Nontraumatic Subarachnoid Hemorrhage in Maintenance Dialysis Hospitalizations
Trends and Outcomes
Background and Purpose—Subarachnoid hemorrhage (SAH) is associated with high mortality, and patients on maintenance dialysis have been shown to be at higher risk for stroke including SAH. However, the outcomes of patients on maintenance dialysis with SAH are not well known. This study was designed to look at incidence and outcomes of SAH in those on maintenance dialysis.
Methods—Using the Nationwide Inpatient Sample Database, hospitalizations with nontraumatic SAH were identified. Age-adjusted incidence rates were calculated by direct standardization to the 2000 US standard population. Logistic regression was used to assess the risk factors for mortality.
Results—Of an estimated 149 091 hospitalizations with SAH, 1631 patients (10.9%) were on maintenance dialysis. Unadjusted incidence of SAH hospitalizations was higher in maintenance dialysis than in the general population (73.5 versus 11.2 per 100 000 population), and similar results were seen on age-adjusted analysis. The unadjusted all-cause inpatient mortality rate for SAH admissions was higher in maintenance dialysis versus the general population (38.4% versus 21.9%; P<0.001). Maintenance dialysis was an independent predictor of mortality (odds ratio, 2.48; 95% confidence interval, 1.85–3.34), although other significant predictors of mortality were similar in both subgroups. Incidence of SAH hospitalizations has been relatively stable during the study period, but mortality seems to be decreasing.
Conclusions—SAH hospitalizations are more common and associated with higher mortality in patients on maintenance dialysis than in the general population. Although being on maintenance dialysis is an independent predictor for mortality in patients with SAH, other predictors of mortality evaluated in this study are not necessarily different between the 2 groups.
Nontraumatic subarachnoid hemorrhage (SAH), which is usually attributable to rupture of an intracranial aneurysm, is accountable for 3% of all strokes in the United States.1 There is some evidence that the mortality associated with SAH may have decreased during the past few decades, but it is still >25%.2–4 Studies performed in the general population have shown female sex, hypertension, smoking, alcohol abuse, and nonwhite race to be associated with an increased risk of developing SAH.5,6
Patients on maintenance dialysis have been shown to be at a higher risk of stroke including SAH.7,8 The prevalence of end-stage renal disease needing maintenance dialysis is continuing to increase, with a projected prevalence of >700 000 patients by 2015.9 Patients on maintenance dialysis are at 6 to 8× higher risk for mortality than the general population.10 Cardiovascular disease is the leading cause of mortality in patients on maintenance dialysis, with stroke being one of the major causes of cardiovascular mortality.11 Because polycystic kidney disease, a risk factor for end-stage renal disease, is also associated with intracranial aneurysms,12 understanding outcomes for SAH in patients on maintenance dialysis is especially important. However, there is a paucity of studies looking at outcomes of SAH in these patients.
Therefore, we designed this study using nationally representative data from 2005 to 2010 to look at: (1) trends of incidence rate of hospitalizations with SAH in patients on maintenance dialysis and general population; (2) all-cause in-hospital mortality and its trends among maintenance dialysis and general population hospitalizations with SAH; and (3) predictors of mortality for SAH hospitalizations.
Using data from the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (NIS), we designed a retrospective cohort study. NIS is the largest all-payer inpatient care database publicly available in the United States. It contains data from a 20% stratified sample of US community hospitals.13 Each hospitalization is treated as an individual entry in the database. NIS provides information on common demographic variables such as age, race, and sex, along with primary and secondary insurance, hospital characteristics such as teaching status, location (rural versus urban), size of hospital, and hospital region. Facilities are considered to be teaching hospitals if they have an American Medical Association–approved residency program, are a member of the Council of Teaching Hospitals, or have a full-time equivalent of interns and residents to patient ratio of ≥0.25. Data from 2005 to 2010 were used for this study. We used the provided principal diagnosis, up to 14 secondary diagnoses, and 15 procedural diagnoses associated with each hospitalization for this study in the database.
