Persistent pulmonary hypertension of the newborn (PPHN) occurs when the pulmonary circulation fails to decrease in resistance after birth, resulting in right-to-left shunting and hypoxemia. It can be caused by underdevelopment, maldevelopment, or maladaptation of the pulmonary vasculature. Clinically, infants present with respiratory distress and cyanosis unresponsive to oxygen therapy alone. Diagnosis involves finding elevated right-sided pressures on echocardiogram in the absence of structural heart defects, with hypoxemia out of proportion to lung disease. Treatment aims to reduce pulmonary vascular resistance through medications and potentially extracorporeal membrane oxygenation.
Surfactant replacement therapy : RDS & beyondDr-Hasen Mia
This presentation is about Surfactant, its use in Respiratory Distress Syndrome & some other conditions of surfactant deficiency due to inactivation like meconium aspiration syndrome & others
Surfactant replacement therapy : RDS & beyondDr-Hasen Mia
This presentation is about Surfactant, its use in Respiratory Distress Syndrome & some other conditions of surfactant deficiency due to inactivation like meconium aspiration syndrome & others
The SlideShare 101 is a quick start guide if you want to walk through the main features that the platform offers. This will keep getting updated as new features are launched.
The SlideShare 101 replaces the earlier "SlideShare Quick Tour".
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
2. HISTORICAL ASPECTS
Previously k/a Persistent fetal circulation (PFC)
First described as “unripe births of mankind” by
William Harvey in 1628 in Exercitatio Anatomica
De Motu Cordis et Sanguinis in Animalibus .
3. Gersony et al in 1969 rediscovered this syndrome
and labelled it as “persistent foetal circulation
(PFC)”
However this term has now been abandoned (high-
flow, low-resistance circuit through the placenta, is
missing)
5. FETAL vs ADULT CIRCULATION
FETAL ADULTS
Gas exchange Placenta Lungs
RV,LV circuit Parallel Series
Pulmonary circulation Vasoconstricted Dilated
Stroke volume RV>LV(1.2:1 TO 1.5:1) RV= LV
Intracardiac & extracardiac shunts No shunts
6.
7. LA LV AORTA DUCTUS ARTERIOSUS
FORAMEN OVALE
RV
IVC SVC UPPER BODY
hepatic veins
55% THROUGH 45% TO LIVER
DUCTUS VENOSUS (PORTAL CIRCULATION)
UMBILICAL VEIN
Oxy.blood , nutrients
PLACENTA
8. • Upper part of fetal body (including coronary & cerebral arteries and those
to upper extremities) is perfused exclusively from LV with blood that has a
slightly higher PO2 , than the blood perfusing the lower part of the fetal
body, which is derived mostly from RV
Only a small volume of blood from the ascending aorta (10% of fetal
cardiac output) flows across the aortic isthmus to the descending aorta.
10. TRANSITIONAL CIRCULATION:
AT BIRTH
• Expansion of the lungs to normal resting volume,
establishment of adequate alveolar ventilation and
oxygenation, and successful clearance of fetal lung fluid
Rapid fall in PVR
• Removal of the placenta, the catecholamine surge a/w birth,
relatively cold extrauterine environment
Increase in SVR
11. TRANSITIONAL CIRCULATION:
Right ventricle output now flows entirely into
the pulmonary circulation.
Pulmonary vascular resistance becomes lower
than systemic vascular resistance,
Shunt through ductus arteriosus reverses &
becomes left to right.
13. TRANSITIONAL CIRCULATION
Increased volume of pulmonary blood flow
returning to left atrium
Increases left atrial volume and pressure
Closure of foramen ovale (functionally)
(Although the foramen may remain probe patent)
Becomes Fossa Ovalis
14. Removal of the placenta from the circulation
Also results in closure of the ductus venosus
The left ventricle is now coupled to the high-resistance
systemic circulation its wall thickness and mass begin to
increase.
In contrast, the right ventricle is now coupled to the low-
resistance pulmonary circulation its wall thickness and
mass decrease slightly.
15. If, for any reason, right-sided pressures remain
high relative to those on the left side, fetal
circulation will most likely persist through one or
both of the fetal channels mentioned above.
