Original Article
Predictors of Treatment Delay in Aneurysmal Subarachnoid Hemorrhage Patients J. Manuel Sarmiento1 Debraj Mukherjee1 Chirag G. Patil1 Miriam Aracely Nuno1
Kristin Nosova1
1 Department of Neurosurgery, Cedars-Sinai Medical Center,
Los Angeles, California, United States J Neurol Surg A 2015;76:46–55.
Abstract
Keywords
► treatment delay ► timeliness ► aneurysmal subarachnoid hemorrhage (aSAH) ► hospital volume ► weekend effect
Michael J. Alexander1
Address for correspondence Miriam Aracely Nuno, PhD, Department of Neurosurgery, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Suite A6229, Los Angeles, CA 90048, United States (e-mail: [email protected]).
Background and Purpose Expeditious treatment is critical in patients with aneurysmal subarachnoid hemorrhage (aSAH) due to the risk of rebleeding. This study aimed to define predictors of treatment delay among aSAH patients. Methods A retrospective study of the Nationwide Inpatient Sample database identified patients diagnosed with SAH between 2002 and 2007. Patient’s characteristics such as age, gender, race, insurance, SAH severity, treatment (coil versus clip), and other factors were studied. The Cochrane-Armitage test was used to assess delayed care trends by procedure, time of treatment, and hospital volume. Multivariate logistic regression evaluated factors associated with treatment delays. Results A total of 38,827 patients were admitted between 2002 and 2007; 69.0% were women and 61% were white. The overall median age was 52 years. More patients underwent treatment with surgical clipping than with endovascular coiling (60.4% versus 39.6%, respectively). Overall, 74% of hospital admissions occurred on weekdays; the remaining 26% occurred on weekends. Multivariate analysis revealed that older age (odds ratio [OR]: 1.1; p ¼ 0.0004) and surgical clipping versus endovascular coiling (OR: 1.3; p ¼ 0.02) were independent predictors of delayed treatment (i.e., >2 days from admission). Nonwhite patients experienced greater treatment delays on weekdays compared with white patients (OR: 1.4; p ¼ 0.01). Furthermore, patients treated in lowvolume hospitals were significantly more likely to experience delays than those treated in higher volume hospitals (OR: 2.0; p ¼ 0.007). Conclusions Risk factors associated with treatment delay in aSAH patients include older age, nonwhite race, surgical clipping, and admission to low surgical volume hospitals.
Introduction Reducing harmful delays within health care systems is one of the six aims proposed by the Institute of Medicine to improve timely access to health care services.1 Timing is particularly imperative with respect to aneurysmal subarachnoid hemorrhage (aSAH) evaluation and treatment. The 2012 guidelines
received November 21, 2013 accepted January 3, 2014 published online May 12, 2014
Wouter I. Schievink1
for the management of aSAH from the American Heart Association/American Stroke Association recommend prompt surgical clipping or endovascular coiling of ruptured aneurysms in most patients to reduce the rate of rebleeding (Class I; Level of evidence B).2 Expeditious treatment is important for reducing the risk of aneurysmal rebleeding, focal ischemic deficits, and hydrocephalus in patients with
© 2015 Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1372438. ISSN 2193-6315.
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Predictors of Treatment Delay in Aneurysmal SAH
Patients and Methods Data Source Patients satisfying our inclusion/exclusion criteria were selected from the NIS database from years 2002 to 2007, which was obtained from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality. The NIS reflects a stratified sample (20%) of all American hospitals.
Inclusion and Exclusion Criteria for Cases Analyzed We identified adult patients (18 years of age) with a primary diagnosis of ruptured intracranial aneurysm (ICD-9-CM [International Classification of Diseases, Ninth Revision, Clinical Modification]: 430) and a primary procedure of either “clipping of aneurysm” (ICD-9-CM: 39.51) or “coiling of aneurysm” (ICD-9-CM: 39.79, 39.72, or 39.52). Principal diagnosis code is the primary condition requiring treatment, as determined by the admitting physician.10 Patients were excluded if they had a secondary diagnosis of head trauma (ICD-9-CM: 800.0–801.9, 803.0–804.9, 850.0–854.1, or 873.0–873.9), arteriovenous malformation or fistula (ICD-9-CM 747.81), or treatment for
47
arteriovenous malformation (ICD-9-CM: 39.53 or 92.30). Additionally, patients were excluded if there was missing data on day admission (weekday versus weekend). Finally, patients were excluded if they had both coil and clip procedures documented for a single hospitalization or if they had delays in care > 7 days because these were believed to represent significant outliers within the data set. ICD-9-M coil and clip codes have been validated11 and used in other studies.12–16
Patient and Hospital Characteristics Patient age, gender, race, primary insurance type/payer (Medicare, Medicaid, private), median household income, procedure type (coil, clip), day of admission (weekday versus weekend), comorbidities, placement of ventriculostomy, and days from admission to surgery were compiled. Hospital characteristics that were evaluated included teaching status, admission source (direct admit versus transfer), treatment year, and hospital volume. To evaluate factors associated with longer delays, we denoted timely care as instances when patients were treated within 2 days of admission; patients treated > 2 days following admission were considered to have a treatment delay. To adjust for hospital surgical volume, centers were internally classified into quintiles based on combined clipping and coiling volume: quintile 1 (Q1) pertained to hospitals treating 12 cases per year; quintile 5 (Q5) pertained to hospitals treating 88 cases per year. Patient’s preexisting comorbidities were adjusted for using the 30 comorbidity measures developed by Elixhauser et al.17 This weighted score based on the number and type of comorbidities documented during each patient’s hospital stay was thus calculated and used in assessing its impact on delay to treatment.
Disease Severity A reliable and previously validated mortality-risk algorithm was implemented as a surrogate marker for disease severity (SAH grade) because the NIS data does not have a SAHspecific disease severity scale.18,19 This algorithm describes four disease stages according to their biological severity, which is defined as the risk of organ failure or death. Stage 1 corresponds to disease without complications, stage 2 corresponds to disease with local complications, stage 3 corresponds to disease involving multiple sites or systemic complications, and stage 4 corresponds to death.19 Subdivisions (e.g., stage 3.03) capture further details and are changed to reflect the patient’s dynamic clinical status. A SAH patient coded with disease stage 3.01, for example, means that an intracranial hemorrhage was diagnosed with either a computed tomography (CT) scan or magnetic resonance imaging report and is used to reflect the least form of severity. Furthermore, a SAH patient with disease stage 3.01 who develops persistent cranial nerve palsy after the third day of treatment would be classified as disease stage 3.02 to reflect the worsening severity. A SAH patient is recoded as stage 3.03 if he or she experiences pyramidal tract signs with the hemorrhage. Specifically, these clinical signs may include any of the following: (1) acute loss of balance unresolved after 24 hours, (2) acute nystagmus unresolved after Journal of Neurological Surgery—Part A
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SAH.3 A 2002 systematic review including the only randomized clinical trial on timing of surgery after aSAH,4 along with several other observational studies, showed that both early (days 0–3) and intermediate (days 4–7) surgical treatment improved outcome after aSAH compared with late surgery (>7 days posthemorrhage).5 Varying clinical factors have been postulated as contributing toward treatment delays; however, such factors have not been rigorously tested thus far. Despite the fact that the International Cooperative Study evaluating the timing of aneurysm surgery reported that SAH patients who had surgery planned on posthemorrhage days 4 to 10 had increased mortality rates compared with patients with planned surgery on days 0 to 3,3 there is currently no study evaluating the impact of weekend admission, hospital volume, and other potentially important factors on the timing of treatment for aSAH. The risk of rebleeding is maximal in the first 2 to 12 hours, and the incidence of rebleeding within the first 24 hours is between 4% and 13.6%.6–9 Therefore, the general dictum has been to treat ruptured aneurysms surgically or endovascularly within 24 to 48 hours of presentation. Because timeliness of treatment is important in the management of SAH and serves as a quality benchmark, appraisal of our national performance is necessary to ensure that the highest standards of care are being offered across health systems. Additionally, others factors thus far not assessed in the literature may be identified as potential risk factors of delay in care. We utilized the Nationwide Inpatient Sample (NIS), which serves as the largest all-payer inpatient database of U.S. hospitals, to evaluate time to aneurysm treatment following aSAH admissions. The primary objectives of this study were to assess time to treatment for patients with aSAH across the United States and to determine the impact of various factors on possible delays in care including hospital volume, weekend admission, and type of treatment.
Sarmiento et al.
Predictors of Treatment Delay in Aneurysmal SAH
Sarmiento et al.
24 hours, (3) acute spasticity unresolved, or (4) acute poor finger-to-nose or heel-to-shin tests unresolved after 24 hours. Stage 3.04 indicates acute hemiparesis or acute hemiplegia unresolved after 24 hours. Stage 3.05 indicates acute quadriplegia unresolved after 24 hours. SAH patients that meet criteria for stage 3.01 to 3.05 with sepsis (irrespective of the source of sepsis) are classified as having a severity score of stage 3.06, and if respiratory failure is observed, the patient’s severity score is coded as stage 3.07. SAH patients with coma are classified as stage 3.08. SAH patients who died are classified as stage 4.00. Comparisons can be made between disease severity codes and the Hunt and Hess SAH grading scale (Appendix 1).20 For instance, severity score 3.02 and 3.03 roughly correspond to Hunt and Hess grades II and III, respectively. Severity score 3.04 and 3.08 closely correspond to Hunt and Hess grades IV and V, respectively.21
Statistical Analysis Chi-square and t tests were used to evaluate univariate associations for binary and continuous outcome variables, respectively. The Cochran-Armitage test was used to assess delay trends over time. Multivariate logistic regression was used to determine factors associated with treatment delay. Adjusted odds ratios (ORs), 95% confidence intervals (CIs), and corresponding p values were reported. All analyses were completed using SAS v.9.1 for Windows (SAS Institute Inc., Cary, NC, USA).
