ObjectiveTo provide evidence concerning doses of ketamine that affect electroencephalographic (EEG) and autonomic signs of arousal during nociceptive stimulation. Study designProspective psychophysical test in people. Single injection or progressively increasing infusions of ketamine in cats.Animals and people Seven people (20–60 years old) and three cats (3–5 kg) for EEG recording and six cats for EMG recordings. MethodsIn order to define innocuous and nociceptive stimulus intensities which could be applied to cats to evaluate arousal, psychophysical evaluations of sensations elicited by compression of the skin overlying phalangeal bones of the hand were obtained from human subjects. Then, following administration of ketamine, recordings of EEG frequency and of autonomic responses (heart rate, respiratory rate and arterial blood pressure) were obtained before and during stimulation of the tails of cats at pressures identified by human observers as either innocuous or nociceptive. Observations of withdrawal reflexes of the hindlimbs following interdigital skin stimulation were interposed between recording periods. In separate sessions, stretch reflex activity was assessed during awake and anesthetic conditions by recording electromyographic activity from soleus muscles and resistive force to dorsiflexion of the tibiotarsal joint. ResultsThere were no changes in either total EEG (0.5–30.0 Hz), low–frequency (0.6–7.5 Hz) or high–frequency (7.5–30.0 Hz) power produced by nociceptive stimulation for a period of 18–24 minutes following an intramuscular bolus dose of ketamine (33.0 mg kg−1), although withdrawal reflexes were present. Thereafter, nociceptive stimulation produced EEG arousal responses in the low–frequency and total power range and increased systolic blood pressure and respiration rate. In tests after intravenous infusion of ketamine (10.0–22.2 mg kg−1 hour−1), total and low–frequency EEG power and autonomic responses to nociceptive stimulation were eliminated. Organized motor responses were never elicited during IV infusion, but withdrawal reflexes were observed at each dosage. Also, stretch reflexes were shown by quantitative analysis to be retained at all doses of ketamine infusion.Conclusions and clinical relevance These results show that testing of withdrawal reflexes does not reveal the adequacy of ketamine anesthesia. Segmental stretch and withdrawal reflexes are preserved and can be investigated during infusion of ketamine at doses that eliminate arousal from brief periods of nociceptive stimulation.