Pancuronium dose refinement in experimental pigs used in cardiovascular research.

OBJECTIVE: To quantify the dose of pancuronium required to obtain moderate neuromuscular blockade as monitored by acceleromyography (NMB(mod) : train-of-four count of ≤2) as a part of a balanced anaesthetic protocol in pigs used in cardiovascular research. STUDY DESIGN: Prospective cross-sectional study. ANIMALS: Five pigs (median body weight: 60 (range 60-63) kg). METHODS: Anaesthesia was induced with xylazine, ketamine, atropine and midazolam and maintained with isoflurane in O(2) :air and fentanyl. Pigs received 0.1 mg kg(-1) pancuronium initial bolus to reach NMB(mod) followed by 0.1 mg kg(-1) hour(-1) constant rate infusion (CRI). During anaesthesia a twitch count of 3 or measureable T4/T1 ratio indicated unsatisfactory NMB. In this case additional 0.4 mg boluses of pancuronium were administered IV to effect in addition to the CRI. Descriptive statistical analysis was performed to express the median and range of the bolus and CRI dose of pancuronium in pigs. Cardiovascular parameters were analyzed at selected time points with Friedman Repeated Measures Analysis on Ranks. Spearman Rank test was used to evaluate correlation between parameters. RESULTS: Acceleromyographic monitoring of NMB is feasible in anaesthetized pigs. The median initial dose and rate of pancuronium required to achieve NMB(mod) were 0.10 (range 0.10-0.13) mg kg(-1) and 0.11 (range 0.10-0.21) mg kg(-1) hour(-1) , respectively. The administration rate showed considerable individual variation. CONCLUSIONS AND CLINICAL RELEVANCE: These pancuronium doses can be used as a guideline to achieve NMB(mod) in pigs as part of a balanced anaesthetic protocol. Instrumental NMB monitoring is essential because of individual kinetic variations and compliance to monitoring guidelines.

Plasma levels of a low-dose constant-rate-infusion of ketamine and its effect on single and repeated nociceptive stimuli in conscious dogs.

This study quantitatively investigated the analgesic action of a low-dose constant-rate-infusion (CRI) of racemic ketamine (as a 0.5 mg kg(-1) bolus and at a dose rate of 10 microg kg(-1) min(-1)) in conscious dogs using a nociceptive withdrawal reflex (NWR) and with enantioselective measurement of plasma levels of ketamine and norketamine. Withdrawal reflexes evoked by transcutaneous single and repeated electrical stimulation (10 pulses, 5 Hz) of the digital plantar nerve were recorded from the biceps femoris muscle using surface electromyography. Ketamine did not affect NWR thresholds or the recruitment curves after a single nociceptive stimulation. Temporal summation (as evaluated by repeated stimuli) and the evoked behavioural response scores were however reduced compared to baseline demonstrating the antinociceptive activity of ketamine correlated with the peak plasma concentrations. Thereafter the plasma levels at pseudo-steady-state did not modulate temporal summation. Based on these experimental findings low-dose ketamine CRI cannot be recommended for use as a sole analgesic in the dog.