Predictors of Need for Critical Care Support, Adverse Events, and Outcome after Stroke Thrombolysis

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Predictors of Need for Critical Care Support, Adverse Events, and Outcome after Stroke Thrombolysis Panagiotis Papamichalis, MD, PhD,* Spyridon Karagiannis, MD, MSc,* Efthimios Dardiotis, MD, PhD,† Achilleas Chovas, MD, PhD,* Dimitrios Papadopoulos, MD, PhD,* Tilemachos Zafeiridis, MD,* Dimitris Babalis, MD,* Georgios Paraforos, MD, PhD,* Vasiliki Zisopoulou, MD,* Apostolia-Lemonia Skoura, MD,* Ioannis Staikos, MD, MSc,* Konstantinos Bouliaris, MD,* Michail Papamichalis, MD, PhD,‡ Georgios Hadjigeorgiou, MD, PhD,† and Apostolos Komnos, MD, PhD*

Background: Results from trials and international registries exhibit heterogeneity regarding safety, efficacy, markers of prognosis, and markers of the need for critical care support after intravenous thrombolysis (IVT) for strokes. The purpose of our study was to indentify such markers after performance of comparisons among patients who received thrombolysis in our intensive care unit. Materials and Methods: Our study included 124 patients who received IVT in accordance with international criteria. Outcome measures of univariate and regression analyses resulted from comparisons between groups of patients with or without the need for critical care support (advanced life support and neurocritical care interventions), groups of patients developing or not developing primary adverse events (symptomatic intracranial hemorrhage [SICH] and/or Death and/or Serious systemic bleeding and/or New stroke) and groups of patients with different main outcome variables (mortality, functional independence at 3 months). Results: Our results suggested that higher severity scores (Simplified Acute Physiology Score II, National Institutes of Health Stroke Scale) correlated with the need for critical care support, primary adverse events, and main outcome variables, whereas older age was significantly associated with fewer adverse events. Hyperlipidemia, symptom-to-needle time, and vascular disease were associated with functional capacity at 3 months, whereas diabetes mellitus and vascular disease correlated with the need for critical care support. Conclusion: Patients’ age, hyperlipidemia, presence of vascular disease, Simplified Acute Physiology Score II (a novel marker), and National Institutes of Health Stroke Scale at 2 hours and at 7 days are independent predictors of the need for critical care support, adverse events, and clinical outcomes after thrombolysis. Key Words: Ischemic stroke—SAPS II—thrombolysis—outcome—NIHSS. © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

From the *Intensive Care Unit, General Hospital of Larissa, Larissa, Greece; †Department of Neurology, University of Thessaly; and ‡Department of Cardiology, Larissa University Hospital, Larissa, Greece. Received April 11, 2017; accepted September 24, 2017. Conflict of interest: The authors declare that they have no conflicts of interest and no funding sources. Address correspondence to Panagiotis Papamichalis, MD, PhD, Intensive Care Unit, General Hospital of Larissa, Tsakalof 1, 41221 Larissa, Greece. E-mail: [email protected]. 1052-3057/$ - see front matter © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.09.042

Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2017: pp ■■–■■

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Introduction Acute ischemic strokes remain one of the leading causes of morbidity, mortality, and disability worldwide,1 despite major advances regarding their management. One of the most promising interventions for ischemic strokes is intravenous thrombolysis (IVT). When it is performed within the therapeutic window and in accordance with international guidelines,2,3 it improves functional outcome and appears to be both safe and well tolerated. Centers in Europe, the United States of America (USA), and other counties use different inclusion criteria,2,3 different definitions for symptomatic intracranial hemorrhage (SICH)4 and other thrombolysis complications, and different scales for evaluation of functional outcome.5 This diversity leads to confusion regarding thrombolysis efficacy and outcome. When 1 center’s experience is brought under investigation, it allows evaluation of everyday clinical practice in thrombolysis. We conducted this study in our center to contribute to this effort for better understanding of thrombolysis parameters and results. Furthermore, the need for prognostic markers and markers of critical care need is obvious, and is strongly emphasized by international literature.6 If we could predict which patients have greater risk for complications and worse clinical outcome, this would allow better decision making regarding who will receive thrombolysis and closer monitoring for those who are more likely not to achieve good results after thrombolysis and end up in an intensive care unit (ICU). The aim of the current study was to investigate possible clinical or epidemiologic prognostic factors correlating with critical care need, complications, and clinical outcome.

