The Effect of Out-of-Hours Admission on Mortality in Patients Who Underwent Thrombectomy Due to Ischemic Stroke

Abstract

Background

It is important to investigate the factors that may delay the diagnosis and treatment process of ischemic stroke. The aim of this study was to investigate whether in-hospital mortality increased in patients who presented to the emergency department out-of-hours and underwent thrombectomy.

Methods

A total of 59 patients who applied to the emergency department between January 1, 2018 and November 1, 2021 and underwent thrombectomy due to ischemic stroke were included in the study. Patient age, gender, thrombectomy success (successful recanalization), in-hospital mortality status, intracranial hemorrhage status after thrombectomy, and out-of-hours admission status were recorded and compared according to out-of-hours admission status.

Results

Twenty-seven (45.8%) patients were male, and the median age was 74 (61–81) years. Forty-two (71.2%) patients applied to the emergency department out-of-hours. In-hospital mortality occurred in 27 (45.8%) patients. There was no statistically significant difference in out-of-hours admission status between the non-survivor group and the survivor group (non-survivor: 24 [75%]; survivor: 18 [66.7%], p = 0.481). Nor was a statistically significant difference found in the intracranial hemorrhage complication rate of the patients admitted out-of-hours compared to the patients admitted during working hours (out-of-hours: 17 [40.5%]; during working hours: 6 [35.3%], p = 0.712).

Conclusion

No statistically significant difference was found in the rate of in-hospital mortality and intracranial bleeding complications in patients who underwent thrombectomy out of working hours compared to during working hours.

Introduction

Acute cerebrovascular events require rapid diagnosis and are among the leading causes of death. The most common subtype with a rate of 85% is ischemic stroke. 1 While thrombolytic therapy should be performed within the first 4.5 hours, invasive treatments, such as thrombectomy, should be performed within the first 12 hours. 2 , 3 There are many reasons that affect mortality in stroke patients, from the occurrence of depression to the type of stroke. 1 One of the most important reasons for increasing mortality is the delay in the diagnostic process, which is time-sensitive. 4 This delay influences the treatment decision. In addition, even if the delay in the diagnosis process does not affect the treatment decision, it worsens the prognosis. Because performing thrombolytic and thrombectomy procedures at later hours increases mortality and morbidity. 5

It is important to investigate the factors that may delay the diagnosis and treatment process. Out-of-hours treatments are associated with more adverse outcomes. 6 It has been shown that stroke patients admitted on weekends have high mortality. 7 We hypothesized that out-of-hours admission of patients diagnosed with ischemic stroke, which is an indication for thrombectomy, would affect treatment process and mortality.

We investigated whether there was a significant difference in in-hospital mortality according to the time of admission of patients who presented to the emergency department (ED) and underwent thrombectomy due to ischemic stroke.

Methods

Ethical approval was obtained from the local Ethical Committee for this retrospective study. The thrombectomy procedure code on the hospital information system was used to select the patients who were admitted to our tertiary university hospital, and their records were analyzed retrospectively. Patients over the age of 18 who presented to the ED between January 1, 2018 and November 1, 2021, and who underwent thrombectomy due to ischemic stroke were included. Patients who were hospitalized for another reason had a stroke, and underwent thrombectomy in the hospital were excluded.

There is a stroke team in the hospital where the study was conducted. Physicians in the team made the thrombolytic and thrombectomy decision of stroke patients according to the American Heart Association (AHA) and the American Stroke Association (ASA) guideline. 8 , 9 The decision whether the patient is a thrombectomy candidate or not was made by the emergency physician. The emergency physician consulted the patient, who was a thrombectomy candidate, to the neurology and neuroradiology department. The final thrombectomy decision of the patient was made jointly by the neurologist and neuroradiologist. While the neurologist and emergency specialist who made the thrombolytic decision in this team were in the hospital for 24 hours, the neuroradiologist who performed the thrombectomy procedure came to the hospital by phone when needed during non-working hours. FDA-approved Solitaire (Medtronic) and Trevo (Stryker) devices were used in the thrombectomy procedure. 10

