Functional Outcomes and Mortality in Patients With Intracerebral Hemorrhage After Intensive Medical and Surgical Support.

BACKGROUND AND OBJECTIVES: Despite decades of increasingly sophisticated neurocritical care, patient outcomes after spontaneous intracerebral hemorrhage (ICH) remain dismal. Whether this reflects therapeutic nihilism or the effects of the primary injury has been questioned. In this contemporary cohort, we determined the 30- and 90-day mortality, cause-specific mortality, functional outcome, and the effect of surgical intervention in a culture of aggressive medical and surgical support. METHODS: This was a retrospective cohort study of consecutive adult patients with spontaneous ICH admitted to a tertiary neurocritical care unit. Patients with secondary ICH and those subject to limitation of care before 72 hours were excluded. For each ICH score, mortality at 30- and 90-days, and the modified Rankin Scale (mRS) within 1-year were examined. The effect of craniotomy/craniectomy ± hematoma evacuation on the outcome of supratentorial ICH was determined using propensity score matching. Median patient follow-up after discharge was 2.2 (interquartile range [IQR] 0.4-4.4) years. RESULTS: Among 319 patients with spontaneous ICH (median age was 69 [IQR 60-77] years, 60% male), 30- and 90-day mortality were 16% and 22%, respectively, and unfavorable functional outcome (mRS score 4-6) was 50% at a median 3.1 months after ICH. Admission predictors of mortality mirrored those of the original ICH score. Unfavorable outcomes for ICH scores 3 and 4 were 73% and 86%, respectively. The most common adjudicated primary causes of mortality were direct effect or progression of ICH (54%), refractory cerebral edema (21%), and medical complications (11%). In matched analyses, lifesaving surgery for supratentorial ICH did not significantly alter mortality or unfavorable functional outcome in patients overall. In subgroup analyses restricted to (1) surgery with hematoma evacuation and (2) ICH score 3 and 4 patients, the odds of 30-day mortality were reduced by 71% (odds ratio [OR] 0.29, 95% CI 0.09-0.9, p = 0.032) and 80% (OR 0.2, 95% CI 0.04-0.91, p = 0.038), respectively, but no difference was observed for 90-day mortality or unfavorable functional outcome. DISCUSSION: This study demonstrates that poor outcomes after ICH prevail despite aggressive treatment. Unfavorable outcomes appear related to direct effects of the primary injury and not to premature care limitations. Lifesaving surgery for supratentorial lesions delayed mortality but did not alter functional outcomes.

The use of transcranial Doppler pulsatility index to guide hyperosmolar therapy.

Management of intracranial hypertension is a major cornerstone of neurocritical care. Apart from traumatic brain injury, there are no clear guidelines for intracranial pressure (ICP) monitoring. The insertion of ICP monitors is an invasive procedure with inherent risks and could be contraindicated in case of severe coagulopathy. The transcranial Doppler (TCD) pulsatility index (PI) has emerged as a surrogate marker for ICP. This is a technical report with illustrative cases on the use of PI in the management of high ICP, as a guide for optimal dosing of hyperosmolar agents we use in our institution. The use of TCD PI is a useful adjunct to guide the use of hyperosmolar therapy in various conditions with raised intracranial hypertension. We will discuss the combination of the PI determination with an anatomical evaluation of the optic nerve diameter to eliminate confounding factors in PI determination.

Treatment of Subarachnoid Hemorrhage-associated Delayed Cerebral Ischemia With Milrinone: A Review and Proposal.

Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage continues to be associated with high levels of morbidity and mortality. This complication had long been thought to occur secondary to severe cerebral vasospasm, but expert opinion now favors a multifactorial etiology, opening the possibility of new therapies. To date, no definitive treatment option for DCI has been recommended as standard of care, highlighting a need for further research into potential therapies. Milrinone has been identified as a promising therapeutic agent for DCI, possessing a mechanism of action for the reversal of cerebral vasospasm as well as potentially anti-inflammatory effects to treat the underlying etiology of DCI. Intra-arterial and intravenous administration of milrinone has been evaluated for the treatment of DCI in single-center case series and cohorts and appears safe and associated with improved clinical outcomes. Recent results have also brought attention to the potential outcome benefits of early, more aggressive dosing and titration of milrinone. Limitations exist within the available data, however, and questions remain about the generalizability of results across a broader spectrum of patients suffering from DCI. The development of a standardized protocol for milrinone use in DCI, specifically addressing areas requiring further clarification, is needed. Data generated from a standardized protocol may provide the impetus for a multicenter, randomized control trial. We review the current literature on milrinone for the treatment of DCI and propose a preliminary standardized protocol for further evaluation of both safety and efficacy of milrinone.

