Inhaled%20Epoprostenol

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

1. 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.
2. Lowson SM. Inhaled Alternatives to Nitric Oxide.
   Anesthesiology 200296(6)1504-1513
3. 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.
4. 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. 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.

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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)

1. 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.

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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

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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
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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)

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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

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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.

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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

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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
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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

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Occupational Health and Safety

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

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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?