Verapamil causes decreased diaphragm endurance but no decrease of nocturnal O(2) saturation in patients with chronic obstructive pulmonary disease.
OBJECTIVE
In animal studies, it has been shown that verapamil reduces strength and endurance of the diaphragm and inhibits the beneficial effects of theophylline. We examined whether the use of verapamil in patients with severe chronic obstructive pulmonary disease (COPD) who use theophylline leads to a deterioration of diaphragmatic function resulting in a decrease of nocturnal O(2) saturation.


METHODS
A double-blind, placebo-controlled crossover study was designed in eight stabile severe COPD patients [forced expiratory volume in 1 s (FEV(1)) 0.9 +/- 0.1 l] taking theophylline. The doses of theophylline ranged from 600 mg daily to 1200 mg daily (7.0 mg/kg daily to 16.9 mg/kg daily). Nocturnal recordings, maximal respiratory muscle strength and endurance tests, lung function, blood pressure, electrocardiogram and arterial blood gas analysis were performed after 6 days of verapamil and after placebo.


RESULTS
A significant decrease of the endurance time from 7.7 min to 6.4 min was found in the threshold loading test. However, the mean nocturnal saturation values did not change significantly: 89.8% and 89.6%, respectively. Results of pulmonary function tests, arterial blood gas analysis and routine blood samples also did not change.


CONCLUSIONS
The decrease of the respiratory muscle endurance after the use of verapamil is in line with experiments in animal diaphragms. However, the nocturnal saturation did not change. This finding suggests that the effect found on diaphragm endurance is of no clinical significance and that verapamil can be given to COPD patients without risk of worsening nocturnal saturation. However, this must be confirmed by future larger scale studies.
Broeders
M E
ME
Department of Pulmonary Diseases Dekkerswald, University of Nijmegen, P.O. Box 9001, 6560GB Groesbeek, The Netherlands. m.broeders@mailbox.kun.nl
Heijdra
Y F
YF
Smits
P
P
Folgering
H T
HT
Kramers
C
C
D000368:Aged; D001784:Blood Gas Analysis; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000502:physiology; D018592:Cross-Over Studies; D003964:Diaphragm / Q000187:drug effects*; D004311:Double-Blind Method; D004347:Drug Interactions; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000378:metabolism*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D010919:Placebos; D013806:Theophylline / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D010919:Placebos; D014665:Vasodilator Agents; D013806:Theophylline; D014700:Verapamil; D010100:Oxygen