According to Miller, “age does not significantly affect the pharmacodynamics of muscle relaxants… Duration of action may be prolonged, however, if the drug depends on liver or renal metabolism.”
There is approximately a 1% per year reduction in cardiac output after 30 years of age, and a reduction in cardiac output would result in slower distribution of NMB drugs to the neuromuscular junction. This subsequently results in a slower onset of block in elderly patients.
Decreased cardiac output and age-related glomerular sclerosis lead to decreased GFR of about 1% per year after age 40. Therefore, drugs that undergo renal excretion may be significantly prolonged.
Hepatic blood flow falls by about 1% per year and liver mass is reduced in elderly patients, which leads to a reduced elimination of drugs that undergo hepatic metabolism. Additionally, clinically significant prolongation of action occurs with repeated dosing or large boluses in the elderly.
Decreases in muscle mass, reductions in total body water, and an increased proportion of total body fat leads to mild changes in volume of distribution, and doses based on body weight will lead to a prolonged effect in the elderly.
Reduced plasma protein binding does not effect NMBDs because they are not highly protein bound. Potency is also unchanged for NMBD use in the elderly compared with younger patients.
The elderly are also more prone to hypothermia due to impaired temperature regulation and decreased overall body mass. Hypothermia leads to prolongation of the duration of action of NMBDs.
In conclusion, decreased cardiac output leads to a delayed onset of action in the elderly. Also, reductions in clearance and hepatic metabolism as well as changes in volume of distribution and thermal regulation lead to a prolonged duration of action. Therefore, mildly reduced dosing must be adjusted as appropriate for age, especially in elderly patients over the age of 75.
While pancuronium (which is renally excreted) might theoretically be prolonged, this is controversial. Vecuronium duration is slightly prolonged, likely due to changes in renal and hepatic function
Muscle Relaxation in Elderly
- Pancuronium: controversial
- Vecuronium: slight prolongation
- Atracurium: slight prolongation
- Cis-atracurium: no change