Shorter Intensive Care Unit Stay (12 Hours) Post Thrombolysis Is Safe and Reduces Length of Stay for Minor Stroke Patients

Abstract

The current standard of practice for patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator (tPA) requires critical monitoring for 24-hours post-treatment due to the risk of symptomatic intracranial hemorrhage (sICH). This is a costly and resource intensive practice. In this study, we evaluated the safety and efficacy of this standard 24-hour ICU monitoring period compared with a shorter 12-hour ICU monitoring period for minor stroke patients (NIHSS 0-5) treated with tPA only. Stroke mimics and those who underwent thrombectomy were excluded. The primary outcome was length of hospital stay. Secondary outcome measures included sICH, deep venous thrombosis (DVT), pulmonary embolism (PE), pneumonia, favorable discharge to home or acute rehabilitation, readmission within 30 days, and favorable functional outcome defined as modified Rankin scale (mRS) of 0-2 at 90 days. Of the 122 patients identified, 77 were in the 24-hour protocol and 45 were in 12-hour protocol. There was significant difference in length of hospital stay for the 24-hour ICU protocol (2.8 days) compared with the 12-hour ICU protocol (1.8 days) (P < 0.001). Although not statistically significant, the 12-hour group had favorable rates of sICH, 30-day readmission rates, favorable discharge disposition and favorable functional outcome. Rates of DVT, PE and aspiration pneumonia were identical between the groups. Compared with 24-hour ICU monitoring, 12-hour ICU monitoring after thrombolysis for minor acute ischemic stroke was not associated with any increase in adverse outcomes. A randomized trial is needed to verify these findings.

Introduction

The administration of tissue plasminogen activator (tPA) for the treatment of acute ischemic stroke is an established standard of care. Current class I evidence recommendations from the American Heart Association (AHA) are to administer tPA as soon as possible in eligible patients up to a limit of 4.5 hours after the last known well time. ¹ Following its administration, the standard of practice is then to admit these patients to an intensive care unit for 24 hours. This recommendation stems from the necessity for frequent neurological checks and vital sign monitoring due to the increased risk of bleeding. For many institutions, it is difficult to provide this high level of care and attention in a setting outside of the ICU due to the lack of available resources. Data regarding the optimal time for monitoring in the ICU, however, is lacking. Prior studies have evaluated ways to determine which patients will require ICU care, incorporating infarct volumes to determine risk of intracranial hemorrhage. However, safety of care in a general medical floor for select group of patients has not been studied. ² Studies have also shown that the highest risk of ICH after tPA is within the first 12 hours and suggest that longer monitoring in an intensive care setting may be unnecessary for some patients. ³ Deterioration in patients with no critical care needs after 12 hours in patients with low NIHSS is rare. ⁴ Because of the COVID-19 pandemic, the need for ICU capacity grew exponentially and the resources available within our ICUs dwindled. Our approach of early transfer out of ICU for post-tPA patients enabled us to optimize available resources within our ICUs. This study was performed to evaluate the safety and outcomes in this shift in practice and better prepare us for future potential pandemics.

Methods

This was a single center study including patients admitted at Spectrum Health in Grand Rapids, MI. We received IRB approval and conducted a retrospective review of data collected within our stroke registry. This study was conducted between 1/1/2017 and 3/30/2019. Inclusion criteria involved patients age >18 years with a diagnosis of ischemic stroke based on clinical and MRI findings that received tPA only and who had an initial National Institute of Health Stroke Scale (NIHSS) 0-5 without additional ICU needs (ex. intravenous antihypertensives). Stroke mimics and those who underwent thrombectomy were excluded. We evaluated patients who were admitted to the ICU prior to 05/15/2018 for the standard of practice time of 24 hours and compared them with a group of patients admitted to the ICU with a 12-hour protocol after that date. Post tPA neuro check protocols were followed for these patients regardless of location. The primary outcome was length of hospital stay. Secondary outcome measures included sICH, deep venous thrombosis (DVT), pulmonary embolism (PE), pneumonia, favorable discharge to home or acute rehabilitation, readmission within 30 days, and favorable functional outcome defined as modified Rankin scale (mRS) 0-2 at 90 days. Statistical analysis of quantitative variables used independent samples T-Tests and Mann-Whitney U tests, while Chi-Squared test and Fisher’s exact test were used to analyze all categorical variables. A 0.05 level of significance was used in the analysis.

Results

A total of 122 patients with an initial mRS between 0 and 5 who had received tPA and were diagnosed with acute ischemic stroke were included in this study. They were divided into 2 groups, a 24-hour ICU monitoring group and a 12-hour ICU monitoring group with 77 and 45 individuals, respectively. Baseline demographics, primary, and secondary outcomes are outlined in Table 1. The average age was 67.8 years old overall, 67.2 in the 24-hour ICU group, and 68.8 in the 12-hour ICU group. 56 individuals (45.9%) were female with 36 in the 24-hour group and 20 in the 12-hour group. Median admission NIHSS was 3 overall, among both groups. Of these patients, a total of 4.1% experienced symptomatic ICH (p = 0.65), 5.2% in the 24-hour group and 2.2% in the 12-hour group. No patients in either group had complications related to deep venous thrombosis or pulmonary embolism. Aspiration pneumonia was a complication in one patient in each group (p = 1.00). In the 24-hour group, 70 patients (90.1%) had a favorable discharge disposition, meaning discharge home or to acute rehab, compared to 44 patients (97.8%) in the 12-hour group (p = 0.26). 67 (87%) patients in the 24-hour group had a favorable functional outcome, mRS between 0 and 2, versus 42 (93.3%) in the 12-hour group (p = 0.37). A noticeable difference was seen when comparing the 30-day readmission between the 2 groups. The 24-hour group saw 12 patients (15.6%) readmitted within 30 days while the 12-hour group saw just 2 (4.4%) (p = 0.06). The final aspect of evaluation, which did identify a statistically significant difference was length of stay. In the 24-hour group, the median length of stay was 2.8 days compared to the 12-hour group which saw a median of 1.8 days (p < 0.001).

