Blood pressure management during and after thrombolysis

Maintain BP ≤ 180/105 mmHg before starting infusion and during the next 24 hours

  • adequate blood pressure is a critical preventive measure to reduce the risk of intracranial hemorrhagic complications
  • antihypertensive drugs are allowed to reach the target BP
  • if parenteral medication is used, avoid rapid blood pressure (BP) drops (hypoperfusion → failure of collateral supply)
  • do not attempt full BP correction in the first 48h (target BP to 140-160/90-100mmHg)
    • especially with large ischemias or significant stenoses, higher BP is required to ensure adequate CPP
  • first choice drugs: urapidil (EBRANTIL), enalapril (ENAP), and labetalol (TRANDATE)
  • BP monitoring during the first 24h:
    • 0-2h: every 10-15 minutes, if BP is stable
      • in decompensated patients, check BP every 5 minutes until the dose of the antihypertensive drug and BP are stable; consider continuous monitoring (invasive x non-invasive)
    • 2-24h: every 30 minutes
      • with decompensated hypertension and parenteral antihypertensive therapy, measure more frequently
  • use parenteral therapy for as short as possible
  • after 24 hours, (re)start oral medication (e.g., ACE-I, Ca-blockers, sartans, possibly in combination with diuretics) and gradually reduce parenteral medication → see here
  • urapidil (EBRANTIL, TACHYBEN): coarctation of the aorta, grade II and III AV blocks, aortic stenosis. Combination with metoprolol (Betaloc) may enhance the bradycardic effect
  • enalapril (ENAP): angioneurotic edema (history), porphyria
  • Isosorbide dinitrate (ISOKET): use of phosphodiesterase inhibitors (sildenafil), hypertrophic obstructive cardiomyopathy, constrictive pericarditis
  • metoprolol (BETALOC): bronchial asthma, grade II and III AV blocks, significant bradycardia (TF <60/min) before initiation of therapy, inadequately compensated heart failure, sick sinus syndrome
  • sodium nitroprusside (NIPRUSS): aortic coarctation, Leber optic atrophy, tobacco amblyopia, vitamin B12 deficiency, metabolic acidosis, hypothyroidism, intrapulmonary AV shunts, severe hepatic failure, sildenafil therapy, hypotension, severe stenotic valve defects, hypertrophic obstructive cardiomyopathy

SBP 180-229 mmHg / DBP 105-139 mmHg

urapidil (EBRANTIL, TACHYBEN), labetalol (TRANDATE), enalapril (ENAP), esmolol (BREVIBLOCK)

SBP > 230 mmHg / DBP > 140 mmHg

  • in combination with the antihypertensive drugs listed above

Isosorbide dinitrate (ISOKET 0.1%) or sodium nitroprusside (NIPRUSS)

  • the effect is immediate for both drugs
FUROSEMIDE
  • effect starts within 30 minutes

Management of thrombolysis complications

Hypofibrinogenemia

  • usually, there is only a slight decrease in the level of fibrinogen and other clotting factors in the blood; so emergency surgery can be performed shortly after completing IVT
  • with hypofibrinogenemia, there is little correlation between low fibrinogen levels (normal 1.8-4g/l) and the risk of ICH
    • a higher risk of bleeding usually appears at levels < 1 g/l
  • spontaneous correction of hypofibrinogenemia within 24-48h is common
  • in case of bleeding or persistent low levels (< 1 g/l), substitution is necessary:
  • HAEMOCOMPLETTAN P/HS (1amp=1g)
    • fibrinogen content: 900-1300mg /1g; dissolve the product (1g /50ml aqua for injection) and warm to room or body temperature before administration
    • initial dose 1-2 g, the IV infusion must be slow ~5 ml/min
  • fresh frozen plasma (FFP)
    • fibrinogen content: 2mg/ml
    • initially administer 200-400ml, then proceed according to the patient’s condition

Minor bleeding (at the injection site, gingival bleeding, hematuria, etc.)

