Drug Effects on Orthostatic Intolerance Induced by Bedrest

Abstract

Effective and practical preventive procedures for postflight orthostatic intolerance are highly desirable. The current practice of attempts to expand plasma volume by ingestion of salt and fluids before reentry has proven benefits. This study evaluated alternative options using fludrocortisone (F) to expand plasma volume (PV), dextroamphetamine (Dex) to enhance norepinephrine (NE) release and atropine (A) to reduce the effects of vagal stimulation. Seven subjects with proven post-bedrest orthostatic intolerance returned for a 7-day 6 degrees head-down bedrest study. F (0.2 mg) was given at 8:00 AM and 8:00 PM the day before and 8:00 AM the day the subjects got out of bed (2 hours before standing). PV was measured before and 1 hour after the last dose of F. D (5 mg) and A (0.8 mg) were then taken orally 1 hour before the stand test. F expanded PV by 16% and caused sodium retention. Four of the 7 subjects stood for 1 hour post-bedrest and HR, plasma NE and PRA responses to standing were greatly enhanced and sustained. Although there was a narrowing of pulse pressure, the ability to overcome orthostatic intolerance with these countermeasures was largely due to vasoconstriction and sustained high heart rate. The existing literature on pharmacologic countermeasures for post-flight and post-bedrest orthostatic hypotension is reviewed, and the results are discussed in that context.