title: Model-based control of neuromuscular block using mivacurium: design and clinical verification.
abstract: BACKGROUND
  Short-acting agents for neuromuscular block (NMB) require frequent dosing adjustments for individual patient's needs. In this study, we verified a new closed-loop controller for mivacurium dosing in clinical trials.
  
  
  METHODS
  Fifteen patients were studied. T1% measured with electromyography was used as input signal for the model-based controller. After induction of propofol/opiate anaesthesia, stabilization of baseline electromyography signal was awaited and a bolus of 0.3 mg kg-1 mivacurium was then administered to facilitate endotracheal intubation. Closed-loop infusion was started thereafter, targeting a neuromuscular block of 90%. Setpoint deviation, the number of manual interventions and surgeon's complaints were recorded. Drug use and its variability between and within patients were evaluated.
  
  
  RESULTS
  Median time of closed-loop control for the 11 patients included in the data processing was 135 [89-336] min (median [range]). Four patients had to be excluded because of sensor problems. Mean absolute deviation from setpoint was 1.8 +/- 0.9 T1%. Neither manual interventions nor complaints from the surgeons were recorded. Mean necessary mivacurium infusion rate was 7.0 +/- 2.2 microg kg-1 min-1. Intrapatient variability of mean infusion rates over 30-min interval showed high differences up to a factor of 1.8 between highest and lowest requirement in the same patient.
  
  
  CONCLUSIONS
  Neuromuscular block can precisely be controlled with mivacurium using our model-based controller. The amount of mivacurium needed to maintain T1% at defined constant levels differed largely between and within patients. Closed-loop control seems therefore advantageous to automatically maintain neuromuscular block at constant levels.
authors.affiliation: University Hospital, Department of Anesthesiology, Bern. peter.schumacher@dkf.unibe.ch
authors.forename: P M
authors.initials: PM
authors.lastname: Schumacher
authors.forename: K S
authors.initials: KS
authors.lastname: Stadler
authors.forename: R
authors.initials: R
authors.lastname: Wirz
authors.forename: D
authors.initials: D
authors.lastname: Leibundgut
authors.forename: C A
authors.initials: CA
authors.lastname: Pfister
authors.forename: A M
authors.initials: AM
authors.lastname: Zbinden
mesh_terms: D000328:Adult; D000776:Anesthesiology / Q000295:instrumentation*; D016503:Drug Delivery Systems / Q000009:adverse effects / Q000295:instrumentation*; D004576:Electromyography; D004867:Equipment Design; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D000077590:Mivacurium; D008962:Models, Theoretical; D019148:Neuromuscular Blockade / Q000295:instrumentation* / Q000379:methods; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage*; D010880:Piperidines / Q000008:administration & dosage; D015742:Propofol / Q000008:administration & dosage; D000077208:Remifentanil; D015203:Reproducibility of Results; D012449:Safety; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D010880:Piperidines; D000077590:Mivacurium; D000077208:Remifentanil; D005283:Fentanyl; D015742:Propofol