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Acute Stroke Management
Acute Stroke Management

9. Inpatient Prevention and Management of Complications following Stroke

2022 update

Recommendations and/or Clinical Considerations
9.0 Recommendation

Evidence-based investigations and management strategies should be implemented for all hospitalized stroke and transient ischemic attack (TIA) patients to optimize recovery, avoid complications, prevent stroke recurrence, and provide palliative care when required [Strong recommendation; Moderate quality of evidence].

  1. During acute inpatient care, patients with stroke should undergo appropriate investigations to determine stroke mechanism and guide stroke prevention and management decisions [Strong recommendation; Moderate quality of evidence]. 
  2. Patients should be evaluated and treatment plans initiated for secondary prevention of vascular risk factors, including hypertension, diabetes, dyslipidemia and smoking cessation [Strong recommendation; Moderate quality of evidence]. Refer to CSBPR Secondary Prevention of Stroke module for additional information.
  3. Individualized care plans should address nutrition, oral care, mobilization, and incontinence, and reduce the risk of complications such as urinary tract infection (UTI), aspiration pneumonia, and venous thromboembolism [Strong recommendation; Moderate quality of evidence].
  4. Transition planning should begin as a component of the initial admission assessment and continue throughout hospitalization as part of ongoing care of patients with acute stroke [Strong recommendation; Moderate quality of evidence]. Refer to CSBPR Transitions and Community Participation Following Stroke module Section 3 for additional information.
  5. All patients, family members, and informal caregivers should receive timely and comprehensive information, education, and skills training about stroke from interdisciplinary team members [Strong recommendation; Moderate quality of evidence]. Refer to CSBPR Transitions and Community Participation Following Stroke module Sections 1 and 2 for additional information.
  6. Patients should undergo an initial screening for depression, including screening for a history of depression [Strong recommendation; Moderate quality of evidence]. Refer to CSBPR Mood, Cognition and Fatigue Section 1 for additional information. 
  7. Stroke assessments should include evaluation of risk factors for depression, particularly a history of depression [Strong recommendation; Low quality of evidence]. 
  8. Patients should undergo an initial screening for vascular cognitive impairment when indicated [Strong recommendation; Moderate quality of evidence]. Refer to CSBPR Mood, Cognition and Fatigue Section 2 for additional information.
9.1 Cardiovascular Investigations
  1. Patients with suspected ischemic stroke or TIA should have a 12-lead electrocardiogram (ECG) to assess for atrial fibrillation, concurrent myocardial infarction, or structural heart disease (e.g., left ventricular hypertrophy) as potential causes of or risk factors for stroke [Strong recommendation; Moderate quality of evidence]. 
  2. For patients being investigated for an acute embolic ischemic stroke or TIA, ECG monitoring for 24 hours or more is recommended as part of the initial stroke work-up to detect paroxysmal atrial fibrillation in patients who would be potential candidates for anticoagulant therapy [Strong recommendation; High quality of evidence]. 
  3. For patients being investigated for an acute embolic ischemic stroke or TIA of undetermined source whose initial short-term ECG monitoring does not reveal atrial fibrillation but a cardioembolic mechanism is suspected, prolonged ECG monitoring for at least 2 weeks is recommended, as soon as practically possible, to improve detection of paroxysmal atrial fibrillation in selected patients ≥55 years who are not already receiving anticoagulant therapy but would be potential anticoagulant candidates [Strong recommendation; High quality of evidence]. Refer to CSBPR Secondary Prevention of Stroke module for additional information.
  4. Routine echocardiography is not recommended for all patients with stroke. Echocardiography should be considered for patients with an embolic ischemic stroke or TIA of undetermined source, or when a cardioembolic etiology or paradoxical embolism is suspected [Strong recommendation; Moderate quality of evidence]. 
  5. For patients ≤60 years who are being investigated for an embolic ischemic stroke or TIA of undetermined source, echocardiography with saline bubble study is recommended for detection of a patent foramen ovale (PFO) if it may change patient management (i.e., in patients who would be potential candidates for PFO closure or anticoagulant therapy if a PFO were detected) [Strong recommendation; Moderate quality of evidence]. 
    1. Contrast-enhanced (agitated saline) transesophageal echocardiography or transcranial Doppler has greater sensitivity than transthoracic echocardiography for detection of right-to-left cardiac and extra-cardiac shunts and should be conducted when available [Strong recommendation; Moderate quality of evidence].
9.2 Venous Thromboembolism Prophylaxis
  1. All patients with stroke should be assessed for their risk of developing venous thromboembolism (deep vein thrombosis [DVT] and pulmonary embolism [PE]). Patients at high risk include those who are unable to move one or both lower limbs; those who are unable to mobilize independently; those with a previous history of venous thromboembolism, those who are dehydrated; and those with comorbidities such as active or suspected malignancy [Strong recommendation; Moderate quality of evidence].
  2. Patients at high risk of venous thromboembolism should be started on thigh-high intermittent pneumatic compression (IPC) devices or pharmacological venous thromboembolism prophylaxis (e.g., low molecular weight heparin [LMWH] or unfractionated heparin [UFH]) beginning on day of admission if there is no contraindication (e.g., systemic or intracranial hemorrhage) [Strong recommendation; High quality of evidence]. At present, there is no direct evidence to suggest the superiority of one approach over the other. 
    1. Intermittent pneumatic compression devices should be discontinued when the patient becomes independently mobile, at discharge from hospital, if the patient develops adverse effects, or by 30 days, whichever comes first [Strong recommendation; Moderate quality of evidence].
  3. Graduated compression stockings are not recommended for deep vein thrombosis prevention [Strong recommendation; High quality of evidence]. 
  4. For patients with stroke admitted to hospital and who are immobile for >30 days, the use of ongoing venous thromboembolism prophylaxis (e.g., with pharmacological venous thromboembolism prophylaxis) is recommended [Strong recommendation; Low quality of evidence].
  5. If intermittent pneumatic compression is considered after the first 24 hours of admission, venous leg Doppler studies should be considered [Strong recommendation; Low quality of evidence].

