Download - Remifentanil In Icu @ Mri
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Remifentanil in ICU @ Manchester Royal Infirmary
Daniel Conway
Consultant in Critical Care
Manchester Royal Infirmary
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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
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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
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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
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Remifentanil Pharmacokinetics
• Rapid offset 6-8 minutes
• Independent of Renal / Hepatic Function
• Independent of BMI
• Titratable– Analgesia– Respiratory depression
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Stable context sensitive t1/2
Egan Anaesthesiology 1993;79: 881-92
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Hypnotic or Narcotic ????
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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?
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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 ????
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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
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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
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Remifentanil on ICU Breen D, Karabinis A et al Crit Care 2005
• Re-intubations 7/25 remi v 2/12 hypnotic
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Head Injury
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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
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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
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Improved time to neurological assessment with remi
Karabinis A et al Crit Care 2004
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Hypnotic v Analgesic sedationPark, 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
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Hypnotic v Analgesic sedationPark, 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
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Hypnosis v AnalgesiaPark, 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
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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
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Remifentanil and GlycineBonnet 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
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Remifentanil in Manchester
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Implementing Remifentanil @ MRI
• Consultants Agree Patient Group
• Pharmacist produces guidelines
• Nurse Education Practitioner
• Regular Meetings
• Audit use month on month
• Guidelines modified
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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
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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
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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
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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
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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
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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
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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
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• 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.