PPHN PPHN is defined as the failure of normal circulatory - - PowerPoint PPT Presentation

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PPHN PPHN is defined as the failure of normal circulatory - - PowerPoint PPT Presentation

Feb 13, 2023 302 likes •1.65k views

Dr .P.K. Rajiv MBBS DCH MD Fellowship in Neonatology ( Australia) Head of Newborn Services NMC Specialty Hospital Dubai United Arab Emirates Formerly Professor and Head of Neonatology Amrita Institute Of medical Sciences Cochin Kerala PPHN PPHN

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Dr .P.K. Rajiv MBBS DCH MD

Fellowship in Neonatology ( Australia)

Head of Newborn Services NMC Specialty Hospital

Dubai United Arab Emirates

Formerly

Professor and Head of Neonatology Amrita Institute Of medical Sciences

Cochin Kerala

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PPHN is defined as the failure of normal circulatory transition,that occurs after birth.It is a syndrome characterised by marked pulmonary hypertension that causes hypoxemia and right to left shunting of blood.The clinical clue is the labile hypoxemia out of proportion to the disease process.

PPHN

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PPHN

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DIAGNOSIS OF PPHN PATHOGENESIS MANAGEMENT POST INO ERA

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Persistent Pulmonary Hypertension

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Pulmonary Hypertension Outline

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Neonatal Respiratory Failure

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PPHN: A Clinical Syndrome

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Etiology of HRF

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  • Apnea

– neurologic and pharmacologic causes

  • Diffusion barrier

– RDS, aspiration, pneumonia

  • Obstruction

– pneumothorax, head position

Not Enough Oxygen In

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  • Shunting lesions

– cardiac – non-cardiac (like PPHN)

  • Hematologic

– methemoglobinemia – carboxyhemoglobinemia

Oxygen “mal-absorption”

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  • High oxygen consumption

– Sepsis – Low flow, high extraction

  • acrocyanosis
  • hyperviscosity/polycythemia
  • extravasated (ie bruising)

Too Much Oxygen Out

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Vascular Pathogenesis of HRF

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Hemodynamic Changes in HRF

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Common Associations with PPHN

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Pulmonary Vascular Resistance is Increased in Fetal Life

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Variations in PVR and SVR During Gestation Human Fetus

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Normal Fetus

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Mechanisms of Increased Pulmonary Vascular Resistance in Fetal Life

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Dilation of Pulmonary Blood Vessels at Birth

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Pulmonary Vascular Resistance Falls at the Time of Birth

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Regulation of Pulmonary Vascular Tone

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PPHN new modalities of treatment

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PPHN new modalities of treatment

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PPHN new modalities of treatment

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Nitric oxide

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Maturation of the NO-c GMP System

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Nitric Oxide is a Byproduct of the Conversion

  • f Arginine to Citrulline
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Pathogenesis of PPHN

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eNOS: A Double Edged Sword

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eNOS, Heat Shock Protein 90 & Superoxide

radical(O2-)

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Pathology of PPHN

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PPHN & Distribution of Muscle

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Pathophysiology of Pulmonary Hypertension

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Diagnosis of PPHN

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Cyanosis

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Hyperoxia Test

  • Infant on Room Air, get ABG
  • Infant on 100% oxygen, get ABG
  • PaO2 unchanged = fixed shunt = CCHD
  • Max PaO2 <100 = CCHD
  • Max PaO2 >200 = No CCHD
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Hyperoxia Test

  • Jones: 1976

– 8/109 with CCHD had PaO2 > 100mmHg – 7/23 without CCHD (bad RDS etc) had PaO2 < 150mmHg

  • Hypoplastic Left Heart Syndrome > 300mmHg
  • TGA, TAPVR > 200mmHg
  • Don’t be fooled by early high PaO2s
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  • Don’t do the room air part

– Looking for minimal PaO2 change from 21% to 100% fiO2 – Hyperoxia test developed pre pulse-ox – With pulse-ox you can tell when PaO2s are not changing despite big changes in fiO2 (for sats that are between 70 and 95%) – Probably the norm to have some degree of lung disease at the time of the test anyway