Section 9.2 Clinical Consideration:

  1. Use of LMWH or UFH should be weighed against the potential risk for intracerebral hemorrhage for each individual patient.
9.3 Temperature Management
  1. Temperature should be monitored as part of vital sign assessments; ideally every 4 hours for the first 48 hours, and then as per ward routine or based on clinical judgment [Strong recommendation; Moderate quality of evidence].
  2. For temperature >37.5 Celsius, frequency of monitoring should be increased, temperature-reducing measures should be initiated, causes of possible infection such as pneumonia or UTI should be investigated, and antipyretic and antimicrobial therapy should be initiated as required [Strong recommendation; Moderate quality of evidence].
9.4 Mobilization

Definition: Mobilization is the process of getting a patient to move in the bed, sit up, stand, and eventually walk.

  1. All patients admitted to hospital with acute stroke should have an initial assessment, conducted by rehabilitation professionals, as soon as possible after admission and using a standardized tool [Strong recommendation; Moderate quality of evidence].
  2. Initial screening and assessment should be commenced as early as possible, and ideally within 48 hours of admission by rehabilitation professionals who are in direct contact with the patient [Strong recommendation; Moderate quality of evidence]. Refer to the CSBPR Rehabilitation and Recovery Following Stroke module for additional recommendations on mobilization following an acute stroke.
  3. Rehabilitation therapy should begin as early as possible once the patient is determined to be medically able to participate in active rehabilitation [Strong recommendation; High quality of evidence].
  4. Early prolonged mobilization of patients within the first 24 - 48 hours after a stroke, especially a severe stroke, is not recommended [Strong recommendation; High quality of evidence].
  5. Earlier mobilization may be reasonable for some patients with acute stroke (e.g., people with milder strokes or TIA) but caution is advised and clinical judgement should be used [Conditional recommendation; Low quality of evidence].

Note: Contraindications to early mobilization include, but are not restricted to, patients who have had an arterial puncture for an interventional procedure; or patients who have unstable medical conditions, low oxygen saturation, and/or lower limb fracture or injury. 

Refer to CSBPR Rehabilitation and Recovery Following Stroke module for additional recommendations on mobilization following an acute stroke.

