Inhaled Epoprostenol

1
Inhaled Epoprostenol

• Considerations for Use
• in Ventilated Patients
• Shari McKeown, Practice Leader Respiratory
  Services VA

2
Aliases

• Naturally occurring prostaglandin
• Epoprostenol sodium
• Flolan
• Prostacyclin
• PGI2
• PGX

3
the point

• Inhaled vasodilators can reduce PAP and
  redistribute pulm blood flow to ventilated lung
  regions with little systemic effect1,2,3,4,5

• Della Rocca G., Coccia C, Pompei L. et al.
  Inhaled aerosolized prostacyclin and pulmonary
  hypertension during anesthesia for lung
  transplantation. 2001 Transplant Proc, 33,
  1634-1636.
• Lowson SM. Inhaled Alternatives to Nitric Oxide.
  Anesthesiology 200296(6)1504-1513
• Mikhail G, Gibbs S, Richardson G, Wright G,
  Khaghani A, Banner N, Yacoub M. An evaluation of
  nebulized prostacyclin in patients with primary
  and secondary pulmonary hypertension. Eur Heart J
  1997, 181499-1504.
• Olschewski H. et al. Inhaled prostacycin and
  iloprost in severe pulmonary hypertension
  secondary to lung fibrosis. Respiratory and
  Critical Care Medicine 160(2) 1999600-607.
• Walmrath D, Schneider T, Schermuly R, et al.
  Direct comparison of inhaled nitric oxide and
  aerosolized prostacyclin in acute respiratory
  distress syndrome. Am J Respir Crit Care Med
  1996 153991-996.

4
Pharmacologic Actions

• Selective vasodilation of pulmonary vascular
  beds1
• Decreased PVR, PAP
• Inhibition of platelet aggregation
• (but no evidence of platelet dysfunction or
  bleeding noted clinically)
• Increased arterial oxygenation
• Improved V/Q matching in lung (Cochrane review
  planned for 2009)

• Olschewski H. et al. Inhaled prostacycin and
  iloprost in severe pulmonary hypertension
  secondary to lung fibrosis. Respiratory and
  Critical Care Medicine 160(2) 1999600-607.

5
Indications

• Primary and Secondary Pulmonary Hypertension
• Cardiac surgery-associated pulmonary hypertension
  and RV failure
• Lung transplantation-related reperfusion injury
• Liver transplantation portopulmonary hypertension
• Hypoxemia due to single-lung ventilation or ARDS

6
Contraindications

• Hypersensitivity to drug or diluent

7
Cost Analysis (compared with nitric oxide)

• Average runtime 45.6 hours1 (for PPH)
• Flolan (based on average weight 80kg at 31
  mcg/kg/min)
• Medication - 12.50 hour
• PALL filter unit cost - 4.99 (changes Q2H)
  113.77
• Disposable aeroneb system - 50.00
• 733.77
• Nitric Oxide
• 95.00 hour
• 4332.00

1. De Wet CJ. Inhaled prostacyclin is safe,
effective and affordable in patients with
pulmonary hypertension, right heart dysfunction,
and refractory hypoxemia after cardiothoracic
surgery. J Thoracic and Cardiovascular Surgery
20061271058-67
8
Setup

• Must be reconstituted with glycine
• Not compatible with any other solution
• Glycine is sticky and viscous
• Needs to be shielded from light
• Recommended to keep reconstituted solution cold
  with icepacks during administration (2-8 degrees
  C) (stable for 8 hrs room temp, 24 hours
  refrigerated)
• Nebulizer, infusion tubing, connections, changed
  every 24 hrs (refrigerated) or every 8 hrs
  (unrefrigerated) as drug expires
• Option A continuous flow-driven nebulizer
  (Miniheart) infusion pump
• Option B continuous electronically-driven
  nebulizer (Aeroneb) infusion pump

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Option A Miniheart neb

• Continuous flow-driven nebulizer
• Dose delivery is dependent on flowrate
• 8 ml/hr nebulizer output with 2 Lpm flowrate set
  on neb
• Fluctuating dosing may occur during delivery
• Easy to wean by adjusting neb input from pumps
• Added flow to ventilator circuit affects
  ventilation
• patient triggering affected
• Triggering will be made less sensitive or could
  cause autocycling
• Delivered tidal volumes and pressures increased
• Delivered FiO2 changes unless nebulizer connected
  to blender
• Accuracy of monitored values is affected
  exhaled tidal and minute volumes will be
  inaccurate
• Alarm functions may be inaccurate particularly
  low tidal volume/low minute volume/leak alarms
• Certain ventilator modes will malfunction (PRVC,
  CMV with Autoflow, VC, PAV)
• Safest mode to be on is PSV or PCV

