Reversal of opioid-induced respiratory depression (OIRD) by ketamine in healthy volunteers

This is a trial with a prospective double blind, placebo controlled, crossover design in healthy volunteers. The subjects will receive an intravenous infusion of remifentanil and isohypercapnic ventilation (that is ventilation at an elevated and clamped end-tidal PCO2 aimed to increase ventilation to 20 ± 2 L/min) will be measured using a facemask.

Intravenous remifentanil will be administered by target-controlled infusion (TCI), aimed at reducing isohypercapnic ventilation by 50%. After ventilation has reached a steady state, subjects will be randomized to step wise increases in S-ketamine or placebo infusions. The S-ketamine infusion is aimed at restoring ventilation to the baseline value (± 10%). If the baseline value is reached no further infusions are given.

On a separate occasion, we will assess the effect of ketamine on respiration by
performing the step-wise increases in ketamine but without the remifentanil and
without CO2 clamping.

We hypothesize that ketamine stimulates breathing and reverses opioid-induced respiratory depression.

Baseline ventilation, blood sampling, Ventilatory measurements. 3 visits

Ventilation will be elevated by isohypercapnic ventilation to 20L/min, if a steady-state is reached, there will be started with remifentanil. The ventilation will be decreased with 40-50%. After reaching steady-state again with remifentanil there will be started with ketamine or placebo