Intravenous thrombolytic therapy – acute ischemic stroke**: rtPA intravenous thrombolysis, how to use rtPA?

To date, although there are many treatments for ischemic stroke in the clinic, there are only four treatments that have been proven to be definitively effective by evidence-based medicine: stroke unit, ultra-early thrombolytic therapy, antiplatelet therapy, and early onset of formal rehabilitation
.

Randomized controlled trials have shown that intravenous rt-PA thrombolysis within 3 hours of the onset of neurologic symptoms in screened patients with acute ischemic stroke is a very effective treatment (class A evidence) at a recommended dose of 0.

1 The importance of intravenous thrombolytic therapy

1 time is the brain: Acute ischemic stroke (AIS referred to as stroke) is a common disease and multiple diseases in neurology clinics, and is one of the three major diseases that endanger human life and health and lead to human death in today's world, which has the characteristics of
high incidence, high recurrence rate, high mortality rate and high disability rate.

2 Thrombolytic therapy as the first recommendation: At present, reperfusion therapy is recognized worldwide as the only effective means
to reduce the disability and fatality rate of patients.

2rtPA intravenous thrombolysis

From the first international trial in 1995 until the latest international trial completed in 2012, all data confirm that patients benefit from intravenous thrombolysis with rt-PA
.

1 Three "9" ways to use it:

0.

The maximum dose is 90 mg: 90 mg is still used for those who exceed 90 mg
by body weight.

90% of the remaining total: micropump injection
within 1 hour.

2 indications:

1.

2.

3.

4.

5.

3Monitoring and care of venous thrombolysis:

1.

Observe consciousness, pupils, blood pressure, etc.

3.

4.
Nasogastric tube and urinary catheter should be placed delayed;

5.
Timely review the results of blood routine and blood coagulation analysis according to the instructions
.

4 contraindications:

1.
Previous intracranial hemorrhage, including suspected subarachnoid hemorrhage; History of head trauma in the last 3 months; Gastrointestinal or urinary bleeding in the last 3 weeks; Excessive surgical procedures performed in the last 2 weeks; There has been an arterial puncture in the last 1 week at a site that is not easily compressive for hemostasis
.

2.
History of cerebral infarction or myocardial infarction in the past 3 months, but excluding old small space infarction without leaving any signs of neurological function
.
3.
Patients with
severe heart, liver, renal insufficiency or severe diabetes.

4.
Physical examination reveals evidence
of active bleeding or trauma (such as fracture).

5.
Has been oral anticoagulant, and the international standardized ratio > 15; 48 hours have received heparin treatment (APTT beyond the normal range).

6.
The platelet count is lower than 100×109/L, and the blood glucose < 2.
7 mmol/L
.

7.
Blood pressure: > 180/100mmHg
.

8.
Pregnancy
.

9.
Non-cooperation
.

3 US guidelines recommend thrombolysis

In the United States' 2013 "Guidelines for the Early Diagnosis and Treatment of Acute Ischemic Stroke", it can be found that venous thrombolysis is the main theme, and some of the changes are worthy of attention
.

1.
The time window is extended
.
Guidelines make standard intravenous thrombolytic therapy the most basic treatment in the acute phase of ischemic stroke
.

Guidelines recommend intravenous rtPA therapy (0.
9 mg/Kg, maximum dose 90 mg)
to patients within 3 hours of onset.
For patients with ischemic stroke who had onset for 3 to 4.
5 hours, the guidelines adopted the findings of the ECASS-III study, and although there was only one study of evidence, the guidelines gave the highest level of recommendation
.
The guidelines state that intravenous rtPA therapy (0.
9 mg/Kg, maximum dose 90 mg) is recommended for patients who are suitable and can be used within 3 to 4.
5 hours of stroke onset, and that the criteria for treatment are similar to those within 3 hours (inclusion criteria for patients with thrombolysis within 3 hours: diagnosis of ischemic stroke with measurable neurological deficit; Determine the onset time within 3 hours; Age 18 years and older).

Currently intravenous rtPA (Edonli) is the only drug with indications for thrombolytic therapy for acute ischemic stroke and has been recommended by international treatment guidelines that do not recommend the use of any other intravenous thrombolytic drug
other than intravenous rtPA.

2.
Relaxation of indications also gives clear treatment recommendations
for stroke patients with mild and gradually improving symptoms that the previous guidelines did not consider to require thrombolysis.

