Outcomes of Thrombolytic Treatment for Acute Ischemic Stroke in Dialysis-Dependent Patients in the United States

doi:10.1016/j.jstrokecerebrovasdis.2013.03.016

Journal of Stroke and Cerebrovascular Diseases

Volume 22, Issue 8, November 2013, Pages e354-e359

https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.03.016 Get rights and content

Objective

To determine the outcomes of dialysis-dependent renal failure patients who had ischemic stroke and were treated with intravenous (IV) thrombolytics in the United States.

Methods

We analyzed the data from Nationwide Inpatient Sample (2002-2009) for all thrombolytic-treated patients presenting with acute ischemic stroke with or without dialysis dependence. Patients were identified using the International Classification of Disease, Ninth Revision, Clinical Modification codes. Baseline characteristics, in-hospital complications including secondary intracerebral hemorrhage (ICH), sepsis, pneumonia, pulmonary embolism, deep venous thrombosis, urinary tract infections, and discharge outcomes (mortality, minimal disability, and moderate-to-severe disability) were compared between the groups.

Results

Of the 82,142 patients with ischemic stroke who receive thrombolytic treatment, 1072 (1.3%) was dialysis dependent. The ICH rates did not differ significantly between patients with ischemic stroke with or without dialysis who received thrombolytics (5.2% versus 6.1%). The in-hospital mortality rate was higher in dialysis-dependent patients treated with thrombolytics (22% versus 11%, P ≤ .0001). After adjusting for age, sex, and comorbidities, dialysis dependence was associated with higher rates of in-hospital mortality in patients treated with thrombolytics (odds ratio, 1.92; 95% confidence interval, 1.33-2.78, P = .0005).

Conclusions

The 2-fold higher odds of in-hospital mortality associated with administration of IV thrombolytics in dialysis-dependent patients who present with acute ischemic stroke warrant a careful assessment of risk–benefit ratio in this population.

Introduction

Cardiovascular disease is the leading cause of death among dialysis-dependent renal failure patients.¹ Dialysis-dependent renal failure patients have a 9-fold higher mortality rate attributed to stroke (both hemorrhagic and ischemic) compared with general population.² Because of a high prevalence of ischemic stroke and regular medical contact, dialysis-dependent patients are likely to present within the time window of thrombolytic administration. Ischemic strokes are not infrequent during and immediately after dialysis with rapid access to medical care. Up to 34% of the ischemic stroke in patients on maintenance dialysis occur during or less than 30 minutes after the dialysis procedure.³ However, despite the potential of administering thrombolytic treatment to reduce the high rate of death and disability, the NINDS rt-PA trial⁴ and subsequent thrombolytic therapy trials5, 6 did not include patients with renal failure requiring dialysis. There are small reports that document a high rate of intracerebral hemorrhage (ICH) and death in patients with renal dysfunction treated with intravenous (IV) thrombolytics,7, 8 but no large-scale studies have addressed this issue.

We sought to determine the outcomes of dialysis-dependent renal failure patients who had ischemic stroke and were treated with IV thrombolytics in the United States and also compared the outcomes with thrombolytic-treated patients without dialysis dependence using a nationally representative inpatient database.

Section snippets

Methods

We used the data files from National Inpatient Sample (NIS) from 2002 to 2009 for our analysis. NIS is the largest all-payer database in the United States. Using appropriate sampling weights, national estimates are derived based on the data from 20% of nonfederal hospitals. The database contains information on patients' demographic and clinical characteristics, in-hospital procedures, hospital characteristics, and discharge outcomes. A comprehensive synopsis on NIS data is available at //www.hcup-us.ahrq.gov

Results

Of 82,142 patients with ischemic stroke who were treated with IV thrombolytics, 1072 (1.3%) had dialysis-dependent renal failure. Of the 1072 patients, 1007 (94%) were on hemodialysis and 65 (6%) were on peritoneal dialysis. There was a difference in the race/ethnicity of patients in the 2 groups: the proportion of white patients was lower than those of African-American and Hispanic patients among dialysis-dependent patients treated with thrombolytics (Table 1). The proportion of patients with

Discussion

The important finding in our study is the 2-fold higher odds of in-hospital mortality associated with administration of IV thrombolytics in dialysis-dependent renal failure patients who presented with acute ischemic stroke. We also found that dialysis-dependent renal failure patients who underwent thrombolytic treatment had longer inpatient stay and higher rate of in-hospital complications. The hospital charges were more than 2-fold higher in thrombolytic-treated patients undergoing dialysis.

