Nitric oxide therapy in PHTN Basics

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Inhaled Nitric Oxide Therapy

• Shams Ali Shah RT PSCCQ KSA

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Point to Discuss

• gt Pulmonary Hypertension
• gt Nitric Oxide Types
• gt Nitric Oxide structure
• gt Dosage
• gt Calculation
• gt Calibrations
• gt weaning from NO
• gt Hazards of NO and NO2

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Pulmonary hypertension

• An elevation in pulmonary artery pressure or
  progressive increase in the blood pressure in the
  pulmonary vascular bed
•  

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Causes

• Result of left heart failure, Congenital Heart
  Disease pulmonary parenchyma or vascular disease,
  thromboembolism, or a combination of these
  factors.
•  

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DEFINITION 

• A mean pulmonary artery pressure of 8 to 20 mmHg
  at rest is considered normal,.
•  mPAP gt 25 mm Hg at rest is considered PHTN
• PWP lt 15
• Normal LVEF
• No left-sided valvular disease

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How can be Classified the Severity of Pulmonary
Hypertension

• Degree of disease
• Mild
• Moderate
• Severe

• Mean PAP (mmHg)
• 25 - 40
• 41 - 55
• gt55

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Symptoms of PH

• Dyspnea is more reported
• Fatigue
• Near syncope/syncope
• Chest pain
• Palpitations
• Leg edema

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PHT Classification

• Group I This group includes those with
  idiopathic pulmonary arterial hypertension,
  congenital heart defects causing systemic to
  pulmonary shunt (ASD, VSD).
• Group II which is pulmonary hypertension due to
  left atrial, ventricular, or valvular heart
  disease.
• Group III This is due to disorders of the
  respiratory system or hypoxemia (COPD, sleep
  apnea).
• Group IV This is due to chronic thrombotic or
  embolic disease of the pulmonary vasculature
• Group V This is due to inflammation,
  mechanical obstruction, or extrinsic compression
  of the pulmonary vasculature ( sarcoidosis, and
  fibrosing mediastinitis)

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What is Nitric Oxide

• Nitric oxide was first identified as a gas
  by Joseph Priestly in 1772
• First time It was described in 1979 as a potent
  relaxant of peripheral vascular smooth muscle.
• NO is a diatomic free radical consisting of one
  atom of nitrogen and one atom of oxygen
• Lipid soluble and very small for easy passage
  between cell membranes
• Short lived, usually degraded or reacted within a
  few seconds

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• Nitric oxide is a gas that is inhaled. It works
  by relaxing smooth muscle to widen (dilate) blood
  vessels, especially in the lungs.
• Nitric oxide is used together with a breathing
  machine (ventilator) to treat respiratory failure
  in premature babies.
• Your baby will receive this medication in a
  neonatal intensive care unit (NICU) or similar
  hospital setting.

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INDICATION

• iNO is used to treat pulmonary hypertension such
  as primary PHTN and persistent pulmonary
  hypertension of newborns (PPHN).
• Neonates with hypoxic respiratory failure
  associated pulmonary hypertension.
• NO therapy is often used with other forms of
  therapy including high frequency oscillatory
  ventilation and surfactant therapy, both of which
  are aimed at improving oxygen delivery and lung
  compliance.

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Endogenous NO

• Our bodies produce nitric oxide endogenously. In
  the lung, NO controls the vessels that surround
• the alveoli. When nitric oxide is increased,
  the vessels dilate. When vasodilatation occurs,
  the
• inside of a vessel gets larger and more blood
  flows through the vessel. The body is
  self-regulating.

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Exogenous NO

• In low concentrations, nitric oxide is given via
  inhalation (exogenously). A positive response may
  be indicated by an improvement in clinical
  markers such as SPO2, PaO2, or by a reduction in
  PVR. When inhaled NO is delivered to the patient,
  the NO travels down the airways and goes only to
  the areas of the lung where ventilation or gas
  exchange is taking place. It diffuses rapidly
  into the smooth muscle of the blood vessel where
  it causes vasodilatation.

