title: The anesthetic effects on vasopressor modulation of cerebral blood flow in an immature swine model.
abstract: BACKGROUND
  The effect of various sedatives and anesthetics on vasopressor modulation of cerebral blood flow (CBF) in children is unclear. In adults, isoflurane has been described to decrease CBF to a lesser extent than fentanyl and midazolam. Most large-animal models of neurocritical care use inhaled anesthetics for anesthesia. Investigations involving modulations of CBF would have improved translatability within a model that more closely approximates the current practice in the pediatric intensive care unit.
  
  
  METHODS
  Fifteen 4-week-old piglets were given 1 of 2 anesthetic protocols: total IV anesthesia (TIVA) (midazolam 1 mg/kg/h and fentanyl 100 μg/kg/h, n = 8) or ISO (isoflurane 1.5%-2% and fentanyl 100 μg/kg/h, n = 7). Mean arterial blood pressure, intracranial pressure (ICP), CBF, and brain tissue oxygen tension were measured continuously as piglets were exposed to escalating doses of arginine vasopressin, norepinephrine (NE), and phenylephrine (PE).
  
  
  RESULTS
  Baseline CBF was similar in the 2 groups (ISO 38 ± 10 vs TIVA 35 ± 26 mL/100 g/min) despite lower baseline cerebral perfusion pressure in the ISO group (45 ± 11 vs 71 ± 11 mm Hg; P < 0.0005). Piglets in the ISO group displayed increases in ICP with PE and NE (11 ± 4 vs 16 ± 4 mm Hg and 11 ± 8 vs 18 ± 5 mm Hg; P < 0.05), but in the TIVA group, only exposure to PE resulted in increases in ICP when comparing maximal dose values with baseline data (11 ± 4 vs 15 ± 5 mm Hg; P < 0.05). Normalized CBF displayed statistically significant increases regarding anesthetic group and vasopressor dose when piglets were exposed to NE and PE (P < 0.05), suggesting an impairment of autoregulation within ISO, but not TIVA.
  
  
  CONCLUSIONS
  The vasopressor effect on CBF was limited when using a narcotic-benzodiazepine-based anesthetic protocol compared with volatile anesthetics, consistent with a preservation of autoregulation. Selection of anesthetic drugs is critical to investigate mechanisms of cerebrovascular hemodynamics, and in translating critical care investigations between the laboratory and bedside.
authors: Department of Pediatrics, Washington University in St. Louis School of Medicine, Campus Box 8028, 5th Floor MPRB, 660 S. Euclid Ave., St. Louis, MO 63110. Friess_S@kids.wustl.ed.
authors: Benjamin
authors: B
authors: Bruins
authors: Todd J
authors: TJ
authors: Kilbaugh
authors: Susan S
authors: SS
authors: Margulies
authors: Stuart H
authors: SH
authors: Friess
mesh_terms: D000758:Anesthesia / Q000009:adverse effects; D000771:Anesthesia, Intravenous; D000777:Anesthetics / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016638:Critical Illness; D005283:Fentanyl / Q000494:pharmacology; D015278:Intensive Care Units, Pediatric; D007427:Intracranial Pressure / Q000187:drug effects; D007530:Isoflurane / Q000494:pharmacology; D008874:Midazolam / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D010656:Phenylephrine / Q000494:pharmacology; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000777:Anesthetics; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D010656:Phenylephrine; D007530:Isoflurane; D008874:Midazolam; D010100:Oxygen; D005283:Fentanyl; D009638:Norepinephrine