9.5 Seizure Management
  1. New-onset seizures in admitted patients with acute stroke should be treated using appropriate short-acting medications (e.g., lorazepam IV) if the seizures are not self-limiting [Strong recommendation; Moderate quality of evidence]. 
    1. Patients who have an immediate post-stroke seizure should be monitored for recurrent seizure activity [Strong recommendation; Low quality of evidence].
    2. Recurrent seizures in patients with ischemic stroke should be treated as per local treatment recommendations for seizures in other neurological conditions [Strong recommendation; Moderate quality of evidence]. 
  2. A single, self-limiting seizure occurring at the onset or within 24 hours after an ischemic stroke is considered an “immediate” post-stroke seizure and does not require long-term anticonvulsant medications [Conditional recommendation; Low quality of evidence].
  3. Prophylactic use of anticonvulsant medications in patients with ischemic stroke is not recommended [Strong recommendation; Moderate quality of evidence]
  4. Continuous or repeat electroencephalogram monitoring in patients with a stroke and unexplained reduced level of consciousness should be considered [Conditional recommendation; Moderate quality of evidence].
9.6 Nutrition and Dysphagia
  1. Patients should be screened for swallowing impairment before any oral intake, including medications, food, and liquid, by an appropriately trained professional using a valid screening tool [Strong recommendation; Moderate quality of evidence]. Refer to Appendix 3: Table 5 Canadian Stroke Best Practices: Selection of Validated Swallowing Screening Tools
  2. The swallowing, nutritional and hydration status of patients with stroke should be screened as early as possible, ideally on the day of admission, using validated screening tools [Strong recommendation; Moderate quality of evidence].
  3. Abnormal results from the initial or ongoing swallowing screens should trigger a prompt referral to a speech-language pathologist, occupational therapist, dietitian, and/or other trained dysphagia clinicians for more detailed assessment and management of swallowing, feeding, nutritional, and hydration status [Strong recommendation; Moderate quality of evidence].
    1. An individualized management plan should be developed to address therapy for dysphagia, dietary needs, and specialized nutrition plans [Strong recommendation; Moderate quality of evidence].
  4. For patients who cannot safely swallow or meet their nutrient and fluid needs orally, enteral nutrition (e.g., nasogastric tube feeding) should be considered in consultation with the patient, family, or substitute decision-maker, and the interdisciplinary team as early as possible after admission, usually within the first three days of admission [Strong recommendation; Moderate quality of evidence]. Refer to CSBPR Rehabilitation and Recovery Following Stroke module section 7 for additional information on dysphagia screening, assessment, and management. 
    1. Nasogastric feeding tubes should be replaced by gastric-jejunum tube (GJ-tube) if the patient requires a prolonged period of enteral feeding [Strong recommendation; Moderate quality of evidence]
9.7 Continence
  1. Indwelling catheters should be used cautiously due to the risk of UTIs [Strong recommendation; High quality of evidence]. 
    1. If used, indwelling catheters should be assessed daily and removed as soon as possible [Strong recommendation; High quality of evidence]. 
    2. Peri care and infection prevention strategies should be implemented to minimize risk of infection [Strong recommendation; Moderate quality of evidence]. Refer to Section 4.6(iii) for additional information.
  2. Patients with stroke should be screened for urinary incontinence and retention, with or without overflow; fecal incontinence; and constipation [Strong recommendation; Moderate quality of evidence].
  3. The use of a portable ultrasound machine is recommended as the preferred non-invasive method to assess post-void residual [Conditional recommendation; Low quality of evidence].
  4. Patients with stroke with urinary incontinence should be assessed by trained personnel using a structured functional assessment to determine cause and develop an individualized management plan [Strong recommendation; Moderate quality of evidence].
  5. Patients with stroke with urinary incontinence should have a bladder-training program implemented [Conditional recommendation; Low quality of evidence].
    1. The bladder training program should include timed and prompted toileting on a consistent schedule [Conditional recommendation; Moderate quality of evidence].
    2. Appropriate intermittent catheterization schedules should be established based on amount of post-void residual [Conditional recommendation; Moderate quality of evidence].
  6. Patients with stroke with persistent constipation or bowel incontinence should have a bowel management program implemented [Strong recommendation; Moderate quality of evidence].
9.8 Oral Care
  1. At or soon after admission, patients with stroke should have an oral/dental assessment, including screening for signs of dental disease, level of oral care, and appliances [Strong recommendation; Low quality of evidence].
  2. For patients with stroke wearing a full or partial denture it should be determined if they have the neuromotor skills to safely wear and use the appliance(s) [Strong recommendation; Low quality of evidence].
  3. For patients where there are concerns about oral hygiene and/or appliances, a referral to a dentist for consultation and management should be made as soon as possible [Strong recommendation; Moderate quality of evidence].
  4. Patients with stroke should receive oral care consistent with the Canadian Dental Association recommendations, and the oral care should address areas such as frequency of oral care (ideally after meals and before bedtime); types of oral care products (toothpaste, floss, mouthwash); and management for patients with dysphagia [Strong recommendation; Moderate quality of evidence].
Rationale +-

Medical complications are common following acute stroke and are associated with prolonged lengths of stay and increased costs compared to other causes of hospitalization in Canada. Patients with acute stroke are at risk for complications such as venous thromboembolism, pyrexia, and seizures, among others during the early phase of recovery. The priorities for inpatient care are management of stroke sequelae to optimize recovery, prevention of post-stroke complications that may interfere with recovery, and prevention of stroke recurrence. 

People with lived experience valued the person-centred care approach and found it helpful to know why something was happening. They described that at times it can feel as though things are being done to you and shared that having an explanation of what was happening helped them feel more engaged and part of the team. They also emphasized the importance of healthcare providers repeating information as needed for the patient and their family and/or caregivers. Fear and stress from having recently gone through the shock of having a stroke can make it more difficult to absorb information, and so repeating the information can help the person process and understand. They suggested that a one-page handout of “what’s important over the next few days” might be a helpful tool for people with stroke and their families while in acute care. This document could explain what is important in the early days and why; this would also help them absorb and remember the information, and help ensure consistent information is shared by all of the healthcare providers involved in the patient’s care.

System Implications +-

To ensure people experiencing a stroke receive timely stroke assessments, interventions and management, interdisciplinary teams need to have the infrastructure and resources required. These may include the following components established at a systems level.

  1. Standardized evidence-based protocols instituted for optimal inpatient care of all patients with acute stroke, regardless of where they are treated in the healthcare facility (stroke unit or other ward), and across the regional stroke system of care.
  2. Ongoing professional development and educational opportunities for all healthcare professionals who care for patients with acute stroke.
  3. Referral systems to ensure rapid access to specialty care such as dentistry and hematology.
Performance Measures +-

System Indicators:

  1. Median length of stay, stratified by stroke type, during acute phase of care for all patients with stroke admitted to hospital (core).
  2. Proportion of patients with stroke who experience prolonged length of stay beyond expected length of stay as a result of experiencing one or more complications.

Process Indicators:

  1. Median length of stay, stratified by stroke type and complication type, during acute phase of care for all patients with stroke admitted to hospital who experience one or more complications during hospitalization (core). 