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NO Delivery Machine Consists of

• NO Delivery Unit
• NO Cylinder
• NO delivery Line
• NO2 and NO sampling line
• NO2 absorbent
• Calibration NO and NO2 Cylinders

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Calibration of NO Machine

• Zeroing all gases sensors with room air
• Calibrating NO sensor
• Calibrating NO2 sensor
• Calibrating O2 Sensor

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Calculations for NO delivery

• -initial NO flow vent flow (L/min) X desired
  NO ppm (L/min)
• __________________________________________________
  
• source tank NO ppm

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Mechanism of action

• Nitric oxide is a compound produced by many cells
  of the body. It relaxes vascular smooth muscle by
  binding to the heme moiety of cytosolic guanylate
  cyclase, activating guanylate cyclase and
  increasing intracellular levels of
  cyclic-guanosine 3',5'-monophosphate, which then
  leads to vasodilation.

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Mechanism of action

• When iNO is delivered to the patient,it travels
  down the airways and goes only to the areas of
  the lung where ventilation or gas exchange is
  taking place.
• It diffuses immediatly into the smooth muscle of
  the blood vessel where it causes vasodilation.
• After the NO passes into the capillary blood
  stream it is bound by hemoglobin in red blood
  cells. Once it is bound by hemoglobin, creating
  methb, it can no longer exert its vasodilator
  properties.
• At clinically therapeutic applied NO levels, the
  blood that leaves the lungs cannot exert its
  vasodilator effects on the rest of the vessels in
  the body.

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Dosage/ Administartion

• Initial dosage was 20 ppm(particles per million).
• Reduce inhaled nitric oxide dose by (20,15,
  10,5,2, 1 ppm).
• Set NO level is stable over a wide range of flows
  and flow patterns, including spontaneous
  breathing modes.
• Mostly the flow sensor placed in the outlet of
  the ventilator upstream from the humidifier
  measures minute ventilation (lpm).
• Treatment should be maintained until the
  underlying oxygen desaturation has resolved.

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Weaning of Nitric Oxide

• Both the NO and the NO2 levels that are being
  delivered to the patient must be continuously
  analyzed.
• High concentrations of NO may be toxic to the
  tissues. NO2 can possibly cause pulmonary edema,
  acid pneumonitis, and death.
• When the NO is mixed in the patients breathing
  circuit, the FiO2 (fraction of inspired oxygen)
  delivered to the patient will be lower.
• It is important to also monitor inspired oxygen
  levels at a point distal to the point of NO
  delivery.

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Hazards and contraindications

• N O when mixed with O2 produces (NO2)a toxic gas.
• Because of its very minimal half life (0.1
  seconds 5 seconds), it is quickly inactivated
  once it combines with hemoglobin.
• Although rare, the patients as well as health
  care providers can be adversely affected.
• Factors influencing NO2 production are O2
  concentration, NO concentration and time of
  contact between NO and O2.
• Patients most at risk include those receiving
  high oxygen concentration and low ventilator flow
  rates.

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Hazards and Contraindication

• A contraindication of this therapy is children
  who need a right-to-left shunt to survive
• Nitric oxide is rapidly metabolized.
• When NO combines with hemoglobin, NO can no
  longer exert its vasodilator effects and
  methemoglobin is created.
• O2 carrying capacity can be decreased with high
  levels of methemoglobin. When higher
  concentrations of nitric oxide are used, more
  methemoglobin is created.
• When administering NO to patients the
  methemoglobin levels must be measured
•  

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References

• Kinsella JP, Truog WE, Walsh WF, Goldberg RN,
  Bancalari E, Mayock DE, et al. Randomized,
  multicenter trial of inhaled nitric oxide and
  high-frequency ventilation in severe, persistent
  pulmonary hypertension of the newborn. J Pediatr
  1997131 (1 Pt 155-62.
•  
• Rossaint R, Gerlach H, Schmidt-Ruhnke H, Pappert
  D, Lewandowski K, Steudel W, Falke K. Efficacy of
  inhaled nitric oxide in patients with severe
  ARDS. Chest 1995 107(4)1107-1115.
•  
• Dellinger RP, Zimmerman JL, Taylor RW, Straube
  RC, Hauser DL, Criner GJ, et al. Effects of
  inhaled nitric oxide in patients with acute
  respiratory distress syndrome results of a
  randomized phase II trial. Inhaled nitric oxide
  in ARDS Study Group. Crit Care Med 1998
  26(1)15-23

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