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Opioids have no place before cord clamping?

Opioids have no place before cord clamping? . David Bogod, University Hospitals Nottingham. Variation in rapid sequence induction techniques: current practice in Wales . Koerber JP, Roberts GEW, Whitaker R, Thorpe CM. Anaesthesia 2009; 64: 54-59. Anaesthesia 2009; 64: 54-59.

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Opioids have no place before cord clamping?

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  1. Opioids have no place before cord clamping? David Bogod, University Hospitals Nottingham

  2. Variation in rapid sequence induction techniques: current practice in Wales Koerber JP, Roberts GEW, Whitaker R, Thorpe CM Anaesthesia 2009; 64: 54-59

  3. Anaesthesia 2009; 64: 54-59

  4. Anaesthesia 2009; 64: 54-59

  5. Placental Transfer Haemomonochorial villous placenta Cytotrophoblast + Syncytiotrophoblast Vasculosyncytial membrane

  6. Placental Transfer • Fentanyl, alfentanil, sufentanil • Highly lipophylic • Low molecular weight • Readily diffuse across placenta • Equilibrium (unionised and non-bound) in single circulation • Transfer dependent on: • Concentration gradient • Maternal and fetal placental blood flow

  7. Placental Transfer • Fentanyl, alfentanil, sufentanil • Highly lipophylic • Low molecular weight • Readily diffuse across placenta • Equilibrium (unionised and non-bound) in single circulation Flow-dependent transfer

  8. Placental Distribution • Protein binding • pH dependent •  pH   protein binding • Fetal 1-AGP << Maternal 1-AGP (S, A) • Fetal albumin  Maternal albumin (F)

  9. Placental Distribution • Fetal pH < Maternal pH (Ion trapping) • Fetal redistribution and elimination < Maternal • UV/M ratio – placental distribution • UA/UV ratio – fetal compartment equilibration

  10. Fentanyl • Detected within 1 min of maternal iv administration • Peaked at 5 min after 50-100 µg • Maternal 2.5 times fetal at equilibrium • Equilibrium 5 min – 60 min • 5 µg/kg  neonatal 2.1 ng/ml • 1-2 ng/ml  depression of CO2 response • 2-4.6 ng/ml  50% depression

  11. Alfentanil • 10 µg/kg  neonatal ~ 7.5 ng/ml • 30 µg/kg  neonatal ~ 20 ng/ml • 21 ng/ml  31% depression of CO2 response • 110 ng/ml  50% depression

  12. Intravenous Remifentanil: Placental Transfer, Maternal and Neonatal Effects Kan, Randall E.; Hughes, Samuel C.; Rosen, Mark A.; Kessin, Charlize; Preston, Paul G.; Lobo, Errol P Anesthesiology 1998; 88: 1467-1474

  13. Remifentanil • 19 patients – elective LSCS • Epidural lidocaine with adrenaline • 0.1 µg/kg/min for at least 15 min • Continued until skin closure Anesthesiology 1998; 88: 1467-1474

  14. Remifentanil ng/ml Anesthesiology 1998; 88: 1467-1474

  15. SYSTEMIC AND PULMONARY BLOOD PRESSURE DURING CAESAREAN SECTION IN PARTURIENTS WITH GESTATIONAL HYPERTENSION Hodgkinson R, Hussain FJ and Hayashi RH Can. J Anesth 1980, 27, 389

  16. Maternal haemodynamics • 10 patients with BP 160/110 despite treatment, for emergency LSCS • Swan-Ganz and arterial lines • Hydralazine and MgSO4 • Glycopyrrolate 0.2 mg • Standard rapid-sequence induction Can. J Anesth 1980, 27, 389

  17. Can. J Anesth 1980, 27, 389

  18. Maternal haemodynamics • Mean rise in MAP – 45 mmHg • Highest rise – 200/90  360/150 mmHg • Mean rise in PAP, PCWP – 20 mmHg Can. J Anesth 1980, 27, 389

  19. General anaesthesia in mothers with severe pre-eclampsia /eclampsia Connell H, Dalgleish JG, Downing JW British Journal of Anaesthesia 1987, 59, 1375-1380

  20. “All patients received astandard anaesthetic technique designed to control the potentiallydangerous reflex cardiovascular instability associated withlaryngoscopy. The average increase in systolic arterial pressure(SAP) was 56.4 mmHg following laryngoscopy and tracheal intubation” British Journal of Anaesthesia 1987, 59, 1375-1380

