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ANESTHETIC PHARMACOLOGY

Neuromuscular Block Differentially Affects Immobility and Cortical Activation at Near–Minimum Alveolar Concentration Anesthesia

Anthony G. Doufas, MD, PhD^*¶, Ryu Komatsu, MD, Mukadder Orhan-Sungur, MD, Papiya Sengupta, MD, Anupama Wadhwa, MD, Edward Mascha, PhD, Steven L. Shafer, MD, and Daniel I. Sessler, MD^||

From the *Department of Anesthesia, Stanford University School of Medicine, Stanford, California; Outcomes Research Institute, and Department of Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, Kentucky; Departments of Quantitative Health Sciences and Outcomes Research, The Cleveland Clinic, Cleveland, Ohio; Department of Anesthesiology, Columbia University, New York, New York; ||Department of Outcomes Research, The Cleveland Clinic, Cleveland, Ohio; and ¶Outcomes Research Consortium, Cleveland, Ohio.

Address correspondence and reprint requests to Anthony G. Doufas, MD, PhD, Department of Anesthesia, Stanford University School of Medicine, 300 Pasteur Drive, H3590, Stanford, CA 94305-5640. Address e-mail to agdoufas{at}stanford.edu.

BACKGROUND: Anesthesia-induced immobility and cortical suppression are governed by anatomically separate, but interacting, areas of the central nervous system. Consequently, larger volatile anesthetic concentrations are required to suppress cortical activation than to abolish movement in response to noxious stimulation. We examined the effect of decreased afferent input, as produced by neuromuscular block (NMB), on immobility and cortical activation, as measured by Bispectral index (BIS) of the electrocardiogram, in the presence of noxious stimulation during approximately minimum alveolar concentrations (MACs) of desflurane anesthesia.

METHODS: The effect of NMB on the median effective end-tidal concentration of desflurane (EtDes₅₀, or MAC_tetanus) for immobility was estimated using the up-and-down method and isolated forearm technique in 24 healthy volunteers. Each volunteer sequentially received saline, mivacurium, and succinylcholine in a randomized order, while EtDes concentration during each of the treatments was determined based on the movement response of the previous volunteer on the same treatment. Nonlinear mixed-effects modeling was used to evaluate the effect of NMB on BIS versus EtDes concentration relationship at baseline and after noxious stimulation, while the frontal electromyogram (EMG_BIS) effect on BIS was also modeled as a covariate. Cardiovascular responses to noxious stimulation were compared across treatments.

RESULTS: Succinylcholine and mivacurium significantly reduced MAC_tetanus (95% confidence interval) from 5.00% (4.85%–5.13%), during saline, to 4.05% (3.81%–4.29%) and 3.84% (3.60%–4.08%), respectively. Noxious stimulation significantly, although minimally, increased BIS response during all treatments. Succinylcholine increased BIS independently of an effect on EMG_BIS. Succinylcholine administration increased cardiovascular activity. Interestingly, although cardiovascular reaction to the noxious event was ablated by mivacurium, cortical response, as determined by BIS, was retained.

CONCLUSIONS: Both succinylcholine and mivacurium enhanced immobility during near-MAC anesthesia. All treatments were associated with a small, although significant, BIS increase in response to noxious stimulation, whereas succinylcholine increased BIS independently of noxious stimulation or EMG_BIS. Mivacurium suppressed autonomic response to a noxious event.