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What’s new in Neonatal Resuscitation? ¿Qué hay de nuevo en reanimación neonatal?. N. Ambalavanan MD Division of Neonatology, University of Alabama at Birmingham May 2003. Overview . The new NRP Outline Rationale for new guidelines Controversies and new concepts.
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What’s new in Neonatal Resuscitation?¿Qué hay de nuevo en reanimación neonatal? N. Ambalavanan MD Division of Neonatology, University of Alabama at Birmingham May 2003
Overview • The new NRP • Outline • Rationale for new guidelines • Controversies and new concepts
The new NRP Algorithm (4rd Edition, 2000) Birth • Clear of meconium? • Breathing or crying? • Good tone? • Color pink? • Term gestation? • Routine care • Provide warmth • Clear airway • Dry YES 30 sec NO • Provide warmth • Position; clear airway (as necessary) • Dry, stimulate, reposition • Give O2 (as necessary)
The new NRP Algorithm (contd.) Breathing HR>100 and pink • Evaluate respirations, • heart rate, and color Supportive care Apnea or HR<100 30 sec • Provide positive-pressure • ventilation* HR<60 HR>60 30 sec Ventilating HR>100 and pink • Provide positive-pressure ventilation* • Administer chest compressions Ongoing care HR<60 • Administer epinephrine* *ET intubation may be considered at Several steps
Objectives • Review the new guidelines for neonatal resuscitation and understand the rationale underlying these new guidelines • Review current controversies regarding neonatal resuscitation
New Guidelines • Management of meconium stained infants • Emphasis of ventilation as the primary concern for effective resuscitation • Indications for chest compressions • Indications for epinephrine • Others • Impact • New changes
New Guidelines • Management of meconium stained infants • Emphasis of ventilation as the primary concern for effective resuscitation • Indications for chest compressions • Indications for epinephrine • Others • Impact • New changes
Management of Meconium Stained Infants 1. Perform endotracheal suction of meconium-stained infants if any of the following is present: A. Absent or depressed respirations B. Decreased muscle tone or C. HR < 100/min 2. If the HR remains below 100/min or respiration is severely depressed, PPV is indicated following initial suctioning(s).
RCT of Endotracheal Suctioning in Vigorous Meconium-Stained Infants Intubation Expectant Rx* p n=1051 n=1043 MAS (%) 3.2 2.7 NS Other respiratory distress (%) 3.8 4.5 NS All causes 7.0 7.2 NS *61 (6%) of the infants developed respiratory distress and were suctioned. Wiswell, et al. Pediatrics 105:1,2000
New Guidelines • Management of meconium stained infants • Emphasis of ventilation as the primary concern for effective resuscitation • Indications for chest compressions • Indications for epinephrine • Others • Impact • New changes
Emphasis on Ventilation as the Most Important and Effective Action for Resuscitation • Initial steps and ventilation are effective in establishing normal vital signs in over 99.8% of infants (Perlman and Risser. Arch Pediatr Adolesc Med 149:20, 1995) • Chest compressions may interfere with ventilation and should not be initiated until adequate ventilation is established
New Guidelines • Management of meconium stained infants • Emphasis of ventilation as the primary concern for effective resuscitation • Indications for chest compressions • Indications for epinephrine • Others • Impact • New changes
Indications for Chest Compressions • Chest compressions are rarely indicated in the resuscitation of the newly born • Chest compressions are recommended if HR is less than 60 after 30 sec of adequate ventilation • Because of ease of teaching and skill retention, chest compressions are now recommended only if HR is less than 60/min
New Guidelines • Management of meconium stained infants • Emphasis of ventilation as the primary concern for effective resuscitation • Indications for chest compressions • Indications for epinephrine • Others • Impact • New changes
Indications for Epinephrine • Epinephrine is rarely indicated in the resuscitation of the newly born • Epinephrine is indicated if HR remains less than 60/min after a minimum of 30 seconds of adequate ventilation and chest compressions • Endotracheal route is faster, but may not be as effective as the intravenous route • Administration of higher dose epinephrine in neonates is not supported by adequate studies