The patients were categorized according to the time of admission to the ED. The patients who presented between 08:00 and 16:00 hours on weekdays were included in the work hours group, and the patients who attended outside these times were included in the out-of-hours group. Patient age, gender, systolic blood pressure, diastolic blood pressure, fever, oxygen saturation, National Early Warning Score 2 (NEWS2) value, number of hours after the onset of symptoms, National Institutes of Health Stroke Scale (NIHSS) value, comorbidities, blood urea nitrogen (BUN) value, glucose value, albumin value, BUN albumin ratio (BAR) value, thrombus localization, thrombectomy success (Successful recanalization: According to the Thrombolysis In Cerebral Infarction scale [TICI], patients with TICI-3 and TICI-2B), emergency outcome, hospital outcome, in-hospital mortality status (Patients who died when they are in the hospital), ED admission day and time, intracranial hemorrhage status after thrombectomy (brain computed tomography was routinely performed on all patients at the 24th hour), and the recommendation for emergency operation after thrombectomy were recorded. The parameters were compared according to in-hospital mortality. The primary outcome of the study was whether there was a significant difference in the in-hospital mortality rate of the patients who presented to the ED out of work hours compared to the patients who applied to the ED during work hours.

SPSS 20.0 (SPSS Inc., Chicago, IL, USA) software was used for the statistical analysis. The Kolmogorov–Smirnov test was used to analyze the normality of the data. Following the normality analysis, if the data were not normally distributed, the median (25%–75%) was expressed, and if the data were normally distributed the mean ± standard deviation was presented. The categorical variables were expressed as percentages. Student’s t -test was used for intergroup comparison of the normally distributed data, and the Mann–Whitney U test was used for intergroup comparison of the non-normally distributed data. The Chi-square test or Fisher’s exact test were used to compare the categorical variables between the groups. Logistic regression analysis was performed to determine the causes of in-hospital mortality. First, univariate logistic regression analysis was performed with all parameters. Then, a multivariate logistic regression analysis was performed with the backward Wald method for the parameters with p values < 0.25 in the univariate logistic regression analysis. The Hosmer-Lemeshow test was used to assess the model fit of the multivariate logistic regression analysis. A p value < 0.05 was considered statistically significant.

Results

A total of 62 patients underwent thrombectomy. Three patients were excluded from the study because thrombectomy was performed for a stroke that developed after hospitalization. Twenty-seven (45.8%) of the 59 patients included in the study were male, and the median age of the 59 patients was 74 (interquartile range [IQR]: 61–81) years. Twelve (20.3%) patients presented to the ED during the 00.00–08.00 time interval, 28 (47.5%) in the 08.00–16.00 time interval, and 19 (32.2%) in the 16.00–24.00 time interval, regardless of weekdays and weekends. Forty-two (71.2%) patients presented to the ED out-of-hours. The most involved artery was the middle cerebral artery (MCA) in 30 (50.8%) patients. The patients applied to the ED a median of 4 (IQR: 3.5–5) hours after the onset of symptoms. The median NIHSS value of the patients was 16 (IQR: 15–20), while the mean NEWS2 value was 5.9 ± 2.11. Intracranial hemorrhage was detected in 23 (39%) patients after thrombectomy. Detailed characteristics of the participants are given in Table 1 .

Table 1 . Participant characteristics ^a .

^a All values were presented as number (%), mean ± SD, or median (interquartile ranges).

Characteristic	N = 59
Age, y, median (IQR)	74 (61–81)
Gender, n (%)
Male	27 (45.8)
Female	32 (54.2)
Vital Signs
Fever (Cº)	36.3 (36–36.8)
Pulse, min, mean ± SD	82.7 ± 16.81
SBP, mmHg, mean ± SD	146.87 ± 29.71
DBP, mmHg, mean ± SD	81.91 ± 15.97
Oxygen saturation, (%)	95 (92–98)
NIHSS score	16 (15–20)
NEWS2 score	5.9 ± 2.11
Symptom time (hours)	4 (3.5–5)
Thrombolytic therapy	8 (13.6)
Localization
MCA	30 (50.8)
ICA	25 (42.4)
Vertebrobacillary artery	4 (6.8)
Assessment and treatment
Off-hour	42 (71.2)
Complication of intracranial bleeding	23 (39)
Operation recommendation	7 (11.9)
Thrombectomy success	46 (78)
Arrival time (hours)
00–08	12 (20.3)
08–16	28 (47.5)
16–24	19 (32.2)
Laboratory results
Glukoz (mg/dL)	136.6 (111–161.8)
BUN (mg/dL)	21.29 ± 11.5
Albumin (g/dL)	39.29 ± 4.73
BAR	0.43 (0.34–0.69)
Lactate (mEq/L)	1.9 (1.4–2.7)
Medical history
Hypertension	32 (54.2)
Diabetes mellitus	21 (35.6)
Coronary artery disease	19 (32.2)
Cerebrovascular disease	15 (25.4)
Atrial fibrillation	9 (15.3)
Malignancy	8 (13.6)
Length of hospital stay (day)	6 (3–15)
Emergency department outcome
Ward unit	2 (3.4)
ICU	54 (91.5)
Referred	3 (5.1)
Hospital outcome
Discharged	18 (30.5)
Ex	32 (54.2)
Referred	9 (15.3)
In-hospital mortality
Survivor	27 (45.8)
Nonsurvivor	32 (54.2)

