Introduction
Intracerebral Hemorrhage (ICH) is a devastating disease. Although ICH accounts for about 10–15% of all stroke subtypes in the United States (US), this proportion is reported to be as high as 50% in certain regions of the world [
1]. The burden of disease imposed by ICH is tremendous. Approximately 50% of ICH patients do not survive beyond 30 days, and up to 80% fail to achieve functional independence [
2,
3]. Furthermore, approximately 90% of ICH patients report their quality of life (QOL) to be below average, including 20% stating their QOL to be worse than death [
4]. There are no class I evidence-based modalities that improve ICH outcomes. The mainstay of management revolves around hemodynamic stabilization, neurological monitoring, blood pressure titration, reversal of coagulopathy (if indicated), surgical interventions (in selected patients), secondary stroke prevention, and rehabilitation [
5]. It has also been reported that the majority of hospitals do not have well-developed ICH management protocols [
6]. Clinical trials for early blood pressure management and surgical interventions in ICH patients have demonstrated safety with limited and equivocal efficacy [
7,
8].
There are national and regional data showing that a large number of ICH patients are transferred from smaller community hospitals to bigger stroke treatment centers, probably for a perceived need of higher level of care (HLOC) [
9,
10]. Data also suggest that the proportion of transferred patients to large hospitals has been increasing periodically [
10]. However, the impact of management of ICH patients at a certain level of care on long term functional, cognitive, and quality of life outcomes within the current paradigm of stroke care delivery in the US is not understood. Furthermore, a subset of ICH patients that would optimally benefit from transfer to or management at centers with HLOC, such as Comprehensive Stroke Centers (CSCs), has not been identified. Finally, the comparative effectiveness of treating ICH patients at higher-resourced centers has not been provided. The study “
Efficient Resource Utilization for Patients with Intracerebral Hemorrhage (EnRICH)” has been designed and is being implemented to provide evidence to address these important issues.
Rationale
The American Heart Association / American Stroke Association guidelines for management of ICH were updated in 2015. These guidelines added a new Class I, level B evidence stating, “
Initial monitoring and management of ICH patients should take place in an intensive care unit or dedicated stroke unit with physician and nursing neuroscience acute care expertise” [
11]. The guidelines provide reference to three non-randomized studies as the basis for this evidence.
The first reference is made to a retrospective comparative analysis of 1038 ICH patients admitted to a general (non-neurological) intensive care unit (ICU) and those admitted to a neurological ICU (NICU) [
12]. The data were collected under Project Impact that began in 1996. The duration of data collection for patients included in this study is not clear; however, since the study was published in 2001 it is assumed that the 3 years of included data are between 1996 and 2001. The study reported an odds ratio (95% Confidence Interval [CI]) of 3.43 (1.65–7.60) for inpatient mortality among ICH patients admitted to a general ICU as compared to NICUs. The authors did acknowledge that limited data from NICUs (only two were included), and voluntary participation of hospitals in the project can lead to selection bias and lack of generalizability. However, it is also pertinent to note that analyses were done at the patient level, and clustering of patients within ICUs and NICUs was not accounted for.
The second reference is made to a cross-sectional analysis of data from 49 acute care hospitals in Alberta, Canada, including 18,142 patients with diagnoses of acute myocardial infarction, congestive heart failure, chronic obstructive pulmonary disease or stroke between April 1, 1998 and March 31, 1999 [
13]. The analyses were conducted with the aim of evaluating the association between nurse education and skill, continuity of care, quality of the work environment, and 30-day all-cause mortality. The authors correctly identified certain limitations pertaining to the nature of administrative data. However, it is apparent that the patient population included in this study does not allow generalizability of the results to ICH patients. Diagnosis-based stratified analyses have not been presented, and the only reported metric for stroke patients (presumably including ischemic stroke patients) is a 1% difference in 30-day mortality (15% vs. 16%) between patients discharged from low vs. high volume hospitals.
The third observational study is an analysis of the data from the Swedish Stroke Register between 2001 and 2005 [
14]. It compares the risk of death, institutionalization, and dependency between 105,043 stroke patients managed at stroke units and those managed at other types of units. The authors report a benefit for ICH patients managed in stroke units in terms of mortality and dependence. However, the study does not describe the differences between stroke and other units (primary exposure in this case) in care parameters for stroke patients. More importantly, the wider generalizability of such findings from a homogenous health care system remain questionable.
It is clear that the evidence cited in the guidelines falls short in multiple domains. These studies were not conducted during the last decade and they include data from non-stroke and non-ICH patients. Furthermore, their generalizability is highly questionable – particularly to the current paradigm of stroke care delivery and stroke care certification of hospitals in the US. Finally, they largely address broad and short-term outcomes such as inpatient and 30-day mortality. These outcomes, though important administratively, may not be patient-centered.
More recent and contextually relevant evidence, evaluating the association between level of care and outcomes in ICH patients, does not clearly highlight the benefit of managing all ICH patients at a HLOC. Two analyses independently conducted at large CSCs showed that transferred patients had milder disease severity and did not significantly utilize more CSC specific treatment modalities [
9,
15]. However, these data are limited by lack of outcomes for patients who are not transferred to CSCs. A direct comparison between ICH Medicare beneficiaries treated at Primary Stroke Centers (PSC) and those treated at non-certified centers did reveal a reduction in 30-day mortality for PSC patients; however, there were no differences in 30-day readmission [
16]. This analysis did not consider differences between CSCs and PSCs, lacked patient-centered outcomes, and excluded patients < 65 years of age, which may constitute a considerable proportion of ICH patients. A relatively recent comparison of brain hemorrhage patients treated at CSCs vs. PSCs did not reveal any differences in 90-day mortality for ICH patients [
17].
Furthermore, there are limited and conflicting data on the comparative effectiveness of ICH patient transfer for HLOC. A recent simulation-based study provided comparative effectiveness in terms of incremental cost effectiveness ratios of $47,431 per Quality Adjusted Life Years (QALY) for transferring ICH patients to a NICU under a most favorable scenario. However, these estimates are about 93% to 700% higher for less favorable scenarios [
18]. Reliance on probabilistic assumptions behind simulation models, and interpretation of willingness-to-pay thresholds remain significant limitations of such analyses. Other studies based on primary data have reported that cost effectiveness of transfer of ICH patients is not clearly demonstrable, and that an evidence-based triage algorithm for optimal selection of patients is warranted [
19].
Based on the above discussion, there is enough equipoise for EnRICH, which has the following aims:
1.
To examine the association between level of care (as defined by certification status of the hospital) and outcomes in ICH patients
2.
To estimate the health economic impact of management of ICH patients at CSCs, as compared to PSCs and / or non-certified hospitals
3.
To characterize a subset of ICH patients that optimally benefits from care provision and management at HLOC (such as CSCs)