Patients with nontraumatic SAH and ≥20 years of age were included in the study. The patients with SAH were identified using the primary discharge diagnosis code of SAH (International Classification of Diseases, Ninth Revision, and Clinical Modification [ICD-9-CM] code 430). The SAH diagnosis code in primary diagnostic position has been shown to have 90% sensitivity and 97% specificity.14 Patients with diagnosis codes for head trauma (ICD-9-CM codes 800.0–804.9, 850.0–854.1, and 873.0–873.9) and cerebrovascular malformations (747.81) were excluded. In accordance with previous literature,15 maintenance dialysis status was defined as patients with an ICD-9-CM code for end-stage renal disease (585.6) or procedure code for hemodialysis (39.95) or peritoneal dialysis (54.98) but absence of ICD-9-CM code for acute kidney injury (584.X). Since the ICD-9-CM code for end-stage renal disease (585.6) was introduced in 2005, we limited our sample to 2005 to 2010. Patients with renal transplant (ICD-9-CM 996.81, V42.0) were excluded.
Study Variables and Outcomes
Age, sex, race, and primary payer status were identified using appropriate variables from the NIS database. Age was divided into 5 subgroups: 20 to 44, 45 to 54, 55 to 64, 65 to 74, and ≥75 years. Hospital characteristics, teaching status, location, bed-size, and region were also identified using appropriate NIS variables. The hospitals were also divided into tertiles based on the yearly volume of SAH discharges (<24, 24–69, >69 hospitalizations for SAH per year). We used the Deyo modification of Charlson comorbidity index to identify the burden of comorbidity.16 Individual diagnoses of coagulopathy, polycystic kidney disease, and mechanical ventilation use were identified using appropriate ICD-9-CM codes. Discharges with missing data were excluded except for race, which was missing in ≈20% of discharges. Missing race was included as a separate subgroup of race for primary analyses.
Using this registry, we studied the yearly incidence, mortality, and disposition of SAH hospitalizations. We also looked at predictors for all-cause inpatient mortality in SAH admissions.
Using the weights provided in NIS, we generated national estimates of the number of hospitalizations. The number of SAH hospitalizations per 100 000 populations was calculated by using annual population estimates from the United States Census Bureau and United States Renal Data System (USRDS).17,18 Direct standardization of age was performed to standard 2000 US standard population19 to estimate age-adjusted incidence rates. Similarly, we calculated age-adjusted incidence rates for SAH hospitalizations by renal function stratified by sex and race (white and black). Significance of trends for age-adjusted incidence over the years was assessed using linear regression.
Chi square test was used to compare categorical variables. We examined the risk factors for mortality using logistic regression. Univariable logistic regression was used to identify risk factor variables associated with in-hospital mortality. All variables that were significant at P<0.20 were included in the final multivariable model, which was adjusted for age, sex, race, primary payer, Charlson score, hospital teaching status, hospital location, hospital region, hospital volume (small, medium, and large), hospital bed-size, diagnosis of polycystic kidney disease, coagulopathy, and mechanical ventilation use. To control for variability by year, we used year as a predictor in regression model. To assess whether predictors of mortality are different between those on maintenance dialysis and the general population, we checked for an interaction term between maintenance dialysis and significant predictors. The c-statistic for the regression model used was 0.82, suggesting excellent predictive value of the model.
Because information about race was missing in >20% discharges, we performed a sensitivity analysis for predictors of mortality by excluding race from analysis, a method that has been used in literature to overcome the issue of missing information about race from the NIS database.20 This study was approved by the institutional review board.
During the 6 years of the study period, there were an estimated 149 091 (95% confidence interval, 134 368–163 814) discharges with nontraumatic SAH. Of these, an estimated 1631 patients (95% confidence interval, 1 409–1 852) were on maintenance dialysis. Baseline characteristics of these patients are shown in Table 1. Patients on maintenance dialysis tended to be more often nonwhite, on Medicare, and were admitted less often to teaching hospitals or high-volume hospitals (Table 1). Patients on maintenance dialysis also had higher prevalence of hypertension than the general population (91.9% versus 57.4%; P<0.001; Table 1).
Incidence of SAH
Overall unadjusted incidence of SAH hospitalizations in the general population and maintenance dialysis groups was 11.2 and 73.5 per 100 000 persons, respectively, translating into an incidence rate ratio of 6.55 (95% confidence interval, 6.24–6.88) for the maintenance dialysis group compared with the general population group. As shown in Figure 1A, age-adjusted incidence rates of SAH were also higher in the maintenance dialysis population than the general population, but the age-adjusted incidence of hospitalizations remained relatively stable during the 6-year period in both general population and maintenance dialysis hospitalizations. However, as noted in Figure 1A, there was a statistically nonsignificant decline in age-adjusted incidence of SAH hospitalizations in maintenance dialysis group, although the unadjusted incidence remained relatively unchanged (Figure 1B). This is likely a reflection of decrease in SAH hospitalizations in younger age groups. As shown in Figure 2A through 2D, the age-adjusted incidence rates of SAH remained higher in the maintenance dialysis population regardless of sex or race. Moreover, females had a higher age-adjusted incidence of SAH than males, and blacks had a higher age-adjusted incidence of SAH than whites, regardless of maintenance dialysis status.