Results The NIS estimated 38,827 patients were included in our analysis. The median age for all patients was 52 years, with 69% females, 61.5% white, 50.3% with private insurance, and most (49.5%) with a median income of $45,000. Patients generally had a similar proportion of comorbidities across the different Elixhauser comorbidity scores that ranged from 23.4 to 28.5%. Most patients (64.6%) had a disease severity level of 1. Overall, 74% of patients were admitted on a weekday; the remaining 26% of patients were admitted on a weekend. Most patients were treated with surgical clipping (60.4%) and were admitted on a weekday (74.1%). A significant portion (30.7%) of patients underwent a ventriculostomy during their hospitalization (►Table 1). An overwhelming majority of patients (84.4%) were treated in teaching hospitals, and most patients (67.3%) were directly admitted to their respective hospitals, as opposed to the 32.7% that were admitted by transfer. The number of patients treated for aSAH between 2002 and 2006 increased steadily each subsequent year from 12% to 21.8%, respectively. There was a relative decrease in treatment volume in 2007 (14.8%). Patient admission to hospitals with varying treatment volumes was reported in quintiles, and there was an even distribution of admissions across these different hospitals, ranging from 18.4% to 22% (►Table 2).
Univariate Analysis of Treatment Delay Among the total of 38,827 aSAH patients analyzed, a subset of 3620 patients (9.3%) had their aneurysms treated > 2 days Journal of Neurological Surgery—Part A
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after admission. The incidence of patients who experienced delayed care following coiling and clipping was 6.9% and 10.9%, respectively. In univariate analysis comparing those with and without treatment delay, patient-related factors found to be associated with delays included older patient age (p ¼ 0.006), nonprivate insurance (p ¼ 0.003), type of surgery (p < 0.0001), and day of admission (weekday versus weekend; p < 0.0001). Patients undergoing surgical clipping were consistently more likely to encounter delayed treatment than coiling (p < 0.0001) throughout the studied period (►Fig. 1). Overall, patients admitted on the weekend appeared more likely to experience treatment delay than weekday admissions; an overall incidence of delayed care at 10.7% was observed among those with weekend admission compared with an 8.8% incidence for weekday admissions (p ¼ 0.12) (►Fig. 2). Patient gender, race, income, Elixhauser comorbidity score, and severity score were not associated with delays in care. Patients who had a ventriculostomy were more likely to receive timely care compared with those who did not have this procedure (p ¼ 0.03) (►Table 1). Between 2002 and 2007, the fraction of patients experiencing treatment delays varied between 12.9% and 23.6%. Hospital-related factors associated with longer delays included teaching hospital status (p ¼ 0.002), admission source (p ¼0.05), and hospital treatment volume (p < 0.0001). A higher incidence of treatment delay was observed at hospitals within the lowest quintile of volume compared with those within the highest quintile (13.8% versus 7.4%; p < 0.0001) (►Fig. 3). Year of treatment was not associated with delays in care (►Table 2).
Multivariate Analysis of Treatment Delay In a multivariate analysis of all patients, factors associated with delay in treatment included older age by decade (OR: 1.1; p ¼ 0.0004), nonwhite race (OR: 1.2; p ¼ 0.09), surgical clipping (OR: 1.3; p ¼0.02), and treatment at centers within the lowest quintile of volume (OR: 2.0; p ¼ 0.007) (►Table 3). Conversely, patients undergoing a ventriculostomy had a 20% decreased risk of experiencing delay in either surgical or endovascular treatment (OR: 0.8; p ¼ 0.04). Patient gender, insurance status, day of admission (weekend versus weekday), income, admission type (direct admit versus transfer), Elixhauser comorbidity score, and disease severity were adjusted for and were found not to be associated with treatment delay. There was a trend toward a higher risk of delays in patients treated on the weekend, although this effect was not statistically significant.
The Effect of Weekend versus Weekday Admission on Treatment Delay In an attempt to assess two-way interactions between weekend/weekday and all other predictors previously shown to be associated with delayed care, we found that the effect of age, race, treatment type (coil versus clip), and ventriculostomy strongly depended on whether a patient was treated on a weekday or weekend. That is, among weekday admissions, older patients had a 20% increased risk of delayed care (OR: 1.2; p ¼ 0.002) and nonwhite patients had a 40% increased
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Predictors of Treatment Delay in Aneurysmal SAH
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Table 1 Characteristics of 38,827 subarachnoid hemorrhage patients, 2002–2007 All cases (N ¼ 38,827)
p value
Treatment delay 2 d from admission (N ¼ 35,207)
> 2 d from admission (N ¼ 3620)
Age, y Mean (SE)
53.5 (13.3)
53.3 (13.3)
54.9 (14.0)
Median
52.0
52.0
53.0
26,714 (69.0)
24,326 (69.3)
2389 (66.2)
0.07
White
18,137 (61.5)
16,554 (62.0)
1583 (57.0)
0.18
African American
4784 (16.2)
4353 (16.3)
430 (15.5)
Hispanic
1427 (14.0)
3649 (13.7)
478 (17.2)
Asian/Pacific Islander
1173 (4.0)
1038 (3.9)
134 (4.8)
Female, N (%)
0.006
Native American
79 (0.3)
69 (0.2)
10 (0.3)
Other
1170 (4.0)
1031 (3.9)
139 (5.0)
Primary payer, N (%) Medicare
7983 (20.6)
7064 (20.1)
919 (25.4)
Medicaid
5064 (13.1)
4566 (13.0)
498 (13.8)
Private insurance
19,483 (50.3)
17,840 (50.8)
1643 (45.4)
Self-pay
3966 (10.2)
3569 (10.2)
397 (11.0)
No Charge/Other
2223 (5.7)
2063 (5.9)
162 (4.5)
< $24,999
289 (6.4)
250 (6.2)
39 (8.4)
$25,000–34,999
795 (17.7)
691 (17.1)
104 (22.8)
$35,000–44,999
1190 (26.4)
1074 (26.5)
117 (25.5)
> $45,000
2228 (49.5)
2030 (50.2)
198 (43.3)
Coil
15,391 (39.6)
14,323 (40.7)
1068 (29.5)
Clip
23,436 (60.4)
20,884 (59.3)
2552 (70.5)
0.003
Median income in zip code, N (%) 0.41
Surgery type, N (%) < 0.0001
Comorbidity score, N (%) 0
9084 (23.4)
8254 (23.4)
830 (22.9)
1
11,072 (28.5)
10,018 (28.5)
1054 (29.1)
2
9845 (25.4)
8949 (25.4)
895 (24.7)
3þ
8826 (22.7)
7986 (22.7)
841 (23.2)
25,099 (64.6)
22,796 (64.7)
2303 (63.6)
2087 (5.4)
1902 (5.4)
185 (5.1)
440 (1.1)
410 (1.2)
29 (0.8)
2728 (7.0)
2428 (6.9)
301 (8.3)
3.05
9 (0.02)
4 (0.01)
4 (0.1)
3.06
6216 (16.0)
5634 (16.0)
583 (16.1)
3.07
2073 (5.3)
1869 (5.3)
204 (5.6)
175 (0.5)
165 (0.5)
10 (0.3)
0.99
Disease severity level, N (%) 3.01 3.02
a
3.03b 3.04
3.08
c
d
0.44
(Continued)
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Race, N (%)
Predictors of Treatment Delay in Aneurysmal SAH
Sarmiento et al.
Table 1 (Continued) All cases (N ¼ 38,827)
p value
Treatment delay 2 d from admission (N ¼ 35,207)
> 2 d from admission (N ¼ 3620)
26,220 (74.5)
2546 (70.3)
10,061 (25.9)
8987 (25.5)
1074 (29.7)
11,933 (30.7)
10,973 (31.2)
960 (26.5)
Day of admission, N (%) Weekday
28,766 (74.1)
Weekend Ventriculostomy, N (%)
< 0.0001 0.03
Abbreviation: SE, standard error. Note: Missing data in 0.24% of females, 24.1% of race, 0.28% primary payer, and 88.4% of income variables. Rounded percent (%). a Closely corresponds to Hunt and Hess grade II. b Closely corresponds to Hunt and Hess grade III. c Closely corresponds to Hunt and Hess grade IV. d Closely corresponds to Hunt and Hess grade V.
risk of treatment delay (OR: 1.4; p ¼ 0.01) compared with younger patients and white patients, respectively. Surgically clipped patients on weekdays had a 30% increased risk of treatment delay (OR: 1.3; p ¼ 0.04) compared with patients whose aneurysms were coiled. The increased risks of treatments delays were observed in patients treated with surgical clipping on weekends as well; however, this finding was not statistically significant. Hospital surgical volume was consistently significant in predicting delays, independently of whether a patient was treated during the week or the
weekend; however, the effect and level of significance was more apparent among weekend admissions (OR: 2.7; p ¼ 0.04) compared with weekdays (OR: 1.8; p ¼ 0.01). Ventriculostomy placement reduced the risk of treatment delay in the weekdays by 30% (OR: 0.7; p ¼ 0.02).
