Transcript Flolan Summary - UBC Critical Care Medicine, Vancouver BC

Inhaled Epoprostenol
Considerations for Use
in Ventilated Patients
Shari McKeown, Practice Leader Respiratory Services VA
Aliases
Naturally occurring prostaglandin
Epoprostenol sodium
Flolan
Prostacyclin
PGI2
PGX
…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.
2.
3.
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 2002;96(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, 18;1499-1504.
4.
Olschewski H. et al. Inhaled prostacycin and iloprost in severe pulmonary hypertension
secondary to lung fibrosis. Respiratory and Critical Care Medicine 160(2) 1999:600-607.
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; 153:991-996.
Pharmacologic Actions
Selective vasodilation of pulmonary
vascular beds1
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Decreased PVR, PAP
Inhibition of platelet aggregation
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(but no evidence of platelet dysfunction or
bleeding noted clinically)
Increased arterial oxygenation
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1.
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) 1999:600-607.
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
Contraindications
Hypersensitivity to drug or diluent
Cost Analysis
(compared with nitric oxide)
Average runtime 45.6 hours1 (for PPH)
Flolan (based on average weight 80kg at 31 mcg/kg/min)
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Medication - $12.50 hour
PALL filter unit cost - $4.99 (changes Q2H) = $113.77
Disposable aeroneb system - $50.00
= $733.77
Nitric Oxide
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$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 2006;127:1058-67
Setup
Must be reconstituted with glycine
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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
Option A: Miniheart neb
Continuous flow-driven nebulizer
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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
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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
Option A: Miniheart neb
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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)
Option B: Aeroneb
Continuous (mesh screen sifter) electronically-driven neb
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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
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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)
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Nebulizer tipping is possible. Would not spill dose into
endotracheal tube, but may result in sudden stoppage of dose
(no alarm)
Benchmarking
Barnes Jewish Hospital, St. Louis, MO
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126 patients
Miniheart continuous nebulizer
Filter changes Q2 hrs
Adverse event – vent exhalation valve became sticky, significant
autopeep/hypotension
Sudbury Regional Hospital, Sudbury, ON
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Filter changes Q6 hrs and PRN
Kingston General Hospital, Kingston, ON
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Miniheart continuous nebulizer
Filter changes Q4H and PRN
Harborview Medical Centre, Seattle, WA
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Aeroneb
No filtering?
Bench test only
St Pauls Hospital, Vancouver, BC
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Miniheart nebulizer
Filter changes Q 2-4 hrs and PRN
Patient Safety
Neb must run continuously
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Product has biological half-life of 2-3 minutes
Rebound pulmonary hypertension may be lifethreatening
Dyspnea, dizziness, asthenia
Rare reports of death (IV use)1, 2
1.
2.
3.
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; 121:409415.
GlaxoSmithKline Inc. Product Monograph, Flolan for Injection, 2008.
Patient Safety cont’d
Filter clogging
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Glycine is sticky and viscous; quickly clogs
filters
Bench testing for filter resistance1
1. David Sima, RT Clinical Educator, bench testing data June 2009
- 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
20
18
16
14
12
Pre Filter Pressure cm h20
Post Filter Pressure cm h20
Resistance cmh20/L/sec
10
8
6
4
2
0
0 minutes
15 minutes
30 minutes
45 minutes
60 minutes
- 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
24
22
20
18
16
14
Pre filter cmh20
12
post filter cmh20
10
Resistance
8
6
4
2
0
0 minutes
20
minutes
40
minutes
60
minutes
Filter Clogging
↑ expiratory resistance
↑ autopeep
↑ intrathoracic pressure
↑ PVR
Affect V/Q matching in lung
Affect ventilator performance and safety
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Hourly circuit changes may clog vent exp filter
‘Vent-inop’ at 5 cmH20 transducer difference
Would necessitate immediate manual ventilation and
vent change
Occupational Health and Safety
Would require frequent (Q30min) circuit
disconnections
PPE protection for staff during exposure
times
Minimal data on exposure during
pregnancy
Alternatives?
Prostaglandins
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IV Epoprostenol
Iloprost
Treprostinol
Beraprost
PGE1
NO donors
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Inhaled Nitric Oxide
Inhaled sodium nitroprusside
Inhaled nitroglycerine
Phosphodiesterase Inhibitors
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Sildenafil
Milrinone
Endothelin Antagonists
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Bosentan
Nesiritide
Adrenomedullin
Recommendations
Evaluate risk-benefits
Explore alternatives
If we must?
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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
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?