New Guidelines • Management of meconium stained infants • Emphasis of ventilation as the primary concern for effective resuscitation • Indications for chest compressions • Indications for epinephrine • Others • Impact • New changes
Other Important Guidelines – Changes and Revisions • Resuscitation algorithm • Scientific contents • Supplies and equipment • Program contents • Administrative
New Guidelines • Management of meconium stained infants • Emphasis of ventilation as the primary concern for effective resuscitation • Indications for chest compressions • Indications for epinephrine • Others • Impact • New changes
Impact of Training in NRP – Controlled Trial Setting: 14 teaching hospitals in India Design: Historic controls 7,000 control group in 3 months pre-intervention 25,713 experimental group in 12 months post-intervention Outcome: Birth asphyxia (apnea/gasping at 1 and 5 min) Deorari et al. Ann Trop Paed 21:29, 2001
Impact of Training in NRP – Controlled Trial Results: Incidence of Asphyxia Pre-interventionPost-intervention pApnea/gasping 1 min 2.8% 3.8% <0.001 5 min 1.0% 1.4% <0.01 10 min 0.6% 0.7% NS Deorari et al. Ann Trop Paed 21:29, 2001
Pre-intervention Post-intervention p<0.001 Deorari et al. Ann Trop Paed 21:29, 2001
Impact of Training in NRP – Controlled Trial Pre-interventionPost-intervention p All causes 3.7% 3.5% NS Hypoxia 1.6% 1.1% <0.01 Results: Mortality Deorari et al. Ann Trop Paed 21:29,2001
New Guidelines • Management of meconium stained infants • Emphasis of ventilation as the primary concern for effective resuscitation • Indications for chest compressions • Indications for epinephrine • Others • Impact • New changes
Oro- and Nasopharyngeal Suction in MSF Infants Design: Multi-center RCT Inclusive criteria: Any consistency of MSF GA > 37 weeks Cephalic presentation No major congenital anomaly Outcome: Incidence of MAS Vain et al. Pediatr Res 51:379, 2002
Oro- and Nasopharyngeal Suction in MSF Infants Suction No Suction p MAS 3.6% 3.5% NS Mech vent (MAS) 1.1% 1.1% NS Mortality 0.4% 0.2% NS Results: n=2514 infants in 12 centers Vain et al. Pediatr Res 51:379, 2002
Areas of Controversy/Conflict But Insufficient Data • Who should be present at the delivery of an infant at low risk for need of resuscitation? Who should be present at the delivery of an infant at high risk for need of resuscitation?
Areas of Controversy/Conflict But Insufficient Data 2. Should the simultaneous assessment of a newborn during resuscitation include the parts of the Apgar scores not currently used (tone, reflex)? 3. Is nasopharyngeal and oral suction necessary in the infant with clear amniotic fluid?
Areas of Controversy/Conflict But Insufficient Data 4. Is the use of PEEP necessary during PPV? 5. Should air or an air-oxygen blender (mixer) be used during neonatal resuscitation? 6. What is the recommended saturation level that should be maintained during resuscitation?
Areas of Controversy/Conflict But Insufficient Data 7. Can adjunctive airways (e.g. laryngeal mask) be effective in neonatal resuscitation? 8. Is high-dose epinephrine effective when the normal dose of epinephrine is not?
Areas of Controversy/Conflict But Insufficient Data 9. Is THAM better than NaHCO3 in the treatment of metabolic acidosis? 10. Should hypothermia be used during and/or after neonatal resuscitation?
Summary • New guidelines emphasize ventilation as the most effective aspect of neonatal resuscitation • Further evidence of efficacy is needed • Many areas of controversy translates into many research opportunities
Controversies • Room air or 100% O2 resuscitation: Room air may be equivalent or better • Hypothermia or normothermia following resuscitation: trials in progress • Crystalloid and albumin for hypovolemia: no benefit for albumin • High vs standard epinephrine for resuscitation: no benefit for higher doses? • NaHCO3 or not for prolonged resuscitation: no benefit in human studies
Effect of Resuscitation Gas on Room Air – 100% O2 Room air 100% O2 p value Mod/severe asphyxia (n) 304 526 - Overall mortality (n) 1 17 NS Mortality in severe asphyxia (n, %) 1/16, 7% 6/14, 43% 0.053 (OR 0.003- 1.023) Vento et al. Biol Neonate 79:261, 2001.
Time of Onset of Breathing Vento et al. Biol Neonate 79:261,2001
Effect of O2 Resuscitation on Oxidative Stress Room air 100% O2 p value n=51 n=55 Ventilation for resuscitation 5.3+1.5 6.8+1.2 <0.05 (in minutes) PO2 126+22 72+7 <0.05 GSSG (oxidised glutathione) At end of resuscitation 83+10 102+14 <0.05 Clinical stabilization 83+13 111+21 <0.05 Vento et al. J Pediatr 142:240, 2003.