Discussion Patients with aSAH are estimated to have a 10 to 20% rate of long-term disability and a case-fatality rate ranging from 32
Table 2 Characteristics of hospitals treating 38,827 subarachnoid hemorrhage patients (2002–2007) All cases (N ¼ 38,827)
p value
Treatment delay 2 d from admission (N ¼ 35,207)
> 2 d from admission (N ¼ 3620)
32,779 (84.4)
29,933 (85.0)
2846 (78.6)
0.002
Direct-admit
26,117 (67.3)
23,559 (66.9)
2558 (70.7)
0.05
Transfer
12,710 (32.7)
11,648 (33.1)
1062 (29.3)
2002
4678 (12.0)
4210 (12.0)
468 (12.9)
2003
6012 (15.5)
5408 (15.4)
604 (16.7)
2004
7018 (18.1)
6436 (18.3)
583 (16.1)
2005
6972 (17.8)
6290 (17.9)
636 (17.6)
2006
8456 (21.8)
7603 (21.6)
854 (23.6)
2007
5736 (14.8)
5261 (14.9)
475 (13.1)
1
7417 (19.1)
6390 (18.1)
1027 (28.4)
2
7273 (18.7)
6483 (18.4)
790 (21.8)
3
7150 (18.4)
6528 (18.5)
623 (17.2)
4
8540 (22.0)
7983 (22.7)
557 (15.4)
5
8446 (21.7)
7824 (22.2)
623 (17.2)
Teaching hospital Admission source, N (%)
Treatment year 0.54
Hospital volume (quintile)
Note: Rounded percent (%). Journal of Neurological Surgery—Part A
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< 0.0001
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Predictors of Treatment Delay in Aneurysmal SAH
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findings appear to reflect a delay in access or initial referral to a qualified neurosurgeon in a timely manner, particularly at smaller centers.
Fig. 1 Trends in the incidence of delayed care for all patients by type of treatment, 2002–2007.
Aneurysm rebleeding is recognized as one of the worst complications following aSAH. The incidence of rebleeding following aSAH is believed to be as high as 13.6% in the first 24 hours when taking very early rebleeding (i.e., rebleeding during the first 8 hours after aSAH) into consideration.9,23 After the first 24 hours, the incidence rate drops to 1 to 2% per day for the next 14 days.23 Approximately 30% of aSAH patients who do not receive treatment have a rebleed within 1 month of the initial aSAH.24 In a prospective study following 176 aSAH patients, 39 (22%) had a CT-proven rebleed within 4 weeks after initial aSAH, and in 20 (51%) of these patients the rebleed was fatal. Approximately 30% of the patients with a rebleed died from other complications; the remaining 20% of patients survived at 3 months, although most had severe brain damage.25 Delays in treatment of aSAH cause preoperative clinical deterioration due to rebleeding. Even in centers that adopt early surgical intervention (i.e., within 3 days after aSAH), rebleeding has been reported as the most important and most common preventable cause of death in hospitalized patients.26
Timing of Aneurysm Treatment Fig. 2 Trends in the incidence of delayed care for all patients by weekday versus weekend admission, 2002–2007.
to 67%.22 These alarming rates underscore the need for timely intervention for patients who present with aSAH. This study describes risk factors associated with delays in treatment of aSAH using a large administrative database. Our results show that older age, nonwhite race, and surgical clipping are factors that significantly delay treatment, particularly during weekday admissions. In addition, patients treated in the lowestquintile volume centers had more delays compared with those treated at the highest-quintile volume centers. These
Fig. 3 Trends in the incidence of delayed care for all patients by lowest versus highest volume quintile status, 2002–2007.
Timing of aneurysm surgery after aSAH has been assessed by a few prospective studies. In 1990, Kassell et al reported their results from the International Cooperative Study on the Timing of Aneurysm Surgery, a prospective multicenter observational trial that discovered the lowest mortality rate among SAH patients was achieved when surgery was planned on days 0 to 3 or 11 to 14.3 In addition, they reported that the number of patients with rebleeding increased progressively with longer intervals of planned surgery from 6% for days 0 to 3 to 22% for days 15 to 32. A 1989 randomized control study by Ohman and Heiskanen assessed the optimum timing for surgery in 216 patients with ruptured anterior circulation aneurysms in good clinical condition (Hunt and Hess grades I–III).4 They reported a significantly higher number of disabled patients in patients who underwent delayed surgery (days 4–7) compared with the early surgery group (days 0–3) (11 patients versus 2 patients, respectively; p ¼ 0.01). Rebleeding was a common cause of preoperative deterioration, and a significant difference in rebleeding was observed between patients who underwent early surgery versus late surgery (two patients and eight patients, respectively; p ¼ 0.01). In addition, three patients from the intermediate surgery group (4–7 days) and six patients from the late surgery group (> 7 days) died before surgery was undertaken. All deaths were attributed to time-sensitive complications of delayed cerebral ischemia and rebleeding. Numerous other retrospective studies have provided further support for the notion of treating aSAH as early as possible.5,27–32 The primary treatment for aSAH consists of either surgical clipping or endovascular coiling. Dorhout Mees et al explored the ideal timing of coiling and clipping after aSAH by assessing Journal of Neurological Surgery—Part A
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Consequences of Delayed Treatment
Predictors of Treatment Delay in Aneurysmal SAH
Sarmiento et al.
Table 3 Adjusted odds ratio of delayed treatment (> 2 days from admission) for all and stratified patients by admission with corresponding 95% confidence intervals and p values All admissions
Day of admission Weekend
Weekday
OR (95% CI)
p value
OR (95% CI)
p value
OR (95% CI)
p value
1.1 (1.1–1.2)
0.0004
1.1 (0.9–1.2)
0.30
1.2 (1.1–1.3)
0.002
Nonwhite
1.2 (0.9, 1.5)
0.09
0.9 (0.6–1.3)
0.57
1.4 (1.1–1.7)
0.01
Clip versus coil
1.3 (1.0–1.6)
0.02
1.3 (0.9–1.9)
0.23
1.3 (1.0–1.7)
0.04
1.1 (1.0–1.4)
0.12
1.1 (0.8–1.5)
0.57
1.2 (1.0–1.4)
0.15
Weekend versus week
1.2 (0.9–1.4)
0.15
–
–
–
–
Ventriculostomy
0.8 (0.6–1.0)
0.04
0.8 (0.5–1.3)
0.36
0.7 (0.6–1.0)
0.02
Age, y
a
Race (reference: white)
Insurance type (reference: private) Nonprivate Day of admission
Hospital surgical volume (reference: highest quintile) First quintile
2.0 (1.2–3.4)
0.007
2.7 (1.0–6.9)
0.04
1.8 (1.1–2.9)
0.01
Second quintile
1.5 (0.9–2.7)
0.13
1.8 (0.7–4.7)
0.25
1.4 (0.9–2.4)
0.15
Third quintile
1.3 (0.7–2.2)
0.42
1.3 (0.5–3.7)
0.65
1.2 (0.5–1.4)
0.37
Fourth quintile
0. 8 (0.4–1.4)
0.70
0.7 (0.2–2.2)
0.51
0.8 (0.5–1.4)
0.46
Abbreviations: CI, confidence interval; OR, odds ratio. Note: Admission type (transfer versus direct admit), income, Elixhauser comorbidity score, and disease severity (SAH grade) were not associated with longer delays. a Per decade increment.
clinical outcomes between different timings of treatment for coiled and for clipped patients within the International Subarachnoid Aneurysm Trial (ISAT).33 This study included 2106 patients who were randomized to receive either endovascular or neurosurgical treatment. Among these patients, 891 patients (42.3%) were treated on posthemorrhage days 0 to 2, 482 patients (22.9%) were treated on days 3 to 4, 474 patients (22.5%) were treated between days 5 and 10, and 259 patients (12.3%) were treated after 10 days.3 The risk for poor outcomes, defined as a modified Rankin Scale score of 3 (at 2 months), were significantly worse for patients treated after 5 days compared with patients treated during the first 2 days. Patients treated during the 3- to 4-day window showed a trend toward worse outcomes. This is the largest prospective clinical trial to date showing that aneurysm treatment after day 5 is associated with worse outcomes, regardless of what treatment modality was used. Our study goes beyond the confines of the controlled clinical trial setting and describes treatment delays after aSAH on a national level. In our study, surgical clipping was identified as a risk factor for treatment delay, perhaps reflecting a need to coordinate greater health care resources to prepare for clipping versus coiling procedures, although limitations inherent to the NIS did not allow us to fully explore this possible mechanism for delay.
