We investigated the effect of caffeine on the hypercapnic ventilatory
response (HCVR) using steady state (SS) and rebreathing (RB) methods i
n 6 subjects. They received caffeine (5 mg/kg) or saline intravenously
in a randomized, double-blind, crossover manner, with measurement of
serum caffeine levels. PET(CO2) and (VE), normalized for vital capacit
y (VC), were measured continually during RB and during the last 5 min
of SS runs. The slope of the VE-PET(CO2) response increased from 0.21
+/- 0.14 to 0.38 +/- 0.14 and from 0.23 +/- 0.12 to 0.59 +/- 0.45 VC.m
in(-1).mmHg(-1), measured by RB and SS respectively (P<0.05). Plotting
VT vs PET(CO2) revealed a parallel shift (additive effect) in the res
ponse measured by RB after caffeine; fut an increased slope (multiplic
ative effect) in the VT-PET(CO2) relation measured in SS. We conclude
that caffeine acts as a respiratory stimulant and increases the HCVR,
but that assessment of the caffeine-CO2 interaction is dependent on th
e methodology employed.