Patient-oriented outcome and experience indicators:

  1. Proportion of patients admitted to hospital with a diagnosis of acute stroke who experience one or more complications during hospitalization (e.g., deep venous thrombosis, pulmonary embolus, secondary cerebral hemorrhage, gastrointestinal bleeding, pressure ulcers, UTI, pneumonia, seizures, or convulsions) during inpatient stay.
  2. Quality of life rating at 30 and 90 days for people who experience complications during acute inpatient admission following acute stroke, using a validated tool.

Measurement Notes

Note, refer to the Quality of Stroke Care in Canada Key Quality Indicators and Stroke Case Definitions 7th Edition document for more detailed information. www.strokebestpractices.ca

  1. Risk adjustment to account for other comorbidities, age, and sex.
  2. Length of stay analysis should be stratified by presence or absence of in-hospital complications to look for the impact of a complication on length of stay. 
  3. Patient and family experience surveys should be in place to monitor care quality during inpatient stroke admissions.
Implementation Resources and Knowledge Transfer Tools +-

Resources and tools listed below that are external to Heart & Stroke and the Canadian Stroke Best Practice Recommendations may be useful resources for stroke care. However, their inclusion is not an actual or implied endorsement by the Canadian Stroke Best Practices writing group. The reader is encouraged to review these resources and tools critically and implement them into practice at their discretion.

Healthcare Provider Information

Information for people with lived experience of stroke, including family, friends and caregivers

Summary of the Evidence +-

Evidence Table and Reference List

Sex and Gender Considerations Reference List

Medical complications are relatively common following stroke and are associated with increased lengths of stay and higher cost. Appropriate investigations and management strategies should be implemented for all hospitalized patients to avoid complications, prevent stroke recurrence, and improve the odds of a good recovery. Estimates of the percentage of patients who experience at least one medical complication during hospitalization vary widely from 25% (Ingeman et al., 2011) to 85% (Langhorne et al., 2000). Some of the most commonly cited complications include UTIs, fever, pneumonia, and DVT (Otite et al., 2017; Indredavik et al., 2008; Roth et al., 2001).

Cardiovascular Investigations

Detecting atrial fibrillation (AF) after a stroke or TIA is important since it is a major risk factor for subsequent stroke and, once identified, can be effectively treated. However, AF is under-diagnosed because it is frequently paroxysmal and asymptomatic. Additionally, although many abnormalities can be detected within the first few days of monitoring, prolonged screening may be required to detect others. In the Systematic MONitoring for Detection of Atrial Fibrillation in patients with acute Ischaemic Stroke (MonDAFIS) Trial, Haeusler et al. (2021) randomized 3,465 patients with no history of AF, admitted to 38 stroke units with an acute stroke or TIA to receive usual diagnostic procedures for AF detection, which included a baseline 12-lead ECG on admission and at least 24 hours of ECG monitoring (control group) or additional Holter-ECG recording for up to 7 days in hospital (intervention group). At 12 months, there was no significant difference between groups in the number of patients on oral anticoagulants (13.7% vs. 11.8%, OR=1·2, 95% CI 0·9–1·5), although AF was newly detected in significantly more patients in hospital in the intervention group (5.8% vs. 4.0%, HR=1·4, 95% CI 1·0–2·0). The Finding Atrial Fibrillation in Stroke – Evaluation of Enhanced and Prolonged Holter Monitoring FIND-AF trial, (Wachter et al,. 2017) recruited 398 patients, admitted with acute ischemic stroke, within 7 days of symptom onset, in sinus rhythm at admission, and without a history of AF. Patients were randomized to receive prolonged Holter ECG monitoring for 10 days, starting in the first week post-stroke, and repeated at 3 and 6 months or standard care (an average of 73 hours of inpatient telemetry plus an average of 24 hours of Holter monitoring). At both 6 and 12 months, detection of AF was significantly higher in the prolonged monitoring group (13.5% vs. 4.5% and 13.5% vs. 6.1%, respectively). The associated numbers needed to screen were 11 and 13. There were no significant differences between groups in stroke recurrence (2.5 vs. 4.5%, p=0.28) or death (3.0 vs. 4.5%, p=0.45). A systematic review (Kishore et al., 2014) including the results from 32 studies (5,038 patients) of patients with acute ischemic stroke or TIA who had undergone invasive or non-invasive cardiac monitoring for a minimum of 12 hours following the event. The different types of cardiac monitoring evaluated included inpatient cardiac monitoring; 24, 48, 72 hour, and 7-day Holter; external loop recorder; invasive cardiac monitoring; and mobile cardiac outpatient telemonitoring. The overall detection rate of AF was 11.5% (95% CI 8.9%-14.3%) and was higher in selected (pre-screened or cryptogenic) patients (13.4%, 95% CI 9.0%-18.4%) compared with unselected patients (6.2%, 95% CI 4.4%-8.3%). The detection rate of AF in cryptogenic stroke was 15.9% (95% CI 10.9%-21.6%).

