Importance of time

Importance of time

Stroke is a medical emergency, and time is critical. Recognising the symptoms of a stroke and being aware of the time factor involved in seeking immediate medical treatment can greatly reduce the chance of permanent damage or disability.

  • The majority of patients with ischaemic stroke do not reach the hospital soon enough.
  • Education endeavours should inform the public about symptoms and signs of stroke particularly in the case of high-risk patients and their families and colleagues, and of employees and employers in large companies.
  • If the first contact is the general practitioner or family doctor, this frequently leads to delays in transportation and the early start of therapy.
  • Pre-hospital evaluation of potential stroke patients can be accomplished promptly after activation of the emergency medical services (EMS) system.
  • Urgent evaluation and transport of potential stroke patients is essential.

Time is brain: Act FAST!1-3

  • Every minute, in which a large vessel ischaemic stroke is untreated, the average patient loses 1.9 million neurons, 13.8 billion synapses, and 12 km of axonal fibres.
  • Each hour in which treatment fails to occur, the brain loses as many neurons as it does in almost 3.6 years of normal aging.
  • The penumbra area (see Pathophysiology section) represents potentially salvageable brain tissue if perfusion of the tissue can be restored in time (before the tissue becomes completely ischaemic and dies).
  • NINDS recommends a door-to-needle time (DTN) of 1 hour or less.

Streamlining of local guidelines and standard operating procedures may shorten the DTN in experienced stroke centres to <30 min on average.

  • However, only approximately 11% of all stroke patients who are thrombolysed receive rt-PA within 90 minutes of symptom onset.

rt-PA effects are time dependent4-9

  • The 2010 pooled analysis of rt-PA trials for ischaemic stroke showed that the earlier treatment is initiated, the better the outcome, and the lower the number of patients needed to treat (NNT) with rt-PA to achieve one additional favourable outcome (classified as a modified Rankin score of 0-1) (Figure 1):

 

Figure 1: NNT to reach a modified Rankin score of 0-1 according to the time from onset of stroke to the start of treatment4

NNT to reach a modified Rankin score of 0-1 according to the time from onset of stroke to the start of treatment

 

Treatment within 0-90 min → NNT 4-5

Treatment within 90-180 min → NNT 9

Treatment within 3-4.5 hours → NNT 14

 

The SITS-MOST registry shows that:

  • "Real-life" treatment with rt-PA within 3 hours of symptom onset results in greater independence in activities of daily living when compared with treatment given during randomised controlled trials (RCTs) (54.8% vs. 50.1%; SITS-MOST vs. RCTs, respectively).
  • "Real-life" treatment with rt-PA within 3 hours of symptom onset resulted in reduced mortality when compared with RCTs (11.3% vs. 17.3%; SITS-MOST vs. RCTs, respectively).
  • SITS-ISTR confirms the safety and efficacy of rt-PA for the thrombolysis of ischaemic stroke within the approved 3-hour time window as well as in the 3-4.5 hour time window.
  • rt-PA is not licensed for use beyond 4.5 hours after stroke symptom onset.*
  • All patients being considered for rt-PA therapy must undergo urgent brain imaging (CT or MRI), a physical examination, blood tests, a neurological assessment, and a patient history - all within a timeframe that will allow rt-PA treatment to begin within 4.5 hours* of symptom onset.
  • The concept that if a patient arrives early, the doctor has more time, is totally inacceptable, as studies show that the earlier treatment is implemented, the better the outcome.

*As this differs in some countries, please check your local prescribing regulations for the currently recommended time window for the use of rt-PA.

References 
  1. Saver, J. Time is brain--quantified. Stroke 2006;37:263-266.
  2. Hacke W, Donnan G, Fieschi C, et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 2004;363(9411):768-774. Lancet 2004;363:768-774.
  3. NINDS NIH website. Stroke proceedings. Latest update 2008.
  4. Wahlgren N et al. SITS Investigators. Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet 2008;372:1303-1309.
  5. Lees K, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010;375:1695-1703.
  6. Ahmed N, et al; for the SITS Investigators. Implementation and outcome of thrombolysis with alteplase 3-4.5 h after an acute stroke: an updated analysis from SITS-ISTR Lancet Neurol 2010;9:866-874.
  7. Wahlgren N, et al. SITS Investigators. Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet 2008;372:1303-1309.
  8. Wahlgren N, et al; the SITS-MOST Investigators. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007;369:275–282.
  9. SITS-Database https://sitsinternational.org