Conflicts of interest: Arshad Majid has received honoraria from Boehringer Ingelheim and has received grant funding from the National Institute of Health and The American Heart Association.
The influence of bolus to infusion delays on plasma Tissue Plasminogen Activator levels
Article first published online: 4 DEC 2012
© 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization
International Journal of Stroke
Volume 9, Issue 7, pages 939–942, October 2014
How to Cite
Smith, C., Al-Nuaimi, Y., Wainwright, J., Sherrington, C., Singh, A., Kallingal, J., Douglass, C., Parry-Jones, A., Smith, C., Dixit, A. and Majid, A. (2014), The influence of bolus to infusion delays on plasma Tissue Plasminogen Activator levels. International Journal of Stroke, 9: 939–942. doi: 10.1111/j.1747-4949.2012.00924.x
- Issue published online: 18 SEP 2014
- Article first published online: 4 DEC 2012
- Manuscript Accepted: 17 MAY 2012
- Manuscript Received: 25 APR 2012
- National Institute of Health
- The American Heart Association
- ischemic stroke;
- tissue plasminogen activator
Estimates of neuronal loss in acute ischemic stroke show that the typical patient may lose 1·9 million neurons each minute that treatment is delayed. Consequently, significant emphasis has been placed on early evaluation and thrombolysis with tissue plasminogen activator (TPA), the only approved thrombolytic therapy. TPA should be administered as a bolus followed by an immediate infusion because of its short half life. However, in the real life clinical situation, delays in starting the infusion after the bolus can occur. Similarly, once infusion has started, interruptions in the infusion of TPA can also occur. These scenarios may result in lower serum concentrations which could decrease the effectiveness of thrombolysis. We sought to simulate, the influence of bolus infusion delays and also the influence of different intervals of interruptions in the infusion of TPA on serum TPA concentrations.
We simulated the effect of multiple intervals of delay after the bolus on serum TPA concentrations using known pharmacokinetics parameters of TPA. The effect of different intervals of interruptions in the infusion of TPA was also determined. The effect of rebolusing with TPA on serum concentrations in the event of significant bolus to infusion delays or significant infusion interruption was also simulated.
Our data show that delays in starting the infusion may have significant effects on serum TPA concentrations. After the initial bolus, there is a rapid decrease in serum TPA concentrations unless the infusion is started immediately. Greater than 5 min delays in starting the infusion results in a slow gradual increase in serum TPA levels and levels stay well below the target concentrations for significant periods of time. Similarly, interruptions in the infusion of TPA lasting longer than 5 min can also significantly influence TPA levels. Rebolusing with TPA in these scenarios rapidly restores TPA levels to target concentrations.
Because of its short half life, TPA should be administered as a bolus followed by an immediate infusion. Bolus to infusion delays or interruptions in the infusion of TPA after the bolus may significantly impact serum TPA levels and may reduce the efficacy of thrombolysis. Protocols or administration regimens should be employed to prevent delays or interruptions in the infusion. When delays do occur, rebolusing of TPA may be needed to rapidly restore TPA to target levels.