinical judgment of clinicians outperforms formal prognostic scales for accurate determination of outcome after intracerebral hemorrhage (ICH), with the judgment of physicians and nurses having equivalent accuracy. This study assessed specific decisional factors that physicians and nurses incorporate into early predictions of functional outcome.

Methods

This prospective observational study enrolled 121 ICH patients at five US centers. Within 24 h of each patient’s admission, one physician and one nurse on the clinical team were each surveyed to predict the patient’s modified Rankin Scale (mRS) at 3 months and to list up to 10 subjective factors used in prognostication. Factors were coded and compared between (1) physician and nurse and (2) accurate and inaccurate surveys, with accuracy defined as an exact prediction of mRS.

Results

Aside from factors that are components of the ICH or FUNC scores, surveys reported pre-existing comorbidities (40.0%), other clinical or radiographic factors not in clinical scales (43.0%), and non-clinical/radiographic factors (21.9%) as important. Compared to physicians, nurses more frequently listed neurologic examination components (Glasgow Coma Scale motor, 27.3 vs. 5.8%, p < 0.0001; GCS verbal, 12.4 vs. 0.0%, p < 0.0001) and non-clinical/radiographic factors (31.4 vs. 12.4%, p = 0.0005). Physicians more frequently listed neuroimaging factors (ICH location, 33.9 vs. 7.4%, p < 0.0001; intraventricular hemorrhage, 13.2 vs. 2.5%, p = 0.003). There was no difference in listed factors between accurate versus inaccurate surveys.

Conclusions

Clinicians frequently utilize factors outside of the components of clinical scales for prognostication, with physician and nurses focusing on different factors despite having similar accuracy.

     

Systemic Inflammatory Response Syndrome and Outcomes in Intracerebral Hemorrhage

Background

To identify the patients at greatest odds for systemic inflammatory response syndrome (SIRS) and examine the association between SIRS and outcomes in patients presenting with intracerebral hemorrhage (ICH).

Methods

We retrospectively reviewed consecutive patients presenting to a tertiary care center from 2008 to 2013 with ICH. SIRS was defined according to standard criteria as 2 or more of the following: (1) body temperature <36 or >38 °C, (2) heart rate >90 beats per minute, (3) respiratory rate >20, or (4) white blood cell count <4000/mm³ or >12,000/mm³ or >10 % polymorphonuclear leukocytes for >24 h in the absence of infection. The outcomes of interest, discharge modified Rankin Scale (mRS 4–6), death, and poor discharge disposition (discharge anywhere but home or inpatient rehab) were assessed using logistic regression.

Results

A total of 249 ICH patients met inclusion criteria and 53 (21.3 %) developed SIRS during their hospital stay. A score was developed (ranging from 0 to 3) to identify patients at greatest risk for developing SIRS. Adjusting for stroke severity, SIRS was associated with mRS 4–6 (OR 5.25, 95 %CI 2.09–13.2) and poor discharge disposition (OR 3.74, 95 %CI 1.58–4.83) but was not significantly associated with death (OR 1.75, 95 %CI 0.58–5.32). We found that 33 % of the effect of ICH score on poor functional outcome at discharge was explained by the development of SIRS in the hospital (Sobel 2.11, p = 0.03).

Conclusion

We observed that approximately 20 % of patients with ICH develop SIRS, and that patients with SIRS were at increased risk of having poor functional outcome at discharge.

     

Men Experience Higher Risk of Pneumonia and Death After Intracerebral Hemorrhage

Background

Infectious complications worsen outcome after intracerebral hemorrhage (ICH). We investigated the impact of sex on post-ICH infections and mortality.

Methods

Consecutive ICH patients (admitted to a single hospital between 1994 and 2015) were retrospectively assessed via chart review to ascertain the following in-hospital infections: urinary tract infection (UTI), pneumonia, and sepsis. Adjusted logistic regression was performed to identify associations between sex, infection, and mortality at 90 days.

Results

Two thousand and four patients were investigated, 1071 (53.7%) males. Men were more likely to develop pneumonia (21.9 vs 15.5% p < 0.001) and sepsis (3.4 vs 1.6%, p = 0.009), whereas women had higher risk of UTI (19.9 vs 11.7% p < 0.001). Multivariate analyses confirmed association between male sex and pneumonia (Odds Ratio (OR) 1.37, 95% confidence interval (CI) 1.08–1.74, p = 0.011). Male sex (OR 1.40; CI 1.07–1.85; p = 0.015) and infection (OR 1.56; CI 1.11–1.85; p = 0.011) were independently associated with higher 90-day mortality.

Conclusions

Types and rates of infection following ICH differ by sex. Male sex independently increases pneumonia risk, which subsequently increases 90-day mortality. Sex-specific preventive strategies to reduce the risk of these complications may be one strategy to improve ICH outcomes.

     

Fever Burden and Health-Related Quality of Life After Intracerebral Hemorrhage

Background

Fever is associated with worse functional outcomes after intracerebral hemorrhage (ICH); however, there are few prospective data to quantify the relationship with health-related quality of life (HRQoL). We tested the hypothesis that increased burden of fever is independently associated with decreased HRQoL at follow-up.

Methods

In this prospective observational cohort study of 106 ICH patients admitted to a tertiary care hospital between 2011 and 2015, we recorded the highest core temperature each calendar day for 14 days after ICH onset. Fever burden was defined as the number of days with a fever?≥?100.4 °F (38 °C). HRQoL outcomes were measured with Neuro-QoL domains of Cognitive Function and Mobility at 28 days, 3 months, and 1 year. Results were analyzed using mixed effects regression analysis.

Results

Each additional day with a fever was independently associated with lower Mobility HRQoL (T-score ? 0.9, [? 1.6 to ? 0.2]; p?=?0.01) and Cognitive Function HRQoL (T-score ? 1.3 [? 2.0 to ? 0.6]; p?=?0.001) after correction for National Institutes of Health Stroke Scale score on admission, age, and time to follow-up.

Conclusions

Each additional day with a fever was predictive of worse HRQoL domains of Cognitive Function and Mobility after ICH up to 1 year. These data extend previous evidence on the negative association of fever and functional outcomes to the domains of Cognitive Function and Mobility HRQoL. HRQoL outcomes may be a sensitive and powerful way to measure the efficacy of fever control in future research.