The use of transesophageal echocardiography (TEE) has been shown to be more sensitive compared with transthoracic echocardiography (TTE) for detecting cardiac abnormalities following ischemic stroke or TIA, although it is costlier and less acceptable to patients. Common TEE findings following stroke have included atheromatosis, PFO, and atrial septal aneurysm (Marino et al., 2016; Katsanos et al,. 2015). Marino et al. (2016) reported that 42.6% of 263 patients admitted following an acute ischemic stroke had a TEE finding which could explain the etiology of stroke/TIA. De Bruijn et al. (2006) included 231 patients with recent stroke (all types) or TIA whose stroke etiology remained in question following initial ECG, ultrasound assessments, and blood tests. All patients had a TEE followed by a TTE and the identification of major and minor cardiac sources of embolism were compared between the two diagnostic tools. A potential cardiac source of embolism was detected in 55% of the patients. Significantly more abnormalities were identified using TEE. A cardiac source was detected in 39% of patients where TEE was positive and the TTE negative. A major cardiac risk factor was detected based on TEE in 16% of patients. The detection of possible cardiac sources of embolism was statistically significantly greater using TEE compared to TTE in both patients aged ≤45 years and >45 years.

Venous Thromboembolism Prophylaxis

The use of LMWHs has been shown to be more effective for the prevention of venous thromboembolism compared with UFH), and is associated with a lower risk of serious bleeding events. A Cochrane review (Sandercock et al., 2017) included the results from 9 randomized controlled trials (RCTs) (n= 3,137) of patients with acute ischemic stroke who were randomized within 14 days of stroke onset to receive LMWHs or heparinoids, or UFH for an average of 10 to 12 days. The odds of DVT occurrence during the treatment period were significantly lower in the LMWH/heparinoid group (OR=0.55, 95% CI 0.44 -0.70, p<0.0001). There was no difference between groups in mortality during the treatment period or follow-up, nor in the odds of any ICH/hemorrhagic transformation during treatment (OR= 0.75, 95% CI 0.46- 1.23, p=0.25). The authors cautioned that the event rates for serious events (pulmonary embolus, death, and serious bleeding) were too low to provide reliable estimates of the risk and benefits. 

The use of external compression stockings/devices has been investigated in a series of 3 large, related RCTs: the Clots in Legs Or sTockings after Stroke (CLOTS) trials. In CLOTS 1 (Dennis et al., 2009), 2,518 patients, admitted to hospital within 1 week of acute ischemic stroke or ICH and who were immobile, were randomized to either routine care plus thigh-length graded compression stockings (GCS) or to routine care plus avoidance of GCS. Patients wore the garments day and night until the patient became mobile, was discharged, or there were concerns with skin breakdown. At 30 days there was no significant difference between groups in the incidence of proximal DVT (GCS 10.0% vs. avoid GCS 10.5%). GCS use was associated with a non-significant absolute reduction in risk of 0.5% (95% CI -1.9% to 2.9%). The incidence of any DVT or PE was non-significantly lower in the GCS group (17.0% vs. 18.4%, OR=0.91, 95% CI 0.74-1.11), but the frequency of skin ulcers or breakdown were significant higher in the GCS group (5.1% vs. 1.3%, OR=4.18, 95% CI 2.40-7.27). The inclusion criteria for the CLOTS 2 trial (The CLOTS Trials Collaboration, 2010) were similar to those of CLOTS 1. In this trial, 3,114 patients were randomized to wear thigh-length stockings or below-knee stockings while they were in the hospital, in addition to routine care, which could have included early mobilization, hydration, and/or the use of anticoagulants/antiplatelets. At 30 days, there was a significant reduction in the incidence of proximal DVT associated with thigh-length GCS (6.3% vs. 8.8%, adj OR=0.69, 95% CI 0.53-0.91, p=0.008). The incidence of asymptomatic DVT was also lower in the thigh-length GCS group (3.2% vs. 4.8%, adj OR=0.64, 95% CI 0.44-0.93, p=0.02). The use of thigh-length GCS was associated with an increased risk of skin breakdown (9.0% vs. 6.9%, OR=1.33, 95% CI 1.031.73, p=0.03). Finally, in CLOTS 3 (Dennis et al., 2013) 2,876 patients were randomized to wear a thigh-length IPC)device or to no IPC at all times except for washing and therapy, for a minimum of 30 days. The mean duration of IPC use was 12.5 days and 100% adherence to treatment was achieved in only 31% in the IPC group. The incidence of proximal DVT within 30 days was significantly lower for patients in the IPC group (8.5% vs. 12.1%, OR=0.65, 95% CI 0.51-0.84, p=0.001, ARR=3.6%, 95% CI 1.4%-5.8%). There were no significant differences between groups for the outcomes of: death at 30 days (10.8% vs. 13.1%, p=0.057), symptomatic proximal DVT (2.7% vs. 3.4%, p=0.269), or PE (2.0% vs. 2.4%, p=0.453). The incidence of any DVT (symptomatic, asymptomatic, proximal or calf) was significantly lower for the IPC group (16.2% vs. 21.1%, OR=0.72, 95% CI 0.60-0.87, p=0.001). Skin breakdown was more common in the IPC group (3.1% vs. 1.4%, OR=2.23, 95% CI 1.31-3.81, p=0.002). At 6 months, the incidence of any DVT remained significantly lower in the IPC group (16.7% vs. 21.7%, OR=0.72, 95% CI 0.60-0.87, p=0.001). The incidence of any DVT, death, or PE also remained significantly lower for the IPC group (36.6% vs. 43.5%, OR=0.74, 95% CI 0.63-0.86, p<0.0001).

