Optimizing anesthetic regimen for surgery in mice through minimization of hemodynamic, metabolic, and inflammatory perturbations

The role of anesthetics in animal research models is crucial, yet often ignored, and is almost never the primary focus of examination. Here, we investigated the impact of anesthetic regimens on different parameters of hemodynamics (blood pressure (BP) and heart rate (HR)), metabolism (glucose, insulin, and free fatty acids (FFA)), and inflammation (IL-6 and TNF-α) in two frequently used mouse strains (C57BL/6 and FVB). All animals were at a similar surgical plane of anesthesia, mechanically ventilated, and monitored for 60 min. The following anesthetic regimens were studied: (1) fentanyl–ketamine–midazolam (FKM), (2) fentanyl–midazolam–haldol (FMH), (3) pentobarbital (P), (4) fentanyl–fluanisone–midazolam (FFM), (5) fentanyl–midazolam–acepromazine (FMA), (6) ketamine–medetomidine–atropine (KMA), (7) isoflurane (ISO), and (8) propofol–fentanyl–midazolam (PFM). Metabolic and inflammatory parameters were compared with those obtained from non-anesthetized animals. Hemodynamics: BP >80 mm Hg were only obtained with KMA, whereas hypotension (BP <60 mm Hg) was observed with FKM and P. HR >500 beats/min was observed with ISO and PFM, whereas HR <400 beats/min was induced with KMA, FMH (BL/6), P (BL/6), and FKM (FVB). Metabolism: Glucose and insulin were most disturbed by KMA and ISO and mildly disturbed by FMA, whereas FFM, PFM, and P did not have any effect. FFA increased largely by FMA, with ISO and FKM having no effects. Inflammation: Cytokines were increased least with ISO/FFM/FMA, whereas FKM and KMA induced the largest increases in cytokines. When aiming at achieving surgical anesthesia without large disturbances in hemodynamic, metabolic, and inflammatory profiles, FFM, ISO, or PFM may be the most neutral anesthetic regimens in mice.