Hyperoxia Test

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Shunt Curves

  • Hyperoxia

Proper

  • Hyperoxia

CPAP

  • Hyperoxia

hyper- ventilation

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Thumb Rule to Assess Shunt / PPHN

  • Fio 2(%) x 4 optimum pao2
  • Fio2(%) x 3 acceptable pao2 with shunt
  • Any value of pao2 exceeding 15 to 20 % of this value is a

significant shunt

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Information Needed

  • Clinical appearance

– “comfortably tachypneic and blue”

  • Pulses/perfusion

– differential, delayed

  • Pulse-Ox/ABG

– pre and post ductal, max PaO2

  • Auscultation

– S2, Murmur

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  • CXR

– heart shapes

  • snowman = TAPVR1
  • boot = pulm atresia, TOF, tricuspid atresia
  • egg on string = TGA

+ /- pulmonary vascularity

  • EKG

– axis – increased or decreased forces

  • ECHO

– the most important test in PPHN

Information Needed

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Echocardiographic Diagnosis of PPHN

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PDA with Right to Left Shunt

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Novel Methods for Assessment of Right heart Structure and Function in Pulmonary Hypertension

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Novel Methods for Assessment of Right heart Structure and Function in Pulmonary Hypertension

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Novel Methods for Assessment of Right heart Structure and Function in Pulmonary Hypertension

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Accuracy of clinical diagnosis and decision to commence intravenous prostaglandin E1 in neonates presenting with hypoxemia in a transport setting

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Use of Intravenous PGE 1 in Neonates Presenting with Hypoxemia

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Management of Infants with Pulmonary Hypertension

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Control of Blood Pressure

Feel posterior tibial pulsation well DOPAMINE 10 DOBUTAMINE 10 MILRINONE

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XRAY aim for about 8.5 to 9 ribs expansion clearance of haziness

Control of FRC CPAP / PEEP

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DONT BASH THE LUNG

Ph . > 7.25 Co2 < 60 mmhg O2 50 - 70 mmhg Pediatrics oct 1985 76 (4 ) 488 -94 Wung JT

DO SO ONLY IF THE END EXPIRATORY PRESSURE OR CPAP IS RIGHT

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Cardiopulmonary Interactions in PPHN

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The Vicious Cycle of PPHN

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Unproven Therapeutic Strategies in PPHN

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Proven Therapeutic Strategies in PPHN

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Use of Surfactant in PPHN

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Surfactant and Meconium Aspiration Syndrome: Mechanisms of Action

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Use of Surfactant in PPHN

Oxygenation Index

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Surfactant Replacement in the Term Newborn

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Guidelines for Mechanical Ventilation in PPHN

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Effect of Ventilation – Pulmonary Vascular Resistance (PVR) is Minimal at FRC

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The million dollar question of optimisation of PEEP

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Randomized Multicenter Trial of Inhaled NO and High Frequency Oscillatory Ventilation in Severe PPHN

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Randomized Multicenter Trial of Inhaled No and High Frequency Oscillatory Ventilation in Severe PPHN

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Guidelines for Arterial Blood Gases in PPHN

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Pulmonary Vascular Resistance & pH

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Neonatal Lambs

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Model – PPHN with Remodeled Pulmonary Vasculature

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Severe Hypoxic Pulmonary Vasoconstriction in Lambs with PPHN; Change Point – Similar to Control Lambs

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Oxygen Saturation and PVR

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Use of Supplemental Oxygen in PPHN

PO2 mmHg

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Pulmonary Vascular Resistance

% Increase PVR

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Changes in Pulmonary Vascular Resistance in Lambs Ventilated with 21% or 100% O2

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Changes in Pulmonary Vascular Resistance in Lambs PPHN Ventilated with 21%, 50% or 100% O2

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Changes in Pulmonary Vascular Resistance in Lambs PPHN Ventilated with 21%, 50% or 100% O2

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Nitric Oxide and Superoxide Radical

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Combinational effects of SOD and NO in lambs with PPHN

