Transcript Flolan - A & T Lectures LLC

Al Heuer, PhD, MBA, RRT, RPFT
Associate Professor
Rutgers-SHRP
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Describe what is Flolan
Review how is works and on whom it should be
used
Summarize the indications and contraindications
Review the equipment set-up and how to
administer it via a ventilator circuit.
Examine some cases as to how it was introduced
into the hospital and some case applications
Share some additional resources on how to find
out more about Flolan
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Flolan®, or epoprotenol, is an synthetic prostacyclin
which relaxes smooth muscle cells induced by an
increase in intracellular adenosine 3’,5’ cyclic
monophosphate
Results in vasodilation of the pulmonary & systemic
vasculature in a dose-dependent manner
Indications:
• Pulmonary hypertension
• acute right heart dysfunction
• Hypoxemia related to pulmonary vasoconstriction
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In addition, prostaglandin has an inhibitory effect on
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Finally, prostaglandin inhibits activation of leukocytes
and monocytes during the inflammatory reaction
platelet aggregation
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Welte and his colleagues (1993) reported that inhaled
PGI2 resulted in selective PA vasodilation in dogs
Inhaled PGI2 reaches only well ventilated areas of the
lungs, causing selective vasodilation in these regions
than the IV route does, while not causing systemic
hypotension
Analog drugs: Synthetic analogs of prostacyclin
(PGI2).
• Treprostinil (marketed under the trade names Remodulin for
infusion and Tyvaso for inhalation)
• Inhaled Iloprost (Ventavis) by Mask and nebulizer
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It’s NOT a medical gas like Nitric Oxide…but rather a
nebulized drug!!!
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The use of Flolan® causes marked
pulmonary vasodilatation
Also does so while maintaining gas
exchange and systemic arterial pressure.
There is a significant decrease in mean
pulmonary artery pressures (PAPs) without
noticeable change in mean arterial
pressures.
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Post op for Primary Pulmonary Hypertension
Utilized in conjunction with a Ventricular Assist
Device, (most commonly Right Ventricular
Dysfunction).
To reduce and maintain PA pressures allowing for
Heart rest, recovery, and healing.
To treat low (EF) Ejection Fraction of < 20%.
Treatment of hypoxemia secondary to ARDS, Acute
Lung Injury, or V/Q mismatching.
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Comparable beneficial effects of pulmonary
vasodilation without affecting systemic
systems:
- Reduced pulmonary artery pressure
- Reduced pulmonary vascular resistance
- Reduced transpulmonary gradient (Chest 1998; 114;
780-786)
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Improved oxgenation.
Lack of data showing increased survival for
ARDS patients.
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The delivery system for Inhaled Flolan® is
relatively simple to assemble
The drug is generally available in most
hospitals and more available than inhaled
Nitric Oxide
Tends to be less expensive than inhaled Nitric
Oxide.
Data tend to support overall effectiveness in a
clinical setting for treating:
– Pulmonary Htn
– Pul vasoconstriction with ARDS
 Cost--~$100/hour
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vs ~$220/day)
Epoprostenol lacks the toxic
effects/metabolites of nitric oxide and
therefore does not need a complicated
delivery system.
Epoprostenol can inhibit platelet
aggregation.
Epoprostenol does not bind with
hemoglobin (no increase in methemoglobin)
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One 500-Bed NJ hospital has saved over
$400K annually by supplementing their
INO usage with Flolan.
Other hospitals have had similar
experiences.
That’s equivalent to about the salary and
benefits for about four FT Respiratory
Therapists or Nurses.
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In general, Flolan has a favorable safety
(Risk to benefit) profile.
Rarely can exacerbate hypotension &
bleeding.
– Not reported in typical dose range
– Avoid aerosolized PGI2 during active pulmonary hemorrhage
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More common side effects include:
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Flushing
Headache
Nausea & vomiting
Hypotension
Anxiety
Chest pain
Dizziness
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Limited, but growing body of evidence
Mostly case reports and small studies
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Some case studies
Many studies had a small number of patients/subjects
No control or placebo groups
Not all results are attributable to inhaled PGI2
Incomplete data for some variables, such as PVR, wedge
pressure, CVP
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Rabinovich, et al. (2011) Chest Physician-Review
Article: Inhaled PGI2 is as effective as iNO for S/T mgt of PH
and impaired oxygenation with potentially fewer side effects,
lower costs, and greater ease of administration. However,
further randomized, controlled studies are needed.
