Safety and Feasibility of a “Fast‐Track” Monitoring Protocol for Patients Treated With Intravenous Thrombolytic Therapy

Abstract

Background

Our health care systems continue to face significant strain due to chronically taxed intensive care resources. A subgroup of patients following thrombolytic stroke may not require prolonged intensive monitoring, alleviating some burden. Here, we describe the safety, feasibility, and utility of a Fast‐Track Protocol (FTP) for early deescalation of high‐acuity monitoring.

Methods

We compared a prospective cohort of patients on the FTP at our stroke centers from April 2020 to February 2022 to a similar retrospective cohort. Those who presented with a National Institutes of Health Stroke Scale  <10 and without large‐vessel occlusion or flow‐limiting stenosis, intravenous antihypertensive use, and any hemodynamic or respiratory concerns were eligible. Primary outcomes included early neurologic deterioration, defined as worsening of National Institutes of Health Stroke Scale score of ≥4 points at 24 hours, parenchymal hemorrhage, and symptomatic intracranial hemorrhage.

Results

Of 574 patients undergoing thrombolysis, 119 (21%) were eligible for the FTP. A total of 100 (88%) were included for analysis. The median±interquartile range hospitalization was 2.0±1.6 days. None of the 4 cases of early neurologic deterioration were due to hemorrhage. No symptomatic intracranial hemorrhages occurred, and no patients on the FTP were transferred back to the intensive care unit. Median±interquartile range 90‐day modified Rankin scale score was 1±1.

Conclusion

FTP is a safe and feasible strategy to triage intensive care unit patients and decrease unnecessary intensive care unit monitoring. This is important in a postpandemic era as intensive care unit resources continue to fluctuate. Future studies are needed to establish the optimal level of monitoring in patients following thrombolysis.

Nonstandard Abbreviations and Acronyms

END

early neurological decline

FTP

Fast‐Track Protocol

ICH

intracranial hemorrhage

IVT

intravenous thrombolysis

NIHSS

National Institutes of Health Stroke Scale

OPTIMIST

Optimal Post tPA IV Monitoring in Ischemic Stroke

sICH

symptomatic intracerebral hemorrhage

Clinical Perspective

• The current standard of practice for patients who receive intravenous thrombolysis is critical monitoring for the first 24 hours in an intensive care unit to assess for neurological decline.

• The “Fast‐Track Protocol” safely triages lower‐risk patients with a National Institutes of Health Stroke Scale score <10 without large‐vessel occlusions, flow‐limiting stenoses, or hemodynamic instability to lower‐intensity monitoring after 12 hours.

• This is important in a postpandemic era with rapidly expanding use of reperfusion therapies, as intensive care resources are continuously strained.

Patients who receive intravenous thrombolysis (IVT), irrespective of endovascular thrombectomy, are commonly monitored in a high‐acuity setting, such as an intensive care unit (ICU) typically in the United States, for a minimum of 24 hours with frequent assessments of vital signs and neurological examinations. ¹ This ensures that patients receive close observation to detect any change in their neurological condition, which would warrant emergent medical or surgical intervention. However, many patients may not require such high‐resource monitoring, as is the practice with specialized stroke units in Europe. ² , ³ Analyses of these stroke units show that they are more cost effective and reduce resource usage in the acute and long‐term care phases. ⁴ , ⁵ As reperfusion therapies also rapidly expand in the developing world, simplified and cost‐effective postreperfusion strategies are appealing to improve access and quality of stroke care in underresourced settings. The failure to develop stroke units, with reliance on ICUs instead, has posed significant challenges for US health care systems more recently. Specifically, the COVID‐19 pandemic changed the health care landscape, especially in critical care settings, due to the rapid rise in patient volumes, with nearly 100 million Americans suffering infection and >1 million deaths. ⁶ , ⁷ Health systems of care must adapt to the increased use of interventions for stroke treatment and the risk of future waves of infection, which continue to threaten intensive care resources.

