Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Analgesics and hypnotics (APA Cambridge 20. June 2013 Tom G. Hansen, MD, PhD, Department of Anaesthesia & Intensive Care Odense University Hospital & University of Southern Denmark DENMARK Email: [email protected] Topics covered • Some news about old drugs • Something about a new drug • Focus: neonates and infants • Focus: outcome, safety and toxicity Propofol, neonates and haemodynamics Demographics Haemodynamics NIRS Authors’ conclusions 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 (BSIDII) 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 NSE and CRP Conclusions Dexmedetomidine (2 adrenergic agonist) Dexmedetomedine (Mason & Lerman Anesth Analg 2011) Licenced for PICU OR+sedation (resp) Problems: PK/PD Infants & neonates? slow onset/prolonged duration indication? haemodynamics (BP↓↑,HR↓) premedication? drug synergism? Dexmedetomidine attenuates isofluraneinduced neuroapoptosis Sanders et al. Acta Anaesthesiol Scand 2010 Sanders et al. Anesthesiology 2009 (Caspase 3-activation↓) Context sensitive half times of opioids Ideal opioid for neonates and infants? Tolerance and hyperalgesia? NICU/PICU? MAC↓ Neurotoxcicity? 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 groups Composite primary outcome: Death, IVH and PVL Results: 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 Long term outcome The original Dutch studies (2000-2002) Simons et al. JAMA 2003; 290: 2419-27 Simons et al. Arch Dis Child Fetal Neonatal Ed 2005; 90: F36-40 Simons et al. Arch Dis Child Fetal Neonatal Ed 2006; 91: F46-51 Placebo-controlled RCT (n=150) in preterms on IPPV 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/h IVH in morphine group, but similar analgesia and neurological outcome Conclusions • Carefull dosing of anaesthetics and analgesics in very premature infants • Impact of haemodynamics on anaesthesiainduced neurotoxicity? • Normal blood pressure? • How do we treat hypotension?