Conclusion

We observed that there is substantially a high rate of complications and mortality in dialysis-dependent renal failure patients treated with IV thrombolytics for acute ischemic stroke. Ischemic stroke frequently occurs during or immediately after the dialysis procedure3, 20 within a health care setting. Therefore, a substantial number of these patients have access to time-dependent interventions such as thrombolytics. However, careful assessment of risks versus benefits must be undertaken in

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Cited by (28)

Definitions of Urinary Tract Infection Used in Interventional Studies Involving Neurourological Patients—A Systematic Review
2022, European Urology Focus
Citation Excerpt :
However, when we specifically focus on the definitions used in interventional studies in this population, the descriptions are commonly “UTI was self-reported by patients” [49], “the diagnosis of a UTI […] was accepted if the participant’s doctor had diagnosed, or confirmed the patient’s diagnosis of a UTI and had prescribed or authorised the use of antibiotics as a treatment” [50], or “[UTIs] were reported per the investigator’s clinical assessment” [51], with no more explanation about the diagnostic methods employed or the symptoms considered as suspicious. Other authors just published the percentage of UTIs (with or without symptoms, usually not differentiating them) diagnosed after an intervention [52] or reported the frequency of infections reviewing the medical records of the patients and checking the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes for UTIs [53]. Therefore, the Guidelines Panel decided that it was important to verify whether the definitions used in interventional studies focused on neurourological patients were following these recommendations and whether more precise cut-off values could be given.
Neurourological patients often encounter bacteriuria without any symptoms or may experience symptoms suspicious of urinary tract infections (UTIs). However, there is a lack of guidelines that unequivocally state the definition of UTIs in this specific patient group.
To present all used definitions of UTIs in neurourological patients.
This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Studies were identified by electronic search of Medline, Embase, Cochrane controlled trials databases, and clinicaltrial.gov without a time limitation (last search September 2020) and by screening of reference lists and reviews. The occurrences of the various UTI definitions were counted and the frequencies calculated.
After screening 7164 abstracts, we included 32 studies enrolling a total of 8488 patients with a neurourological disorder who took part in an interventional clinical study. UTI definitions were heterogeneous. The concordance to predefined definitions was low.
Interventional clinical studies rarely report specific definitions for UTIs, and both clinical and laboratory criteria used are heterogeneous. A generally accepted UTI definition for neurourological patients is urgently needed.
Patients suffering from neurological disorders often experience symptoms in their lower urinary tract that resemble urinary tract infections. Furthermore, they can have positive urine cultures without symptoms (the so-called asymptomatic bacteriuria). However, clinical studies rarely report specific definitions for urinary tract infections, and when it is done, they are heterogeneous. A generally accepted urinary tract infection definition for neurourological patients is urgently needed.
Interventional clinical studies on neurourological patients rarely report specific definitions for urinary tract infections (UTIs), and both clinical and laboratory criteria used are heterogeneous. A generally accepted UTI definition for neurourological patients is urgently needed.
Renal Dysfunction Associated with Symptomatic Intracranial Hemorrhage after Intravenous Thrombolysis
2019, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
Studies consistently revealed that renal impairment independently predicted poor outcome in stroke patients after thrombolysis. As for the association between RD and SICH post IV rtPA thrombolysis in acute stroke patients, 4 studies suggested SICH occurred significantly more often in patients with RD,5,6,8,21 2 studies revealed nonsignificantly important tendency,22,23 whereas 6 other studies could not find such an association.9-12,24,25 The discrepancies might be due to the relatively small sample sizes in some studies (N = 200-600).