Those who experience a National Institutes of Health Stroke Scale (NIHSS) decline of ≥4 points within 24 hours of IVT are defined as having early neurological decline (END). ⁸ Furthermore, if the pathogenesis of END is secondary to an intracranial hemorrhage (ICH), this is defined as a symptomatic ICH (sICH). ⁹ It is reassuring that this feared complication occurs in a minority of patients. ¹⁰ , ¹¹ , ¹² Prior studies have shown that the majority (80%) of sICHs associated with intravenous tissue plasminogen activator occur within the first 12 hours of treatment. ¹³ , ¹⁴ , ¹⁵ Several factors predict END and any ICH, including an untreated large‐vessel occlusion, higher baseline NIHSS score, uncontrolled hypertension, and hyperglycemia. ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ Moreover, the OPTIMIST (Optimal Post tPA IV Monitoring in Ischemic Stroke) safety trial found that all patients in their population with NIHSS score <10 on presentation without initial ICU needs remained clinically stable and could be safely monitored with a lower‐intensity protocol. ²⁰ The ongoing OPTIMIST main trial continues to evaluate whether less intensive monitoring may be indicated in patients with mild neurological deficits.

Given the current landscape and these findings, we implemented a Fast‐Track Protocol (FTP) to permit early deescalation of high‐acuity clinical monitoring in a selected cohort of patients undergoing IVT. We sought to evaluate the protocol's safety, feasibility, and utility on our selected patient population.

Methods

The authors declare that all supporting data are available within the article. After Quality Improvement Review Committee approval, we performed a retrospective analysis of a prospectively maintained database of acute ischemic stroke receiving IVT (either intravenous alteplase or tenecteplase) between April 2020 and February 2022. From April 2020 to March 2021, patients received intravenous alteplase, and after March 24, 2021, all patients received intravenous tenecteplase, consistent with our health systems’ planned change, unrelated to our study. Demographic characteristics, treatment information, and clinical and radiological data were extracted and compared with a similar retrospective database of patients with acute ischemic stroke at our institution who received intravenous alteplase from 2013 to 2019. ¹⁵

Patient Selection

All patients with acute ischemic stroke who received IVT after presenting directly or transferring to 1 of our comprehensive stroke centers or thrombectomy‐capable stroke center from 1 of our referring hospitals during the study period were included for analysis. These patients must have presented within 4.5 hours of last seen well and received IVT on the basis of American Heart Association/American Stroke Association guidelines. All patients were subsequently admitted to the ICU for post‐IVT monitoring and management. In addition, patients were eligible for and enrolled in the FTP on the basis of the following criteria:

• Presenting NIHSS score <10;

• No intravenous antihypertensive medications administered to maintain blood pressure below established guidelines of 180/105;

• Absence of large‐ or medium‐vessel occlusions;

• Eligibility for mechanical thrombectomy on noninvasive angiographic imaging;

• Absence of moderate to severe extracranial internal carotid artery stenosis or intracranial internal carotid artery stenosis;

• Absence of hemodynamic or respiratory instability.

For patients to remain on FTP, they must have maintained an NIHSS score of <10, not received any intravenous antihypertensive medication to maintain blood pressure below established guidelines, and have no additional hemodynamic or respiratory concerns during their ICU stay. If patients experienced significant hemodynamic changes requiring intravenous medications, they were reverted to the standard monitoring protocol. Before transferring out of the ICU to the floor with neurochecks every 4 hours, a vascular neurology fellow, neurocritical care attending, or vascular neurology attending must have reviewed a 12‐hour computed tomography of the head or magnetic resonance imaging to ensure that there was no evidence of hemorrhagic conversion or finding warranting a continued higher level of care (Figure 1A). Twenty‐four hour scans (computed tomography or magnetic resonance imaging) were also performed per standard postthrombolysis protocol. Patients in the historical cohort were previously described ¹⁵ and monitored by American Heart Association guidelines (vital signs and neurological checks every 15 minutes for 2 hours, every 30 minutes for 6 hours, and every hour for 16 hours) (Figure 1B). ²¹

Figure 1.

