Pharmacokinetic differences between peripheral and central drug administration during cardiopulmonary resuscitation

Advanced resuscitation techniques are dependent on drug therapy to increase survival. Because drugs must reach their site of action instantaneously, the choice of appropriate route of administration may be critical. To study the pharmacokinetics of drug administration by peripheral and central venous routes during resuscitation, nine mongrel dogs were studied. Arterial blood pressure and electrocardiograms were monitored continuously. Cardiac output was evaluated before resuscitation to determine control levels. After thoracotomy and fibrillation of the heart, cardiac massage was started with a frequency of compression maintained at 60/min. Bolus injections of two different radioisotopes were given simultaneously through a peripheral and a central vein. Isotope activity was sampled through a catheter in the right femoral artery at 5 second intervals for 90 seconds and at 30 second intervals for 210 seconds. The major differences between the two routes of administration were that central injection produced a 270% higher peak concentration (p < 0.001) and significantly shorter lag times to the first appearance of tracer (16 ± 7 versus 38 ± 13 seconds, p < 0.05) and times to peak concentration (13 ± 5 versus 27 ± 12 seconds, p < 0.01). In contrast, there were no significant differences in area under the time-counts curve, mean residence time, total body clearance and steady state volume of distribution. The central compartment volume of distribution was significantly smaller after central than after peripheral injection (26.1 ± 56 versus 76.3 ± 16.5 ml, p < 0.01). The therapeutic implications of these findings must be investigated for individual drugs used during cardiorespiratory resuscitation to determine the most appropriate route and dosage for each agent.