Mortality and Disposition of Survivors
The overall unadjusted all-cause inpatient mortality rate for SAH admissions was 21.9% in general population patients and 38.4% in patients on maintenance dialysis (P<0.001; Table 2). Compared with SAH hospitalizations not on dialysis, maintenance dialysis SAH admissions were more likely to need mechanical ventilation (44.0% versus 35.0%; P<0.001) and were less likely to be discharged home (20.2% versus 35.4%; P<0.001).
Risk Factors for Mortality
After adjusting for different patients and hospital characteristics, maintenance dialysis was associated with 2.48 times increased mortality for SAH hospitalizations (odds ratio, 2.48; 95% confidence interval, 1.85–3.34). In addition, increasing age, coagulopathy diagnosis, self-pay insurance status, and need for mechanical ventilation were associated with higher all-cause in-hospital mortality. In comparison, black or Hispanic race, admission to teaching hospital, urban hospital, medium or large volume hospital, and later year of hospitalization were associated with decreased odds of all-cause inpatient mortality. There was no significant difference in different predictors of mortality between maintenance dialysis and general population groups as assessed using interaction terms (Table 3).
After excluding race from analysis, predictors for all-cause inpatient mortality in those with nontraumatic SAH remained unchanged (Table I in the online-only Data Supplement).
This study, using large nationally representative data, shows that the incidence of nontraumatic SAH is much higher in those on maintenance dialysis than in the general population. In addition, mortality in maintenance dialysis group is higher than in the general population (38.4% versus 21.9%). We also showed that maintenance dialysis status is an independent predictor for mortality in those with SAH.
Patients on maintenance dialysis are at a higher risk of bleeding than the general population. Higher risk of gastrointestinal bleeding and subdural hematomas in this population have been described previously.21,22 Defects in coagulation pathway and use of anticoagulation in dialysis are thought to contribute toward this increased risk of bleeding in patients on maintenance dialysis. We found the incidence of SAH hospitalizations to be higher in females and blacks irrespective of need for maintenance dialysis. These results are in concert with studies in the general population.5,23 We also found that the age-adjusted incidence of SAH hospitalizations decreased in 2008 compared with previous years especially in maintenance dialysis group; however, the unadjusted incidence remained relatively unchanged. This was likely because of decreased SAH hospitalizations in younger age groups. The reasons for this change are not clear, but increasing evidence against use of anticoagulants to prevent dialysis access thrombosis in patients on maintenance dialysis24 may have also contributed. Overall, there was no significant change in the incidence rate of SAH hospitalizations.
SAH is associated with high morbidity and mortality in the general population. We found that all-cause inpatient mortality for SAH in maintenance dialysis group was even higher than in the general population group. This is an important observation considering already poor outcomes in patients with SAH. On the contrary, similar to few studies in literature,2,25 we found that during the years studied, the mortality rate in patients with SAH has been declining, and this trend was seen regardless of maintenance dialysis status as evidenced by lack of significant interaction between maintenance dialysis status and the variable year in logistic regression model. Better care has been postulated to be a reason for improved outcomes in this population;26,27 however, it is important to note that although the mortality in the maintenance dialysis group has decreased from 31.1% in 2005 to 29.3% in 2010, it is still much higher than mortality in the general population group, in which it has decreased from 23.5% in 2005 to 21.0% in 2010.
We found that increasing age, coagulopathy diagnosis, self-pay insurance status, and need for mechanical ventilation were associated with higher all-cause in-hospital mortality. In comparison, black or Hispanic race, admission to a teaching hospital, urban hospital, medium or large volume hospital, and later year of hospitalization were associated with decreased odds of all-cause inpatient mortality. Interestingly, we did not find hospital size based on number of beds to be associated with mortality. Teaching hospitals28 and higher volume hospitals29,30 have previously been shown to be associated with lower mortality in the general population with SAH, with the differences thought to be because of higher availability of specialized care in these hospitals. To explore the reasons for higher mortality in patients on maintenance dialysis, we looked for a difference in predictors of mortality between the general population and the maintenance dialysis group; however, we did not find any significant differences between different predictors of mortality between the 2 groups. This lack of significant differences in predictors of mortality between maintenance dialysis and the general population emphasizes the need for further studies to explore the reasons for higher mortality in patients on maintenance dialysis.