The guidelines adopt a more positive approach
to situations previously considered relatively contraindicated, such as a history of major surgery and myocardial infarction in the previous 3 months.

The guidelines note that rtPA may be considered for patients with mild symptoms, rapid resolution of stroke symptoms, major surgery within nearly 3 months, recent myocardial infarction, and prior stroke and diabetes
.

Most notably, thrombolytic therapy should also be done for patients with mild stroke (NIHSS scores below 4), which is a big change
.
The reason for this is that studies have confirmed that these mild patients have a high chance of worsening to severe stroke, and early thrombolysis is to curb the development of the
disease.

3.
Introduce the concept
of DNT time.
In order to avoid unnecessary delays after patients arrive at the hospital and miss the opportunity to thrombolysis, the new guidelines introduce the concept of emergency process time control for the first time, making the patient's door-to-needle time (DNT) an important part of
the guide.

DNT refers to the time between the time
the patient is sent to the hospital and the rtPA is given intravenously.
The new guidelines state that the therapeutic benefit of patients suitable for intravenous rtPA thrombolytic therapy is time-dependent, treatment should be started as soon as possible, and DNT should be within
60 minutes.
Limiting this time to 60 minutes is supported by a large amount of evidence-based evidence, and strict control time can reduce mortality in thrombolytic patients by 22%.

4 The current situation of intravenous thrombolytic therapy in China

In medical quality management, there are 10 key performance indicators for stroke treatment, including acute thrombolysis, prevention of deep vein thrombosis in the acute stage, whether antiplatelet drugs are used in the early stage, whether antiplatelet drugs are prescribed at discharge, whether statins are prescribed at discharge, whether antihypertensive is given, whether health education is available, and whether rehabilitation treatment is available
.
After comparing China and the United States, it was found that there are two indicators in China's clinical practice that are the worst, one is the anticoagulation therapy of patients with atrial fibrillation who have had stroke, and the other is thrombolytic therapy
in the acute stage.

Although thrombolytic therapy is the first recommended means in the treatment guidelines for acute ischemic stroke around the world, and the latest diagnosis and treatment guidelines for acute ischemic stroke in China in 2010 have also included acute phase thrombolytic therapy, the actual implementation of acute phase thrombolysis is indeed unsatisfactory
.

According to the survey during the "Eleventh Five-Year Plan" period, the thrombolytic rate of patients admitted to the hospital within two hours of acute ischemic stroke in China is only 9%, while it can reach 70% in the United States, and we are far from
the United States.
The time from imaging to thrombolysis treatment averaged 150 minutes, significantly longer than 70-80 minutes
in the United States or Canada.
Previous studies have shown that the same two groups of patients, one group was given 60 minutes after arriving in the hospital, and the other group was given more than 60 minutes, and the death rate of the two groups was about 22%.

So, reducing hospital delays could give about one in five patients a chance of
survival.
Today, when the overall medical quality in China is improving, in 2012, through the investigation of more than 200 hospitals across the country, it was found that the thrombolytic treatment of patients with acute ischemic stroke has not improved
.
This has also become a short board
in the prevention and treatment of stroke in China.

The analysis of the reasons found that it is not directly related to the economic development or not, and may be due to the following two aspects:

1.
In addition to CT examination, there is a delay in the examination of other items, such as the examination of coagulation items
.

Second, the communication between doctors and patients is not smooth, and it takes time
to sign informed consent.
Because of the risk of bleeding with rtPA, informed consent must be signed by the family before treatment, and if the family refuses, then the treatment cannot be carried out
.
On the one hand, this delays the treatment time, and on the other hand, some patients will lose the opportunity to
treat because of their families.

However, in the United States, on the contrary, no thrombolysis treatment is required to sign an informed consent form, and doctors do not need to consult patients and their families at all for conventional thrombolytic treatment, which greatly saves the time
of thrombolytic treatment for patients with acute ischemic stroke.

To this end, in order to improve the overall level of intravenous thrombolysis treatment of acute ischemic stroke in China, in 2012, a sub-project was set up under the national "Twelfth Five-Year" science and technology plan led by Professor Wang Yongjun, that is, the intravenous thrombolysis treatment (MOST) project
for acute ischemic stroke.
After two years of implementation, more and more hospitals have joined the project
.
Many hospitals can already perform thrombolytic therapy in about 60 minutes, which is the most significant result achieved so far
.

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