Jill. E. Boulton MD, FRCPC

MedicationsMedications

2:1000 newborns

MEDICATIONSMEDICATIONS

NRP 2006 AlgorithmNRP 2006 Algorithm

With skillful and timely With skillful and timely implementation of implementation of

resuscitation steps, 99% of resuscitation steps, 99% of newborns will improve newborns will improve without the need for without the need for

medicationsmedications

No drugs for me!No drugs for me!

MEDICATIONSMEDICATIONS

EpinephrineEpinephrine Volume expansionVolume expansion NaloxoneNaloxone What about Bicarb?What about Bicarb?

Epinephrine AdministrationEpinephrine AdministrationEpinephrine AdministrationEpinephrine Administration

“If the heart rate remains below 60 bpm, despite administration of ventilation and chest compressions, your first action is to ensure that ventilation and chest compressions are being given optimally and that you are using 100% oxygen” !

EpinephrineEpinephrineEpinephrineEpinephrine

EpinephrineEpinephrine Endogenous catecholamine with both Endogenous catecholamine with both α α

and β adrenergic propertiesand β adrenergic properties α effects cause vasoconstriction elevating α effects cause vasoconstriction elevating

aortic pressure and increasing coronary aortic pressure and increasing coronary perfusionperfusion

Stimulates and enhances cardiac Stimulates and enhances cardiac contractions and increases heart ratecontractions and increases heart rate

NEWBORNS ARE NOT LITTLE ADULTS NEWBORNS ARE NOT LITTLE ADULTS

(Burchfield, Ann Emerg Med 1993)(Burchfield, Ann Emerg Med 1993)

Terminal rhythm is bradyarrhythmia not Terminal rhythm is bradyarrhythmia not ventricular fibrillation ventricular fibrillation

Safety issues around fluid and Safety issues around fluid and hypertonic boluses due to lack of hypertonic boluses due to lack of cerebral blood flow auto regulationcerebral blood flow auto regulation

Transitional circulationTransitional circulation• Cardio/pulmonary/hepatic shuntsCardio/pulmonary/hepatic shunts• Fluid filled lungsFluid filled lungs

Science?Science?

Studies on Epinephrine in newborns are Studies on Epinephrine in newborns are sorely lackingsorely lacking

Current practices based on history and/or Current practices based on history and/or extrapolation from adult and animal extrapolation from adult and animal studiesstudies

? Higher dose Epinephrine? Higher dose Epinephrine

Experimental and Adult clinical studies – Experimental and Adult clinical studies – higher doses needed to achieve higher higher doses needed to achieve higher epinephrine levels and have sustained epinephrine levels and have sustained improvements in myocardial and cerebral improvements in myocardial and cerebral blood flowblood flow

BUTBUT Not translated into clinical benefit in either Not translated into clinical benefit in either

survival or neurologic outcomesurvival or neurologic outcome

Data in children shows no benefit to high Data in children shows no benefit to high dose therapy dose therapy Peroni 2004 – worse outcomes in paediatric Peroni 2004 – worse outcomes in paediatric

population with high dose epinephrinepopulation with high dose epinephrine No data specific to neonatal populationNo data specific to neonatal population Insufficient data to support routine use of Insufficient data to support routine use of

High-dose epinephrine High-dose epinephrine Class IndeterminateClass Indeterminate

Endotracheal EpinephrineEndotracheal Epinephrine

No randomized trials using endotracheal No randomized trials using endotracheal epinephrineepinephrine

One neonatal cohort study and one case series One neonatal cohort study and one case series showed benefit at 10X the doseshowed benefit at 10X the dose

Most animal trials that showed any positive Most animal trials that showed any positive effect used 5 –10 times the currently effect used 5 –10 times the currently recommended doserecommended dose

One neonatal model trial using the currently One neonatal model trial using the currently recommended dose showed no benefitrecommended dose showed no benefit

