Implementation of Remifentanil Intensive Care Sedation

1. daniel.conway
@cmmc.nhs.uk
Remifentanil in ICU @
Manchester Royal Infirmary
Daniel
Conway
Consultant in
Critical Care
Manchester
Royal Infirmary

2. Sedation & Analgesia on ICU –
an uncomfortable paradigm
Traditional analgesics
will accumulate over
time + metabolites
Painful procedures,
general discomfort
should be treated
Excess sedation extends
length of stay and may
worsen PTSD symptoms
Inadequate sedation or
analgesia may worsen
PTSD symptoms

3. Moving Away from Sedation
• Early detection of neurological problems
– Stroke / bleeds / hypoxia
– Delirium
• Early extubation before tracheostomy
• ‘Fast track’ major surgery with regional
analgesia
• Withdrawal and weaning
• Reduced ICU length of stay

4. Shorter Acting Agents
• Propofol Carsson, Kress Crit Care Med 2006
– Rapid offset due to redistribution
– Hypotension & ? acidosis
• Alfentanil
– Minimal metabolites
– Less accumulation than morphine & fentanyl
• Remifentanil
– Esterase metabolism
– Rapid offset

5. Remifentanil Pharmacokinetics
• Rapid offset 6-8 minutes
• Independent of Renal / Hepatic Function
• Independent of BMI
• Titratable
– Analgesia
– Respiratory depression

6. Stable context sensitive t1/2
Egan Anaesthesiology 1993;79: 881-92

7. Hypnotic or Narcotic ????

8. Hypnotic or Narcotic ????
BDZ & Propofol
• GABA agonist
• Anxiolytic / amnesic
• Prolong Ventilation
• Cause delirium
• Contribute to long
term cognitive
dysfunction
Opioids & α2 agonists
• Hypotensive
• Analgesic
• Withdrawal phenomena
• Less delirium ?
• Long term cognition?

9. Remifentanil on ICU?
• Neurological examination
• Analgesia for procedures
• Patients with hepatic and renal impairment
• Fast track extubations
– Surgical
– Short stay medical eg overdose
• All Patients who require analgesia ????

10. Remifentanil on general ICU
Breen D, Karabinis A et al Crit Care 2005
• Open Label RCT remi v midaz/ morph fent
• 105 patients in 15 ICU’s
• Exclusions: NMBA, surgery, epidural, sensit
• Remi dose 0.2 mcg/kg/min
• Time to extubation, LOS on ICU
• SAS, Pain Index, mAP, 6 day follow up

11. Remifentanil on ICU
Breen D, Karabinis A et al Crit Care 2005
• ↓ Midaz dose
• Similar Sedation &
Pain scores
• ↑ Vomiting with remi
• Non-sig ↓ in ICU
LOS with remi

12. Remifentanil on ICU
Breen D, Karabinis A et al Crit Care 2005
• Re-intubations 7/25 remi v 2/12 hypnotic

13. Head Injury

14. Remifentanil With Head Injury
Karabinis A et al Crit Care (2004)
• Analgesia based v hypnotic regime
– Remifentanil v Fentanyl v Morphine
– Midazolam or propofol also used
Remifentanil 15mcg/kg/hr (0.25mcg/kg/min)
• 161 patients in 17 hospitals open label RCT
• LOS, SAS, mAP, HR, ICP and CPP
• Time to extubation

15. Remifentanil With Head Injury
Karabinis A et al Crit Care 2004
• Similar mAP HR
• No difference in ICP or
CPP
• ↓ Propofol requirement
• Optimal sedation
– 95% of time – remi
– 99% of time -
fentanyl

16. Improved time to neurological assessment with remi
Karabinis A et al Crit Care 2004

17. Hypnotic v Analgesic sedation
Park, Lane B J Anaes 2007
• 12 wk hypnotic based drugs
• 12 wk analgesics (predominantly remi)
• All ventilated patients
• Excluded if NMBA
• Looked at Mortality / LOS / dreams memory
• Looked at drug use

18. Hypnotic v Analgesic sedation
Park, Lane B J Anaes 2007
• 111 Hyp and 96 Ana patients
• Age 58 v 56
• APACHE II 16.5 v 18.1
• ICU Mortality 23% v 26%
• Hosp Mortality 31% v 35%
• Time on Vent 37h v 71h n/s
• LoS ICU 67 v 118

19. Hypnosis v Analgesia
Park, Lane BJA 2007
• 37% of patients could be managed with
remifentanil alone
• 40-50% experienced dreams or
hallucinations which most found unpleasant
• 5 accidental extubations in analgesic (3 on
remi) vs 2 in hypnotic
• Remi reduced propofol requirements