  21. Intravenous Remifentanil: Placental Transfer, Maternal and Neonatal Effects Kan, Randall E.; Hughes, Samuel C.; Rosen, Mark A.; Kessin, Charlize; Preston, Paul G.; Lobo, Errol P Anesthesiology 1998; 88: 1467-1474

  22. Remifentanil

  23. Maternal and neonatal effects of remifentanil at induction of general anesthesia for cesarean delivery: a randomized, double-blind, controlled trial Ngan Kee WD, Khaw KS, Ma KC, Wong AS, Lee BB, Ng FF Anesthesiology 2006; 104:14-20

  24. Remifentanil • 40 patients for elective LSCS under GA • 20  1 µg/kg remifentanil bolus • 20  saline • Rapid-sequence induction Anesthesiology 2006; 104:14-20

  25. Remifentanil p <0.0001 Anesthesiology 2006; 104:14-20

  26. Remifentanil • Apgar scores + TSR – no significant difference • Two neonates in remi group needed naloxone • UV/M ratio – 0.73 • UA/UV ratio – 0.60 Anesthesiology 2006; 104:14-20

  27. Remifentanil “A single bolus of 1 µg/kg of remifentanil effectively attenuated hemodynamic changes after induction and tracheal intubation. However, remifentanil crosses the placenta and may cause mild neonatal depression, and thus should be used for clear maternal indications when adequate facilities for neonatal resuscitation are available.” Anesthesiology 2006; 104:14-20

  28. Uterine blood flow and plasma norepinephrine changes during maternal stress in the pregnant ewe Shnider SM, Wright RG, Levinson G et al Anesthesiology 1979; 50:524-7

  29. Uterine blood flow • 18 near-term pregnant ewes • Maternal, fetal and umbilical arterial monitoring • 10  “unintentional episodes of stress” • 8  30 V / 167 Hz shock for 30-60 seconds • Norepinephrine levels at 1, 3 and 10 min • Cardiovascular data at 1, 3, 5, and 10 min Anesthesiology 1979; 50:524-7

  30. Anesthesiology 1979; 50:524-7

  31. Anesthesiology 1979; 50:524-7

  32. Alfentanil Given Immediately Before the Induction of Anesthesia for Elective Cesarean Delivery Gin T, Ngan Kee WD, Siu YK, Stuart JC, Tan PE and Lam KK Anesth Analg 2000; 90: 1167–72

  33. Alfentanil for CS • 40 women randomised to saline or alfentanil 10 µg/kg before RSI • NIBP at 1-min intervals • Maternal catecholamines at 0, 1, 2, 3 and 4 min after induction, 1 min after incision, at delivery • UV / UA catecholamines after delivery Anesth Analg 2000; 90: 1167–72

  34. Anesth Analg 2000; 90: 1167–72

  35. Anesth Analg 2000; 90: 1167–72

  36. Anesth Analg 2000; 90: 1167–72

  37. Anesth Analg 2000; 90: 1167–72

  38. Anesth Analg 2000; 90: 1167–72

  39. Maternal and Neonatal Effects of Remifentanil at Induction of General Anesthesia for Cesarean Delivery Ngan Kee WD, Khaw KS, Ma KC et al Anesthesiology 2006; 104: 14-20

  40. Remifentanil for CS • 40 patients - 1 µg/kg remifentanil or saline over 30 s, followed by RSI • NIBP at 1-min intervals • Maternal, UV and UA remifentanil levels at delivery Anesthesiology 2006; 104: 14-20

  41. Anesthesiology 2006; 104: 14-20

  42. Anesthesiology 2006; 104: 14-20

  43. Anesthesiology 2006; 104: 14-20

  44. Conclusion • Short-acting opioids cross the placenta rapidly and achieve significant fetal levels, sufficient to cause reduced Apgar scores and a longer time to sustained respiration. • However, they are effective in suppressing maternal hypertensive surges, which can reach hazardous levels especially in patients with PIH / PET • They also suppress catecholamine surges, which have been shown to cause reduction in placental blood flow in animal models.

  45. Conclusion • Maternal opioids do not influence need for neonatal resuscitation, admission to SCBU or fine neurobehavioural scores • They do not affect neonatal blood gases, and may even improve them • There is no reason not to use opioids in at-risk patients at induction for Caesarean section, and every good reason to use them

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