title: Urine and plasma catecholamine and cortisol concentrations after myocardial revascularization. Modulation by continuous sedation. Multicenter Study of Perioperative Ischemia (McSPI) Research Group, and the Ischemia Research and Education Foundation (IREF).
abstract: BACKGROUND
  Cardiopulmonary bypass is associated with substantial release of catecholamines and cortisol for 12 or more h. A technique was assessed that may mitigate the responses with continuous 12-h postoperative sedation using propofol.
  
  
  METHODS
  One hundred twenty-one patients having primary elective cardiopulmonary bypass graft (CABG) surgery were enrolled in a double-blind, randomized trial and anesthetized using a standardized sufentanil-midazolam regimen. When arriving at the intensive care unit (ICU), patients were randomly assigned to either group SC (standard care), in which intermittent bolus administration of midazolam and morphine were given as required to keep patients comfortable; or group CP (continuous propofol), in which 12 h of continuous postoperative infusion of propofol was titrated to keep patients deeply sedated. Serial perioperative measurements of plasma and urine cortisol, epinephrine, norepinephrine, and dopamine were obtained; heart rate and blood pressure were recorded continuously, and medication use, including requirements for opioids and vasoactive drugs, was recorded. Repeated-measures analysis was used to assess differences between study groups for plasma catecholamine and cortisol levels at each measurement time.
  
  
  RESULTS
  In the control state-before the initiation of postoperative sedation in the ICU-no significant differences between study groups were observed for urine or plasma catecholamine or cortisol concentrations. During the ICU study period, for the first 6-8 h, significant differences were found between study groups SC and CP in plasma cortisol (SC = 28 +/- 15 mg/dl; CP = 19 +/- 12 mg/dl; estimated mean difference [EMD] = 9 mg/dl; P = 0.0004), plasma epinephrine (SC = 132 +/- 120 micrograms/ml; CP = 77 +/- 122 micrograms/ml; EMD = 69 micrograms/ml; P = 0.009), urine cortisol (SC = 216 +/- 313 micrograms/ml; CP = 93 +/- 129 micrograms/ml; EMD = 127 micrograms/ml; P = 0.007), urine dopamine (SC = 85 +/- 48 micrograms; CP = 52 +/- 43 micrograms; EMD = 32 micrograms; P = 0.002), urine epinephrine (SC = 7 +/- 8 micrograms; CP = 4 +/- 5 micrograms; EMD = 3 micrograms; P = 0.0009), and urine norepinephrine (SC = 24 +/- 14 mg; CP = 13 +/- 9 mg; EMD = 11 mg; P = 0.0004). Reductions in urine and plasma catecholamine and cortisol concentrations found for the CP group generally persisted during the 12-h propofol infusion period and then rapidly returned toward control (SC group) values after propofol was discontinued. Postoperative opioid use was reduced in the CP group (SC = 97%; CP = 49%; P = 0.001), as was the incidence of tachycardia (SC = 79%; CP = 60%; P = 0.04) and hypertension (SC = 58%; CP = 33%; P = 0.01), but the incidence of hypotension was increased (SC = 49%; CP = 81%; P = 0.001).
  
  
  CONCLUSIONS
  Cardiopulmonary bypass graft surgery is associated with substantial increases in plasma and urine catecholamine and cortisol concentrations, which persist for 12 or more h. This hormonal response may be mitigated by a technique of intensive continuous 12-h postoperative sedation with propofol, which is associated with a decrease in tachycardia and hypertension and an increase in hypotension.
authors.affiliation: Department of Anesthesiology of Kaiser Permanente Medical Center, San Francisco, California, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Plunkett
authors.forename: J D
authors.initials: JD
authors.lastname: Reeves
authors.forename: L
authors.initials: L
authors.lastname: Ngo
authors.forename: W
authors.initials: W
authors.lastname: Bellows
authors.forename: S L
authors.initials: SL
authors.lastname: Shafer
authors.forename: G
authors.initials: G
authors.lastname: Roach
authors.forename: J
authors.initials: J
authors.lastname: Howse
authors.forename: A
authors.initials: A
authors.lastname: Herskowitz
authors.forename: D T
authors.initials: DT
authors.lastname: Mangano
mesh_terms: D000368:Aged; D002395:Catecholamines / Q000378:metabolism*; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D015742:Propofol / Q000494:pharmacology*
chemical_list: D002395:Catecholamines; D006993:Hypnotics and Sedatives; D006854:Hydrocortisone; D015742:Propofol