A, Fast‐Track Protocol. (B) Standard monitoring protocol (top) versus Fast‐Track Protocol (bottom). CTH indicates computed tomography of the head; ICU, intensive care unit; MRI, magnetic resonance imaging; NIHSS, National Institutes of Health Stroke Scale; and VS, Vital Signs.

Baseline Characteristics

Baseline demographic (age, sex, race), clinical (presenting NIHSS, NIHSS at all prespecified intervals within 24 hours of IVT administration, last seen well, risk factor profile including medical history, baseline glucose levels, baseline modified Rankin scale score), and radiographic (pretreatment Alberta Stroke Program Early Computed Tomography Score, presence of large‐vessel occlusion, and post‐IVT computed tomography of the head findings) information were collected and analyzed by a vascular neurologist (K.S., B.J.M., K.A.F.).

Outcomes

Primary outcomes included END (≥4‐point NIHSS score worsening at 24 hours) from any cause, parenchymal hemorrhage (homogeneous hyperdensity occupying <30% or >30% of the infarct zone), and sICH. ⁹

Statistical Analysis

Continuous variables are reported as mean±SD or median with interquartile range (as appropriate), and categorical variables are reported as proportions. Between‐group comparison for continuous variables was performed using Student's t‐test, multiple t‐test, or Mann–Whitney U test, as appropriate, and categorical variables using the χ² test or Fisher exact test, as appropriate. Logistic regression analysis was performed to identify potential independent predictors in subgroups. Significance was defined as P≤0.05. Images were developed using Microsoft Office version 2022 (Microsoft, Redmond, WA). Statistical analysis was performed using IBM SPSS Statistics 28.0 (IBM, Armonk, NY).

Results

A total of 574 patients received IVT from April 2020 through February 2022. Seventy‐nine percent were not eligible for the FTP as they did not meet the criterion of an NIHSS score on presentation of ≥10, presence of a large‐ or medium‐vessel occlusion, presence of a flow‐limiting stenosis, or use of intravenous antihypertensive medications. Of those who received IVT, 119 (21%) were intended for FTP. A total of 100 (17%) of these patients were included for analysis. Of the excluded patients, 14 had FTP criteria violations on admission upon further review, 3 were eligible and intended for FTP but not timely protocolized, and 2 reverted to the standard protocol due to hemodynamic instability (Figure 2). Mean age was 61±14 years, 48% were women, and mean NIHSS±SD on presentation was 4.4±2.4, which was significantly lower than the retrospective population. Median blood glucose levels, platelet counts, and international normalized ratios±SD on presentation were 112±58, 221±86, and 1.0±0.1, respectively. The remaining baseline characteristics are as shown in Table 1, without significant differences between the 2 populations.

Figure 2.

Flowchart of excluded and included patients.

Table 1.

Baseline Patient Characteristics

	Characteristics	FTP patients (n=100)	2013–2019 FTP‐eligible patients (n=315)
Demographics	Age, mean±SD	61±14	64±15
	Female, n (%)	48 (48)	147 (47)
	Mean NIHSS score pre‐IVT±SD	4.4±2.4	5.5±2.0
Risk factors	Hypertension, n (%)	61 (61)	207 (66)
	Diabetes, n (%)	26 (26)	95 (30)
	Hyperlipidemia, n (%)	52 (52)	159 (50)
	Smoking history, n (%)	23 (23)	83 (26)
	Atrial fibrillation, n (%)	5 (5.6)	235 (19)

FTP indicates Fast‐Track Protocol; IVT, intravenous thrombolysis; and NIHSS, National Institutes of Health Stroke Scale.

Among the FTP population, 42% presented directly to our comprehensive stroke centers or thrombectomy‐capable stroke center hospitals, which was significantly higher than our retrospective cohort. This was likely due to the inclusion of our rural thrombectomy‐capable stroke center in our current cohort. Median time from IVT to initiation of FTP was 1 hour and 56 minutes. Only 55% had a final diagnosis of stroke. Of the remaining, 31% had a stroke mimic (migraine or conversion disorder), 10% had alternate pathogeneses for neurologic deficits (encephalopathy, metabolic/toxic causes, or peripheral nerve disorder), and 4% were secondary to seizure. Median±interquartile range length of hospitalization was 2.0±1.6 days. Discharge disposition was primarily to home (74%), followed by inpatient rehabilitation (23%) and skilled nursing facility (3%). No patients expired in the hospital in the FTP group.

