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Pharmacists in Critical
Care: Acute Liver
Failure
Jane Booth
Senior Medicines Information Pharmacist
Austin Health (Melbourne, Australia)
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Pharmaceutical care for critically-Ill
patients

The role of clinical pharmacist in ICU

The type of medications commonly used in ICU

Case study of medication use in ICU


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Acute liver failure

Presentation:
Rapid decline in liver function
Symptomatic: jaundice, coagulopathy, hepatic encephalopathy

Considered rare but commonly seen at Austin Health (liver


transplant centre)
Common causes:
50% from drug causes:
Paracetamol overdose (intentional and unintentional)
Idiosyncratic drug-induced liver injury
Hepatitis B, autoimmune hepatitis

Prognosis is poor: may require liver transplant


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Role for the pharmacist #1

Patient presents with acute liver failure, presumed drug


cause.
Which of their medicines could have contributed?

No recent paracetamol intake, no reason to suspect


overdose

LiverTox database (free access):


https://livertox.nlm.nih.gov

Dont forget herbal and non-prescription medicines


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Key issues: acute liver failure

Cerebral oedema

Vasodilatory shock

Sepsis

Coagulopathy

Renal failure

Fluid and electrolyte management


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Cerebral oedema

Significant cause of mortality

Hyperammonaemia, cerebral hyperaemia (increased perfusion)

Commence Quad-H therapy for all Patients with high-grade encephalopathy


requiring intubation:
Hyperventilation
Haemofiltration (assists with clearing ammonia)
Hypernatraemia
Hypothermia

Therapeutic Targets of Quad-H:


Lower of PaCO2 32-35 mmHg or the PaCO2 achieved by the patient prior to
intubation
Serum ammonia levels <60 mol/L
Serum sodium 148-152 mmol/L
Temperature 35C

Warrillow & Bellomo Anaesth Intensive Care 2014;42(1):78-88


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Role for the pharmacist #2

Drug dosing in renal replacement therapies

Haemodialysis:
Intermittent (three days per week)
Timing of medicines can be important

Haemofiltration (CVVH):
Continuous
Approximately equivalent to eGFR 30 (depending on the
system used)

Picture changes frequently


On and off filtration
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Renal Replacement Therapy
References

Renal Drug Database and Handbook (UK)


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Other resources for renal
dosing
Product Information
sometimes

Specialist antibiotic references


Therapeutic Guidelines
Sandford Guide to Antimicrobial Therapy
Kucers Use of Antibiotics

Primary literature
Dr Jason Roberts publishes extensively in this area
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Role for the pharmacist #3

Safe use of hypertonic sodium chloride


1.8%, 3% or 20% products available
Store separately from standard sodium chloride 0.9%
Hypertonic
Give via a central line
Rapid correction of low sodium can be fatal
Osmotic demyelination
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Sepsis

Gram negative and fungal sepsis are leading causes of


death in acute liver failure

Broad spectrum beta-lactam antibiotics

Antifungal prophylaxis (prior to liver transplantation):


Liposomal amphotericin 3 mg/kg
Anidulafungin
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Role for the pharmacist #4

Antimicrobial stewardship
appropriate medicine choice
appropriate dose
appropriate duration
drug/disease interactions
therapeutic drug monitoring
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Cardiovascular management

Aim for mean arterial pressure >60 mmHg


noradrenaline
vasopressin
hydrocortisone
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Airway support

Intubate and ventilate if


Glascow Coma Score (GCS) <8
and/or PaCO2 >45 mmHg with pH <7.3 and severe
encephalopathy

Why?
Comatose patients cannot protect their airway from
aspiration and obstruction
normal reflexes not functioning
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Role for the pharmacist #5 and
#6
What else is wrong with the patient?
take an accurate medication history
consider IF regular medicines should be continued in ICU
appropriate in critical illness, renal/hepatic impairment?
consider HOW regular medicines should be continued in ICU
antidepressants, mood stabilisers, Parkinsons Disease
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Role for the pharmacist #7

Compatibility of parenteral medicines

Consider a patient post liver transplant:


Vancomcycin 15 mg/kg IV bd for 48 hours
Ceftriaxone 1g IV bd for 48 hours
Ranitidine 50 mg IV tds
Vitamin K (phytomenadione) 10 mg IV d
Heparin 5000 units sc bd (when INR <2.0)
Methylprednisolone 50 mg IV qid day 1 (then weaning to oral prednisolone by Day 6)
Mycophenolate 500 - 1000 mg IV bd
Tacrolimus 0.1 mg/kg/day (oral/NGT preferred)
Noradrenaline infusion
Alprostadil 0.1-0.6 microg/kg/hour (when inotropes not required)
Dextran 40 10 mL/hour
Insulin infusion
Glucose 5% as drug and flush line
Ganciclovir?
Anidulafungin?
TPN?
Morphine or fentanyl infusion/patient-controlled analgesia
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Parenteral compatibiltiy

