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Opioid-induced respiratory depression: implications & prevention
The goal of this thesis was to study the ability to reverse opioid-induced respiratory depression with respiratory stimulants and to study drugs that might prevent opioid-induced respiratory depression. The benefit-harm composite of opioids is discussed, followed by a recapitulation of the possible treatments of opioid-induced respiratory depression. Based on the data presented in this thesis, the following can be concluded:
1) Doxapram reduces alfentanil-induced antinociception due to an increase in alfentanil distribution and elimination.
2) GAL021, a novel calcium-activated potassium channel blocker, produces an increase in tidal volume and respiratory rate during opioid-induced respiratory depression without affecting the analgesic effect
3) GAL021 efficacy reduces at low ventilation levels and demonstrates ceiling in its efficacy to reverse opioid-induced respiratory depression
4) The utility...
The goal of this thesis was to study the ability to reverse opioid-induced respiratory depression with respiratory stimulants and to study drugs that might prevent opioid-induced respiratory depression. The benefit-harm composite of opioids is discussed, followed by a recapitulation of the possible treatments of opioid-induced respiratory depression. Based on the data presented in this thesis, the following can be concluded:
1) Doxapram reduces alfentanil-induced antinociception due to an increase in alfentanil distribution and elimination.
2) GAL021, a novel calcium-activated potassium channel blocker, produces an increase in tidal volume and respiratory rate during opioid-induced respiratory depression without affecting the analgesic effect
3) GAL021 efficacy reduces at low ventilation levels and demonstrates ceiling in its efficacy to reverse opioid-induced respiratory depression
4) The utility function of alfentanil is further developed to assess specific conditions in terms of wanted and unwanted effects. The utility function may be used to compare the respiratory effects of analgesics and might allow for comparison between different opioid treatments
5) RM101 causes respiratory depression in all subjects with a rapid effect on ventilation and a slower effect on CO2 sensitivity.
- All authors
- Roozekrans, M.H.J.
- Supervisor
- Dahan, A.
- Co-supervisor
- Niesters, M.; Velzen, M. van
- Committee
- Aarts, L.P.H.J.; Sarton, E.Y.; Dorp, E.L.A. van; Jonge, E. de; Cohen, A.F.; Henthorn, T.K.; Kalkman, C.J.
- Qualification
- Doctor (dr.)
- Awarding Institution
- Medicine, Leiden University Medical Center (LUMC) , Leiden University
- Date
- 2018-05-19
- ISBN
- 9789492336019