title: Serum anticholinergic activity and postoperative cognitive dysfunction in elderly patients.
abstract: BACKGROUND
  Cerebral cholinergic transmission plays a key role in cognitive function, and anticholinergic drugs administered during the perioperative phase are a hypothetical cause of postoperative cognitive dysfunction (POCD). We hypothesized that a perioperative increase in serum anticholinergic activity (SAA) is associated with POCD in elderly patients.
  
  
  METHODS
  Seventy-nine patients aged >65 years undergoing elective major surgery under standardized general anesthesia (thiopental, sevoflurane, fentanyl, and atracurium) were investigated. Cognitive functions were assessed preoperatively and 7 days postoperatively using the extended version of the CERAD-Neuropsychological Assessment Battery. POCD was defined as a postoperative decline >1 z-score in at least 2 test variables. SAA was measured preoperatively and 7 days postoperatively at the time of cognitive testing. Hodges-Lehmann median differences and their 95% confidence intervals were calculated for between-group comparisons.
  
  
  RESULTS
  Of the patients who completed the study, 46% developed POCD. Patients with POCD were slightly older and less educated than patients without POCD. There were no relevant differences between patients with and without POCD regarding gender, demographically corrected baseline cognitive functions, and duration of anesthesia. There were no large differences between patients with and without POCD regarding SAA preoperatively (pmol/mL, median [interquartile range]/median difference [95% CI], P; 1.14 [0.72, 2.37] vs 1.13 [0.68, 1.68]/0.12 [-0.31, 0.57], P = 0.56), SAA 7 days postoperatively (1.32 [0.68, 2.59] vs 0.97 [0.65, 1.83]/0.25 [-0.26, 0.81], P = 0.37), or changes in SAA (0.08 [-0.50, 0.70] vs -0.02 [-0.53, 0.41]/0.1 [-0.31, 0.52], P = 0.62). There was no significant relationship between changes in SAA and changes in cognitive function (Spearman rank correlation coefficient preoperatively of 0.03 [95% CI, -0.21, 0.26] and postoperatively of -0.002 [95% CI, -0.24, 0.23]).
  
  
  CONCLUSIONS
  In this panel of patients with low baseline SAA and clinically insignificant perioperative anticholinergic burden, although a relationship cannot be excluded in some patients, our analysis suggests that POCD is probably not a substantial consequence of anticholinergic medications administered perioperatively but rather due to other mechanisms.
authors.affiliation: From the Department of Anesthesia, Lausanne University Hospital, Lausanne, Switzerland; Department of Anesthesia, Surgical Intensive Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, Basel, Switzerland; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada; Centre for Addiction and Mental Health, Toronto, Canada; and Memory Clinic, University Center for Medicine of Aging, Felix Platter Hospital, Basel, Switzerland.
authors.forename: Ariane
authors.initials: A
authors.lastname: Rossi
authors.forename: Christoph
authors.initials: C
authors.lastname: Burkhart
authors.forename: Salome
authors.initials: S
authors.lastname: Dell-Kuster
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.forename: Stephan P
authors.initials: SP
authors.lastname: Strebel
authors.forename: Andreas U
authors.initials: AU
authors.lastname: Monsch
authors.forename: Christian
authors.initials: C
authors.lastname: Kern
authors.forename: Luzius A
authors.initials: LA
authors.lastname: Steiner
mesh_terms: D000368:Aged; D000768:Anesthesia, General / Q000009:adverse effects*; D018680:Cholinergic Antagonists / Q000097:blood*; D003072:Cognition Disorders / Q000097:blood* / Q000175:diagnosis / Q000523:psychology*; D017558:Elective Surgical Procedures / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011183:Postoperative Complications / Q000097:blood* / Q000175:diagnosis / Q000523:psychology*
chemical_list: D018680:Cholinergic Antagonists
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