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H1N1 FLU PANDEMIC THE NOVA SCOTIA EXPERIENCE
EXTRACORPOREAL MEMBRANE OXYGENATION/TAKING A HIT
STEPHEN G. MORRISON
SATURDAY SEPTEMBER 10, 2009

QEII HEALTH SCIENCES
CENTER

INCIDENCE OF H1N1 IN CANADA
Cases of H1N1 continue to be reported in Nova Scotia. There have been 17
hospitalized cases and one death associated with the HINI virus since the outbreak
started on April 26.
As of 1 August, 2009, a total of 1,315 hospitalized cases and 227 cases admitted to
an intensive care unit (ICU) had been reported so far to the Public Health Agency of
Canada. This week, three deaths were reported for a total of 60 deaths since the
beginning of the pandemic. The peak period of hospitalizations was observed during
the first 3 weeks of June.

Message from The Department Of Health
If You Woke up This Morning Looking Like This
Don’t Go To Work

• 25 Year old female presented to
community medical center, June 28. 2009
• C/O dry cough, fever, chills, general
malaise, shortness of breath
• Duration of symptoms six days

Past medical history
• Gastro-esophageal reflux
• Endometriosis
• Smokes .5 packs cigarettes day
• Allergies to Azithromycin
• Height- 170cm
• Weight- 90 Kg
• BSA-2.06 ms

• Chest x-ray showed bi-lateral infiltrates in
all lung segments
• Started on Erythromycin 1gm
• Tami-flu 75 mg x 10 days
• Throat swabs taken for Dx of H1N1
• She claimed she was exposed to a co-
worker positive for H1N1

• Clinically became more short of breath
• Hypoxemic, decreasing arterial O2
saturations to 82% on 100 % O2
• Transferred to Regional Hospital

• Following initial assessment
• Transferred to Medical Surgical Intensive Care
unit
• Sedated, intubated/ventilated, received paralytic
drug Nimbex 20 mg IV
• Ventilator settings, g, Fi02 0.7 (Sechrist Blender),
peep 12 cm/H20, respiratory rate 20 bpm,
• Arterial O2 saturation improved to 91%
• Nitric oxide initiated at 5 parts per million
increased to 70 PPM
• Discontinued day 2, felt to be ineffective

• Throat swabs confirmed the pt. positive for
H1N1
• Also Dx with community acquired bacterial super
infection, methecillin resistant staphylococcus
aureus
• Repeat x-ray showed persistent bi-lateral
infiltrates t with progression
• Cardiac function as assessed by ultra sound
showed normal left and right ventricular and
atrial function with slight mitral valve
regurgitation

X-ray June 2nd

• She deteriorated that evening
• Arterial Oxygen saturation declined to 52% on
Fio2 of 1.0
• Arterial blood gas obtained, PaO2 32 mmhg,
CO2 43 mmhg, hemoglobin 125 g/l
• Respiratory initiated hand bagging with 100%
O2
• Saturation rose to 88%
• PaO2 56 mmhg

• Cardiac surgery consulted
• ECMO protocol initiated
• Team arrived
• Surgeon prepped groins for ECMO cannulation
• Perfusion arrived with primed, de-aired ECMO circuit
• 3/8/3/8 inch Carmeda coated (heparin coated) tubing
• 32 ml Rotoflow cone (Bioline coated)
• Quadrox D oxygenator, (Bioline coated)
• Biiomedicus, Minneapolis, Minesota 540 console
• Biomedicus Bio Cal 370 heater cooler

• 5000 unit bolus of heparin (hepalean) ea given to
patient, prior to initating ECMO
• Cannulation of right internal jugular via seldinger
technique, with an uncoated 17 French DLP
venous cannula (Medtronic)
• Left groin cannulated with an uncoated 17
French DLP arterial cannula (Medtronic)
• Could not pass a venous cannula
• Cannulas clamped distally connected to
crystalloid (Normosol-R) primed circuit

• ECMO initiated
• Flow of 2.8 LPM achieved
• Fi02 1.0, sweep gas of 4.0 liters,
• Arterial oxygen saturation 98% on oxysat monitor, CDI 100
• Negative pressure -56 mmhg (measured pre Rotoflow cone), with
chatter noted in lines
• To bring down the inlet pressure, Voluven 250 mls given , pressure
dropped to – 27 mmhg
• ACT drawn with results of 360 seconds
• Heparin infusion started at 1600 units per hour
• ACT’s remained in the 160-210 sec range with minor adjustments of
heparin drip. 1500-1800 1800 units per hour
• ACT’s drawn every hour