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De Wet, et al. (2004) – Prospective interventional
study of 126 cardiothoracic surgical patients with
pulmonary Hypertension
– PGI2 decreased mean PA pressures without altering mean
arterial pressure
– There was a significant improvement in the PaO2/FiO2 ratio
in patients with refractory hypoxemia
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Haché, et al. (2001) Chart review of 27 patients who
received inhaled PGI2 over a one-year period
– Selective pulmonary vasodilation occurred in 78% of
patients
– Improvement in PaO2/FiO2 ratio in 88%
– Concluded that inhaled PGI2 can be useful in the
treatment of patients with pulmonary hypertension &
severe hypoxia
◦ Though it may be used on spontaneously
breathing patients
◦ Patients should in an area capable of continuous
cardiac monitoring.
 Post-Open Heart ICU
 CCU
 OR
 CATH LAB
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When started in the cardiac cath. lab or OR
setting, it is recommended that there be no
break in delivery during transport of the
patient from one area to another, (i.e.
ICU/CCU). When transported from area to
area there needs to be an oxygen cylinder
to nebulize the Flolan® and another cylinder
to ventilate the patient.
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In general, there are 3 recommended
dosages:
◦ Full strength 10mcg/ml
◦ Half strength 5mcg/ml
◦ Quarter strength 2.5mcg/ml
At many hospitals, the dosing is 10mcg/ml
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Flolan® will be received from pharmacy in
appropriate dosages as ordered by the physician.
Flolan® will be stored in the unit medication
refrigerator until needed.
When initiating, or starting a subsequent
treatment, always confirm that there is an
additional new vial of Flolan® available in the
refrigerator in the correct dosage for the next
treatment. If not, notify pharmacy and obtain the
verbal or written prescription for the continuation
of therapy.
Flolan® 10mcg/ml will be the most commonly used dosage. All
meds will be delivered from the pharmacy premixed.
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Flolan® generally comes to the clinical area
from pharmacy premixed, in the prescribed
dosage. Any vial of medication not mixed to
the physician’s prescribed dosage should
generally be returned to pharmacy to be
reconstituted.
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Confirm prescription, typical dose is 10mcg/ml, at
8ml/hr
Flolan® will be drawn up from individual bottles when
needed by use of a syringe and blunt needle.
24ml of Flolan® will be added to a Mini Heart
Nebulizer.
The nebulizer will be inserted into the inspiratory
limb of the circuit at the wye.
– Use caution to stabilize the nebulizer to prevent spillage of the contents, due to
it’s viscous nature.
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The Nebulizer will be covered to protect the contents
from light due to a light sensitivity.
The Flolan® will be nebulized at a flow rate of 2 lpm.
– At a flow of 2 lpm the contents should nebulized in approximately 3 hours.
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The mechanical ventilator will be assembled with
a heated circuit and humidification device.
There will be an Oxygen Blender on the ventilator
to generate the 2 liter per minute flow to power
the Mini Heart Nebulizer at the same FiO2 as the
Ventilator.
The circuit will have 2 hepa filters located on the
expiratory limb of the circuit.
– The first filter is just after the patient wye, and the second is at the
end of the circuit prior to the collection bottle.
– The Hepa filters will be changed every three hours when a new Mini
Heart of Flolan® is started or as needed, if the peak airway pressures
reflect an unexpected increase.
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Expired minute volume, ventilation pressures,
patient-initiated triggering, FiO2, & heated
humidifier settings may vary due to nebulizer
flow into circuit
Glycine buffer makes aerosol sticky
Change expiratory filters Q4H or sooner to
prevent sticking of expiratory valve and auto
PEEP
An oxygen blender must be used to power
the nebulizer to achieve the same FiO2 as
the ventilator settings.
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The Mini Heart nebulizer must be shielded from light.
The IV
pump will
be labeled
for RT use
only and
will only be
handled by
respiratory
therapy.
Note: 2
filters
connected
to the
exhalation
port on vent.
Make sure to use only
a heated wire circuit.
On/Off
switch
Miniheart nebulizer in
alternate location just
distal to the humidifier.
Use the blender to match the
patient’s set FiO2 and run the
flowmeter at 2-3 lpm.