Temperature Management

Elevated body temperature in the early post-stroke period has been associated with worse clinical outcomes. A meta-analysis conducted by Prasad & Krishnan (2010), including the results from six studies demonstrated that fever within the first 24 hours of ischemic stroke onset was associated with twice the risk of short-term mortality (OR= 2.20, 95% CI 1.59–3.03). Fever may result from a secondary infection, such as pneumonia, or may have occurred as a cause of stroke (e.g. infective endocarditis). While interventions to reduce temperature may improve the viability of brain tissue and/or prevent other medical complications post stroke, efforts to reduce fever, through a wide range of modalities including pharmacological agents (e.g., paracetamol) and physical interventions (e.g., cooling blankets and helmets and endovascular treatments) have not been convincingly shown to be effective in reducing or avoiding poorer outcomes. The largest trial examining the use of pharmacological agents for the reduction of fever was Paracetamol (Acetaminophen) In Stroke (PAIS) trial (den Hertog et al., 2009). In this trial, 1,400 patients were randomized to receive one gram of paracetamol, 6 times daily for 3 days or placebo within 12 hours of symptom onset. While treatment with paracetamol did significantly lower body temperature by a mean of 0.26°C, it was not associated with improvement beyond expectation (adjusted OR=1.20, 95% CI 0.96-1.50), nor did it increase the odds of a favourable outcome. Treatment with paracetamol was associated with a decrease in 14-day mortality (OR=0.60, 95% CI 0.36-0.90), but there was no difference at 3 months (OR=0.90, 95% CI 0.68-1.18). The PAIS 2 trial (De Ridder et al., 2017) was terminated after enrolling 26 of 1,500 planned patients. In this trial, high-dose (2 grams) or placebo was given for 3 days to patients with a temperature of ≥36.5o C. There was no significant difference between groups in the shift in mRS scores at 90 days associated with paracetamol (common adj OR=1.15, 95% CI 0.74-1.79). 
In a Cochrane review, den Hertog et al. (2009) included the results from 8 RCTs, 5 of which examined pharmacological agents (paracetamol, n=3, metamizole n=1, ibuprofen placebo n=1) versus placebo. Pharmacological treatment significantly reduced temperature at 24 hours following treatment (mean difference of -0.21o C 95% CI -0.28, -0.15, p<0.0001), but was not associated with a reduction in the odds of death or dependency at 1 to 3 months (OR= 0.92, 95% CI 0.59- 1.42, p=0.69).

Mobilization

Early mobilization post-stroke is intended to reduce the risk of medical complications including DVT, pressure sores, and respiratory infections. The potential benefits of early mobilization have been examined in several RCTs, with ambiguous results. Recently, a Cochrane review (Langhorne et al., 2018) included the results from 9 RCTs (n= 2,958) of participants who had sustained an acute stroke and could be mobilized within 48 hours. Trials included the AVERT trials (Bernhardt et al., 2008, 2015), AKEMIS (Sundseth, 2012), SEVEL (Herisson et al., 2016) and VERITAS (Langhorne et al., 2010). The median delay to starting mobilization after stroke onset was 12.7 hours shorter in the early mobilization group (18.5 vs. 33.3 hours). There were no significant differences in the odds of death or poor outcome at 3 months between groups (51% vs. 49%; OR= 1.08, 95% CI 0.92 to 1.26, p = 0.36), or the odds of death (7% vs. 8.5%; OR=1.27, 95% CI 0.95 to 1.70; p = 0.11). These results were supported by medium quality of evidence. The mean Barthel Index (20-point scale) was significantly higher in the early mobilization group (mean difference of 1.94, 95% CI 0.75 to 3.13, p = 0.001) at a median follow-up of 3 months. The mean length of hospital stay was 1.44 days shorter in the early mobilization group. Additional analysis of the AVERT 3 trial (Bernhardt et al., 2016) indicate that after controlling for age and stroke severity, regardless of group assignment, keeping time to first mobilization and frequency constant, every extra 5 minutes of out-of-bed activity per day reduced the odds of a favourable outcome by 6%, while increasing the frequency of each out-of-bed session improved the odds of favourable outcome by 13%, In 2021, Bernhardt et al. reported that by day 14, the risk of mortality was significantly higher in the very early mobilization group (OR=1.76, 95% CI 1.06-2.92). 

Seizure Management

The incidence of post-stroke seizure ranges from 5%-15%, depending on stroke etiology, severity, and location (Gilad, 2012). Hemorrhagic events and cortical lesions are associated with the highest risk of both first and recurrent seizure (Gilad et al. ,2013). Evidence on the effectiveness of pharmacological treatment for post- stroke seizures is limited. A recent Cochrane review (Chang et al., 2022) sought studies including patients of any age recovering from ischemic stroke or intracerebral hemorrhage that evaluated antiepileptic drugs compared with a placebo or no drug for the primary and secondary prevention of post stroke seizures. Two publications were included. Gilad et al. (2011) randomized 72 patients to receive 800 mg/day valproic acid or placebo daily for one month. In the second trial, based on data presented in an abstract (Tujil et al., 2021), 784 patients were randomized to receive 10 mg diazepam or placebo, which was given within 12 hours after stroke onset, followed by oral 10 mg tablets twice daily for 3 days. The use of antiepileptic drugs was not associated with a significant reduction in the risk of primary seizure prevention at the end of follow-up, the durations of which were 3 months and 1 year (RR= 0.65, 95% CI 0.34 to 1.26). The certainty of the associated evidence was low to moderate.

