ECMO-/ECLS

 Dimunition of fourth twitch response compared with first twitch

response following four 2-Hz stimuli

 Abolition of single twitch corresponds to 95% receptor

blockade

VII. Tolerance and Withdrawal

A. Tolerance [3,18] receptor desensitization causing decreasing clinical effects
after prolonged exposure. This is thought to be due to upregulation of cAMP
pathway and desensitization of opioid receptors.^
 Factors that affect development of tolerance
o duration of therapy
 develops 10-21 days of morphine use
o infants in early developmental stages develop long term
tolerance to developing brain
o greater tolerance with shorter acting opioids
 Approaches to address tolerance
o dose escalation
o use longer acting opioids
o add non opioid analgesics
o add drugs that prevent or delay tolerance