PPHN is defined as postnatal persistence of right
to left ductal or atrial shunting, or both in
presence of elevated pulmonary pressures & in
absence of congenital heart disease
17. Factors contributing to high PVR in-
utero:
Mechanical factors (compression of the small
pulmonary arterioles by the fluid-filled alveoli and a
lack of rhythmic distension)
Presence of low-resting alveolar and arteriolar
oxygen tensions, and a relative lack of
vasodilators(NO, prostacyclins)
Elevated levels of vasoconstictors (endothelin-
1,thromboxane,serotonin)
18. Normal Pulmonary Vascular Transition
The pulmonary vascular transition at birth is
characterized by :
rapid increase in pulmonary blood flow
reduction in PVR
clearance of lung liquid.
19.
20. Central role in the pulmonary vascular
transition
Pulmonary endothelial cells
NO
Arachidonic acid metabolites
21. Vascular endothelium releases several vasoactive
products that play a primary role in pulmonary
transition at birth.
Pulmonary endothelial NO production increases
markedly at the time of birth.
22. NO
Oxygen-important catalyst for increased NO
production
Shear stress resulting from increased pulmonary
blood flow- induce endothelial nitric oxide synthase
(eNOS) expression
Nitric oxide exerts its action through sGC and cGMP.
23. Increased cGMP concentrations produce
vasorelaxation via decreasing intracellular calcium
concentrations.
Pulmonary expression of both endothelial nitric
oxide synthase (eNOS) and its downstream
target, soluble guanylate cyclase (sGC), increases
during late gestation.
24. THE PROSTACYCLIN PATHWAY
Cyclooxygenase (COX)- rate-limiting enzyme that
generates prostacyclin from arachidonic acid.
COX-1 in particular is upregulated during late
gestation
Increased O2 concentration also stimulates COX-1
activity
25. - There is evidence that the increase in estrogen
concentrations in late gestation play a role in
upregulating PGI synthesis.
- Prostacyclin interacts with adenylate cyclase to
increase intracellular cyclic adenosine
monophosphate levels, which leads to
vasorelaxation.
- Inhibition of prostacyclin production by NSAIDs
during late pregnancy has been associated with PPHN
although this association has been recently called
into question
26. Oxygenation also causes pulmonary dilatation
through the activation of K channels and inhibition
in Ca channels in pulmonary artery smooth muscles
Atrial natriuretic peptide (ANP), B-type natriuretic
peptide (BNP) and C-type natriuretic peptide (CNP)
dilate fetal pulmonary vasculature by increasing
cGMP and may play a role in pulmonary vascular
transition at birth.
27. PPHN
Presence of elevated PVR and rightleft shunt
through the ductus arteriosus and/or foramen ovale(
in absence of congenital heart disease) , resulting in
hypoxemia and labile oxygen saturations
Contrary to primary pulmonary hypertension in
adults, the newborn syndrome is not defined by a
specific pressure of the pulmonary circulation
28. Occurs due to failure of the pulmonary circulation
to undergo the normal transition after birth
29. Incidence and mortality
Affects mainly at-term or post-term newborns,
although also present in premature infants
Reported incidence: 0.43-6.8 per thousand
newborns.
It is likely to be much more in developing
countries, where little data is available
30. North America- 1.9/1,000 in the population of
neonates born at term, with a mortality of 11%
UK- 0.4 to 0.68/1,000 live births
Brazil- 2 /1,000 live births, and mortality rates of
11.6%.
31. PATHOGENIC MECHANISMS FOR
PPHN
Pulmonary vascular underdevelopment (decreased
vascular growth)
Mal-development (abnormal vascular structure)
Mal-adaption (perinatal hypoxia-induced vascular spasm)
Functional obstruction to pulmonary blood flow due to
increased blood viscosity (polycythemia)
32. UNDERDEVELOPMENT
Reduced cross sectional area of pulmonary
vasculature resulting in a relatively fixed elevation
of PVR
Occurs with pulmonary hypoplasia associated
with a variety of conditions like:
congenital diaphragmatic hernia (CDH),
cystic adenomatoid malformation of the lung,
renal agenesis, oligohydramnios
accompanying obstructive uropathy
intrauterine growth restriction.
33. Although some degree of postnatal pulmonary
vasodilatation can occur, this adaptive
mechanism is limited.