Table 1.

Baseline Demographics, Primary and Secondary Outcomes of the Study Cohorts.

	Overall (N = 122)	At least 24-hour, neuro ICU stay (N = 77)	12-hour, neuro ICU stay (N = 45)	P value
Age years, mean + SD	67.8 ± 15.1	67.2 ± 15.9	68.8 ± 13.7	0.56
Female, n (%)	56 (45.9)	36 (46.8)	20 (44.4)	0.81
Admission NIHSS, median [IQR]	3.0 [3.0]	3.0 [3.0]	3.0 [1.0]	0.69
Length of Stay (days), median [IQR]	2.1 [1.3]	2.8 [1.7]	1.8 [1.0]	< 0.001
Favorable Discharge Outcome, n (%)	114 (93.4)	70 (90.1)	44 (97.8)	0.26
Favorable Functional Outcome, n %	109 (89.3)	67 (87.0)	42 (93.3)	0.37
30-day Readmission, n (%)	14 (11.5)	12 (15.6)	2 (4.4)	0.06
Symptomatic ICH, n (%)	5 (4.1)	4 (5.2)	1 (2.2)	0.65
Deep Venous Thrombosis, n (%)	0 (0.0)	0 (0.0)	0 (0.0)	NA
Pulmonary Embolism, n (%)	0 (0.0)	0 (0.0)	0 (0.0)	NA
Aspiration Pneumonia, n (%)	2 (1.6)	1 (1.3)	1 (2.2)	1.00

Note. Numerical values are expressed as mean ± standard deviation or median [IQR], depending on assumptions being met for parametric test. Categorical values are expressed as frequency (percent). Admission NIHSS was normally distributed. Favorable discharge disposition = home or acute rehab; favorable functional outcome = modified Rankin scale between 0 and 2.

Discussion

Treating patients for ischemic stroke in the acute setting is a practice that has been standardized to identify the best candidates for treatment in order to optimize outcomes and reduce the risk of adverse events. Several studies have been performed to inspect different aspects of what qualifies a patient for treatment, specifically in regard to the administration of tPA, however, studies to better standardize care following its administration are lacking. This study suggests that there may be a subgroup of patients who do not require the standard monitoring of 24-hours in an ICU without compromising safety. When comparing patients who were transferred out of the ICU after 12-hours as opposed to the standard 24-hours, we saw a statistically significant difference in length of hospital stay favoring the 12-hour group. We also noted lower 30-day readmissions, higher favorable functional outcomes, and favorable discharge dispositions, though these were not statistically significant. There was also not a statistically significant difference in sICH between the 2 groups.

Prior studies have shown that the risk of symptomatic intracranial hemorrhage in patients after receiving tPA is roughly 6%. Several factors have been used to identify those who may be at an increased risk including race, systolic blood pressure, and NIHSS >10.^5,6 It has also been suggested that MRI may be used post-tPA administration to assess risk with one study showing that only a small portion of patients with a negative diffusion weighted imaging on MRI required critical care. ⁷ In order to observe for signs of possible hemorrhage, close monitoring with blood pressure and neurological checks progressively spaced from 15 minutes, to 30 minutes, to every 1 hour following the administration of tPA is very important. ⁸ If new deficits are noted, a stat CT head is obtained and if intracranial hemorrhage is noted, the current recommendations for reversal include the administration of cryoprecipitate and, depending on the patient, possible antifibrinolytics, vitamin K, or prothrombin complex concentrates. Data regarding reversal with asymptomatic intracranial hemorrhage seen on 24-hour post tPA head CT is limited. ⁹ In patients who have remained stable during this initial 12-hour period with low NIHSS and no critical care needs, complications in the 12 to 24 hour post-tPA time frame are rare.

Prior to the COVID-19 pandemic, the current 24-hour guideline was largely followed at our institution with exceptions usually related to limitations on the number of available beds in the ICU. Patients with minor acute ischemic stroke (NIHSS 0-5) were able to be transferred to a neurological floor to continue monitoring outside the ICU setting after 12 hours if they had remained stable throughout that time. The COVID-19 pandemic, however placed incredible amounts of stress on our health systems and our ICUs. Bed space and resources have become increasingly valuable and uncovering ways to safely help decompress the ICU and increase available resources is crucial in ensuring the care provided to critical patients as well as our post-tPA patients is optimized.

Our study suggests that reducing ICU length of stay in a specific subset of stroke patients is safe, though our data is limited by the small sample size as well as the lack of baseline characteristics described in these 2 groups. This would be useful in future studies to determine if there are other confounding factors that influence the ability to safely transfer these patients early or that may have lead to a higher rate of readmission in the 24-hour group as observed in this study. Further studies should be performed to better assess safety data and explore these trends in greater detail.