Limitations Another limitation of our study is that the NIS does not provide a comprehensive clinical profile of each patient. Journal of Neurological Surgery—Part A
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This prevented us from obtaining information about patients’ chief complaints, associated symptoms, and data on the specific location and size of ruptured aneurysms. We also do not know when the patients had their SAH and what postbleed day they presented for care. Furthermore, aSAHspecific complications, such as rebleeding and delayed cerebral ischemia rates, could not be assessed due to limitations of the NIS. Additionally, given that the NIS is primarily an administrative inpatient data set, data beyond the initial hospitalization are not available to track patient outcomes longitudinally. Other factors that we were unable to evaluate but have been shown to cause treatment delays among aSAH patients are the failure of patients to seek prompt medical care and physician diagnostic errors.34 Moreover, the impact of specialist availability could not be assessed. Indeed, given that administrative personnel rather than clinicians are primarily responsible for collection of data elements, and given that these data elements are compiled retrospectively rather than prospectively at participating sites, there remains significant risk for information and selection bias inclusive of coding errors within the data set.
Weekend Effect Some studies have described increased mortality in those with emergent conditions when such patients are admitted on weekends.35–38 This “weekend effect” may be attributable to several factors including restrictions on the availability of diagnostic imaging,39 decreased staffing,40 less experience among health care personnel,35 or the delayed provision of
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Predictors of Treatment Delay in Aneurysmal SAH
Effects of Age on Treatment Delay Our study found that older patients were significantly more likely to experience treatment delay. Previous literature focusing on the impact of age on the timeliness of interventional care has been limited and variable. For instance, a 6year retrospective study on the timeliness of percutaneous coronary interventions found that older patients were more likely than younger counterparts to have delayed door-toballoon times, although the mechanistic reason for these findings were unable to be elucidated in this national registry study.45 The relationship between age, comorbidities, patient’s overall clinical status, and timing of aneurysm treatment is complex and has been challenging to study.
Effects of Race on Treatment Delay Racial differences in SAH incidence and mortality have been established in the literature.46–51 Our study showed that nonwhite patients admitted on weekdays have a higher risk of treatment delay compared with their white counterparts. Such delays may explain the differences in mortality observed among minority populations. In a study by Schievink et al evaluating the racial distribution of aSAH mortality in Los Angeles County, the most ethnically diverse jurisdiction in the United States, marked racial differences in SAH mortality were found.43 This study found that overall whites were at the lowest risk, followed by Hispanics and Asians at intermediate risk, and African Americans at the highest risk of mortality. The differences for these racial disparities in SAH mortality are not entirely clear.
Placement of Ventriculostomy Our study demonstrated placement of ventriculostomy as the only covariate significantly associated with decreased delays in care. The limitations of the NIS data set did not allow us to further explore this association. Perhaps this finding may relate to ventriculostomy acting as a surrogate marker for neurosurgeon availability; that is, the fact that the patient had a ventriculostomy meant that a neurosurgeon was available
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to place it and hence also provide timely treatment. Although there generally has not been a large pool of data assessing the timing of intervention with placement of ventriculostomy in aSAH patients, the retrospective single-institution study by McIver et al demonstrated no significant difference in mean time interval between presentation and surgery in those with or without ventriculostomy placed preoperatively.52 Although the relationship between clinical presentation, ventriculostomy placement, and timing of surgery or endovascular intervention among aSAH patients may be somewhat complex, our findings coupled with those of McIver et al seem to at least demonstrate that placement of ventriculostomy does not delay care in patients with aSAH.
Centralization of Care The treatment of ruptured cerebral aneurysms is increasingly taking place at high-volume hospitals within the United States.53 This trend is in accordance with the recommendations of the 2012 guidelines for management of ruptured cerebral aneurysms that advocate for low-volume hospitals (defined as hospitals that treat < 10 aSAH cases per year) to transfer patients to high-volume centers (defined as hospitals that treat > 35 aSAH cases per year) with experienced cerebrovascular surgeons, endovascular specialists, and multidisciplinary neuro-intensive care services (class I; level of evidence B).2 Various reports from the literature have showed that hospitals with high case volumes of aSAH have superior outcomes than hospitals with low case volumes.15,21,44 Our data indicate that patients who present with aSAH at the lowest quintile volume hospitals experience greater delays in treatment compared with those who are treated at the highest quintile volume hospitals. These differences in mortality between high- and low-volume centers were previously attributed to varying hospital resources, specialty training, specialist availability, and care in the neuro-intensive care unit.44 Our findings of delay of care at lower volume hospitals may also contribute to the worse outcomes previously reported in lower volume centers. Even after acknowledging the benefits of expeditious treatment for aSAH patients, some providers may hesitate to transfer critically ill patients, recognizing that outcomes for transfer patients have been shown to be worse than directadmit patients.54–56 However, the findings of Nuño et al recently demonstrated similar outcomes between aSAH patients regardless of whether they were directly admitted or transferred to a higher volume hospital.21 Our findings that lower volume hospitals have more delays in aneurysm treatment coupled with the data showing similar outcomes for direct-admit versus transfer patients further supports the recent centralization of care efforts for aSAH.2 Expedited referrals to qualified neurosurgeons at high-volume institutions may mitigate critical delays in the care of patients with aSAH.
Conclusions Neurologic emergencies such as aSAH often have dire morbidity and mortality. As such, it is imperative that all aSAH Journal of Neurological Surgery—Part A
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intensive procedures on weekends.41 Although a “weekend effect” on mortality was not demonstrated in the analysis by Crowley et al among aSAH patients, potential delays in care on weekends may still increase morbidity and complications among aSAH patients given the risk of rebleeding and increased risk of treatment while in the vasospasm period.38 This idea is supported by a 2012 study by Siddiq et al that found weekend admission among patients with aSAH reduced the likelihood of early treatment, which was defined as treatment performed within 48 hours of admission, by 30% (OR: 0.7; 95% CI, 0.6–0.8; p < 0.001).42 Our study showed a strong trend toward a higher risk of treatment delays in patients admitted on weekends, although this finding proved not to be statistically significant after adjusting for several relevant covariates in our multivariate model. We found that weekend admission had a milder effect on treatment delays after adjusting for race43 and hospital treatment volume,15,21,44 two potential confounders that have been demonstrated to influence survival in aSAH patients.
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patients be referred to a qualified neurosurgeon at a highvolume institution to allow for treatment in an expeditious manner irrespective of the time, place, or date on which they present for care. In this retrospective nationwide analysis, we show that > 90% of aSAH patients in the United States are being treated within the recommended 2-day window. Older age and surgical clipping were independently associated with delay to treatment. Racial differences in treatment delays were more apparent in weekdays, with nonwhite patients experiencing more delays in treatment than white patients. We also present evidence suggesting that patients treated in the lowest quintile volume hospitals are more likely to experience greater delays to treatment. Minimizing treatment delays for aSAH remains an important area of concern both for clinicians and policymakers.
References
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of aneurysm treatment after subarachnoid hemorrhage: relationship with delayed cerebral ischemia and poor outcome. Stroke 2012;43(8):2126–2129 Schievink WI, van der Werf DJ, Hageman LM, Dreissen JJ. Referral pattern of patients with aneurysmal subarachnoid hemorrhage. Surg Neurol 1988;29(5):367–371 Bell CM, Redelmeier DA. Mortality among patients admitted to hospitals on weekends as compared with weekdays. N Engl J Med 2001;345(9):663–668 Kostis WJ, Demissie K, Marcella SW, Shao YH, Wilson AC, Moreyra AE; Myocardial Infarction Data Acquisition System (MIDAS 10) Study Group. Weekend versus weekday admission and mortality from myocardial infarction. N Engl J Med 2007;356(11): 1099–1109 Hasegawa Y, Yoneda Y, Okuda S, et al; Acute Stroke Rehabilitation Study Group. The effect of weekends and holidays on stroke outcome in acute stroke units. Cerebrovasc Dis 2005;20(5): 325–331 Crowley RW, Yeoh HK, Stukenborg GJ, Ionescu AA, Kassell NF, Dumont AS. Influence of weekend versus weekday hospital admission on mortality following subarachnoid hemorrhage. Clinical article. J Neurosurg 2009;111(1):60–66 Bell CM, Redelmeier DA. Waiting for urgent procedures on the weekend among emergently hospitalized patients. Am J Med 2004;117(3):175–181 Saposnik G, Baibergenova A, Bayer N, Hachinski V. Weekends: a dangerous time for having a stroke? Stroke 2007;38(4): 1211–1215 Becker DJ. Do hospitals provide lower quality care on weekends? Health Serv Res 2007;42(4):1589–1612 Siddiq F, Chaudhry SA, Tummala RP, Suri MF, Qureshi AI. Factors and outcomes associated with early and delayed aneurysm treatment in subarachnoid hemorrhage patients in the United States. Neurosurgery 2012;71(3):670–677; discussion 677–678 Schievink WI, Riedinger M, Jhutty TK, Simon P. Racial disparities in subarachnoid hemorrhage mortality: Los Angeles County, California, 1985–1998. Neuroepidemiology 2004;23(6):299–305
subarachnoid hemorrhage: variations according to hospital case volume in 18 states. J Neurosurg 2003;99(5):810–817 Krumholz HM, Herrin J, Miller LE, et al. Improvements in door-toballoon time in the United States, 2005 to 2010. Circulation 2011; 124(9):1038–1045 Broderick JP, Brott T, Tomsick T, Huster G, Miller R. The risk of subarachnoid and intracerebral hemorrhages in blacks as compared with whites. N Engl J Med 1992;326(11):733–736 Sacco RL, Boden-Albala B, Gan R, et al. Stroke incidence among white, black, and Hispanic residents of an urban community: the Northern Manhattan Stroke Study. Am J Epidemiol 1998;147(3):259–268 Johnston SC, Selvin S, Gress DR. The burden, trends, and demographics of mortality from subarachnoid hemorrhage. Neurology 1998;50(5):1413–1418 Bruno A, Carter S, Qualls C, Nolte KB. Incidence of spontaneous subarachnoid hemorrhage among Hispanics and non-Hispanic whites in New Mexico. Ethn Dis 1997;7(1):27–33 Ayala C, Greenlund KJ, Croft JB, et al. Racial/ethnic disparities in mortality by stroke subtype in the United States, 1995–1998. Am J Epidemiol 2001;154(11):1057–1063 Ayala C, Croft JB, Greenlund KJ, et al. Sex differences in US mortality rates for stroke and stroke subtypes by race/ethnicity and age, 1995–1998. Stroke 2002;33(5):1197–1201 McIver JI, Friedman JA, Wijdicks EF, et al. Preoperative ventriculostomy and rebleeding after aneurysmal subarachnoid hemorrhage. J Neurosurg 2002;97(5):1042–1044 Leake CB, Brinjikji W, Kallmes DF, Cloft HJ. Increasing treatment of ruptured cerebral aneurysms at high-volume centers in the United States. J Neurosurg 2011;115(6):1179–1183 Schiff RL, Ansell DA, Schlosser JE, Idris AH, Morrison A, Whitman S. Transfers to a public hospital. A prospective study of 467 patients. N Engl J Med 1986;314(9):552–557 Gordon HS, Rosenthal GE. Impact of interhospital transfers on outcomes in an academic medical center. Implications for profiling hospital quality. Med Care 1996;34(4):295–309 Obremskey W, Henley MB. A comparison of transferred versus direct admission orthopedic trauma patients. J Trauma 1994; 36(3):373–376
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Appendix 1 Hunt and Hess subarachnoid hemorrhage grading scale Grade I
Asymptomatic, mild headache, slight nuchal rigidity
Grade II
Moderate to severe headache, nuchal rigidity, no neurologic deficit other than cranial nerve palsy
Grade III
Drowsiness/confusion, mild focal neurologic deficit
Grade IV
Stupor, moderate to severe hemiparesis
Grade V
Coma, decerebrate posturing
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Predictors of Treatment Delay in Aneurysmal SAH
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Predictors of Treatment Delay in Aneurysmal Subarachnoid Hemorrhage Patients J. Manuel Sarmiento1 Debraj Mukherjee1 Chirag G. Patil1 Miriam Aracely Nuno1
Kristin Nosova1
1 Department of Neurosurgery, Cedars-Sinai Medical Center,
Los Angeles, California, United States J Neurol Surg A 2015;76:46–55.