Nutrition and Dysphagia

A standardized program for screening, diagnosis, and treatment of dysphagia following acute stroke has been shown to reduce the incidence of pneumonia and feeding tube dependency. Bedside screening may include components related to a patient’s level of consciousness, an evaluation of the patient’s oral motor function and oral sensation, as well as the presence of a cough. It may also include trials of fluid. Coughing during and up to 1 minute following test completion and/or “wet” or hoarse voice are suggestive of an abnormal swallow. A recent Cochrane review (Boaden et al. 2021), evaluated the test characteristics of 37 dysphagia screening tests. Tests evaluated water only, water + other consistencies and water swallow test combined with an instrumental assessment. Among these three categories, the best performing screening tests were the Toronto Bedside Swallowing Screening Test (water only), the Gugging Swallowing Screen (water + other consistencies) and the Bedside Aspiration test (combined water + an instrumental assessment). The sensitivity of all tests was 100% with specificities of 64%, 69% and 71%. 

Silent aspiration may occur in patients who do not cough or complain of any problems with swallowing or have no wet-sounding voice, highlighting the importance of dysphagia screen for all patients as soon as possible following stroke. A prospective study (Ouyang et al., 2020) of 11,093 patients with acute stroke included in the HeadPoST trial examined the association between dysphagia screening and assessment, and outcome. In 362 (3.3%) patients who developed pneumonia, compared to patients who passed a dysphagia screen, screen-fail patients had a significantly higher risk of pneumonia (1.5% vs. 10.0%; adj OR= 3.00, 95% CI 2.19–4.10) and poor outcome at 90 days (68.1% vs. 30.8%, adj OR= 1.66, 95% CI 1.41–2.95). Using United Kingdom registry data, Bray et al. (2017) reported a higher risk of stroke-associated pneumonia with increasing times to dysphagia screening and assessment. The overall incidence of stroke-associated pneumonia was 8.7% (13.8% for patients who were not screened, 8.0% for patients who were screened, and 14.7% for patients who received a comprehensive assessment). 

Dietary modifications, including altered texture of solids and fluids and the use of restorative swallowing therapy, and compensatory techniques, are the most commonly used treatments for the management of dysphagia in patients who are still safe to continue oral intake. Unfortunately, there is little direct evidence of their benefit. Carnaby et al. (2006) randomized 306 patients with dysphagia admitted to hospital within 7 days of acute stroke, to receive usual care, standard low-intensity intervention (composed of environmental modifications, safe swallowing advice, and appropriate dietary modifications), or standard high-intensity intervention and dietary prescription (daily direct swallowing exercises, dietary modification), for up to 1 month. When the results from the high-intensity and low-intensity groups were combined and compared with the usual care group, patients in the active therapy group regained functional swallow sooner and had a lower risk of chest infections at 6 months. 

For patients who cannot obtain nutrient and fluid needs orally, enteral nutrition may be required. The decision to use enteral support should be made within the first 7 days post-stroke. The largest trial that addresses both the issues of timing of initiation of enteral feeding and the choice of feeding tube was the FOOD trial (Dennis et al., 2005), which included 1,210 patients admitted within 7 days of stroke from 47 hospitals in 11 countries. In one arm of the trial, patients were randomized to receive either a percutaneous endoscopic gastrostomy or nasogastric feeding tube within 3 days of enrollment into the study. Percutaneous endoscopic gastrostomy feeding was associated with an absolute increase in risk of death of 1.0% (–10.0 to 11.9, p=0.9) and an increased risk of death or poor outcome of 7.8% (0.0 to 15.5, p=0.05) at 6 months. In the second part of the trial patients were randomized to receive feeds as early as possible or to avoid feeding for 7 days. Early tube feeding was associated with non-significant absolute reductions in the risk of death or poor outcome (1.2%, 95% CI -4.2 to 6.6, p=0.7) and death (15.8%, 95% CI -0.8 to 12.5, p=0.09) at 6 months.