In-hospital mortality was observed in 27 (45.8%) patients. There was no statistically significant difference between the out-of-hours ED admission rate in the non-survivor group and the out-of-hours ED admission rate in the survivor group (non-survivor: 24 [75%]; survivor: 18 [66.7%], p = 0.481). Nor was there any statistically significant difference between the vital signs and laboratory findings of the patients in the non-survivor and the survivor groups. The rate of successful recanalization after thrombectomy in the survivor group was statistically significantly higher than in the non-survivor group (survivor: 24 [92.3%]; non-survivor: 22 [68.8%], p = 0.028). The incidence of intracranial hemorrhage after thrombectomy in the non-survivor group was statistically significantly higher than in the survival group (non-survivor: 19 [59.4%]; survivor: 4 [14.8%], p < 0.001). The median NIHSS value of the patients in the non-survivor group was statistically significantly higher than in the survivor group (non-survivor: 20 [IQR: 16–20.75]; survivor: 16 [IQR: 15–20], p = 0.035). The MCA occlusion rate of the patients in the survivor group was statistically significantly higher than in the non-survivor group (survivor: 18 [66.7%]; non-survivor: 12 [37.5%], p = 0.034). Table 2 shows the detailed comparisons between the patients according to in-hospital mortality.

Table 2 . Parameters according to in-hospital mortality ^a .

^a All values were presented as number (%), mean ± SD, or median (interquartile ranges).

^b Fisher’s exact test was used.

BAR: BUN albumin ratio; BUN: blood urea nitrogen; CAD: coronary artery disease; CVD: cerebrovascular disease; DBP: diastolic blood pressure; NIHSS: National Institutes of Health Stroke Scale; ICA: internal carotid artery; MCA: middle cerebral artery; NEWS2: National Early Warning Score 2; SBP: systolic blood pressure; SD: standard deviation.

Characteristic	Non-survivor (n = 32)	Survivor (n = 27)	p value
Age	71.5 (54.5–78.25)	75(60–82)	0.276
Gender
Male	14 (43.8)	13 (48.1)	0.735
Female	18 (56.3)	14 (51.9)
Length of hospital stay (day)	4.5 (2–13)	9 (2–35)	0.289
Vital signs
Fever (Cº)	36.25 (36.1–36.72)	36.1 (35.7–36.8)	0.682
Pulse (per minute)	81.32 ± 16.72	84.29 ± 17.08	0.507
SBP (mmHg)	147.54 ± 33.23	146.11 ± 25.69	0.856
DBP (mmHg)	82.12 ± 18.15	81.66 ± 13.38	0.912
Saturation (%)	94 (90.25–98)	95 (94–98)	0.994
Medical history
Hypertension	21 (65.6)	11 (40.7)	0.056
Diabetes mellitus	11 (34.4)	10 (37)	0.832
CAD	11 (34.4)	8 (29.6)	0.698
CVD	8 (25)	7 (25.9)	0.935
NIHSS	20 (16–20.75)	16 (15–20)	0.035
Symptom time (hours)	4.5 (3.5–5)	4 (3–5)	0.636
Thrombolytic therapy	2 (6.3)	6 (22.2)	0.126 b
Thrombectomy success	22 (68.8)	24 (92.3)	0.028
Complication of intracranial bleeding	19 (59.4)	4 (14.8)	< 0.001
Operation recommendation	6 (18.8)	1 (3.7)
Localization
MCA	12 (37.5)	18 (66.7)	0.034
ICA	16 (50)	9 (33.3)
Vertebrobacillary artery	4 (12.5)	0 (0)
Out-of-hours	24 (75)	18 (66.7)	0.481
Arrival time (hours)
00–08	4 (12.5)	8 (29.6)	0.161
08–16	15 (46.9)	13 (48.1)
16–24	13 (40.6)	6 (22.2)
Laboratory results
Glukoz (mg/dL)	157.5 (116.92–182.77)	137.8 (120.7–161.8)	0.670
BUN (mg/dl)	21.53 ± 8.5	21 ± 14.45	0.867
Albumin (g/dl)	38.86 ± 4.95	39.62 ± 4.63	0.612
BAR (mg/g)	0.47 (0.4–0.75)	0.4 (0.34–0.6)	0.261
Lactate (mEq/L)	1.9 (1.25–3.1)	2 (1.6–2.7)	0.600
NEWS2	6.19 ± 2.15	5.56 ± 2.06	0.254

