Inhaled Nitric Oxide (iNO)

1
Inhaled Nitric Oxide (iNO)

• Promotes pulmonary vasodilation.
• Only approved for treating PPHN.
• All other uses are experimental as of
• 2005.

2

• I.V. vasodilators (D) or diseases that
  dysregulate pulmonary vascular tone such sepsis
  or ALI (E) counteract hypoxic pulmonary
  vasoconstriction leading to worsening oxygenation.

Griffiths Evans
3

• In the vascular space NO is inactivated by
  O2Hgb and forms methemoglobin and nitrate.
• Methemoglobin levels should be measured w/in 6
  hours of pts receiving NO and after each increase
  in dose. Generally, iNO up to 40 ppm should not
  cause methemoglobin.

Griffiths Evans
4

• NO regulates and promotes vascular smooth
  muscle relaxation.

Griffiths Evans
5
Nitric Oxide

• Regulates and promotes vascular smooth muscle
  relaxation
• Free radical and reacts rapidly with other free
  radicals
• Unstable in the atmosphere
• Highly soluble in lipid
• Reacts with O2 to form the more toxic nitrogen
  dioxide (NO2)
• OSHA limits exposure levels for NO to 25 ppm
  averaged over 8o
• NO2 limited to 5 ppm averaged over 8o

6
Nitric Oxide Toxic Gas

• Atm concentration from air pollution
• 10 100 parts per billion (ppb)
• Concentration in cigarette smoke
• 400 - 1000 parts per million (ppm)
• Prior medical interest was as contaminant of
  nitrous oxide (N2O) cylinders.

7
LC50 for pure NO or NO2 is 115 ppm

• LC50 is the lethal concentration (gas
  concentration that kills 50 of the laboratory
  animals).
• NO/N2 tanks typically contain 800 ppm of NO
• LC50 of 800 ppm gas mixture is 115/800 x
  1,000,000 143,750 ppm
• NO2 should be lt 2 of NO concentration
• Therapeutic range of iNO is 1- 80 ppm

8
800 ppm NO

• Allows 80 ppm doses at an FIO2 of 0.90
• A typical dose of 20 ppm added to 100 O2
  reduces the highest possible O2 concentration to
  97.5
• The lower the tank NO ppm the greater the tank
  flow required to deliver the NO dose and the
  lower the oxygen concentration that is possible
  to deliver (since essentially bleeding NO into
  system)
• NO tanks of either 100 or 800 ppm contain 1963 L
  at 2000 psig. There are also D sized tanks.

9
NO/N2 gas mixtures

• Do not support combustion
• Are not flammable
• Classified as asphyxiating since NO gas
  contains no oxygen (to prevent formation of NO2)
• Tank storage rooms must be well ventilated to
  maintain ambient FIO2 gt 0.18 in the case of a
  cylinder leak.

10
Regulator and high pressure hose must be purged
to eliminate NO2

• When regulator and high pressure hose connected
  to NO cylinder, oxygen in the regulator and hose
  combines with NO to form NO2
• As little as 2 ppm NO2 have been reported to
  increase airway responsiveness, produce alveolar
  cell hyperplasia and damage cilia.
• NO2 combines with water to form nitric acid that
  may remain in lungs when nitric acid is absorbed
  by alveolar epithelial lining.

11
iNO Delivery

• Continuous NO flow into inspiratory limb okay for
  cont flow pediatric vents but not for adult
  ventilators
• Estimated mean NO concentration
• (NO flow x NOsource)
• VE
• NO may also be injected only during inspiration.
• NO calculated (NOsource x NO flow x IT)
• 
  VE

12
Pediatric Ventilators

• Continuous NO flow
• Introduced after ventilator outlet and before
  humidifier
• FIO2 monitored downstream at least a foot from
  injection site
• NO and NO2 monitored close to pt wye
• Expected NO (NO flow x source ppm)
• (NO flow ventilator flow)

13
NO successfully used

• With pediatric and adult ventilators
• With HFO
• But not with HFJV
• Manual resuscitators (bags) where
• Expected NO (NO flow x source ppm)
• (NO flow
  O2 flow)
• NO should be analyzed before connecting to
  patient.
• Bag should be flushed with 100 O2 (squeeze bag
  3-5 times) after each use to purge NO2.
• Scavenger systems for exhalation generally not
  necessary

14
iNOvent by Ohmedaonly FDA approved NO delivery
system

• Delivery system mounted on transport cart
• Used with inspiratory only or continuous flow
  vents
• Holds 1 NO cylinder (800 ppm) and 1 O2 E tank

15
iNOvent

• Injection module inserted into inspiratory
  circuit between vent and humidifier.
• Injection module includes hot wire flow sensor to
  precisely measure flow from vent so that
• NO can be injected proportional to vent flow and
  to provide the desired dose
• Reduces the accidental production of NO2
• iNO vent samples gas downstream of injection site
  6 inches from pt wye to monitor gas
  concentrations of O2, NO and NO2.

16
Gas Concentrations

• Measured by electrochemical cells
• Low NO concentrations calibrated easily
• More involved in calibrating high NO
  concentrations
• Can set alarms for Hi, Lo NO, NO2 and O2
• iNOvent has dual channel for independent
  monitoring of gas delivery system
• This means the monitoring system can be
  calibrated without interrupting gas delivery
• Manual NO delivery system (bag)
• O2 at 15 LPM
• NO injects gas to provide 20 ppm

17
Electrochemical Analyzers

• Slow response time of 30 40 seconds
• Adversely affected by humidity, temperature, and
  ventilator pressure
• Humidity reduces diffusion of NO into sensor
• Temperatures between 20 40o C have negligible
  affects on NO analysis
• As ventilator pressures increase, NO and NO2
  readings become falsely high.
• Accurate to 1 ppm

18
Chemiluminescence Analyzers

• Much faster response time
• Much more accurate (in pp billion and pp trillion
  range) used to measure cylinder NO/N2 gas
  mixtures
• Much more expensive
• Measures photon emissions when NO reacts with
  ozone (O3) to produce NO2 with an electron in an
  excited state.
• A photon is released when the electron decays to
  its original energy level.
• A photon has a wavelength of 600 3000 nm
• NO2 measured by converting it to NO and repeating
  process.
• Chemiluminescence not appropriate for ventilator
  use

19
Occupational Safety and Health Administration
(OSHA)

• Recommend environmental concentrations of NO not
  exceed an average of 25 ppm over an eight hour
  period.
• 25 ppm higher than typical dose for ARDS ( 20
  ppm)
• NO2 should not exceed 5 ppm over an eight hour
  period USA.
• Unlikely such levels would accumulate in a well
  ventilated room (10 -12 air changes per hour) so
  scavenging NO in clinical setting unnecessary.

20
Branson, R. D., Hess, D.R., Campbell, R.S.
Johannigman, J.A. (1999). iNO Delivery systems
and monitoring. Respiratory Care, 44 (3),
281-307. Griffiths, M.J., Evans, T.W. (2005)
Inhaled nitric oxide therapy in adults. N Engl J
Med, 353 (25),2683-95.
References