Materials and Methods In the absence of High Dependency Unit and Neurology Department in our hospital and Stroke Unit in our territory, IVT is performed at the ICU of General Hospital of Larissa. It is the only facility in our hospital in which IVT can be performed according to international standards2,3 (vigorous noninvasive blood pressure monitoring and monitoring of the rest of the vital signs, frequent assessment of oxygen saturation and Glasgow Coma Scale, evaluation for the occurrence of complications, especially for the first 24 hours). According to our hospital’s protocol at the emergency department, triage is applied for identification of patients with symptoms of acute ischemic stroke. Those who are eligible for thrombolysis are vigorously brought to the ICU after having a brain computed tomography (CT) scan. Standard international protocols for thrombolysis2 are used. Demographic characteristics, baseline clinical data, severity scores (Simplified Acute Physiology Score II [SAPS II]), and details regarding thrombolysis procedures

(symptom-to-needle time, actilyse dose, CT imaging details) are recorded. Patients’ neurologic status is evaluated using the National Institutes of Health Stroke Scale (NIHSS) before thrombolysis and at 2, 24 hours, and 7 days after thrombolysis. All patients undergo the appropriate diagnostic workup for the cause of the stroke (transthoracic/ transesophageal heart ultrasound, Holter monitor of heart’s rhythm, triplex vascular ultrasound for evaluation of carotids and cerebrovascular circulation) and start secondary prevention (anticoagulation, statins). Those without complication, within 24 hours and right after a second brain CT scan that confirms the absence of intracranial hemorrhage, are discharged from the ICU and transferred either to the general medicine departments of our hospital or to the Neurology Department of Larissa University Hospital, if more specialized diagnostic tests are required (molecular thrombophilic tests, test for vasculitis, etc.). However, in case of complication (SICH, aspiration, reduction of level of consciousness, brain edema), patients remain in the ICU and receive the appropriate advanced life support or neurocritical care intervention (intubation, craniectomy, intracranial pressure monitoring, multimodal brain monitoring, etc.). Patients were re-evaluated at 3 months after thrombolysis, regarding their medication use (anticoagulants, statins), and their performance/disability status, by means of the modified Rankin Scale (mRS). Every patient who has received IVT is enrolled at our local ICU thrombolysis database and at the international Safe Implementation of Treatments in Stroke—International Stroke Thrombolysis Register (SITS-ISTR). Our 10-year (2004-2014) thrombolysis database was retrospectively evaluated and included a total of 124 patients with acute ischemic stroke, with a mean age of 65 years and a median NIHSS at admission 11 (range 2-28). They fulfilled international inclusion criteria.2 However, 41 (33.1%) of them had 1 or more license contraindications to alteplase7 or relative contraindications to thrombolysis.2,3,8,9 In particular 10 patients were more than 80 years old, 13 patients had mild stroke with an NIHSS less than 5, and 22 patients had symptom-to-needle time of 3-4.5 hours. The relevant demographic and clinical data of our patients are shown in Table 1. Database retrieved data included demographic characteristics, patients’ medical history regarding predisposing factors (diabetes mellitus, arrhythmia, hypertension, smoking habit, hyperlipidemia, vascular disease, former ischemic stroke), severity scores (SAPS II at 24 hours, NIHSS at various time points), the therapeutic window (symptom-to-needle time), critical care need (patients who demanded advanced life support and neurocritical care interventions), all primary adverse events, mortality, and functional independence at 3 months. All procedures performed in our study were in accordance with the ethical standards of the institutional or national research committee, and with the 1964 Helsinki

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Table 1. Patients’ characteristics Patients received intravenous thrombolysis

(Patients’ number = 124)

Gender (female/male) Age—mean ± standard error (y) Days of hospitalization— mean ± standard error Median time-window SAPS II—mean ± standard error NIHSS (admission)—median (range) Diabetes mellitus (yes/no) Arrhythmia (yes/no) Hypertension (yes/no) Smoking (yes/no) Hyperlipidemia (yes/no) Vascular disease (yes/no) Former ischemic stroke (yes/no)

42/82 65 ± 1.1 5.9 ± .9 145 25 ± .9 11 (2-28) 28/96 37/87 80/44 29/95 33/91 22/102 12/112

Abbreviations: SAPS II, Simplified Acute Physiology Score II; NIHSS, National Institutes of Health Stroke Scale.