No statistically significant difference was found in the successful recanalization rate of the patients admitted out of working hours compared to the patients admitted during working hours (out-of-hours: 30 [71.4%]; during working hours: 16 [94.1%], p = 0.084). No statistically significant difference was found in the intracranial hemorrhage complication rate of the patients admitted out-of-hours compared to the patients admitted during working hours (out-of-hours: 17 [40.5%]; during working hours: 6 [35.3%], p = 0.712). A detailed comparison of the parameters according to out-of-hours admission is given in Table 3 .

Table 3 . Evaluation of parameters according to out-of-hours admission ^a .

^a All values were presented as number (%) or median (interquartile ranges).

^b Fisher’s exact test was used.

ICA: internal carotid artery; MCA: middle cerebral artery; NIHSS: National Institutes of Health Stroke Scale.

Characteristic	Out-of-hours (n = 42)	During working hours (n = 17)	p value
Sex (male)	21 (50.0)	11 (64.7)	0.304
Localization
MCA	24 (57.1)	6 (35.3)	0.261
ICA	15 (35.7)	10 (58.8)
Vertebrobacillary artery	3 (7.1)	1 (5.9)
Thrombectomy success	30 (71.4)	16 (94.1)	0.084 b
In-hospital mortality	24 (57.1)	8 (47.1)	0.481
Complication of intracranial bleeding	17 (40.5)	6 (35.3)	0.712
Hypertension	21 (50.0)	11(64.7)	0.304
Diabetes mellitus	13 (31.0)	8 (47.1)	0.242
Coronary artery disease	15 (35.7)	4 (23.5)	0.364
Cerebrovascular disease	13 (31.0)	2 (11.8)	0.190 b
Length of hospital stay (day)	6.5 (2–14)	6 (3–26)	0.569
NIHSS score	17 (15–22)	16 (15–20)	0.423

According to the results of the multivariate logistic regression analysis, intracranial bleeding complication was found to be the strongest independent predictor increasing in-hospital mortality with an odds ratio of 7.501, while MCA localization was found to be the strongest independent predictor decreasing in-hospital mortality with an odds ratio of 0.11. The logistic regression analysis results are given in Table 4 .

Table 4 . Logistic regression analysis results .

CI: confidence interval; NIHSS: National Institutes of Health Stroke Scale; MCA: middle cerebral artery.

Parameters	Univariate				Multivariate
	Odds rate (95% CI)	Beta	p value		Odds rate (95% CI)	Beta	p value
Age	1.023 (0.989–1.059)	0.023	0.194
Length of hospital stay (day)	0.966 (0.933–1.000)	-0.350	0.053		0.949 (0.91–0.99)	-0.53	0.015
Hypertension	2.777 (0.963–8.007)	1.021	0.059
NIHSS	1.121 (0.999–1.259)	0.115	0.052
Thrombolytic therapy	0.233 (0.043–1.270)	-1.455	0.092
Thrombectomy success	3.636 (0.884–14.954)	1.291	0.074
Complication of intracranial bleeding	8.404 (2.349–30.068)	2.129	0.001		7.501 (1.565–35.948)	2.015	0.012
MCA	0.300 (0.103–0.878)	-1.204	0.028		0.110 (0.024–0.509)	-2.206	0.005

