HELIOX
AND
INHALED NITRIC OXIDEIS IT USEFUL?
DR.NANDAKUMAR.V.,M.D.,I.D.C.C.M.,E.D.I.C
KMCH
Heliox- helium + oxygen
• 1 st clinical use – Charles Look 1923 for
decompression sickness
• 1934 – Barach – grandfather of heliox therapy
• Inert/ Non toxic/tasteless/non- flammable gas.
• Non carcinogenic, no lasting effect on human
organ
• Lower in density than in Nitrogen/ O2
Physical properties
Composition
Density (p) kg/m
3
Viscosity (ή)
microPoise
Thermal
conductivity W/m K
Air
1.184
184.33
0.025
CO2
1.81
148.71
0.017
Helium
0.166
197.61
0.14
Nitrogen
1.167
177.82
0.026
oxygen
1.33
205.35
0.026
Physiological issue
• To improve ventilation
↑ compliances
Resistances airway
or Both
• Bronchodilator and Steroids used to increase
Airway caliber.
Heliox = Helium+ Oxygen
• No broncho dilating or anti inflammatory
properties.
• Airway resistance in turbulent flow is directly
related to density of gas
• Heliox -low density than N2 or O2– lower
airway resistances
• Low density exert important potential benefits
with regards to airway’s dynamic of fluids.
Heliox = Helium + Oxygen
• Reduces resistances by reducing REYNOLDS
number,
• the density of mixture is an important
determinent of Reynold’s number
TURBULENT FLOW
LAMINAR FLOW.
• Reduces work of breathing and improves
Gas exchanges
Reynolds Number
Reynolds number is a dimensionless number
that can used to predict conditions of laminar or
turbulences flow depending on the situation
Re = pdv
ή
p=density of gas (kg/L)
d= diameter of tube(m)
v=linear velocity(m/s)
ή= gas viscosity(kg/m/s)
Reynolds Number
• Re < 2000
- Laminar flow
• Re 2000-4000 - Transition flow
• Re > 4000
- Turbulent flow
Normal physiology:
Upper airway & proximal trachea- TURBULENT
FLOW
Asthma and COPD :
Turbulent flow observed more distally.
Laminar and Turbulent flow
Different type of flow
Laminar flow- flow characterized by smooth, parallel layer of fluid
Turbulent flow – flow characterized by mixing of adjacent fluid layer
Medical Application
Upper airway
Lower airway
Infection
Asthma,
COPD,
Bronchiectasis
Bronchiolitis
Lung cancer
HFOV
– croup,
epiglottitis, laryngitis, tracheitis.
Trauma and Mass effect
– foreign body aspiration, post
extubation stridor, Tumour.
Other – Tracheomalacia,
Tracheal stenosis
Medical applications
• Others
Assessment of FRC
IABP
Operation and Cooling of MRI scanner
• Treatment for
Decompression sickness
Pneumatosis cystoides
Hyperammonaemia
NEBULIZED DRUG DELIVERY
•
•
Nebulized drug delivery improve gas exchange .
Air /O2 vs He-O2 nebulized albuterol in acute severe
asthma
NO shorten hospital stay
NO clinical improvement. (Respiratory care 2013)
• In COPD acute exacerbation- (FEF25-75) and (FEV1)–
no improvement in FEV1,
faster improvementin FEF25-75
(Critical care med 2000)
HELIOX DELIVERY
Upper airway obstruction
B/L Vocal cord palsy, post extubation
stridor-compared Heliox vs Adrenaline
neb.
(PEDIATRICS2001)
Asthma
Metaanalysis
USEFULLNESS IN MORE SEVERE PATIENTS
Risk of intubation, while awaiting the effects of
standard therapy.
(database systemic review 2006)
Level of evidences is low.
COPD
• Multicenter, randomized trial on NIV with heliox
mixture vs standard therapy in COPD exacerbation.
(critical care 2010 Jan; maggiore SM,)
• Complication of NIV and MV,
– ET intubation,
– Icu and hospital discharge,
– 28 days mortality,
– Serious adverse effect were recorded– didn’t show any
statistical superiority
Problem in using
• Difficult to obtain
• Real benefit - ↓ density, Fio2 < 40%
• Thermal conductivity – Heated humdifier
• Different function of the valve within the
ventilator that controls flow
• Expensive
Clinically not applicable
• Turbulent flow- depends on density of the
solution.
• Laminar flow- depends on viscosity.
• In distal airways laminar flow is maintained
in COPD & Asthma due to large cross
sectional area.
• Poisueille’s law:
R = ( 8.1.ń/π.r⁴)
Nitric oxide
Pathophysiology of ARDS
Insult
Activation of inflammatory mediators and
cellular components
Cytokines ( TNF, IL-1, IL-6, IL-8)
Neutrophilic infiltartion
Damage to capillary endothelial and
alveolar epithelial cells
Pathophysiology of ARDS
• Starling forces fall out of balance
- ↑ in capillary hydrostatic pressure ↑ pulmonary capillary
- ↓ oncotic pressure gradient.
permeability
• Exudative fluid in interstitium and alveoli
- Impaired gas exchange --- ventilation- perfusion mismatch
- Physiological shunting, decreased compliance
- Increased pulmonary arterial pressure
- Type 2 pneumocyte damage,
- Atelectasis
• Nitric oxide was formerly known as
endothelium-derived relaxing factor (EDRF).