• In order to achieve a negative fluid balance of 1 liter in
24 hrs
• Bolus of lasix 40 mg was given and a drip started
• 100 mls per hour was taken off via hemoconcentrator
• A Propofol infusion was started at 400 mg/hr, later
decreased to 200 mg/hr
• Voluven was needed at regular intervals to keep
negative pressure less than -30 mmhg
• Order by physician was to give voluven 250 mls Prn.
• Negative fluid balance was never achieved

• To improve venous drainage and
increase ECMO flows
• Second venous cannula ( 21 French
Medtronic DLP) inserted in right groin
• After this the negative inlet pressure
decreased from -95 mmhg to -45 mmhg
• Increased back to -80 mmhg over next
two hours, volume had to be added

• ECMO day 7, platelets decreased from 100 x
10(9)L to 80 x 10(9)L, Hemoglobin, 69 G/L
• Large amount of blood was seen on dressings
over cannulas
• 2 units of platelets were given
• 2 units of packed red blood cells were given
• Dressings were removed to assess bleeding
• The dressings were completely soaked with
blood

• Upon inspection of the cannula sites, the
Left femoral cannula was noted to be
kinked almost in half
• Flow was assessed by individually
clamping femoral cannulas and assessing
flow from the console
• Flow through h the left cannula was no
greater than 75 mls minute

• The eca cannula ua was asca clamped peda and dc changed gedtoa 20
French Edwards venous cannula by cardiac
surgery
• This cannula was larger in diameter so it
effectively stopped bleeding at the insertion site
• A stay suture was placed at the site of the right
femoral cannula
• Full ECMO support was resumed
• The negative pressure did not go any higher
than -35 mmhg at any time

20 FRENCH EDWARDS VENOUS
CANNULA

• ECMO day 12, perfusionist noted 4-5
areas of white lipid like deposits
approximately 2-5 cm on the inflow of the
oxygenator
• There was also a rise in negative pressure,
-25 mmhg to -52 mmhg
• Flows had decreased d from 3.2 Lpm to 2.1
Lpm

• The residue was thought t to be propofol o deposits
• Propofol was discontinued on order from
attending
• Clonodine was used as an alternative drug for
sedation (I.V. infusion 1.3 mcg/kg hr)
• Throughout h the night pt exhibited signs of
wakefulness
• Rapid eye movement, finger and toe
movements, and slight response to verbal
commands ( squeezing fingers)

• During morning rounds heparin induced
thrombocytopenia was discussed as a
possibility
• A blood gas was obtained with the
following result
• Platelets 52 x 10 (9)L
• Fibrinogen level was 1.07 g/l ( normal 1.7-
4.1 g/l)
• 10 units of cryoprecipitate was given

WHAT IS HIT
• What is heparin induced thrombocytopenia
• Ordinarily, heparin prevents clotting and does not affect
the platelets
• Triggered by the immune system in response to heparin,
HIT causes a low platelet count (thrombocytopenia)
• Two types of HIT occur; nonimmune and immune
mediated
• Type 1 nonimmune mediated has a mild decrease in
platelets and is not harmful
• Immune-mediated HIT occurs less frequently but is
dangerous

• Immune mediated HIT causes much lower platelet
counts
• Despite very low platelet counts, type 2 patients are at
risk for major clotting problems
• After heparin administration, an immune complex can
form between heparin and platelet factor 4 (PF4)
• The body views this immune complex as foreign
• An antibody binds to the complex and platelets are
destroyed
• This disruption of platelets can lead to the formation of
new blood clots and result in deep vein thrombosis,
pulmonary embolism,or heart attack or stroke

• An ELISA ( enzyme-linked
immunoabsorbant) assay was sent which
later came back positive for Hit
• Heparin-induced induced serotonin release assay
done
• Considered the gold standard in Dx of HIT
• Did not receive result until 4 days later,
also positive

• Decision was made to use an alternative anticoagulant and to
change the ECMO circuit to a synthetic coated circuit
• The Capiox SX 18 (Terumo) oxygenator was chosen (X-coated)
• Assembled along with 3/8 phospholocholine (synthetic) coated AV
loop
• A Biomedicus Bio cone (Carmeda coated) was used due to the fact
that t we have no non heparin Bio cones available
• The circuit was primed with Normosol-R, deaired and warmed
• The crystalloid was then chased with one unit of packed red blood
cells and tubing connected to existing cannulas

Capiox SX-18 Oxygenator

• Heparin was discontinued
• An alternative anticoagulation strategy,
utilizing Angiomax (Bivalirudin) was
employed
• Angiomax directly inhibits thrombin and
thrombin mediated platelet activation