Regarding our primary outcomes, no sICHs occurred, and none of the patients on FTP required transfer back to the ICU or escalation of care due to clinical deterioration after transfer out. Four patients experienced END, defined as an increase in NIHSS score of ≥4 points from presentation within the first 24 hours. Three cases of END had NIHSS difference of ≥4 immediately upon transfer to our comprehensive stroke centers or from emergency department to ICU, likely in part representing interinstitutional or interrater variability. One case was due to symptomatic worsening of stroke mimics, including conversion and migraine disorder without acute infarcts found on magnetic resonance imaging. One patient reverted to the standard postthrombolytic protocol due to stuttering lacunar evolution without hemodynamic instability or hemorrhagic transformation. None were due to ICH for any reason. Median±interquartile range 90‐day modified Rankin scale score was 1±1. There was no significant difference in END, ICH, or median hospitalization length compared with a historical cohort that received standard monitoring, including hourly neurological examinations, for the full 24 hours (Table 2). Subgroup analysis excluding patients with stroke mimic found no differences in the specified safety outcomes (Table 3).

Table 2.

Safety Outcomes

Safety outcomes	FTP (n=100)	2013–2019 FTP‐eligible patients (n=315)	P value
Home, n (%)	75 (75)	233 (74)	0.83
Inpatient rehabilitation, n (%)	22 (22)	67 (31)
Skilled Nursing Facility, n (%)	3 (3)	13 (4)
Expired, n (%)	0 (0)	2 (0.6)
END, n (%)	4 (4)	9 (3)	0.56
sICH, n (%)	0 (0)	1 (0.3)	0.57
Median hospitalization length, d (IQR)	2.0±1.6	2.2±2.1	0.78

END indicates early neurological decline; FTP, Fast‐Track Protocol; IQR, interquartile range; and sICH, symptomatic intracranial hemorrhage.

Table 3.

Subgroup Analysis of Stroke Versus Mimic Patients Enrolled in FTP

Safety outcomes by subgroups	FTP – Ischemic Stroke (n=69), n (%)	FTP – Stroke mimics (n=31), n (%)	Adjusted OR (95% CI)
Home	48 (70)	27 (87)
Inpatient rehabilitation	20 (29)	2 (6.5)	3.43 (0.66–17.83)
Skilled Nursing Facility	1 (1.4)	2 (6.5)	0.18 (0.01–2.33)
END	2 (2.9)	2 (6.5)	0.51 (0.07–3.86)
sICH	0 (0)	0 (0)
Median hospitalization length, d (IQR)	2.2±2.3	1.5±1.4	1.25 (0.85–1.84)

END indicates early neurological decline; FTP, Fast‐Track Protocol; IQR, interquartile range; OR, odds ratio; and sICH, symptomatic intracranial hemorrhage.

Discussion

FTP is a safe method of transferring patients following thrombolysis out of the ICU who are unlikely to deteriorate and require additional monitoring. None of our patients experienced a primary outcome of ICH for any reason, most importantly sICH. Selecting low‐risk patients with low initial NIHSS score without flow‐limiting stenoses, large‐vessel occlusions, and hemodynamic changes contributed to the protocol's overall safety. The patients’ low NIHSS score on presentation and absence of large‐vessel occlusions and hemodynamic instability also likely selected for a higher rate of stroke mimics (31%), lending to the favorable safety outcomes of FTP. The subgroup analysis excluding stroke mimics in our population shows their minimal impact, which may optimize resources on the basis of these parameters in the future.