• It is one of the nitrogen oxides ("NOx")
• Synthesized within cells by an enzyme NO
synthase (NOS).
• This enzyme catalyses the oxidation of Larginine to L-citrulline, producing NO.
METABOLISM
NOS is present in two forms
•
The constitutive form (eNOS)
Present in vascular, neuronal, cardiac tissue, skeletal muscle and
platelets, producing small quantities of NO continuously.
Here NOS is Ca2+/calmodulin dependant-stimulated by cGMP.
•
The inducible form (iNOS)
Present in endothelium, myocytes, macrophages and neutrophils, which
produces relatively large quatities of NO after exposure to endotoxins in
sepsis.
Following induction high levels of NO produced may form cytotoxic
radicals and cause capillary leakage.
Goal of Inhaled NO
• Improve oxygenation
• Decrease PVR
• Decrease pulmonary edema
• Reduction or Prevention of inflammation
• Cytoprotection
• Protection against infection
Respiratory
• Basal vasodilatation in pulmonary vessels
- reverses hypoxia.
• Nitric oxide inhibits
– hypoxic pulmonary vasoconstriction
– increases blood flow through well ventilated
areas of the lung
• Improves V/Q relationships.
Effect of PO2 in ARDS
Benefit of inhaled NO
Effect of inhaled NO vs NTP
Mechanism of action
Inhaled vasodilators
• In ARDS
• Inhaled vasodilators
(green circles)
preferentially dilate the
pulmonary vessels that
perfuse functioning alveoli
(white circles), recruiting
blood flow away from
poorly ventilated units
(black circles).
•
The net effect is
improved
ventilation/perfusion
matching.
Basic Concept in using NO
• Pulmonary hypertension - one of the hallmark
of ARDS
• Severe hypoxemia caused by physiologic
shunting and V/Q mismatching.
• Inhaled vasodilators selectively dilate
vessels that has perfuse well ventilated lung
zones  resulting in
– improved V/Q matching
– ↓shunting
Improves oxygenation
Dosing
Inhaled NO is typically administered
at a dose between 1.25 and 40 parts
per million (ppm).
• Continuous inhaled NO might become
sensitized
-Lowerdoses improve oxygenation
-Continued higher doses have little or
no effect.
• When used continuously and weaned, it
causes
– worsened oxygenation
– increased pulmonary artery pressure
DELIVERY OF NO IN MV
Monitoring
Chemiluminescence and
electrochemical analysers should be
used and are accurate to
1 ppm.
Storage
• NO is stored in aluminium
or stainless steel
cylinders which are
typically 40 liters.
• These contain
100/1000/2000 p.p.m.
nitric oxide in nitrogen.
• Pure NO is corrosive and
toxic.
Administration
• The drug is injected via the inspiratory
circuit of a ventilator.
• The delivery system is designed to
minimize the oxidation of nitric oxide to
nitrogen dioxide.
Other Organ Effects-Cardiovascular
•
•
Nitric oxide is a potent vasodilator.
Shear stresses in vessels increase NO production and
may account for flow dependant vasodilatation.
• Endothelial NO inhibits platelet aggregation.
•
In septic shock the overproduction of NO results in
hypotension and capillary leak.
• NOS inhibitors have been investigated experimentally in
the treatment of sepsis.
OTHER ORGAN EFFECTS
• GIT – determinant of gastro intestinal motility
appears to modulate morphine – induced
constipation
• GENITOURINARY – play sodium homeostasis in
kidney
• IMMUNE – macrophage and neutrophils
synthesize NO which can be toxic to certain
pathogens and may be important in host defence
mechanisms
Potential harms
• Inhaled NO may produce toxic radicals.
• However, it is unknown whether the
toxic radicals are more harmful than
ongoing exposure to high fractions of
inspired oxygen.
Side effects
• Methemoglobin and NO2 concentrations
may increase when high doses of NO are
given(500-2000 ppm of NO).
• Concentration of both should be
monitored frequently.
Metabolism
• Nitric oxide combines with hemoglobin that is 60% to
100% oxygenated.
• Nitric oxide combines with oxyhemoglobin to produce
methemoglobin and nitrate.
• Within the pulmonary system, nitric oxide can combine
with oxygen and water to produce nitrogen dioxide and
nitrite respectively, which interact with oxyhemoglobin
to then produce methemoglobin and nitrate.
• At 80 ppm the methemoglobin percent is ~5% after 8
hours of administration.
• Methemoglobin levels >7% were attained only in
patients receiving 80 ppm.
Side effects
• Inhaled NO is associated with renal
dysfunction.
• Inhaled NO has immunosuppressant
properties that, in theory, could increase
the risk of nosocomial infection.
• NO can cause DNA strand breaks and
base alterations, which are potentially
mutagenic.
Other uses
• Licensed – persistent Pul.Hypertension
• RV failure
• Post cardiac surgery
• Orthotopic heart and lung transplant
• Ventricular assist device
• Ischemic- reperfusion injury- no role
Thank you!