As a result, mortality risk is greatest in this
category of patients.
34. MALDEVELOPMENT
Lungs have normal branching and alveolar
differentiation, and have a normal number of
pulmonary vessels.
Abnormal thickening of muscle layer of pulmonary
arterioles, and extension of this layer into small
vessels that normally have thin walls and no muscle
cells
Excessive extracellular matrix
35. Pulmonary vasculature responds poorly to stimuli
that normally result in a decrease in PVR, such as
↑ed O2 tension and the establishment of effective
ventilation
• Egs: Chronic intrauterine asphyxia, post-term
delivery, meconium staining
Remodeling of the pulmonary vascular bed is
thought to occur during the first 7 to 14 days after
birth, with an accompanying fall in PVR.
36. Disorders producing excessive perfusion of the
fetal lung also may predispose to vascular
maldevelopment.
Egs: premature closure of the ductus arteriosus
(eg, caused by nonsteroidal antiinflammatory
drugs) or foramen ovale, high placental vascular
resistance, and total anomalous pulmonary
venous drainage.
37. It is believed that in these cases, the maintenance
of pulmonary vasoconstriction with an increase in
pulmonary artery pressure for a prolonged period
of time leads to vascular remodeling
Central role of vasoactive mediator imbalance
(eg: ↑ed endothelin, ↓ed NO)
38. Genetic predisposition may influence the
availability of precursors for NO synthesis and
affect cardiopulmonary adaptation at birth.
This was illustrated in a report in which infants
with pulmonary hypertension had lower plasma
concentrations of arginine (a precursor of NO and
a urea cycle intermediate), and NO metabolites
than control infants with respiratory distress
39. A functional polymorphism of the gene encoding
carbamoyl-phosphate synthetase, which controls
the rate-limiting step in the urea cycle, has also
been implicated in genesis of pulmonary
hypertension
40. MALADAPTATION
Pulmonary vascular bed is normally developed
However, adverse perinatal conditions cause
active vasoconstriction and interfere with the
normal postnatal fall in PVR.
Conditions include perinatal depression,
pulmonary parenchymal diseases, and bacterial
infections, especially those caused by group B
streptococcus (GBS).
41. ETIOLOGY OF PPHN
IDIOPATHIC PPHN-: 10-20% cases
No obvious predisposing factors
Possible causes include hypoxia, acidosis,
hypothermia, hypoglycemia, etc, and some of
them may not have been documented.
42. SECONDARY PPHN
Most commonly seen in
infants with lung diseases
Other causes
• Asphyxia
• Sepsis/infection
• Pneumonia (bacterial)
• Congenial Diaphragmatic
Hernia
• Transient Tachypnea of
the Newborn
• Respiratory Distress
Syndrome (RDS/HMD)
most common cause being
meconium aspiration
• Polycythemia/hyperviscosity
• Metabolic disturbances
(hypoglycemia, hypocalcemia,
hypomagnesemia)
• Hypothermia
• Systemic hypotension
43. Potential risk factors for the
development of PPHN
Male gender
African or Asian maternal race
Pre-conception maternal overweight
Maternal diabetes, Maternal asthma
Late preterm and large for gestational age
Chorioamnionitis
Antenatal exposure to SSRIs, NSAIDs
Infection(mainly GroupB Streptococcus)
Hypothermia
Hypocalcemia
Polycythemia
44. CLINICAL MANIFESTATIONS
Usually occurs in term infants, although it may
also present in late preterm or postterm infants
The diagnosis is rare in very low birth weight
(VLBW) infants
PPHN is characterized by both prenatal and
neonatal features
45. Prenatal factors - signs of intrauterine and
perinatal asphyxia including fetal heart
abnormalities (ie, bradycardia and tachycardia)
and meconium-stained amniotic fluid
46. Neonatal findings
Most present within 1st 24 hours of life with signs
of respiratory distress (eg, tachypnea, retractions,
and grunting) and cyanosis, low apgar scores
Physical examination : cyanosis, signs of respiratory
distress; there may be meconium staining of skin
and nails, which may be indicative of intrauterine
stress.