Milrinone for refractory cerebral vasospasm with delayed cerebral ischemia.

OBJECTIVE: Intravenous (IV) milrinone is a promising option for the treatment of cerebral vasospasm with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, data remain limited on the efficacy of treating cases that are refractory to standard therapy with IV milrinone. The aim of this study was to determine predictors of refractory vasospasm/DCI despite treatment with IV milrinone, and to analyze the outcome of rescue therapy with intraarterial (IA) milrinone and/or mechanical angioplasty. METHODS: The authors conducted a retrospective cohort study of all patients with aSAH admitted between 2010 and 2016 to the Montreal Neurological Institute and Hospital. Patients were stratified into 3 groups: no DCI, standard therapy, and rescue therapy. The primary outcome was frequency of DCI-related cerebral infarction identified on neuroimaging before hospital discharge. Secondary outcomes included functional outcome reported as modified Rankin Scale (mRS) score, and segment reversal of refractory vasospasm. RESULTS: The cohort included 322 patients: 212 in the no DCI group, 89 in the standard therapy group, and 21 in the rescue therapy group. Approximately half (52%, 168/322) were admitted with poor-grade aSAH at treatment decision (World Federation of Neurosurgical Societies grade III-V). Among patients with DCI and imaging assessing severity of vasospasm, 62% (68/109) had moderate/severe radiological vasospasm on DCI presentation. Nineteen percent (21/110) of patients had refractory vasospasm/DCI and were treated with rescue therapy. Targeted rescue therapy with IA milrinone reversed 32% (29/91) of the refractory vasospastic vessels, and 76% (16/21) of those patients experienced significant improvement in their neurological status within 24 hours of initiating therapy. Moderate/severe radiological vasospasm independently predicted the need for rescue therapy (OR 27, 95% CI 8.01-112). Of patients with neuroimaging before discharge, 40% (112/277) had developed new cerebral infarcts, and only 21% (23/112) of these were vasospasm-related. Overall, 65% (204/314) of patients had a favorable functional outcome (mRS score 0-2) assessed at a median of 4 months (interquartile range 2-8 months) after aSAH, and there was no difference in functional outcome between the 3 groups (p = 0.512). CONCLUSIONS: The aggressive use of milrinone was safe and effective based on this retrospective study cohort and is a promising therapy for the treatment of vasospasm/DCI after aSAH.

Mortality after Spontaneous Subarachnoid Hemorrhage: Causality and Validation of a Prediction Model.

OBJECTIVE: To evaluate primary causes of death after spontaneous subarachnoid hemorrhage (SAH) and externally validate the HAIR score, a prognostication tool, in a single academic institution. METHODS: We reviewed all patients with SAH admitted to our neuro-intensive care unit between 2010 and 2016. Univariate and multivariate logistic regressions were performed to identify predictors of in-hospital mortality. The HAIR score predictors were Hunt and Hess grade at treatment decision, age, intraventricular hemorrhage, and rebleeding within 24 hours. Validation of the HAIR score was characterized with the receiver operating curve, the area under the curve, and a calibration plot. RESULTS: Among 434 patients with SAH, in-hospital mortality was 14.1%. Of the 61 mortalities, 54 (88.5%) had a neurologic cause of death or withdrawal of care and 7 (11.5%) had cardiac death. Median time from SAH to death was 6 days. The main causes of death were effect of the initial hemorrhage (26.2%), rebleeding (23%) and refractory cerebral edema (19.7%). Factors significantly associated with in-hospital mortality in the multivariate analysis were age, Hunt and Hess grade, and intracerebral hemorrhage. Maximum lumen size was also a significant risk factor after aneurysmal SAH. The HAIR score had a satisfactory discriminative ability, with an area under the curve of 0.89. CONCLUSIONS: The in-hospital mortality is lower than in previous reports, attesting to the continuing improvement of our institutional SAH care. The major causes are the same as in previous reports. Despite a different therapeutic protocol, the HAIR score showed good discrimination and could be a useful tool for predicting mortality.

Health Care-Associated Infections after Subarachnoid Hemorrhage.