Abstract
Keywords
► treatment delay ► timeliness ► aneurysmal subarachnoid hemorrhage (aSAH) ► hospital volume ► weekend effect
Michael J. Alexander1
Address for correspondence Miriam Aracely Nuno, PhD, Department of Neurosurgery, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Suite A6229, Los Angeles, CA 90048, United States (e-mail: [email protected]).
Background and Purpose Expeditious treatment is critical in patients with aneurysmal subarachnoid hemorrhage (aSAH) due to the risk of rebleeding. This study aimed to define predictors of treatment delay among aSAH patients. Methods A retrospective study of the Nationwide Inpatient Sample database identified patients diagnosed with SAH between 2002 and 2007. Patient’s characteristics such as age, gender, race, insurance, SAH severity, treatment (coil versus clip), and other factors were studied. The Cochrane-Armitage test was used to assess delayed care trends by procedure, time of treatment, and hospital volume. Multivariate logistic regression evaluated factors associated with treatment delays. Results A total of 38,827 patients were admitted between 2002 and 2007; 69.0% were women and 61% were white. The overall median age was 52 years. More patients underwent treatment with surgical clipping than with endovascular coiling (60.4% versus 39.6%, respectively). Overall, 74% of hospital admissions occurred on weekdays; the remaining 26% occurred on weekends. Multivariate analysis revealed that older age (odds ratio [OR]: 1.1; p ¼ 0.0004) and surgical clipping versus endovascular coiling (OR: 1.3; p ¼ 0.02) were independent predictors of delayed treatment (i.e., >2 days from admission). Nonwhite patients experienced greater treatment delays on weekdays compared with white patients (OR: 1.4; p ¼ 0.01). Furthermore, patients treated in lowvolume hospitals were significantly more likely to experience delays than those treated in higher volume hospitals (OR: 2.0; p ¼ 0.007). Conclusions Risk factors associated with treatment delay in aSAH patients include older age, nonwhite race, surgical clipping, and admission to low surgical volume hospitals.
Introduction Reducing harmful delays within health care systems is one of the six aims proposed by the Institute of Medicine to improve timely access to health care services.1 Timing is particularly imperative with respect to aneurysmal subarachnoid hemorrhage (aSAH) evaluation and treatment. The 2012 guidelines
received November 21, 2013 accepted January 3, 2014 published online May 12, 2014
Wouter I. Schievink1
for the management of aSAH from the American Heart Association/American Stroke Association recommend prompt surgical clipping or endovascular coiling of ruptured aneurysms in most patients to reduce the rate of rebleeding (Class I; Level of evidence B).2 Expeditious treatment is important for reducing the risk of aneurysmal rebleeding, focal ischemic deficits, and hydrocephalus in patients with
© 2015 Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1372438. ISSN 2193-6315.
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Predictors of Treatment Delay in Aneurysmal SAH
Patients and Methods Data Source Patients satisfying our inclusion/exclusion criteria were selected from the NIS database from years 2002 to 2007, which was obtained from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality. The NIS reflects a stratified sample (20%) of all American hospitals.
Inclusion and Exclusion Criteria for Cases Analyzed We identified adult patients (18 years of age) with a primary diagnosis of ruptured intracranial aneurysm (ICD-9-CM [International Classification of Diseases, Ninth Revision, Clinical Modification]: 430) and a primary procedure of either “clipping of aneurysm” (ICD-9-CM: 39.51) or “coiling of aneurysm” (ICD-9-CM: 39.79, 39.72, or 39.52). Principal diagnosis code is the primary condition requiring treatment, as determined by the admitting physician.10 Patients were excluded if they had a secondary diagnosis of head trauma (ICD-9-CM: 800.0–801.9, 803.0–804.9, 850.0–854.1, or 873.0–873.9), arteriovenous malformation or fistula (ICD-9-CM 747.81), or treatment for
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arteriovenous malformation (ICD-9-CM: 39.53 or 92.30). Additionally, patients were excluded if there was missing data on day admission (weekday versus weekend). Finally, patients were excluded if they had both coil and clip procedures documented for a single hospitalization or if they had delays in care > 7 days because these were believed to represent significant outliers within the data set. ICD-9-M coil and clip codes have been validated11 and used in other studies.12–16
Patient and Hospital Characteristics Patient age, gender, race, primary insurance type/payer (Medicare, Medicaid, private), median household income, procedure type (coil, clip), day of admission (weekday versus weekend), comorbidities, placement of ventriculostomy, and days from admission to surgery were compiled. Hospital characteristics that were evaluated included teaching status, admission source (direct admit versus transfer), treatment year, and hospital volume. To evaluate factors associated with longer delays, we denoted timely care as instances when patients were treated within 2 days of admission; patients treated > 2 days following admission were considered to have a treatment delay. To adjust for hospital surgical volume, centers were internally classified into quintiles based on combined clipping and coiling volume: quintile 1 (Q1) pertained to hospitals treating 12 cases per year; quintile 5 (Q5) pertained to hospitals treating 88 cases per year. Patient’s preexisting comorbidities were adjusted for using the 30 comorbidity measures developed by Elixhauser et al.17 This weighted score based on the number and type of comorbidities documented during each patient’s hospital stay was thus calculated and used in assessing its impact on delay to treatment.