Endotracheal EpinephrineEndotracheal Epinephrine

If endotracheal route is used, the limited If endotracheal route is used, the limited available evidence suggests that a dose up to available evidence suggests that a dose up to 10X the current dose should be used10X the current dose should be used Class indeterminateClass indeterminate

Given the paucity of high quality clinical data Given the paucity of high quality clinical data regarding endotracheal epinephrine, the IV route regarding endotracheal epinephrine, the IV route should be used as soon as venous access is should be used as soon as venous access is establishedestablished

Endotracheal epinephrine must not interfere with Endotracheal epinephrine must not interfere with the establishment of good quality ventilation – the establishment of good quality ventilation – not effective in any dose without ventilationnot effective in any dose without ventilation

Epinephrine AdministrationEpinephrine Administration

Concentration = 1:10,000

Preferred route is IV but give first dose endotracheally while IV is obtained.

Dose IV = 0.1 ml/kg

Dose Endotracheal = 1.0 ml/kg

Administration Rate = rapidly

AAP Canadian Addendum

Medication Given: No Medication Given: No ImprovementImprovement

“If the baby appears to be in shock and is not responding to resuscitation, administration of a volume expander may be indicated” !

Shock - HypovolemiaShock - Hypovolemia Shock - HypovolemiaShock - Hypovolemia

Signs of HypovolemiaSigns of Hypovolemia

Pallor persisting beyond oxygenationPallor persisting beyond oxygenation Weak pulsesWeak pulses Low blood pressureLow blood pressure Lack of response to resuscitationLack of response to resuscitation

Hypovolemia is a common but often Hypovolemia is a common but often unrecognized cause of need for unrecognized cause of need for resuscitationresuscitation

HypovolemiaHypovolemia

Overt bleedingOvert bleeding• Placenta previa Placenta previa • Vaso previa, cord avulsionVaso previa, cord avulsion• AbruptionAbruption

Occult blood lossOccult blood loss• Feto-maternal hemorrhageFeto-maternal hemorrhage• Feto-fetal hemorrhageFeto-fetal hemorrhage• ““Feto-placental” hemorrhage (e.g. nuchal Feto-placental” hemorrhage (e.g. nuchal

cord)cord)

Volume ExpansionVolume Expansion

Indicated when there is no response to Indicated when there is no response to resuscitation and there is evidence of resuscitation and there is evidence of blood loss or hypovolemia blood loss or hypovolemia

Repeated doses may be necessary if Repeated doses may be necessary if there is minimal response after the first there is minimal response after the first dosedose

Umbilical vein remains preferred route but Umbilical vein remains preferred route but intraosseous acceptable (class IIb)intraosseous acceptable (class IIb)

Medication Administration via Medication Administration via Umbilical VeinUmbilical Vein

Preferred route for Preferred route for intravenous accessintravenous access

3.5F or 5F end-hole 3.5F or 5F end-hole cathetercatheter

Sterile techniqueSterile technique

Placing catheter in Placing catheter in

umbilical veinumbilical vein

Intraosseous Vascular AccessIntraosseous Vascular Access

IO route is recommended when other IO route is recommended when other routes are not available/unsuccessful. routes are not available/unsuccessful.

IO route may be established first in out-of-IO route may be established first in out-of-hospital locations or when providers with hospital locations or when providers with skills at providing venous access are not skills at providing venous access are not availableavailable Class II b recommendationClass II b recommendation

Volume ExpandersVolume Expanders

Isotonic crystalloid is the preferred solution Isotonic crystalloid is the preferred solution for volume expansion in neonatal for volume expansion in neonatal resuscitationresuscitation Class IIa recommendationClass IIa recommendation

AlbuminAlbumin

Observed association with increased Observed association with increased mortality in adults mortality in adults (Cochrane review, BMJ 1998)(Cochrane review, BMJ 1998)

Potential transmission of infectious agentsPotential transmission of infectious agents Limited availabilityLimited availability Studies have shown that it is volume of Studies have shown that it is volume of

fluid infused rather than solute load that fluid infused rather than solute load that corrects hypotension corrects hypotension (Emery, Arch Dis Child (Emery, Arch Dis Child 1992)1992)