Differential cyanosis may appear in severe cases
(with a pink upper body and a cyanotic lower body)
47. Chest Examination-
A prominent RV impulse and a single and loud S2
Occasional gallop rhythm (from myocardial
dysfunction) and a soft regurgitant systolic
murmur of TR may be audible.
Breath sounds may be normal (If pneumonia or
meconium staining exists, crackles or wheezes
may be present)
Severe cases of myocardial dysfunction may
manifest with systemic hypotension.
48. DIAGNOSIS
Consider PPHN when hypoxemia is out of
proportion to the degree of parenchymal
lung disease and there is no e/o cyanotic
CHD.
49. Laboratory Studies
Pulse oximetry -Hypoxia is universal,labile and is
unresponsive to 100% oxygen given by hood, but
may respond transiently to hyperoxic
hyperventilation(by bag and mask or after
intubation)
A difference >10% between the pre- and
postductal (right thumb and either great toe)
oxygen saturation (d/t RL shunt through PDA)
50. However, absence of a pre- and postductal
gradient in oxygenation does not exclude the
diagnosis of PPHN, since right-to-left shunting can
occur predominantly through the foramen ovale
rather than the PDA.
51. Arterial blood gas- PaO2 gradient of > 20 mmHg
between pre-ductal (upper extremity or head)
and post-ductal (lower extremity or abdomen)
ABGs
In contrast to infants with cyanotic lesions, many
infants with PPHN have at least one
measurement of PaO2 >100 mmHg early in the
course of their illness
52. Hyperoxia test
To distinguish PPHN & CHD from parenchymal
lung disease
Give 100% O2 x 10-15 min.
PPHN or CHD = PaO2 < 100 mmHg
Parenchymal = PaO2 >100 mmHg
If PaO2 > 100 mm of Hg , CHD more or less ruled
out
53. Hyperoxia - hyperventilation
test
To distinguish PPHN from CHD
Administer 100% O2
Hyperventilate (face mask or ET tube) to
"critical“ PaCO2 level(20-25 mm Hg)
PPHN = PaO2 > 100 mmHg
CHD = PaO2 little change (< 100 mmHg
Caution: Should be performed by skilled
personnel only
54. Response to iNO may help to differentiate PPHN
from cyanotic CHD
Most neonates with PPHN respond rapidly to
iNO, with an increase in PaO2 and oxygen
saturations.
Some neonates who have severe PPHN and
infants who have cyanotic CHD may experience a
small or no increase in oxygenation with iNO
55. CHEST RADIOGRAPH
Usually normal or demonstrates the findings of an
associated pulmonary condition (eg, parenchymal
disease, air leak, or congenital diaphragmatic
hernia).
The heart size typically is normal or slightly
enlarged.
Pulmonary blood flow may appear normal or
reduced.
57. ECHOCARDIOGRAPHY
Gold standard for diagnosing PPHN
Normal structural cardiac anatomy with evidence
of pulmonary hypertension (eg, flattened or
displaced ventricular septum).
Right-to-left or bidirectional shunting of blood at
the foramen ovale and/or the ductus arteriosus
58. High pulmonary arterial/right ventricular systolic
pressure estimated by Doppler velocity
measurement of TR jet
In addition, echocardiography may be used to
assess ventricular function, which may be
impaired.
59. Cardiac catheterization
Needed rarely when echo is not definitive
A vasodilator trial using hyperoxia or short-acting
agents such as inhaled NO, at the time of the
catheterization, may be useful to identify those
likely to have a favorable long-term response to
pulmonary vasodilators.
60. DIFFERENTIAL DIAGNOSIS
Congenital heart disease, including transposition of the
great arteries, total and partial anomalous pulmonary
venous connection, tricuspid atresia, and pulmonary
atresia with intact ventricular septum
Primary parenchymal lung disease such as
bronchopulmonary dysplasia (BPD), neonatal
pneumonia, respiratory distress syndrome, pulmonary
sequestration, and pulmonary hypoplasia
Sepsis
Alveolar capillary dysplasia
Surfactant protein B deficiency
61. MANAGEMENT
General supportive cardiorespiratory care.
In severe/ non-responsive cases- use of vasodilatory
agents (eg, inhaled nitric oxid [iNO]), or
extracorporeal membrane oxygenation (ECMO)
Specific treatment for any associated parenchymal
lung disease (eg, antibiotic therapy for pneumonia, or
surfactant for neonatal respiratory distress
syndrome).