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Regulation of Pulmonary Vascular Tone

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Nitric Oxide

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Guidelines for Using NO

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Initiation of INO and ECMO

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Response Rate by Diagnoses

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Mechanisms for Poor NO Response

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Inhaled NO vs Control: Outcome Requirement for ECMO

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Comparison Inhaled NO vs Control, Outcome Death

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Inhaled NO vs Control: Outcome Neurodevelopmental Disability at 18 to 24 Months Aamong survivors

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Discontinuing Nitric Oxide

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No Levels Before Stopping Treatment

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Oxygenation Index

Oxygenation Index

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Post Nitric Oxide Era

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Post – INO Era

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Use of Sildenafil in PPHN

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Viagra used first time in the world successfully in severe PPHN Dr Rajiv and team June 2002

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Viagra on Pulmonary Hypertension

Hour of age after sildenafil

0hr 6hr

12 hr 18hr

case-1 29 25 24 19 case-2 26 26 25 20 case-3 33 31 31 24 acse-4 35 34 32 29 case-5 32 30 29 25 case-6 29 26 24 20 case-7 37 36 34 30 case-8 33 31 29 25 case-9 27 27 25 24 case-10 34 32 31 25 case-11 34 34 30 28

Rajiv et al BMJ. june 2002

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Oral Sildenafil Produced Significant Changes in OI

Oxygenation Index

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Intravenous Sildenafil in PPHN

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Oxygenation Index Over Time with Intravenous Sildenafil

Oxygenation Index

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Intravenous Sildenafil

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Intravenous Sildenafil in PPHN

Blood pressure did not drop abruptly if loading dose was given over 3 hours

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Response to Sildenafil Infusion without iNO

Oxygenation Index

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PDE 5 Inhibitor - Sildenafil

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PDE – 5 Inhibitor - Sildenafil

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Viagra and HIE Follow up

Age in yrs

1yr

2yrs 3yrs 4yrs 5yrs

case-1 75 80 90 85 85 case-2 90 80 75 85 80 case-3 80 75 80 70 90 acse-4 79 80 85 75 75 case-5 80 80 90 90 85 case-6 80 75 80 80 75 case-7 70 75 80 75 80 case-8 80 90 90 85 90 case-9 75 85 75 75 85 case-10 90 85 90 85 85 case-11 75 80 70 75 75

AWAITING PUBLICATION 2012

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PDE – 3 Inhibitor - Milrinone

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Milrinone Improves Oxygenation in Severe PPHN

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Milrinone Improves Oxygenation in newborns with Severe PPHN treated with Nitric Oxide

Oxygenation Index

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Prostacyclin: Mechanism of Action

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PPHN new modalities of treatment

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Use of Prostacyclin in PPHN

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PGE1 PGI2 Nitroprusside Tolazoline Sildenafil

  • Selective
  • Pulmonary
  • Ventilated regions
  • Non selective

INTRAVENOUS AGENTS

Old Wine in New Bottles

Adapted from Sood et al 2010

INHALATION

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SPV – Inhaled Vasodilators

Adapted from Sood et al 2010

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PGE 1 - Metabolism

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Phase I Clinical Trial of IPGE1 in NHRF

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Phase I Trial: Change in Pa O2

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Phase I Trial: Dose Response

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Therapies Prior to ECMO

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Effect of Therapy on ECMO Mortality

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What did you do Rajiv

mmhg DON’T USE REMOTE CONTROL DON’T CHANGE PEEP INADVERTENTLY AVOID PEEP PHOBIA Keep Ph > 7.25 KEEP PaO2 > 50 – 70 mmhg Keep Paco2 < 55 mmhg target paco2 40 ‐45 mmhg Tidal volume 4 ‐5 ml / kg Reduce Fio2 at earliest signs of pao2 stability Use pulmonary mechanics judiciously.

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Alogarithmic Approach to PPHN

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PPHN new modalities of treatment

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Emerging Therapies for Treatment of PPHN

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Conclusions

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Anticipation Balance Strategy Skill God