Background and Aim: Renal dysfunction (RD) is prevalent in patients with acute ischemic stroke requiring intravenous thrombolysis. The relationship between renal function and thrombolysis related intracranial hemorrhagic (ICH) complications is contradictory according to previous studies. The current study is to clarify whether RD could increase the risk of symptomatic intracranial hemorrhage (SICH) after recombinant tissue plasminogen activator (IV rtPA) in acute ischemic stroke patients. Methods: In this observational study, acute ischemic stroke patients who received IV rtPA within 4.5 hours of symptom onset were retrospectively analyzed. Creatinine levels on admission served to calculate glomerular filtration rate (GFR) to estimate RD. SICH was defined with National Institute of Neurological Disorder and Stroke (NINDS, SICH_NINDS) or European Cooperative Acute Stroke Study II (ECASS II, SICH_ECASSII) criteria. Association of RD with SICH was assessed using continuous GFR or binary GFR (RD defined as GFR < 90 ml/minute/1.73 m²). Results: Of 312 patients included, the incidence of SICH_NINDS was 7.69%, of SICH_ECASSII was 5.45%. Patients with RD had higher prevalence of SICH_NINDS (12.80% versus 2.03%, P < .001) and SICH_{ECASS II} (9.15% versus 1.35%, P = .002)_. GFR as a continuous variable was associated with SICH_NINDS (OR_adjust = .97, P = .003), but not with SICH_{ECASS II}. GFR less than 90 ml/minute/1.73 m² remained independently associated with SICH_NINDS (OR_adjust = 4.79, P = .016), and SICH_{ECASS II} (OR_adjust = 2.99, P = .032) in multiple logistic regression analysis. Conclusions: Renal function is independently associated with SICH after IV rtPA thrombolysis. RD is an independent predictor for both SICH_NINDS and SICHE_{CASS II}. RD should be considered when evaluating the risk of intravenous thrombolysis with IV rtPA.
Pre-Existing Renal Failure Increases In-Hospital Mortality in Patients with Intracerebral Hemorrhage
2019, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
However, in our multivariate analysis model with alive patients, we did not find statistically significant association. Our study is observational, based on NIS dataset and limitations are similar as previously described in analysis of this dataset.11 We do not know the exact impact of interfacility transfer on ICH admission counts in our dataset.
To determine the clinical outcome for intracerebral hemorrhage (ICH) patients with pre-existing renal failure in the United States.
We analyzed the data from Nationwide Inpatient Sample (2008-2012) for all ICH patients with or without pre-existing renal failure. Patients were identified using the International Classification of Disease, Ninth Revision, Clinical Modification codes. Baseline characteristics, in-hospital complications, and exposure to invasive procedures were compared between groups. Discharge outcomes (mortality, minimal disability, and moderate-to-severe disability) were compared between the two groups, before and after adjusting for the presence of other medical comorbidities, in-hospital complications, and exposure to invasive procedures.
Of the 328,728 patients with ICH, 36,067 (11.8%) had pre-existing renal failure as a comorbidity. There were higher rates for in-hospital complications like myocardial infarction (3.5% versus 1.9%, P ≤ .0001), sepsis (5.4% versus 3.0%, P ≤ .0001), pneumonia (7.1% versus 5.3%, P ≤ .0001), deep venous thrombosis (1.6% versus 1.2%, P = .0041), urinary tract infections (16.9% versus 15.1%, P = .0101), and gastrointestinal bleeding (0.4% versus 0.2%, P ≤ .0154), longer hospital stay (9.4 ± 14.4 versus 7.7 ± 11.4; P < .0001), and higher mean hospital charges ($86497.9 ± 131708.1 versus $69583.4 ± 110629.1; P < .0001) in patients with pre-existing renal failure . The in-hospital mortality was also higher among patients with pre-existing renal failure as comorbidity in both univariate (26.4% versus 25.3 %, P = .0010) and multivariate analysis (odds ratio [OR] = 1.124 [1.042-1.213], P = .0025). There was no statistically significant difference for in terms of moderate to severe disability between 2 groups (OR = 1.030 [0.962-1.104], P value: .3953 in multivariate analysis when analysis was limited to alive patients.
Patients with ICH, who present with pre-existing renal failure, have higher rates of in-hospital mortality but not for disability, the difference remained significant after adjusting for the presence of other medical comorbidities, in-hospital complications or exposure to invasive procedures.
Stroke and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Management Across Kidney Disease Stages