62. Assessment of severity using oxygenation
index(OI)
OI - used to assess the severity of hypoxemia in
PPHN and to guide the timing of interventions
such as iNO administration or ECMO support.
OI = [mean airway pressure x FiO2 ÷ PaO2] x 100
A high OI indicates severe hypoxemic respiratory
failure.
63. Patients with OI ≥25 should receive care in a
center where high-frequency oscillatory
ventilation (HFOV), iNO, and ECMO are readily
available
In patients with OI <25, general supportive care is
typically adequate and no further invasive
intervention is usually required
65. Hyperventilation & alkali infusions to maintain an
alkaline pH- strategies previously in use, now
considered outdated.
Lack of conclusive benefit & concerns of
neurological injury & sensorineural deafness with
respiratory alkalosis
66. Oxygen and optimal oxygen saturations
Providing adequate oxygenation forms the mainstay
of PPHN therapy.
However, there are currently no randomized studies
comparing different PaO2 levels in the management
of PPHN in a term infant
Hypoxia increases PVR and contributes to the
pathophysiology of PPHN, although hyperoxia does
not further decrease PVR and instead results in free
radical injury
67. It has been shown that brief exposure to 100%
oxygen in newborn lambs results in increased
contractility of pulmonary arteries and reduces
response to iNO
Maintaining preductal oxygen saturations of 90-
95% with PaO2 levels b/w 55-80 mmHg is
recommended
68. Intubation and mechanical ventilation
Indication
• Persistent hypoxaemia despite maximal
administration of supplemental oxygen
69. Ventilatory strategies include conventional positive
pressure ventilation with initial rates of 60–
80/minute, an I:E ratio of 1:1.2, a PEEP of 3 cm H2O,
and sufficient peak pressure to achieve a PaCO2 of
not greater than 35–45 mmHg with the pH between
7.35 and 7.45.
PaO2 should be maintained at 60–90 mmHg
70. If high frequency oscillatory ventilation (HFOV) is
available it can be advantageously used in infants
with pulmonary parenchymal disease and those
awaiting inhaled nitric oxide therapy.
However a recent meta analysis has failed to show a
clear benefit of HFOV over conventional ventilation
as an elective or as a rescue mode of ventilation in
term or preterm infants with PPHN
71. Sedation to minimize agitation (which ↑PVR)-
fentanyl(1 to 5 mcg/kg per hour), or morphine
sulphate(loading dose of 100 to 150 mcg/kg over
one hour followed by a continuous infusion of 10
to 20 mcg/kg per hour)
72. Surfactant
Does not appear to be effective when PPHN is the
primary diagnosis
Should be considered in patients with associated
parenchymal lung disease, in whom there is
either a suspected surfactant deficiency (eg,
neonatal respiratory distress syndrome) or
impairment (meconium aspiration syndrome)
73. Interventions for severe cases
Infants with OI>25 despite the use of HFOV are
candidates for iNO therapy or other vasodilatory
agents that decrease PVR.
Patients who fail to respond to these agents may
require ECMO
74. Nitric Oxide
FDA approved in 1999
Mainstay of PPHN treatment
Achieves potent and selective pulmonary
vasodilation without ↓ing SVR
In intravascular space combines with hemoglobin
to form methemoglobin, which prevents systemic
vasodilation (selective effect).
iNO reduces V/Q mismatch by entering only
ventilated alveoli and redirecting pulmonary
blood by dilating adjacent pulmonary arterioles
75. Large multi-center trials- demonstrated that iNO
reduces the need for ECMO by 40%.
A meta-analysis of 7 RCTs- revealed that 58% of
hypoxic near-term and term infants responded to
iNO within 30 to 60 minutes
While use of iNO did not reduce mortality in any
study analyzed, but the need for rescue ECMO
therapy was significantly↓ed
76. Indicated for patients with OI ≥25
Earlier initiation (for an OI of 15-25) does not
decrease the incidence of ECMO use and/or
death or improve other patient outcomes
77. Currently, the initial recommended concentration
of iNO is 20 ppm.
