title: Neuromuscular block differentially affects immobility and cortical activation at near-minimum alveolar concentration anesthesia.
abstract: 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 (EtDes(50), 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.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, 300 Pasteur Drive, H3590, Stanford, CA 94305-5640, USA. agdoufas@stanford.edu
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Doufas
authors.forename: Ryu
authors.initials: R
authors.lastname: Komatsu
authors.forename: Mukadder
authors.initials: M
authors.lastname: Orhan-Sungur
authors.forename: Papiya
authors.initials: P
authors.lastname: Sengupta
authors.forename: Anupama
authors.initials: A
authors.lastname: Wadhwa
authors.forename: Edward
authors.initials: E
authors.lastname: Mascha
authors.forename: Steven L
authors.initials: SL
authors.lastname: Shafer
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler
mesh_terms: D000293:Adolescent; D000328:Adult; D000344:Afferent Pathways / Q000187:drug effects; D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D002540:Cerebral Cortex / Q000187:drug effects*; D000077335:Desflurane; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004569:Electroencephalography; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007103:Immobilization; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007530:Isoflurane / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007546:Isoquinolines / Q000008:administration & dosage*; D008297:Male; D000077590:Mivacurium; D009466:Neuromuscular Blocking Agents / Q000008:administration & dosage*; D017711:Nonlinear Dynamics; D017288:Pain Threshold / Q000187:drug effects; D013390:Succinylcholine / Q000008:administration & dosage*; D013997:Time Factors; D055815:Young Adult
chemical_list: D018685:Anesthetics, Inhalation; D007546:Isoquinolines; D009466:Neuromuscular Blocking Agents; D000077590:Mivacurium; D000077335:Desflurane; D007530:Isoflurane; D013390:Succinylcholine