2015, Seminars in Nephrology
Citation Excerpt :
Of 82,142 patients receiving tPA, 1,007 were receiving hemodialysis and 65 were receiving peritoneal dialysis. In this select population of dialysis patients treated with tPA, the occurrence of ICH after tPA did not differ significantly from nondialysis patients, although the in-hospital mortality was significantly higher.106 This lack of experience and comfort with treating dialysis patients with tPA was reflected in a recent survey of 40 stroke experts; only one third of the experts had experience with using tPA for ischemic stroke in dialysis patients whereas half reported reservations related to concerns about higher bleeding risk.107
Cerebrovascular disease and stroke are very common at all stages of chronic kidney disease (CKD), likely representing both shared risk factors as well as synergy among risk factors. More subtle ischemic brain lesions may be particularly common in the CKD population, with subtle manifestations including cognitive impairment. For individuals with nondialysis CKD, the prevention, approach to, diagnosis, and management of stroke is similar to the general, non-CKD population. For individuals with end-stage renal disease, far less is known regarding strategies to prevent stroke. Stroke prophylaxis using warfarin in dialysis patients with atrial fibrillation in particular remains of uncertain benefit. End-stage renal disease patients can be managed aggressively in the setting of acute stroke. Outcomes after stroke at all stages of CKD are poor, and improving these outcomes should be the subject of future clinical trials.
Acute renal failure worsens in-hospital outcomes in patients with intracerebral hemorrhage
2015, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
However, association of ARF with poor discharge outcomes and high mortality persisted even after adjustment of confounders in the multivariate model. Our study is observational and based on NIS data set, and limitations are previously described.12 We did not aim to look at the mechanistic explanation of ARF.
Occurrence of acute renal failure (ARF) is more common in patients with intracerebral hemorrhage (ICH) compared with those with other stroke subtypes. We sought to determine the frequency and effect of ARF on in-hospital outcomes of patients with ICH.
We analyzed data from all patients admitted to the United States' hospitals between 2005 and 2011 with the primary discharge diagnosis of ICH and secondary diagnosis of ARF. The associations of ARF with mortality and discharge outcomes in ICH patients were analyzed after adjusting for potential confounders using logistic regression analyses.
Of the 614,454 patients admitted with ICH, 41,694 (6.8%) had ARF. In-hospital dialysis was required in 700 (1.7%) patients. ICH patients with ARF had higher rates of moderate-to-severe disability (49.5% versus 44.2%; P < .0001) and in-hospital mortality (28.7% versus 22.4%; P < .0001) compared with those without ARF. After adjusting for age, gender, and potential confounders defined as statistically significant variables on univariate analysis, ICH patients with ARF had higher odds of moderate-to-severe disability (odds ratio [OR] 1.2; 95% confidence interval [CI], 1.1-1.3; P < .0001) and death (OR, 1.5; 95% CI, 1.4-1.6; P < .0001). The rates of moderate-to-severe disability and death were 37.5% and 50.2% among those who required dialysis, respectively.
In patients with ICH, ARF is associated with significantly higher rates of in-hospital mortality and moderate-to-severe disability at the time of discharge.
More studies required to understand mortality rates of dialysis-dependent patients after acute thrombolysis for stroke
2013, Journal of Stroke and Cerebrovascular Diseases

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Original ArticleOutcomes of Thrombolytic Treatment for Acute Ischemic Stroke in Dialysis-Dependent Patients in the United States

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Conclusion

J Thromb Haemost

Am J Kidney Dis

Lancet Neurol

Arch Phys Med Rehabil

Am J Kidney Dis

Am J Kidney Dis

Kidney Int

Kidney Int

Am J Kidney Dis

Kidney Int

Am J Kidney Dis

Cardiovascular and noncardiovascular mortality among patients starting dialysis

JAMA

Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group

N Engl J Med

Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism

JAMA

Original Article
Outcomes of Thrombolytic Treatment for Acute Ischemic Stroke in Dialysis-Dependent Patients in the United States