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stroke during thrombolysis. (3) The mortality rate at 3 months: 108 patients of our group were alive at 3 months, whereas 16 patients died within 3 months time. (4) The functional independence, as measured by the mRS at 3 months: 82 patients were functionally independent (mRS: 0-2), whereas 42 patients were not (mRS ≥3).

Statistical Analysis Results are expressed as mean ± standard error, median (range), or patients (%). Data were analyzed by 2 by 2 x square (x2) after Yates’ correction test, Fisher’s exact test, and Mann-Whitney U test, where applicable. A 2-tailed P value less than or equal to .05 was considered significant. P values between .05 and .10 were considered as trends for statistical significance. The variables significant in the univariate analysis entered a binary logistic regression model. Statistical analyses were performed using the SPSS statistical package (SPSS, 16th Edition, SPSS Inc., Chicago, IL ).

Results Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. The protocol of this study was approved without the need for informed consent by the Scientific Council of the General Hospital of Larissa. For this type of study (retrospective), formal consent is not required.

Outcome Measurements For the assessment of SICH, the Safe Implementation of Thrombolysis in Stroke—MOnitoring STudy (SITSMOST) definition,10 which includes local or remote type 2 parenchymal hemorrhage detected on an imaging scan 22-36 hours after treatment or earlier if clinically indicated, combined with neurologic deterioration of 4 points or more (as measured by the NIHSS) between baseline and 24 hours or death. Our group was categorized according to the following 4 end points of our study: (1) The need for critical care support: 110 patients were discharged without the need for advanced support by our ICU, whereas 14 demanded advanced life support (intubation, mechanical ventilation, hemodynamic support with inotrops) and neurocritical care interventions (craniectomy, intracranial pressure monitoring, multimodal brain monitoring). (2) The occurrence of primary adverse events: 117 patients presented no primary adverse event, whereas 7 patients had primary adverse events as defined by the international literature11 (SICH and/or Death and/or Serious systemic bleeding and/or New stroke). In particular, 1 patient had SICH (according to SITS-MOST definition), 5 patients died during their hospitalization after thrombolysis, and 1 patient had recurrence of embolic

Factors Correlating with the Need for Critical Care Support Patients with need for critical care support (n = 14) had significantly higher SAPS II (P = .05), higher NIHSS at 2 hours (P = .03), at 24 hours (P < .001), and at 7 days (P < .001), and higher rates of vascular disease (P = .003) when compared with those without need for critical care support (n = 110) in the univariate analysis while rates of history for diabetes mellitus tended to be different between the 2 groups (P = .09) (Table 2). However, the binary logistic regression analysis showed that NIHSS at 2 hours (P = .04) and at 7 days (P = .009) were the only independent predictive factors of the need for critical care support, whereas the presence of vascular disease tended to be independently associated with critical care need (P = .06) (Table 4).

Factors Correlating with Primary Adverse Events In the univariate analysis, parameters that significantly differed between patients who developed primary adverse events (SICH and/or Death and/or Serious systemic bleeding and/or New stroke) (n = 7) and those who did not develop any primary adverse event (n = 117) were as follows: (a) age (P = .05), (b) SAPS II (P = .02), and (c) NIHSS at 7 days (P = .01) (Table 2). After binary logistic regression analysis we found that age was the only independent factor that was significantly associated with manifestation of primary adverse events (P = .04), with younger patients being more prone to primary adverse events. In addition, higher SAPS II tended to be an independent predictive factor for the presentation of primary adverse events (P = .07) (Table 4).

