analgesics and hypnotics (apa cambridge 20. june 2013 tom g. hansen, md, phd, department of...
TRANSCRIPT
Analgesics and hypnotics (APA Cambridge 20. June 2013
Tom G. Hansen, MD, PhD, Department of Anaesthesia & Intensive Care Odense University Hospital & University of Southern DenmarkDENMARKEmail: [email protected]
Topics covered
• Some news about old drugs• Something about a new drug• Focus: neonates and infants• Focus: outcome, safety and
toxicity
Endpoints?
• Biomarkers for CNS injury (Neuron-specific enolase (NSE) and s-100β protein (t=0 h, after CPB, 6 h, 24 h, 48 h)
• Inflammatory mediators• Bayley Scales of Infant Development, 2nd Ed (BSID-
II) before and 2-3 w after surgery• MRI with spectroscopy (MRS) just before surgery
and just before hospital discharge (n=5): N-acetyl aspartate (NAA), creatine (Cr) and glutamate/glutamine sum
• NIRS < 24 h
Dexmedetomedine(Mason & Lerman Anesth Analg 2011)
Licenced for PICU OR+sedation (resp)
Problems: PK/PDInfants & neonates?slow onset/prolonged durationindication?haemodynamics (BP↓↑,HR↓)premedication?drug synergism?
Dexmedetomidine attenuates isoflurane-induced neuroapoptosis
Sanders et al. Acta Anaesthesiol Scand2010
Sanders et al. Anesthesiology 2009
(Caspase 3-activation↓)
NEOPAIN (Anand et al Lancet 2004; 363: 1673-82)
RCT, 16 centers: IPPV treated preterm infants, Morphine group(MG; n=449) and placebo group (PG; n=449) Intervention: preemptive morphine in IPPV LD 0.1 mg/kg, followed by CI 10 g/kg/h (GA 23-26) 20 g/kg/h (GA 27-29) 30 g/kg/h (GA 30-32) + open label morphine (OLM) for both groupsComposite primary outcome: Death, IVH and PVLResults: Analgesia but similar rates of deaths, IVH and PVL - OLM ↑CO and ↑severe IVH in MG vs. PG + OLM ↑CO in PG +OLM IVH in MG
Long term outcome The original Dutch studies (2000-2002)
Simons et al. JAMA 2003; 290: 2419-27Simons et al. Arch Dis Child Fetal Neonatal Ed2005; 90: F36-40 Simons et al. Arch Dis Child Fetal Neonatal Ed2006; 91: F46-51Placebo-controlled RCT (n=150) in preterms onIPPV receiving morphine: LD 0.1 mg/kg CI 10 g/kg/h+open label morphine: LD 0.05 mg/kg, CI 5-10 g/kg/hIVH in morphine group, but similar analgesia andneurological outcome