20. Remifentanil on ICU:
Tolerance, Side Effects and Withdrawal
It’s an opioid !
• Tolerance with prolonged infusion Vinik An Anal 98
• Side Effects
– Bradycardia and Hypotension
– Nausea/Vomiting/Ileus
– Respiratory Depression
• Withdrawal phenomena Apitzsch Anaesthetist 99

21. Remifentanil and Glycine
Bonnet MP, Benhamou D et al Int Care Med 07
• Glycine: inhibitory
neurotransmitter
• Remi powder has 3mg
glycine for each mg remi
• 72 hour infusion, toxic
levels NOT reached
• Correlation between remi
rate and glycine levels
• Glycine accumulation
with ↓ Creat CL

22. Remifentanil in Manchester

23. Implementing Remifentanil @ MRI
• Consultants Agree Patient Group
• Pharmacist produces guidelines
• Nurse Education Practitioner
• Regular Meetings
• Audit use month on month
• Guidelines modified

24. Remifentanil on ICU @ MRI
• Indication
– Analgesia and sedation
– Head injury / early extubation
– Hepatic and Renal Impairment
• Contra-indications
– Spont Vent or NIV or paralysed
– Opioid intolerance
– Bolus administration

25. Remifentanil Guideline MRI
• Duration 3 Days max
• Constitution
– 100μg/ml in 50 ml N/Sal or 5%Dex
• Withdrawal
– Stop infusion if no further analgesia
– Reduce by 25% every 15min if alt analgesic

26. Start Anxiolysis
propofol or
midazolam
Patient needs
analgesia/sedation
Patient needs further
analgesia/sedation
Not For
Remifentanil
Patient paralysed/
encephalopathic
6mcg/kg/h
Remifentanil
Increase
Remifentanil
1.5 mcg/kg/h
At 12mcg/kg/h
Remifentanil
Patient still needs
analgesia/sedation
If remains in pain
increase
remifentanil
15mcg/kg/h +
propofol or
midazolam AND
D/W Doctor

27. Case Study 1
• 72 yr man, alcoholic liver disease
• Urinary obstruction and sepsis
• Acute on chronic renal failure
• Agitated & Hypoxic ?? needs CVVH,
• Ventilated 40 hours
• Renal function improves without CVVH
• Remifentanil and propofol stopped
• Extubated & sent to ward next day

28. Case Study 2
• 38 yr woman, Tracheal reconstruction
surgery. Surgeons want sedated 48hrs
• Remifentanil peri-op
• Taken back to theatre day 1
• Remifentanil & propofol continued 48 h
• Controlled titration of remifentanil until
patient awake and not agitated / coughing

29. Summary: Remifentanil on ICU
• Short acting opioid for analgesia & sedation
• Useful in renal patients
• May facilitate early extubation
• Take care when stopping infusions
• Staff training was essential
• Start Pain Scores

30. nfusion rates of remifentanil by body weight using a 100μg/mL solution
Body
weight
(kg)
6
μg/kg/h
(mL/h)
9
μg/kg/h
(mL/h)
12
μg/kg/h
(mL/h)
15
μg/kg/h
(mL/h)
40 2.4 3.6 4.8 6.0
45 2.7 4.1 5.4 6.8
50 3.0 4.5 6.0 7.5
55 3.3 5.0 6.6 8.3
60 3.6 5.4 7.2 9.0
65 3.9 5.9 7.8 9.8
70 4.2 6.3 8.4 10.5
75 4.5 6.8 9.0 11.0
80 4.8 7.2 9.6 12.0
85 5.1 7.7 10.2 12.8
90 5.4 8.1 10.8 13.5
95 5.7 8.6 11.4 14.3
100 6.0 9.0 12.0 15.0
105 6.3 9.5 12.6 15.8
110 6.6 9.9 13.2 16.5
115 6.9 10.4 13.8 17.3
120 7.2 10.8 14.4 18.0

31. • Key messages
In neurotrauma patients requiring intensive care for up to 5 days,
analgesia-based sedation using remifentanil compared with a
standard hypnotic-based technique provided the following:
• • a significant reduction in the mean time taken to wake the patient
for assessment of neurological function;• a significantly reduced
mean between-patient variability in the time to wake-up, making the
performance of this assessment more predictable;• a significantly
shorter time to extubation than with a hypnotic-based regimen using
morphine as the analgesic;• no clinical differences in pain and
sedation scores;• a trend towards reduced dosing with propofol;•
comparable haemodynamic and cerebral haemodynamic stability;•
higher user satisfaction rating by physicians and nurses;• a similar
safety profile.