title: Closed-loop control of mean arterial blood pressure during surgery with alfentanil: clinical evaluation of a novel model-based predictive controller.
abstract: BACKGROUND
  In contrast to hypnosis, there is no surrogate parameter for analgesia in anesthetized patients. Opioids are titrated to suppress blood pressure response to noxious stimulation. The authors evaluated a novel model predictive controller for closed-loop administration of alfentanil using mean arterial blood pressure and predicted plasma alfentanil concentration (Cp Alf) as input parameters.
  
  
  METHODS
  The authors studied 13 healthy patients scheduled to undergo minor lumbar and cervical spine surgery. After induction with propofol, alfentanil, and mivacurium and tracheal intubation, isoflurane was titrated to maintain the Bispectral Index at 55 (+/- 5), and the alfentanil administration was switched from manual to closed-loop control. The controller adjusted the alfentanil infusion rate to maintain the mean arterial blood pressure near the set-point (70 mmHg) while minimizing the Cp Alf toward the set-point plasma alfentanil concentration (Cp Alfref) (100 ng/ml).
  
  
  RESULTS
  Two patients were excluded because of loss of arterial pressure signal and protocol violation. The alfentanil infusion was closed-loop controlled for a mean (SD) of 98.9 (1.5)% of presurgery time and 95.5 (4.3)% of surgery time. The mean (SD) end-tidal isoflurane concentrations were 0.78 (0.1) and 0.86 (0.1) vol%, the Cp Alf values were 122 (35) and 181 (58) ng/ml, and the Bispectral Index values were 51 (9) and 52 (4) before surgery and during surgery, respectively. The mean (SD) absolute deviations of mean arterial blood pressure were 7.6 (2.6) and 10.0 (4.2) mmHg (P = 0.262), and the median performance error, median absolute performance error, and wobble were 4.2 (6.2) and 8.8 (9.4)% (P = 0.002), 7.9 (3.8) and 11.8 (6.3)% (P = 0.129), and 14.5 (8.4) and 5.7 (1.2)% (P = 0.002) before surgery and during surgery, respectively. A post hoc simulation showed that the Cp Alfref decreased the predicted Cp Alf compared with mean arterial blood pressure alone.
  
  
  CONCLUSIONS
  The authors' controller has a similar set-point precision as previous hypnotic controllers and provides adequate alfentanil dosing during surgery. It may help to standardize opioid dosing in research and may be a further step toward a multiple input-multiple output controller.
authors.affiliation: Department of Anesthesiology, University Hospital of Bern, Switzerland. martin.luginbuehl@dkf.unibe.ch
authors.forename: Martin
authors.initials: M
authors.lastname: Luginbühl
authors.forename: Christian
authors.initials: C
authors.lastname: Bieniok
authors.forename: Daniel
authors.initials: D
authors.lastname: Leibundgut
authors.forename: Rolf
authors.initials: R
authors.lastname: Wymann
authors.forename: Andrea
authors.initials: A
authors.lastname: Gentilini
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Schnider
mesh_terms: D000328:Adult; D015760:Alfentanil / Q000008:administration & dosage* / Q000097:blood; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000764:Anesthesia, Closed-Circuit; D001794:Blood Pressure / Q000187:drug effects*; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000701:Analgesics, Opioid; D015760:Alfentanil