RCT of Room Air Resuscitation Setting: 11 centers, 6 countries Entry: BW > 999 grams Design: Randomized by birth date, not masked Primary outcome: Death by 1 week and/or HIE Enrolled: 703 from 11 centers, 94 patients Excluded: 94 patients from one center Saugstad et al. Pediatrics 102:e1, 1998
RCT of Room Air Resuscitation Room Air Oxygen OR CI Gestational age (wks) 38 38 Birthweight (gm) 2600 2560 7 day mort/HIE (%) 21 24 0.94 0.53-1.40 7 day mortality (%) 12 15 0.82 0.50-1.35 28 day mortality (%) 12 19 0.72 0.45-1.15 Resuscitation failure (%) 26 35 0.81 0.56-1.19 Saugstad et al. Pediatrics 102:e1, 1998
SummaryRoom Air vs 100% O2 • Room air resuscitation results in comparable (maybe better) survival and less oxidant injury • Further research is necessary, but room air resuscitation can be an alternative for neonatal resuscitation
Controversies In Neonatal Resuscitation • Room air or 100% O2 resuscitation • Hypothermia or normothermia following resuscitation • Crystalloid and albumin for hypovolemia • High vs standard epinephrine for resuscitation • NaHCO3 or not for prolonged resuscitation
Head Cooling in Neonates Study: 10 control, 12 head cooling infants Mild selective head cooling is a safe and convenient method of quickly reducing cerebral temperature (masopharyngeal temperature 34.5 ± 0.3ºC) Gunn et al. Pediatrics 102:885, 1998
Body Cooling in Neonates Mild hypothermia (33.2 ± 0.6ºC) resulted in: • Mild metabolic acidosis/high lactate • Low potassium (3.9 mmol/L) • Lower heart rate • Higher blood pressure But was well tolerated Azzopardi et al. Pediatrics 106:684, 2000
Summary : Hypothermia in Neonatal Resuscitation • Experiments demonstrated benefits of hypothermia • Small studies reveal mild physiologic abnormalities • RCTs of hypothermia in neonates following resuscitation are needed
Controversies In Neonatal Resuscitation • Room air or 100% O2 resuscitation • Hypothermia or normothermia following resuscitation • Crystalloid and albumin for hypovolemia • High vs standard epinephrine for resuscitation • NaHCO3 or not for prolonged resuscitation
RCT of Colloid Infusion in Hypotensive Infants (62 infants 24-36 weeks) Infusion BP Change 5 ml/kg of 20% albumin 9% 15 ml/kg of 4.5% albumin 17% 15 ml/kg of FFP 19% Volume rather than oncotic load affects BP Emery et al. Arch Dis Child 57:1185, 1982
RCT of Albumin in Hypoalbuminemic Infants (25–34 week infants) Design: 5 ml/kg of 20% albumin vs 5 ml/kg of maintenance fluids Results: Albumin infusion increased albumin levels, but did not improve the cardiorespiratory status Greenough et al. Eur J Pediatr 2:157, 1993
RCT of Albumin vs Crystalloid in Hypothermic Infants (63 infants 23-34 weeks) Design: 10 mL/kg 5% albumin vs 10 mL/kg NSS Results: Albumin group required more volume expander (27 vs 10 ml/kg) to maintain normal blood pressure So et al. Arch Dis Child 76:F43, 1997
RCT of Prophylactic FFP/Gelatin in Infants (776 infants < 32 weeks) FFP Gelatin Control p (glucose) Death or IVH 23% 27% 23% NS Death by 2 year 21% 25% 20% NS Death or disability 32% 36% 36% NS Greenough et al. Eur J Pediatr 155:580, 1996; Lancet 348:229, 1996
Volume Expansion in Normothermic Infants (940 stable infants <32 weeks or < 1500g) Volume vs no treatment RR CI Mortality 1.11 0.9-1.4 Severe disability 0.80 0.5-1.2 Mortality or disability 1.00 0.8-1.2 Osborn and Evans. Cochrane Data Syst Rev 2:CD002055, 2001
Summary Albumin in Neonatal Resuscitation Several randomized controlled trials do not demonstrate benefits of albumin administration in neonates