Disease Severity A reliable and previously validated mortality-risk algorithm was implemented as a surrogate marker for disease severity (SAH grade) because the NIS data does not have a SAHspecific disease severity scale.18,19 This algorithm describes four disease stages according to their biological severity, which is defined as the risk of organ failure or death. Stage 1 corresponds to disease without complications, stage 2 corresponds to disease with local complications, stage 3 corresponds to disease involving multiple sites or systemic complications, and stage 4 corresponds to death.19 Subdivisions (e.g., stage 3.03) capture further details and are changed to reflect the patient’s dynamic clinical status. A SAH patient coded with disease stage 3.01, for example, means that an intracranial hemorrhage was diagnosed with either a computed tomography (CT) scan or magnetic resonance imaging report and is used to reflect the least form of severity. Furthermore, a SAH patient with disease stage 3.01 who develops persistent cranial nerve palsy after the third day of treatment would be classified as disease stage 3.02 to reflect the worsening severity. A SAH patient is recoded as stage 3.03 if he or she experiences pyramidal tract signs with the hemorrhage. Specifically, these clinical signs may include any of the following: (1) acute loss of balance unresolved after 24 hours, (2) acute nystagmus unresolved after Journal of Neurological Surgery—Part A
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SAH.3 A 2002 systematic review including the only randomized clinical trial on timing of surgery after aSAH,4 along with several other observational studies, showed that both early (days 0–3) and intermediate (days 4–7) surgical treatment improved outcome after aSAH compared with late surgery (>7 days posthemorrhage).5 Varying clinical factors have been postulated as contributing toward treatment delays; however, such factors have not been rigorously tested thus far. Despite the fact that the International Cooperative Study evaluating the timing of aneurysm surgery reported that SAH patients who had surgery planned on posthemorrhage days 4 to 10 had increased mortality rates compared with patients with planned surgery on days 0 to 3,3 there is currently no study evaluating the impact of weekend admission, hospital volume, and other potentially important factors on the timing of treatment for aSAH. The risk of rebleeding is maximal in the first 2 to 12 hours, and the incidence of rebleeding within the first 24 hours is between 4% and 13.6%.6–9 Therefore, the general dictum has been to treat ruptured aneurysms surgically or endovascularly within 24 to 48 hours of presentation. Because timeliness of treatment is important in the management of SAH and serves as a quality benchmark, appraisal of our national performance is necessary to ensure that the highest standards of care are being offered across health systems. Additionally, others factors thus far not assessed in the literature may be identified as potential risk factors of delay in care. We utilized the Nationwide Inpatient Sample (NIS), which serves as the largest all-payer inpatient database of U.S. hospitals, to evaluate time to aneurysm treatment following aSAH admissions. The primary objectives of this study were to assess time to treatment for patients with aSAH across the United States and to determine the impact of various factors on possible delays in care including hospital volume, weekend admission, and type of treatment.
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24 hours, (3) acute spasticity unresolved, or (4) acute poor finger-to-nose or heel-to-shin tests unresolved after 24 hours. Stage 3.04 indicates acute hemiparesis or acute hemiplegia unresolved after 24 hours. Stage 3.05 indicates acute quadriplegia unresolved after 24 hours. SAH patients that meet criteria for stage 3.01 to 3.05 with sepsis (irrespective of the source of sepsis) are classified as having a severity score of stage 3.06, and if respiratory failure is observed, the patient’s severity score is coded as stage 3.07. SAH patients with coma are classified as stage 3.08. SAH patients who died are classified as stage 4.00. Comparisons can be made between disease severity codes and the Hunt and Hess SAH grading scale (Appendix 1).20 For instance, severity score 3.02 and 3.03 roughly correspond to Hunt and Hess grades II and III, respectively. Severity score 3.04 and 3.08 closely correspond to Hunt and Hess grades IV and V, respectively.21
Statistical Analysis Chi-square and t tests were used to evaluate univariate associations for binary and continuous outcome variables, respectively. The Cochran-Armitage test was used to assess delay trends over time. Multivariate logistic regression was used to determine factors associated with treatment delay. Adjusted odds ratios (ORs), 95% confidence intervals (CIs), and corresponding p values were reported. All analyses were completed using SAS v.9.1 for Windows (SAS Institute Inc., Cary, NC, USA).
Results The NIS estimated 38,827 patients were included in our analysis. The median age for all patients was 52 years, with 69% females, 61.5% white, 50.3% with private insurance, and most (49.5%) with a median income of $45,000. Patients generally had a similar proportion of comorbidities across the different Elixhauser comorbidity scores that ranged from 23.4 to 28.5%. Most patients (64.6%) had a disease severity level of 1. Overall, 74% of patients were admitted on a weekday; the remaining 26% of patients were admitted on a weekend. Most patients were treated with surgical clipping (60.4%) and were admitted on a weekday (74.1%). A significant portion (30.7%) of patients underwent a ventriculostomy during their hospitalization (►Table 1). An overwhelming majority of patients (84.4%) were treated in teaching hospitals, and most patients (67.3%) were directly admitted to their respective hospitals, as opposed to the 32.7% that were admitted by transfer. The number of patients treated for aSAH between 2002 and 2006 increased steadily each subsequent year from 12% to 21.8%, respectively. There was a relative decrease in treatment volume in 2007 (14.8%). Patient admission to hospitals with varying treatment volumes was reported in quintiles, and there was an even distribution of admissions across these different hospitals, ranging from 18.4% to 22% (►Table 2).
Univariate Analysis of Treatment Delay Among the total of 38,827 aSAH patients analyzed, a subset of 3620 patients (9.3%) had their aneurysms treated > 2 days Journal of Neurological Surgery—Part A
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after admission. The incidence of patients who experienced delayed care following coiling and clipping was 6.9% and 10.9%, respectively. In univariate analysis comparing those with and without treatment delay, patient-related factors found to be associated with delays included older patient age (p ¼ 0.006), nonprivate insurance (p ¼ 0.003), type of surgery (p < 0.0001), and day of admission (weekday versus weekend; p < 0.0001). Patients undergoing surgical clipping were consistently more likely to encounter delayed treatment than coiling (p < 0.0001) throughout the studied period (►Fig. 1). Overall, patients admitted on the weekend appeared more likely to experience treatment delay than weekday admissions; an overall incidence of delayed care at 10.7% was observed among those with weekend admission compared with an 8.8% incidence for weekday admissions (p ¼ 0.12) (►Fig. 2). Patient gender, race, income, Elixhauser comorbidity score, and severity score were not associated with delays in care. Patients who had a ventriculostomy were more likely to receive timely care compared with those who did not have this procedure (p ¼ 0.03) (►Table 1). Between 2002 and 2007, the fraction of patients experiencing treatment delays varied between 12.9% and 23.6%. Hospital-related factors associated with longer delays included teaching hospital status (p ¼ 0.002), admission source (p ¼0.05), and hospital treatment volume (p < 0.0001). A higher incidence of treatment delay was observed at hospitals within the lowest quintile of volume compared with those within the highest quintile (13.8% versus 7.4%; p < 0.0001) (►Fig. 3). Year of treatment was not associated with delays in care (►Table 2).
Multivariate Analysis of Treatment Delay In a multivariate analysis of all patients, factors associated with delay in treatment included older age by decade (OR: 1.1; p ¼ 0.0004), nonwhite race (OR: 1.2; p ¼ 0.09), surgical clipping (OR: 1.3; p ¼0.02), and treatment at centers within the lowest quintile of volume (OR: 2.0; p ¼ 0.007) (►Table 3). Conversely, patients undergoing a ventriculostomy had a 20% decreased risk of experiencing delay in either surgical or endovascular treatment (OR: 0.8; p ¼ 0.04). Patient gender, insurance status, day of admission (weekend versus weekday), income, admission type (direct admit versus transfer), Elixhauser comorbidity score, and disease severity were adjusted for and were found not to be associated with treatment delay. There was a trend toward a higher risk of delays in patients treated on the weekend, although this effect was not statistically significant.
The Effect of Weekend versus Weekday Admission on Treatment Delay In an attempt to assess two-way interactions between weekend/weekday and all other predictors previously shown to be associated with delayed care, we found that the effect of age, race, treatment type (coil versus clip), and ventriculostomy strongly depended on whether a patient was treated on a weekday or weekend. That is, among weekday admissions, older patients had a 20% increased risk of delayed care (OR: 1.2; p ¼ 0.002) and nonwhite patients had a 40% increased
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Predictors of Treatment Delay in Aneurysmal SAH
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Table 1 Characteristics of 38,827 subarachnoid hemorrhage patients, 2002–2007 All cases (N ¼ 38,827)
p value
Treatment delay 2 d from admission (N ¼ 35,207)
> 2 d from admission (N ¼ 3620)
Age, y Mean (SE)
53.5 (13.3)
53.3 (13.3)
54.9 (14.0)
Median
52.0
52.0
53.0
26,714 (69.0)
24,326 (69.3)
2389 (66.2)
0.07
White
18,137 (61.5)
16,554 (62.0)
1583 (57.0)
0.18
African American
4784 (16.2)
4353 (16.3)
430 (15.5)
Hispanic
1427 (14.0)
3649 (13.7)
478 (17.2)
Asian/Pacific Islander
1173 (4.0)
1038 (3.9)
134 (4.8)
Female, N (%)
0.006
Native American
79 (0.3)
69 (0.2)
10 (0.3)
Other
1170 (4.0)
1031 (3.9)
139 (5.0)
Primary payer, N (%) Medicare
7983 (20.6)
7064 (20.1)
919 (25.4)
Medicaid
5064 (13.1)
4566 (13.0)
498 (13.8)
Private insurance
19,483 (50.3)
17,840 (50.8)
1643 (45.4)
Self-pay
3966 (10.2)
3569 (10.2)
397 (11.0)
No Charge/Other
2223 (5.7)
2063 (5.9)
162 (4.5)
< $24,999
289 (6.4)
250 (6.2)
39 (8.4)
$25,000–34,999
795 (17.7)
691 (17.1)
104 (22.8)
$35,000–44,999
1190 (26.4)
1074 (26.5)
117 (25.5)
> $45,000
2228 (49.5)
2030 (50.2)
198 (43.3)
Coil
15,391 (39.6)
14,323 (40.7)
1068 (29.5)
Clip
23,436 (60.4)
20,884 (59.3)
2552 (70.5)
0.003
Median income in zip code, N (%) 0.41
Surgery type, N (%) < 0.0001
Comorbidity score, N (%) 0
9084 (23.4)
8254 (23.4)
830 (22.9)
1
11,072 (28.5)
10,018 (28.5)
1054 (29.1)
2
9845 (25.4)
8949 (25.4)
895 (24.7)
3þ
8826 (22.7)
7986 (22.7)
841 (23.2)
25,099 (64.6)
22,796 (64.7)
2303 (63.6)
2087 (5.4)
1902 (5.4)
185 (5.1)
440 (1.1)
410 (1.2)
29 (0.8)
2728 (7.0)
2428 (6.9)
301 (8.3)
3.05
9 (0.02)
4 (0.01)
4 (0.1)
3.06
6216 (16.0)
5634 (16.0)
583 (16.1)
3.07
2073 (5.3)
1869 (5.3)
204 (5.6)
175 (0.5)
165 (0.5)
10 (0.3)
0.99
Disease severity level, N (%) 3.01 3.02
a
3.03b 3.04
3.08
c
d
0.44
(Continued)
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Race, N (%)
Predictors of Treatment Delay in Aneurysmal SAH
Sarmiento et al.