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Table 2. Correlation with need for critical care support* and primary adverse events†

Sex Female [patients (%)] Male [patients (%)] Age—mean ± standard error (y) SAPS II—mean ± standard error NIHSS (admission)—median (range) NIHSS (after 2 h)—median (range) NIHSS (after 24 h)—median (range) NIHSS (after 7 d)—median (range) Diabetes mellitus No [patients (%)] Yes [patients (%)] Arrhythmia No [patients (%)] Yes [patients (%)] Hypertension No [patients (%)] Yes [patients (%)] Smoking No [patients (%)] Yes [patients (%)] Hyperlipidemia No [patients (%)] Yes [patients (%)] Vascular disease No [patients (%)] Yes [patients (%)] Former ischemic stroke No [patients (%)] Yes [patients (%)] Off-label thrombolysis No [patients (%)] Yes [patients (%)] NIHSS <5 No [patients (%)] Yes [patients (%)] Age >80 y No [patients (%)] Yes [patients (%)] Therapeutic window Within 3 h [patients (%)] 3-4.5 h [patients (%)] Aggregate thrombolysis time Mean ± standard error (min)

No advanced critical care support (n = 110)

Advanced critical care support (n = 14)

39 (35.5) 71 (64.5) 65.5 ± 1.2 22.8 ± 1 10 (2-28) 7 (0-28) 3 (0-23) 2 (0-28)

3 (21.4) 11 (78.6) 61.1 ± 1.7 30 ± 1.4 12 (3-22) 12 (0-23) 18 (0-27) 18 (5-26)

P value 0.38‡ 3.6§ 0.05§,‖ 0.3‖ 0.03§,‖ <0.001§,‖ <0.001§,‖

No major complication (n = 117)

Primary adverse event (n = 7)

38 (32.5) 79 (67.5) 65.6 ± 1.1 24.6 ± .8 11 (2-28) 7 (0-28) 3 (0-27) 2 (0-26)

4 (57.1) 3 (42.9) 56.1 ± 4.3 36.1 ± 5.4 11 (3-17) 11 (0-17) 17 (0-25) 17 (0-28)

P value 0.23‡ 0.05§,‖ 0.02§,‖ 0.86§ 0.5§ 0.2§ 0.01§,‖

88 (80) 22 (20)

8 (57.1) 6 (42.9)

0.09‡,¶

90 (76.9) 27 (23.1)

6 (85.7) 1 (14.3)

79 (71.8) 31 (28.2)

8 (57.1) 6 (42.9)

0.35‡

81 (69.2) 36 (30.8)

6 (85.7) 1 (14.3)

0.68‡

39 (35.5) 71 (64.5)

5 (35.7) 9 (64.3)

41 (35) 76 (65)

3 (42.9) 4 (57.1)

0.7‡

85 (77.3) 25 (22.7)

10 (71.4) 4 (28.6)

0.74‡

91 (77.8) 26 (22.2)

4 (57.1) 3 (42.9)

0.35‡

78 (70.9) 32 (29.1)

13 (92.9) 1 (7.1)

0.11‡

84 (71.8) 33 (28.2)

7 (100) 0 (0)

0.2‡

95 (86.4) 15 (13.6)

7 (50) 7 (50)

0.003‡,‖

96 (82.1) 21 (17.9)

6 (85.7) 1 (14.3)

1‡

1‡

1‡

99 (90) 11 (10)

13 (92.9) 1 (7.1)

1‡

106 (90.6) 11 (9.4)

6 (85.7) 1 (14.3)

0.52‡

73 (66.4) 37 (33.6)

10 (71.4) 4 (28.6)

1‡

77 (65.8) 40 (34.2)

6 (85.7) 1 (14.3)

0.42‡

98 (89.1) 12 (10.9)

13 (92.9) 1 (7.1)

1‡

105 (89.7) 12 (10.3)

6 (85.7) 1 (14.3)

0.55‡

102 (92.7) 8 (7.3)

12 (85.7) 2 (14.3)

107 (91.5) 10 (8.5)

7 (100) 0 (0)

90 (81.8) 20 (18.2)

12 (85.7) 2 (14.3)

95 (81.2) 22 (18.8)

7 (100) 0 (0)

140.2 ± 4.8

158.6 ± 6.6

0.31‡

1‡

0.64§

146.2 ± 4.2

149.3 ± 8.9

Abbreviations: SAPS II, Simplified Acute Physiology Score II; NIHSS, National Institutes of Health Stroke Scale. *Advanced life support and neurocritical care interventions. †Symptomatic intracranial hemorrhage and/or Death and/or Serious systemic bleeding and/or New stroke. ‡Fisher’s exact test. §Mann-Whitney U test. ‖Statistically significant. ¶Trend for statistical significance.

