title: Is the maximum dose of 90 mg alteplase sufficient for patients with ischemic stroke weighing >100 kg?
abstract: OBJECTIVE
  Intravenous alteplase for acute ischemic stroke has a maximum dose limit of 90 mg. Consequently, patients >100 kg body weight receive a lower per-kilogram dose compared with those ≤100 kg. We investigated if the lower per-kilogram dose is associated with poor early neurological improvement and worse outcome after thrombolysis.
  
  
  METHODS
  Of 27 910 patients registered in Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Register (SITS-ISTR; 2002 to 2009), 1190 (4.3%) weighed >100 kg. Major neurological improvement was used to estimate recanalization (National Institutes of Health Stroke Scale improvement ≥8 points or score of 0 at 24 hours). Outcome measures included symptomatic intracerebral hemorrhage (National Institutes of Health Stroke Scale deterioration ≥4 points within 24 hours and Type 2 parenchymal hemorrhage), functional independence (modified Rankin Scale 0 to 2), and mortality at 3 months.
  
  
  RESULTS
  Patients >100 kg received a lower per-kilogram alteplase dose (0.82 versus 0.90, P<0.001), were younger (62 versus 70 years, P<0.001), had a lower baseline National Institutes of Health Stroke Scale (10 versus 12, P<0.001), but more frequently had cardiovascular risk factors. Major neurological improvement at 24 hours occurred in 27.7% in both groups. Symptomatic intracerebral hemorrhage occurred in 2.6% versus 1.7% (P=0.03) in >100 kg versus ≤100 kg. Functional independence was 59.7% versus 53.6% (P<0.001) and mortality was 14.4% versus 15.1% (P=0.54). After adjustment for baseline characteristics, there was no significant difference for major neurological improvement or functional independence between >100 kg and ≤100 kg, but >100-kg patients had a higher odds ratio for symptomatic intracerebral hemorrhage (OR, 1.6; 95% CI, 1.06 to 2.41; P=0.02) and mortality (OR, 1.37; 95% CI, 1.08 to 1.74; P=0.01).
  
  
  CONCLUSIONS
  Our results support the current upper dose limit. There was a higher incidence of symptomatic intracerebral hemorrhage in patients >100 kg despite the lower per-kilogram recombinant tissue plasminogen activator dose. Major neurological improvement and functional independence were similar.
authors.affiliation: Department of Neurology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Diedler
authors.forename: Niaz
authors.initials: N
authors.lastname: Ahmed
authors.forename: Jörg
authors.initials: J
authors.lastname: Glahn
authors.forename: Martin
authors.initials: M
authors.lastname: Grond
authors.forename: Svetlana
authors.initials: S
authors.lastname: Lorenzano
authors.forename: Miroslav
authors.initials: M
authors.lastname: Brozman
authors.forename: Marek
authors.initials: M
authors.lastname: Sykora
authors.forename: Peter
authors.initials: P
authors.lastname: Ringleb
mesh_terms: D001835:Body Weight; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D010959:Tissue Plasminogen Activator