Considering that patients on maintenance dialysis not only have a higher incidence of hospitalizations with SAH as well as a much higher mortality when admitted despite the fact that the predictors of mortality between those on maintenance dialysis versus the general population are not different, prevention of SAH in maintenance dialysis population may be the best management strategy. Of the reversible causes of SAH, hypertension was found to be much higher in maintenance dialysis population. Although treatments directed toward improving blood pressure control in maintenance dialysis populations may help decrease the incidence of SAH in this population, the optimal predialysis blood pressure target remains unclear, and further research is needed in this area.
Although we have used a well-described, nationally representative database, our study has some limitations. We have used ICD-9-CM codes to identify patients with SAH and those on maintenance dialysis. SAH codes have been shown to have 90% sensitivity and 97% specificity. Although the codes to identify patients on maintenance dialysis have not been validated, they have been used in literature previously. The NIS database also does not provide information on medication use among patients, and therefore, we were unable to adjust for the use of antiplatelets and anticoagulants in this study. The database does not provide unique patient identifiers, and so it is not possible to identify readmissions. Therefore, we may have overestimated the incidence of SAH. Race is missing in >20% of discharges in the database; however, the results were unchanged after excluding race from regression analysis to allow for compete case analysis, suggesting the robustness of our results. The c-statistic of 0.82 also shows excellent predictive power of the regression model used.
In summary, we have shown that nontraumatic SAH is not only more common in patients with maintenance dialysis, it is in fact associated with even higher mortality than in the general population group. We have further shown that although being on maintenance dialysis is an independent predictor for mortality in patients with SAH, other predictors of mortality evaluated in this study are not necessarily different between the 2 groups. To the best of our knowledge, this is the first study describing the mortality rates for SAH hospitalizations in those on maintenance dialysis and exploring the differences in predictors of mortality between patients with SAH with and without need for maintenance dialysis. Persistent high incidence rates and high mortality in maintenance dialysis population call for further studies to help understand the reasons and to improve outcomes in this subgroup.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.113.003012/-/DC1.
- Received July 26, 2013.
- Accepted October 9, 2013.
- © 2013 American Heart Association, Inc.
- Lloyd-Jones D,
- Adams RJ,
- Brown TM,
- Carnethon M,
- Dai S,
- De Simone G,
- et al
- Feigin VL,
- Rinkel GJ,
- Lawes CM,
- Algra A,
- Bennett DA,
- van Gijn J,
- et al
- Sandvei MS,
- Romundstad PR,
- Müller TB,
- Vatten L,
- Vik A
- Gilbertson DT,
- Liu J,
- Xue JL,
- Louis TA,
- Solid CA,
- Ebben JP,
- et al
- 10.↵Mortality. 2011 USRDS annual data report. http://www.Usrds.Org/2011/view/v2_05.Asp. Accessed January 4, 2013.
- 11.↵Cardiovascular disease in patients with end-stage renal disease. http://www.Usrds.Org/2011/view/v2_04.Asp. Accessed January 4, 2013.
- 13.↵Introduction to the HCUP nationwide inpatient sample 2010. http://www.Hcup-us.Ahrq.Gov/db/nation/nis/nisintroduction2010.Pdf. Accessed January 5, 2013.
- Tirschwell DL,
- Longstreth WT Jr.
- Kumar G,
- Sakhuja A,
- Taneja A,
- Majumdar T,
- Patel J,
- Whittle J,
- et al
- 17.↵US census bureau: American factfinder. http://factfinder2.Census.Gov/faces/nav/jsf/pages/index.Xhtml. Accessed January 5, 2013.
- 18.↵United States renal data system: Render. http://www.Usrds.Org/render/xrender_home.Asp. Accessed January 5, 2013.
- Klein RJ,
- Schoenborn CA
- Sood P,
- Sinson GP,
- Cohen EP
- Bardach NS,
- Zhao S,
- Gress DR,
- Lawton MT,
- Johnston SC