In my study, I need to maintain anesthesia and ventilation for about 6-7 hours in rats. However, I often encounter stability issues after 3-4 hours, where the rats develop bradycardia and even arrhythmia. Here's what I have experienced so far:

I anesthetize the rats with urethane (1,3-1,4 g/kg). For intubation and ventilation, I start with a 3 mg/kg bolus rocuronium, which works well initially for several minutes. The rats ventilate and saturate (oxygen saturation rises to 98-99) without any issues. After this, I begin a maintenance infusion of rocuronium. I've experimented with different doses, with the lowest being 600 mcg/kg/h. At this dose, I have to supplement with intermittent boluses of 1-2 mg/kg about every 30 minutes. Additional boluses help, increasing the oxygen saturation again to 98-99%. Despite this, the rats eventually become unstable, showing fluctuations in pulse, oxygen saturation, and heart rate after 3-4 hours, culminating in arrythmia.

I strongly suspect that this arrhythmia is due to rocuronium overdose and not anything else, as I start to see the irregularity of heart rate just before the decrease in oxygen saturation and administering more rocuronium during periods of instability makes the situation worse. However, even the lowest maintenance dose I tried (600 mcg/kg/h) wasn't enough on its own to provide sufficient oxygen saturation, necessitating additional bolus doses.

I would greatly appreciate any insights or suggestions on optimizing the dosing to maintain stable anesthesia and ventilation for the desired duration.