The dose-dependent effect of S(+)-ketamine on cardiac output in healthy volunteers and complex regional pain syndrome type 1 chronic pain patients

Anesthesia and Analgesia
Erik OlofsenAlbert Dahan

Abstract

Ketamine is used as an analgesic for treatment of acute and chronic pain. While ketamine has a stimulatory effect on the cardiovascular system, little is known about the concentration-effect relationship. We examined the effect of S(+)-ketamine on cardiac output in healthy volunteers and chronic pain patients using a pharmacokinetic-pharmacodynamic modeling approach. In 10 chronic pain patients (diagnosed with complex regional pain syndrome type 1 [CRPS1] with a mean age 43.2 ± 13 years, disease duration 8.4 years, range 1.1 to 21.7 years) and 12 healthy volunteers (21.3 ± 1.6 years), 7 increasing IV doses of S(+)-ketamine were given over 5 minutes at 20-minute intervals starting with 1.5 mg with 1.5-mg increments. Cardiac output (CO) was calculated from the arterial pressure curve obtained from an arterial catheter in the radial artery. Ketamine and norketamine plasma concentrations were measured. A novel pharmacokinetic-pharmacodynamic model was constructed to quantify the direct stimulatory effect of ketamine on CO and the following adaptation/inhibition. Significant differences in pharmacokinetic estimates were observed between study groups with 15% and 40% larger S(+)-ketamine S(+)-norketamine concentrations in healthy vol...Continue Reading

References

Dec 1, 1972·British Journal of Anaesthesia·S TakkiT Tammisto
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Sep 22, 2005·Journal of Pharmacokinetics and Pharmacodynamics·Rune V OvergaardHenrik Madsen
Feb 10, 2007·Journal of Cardiothoracic and Vascular Anesthesia·Gerard R Manecke, William R Auger
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Feb 14, 2008·Der Anaesthesist·Claudia TimmC Maier
May 14, 2009·European Journal of Anaesthesiology·Morten ØstergaardEigil Nygaard

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Citations

Jan 15, 2015·Pain Medicine : the Official Journal of the American Academy of Pain Medicine·Sara B ConnollyR Norman Harden
Jul 4, 2015·British Journal of Pharmacology·Nagendra S SinghIrving W Wainer
Oct 1, 2020·Anesthesiology·Jasper KampUNKNOWN Ketamine Pharmacokinetic Study Group
Aug 2, 2017·Anesthesiology·Kelly JonkmanAlbert Dahan

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