Useful resources:
Local guidelines
Australian Injectable Drugs Handbook (SHPA)
Trissel: Handbook on Injectable Drugs (US)
Trissels Tables (US)
Gray et al: Injectable Drugs Guide (UK)
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Parenteral compatibility

Approach:
1. Identify which medicines are continuous infusions or take a
long time to run
2. Identify the medicines that need to be given via a central
line
3. Identify any medicines that should not be mixed with other
medicines or are grouped together
4. Check compatibilities for remaining medicines
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Parenteral compatibilty
1. Identify which medicines are continuous
infusions or take a long time to run
Vancomycin 10 mg/minute (eg 2g over 200 minutes)
Ceftriaxone over 3-5 minutes
Ranitidine over at least 5 minutes
Vitamin K (phytomenadione) over 30 seconds
Methylprednisolone over at least 5 minutes
Mycophenolate over at least 2 hours
Noradrenaline infusion
Alprostadil 0.1-0.6 microg/kg/hour (when inotropes not required)
Dextran 40 10 mL/hour
Insulin infusion
Glucose 5% as drug and flush line
Ganciclovir over 1 hour
Anidulafungin 1.1 mg/minute
TPN
Morphine or fentanyl infusion/patient-controlled analgesia
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Parenteral compatibilty
2. Identify the medicines that need to be given via
a central line
Vancomycin 10 mg/minute (eg 2g over 200 minutes)
Ceftriaxone over 3-5 minutes
Ranitidine over at least 5 minutes
Vitamin K (phytomenadione) over 30 seconds
Methylprednisolone over at least 5 minutes
Mycophenolate over at least 2 hours
Noradrenaline infusion
Alprostadil 0.1-0.6 microg/kg/hour (when inotropes not required)
Dextran 40 10 mL/hour
Insulin infusion
Glucose 5% as drug and flush line
Ganciclovir over 1 hour
Anidulafungin 1.1 mg/minute
TPN
Morphine or fentanyl infusion/patient-controlled analgesia
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Parenteral compatibilty
3. Identify any medicines that should not be mixed
with other medicines or are grouped together
Try to keep similar things together if compatible:
Insulin infusion, Glucose 5% as drug and flush line
Noradrenaline with other vasopressors
Generally keep separate:
TPN
Morphine or fentanyl infusion/patient-controlled analgesia
Blood products
Leaves us with:
Vancomycin 10 mg/minute (eg 2g over 200 minutes)
Ceftriaxone over 3-5 minutes
Ranitidine over at least 5 minutes
Vitamin K (phytomenadione) over 30 seconds
Methylprednisolone over at least 5 minutes
Mycophenolate over at least 2 hours
Dextran 40 10 mL/hour
Ganciclovir over 1 hour
Anidulafungin 1.1 mg/minute (100 200 minutes)
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Parenteral compatibilty
4. Check compatibilities for remaining medicines

Vancomycin 10 mg/minute (eg 2g over 200 minutes)


Ceftriaxone over 3-5 minutes
Ranitidine over at least 5 minutes
Vitamin K (phytomenadione) over 30 seconds
Methylprednisolone over at least 5 minutes
Mycophenolate over at least 2 hours
Dextran 40 10 mL/hour
Ganciclovir over 1 hour
Anidulafungin 1.1 mg/minute (100 200 minutes)
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Parenteral compatibilty
4. Check compatibilities for remaining medicines

Could use a compatibility checker or table:


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Parenteral compatibilty
4. Check compatibilities for remaining medicines

Could use a compatibility checker or table


First consider if any of the medicines need to be given
concurrently:
Vancomycin 10 mg/minute (eg 2g over 200 minutes)
Ceftriaxone over 3-5 minutes
Ranitidine over at least 5 minutes
Vitamin K (phytomenadione) over 30 seconds
Methylprednisolone over at least 5 minutes
Mycophenolate over at least 2 hours
Dextran 40 10 mL/hour
Alprostadil 0.1-0.6 microg/kg/hour
Ganciclovir over 1 hour
Anidulafungin 1.1 mg/minute (100 200 minutes)
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Contact details
jane.booth@austin.org.au

Twitter: @MI_JaneBooth

Further reading:
Warrillow SJ, Bellomo R. Preventing cerebral oedema in acute
liver failure: the case for quadruple-H therapy. Anaesthesia
and Intensive Care. 2014;42(1):78-88.

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