Table 1 (Continued) All cases (N ¼ 38,827)
p value
Treatment delay 2 d from admission (N ¼ 35,207)
> 2 d from admission (N ¼ 3620)
26,220 (74.5)
2546 (70.3)
10,061 (25.9)
8987 (25.5)
1074 (29.7)
11,933 (30.7)
10,973 (31.2)
960 (26.5)
Day of admission, N (%) Weekday
28,766 (74.1)
Weekend Ventriculostomy, N (%)
< 0.0001 0.03
Abbreviation: SE, standard error. Note: Missing data in 0.24% of females, 24.1% of race, 0.28% primary payer, and 88.4% of income variables. Rounded percent (%). a Closely corresponds to Hunt and Hess grade II. b Closely corresponds to Hunt and Hess grade III. c Closely corresponds to Hunt and Hess grade IV. d Closely corresponds to Hunt and Hess grade V.
risk of treatment delay (OR: 1.4; p ¼ 0.01) compared with younger patients and white patients, respectively. Surgically clipped patients on weekdays had a 30% increased risk of treatment delay (OR: 1.3; p ¼ 0.04) compared with patients whose aneurysms were coiled. The increased risks of treatments delays were observed in patients treated with surgical clipping on weekends as well; however, this finding was not statistically significant. Hospital surgical volume was consistently significant in predicting delays, independently of whether a patient was treated during the week or the
weekend; however, the effect and level of significance was more apparent among weekend admissions (OR: 2.7; p ¼ 0.04) compared with weekdays (OR: 1.8; p ¼ 0.01). Ventriculostomy placement reduced the risk of treatment delay in the weekdays by 30% (OR: 0.7; p ¼ 0.02).
Discussion Patients with aSAH are estimated to have a 10 to 20% rate of long-term disability and a case-fatality rate ranging from 32
Table 2 Characteristics of hospitals treating 38,827 subarachnoid hemorrhage patients (2002–2007) All cases (N ¼ 38,827)
p value
Treatment delay 2 d from admission (N ¼ 35,207)
> 2 d from admission (N ¼ 3620)
32,779 (84.4)
29,933 (85.0)
2846 (78.6)
0.002
Direct-admit
26,117 (67.3)
23,559 (66.9)
2558 (70.7)
0.05
Transfer
12,710 (32.7)
11,648 (33.1)
1062 (29.3)
2002
4678 (12.0)
4210 (12.0)
468 (12.9)
2003
6012 (15.5)
5408 (15.4)
604 (16.7)
2004
7018 (18.1)
6436 (18.3)
583 (16.1)
2005
6972 (17.8)
6290 (17.9)
636 (17.6)
2006
8456 (21.8)
7603 (21.6)
854 (23.6)
2007
5736 (14.8)
5261 (14.9)
475 (13.1)
1
7417 (19.1)
6390 (18.1)
1027 (28.4)
2
7273 (18.7)
6483 (18.4)
790 (21.8)
3
7150 (18.4)
6528 (18.5)
623 (17.2)
4
8540 (22.0)
7983 (22.7)
557 (15.4)
5
8446 (21.7)
7824 (22.2)
623 (17.2)
Teaching hospital Admission source, N (%)
Treatment year 0.54
Hospital volume (quintile)
Note: Rounded percent (%). Journal of Neurological Surgery—Part A
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< 0.0001
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Predictors of Treatment Delay in Aneurysmal SAH
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51
findings appear to reflect a delay in access or initial referral to a qualified neurosurgeon in a timely manner, particularly at smaller centers.
Fig. 1 Trends in the incidence of delayed care for all patients by type of treatment, 2002–2007.
Aneurysm rebleeding is recognized as one of the worst complications following aSAH. The incidence of rebleeding following aSAH is believed to be as high as 13.6% in the first 24 hours when taking very early rebleeding (i.e., rebleeding during the first 8 hours after aSAH) into consideration.9,23 After the first 24 hours, the incidence rate drops to 1 to 2% per day for the next 14 days.23 Approximately 30% of aSAH patients who do not receive treatment have a rebleed within 1 month of the initial aSAH.24 In a prospective study following 176 aSAH patients, 39 (22%) had a CT-proven rebleed within 4 weeks after initial aSAH, and in 20 (51%) of these patients the rebleed was fatal. Approximately 30% of the patients with a rebleed died from other complications; the remaining 20% of patients survived at 3 months, although most had severe brain damage.25 Delays in treatment of aSAH cause preoperative clinical deterioration due to rebleeding. Even in centers that adopt early surgical intervention (i.e., within 3 days after aSAH), rebleeding has been reported as the most important and most common preventable cause of death in hospitalized patients.26
Timing of Aneurysm Treatment Fig. 2 Trends in the incidence of delayed care for all patients by weekday versus weekend admission, 2002–2007.
to 67%.22 These alarming rates underscore the need for timely intervention for patients who present with aSAH. This study describes risk factors associated with delays in treatment of aSAH using a large administrative database. Our results show that older age, nonwhite race, and surgical clipping are factors that significantly delay treatment, particularly during weekday admissions. In addition, patients treated in the lowestquintile volume centers had more delays compared with those treated at the highest-quintile volume centers. These
Fig. 3 Trends in the incidence of delayed care for all patients by lowest versus highest volume quintile status, 2002–2007.
Timing of aneurysm surgery after aSAH has been assessed by a few prospective studies. In 1990, Kassell et al reported their results from the International Cooperative Study on the Timing of Aneurysm Surgery, a prospective multicenter observational trial that discovered the lowest mortality rate among SAH patients was achieved when surgery was planned on days 0 to 3 or 11 to 14.3 In addition, they reported that the number of patients with rebleeding increased progressively with longer intervals of planned surgery from 6% for days 0 to 3 to 22% for days 15 to 32. A 1989 randomized control study by Ohman and Heiskanen assessed the optimum timing for surgery in 216 patients with ruptured anterior circulation aneurysms in good clinical condition (Hunt and Hess grades I–III).4 They reported a significantly higher number of disabled patients in patients who underwent delayed surgery (days 4–7) compared with the early surgery group (days 0–3) (11 patients versus 2 patients, respectively; p ¼ 0.01). Rebleeding was a common cause of preoperative deterioration, and a significant difference in rebleeding was observed between patients who underwent early surgery versus late surgery (two patients and eight patients, respectively; p ¼ 0.01). In addition, three patients from the intermediate surgery group (4–7 days) and six patients from the late surgery group (> 7 days) died before surgery was undertaken. All deaths were attributed to time-sensitive complications of delayed cerebral ischemia and rebleeding. Numerous other retrospective studies have provided further support for the notion of treating aSAH as early as possible.5,27–32 The primary treatment for aSAH consists of either surgical clipping or endovascular coiling. Dorhout Mees et al explored the ideal timing of coiling and clipping after aSAH by assessing Journal of Neurological Surgery—Part A
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Consequences of Delayed Treatment
Predictors of Treatment Delay in Aneurysmal SAH
Sarmiento et al.
Table 3 Adjusted odds ratio of delayed treatment (> 2 days from admission) for all and stratified patients by admission with corresponding 95% confidence intervals and p values All admissions
Day of admission Weekend
Weekday
OR (95% CI)
p value
OR (95% CI)
p value
OR (95% CI)
p value
1.1 (1.1–1.2)
0.0004
1.1 (0.9–1.2)
0.30
1.2 (1.1–1.3)
0.002
Nonwhite
1.2 (0.9, 1.5)
0.09
0.9 (0.6–1.3)
0.57
1.4 (1.1–1.7)
0.01
Clip versus coil
1.3 (1.0–1.6)
0.02
1.3 (0.9–1.9)
0.23
1.3 (1.0–1.7)
0.04
1.1 (1.0–1.4)
0.12
1.1 (0.8–1.5)
0.57
1.2 (1.0–1.4)
0.15
Weekend versus week
1.2 (0.9–1.4)
0.15
–
–
–
–
Ventriculostomy
0.8 (0.6–1.0)
0.04
0.8 (0.5–1.3)
0.36
0.7 (0.6–1.0)
0.02
Age, y
a
Race (reference: white)
Insurance type (reference: private) Nonprivate Day of admission
Hospital surgical volume (reference: highest quintile) First quintile
2.0 (1.2–3.4)
0.007
2.7 (1.0–6.9)
0.04
1.8 (1.1–2.9)
0.01
Second quintile
1.5 (0.9–2.7)
0.13
1.8 (0.7–4.7)
0.25
1.4 (0.9–2.4)
0.15
Third quintile
1.3 (0.7–2.2)
0.42
1.3 (0.5–3.7)
0.65
1.2 (0.5–1.4)
0.37
Fourth quintile
0. 8 (0.4–1.4)
0.70
0.7 (0.2–2.2)
0.51
0.8 (0.5–1.4)
0.46
Abbreviations: CI, confidence interval; OR, odds ratio. Note: Admission type (transfer versus direct admit), income, Elixhauser comorbidity score, and disease severity (SAH grade) were not associated with longer delays. a Per decade increment.