The cases in which END occurred were low risk and did not pose significant safety concerns inherent to FTP. Three of the 4 instances of END occurred in stroke mimics, and the fourth eventually improved after thrombolysis to the point of discharging home. The 2 patients who reverted from FTP to the standard monitoring protocol due to hemodynamic instability were not included in the analysis due to the use of intravenous medications. One patient had continued evolution of their infarct, but neither suffered sICH.

Previous studies of stroke systems of care show that >80% of those with END occur within the first 6 hours from IVT, providing further proof of the safety of transferring patients out of the ICU sooner. ¹⁵ The guidelines to ensure adequate care of critically ill neurology patients during a pandemic highlight the need for alternate strategies beyond currently routine practices. ²² , ²³

Potential solutions to acute shortages include increasing ICU capacity by discharging suitable patients earlier to lower‐intensity units. The COVID‐19 pandemic has led to the development of new guidelines for triage with strategies such as FTP to ensure that ICU and stroke unit resources are reserved for those who will benefit the most and survive with a good quality of life. ⁷ , ²² , ²³ FTP's selection for patients with small‐vessel ischemic strokes or stroke mimics could also support transferring these lower‐risk patients out of the ICU earlier in the future.

Despite reduced hospitalizations and use of critical care services, ²⁴ , ²⁵ there was no significant increase in mortality rates after the onset of the COVID‐19 pandemic among critically ill neurology patients who needed ICU care. ²⁶ This may indicate that ICU care was likely not impacted at most centers. Previous data have shown that among patients hospitalized with these diagnoses but not receiving critical care, there was a slight increase in mortality rates during the pandemic compared with previous years, possibly due to reduced ICU bed availability, leading to patients who would ordinarily have been cared for in the ICU being managed in non–critical care settings and by providers who lack specific expertise. ²⁷ FTP allows for greater bed availability for the critically ill. While not significant, FTP did show a trend toward shortening the overall length of stay, which could assist in decompressing hospitals and reduce associated hospitalization costs.

While a randomized clinical trial may more specifically address the merits of FTP, a more practical and cost‐effective approach may be through assessing quality outcomes before and after implementation of FTP. This would allow for regional practices to evolve and not be restricted by the standardization of randomized clinical trials. Additional considerations to further expand on FTP would be evaluating outcomes at even shorter thresholds, such as 6 hours from IVT, on the basis of prior studies, ¹⁵ or in those with large‐ or medium‐vessel occlusions, who otherwise meet current FTP criteria.

Strengths of this study include its prospective nature, which provides stronger support for earlier deescalation of monitoring in these lower‐risk patients. However, there was a notable number of excluded protocol violations on enrollment, primarily due to NIHSS score of >9 on presentation. Other violations included the presence of a flow‐limiting stenosis and the use of intravenous antihypertensive medications before transfer. Of note, no instances of END occurred in those excluded due to protocol violations. Such enrollment errors should be considered and expected when new protocols like FTP are implemented into long‐standing institutional practices, even at experienced centers like ours. The majority of subjects were also transferred from referring facilities after receiving IVT. This led to a longer median period from IVT to FTP initiation and may have resulted in the possibility of excluding a subset of patients who became symptomatic before initiating FTP in our cohort.

Conclusion

The FTP for selected patients with stroke after IVT is a safe and feasible strategy to triage ICU patients for transfer and decrease unnecessarily prolonged ICU monitoring. This strategy is particularly relevant in a postpandemic era, as the need for intensive resources will continue to fluctuate for the foreseeable future. Triaging lower‐risk patients to lower‐intensity stroke units with the FTP is a forthcoming consideration given its safety and feasibility. Future randomized controlled studies may further clarify the optimal level of monitoring for patients following thrombolysis.

Sources of Funding

The study received no funding.

Disclosures

Ashutosh P. Jadhav is the Editor in Chief for Stroke: Vascular and Interventional Neurology and was not involved in the handling or final disposition of this article. Disclosures provided by Ashutosh P. Jadhav in compliance with the American Heart Association's annual Journal Editor Disclosure Questionnaire are available at https://www.ahajournals.org/editor‐coi‐disclosures.