Discussion

Ischemic stroke requires rapid diagnosis and treatment. 11 It is important to investigate the factors that affect delays in the thrombectomy procedure, which is among the treatment steps. In our study, no statistically significant difference was found in the in-hospital mortality rate of the patients who presented to the ED out of working hours or who underwent thrombectomy due to stroke compared to the patients who were admitted during working hours. In addition, no statistically significant difference was found between the two groups in the thrombectomy success rate and the intracranial hemorrhage complication rate.

Stroke treatment should be available 24 hours a day in hospitals. 5 , 6 It is also important that thrombectomy treatment for suitable patients can be performed 24 hours a day. However, factors such as the professional team coming from home outside working hours and increased fatigue at night cause an increase in negative side effects. 12 In addition, patients who present during the night hours tend to delay coming to the ED. Despite these negative factors, there was no increase in in-hospital mortality or bleeding complications in our study. There are conflicting results regarding the relationship between stroke and out-of-hours presentation in the literature. Kaaouana et al. 13 showed that out-of-hours treatment did not cause worse outcomes in patients who underwent thrombectomy for anterior circulation. The reason why the out-of-hours effect does not increase in-hospital mortality could be due to preventing the disadvantage of the out-of-hours effect. In our study, although there was no difference in the in-hospital mortality rates, the thrombectomy success rate was higher in the patients who presented during working hours than out-of-hours (out-of-hours: 30 [71.4%]; during working hours: 16 [94.1%]). However, no statistically significant difference was detected due to the small number of patients ( p = 0.084). In the study by Almallouhi et al. 14 better functional results were obtained in the patients who presented during working hours and underwent thrombectomy due to stroke. At the same time, it has been shown in the literature that the weekend effect increases in-hospital mortality in patients with hemorrhagic stroke. 15 , 16 These results show that an out-of-hours impact can potentially have negative consequences but is preventable. Training the stroke team personnel, the availability of advanced neuroimaging, and the 24-hour availability of the relevant specialist minimize the weekend effect. 17

In our study, the number of patients who presented outside working hours was higher than during working hours. In the study by Tschoe et al. 12 the number of patients who underwent thrombectomy due to out-of-hours stroke was also higher than those who applied during working hours. The reason is that the number of out-of-hours more than the working hours. In our study, no statistically significant difference was found in the rate of thrombolytic treatment in the non-survivor group compared to the survivor group. In Yang et al.’s study, the 90-day mortality rate of patients who underwent only thrombectomy was found to be like those who underwent thrombectomy and thrombolytic therapy. 18 In our study, the NIHSS score of the deceased patients was statistically significantly higher than the NIHSS score of the patients who survived, and the rate of successful thrombectomy was statistically significantly higher in the patients who survived than in deceased patients. Two studies also found that a high NIHSS score and unsuccessful recanalization rate were associated with high mortality in stroke patients who underwent thrombectomy. 19 , 20 In our study, the MCA infarct rate in the deceased patients was statistically significantly lower than in the patients who survived. In our study, MCA infarct rate was also an independent predictor of decreasing in-hospital mortality. Mbroh et al. 21 found lower 90-day mortality rates in patients who underwent anterior circulation thrombectomy compared to posterior circulation. The study data are generally compatible with the literature.

Limitations

This study has some limitations. The small number of patients, the single-center study design, and its retrospective nature are the most important limitations. The fact that modified rankin scale data of discharged patients was not collected is a limitation. The fact that the device information on which the thrombectomy procedure is applied was not compared between the groups creates a limitation. The inability to compare the TICI score and Alberta stroke program early CT score between groups creates a limitation.

Conclusions

No statistically significant difference was found in the rate of in-hospital mortality and intracranial bleeding complication ns in patients who presented to the ED out of working hours and underwent thrombectomy due to ischemic stroke compared to those who were admitted during working hours. In addition, a lower successful recanalization rate was found in patients who applied out of working hours compared to those who applied during working hours, but this difference was not statistically significant due to the small number of patients. Intracranial bleeding complication and MCA infarct rate were independent predictors of in-hospital mortality.