1‡

0.35‡

0.8§

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Factors Correlating with Main Outcome Variables After comparisons among the group of patients who were alive at 3 months (n = 108) and those who died within 3 months’ time (n = 16), we found in the univariate analysis that mortality at 3 months was associated with higher SAPS II (P = .002) and higher NIHSS at admission (P = .005), at 2 hours (P = .01), at 24 hours (P = .001), and at 7 days (P < .001) (Table 3). However, after binary logistic regression analysis, NIHSS at 7 days was identified as the only independent predictor for death within 3 months (P = .004), while higher SAPS II tended to be an independent predictive factor for death within 3 months (P = .06) (Table 4). In the univariate analysis, patients with functional independence at 3 months [mRS 0-2, (n = 82)] had significantly lower SAPS II (P < .001), higher rates of hyperlipidemia (P = .002), shorter symptom-to-needle time (P = .05), lower NIHSS at admission (P < .001), at 2 hours (P < .001), at 24 hours (P < .001), and at 7 days (P < .001), compared with patients without functional independence at 3 months [mRS ≥3, (n = 42)]. In addition, patients who had off-label thrombolysis with mild stroke (NIHSS <5) and patients without vascular disease tended to have higher rates of functional independence (P = .06 and P = .08, respectively) (Table 3). The binary logistic regression analysis showed that lower NIHSS at 7 days (P = .001) and hyperlipidemia (P = .01) were the only independent predictive factors of functional independence at 3 months, whereas lower SAPS II (P = .1) tended to be an independent predictor of functional independence at 3 months (Table 4).

Discussion The correlation of NIHSS at different time points with the need for critical care support, primary adverse events, and main outcome variables found in our study is in accordance with international experience: NIHSS is considered to be more sensitive than other scales and thus has been proposed as a prognosis-adjusted end point in clinical trials.5 It constitutes a predictor for SICH,12 unfavorable outcome, in-hospital mortality,13 and critical care need.14 In our study, NIHSS at 2 hours and at 7 days was found to be an independent predictor of the need for critical care support, whereas NIHSS at 7 days was independently associated with mortality and functional independence at 3 months. The relationship of the therapeutic window (symptomto-needle time) with safety and efficacy of IVT is widely known,12 as emphatically stated by the phrase: “time is brain.”2 So it is of no surprise that in our study, functional independence at 3 months was associated with shorter therapeutic window. Contrary to publications in which older age is associated with worse functional outcome, SICH, and higher mortality rates12 but in accordance with other publications who claim that thrombolysis in older age is both effective and safe,15-17 in our study, older age was associated

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with less primary adverse events, while it had no impact on functional outcome and mortality rates. History of hyperlipidemia was identified as an independent predictor of functional independence at 3 months. This result is opposed to older publications, in which pretreatment or intake of statins during acute phase was associated with increased risk for SICH18 and 3 months’ mortality after thrombolysis. However, our results are in line with a more recent publication, which found that statin pretreatment was not associated with SICH or 3 months mortality but on the contrary it was associated with early clinical recovery.19 Although we did not investigate whether our patients were receiving statins before thrombolysis, for most of them therapy was initiated or continued after admission to our department. Our results suggest the necessity for both continuing statin treatment to those pretreated before the acute ischemic stroke, as suggested by current guidelines,3 and further investigating the relationship of hyperlipidemia and statin therapy with better functional outcome after thrombolysis. The correlation of diabetes mellitus and vascular disease with critical care need and functional dependence at 3 months seems logical. Diabetes mellitus and former ischemic stroke is a relative contraindication, according to international guidelines.2,3 Patients with these predisposing factors are more likely to have severe strokes with complications resulting in prolonged hospitalization and ICU need. Furthermore, due to their underlying conditions (coronary heart disease, vasculopathy), it is more difficult for them to receive proper rehabilitation care. Our results regarding off-label thrombolysis are worth noticing. Many patients are deprived of thrombolysis benefits due to license contraindications to alteplase that are not the same in Europe and in the USA, or contraindications, which originated as exclusion criteria in major stroke trials, unnecessarily restrictive in clinical practice. We examined 3 of them: more than 3 hours therapeutic window (license contraindication in the USA), patients’ age greater than 80 years (relative contraindication in the 3- to 4.5hour therapeutic window in American Heart Association [AHA]/American Stroke Association [ASA] guidelines3) and minor symptoms of stroke (NIHSS <5) (relative contraindication in AHA/ASA guidelines3). In our study, none of these contraindications was associated with primary adverse events or 3 months’ mortality rates, whereas minor stroke thrombolysis tended to be associated with better functional outcome at 3 months, in agreement with recent publications that favor thrombolysis at patients with low NIHSS.8 What is more interesting as a result of our study is that SAPS II was associated with all the outcomes measured in our study: critical care need, primary adverse events, mortality, and functional outcome at 3 months. SAPS II is a severity of disease classification system. It is designed to measure the severity of disease for patients admitted to ICUs.20 It is calculated 24 hours after