Volume ExpandersVolume Expanders

Isotonic crystalloid is the preferred solution Isotonic crystalloid is the preferred solution for volume expansion in neonatal for volume expansion in neonatal resuscitationresuscitation Class IIa recommendationClass IIa recommendation

O-negative blood used for large volume O-negative blood used for large volume blood lossblood loss

Volume ExpandersVolume Expanders

Dose and Rate:Dose and Rate: 10 ml /kg slow IV push10 ml /kg slow IV push

““Acute hypovolemia resulting in a need for Acute hypovolemia resulting in a need for resuscitation, should be corrected fairly quickly resuscitation, should be corrected fairly quickly although some clinicians are concerned that rapid although some clinicians are concerned that rapid administration in a newborn my result in intracranial administration in a newborn my result in intracranial hemorrhage, particularly in preterm infants . No hemorrhage, particularly in preterm infants . No clinical trials have been conducted to define an clinical trials have been conducted to define an optimal rate, but a steady infusion rate over 5 – 10 optimal rate, but a steady infusion rate over 5 – 10 minutes is reasonable”minutes is reasonable”

Expected Response: Volume Expected Response: Volume ExpandersExpanders

Expected signs of volume expansionExpected signs of volume expansion Heart rate increasesHeart rate increases Pulses strongerPulses stronger Pallor lessensPallor lessens Blood pressure increasesBlood pressure increases

Follow up if hypovolemia persistsFollow up if hypovolemia persists Repeat volume expanders (dose 10 mL/kg)Repeat volume expanders (dose 10 mL/kg)

NaloxoneNaloxone

No studies examining the recommended dose of No studies examining the recommended dose of 0.1mg/kg in any clinical situation in newborns.0.1mg/kg in any clinical situation in newborns.

Endotracheal route has been evaluated in adults Endotracheal route has been evaluated in adults but no evidence for the use of this route in but no evidence for the use of this route in newborns.newborns.

Not necessary during the acute phase of Not necessary during the acute phase of resuscitationresuscitation

““Giving a narcotic antagonist is not the correct first therapy for a baby Giving a narcotic antagonist is not the correct first therapy for a baby who is not breathing. The first corrective action is positive pressure who is not breathing. The first corrective action is positive pressure ventilation”ventilation”

NaloxoneNaloxone

Indications for use:Indications for use: Continued respiratory depression after PPV Continued respiratory depression after PPV

has restored a normal heart rate and colourhas restored a normal heart rate and colourANDAND History of maternal narcotic administration in History of maternal narcotic administration in

the 4 hours prior to birththe 4 hours prior to birth Contraindicated in presence of maternal narcotic Contraindicated in presence of maternal narcotic

dependence dependence Class Indeterminate recommendationClass Indeterminate recommendation

Sodium BicarbonateSodium Bicarbonate

““Sodium bicarbonate is discouraged Sodium bicarbonate is discouraged during brief CPR but may be useful during during brief CPR but may be useful during prolonged arrests after adequate prolonged arrests after adequate ventilation is established and there is no ventilation is established and there is no response to other therapies”response to other therapies” Class II b recommendationClass II b recommendation

Summary of Clinical and Animal Summary of Clinical and Animal ObservationsObservations

Known and potential side effects:Known and potential side effects: Rapid infusion may reduce myocardial functionRapid infusion may reduce myocardial function Bicarbonate increases extra cellular pH, but Bicarbonate increases extra cellular pH, but

intracellular pH may remain unchangedintracellular pH may remain unchanged Decreased cerebral blood flow described in Decreased cerebral blood flow described in

infants post bicarbonate infusioninfants post bicarbonate infusion Risk of IVH in preterm infantsRisk of IVH in preterm infants

IF NO IMPROVEMENT …IF NO IMPROVEMENT … IF NO IMPROVEMENT …IF NO IMPROVEMENT …

Thank youThank you