clinical outcomes between different timings of treatment for coiled and for clipped patients within the International Subarachnoid Aneurysm Trial (ISAT).33 This study included 2106 patients who were randomized to receive either endovascular or neurosurgical treatment. Among these patients, 891 patients (42.3%) were treated on posthemorrhage days 0 to 2, 482 patients (22.9%) were treated on days 3 to 4, 474 patients (22.5%) were treated between days 5 and 10, and 259 patients (12.3%) were treated after 10 days.3 The risk for poor outcomes, defined as a modified Rankin Scale score of 3 (at 2 months), were significantly worse for patients treated after 5 days compared with patients treated during the first 2 days. Patients treated during the 3- to 4-day window showed a trend toward worse outcomes. This is the largest prospective clinical trial to date showing that aneurysm treatment after day 5 is associated with worse outcomes, regardless of what treatment modality was used. Our study goes beyond the confines of the controlled clinical trial setting and describes treatment delays after aSAH on a national level. In our study, surgical clipping was identified as a risk factor for treatment delay, perhaps reflecting a need to coordinate greater health care resources to prepare for clipping versus coiling procedures, although limitations inherent to the NIS did not allow us to fully explore this possible mechanism for delay.
Limitations Another limitation of our study is that the NIS does not provide a comprehensive clinical profile of each patient. Journal of Neurological Surgery—Part A
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This prevented us from obtaining information about patients’ chief complaints, associated symptoms, and data on the specific location and size of ruptured aneurysms. We also do not know when the patients had their SAH and what postbleed day they presented for care. Furthermore, aSAHspecific complications, such as rebleeding and delayed cerebral ischemia rates, could not be assessed due to limitations of the NIS. Additionally, given that the NIS is primarily an administrative inpatient data set, data beyond the initial hospitalization are not available to track patient outcomes longitudinally. Other factors that we were unable to evaluate but have been shown to cause treatment delays among aSAH patients are the failure of patients to seek prompt medical care and physician diagnostic errors.34 Moreover, the impact of specialist availability could not be assessed. Indeed, given that administrative personnel rather than clinicians are primarily responsible for collection of data elements, and given that these data elements are compiled retrospectively rather than prospectively at participating sites, there remains significant risk for information and selection bias inclusive of coding errors within the data set.
Weekend Effect Some studies have described increased mortality in those with emergent conditions when such patients are admitted on weekends.35–38 This “weekend effect” may be attributable to several factors including restrictions on the availability of diagnostic imaging,39 decreased staffing,40 less experience among health care personnel,35 or the delayed provision of
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52
Predictors of Treatment Delay in Aneurysmal SAH
Effects of Age on Treatment Delay Our study found that older patients were significantly more likely to experience treatment delay. Previous literature focusing on the impact of age on the timeliness of interventional care has been limited and variable. For instance, a 6year retrospective study on the timeliness of percutaneous coronary interventions found that older patients were more likely than younger counterparts to have delayed door-toballoon times, although the mechanistic reason for these findings were unable to be elucidated in this national registry study.45 The relationship between age, comorbidities, patient’s overall clinical status, and timing of aneurysm treatment is complex and has been challenging to study.
Effects of Race on Treatment Delay Racial differences in SAH incidence and mortality have been established in the literature.46–51 Our study showed that nonwhite patients admitted on weekdays have a higher risk of treatment delay compared with their white counterparts. Such delays may explain the differences in mortality observed among minority populations. In a study by Schievink et al evaluating the racial distribution of aSAH mortality in Los Angeles County, the most ethnically diverse jurisdiction in the United States, marked racial differences in SAH mortality were found.43 This study found that overall whites were at the lowest risk, followed by Hispanics and Asians at intermediate risk, and African Americans at the highest risk of mortality. The differences for these racial disparities in SAH mortality are not entirely clear.
Placement of Ventriculostomy Our study demonstrated placement of ventriculostomy as the only covariate significantly associated with decreased delays in care. The limitations of the NIS data set did not allow us to further explore this association. Perhaps this finding may relate to ventriculostomy acting as a surrogate marker for neurosurgeon availability; that is, the fact that the patient had a ventriculostomy meant that a neurosurgeon was available
53
to place it and hence also provide timely treatment. Although there generally has not been a large pool of data assessing the timing of intervention with placement of ventriculostomy in aSAH patients, the retrospective single-institution study by McIver et al demonstrated no significant difference in mean time interval between presentation and surgery in those with or without ventriculostomy placed preoperatively.52 Although the relationship between clinical presentation, ventriculostomy placement, and timing of surgery or endovascular intervention among aSAH patients may be somewhat complex, our findings coupled with those of McIver et al seem to at least demonstrate that placement of ventriculostomy does not delay care in patients with aSAH.
Centralization of Care The treatment of ruptured cerebral aneurysms is increasingly taking place at high-volume hospitals within the United States.53 This trend is in accordance with the recommendations of the 2012 guidelines for management of ruptured cerebral aneurysms that advocate for low-volume hospitals (defined as hospitals that treat < 10 aSAH cases per year) to transfer patients to high-volume centers (defined as hospitals that treat > 35 aSAH cases per year) with experienced cerebrovascular surgeons, endovascular specialists, and multidisciplinary neuro-intensive care services (class I; level of evidence B).2 Various reports from the literature have showed that hospitals with high case volumes of aSAH have superior outcomes than hospitals with low case volumes.15,21,44 Our data indicate that patients who present with aSAH at the lowest quintile volume hospitals experience greater delays in treatment compared with those who are treated at the highest quintile volume hospitals. These differences in mortality between high- and low-volume centers were previously attributed to varying hospital resources, specialty training, specialist availability, and care in the neuro-intensive care unit.44 Our findings of delay of care at lower volume hospitals may also contribute to the worse outcomes previously reported in lower volume centers. Even after acknowledging the benefits of expeditious treatment for aSAH patients, some providers may hesitate to transfer critically ill patients, recognizing that outcomes for transfer patients have been shown to be worse than directadmit patients.54–56 However, the findings of Nuño et al recently demonstrated similar outcomes between aSAH patients regardless of whether they were directly admitted or transferred to a higher volume hospital.21 Our findings that lower volume hospitals have more delays in aneurysm treatment coupled with the data showing similar outcomes for direct-admit versus transfer patients further supports the recent centralization of care efforts for aSAH.2 Expedited referrals to qualified neurosurgeons at high-volume institutions may mitigate critical delays in the care of patients with aSAH.
Conclusions Neurologic emergencies such as aSAH often have dire morbidity and mortality. As such, it is imperative that all aSAH Journal of Neurological Surgery—Part A
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intensive procedures on weekends.41 Although a “weekend effect” on mortality was not demonstrated in the analysis by Crowley et al among aSAH patients, potential delays in care on weekends may still increase morbidity and complications among aSAH patients given the risk of rebleeding and increased risk of treatment while in the vasospasm period.38 This idea is supported by a 2012 study by Siddiq et al that found weekend admission among patients with aSAH reduced the likelihood of early treatment, which was defined as treatment performed within 48 hours of admission, by 30% (OR: 0.7; 95% CI, 0.6–0.8; p < 0.001).42 Our study showed a strong trend toward a higher risk of treatment delays in patients admitted on weekends, although this finding proved not to be statistically significant after adjusting for several relevant covariates in our multivariate model. We found that weekend admission had a milder effect on treatment delays after adjusting for race43 and hospital treatment volume,15,21,44 two potential confounders that have been demonstrated to influence survival in aSAH patients.
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patients be referred to a qualified neurosurgeon at a highvolume institution to allow for treatment in an expeditious manner irrespective of the time, place, or date on which they present for care. In this retrospective nationwide analysis, we show that > 90% of aSAH patients in the United States are being treated within the recommended 2-day window. Older age and surgical clipping were independently associated with delay to treatment. Racial differences in treatment delays were more apparent in weekdays, with nonwhite patients experiencing more delays in treatment than white patients. We also present evidence suggesting that patients treated in the lowest quintile volume hospitals are more likely to experience greater delays to treatment. Minimizing treatment delays for aSAH remains an important area of concern both for clinicians and policymakers.
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Appendix 1 Hunt and Hess subarachnoid hemorrhage grading scale Grade I
Asymptomatic, mild headache, slight nuchal rigidity
Grade II
Moderate to severe headache, nuchal rigidity, no neurologic deficit other than cranial nerve palsy
Grade III
Drowsiness/confusion, mild focal neurologic deficit
Grade IV
Stupor, moderate to severe hemiparesis
Grade V
Coma, decerebrate posturing
Journal of Neurological Surgery—Part A
Vol. 76
No. A1/2015
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Predictors of Treatment Delay in Aneurysmal SAH
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