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Table 3. Correlation with main outcome variables at 3 months Alive at 3 months (n = 108) Sex Female [patients (%)] Male [patients (%)] Age—mean ± standard error (y) SAPS II—mean ± standard error NIHSS (admission)—median (range) NIHSS (2 h)—median (range) NIHSS (24 h)—median (range) NIHSS (7 d)—median (range) Diabetes mellitus No [patients (%)] Yes [patients (%)] Arrhythmia No [patients (%)] Yes [patients (%)] Hypertension No [patients (%)] Yes [patients (%)] Smoking No [patients (%)] Yes [patients (%)] Hyperlipidemia No [patients (%)] Yes [patients (%)] Vascular disease No [patients (%)] Yes [patients (%)] Former ischemic stroke No [patients (%)] Yes [patients (%)] Off-label thrombolysis No [patients (%)] Yes [patients (%)] NIHSS <5 No [patients (%)] Yes [patients (%)] Age >80 y No [patients (%)] Yes [patients (%)] Therapeutic window 3 h [patients (%)] 3-4.5 h [patients (%)] Aggregate thrombolysis time Mean ± standard error (min)

Dead at 3 months (n = 16)

P value 0.37‡

Independent* (n = 82)

Not Independent† (n = 42)

24 (29.3) 58 (70.7) 63.7 ± 1.4 22.8 ± 1 8 (2-23) 4 (0-24) 1 (0-25) 0 (0-25)

18 (42.9) 24 (57.1) 67.5 ± 1.7 30 ± 1.4 15 (3-28) 12 (0-28) 12 (0-27) 13 (0-28)

P value 0.13‡

35 (32.4) 73 (67.6) 64 ± 1.2 24 ± .8 10 (2-25) 7 (0-24) 3 (0-27) 2 (0-25)

7 (43.8) 9 (56.2) 67.6 ± 2.9 33 ± 2.9 15 (6-28) 12 (0-28) 13 (0-26) 13 (0-28)

84 (77.8) 24 (22.2)

12 (75) 4 (25)

0.8‖

64 (78) 18 (22)

32 (76.2) 10 (23.8)

0.8‡

75 (69.4) 33 (30.6)

12 (75) 4 (25)

0.8‖

58 (70.7) 24 (29.3)

29 (69) 13 (31)

0.8‡

40 (37) 68 (63)

4 (25) 12 (75)

0.35‡

31 (37.8) 51 (62.2)

13 (31) 29 (69)

0.45‡

83 (76.9) 25 (23.1)

12 (75) 4 (25)

62 (75.6) 20 (24.4)

33 (78.6) 9 (21.2)

0.7‡

77 (71.3) 31 (28.7)

14 (87.5) 2 (12.5)

0.23‖

53 (64.6) 29 (35.4)

38 (90.5) 4 (9.5)

0.002‖,¶

91 (71.3) 17 (15.7)

11 (68.8) 5 (31.2)

0.2‖

71 (86.6) 11 (13.4)

31 (73.8) 11 (26.2)

0.08‡,#

98 (90.7) 10 (9.3)

14 (87.5) 2 (12.5)

0.65‖

74 (90.2) 8 (9.8)

38 (90.5) 4 (9.5)

1‖

71 (65.7) 37 (34.3)

12 (75) 4 (25)

0.46‡

55 (67.1) 27 (32.9)

28 (66.7) 14 (33.3)

1‡

95 (88) 13 (12)

16 (100) 0 (0)

0.2‖

70 (85.4) 12 (14.6)

41 (97.6) 1 (2.4)

0.06‖,#

100 (92.6) 8 (7.4)

14 (87.5) 2 (12.5)

0.6‖

77 (93.9) 5 (6.1)

37 (88.1) 5 (11.9)

0.3‖

12 (75) 4 (25)

0.5‖

70 (85.4) 12 (14.6)