  • patients treated with IVT should be monitored for bleeding at the injection site, from the gingiva, the GIT, UGT, etc.
  • minor bleeding (e.g., gingival bleeding) does not require t-PA to be discontinued
  • if the progression of bleeding occurs, check hemocoagulation and platelets and proceed to the next section
  • to assess whether the thrombolytic effect persists, test:
    • thrombin time (TT) and plasma fibrinogen levels
    • fibrin degradation product (FDP) levels
    • euglobulin fibrinolysis (time-consuming test, short version takes approx. 60 minutes)

Massive extracerebral hemorrhage, suspected intracerebral hemorrhage

  • immediately discontinue the tPA application
  • check blood samples (CBC, coagulation, fibrinogen)
  • perform NCCT of the brain
  • clotting factor substitution is usually not necessary because of the short biological half-life of tPA
  • following drugs can be given if required:
Substitution of clotting factors
  • Fresh Frozen Plasma (FFP)
    • start with 200-400ml and proceed according to clinical course
    • up to dose of 20 ml/kg
  • PROTHROMPLEX (amp/600IU/20ml)
    • 4FPCC concetrate
    • dose: 25 IU/kg IV., infusion rate:  60j(2ml)/min (600jj=20ml)
  • with severe hypofibrinogenemia use HAEMOCOMPLETTAN P/HS (1amp=1g)
Syntetic antifibrinolytics
  • tranexamic acid (EXACYL) inj. IV during 10 min – 10ml (=2 amp/1000 mg) every 8h
    • reduce dose in patients with nephropathy !
  • aminocaproic acid
  • aprotinin (ANTILYSIN SPOFA) inj.  (10 tis. trypsin inhibičních jednotek-TIJ  v 1 ml)
    • bolus of 100 000 TIJ (10ml) IV  + infusion 200-300 000. TIJ (diluted in 5% glucose) within 3-4 h
Bleeding classification after Stroke and Reperfusion Therapy (ECASS II)
Post-thrombolysis SDH on CT

Orolingual angioedema (anaphylactoid reaction)

  • angioedema (incidence ~1-5%) is more common in patients taking ACEIs (RR 13.6!) and in patients with frontal lobe and operculo-insular lesions (RR 9)  [Hill, 2003]  [Fröhlich, 2019]   Orolingual angioedema
  • often, only half of the tongue (contralateral to the lesion) or only the lip is affected
  • probably it is an anaphylactoid (not anaphylactic) reaction – caused by the activation of complement system and kinin cascade by plasmin
    • complement activation causes degranulation of mast cells with histamine release ⇒ vasodilation
    • activation of the kinin cascade leads to increased levels of bradykinin, which causes vasodilation (the higher prevalence in patients taking ACEIs may be due to inhibition of plasma kinases responsible for removing bradykinin)  [Gauberti, 2018
    • bradykinin is also associated with adverse effects of tPA on the CNS (↑ risk of ICH, greater edema)
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Therapy

  • stop tPA infusion
  • intravenously administer:
    • promethazine (PROTHAZIN)1 amp/25mg IV or bisulepin (DITHIADEN) 1 amp/1mg  IV
    • famotidine (QUAMATEL)  20 mg IV inj.
    • methylprednisolone (SOLU-MEDROL) 125 mg/2ml IV (repeat bolus if needed)
    • or ADRENALIN IM/SC 0.3-0.5 ml
  • for angioedema associated with ACE-I, a selective bradykinin B2 receptor antagonist icatibant (FIRAZYR) can be used
    • dose: 30 mg/3ml SC in the abdominal area; it can be repeated in 6 and 12 h
  • orotracheal intubation (OTI) if conservative treatment fails
    • increased risk of severe respiratory distress is present with edema extending to the larynx and pharynx

Anaphylactic reaction

→ management of anaphylactic reaction

Less frequent adverse events

  • nausea, vomiting, shivering, fever, urticaria, headache, cramps, confusion
  • treatment is symptomatic
  • the decision to discontinue the tPA infusion depends on the severity of the AEs
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