• 4.6 mls of 50 mg gp
per ml of angiomax was
injected into a 100 cc bag of normal saline
• Giving a concentration of 2.3 mg/ml
• 30 mls was drawn and given as a bolus through
the cordis
• Bolus dose was 69 miligrams
• A 25 mg bolus was injected into the circuit
• Attending ordered the infusion to be decreased
by 30% if ACT greater than 225 second and to
bolus 50 mg (0.6 ml if ACT less than 225
seconds

• ECMO was restarted
• The initial ACT immediately following
attaining a flow of 2 Lpm was 240 seconds
• Angimax infusion was at 35 mls per hour

• The circuit cu change out took approximately ate 6
minutes and was tolerated well
• Pa02 56 mmhg, 02 saturation 88% C02 46
mmhg. The ventilator Fi02 during change out
was at 0.8, peep of 11 cm H2o
• Flows of 2 liters per minute were maintained
• Negative pressure -19 mmhg, and rpm’s 2270
• ABG’s on resumption of ECMO, Pa02 82 mmhg,
arterial oxygen saturation 0f 97%, venous
oxygen saturation of 65%

• ECMO day 14 ( day two with non coated
circuit) clinical improvement continued
• Fi02 on ECMO lowered to 0.4
• Flow reduced to 1.08 Lpm, sweep of 5.0
liters
• Pa02 88%, HC03 28 Meq, arterial oxygen
saturation 98%, base excess 3 Meq/L
• Lactate 1.0 mmol/L

• A trial run discontinuing ECMO support
was decided
• The AV bridge in the circuit was slowly
opened
• Rpm’s lowered to 1000
• The gas line to the blender was
disconnected, providing only a large
veno/venous shunt
• Support was provided by ventilator only

• Ventilator setting
• Fi02 0.8
• Peep 11 cm H20
• Arterial Oxygen saturations 91%
• Pa02 62 mmhg
• CO2 50 mmhg
• Trial run lasted seven minutes
• Rpm’s returned to 2000, flows increased to 1.5
liters/min, Fi02 at 40%

• ECMO day fifteen
• In the early afternoon the decision was made to
discontinue ECMO support
• The bridge was again opened, flows decreased,
once it was determined the pt. was stable the
cannulas were clamped out and then removed
• A connector was inserted between the AV lines
and flow continued to maintain the circuit
• 15 minutes prior to the discontinuation of ecmo,
Angiomax had been discontinued

Outcome
• The patient remained in the intensive care unit
for five days
• She was transferred to a step down unit, then a
general surgery floor
• She was discharged to home in good condition
with the only sequela being pain in her left foot
from foot drop
• Likely related to the length of time bedridden
and lack of range of motion exercises

Discussion
• 25 year old female with H1N1
• Requiring full ventilator support
• Placed on ECMO after clinical i l deterioration
ti
in respiratory function despite ventilator
support

• There were many interesting issues and
opportunities for learning with this case
• The pt. had increased bleeding which was
remedied by placement of a larger
cannula
• The goal of achieving a negative fluid
balance was never achieved
• Large volumes of fluid had to be added to
provide ECMO support

• Patient went on to develop a late stage
heparin induced thrombocytopenia (Hit)
• The entire circuit had to be converted to
synthetic coated
• The recommended length of use for the
SX-18 oxygenator was 6 hours
(manufacturer)
• It performed very well for several days
without incident

• Alternative anticoagulation ( Angiomax)
was chosen as a heparin alternative
• The ACT’s remained stable in the 220
second range
• However the International normalized
ratio (INR) elevated initially to 6.0 then
lowered and stayed at 4.0
• Thus there was always a risk and concern
of bleeding

• There was no algorithm available or policy
to direct the use of Angiomax while on
ECMO
• The recommendations from the Cardiac
Catheterization lab for PCI’s were followed
• We have available synthetic (non-heparin)
coated circuits and oxygenators, but do
not have non heparin coated Bio cones at
this time at our facility

• This case documents a positive outcome
in the use of ECMO support for a patient
with H1N1 viral infection
• The perfusion team will now be better
prepared to handle future cases as a
result

September 15
th X-ray

Alternative Treatments Discussed
• Turning patient prone utilizing different
ventilator approaches
• Placing patient in reverse trendelenberg
position while on ECMO
• Both of these options were not deemed
wise due to the difficulty in maintaining
ECMO support, with just minor
manipulations of the cannula, and
decreased outflow return