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Option A Miniheart neb

• Accidental disconnection of nebulizer tubing is
  possible due to backpressure from nebulizer
  causing sudden stoppage of dosing (no alarm)
• Accidental disconnection or maladjustment from
  wall flowmeter is possible (causing increased or
  stoppage of dosing) (no alarm)
• Nebulizer tipping is possible, causing accidental
  instillation of entire dose into endotracheal
  tube or sudden stoppage of dosing (no alarm)

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Option B Aeroneb

• Continuous (mesh screen sifter)
  electronically-driven neb
• Dose delivery is dependent on constant output
• On-off switch only nebulizer output is set at
  30 ml/hr
• Dosage depends on concentration of medication in
  nebulizer
• Difficult to wean med must be remixed
• Does not affect ventilator performance no flow
  added to circuit
• Nebulizer dysfunction is likely (no alarm)
• Unit stops functioning if battery dies
• Have had to replace batteries in all of our
  controllers
• Cables can be kinked
• Powercords malfunction frequently
• Limited number of controllers available would
  need backup unit on standby
• Cost of controller unit is 1425. ( we have 3,
  often all are in use for nebulized antibx)
• Nebulizer tipping is possible. Would not spill
  dose into endotracheal tube, but may result in
  sudden stoppage of dose (no alarm)

12
Benchmarking

• Barnes Jewish Hospital, St. Louis, MO
• 126 patients
• Miniheart continuous nebulizer
• Filter changes Q2 hrs
• Adverse event vent exhalation valve became
  sticky, significant autopeep/hypotension
• Sudbury Regional Hospital, Sudbury, ON
• Filter changes Q6 hrs and PRN
• Kingston General Hospital, Kingston, ON
• Miniheart continuous nebulizer
• Filter changes Q4H and PRN
• Harborview Medical Centre, Seattle, WA
• Aeroneb
• No filtering?
• Bench test only
• St Pauls Hospital, Vancouver, BC
• Miniheart nebulizer
• Filter changes Q 2-4 hrs and PRN

13
Patient Safety

• Neb must run continuously
• Product has biological half-life of 2-3 minutes
• Rebound pulmonary hypertension may be
  life-threatening
• Dyspnea, dizziness, asthenia
• Rare reports of death (IV use)1, 2

• Augoustides J, Culp K, Smith S. Rebound pulmonary
  hypertension and cardiogenic shock after
  withdrawl of inhaled prostacyclin. (Case Report)
  Anesthesiology 2004(100)1023-1025
• Barst RJ. Rubin LJ. McGoon MD, et al. Survival in
  primary pulmonary hypertension with long-term
  continuous intravenous prostacyclin. Ann Intern
  Med 1994 121409-415.
• GlaxoSmithKline Inc. Product Monograph, Flolan
  for Injection, 2008.

14
Patient Safety contd

• Filter clogging
• Glycine is sticky and viscous quickly clogs
  filters
• Bench testing for filter resistance1
• 1. David Sima, RT Clinical Educator, bench
  testing data June 2009

15
Standard dose (31 mcg/kg/min, 80 kg)- 10 Lpm
minute volume- calibrated equipment,
reproducible results- filter resistance after 1
hour 18.8 cmH20/Lps
16
Standard dose (31 mcg/kg/min, 80 kg)- 20 Lpm
minute volume- calibrated equipment,
reproducible results- filter resistance at 1
hour 23.09 cmH20/Lps
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Filter Clogging

• ? expiratory resistance
• ? autopeep
• ? intrathoracic pressure
• ? PVR
• Affect V/Q matching in lung
• Affect ventilator performance and safety
• Hourly circuit changes may clog vent exp filter
• Vent-inop at 5 cmH20 transducer difference
• Would necessitate immediate manual ventilation
  and vent change

18
Occupational Health and Safety

• Would require frequent (Q30min) circuit
  disconnections
• PPE protection for staff during exposure times
• Minimal data on exposure during pregnancy

19
Alternatives?

• Prostaglandins
• IV Epoprostenol
• Iloprost
• Treprostinol
• Beraprost
• PGE1
• NO donors
• Inhaled Nitric Oxide
• Inhaled sodium nitroprusside
• Inhaled nitroglycerine
• Phosphodiesterase Inhibitors
• Sildenafil
• Milrinone
• Endothelin Antagonists
• Bosentan
• Nesiritide
• Adrenomedullin

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Recommendations

• Evaluate risk-benefits
• Explore alternatives
• If we must?
• Aeroneb recommended as best delivery system
• Q 30 minute filter changes
• Purchase additional controller sets
• Backup equipment on standby
• Patient care guideline development, education and
  vigilance for patient safety
• Investigate alarm possibility with manufacturer

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Summary

• Patient benefit for use (PPH, ARDS?)
• Inexpensive in comparison with N.O.
• 2 delivery systems, both have significant safety
  concerns
• Is it worth it? Or investigate alternatives?