OBJECTIVE: Health care-associated infections (HAIs) after subarachnoid hemorrhage (SAH) are prevalent; however, data describing epidemiology of infection are limited. This study reports incidence rates, risk factors, and the resulting SAH patient-related outcomes. METHODS: We studied the incidence of HAIs acquired in the intensive care unit (ICU) over a 6-year period. We used Bayesian Model Averaging to identify risk factors associated with an increased risk of HAIs, particularly urinary tract infections (UTI), pneumonia, and ventriculostomy-associated infections (VAI). We also examined the impact of HAIs on risk of vasospasm, ICU and hospital length of stay, and discharge disposition and adjusted for other risk factors. RESULTS: Of 419 patients with SAH, 66 (15.8%) developed 79 HAI episodes. Mean HAI incidence rates (per 1000 ICU-days) were UTI, 7.1; pneumonia, 4.3; and VAI, 2.4. The admission characteristic associated with increased risk of overall HAI, UTI, and VAI was diabetes mellitus. Hunt and Hess grades III-V were associated with increased risk of overall HAI and VAI. Male gender, intraventricular hemorrhage, and blood glucose level (>10) were associated with increased risk of pneumonia, whereas the incidence was lower in the presence of steroids. HAI was associated with increased length of stay of 10 ICU-days and 22 hospital-days, but not vasospasm or poor discharge disposition. CONCLUSIONS: HAIs are serious complications after SAH associated with prolonged ICU and hospital length of stay. Additional rigorous infection control measures aimed at patients with identifiable risk factors should trigger prevention, and early detection of nosocomial infections is warranted to further reduce the prevalence of HAIs.

Healthcare-associated infections in the neurological intensive care unit: Results of a 6-year surveillance study at a major tertiary care center.

BACKGROUND: Healthcare-associated infections (HAIs) occur frequently in neurological intensive care units (neuro-ICUs); however, data differentiating associations with various diagnostic categories and resulting burdens are limited. This prospective cohort study reported incidence rates, pathogen distribution, and patient-related outcomes of HAIs in a neuro-ICU population from April 2010 to March 2016. METHODS: Laboratory results and specific clinical indicators were used to categorize infections as per National Healthcare Safety Network nosocomial infection surveillance definitions. Patient outcomes studied included length of stay and mortality. RESULTS: There were 6,033 neuro-ICU admissions resulting in 20,800 neuro-ICU days over the 6-year study period. A total of 227 HAIs were identified for a rate of 10.9/1,000 ICU days. Device-associated infections accounted for 80.6% of HAIs, with incidence rates (per 1,000 device days) being 18.4 for ventilator-associated pneumonia; 4.9 for catheter-associated urinary tract infections (CAUTIs); 4.0 for ventriculostomy-associated infections; and 0.6 for central line-associated blood stream infections (CLABSIs). Of the various diagnostic categories, subdural hematoma and intracerebral/intraventricular hemorrhage were associated with the highest pooled HAIs, with incidence rates of 21.3 and 21.1 per 1,000 neuro-ICU days, respectively. Prolonged neuro-ICU length of stay was strongly associated with all HAIs. CONCLUSIONS: This large-scale surveillance study provides estimates of the risk of common HAIs in neurocritical care patients and their effect on hospitalization. Preventive strategies kept rates of infection very low, in particular CAUTI, CLABSI, and Clostridium difficile infections, and inhibited the emergence of resistant organisms.

Modulation of rat pial arteriolar responses to flow by glucose.

BACKGROUND: Pial arteriolar responses to flow contribute to regulation of cerebral perfusion and vary according to the transmural pressure to which the vessel is exposed. This study determined the effect of increased glucose concentration on the flow responses of pial arterioles at low and high levels of transmural pressure. METHODS: Pial arterioles from Sprague-Dawley rats were mounted in a perfusion myograph. In some arterioles, the endothelium was removed by perfusion with air. Diameters were recorded at transmural pressures of 60 and 120 mmHg during superfusion with physiologic saline containing 5 mm D-glucose, 20 mm D-glucose, or 5 mm D-glucose and 15 mm L-glucose. Diameters during superfusion with saline containing 44 mm D-glucose were measured at an intraluminal pressure of 60 mmHg. Flow-diameter relationships (5-30 microl/min) were recorded during perfusion with the same solutions. RESULTS: Increasing D-glucose concentration caused constriction (P < 0.05) in endothelium-denuded but not in endothelium-intact arterioles. Addition of L-glucose caused constriction in endothelium-intact and -denuded vessels (P < 0.05 for both). At a D-glucose concentration of 5 mm and at low intraluminal pressure, flow elicits endothelium-dependent dilation such that shear stress remains constant. At a D-glucose concentration of 20 or 44 mm, after addition of L-glucose (15 mm), and at high intraluminal pressures, flow elicits constriction and shear stress is unregulated. CONCLUSIONS: High glucose concentrations elicit increased basal arteriolar smooth muscle tone that is counteracted by release of endothelium-derived relaxing factors. Endothelium-dependent relaxation to flow (shear stress) is inhibited at high glucose concentrations.