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One common approach is to titrate medication,
from full strength (10mcg/ml), to half strength
(5mcg/ml), and then to quarter strength
(2.5mcg/ml), prior to discontinuation.
Titration of Flolan® will be reconsidered if a
patient demonstrates an increase of PA pressures
within 30 minutes of titration or discontinuation
If patients display a significant increase of PA pressure, the
physician should be contacted to resume Flolan® at either initial
or half-dose/concentration (either 10 or 5 mcg/ml.
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Per Protocol, no weaning is necessary.
Flolan® effect is completely resolved
within 24 minutes of termination.
– After discontinuation of Flolan®, close observation of PA
pressures are required.
– If a significant increase in pressures, (≥ 20%), are observed,
restarting the medication is indicated.
– When restarting Flolan® a new Mini-Heart® Nebulizer should
be used and a new vial of medication obtained, so that dosage
and duration can be precisely determined.
– When restarting the med, resume administration at full
or ½ strength, (5mcg/ml), and titrate to ¼ strength,
(2.5mcg/ml), at 30 minutes. If PA pressure is acceptable
attempt stopping the Flolan and attempt extubation
again.
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Per any Medication, an order to discontinue the
medication must be obtained prior to discontinuation.
Documentation of PA pressures should be documented
and followed closely for up to 30 minutes following
Flolan® termination. (All effects of Flolan® should be
resolved after 24 minutes of termination.)
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In the event of elevated PA pressures Flolan® may need
to be resumed. Do not discard the Nebulizer set-up
until 30 minutes has passed and Hemodynamic stability
has been confirmed.
If the patient demonstrates Hemodynamic and
Pulmonary Stability beyond 30 minutes, this suggests
that Flolan will no longer be neeeded.
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If a patient is unable to tolerate termination of
Flolan prior to extubation, there are alternatives.
Alternatives include the following:
 Intravenous route Flolan®
 Oral Silendafil, (Viagra®)
 Inhaled Iloprost® (Ventavis) by Mask and nebulizer
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At this time there are no studies
documenting the safe administration of any
Bronchodilator in conjunction with the use
of Flolan. There is no FDA approval for any
Bronchodilator to be given with Flolan
running.
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To Pharmaceuticals & Therapeutics
Committee in December 2005 (since delivery
route not HPB approved)
Implemented PGI2
guidelines/policies/procedures for adult
patients in April 2006 in surgical suites, ICU,
& cardiac surgical unit
Revised policies & procedures in March 2008
to include pediatric patients
Currently reviewing case reports of PGI2 use
in newborn patient population
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69 YO male with a history of cardiomyopathy is
intubated and mechanically ventilated due to a
severe exacerbation of CHF. He currently has
Swan Ganz catheter in place and his cardiac
output is 2.9 L and PAP is 52/35 torr. His FIO2
was recently raised to 65% to maintain an SPO2
of 92%.
Patient was started on Flolan, 10mcg/ml, at
8ml/hr.
◦ Within 6 hours: PAP decreased to 35/19 torr, CO 3.6 L,
SPO2 95% on FIO2 50%
◦ Within 2 days, other clinical indicators (renal function)
improved.
◦ Patient successfully extubated 5 days later.
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57 Yo intubated/ventilated female post-trauma
patient becomes septic and develops ARDS. Her
CXR has bilateral obtuse infiltrates (ground-glass
appearance), she has refractory hypoxemia (P:F
ratio < 150) and A/W pressures have increased
to the mid-40s cm H2O.
She was switched to PCV (from volume control)
and started on Flolan, 10mcg/ml, at 8ml/hr.
◦ Within one day, P:F increased to 245, FIO2 successfully
weaned to 50% from 75% . ABG’s were within acceptable
limits.
◦ One week later the patient was successfully extubated.
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Use of inhaled PGI2 is a promising therapy for
the treatment of pulmonary hypertension &
hypoxia of various origins
Therapy must be based on:
– Suitable patients
– Proper procedures and training
– Continual therapy, until intentionally withdrawn
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Further studies are required to determine doseresponsiveness, optimal condition of utilization,
and impact on survival
The pursuit of its use requires the collaborative
effort of respiratory therapists, nurses,
physicians, and pharmacists
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Flolan Information Center: http://www.flolancenter.com/
US Food & Drug Administration:
http://www.accessdata.fda.gov/drugsatfda
"epoprostenol" at Dorland's Medical
Dictionary