32 (76.2) 10 (23.8)

0.2‡

158.1 ± 10.4

0.33§

90 (83.3) 18 (16.7) 144.8 ± 4.3

0.44§ 0.002§,¶ 0.005§,¶ 0.01§,¶ 0.001§,¶ <0.001§,¶

1‖

140.2 ± 4.8

158.6 ± 6.6

Abbreviations: SAPS II, Simplified Acute Physiology Score II; NIHSS, National Institutes of Health Stroke Scale. *Modified Rankin Scale 0-2 (at 3 months). †Modified Rankin Scale ≥ 3 (at 3 months). ‡2 by 2 x2 after Yates correction. §Mann-Whitney U test. ‖Fisher’s exact test. ¶Statistically significant. #Trend for statistical significance.

0.2§ <0.001§,¶ <0.001§,¶ <0.001§,¶ <0.001§,¶ <0.001§,¶

0.05§,¶

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Table 4. Variables that were independent predictors for critical care need, manifestation of primary adverse events*, death within 3 months, and functional independence† at 3 months after binary logistic regression analysis

Association with critical care need

Manifestation of primary adverse events

Death within 3 mo

Functional independence* at 3 mo

Variable

Regression coefficient

Standard error

P value

SAPS II NIHSS (after 2 h) NIHSS (after 24 h) NIHSS (after 7 d) Diabetes mellitus Vascular disease Age SAPS II NIHSS (after 7 d) SAPS II NIHSS (admission) NIHSS (after 2 h) NIHSS (after 24 h) NIHSS (after 7 d) SAPS II NIHSS (admission) NIHSS (after 2 h) NIHSS (after 24 h) NIHSS (after 7 d) Hyperlipidemia Vascular disease NIHSS <5 Aggregate thrombolysis time

.06 −.29 .19 .24 .16 −1.92 −.076 .08 .077 .061 .075 −.027 −.146 .24 .064 .15 −.04 −.03 .36 2.6 .27 .9 .009

.06 .14 .14 .09 1.05 1.01 .037 .045 .058 .033 .077 .09 .106 .084 .04 .09 .1 .1 .1 1 .8 2.2 .007

.28 0.04‡ .17 0.009‡ .9 0.06§ 0.04‡ 0.07§ .2 0.06§ .3 .77 .17 0.004‡ 0.1§ .12 .7 .8 0.001‡ 0.01‡ .75 .7 .2

Abbreviations: SAPS II, Simplified Acute Physiology Score II; NIHSS, National Institutes of Health Stroke Scale. *Symptomatic intracranial hemorrhage and/or Death and/or Serious systemic bleeding and/or New stroke. †Modified Rankin Scale 0-2. ‡Statistically significant. §Trend for statistical significance.

admission to the ICU and is mostly used to describe the morbidity of a patient when comparing the outcome with other patients. It is considered the simplest system to measure ICU performance and compare performance over the years. Although it is a non–disease-specific system, it performs well in specific disease categories such as obstetric complications,21 coronary artery disease-cardiac surgery operations,22 and neurosurgical disorders (subarachnoid hemorrhage, traumatic brain injury).23 Its performance at these diseases is similar to that reported for heterogeneous ICU patients. It has never been applied in stroke patients in the past. Our results are very encouraging for the use of SAPS II in patients receiving thrombolysis for stroke. Although the need for better validation in larger studies is obvious, it seems that SAPS II exhibits excellent performance at the prediction of the need for critical care support, primary adverse events, and main outcome variables. One possible explanation for this is that stroke is a systemic disorder affecting patients as a whole, and this results in greater SAPS II and mortality rates for patients with more severe strokes who develop more complications and have worse outcome after thrombolysis.

Conclusions Our study suggests that ability to predict thrombolysis outcome may become a useful tool for improving patients’ management after thrombolysis. Patients’ age, hyperlipidemia, presence of vascular disease, SAPS II, and NIHSS at 2 hours and at 7 days are independent predictors of critical care need, adverse events, and clinical outcomes, and should be taken into account when we perform thrombolysis. The ability of SAPS II to predict thrombolysis outcomes and its possible use as prognostic marker needs further validation in a large series of patients. Acknowledgments: We thank the nursing staff and the physiotherapist team of Larissa Intensive Care Unit for their everyday care of our stroke patients.

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