Incontinence

To avoid the onset of UTIs, the use of indwelling catheters is largely discouraged in clinical settings and is typically limited to patients with incontinence that cannot be managed any other way. If used, the catheter should be changed or removed as soon as possible. Ersoz et al. (2007) reported that among 110 patients consecutively admitted for rehabilitation following stroke, 30 developed a symptomatic UTI during hospitalization. UTIs occurred more frequently in patients with indwelling catheters, compared with patients who could void spontaneously (7/14 vs. 23/96, p=0.041) and in patients with residual urine volumes of >50 mL (41.2% vs. 19.5%, p=0.039). Several infection prevention strategies that have been identified to prevent or delay the onset of catheter-associated UTIs include inserting the catheter using aseptic technique, correctly positioning the drainage tube and the collection bag, maintaining uncompromising closed drainage, achieving spontaneous voiding, and administering intermittent catheterizations. The effectiveness of bladder-training programs, which typically include timed/prompted voiding, bathroom training, pelvic floor exercises, and/or drug therapy, has been evaluated in a small number of studies. In one study, 42 patients admitted to a single acute stroke unit were each was prescribed an individualized bladder program consisting of bladder scanning, intermittent catheterizations/ post-void residual regimen, non-invasive voiding strategies (e.g., pelvic muscle exercises) and/or drug therapy. The regimen was continued until the post-void urine residual was below 100 ml for three consecutive days (Chan et al., 1997). Eighty-four percent of all patients achieved urinary continence within the first month of stroke. Among this group, all females became continent, while 23% of the male patients did not. In a Cochrane review, Eustice et al. (2000) included the results of 9 RCTs (n= 674), examining the potential benefit of prompted voiding (vs. no prompted voiding) provided for 10 days to 13 weeks. Prompted voiding was associated with a reduction in the number of incontinent episodes in 24 hours (MD= -0.92, 95% CI -1.32 to -0.53, p<0.0001). Thomas et al. (2014) conducted a cluster feasibility trial, Identifying Continence Options after Stroke (ICONS). Compared with usual care, the systematic voiding program was not associated with significantly increased odds of being continent at 6 or 12 weeks.

Oral Care 

Physical weakness following stroke may prevent patients from independently completing their activities of daily living, including oral care. Poor oral care, combined with potential side effects of medication (e.g., dry mouth, oral ulcers, stomatitis), may contribute to a greater amount of bacteria in the mouth, leading to the development of pneumonia. Patients have also reported lower oral health-related quality of life as a result of poor or inadequate dental care following stroke (Schimmel et al., 2011). Therefore, on admission to hospital, all patients should have an oral/dental assessment to examine mastication, tooth wear, oral disease, and use of appliances following stroke. However, few studies have examined interventions to improve oral hygiene in patients following stroke. A Cochrane review conducted by Brady et al. (2006) included the results of three RCTs (n=470) that included patients receiving some form of assisted oral healthcare in a healthcare facility following stroke. Treatments evaluated included oral healthcare plus timed tooth brushing, healthcare education, and selective decontamination of digestive tract using an antimicrobial gel applied to the mucous membranes of the mouth several times per day. Due to the small number of studies and variability in treatments, pooled analyses were not possible. The use of decontamination gel was associated with a reduction in the incidence of pneumonia (OR=0.20, CI 95% 0.05 to 0.84). A single education session was not associated with a reduction in dental plaque tooth coverage, the presence of gingivitis, or denture-induced stomatitis at 1 or 6 months following training, but was associated with a significant reduction in denture plaque at both assessment points and higher knowledge scores among care providers. 

Sex and Gender Considerations

Medical Complications

Otite et al. (2017) reported sex differences in the frequencies of various post stoke complications. Urinary tract infections, the most common complication, was reported in 19.8% of women compared with 9.9% in men. Acute renal failure was more commonly reported in men (10.6% vs. 5.9% in women). Overall, the risks of other complications including pneumonia, DVT and pulmonary embolism were approximately 30% greater in men. Older age and female sex were identified as risk factors for urinary tract infection in a systematic review of acute post-stroke infections (Westendorp et al. 2011).

Cardiovascular Investigations

In the FIND-AF trial (Wachter et al. 2017), in which patients were randomized to receive prolonged Holter ECG monitoring (10-days) and repeated at 3 and 6 months or standard care (minimum of 24 hours of cardiac monitoring), there were no interactions in subgroup analyses based on age, sex, baseline NIHSS, CHADS-2 score, symptoms at admission and imaging (lacunar vs. non-lacunar). Sex was not examined as a potential effect modifier in the MonDAFIS trial (Haeusler et al. 2021).

Venous Thromboembolism Prophylaxis

In the Cochrane review of (Sandercock et al. 2017) comparing LMWH with UFH, no subgroup analyses (including sex) were conducted. Sex was not a variable examined in prespecified subgroup analyses in the CLOTS trials (2009, 2010, 2013).

Temperature Management

Sex was not among the variables included in prespecified analysis of the PAIS 2 trial (De Ridder et al. 2017). However, in a systematic review (Carcel et al. 2019) including data from 5 acute randomized controlled trials examining sex differences on stroke outcomes, was the finding that women were less likely to be treated for fever (OR=0.82, 95% CI 0.70-0.95).

Mobilization

In the Cochrane review (Langhorne et al. 2018) comparing early mobilization with usual care, no subgroup analyses based on sex, were conducted. No subgroup analyses were conducted in any of the primary trials included in the review.

Seizure Management

The frequency of post-stroke seizures in the literature review was low. No subgroup analyses based on sex were conducted in trials examining the effectiveness of oral antiepileptic agents.

Nutrition and Dysphagia

The incidence of dysphagia post stroke and potential differences in treatment effectiveness in men versus women was not examined in any of the literature reviewed. No subgroup analyses based on sex were conducted in any of the trials of enteral feeding.

Incontinence

The effectiveness of behavioral interventions for the treatment of urinary incontinence, based on sex, was not examined in the literature reviewed.

Oral Care

The effectiveness of oral care protocols to promote oral hygiene, based on sex, was not examined in subgroup analyses in any of the literature reviewed.

Stroke Resources
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