Higher concentrations are not more effective and
are associated with a higher incidence of
methemoglobinemia and formation of nitrogen
dioxide
In infants who respond, an improvement in
oxygenation is evident within few minutes.
78. Once initiated, iNO should be gradually weaned to
prevent rebound vasoconstriction.
Use of iNO has not been demonstrated to reduce the
need for ECMO in newborns with congenital
diaphragmatic hernia.
In these newborns, iNO should be used in non-ECMO
centers to allow for acute stabilization, followed by
immediate transfer to a center that can provide
ECMO.
79. Contraindications to iNO include congenital heart
disease characterized by left ventricular outflow
tract obstruction (eg, interrupted aortic arch,
critical aortic stenosis, hypoplastic left heart
syndrome) and severe left ventricular
dysfunction.
80. Extracorporeal membrane
oxygenation
About 40% of infants with severe PPHN remain
hypoxemic on maximal ventilatory support despite
administration of iNO
In these patients ECMO therapy should be
considered.
Goal- maintain adequate tissue oxygen delivery
and avoid irreversible lung injury from mechanical
ventilation while PVR decreases & pulmonary
hypertension resolves.
81. Cochrane review of 4 trials of ECMO showed a strong
benefit in terms of survival, without evidence of
increased risk of severe disability
Criteria for institution- elevated OI that is
consistently ≥40.
However, because mean airway pressures are higher
on HFOV than conventional ventilation, some
clinicians wait until OI is ≥60 when HFOV is used
82. Most patients weaned from ECMO within 7 days
However, occasionally ≥2 weeks may be
necessary for adequate remodeling of the
pulmonary circulation in severe cases.
Who fail to improve may have an irreversible
condition, such as alveolar capillary dysplasia or
severe pulmonary hypoplasia.
In one large series from a single institution from
2000 to 2010, the survival rate following ECMO
support was 81%
83. Other vasodilatory agents
SILDENAFIL, a PDE5 inhibitor- ↓ PVR in both animal
models and adult humans.
Reported to be successful in the treatment of infants
with PPHN in many small studies
In a Cochrane meta-analysis with 37 newborns from
centers that did not have access to NO and HFV,
significant improvement in oxygenation was observed
in the group receiving sildenafil. This study noted that
sildenafil may be a treatment option for PPHN.
Starting doses of 0.25–0.5 mg/kg/dose upto a
maximum of 2 mg/kg/dose; every 6-8 hourly
84. In 2012, the US FDA issued a warning that
sildenafil not be prescribed to children with
pulmonary arterial hypertension (PAH) because of
reports of associated mortality with
administration of high doses of sildenafil in
children between 1 and 17 years of age
Indicates the need for further assessment of the
efficacy and safety of sildenafil, especially with
long-term treatment
85. Inhaled or intravenous prostacyclin
Potential intervention in patients who fail NO
therapy
RCTs in adults and animal models have shown its
efficacy; however in neonates only case reports
are available
No longer commonly used (short t1/2 requiring
permanent vascular access, many adverse effects,
rebound fatal pulmonary hypertension in case of
drug interruption)
86. Bosentan
Endothelin-1 receptor antagonist, was reported to
be effective and safe in short-term treatment of
patients with PPHN in a single trial in 47 neonates
Potential for serious hepatic injury
Larger studies needed
87. Milrinone
Phosphodiesterase III inhibitor, has improved
oxygenation in infants refractory to iNO in small
case series
However, one of these series reported
intraventricular hemorrhage in three of four
treated infants
RCTs needed to evaluate efficacy and safety
88. Magnesium sulfate
Promotes vasodilatation by antagonizing entry of
calcium ions into smooth muscle cells
Small case series reporting its use
One RCT(2010) of iNO versus Mg in treatment of PPHN
in babies receiving HFOV, found better outcomes with
iNO
Pre-term neonates are at high risk for respiratory
depression due to magnesium sulfate
89. OUTCOMES & PROGNOSIS
With availability of both iNO and ECMO, mortality
in PPHN has reduced from 25–50% to 10–15%
Survivors- at ↑ed risk of adverse sequelae
including chronic pulmonary disease and long-
term development of neuro-developmental
disabilities, hearing impairment, and brain injury
and therefore need to be on long term follow-up.