SlideShare a Scribd company logo
REMIFENTANIL: AN ULTRA-SHORT
ACTING OPIOID
Dr. Ravikiran HM MBBS,DNB
ADMO/CH/MLG
Department of Anaesthesiology and Critical care
Central Hospital, NF Railway, Maligaon, GHY-11
INDEX
 Introduction
 Opioids classification
 Mechanism of action of opioids
 Structure
 Pharmacokinetics
 Pharmacodynamics
 Adverse effects
 Uses
 Dosing
 Pharmacoceutics
 Pharmacoeconomics
 Conclusion
INTRODUCTION
 Short acting drugs are desirable in modern clinical anesthesia practice.
 They allow rapid recovery, minimal residual effects.
 Preserve cognitive function for rapid discharge, better patient satisfaction.
 Day care procedures, rapid turn over of case load.
 Ex: Methohexital, Etomidate, Remimazolam, Remifentanil, Gantacurium, Esmolol…
INTRODUCTION cont…
 Balanced / multimodal anesthesia: Administered
with combinations of synergestic agents to induce
desired state.
 Components: 7A
1. Anesthesia: loss of awareness
2. Analgesia: most important
3. Anxiolysis
4. Areflexia: muscle relaxation
5. Autonomic attenuation
6. Amnesia
7. Avoidance of side effects
 Research continues for ideal agents
INTRODUCTION cont…
 Remifentanil is a pure μ-opioid receptor agonist.
 Introduced in the early 1990s
 Its rapid onset and offset coupled with its synergistic effects with other general anaesthetic
agents make it an ideal option for anaesthesia and conscious sedation.
OPIOIDS CLASSIFICATIONS
MECHANISM
The endogenous ligand or drug binds to the opioid receptor and activates the G protein, resulting in multiple effects that are
primarily inhibitory. The activities of adenylate cyclase and the voltage-dependent Ca2+ channels are depressed. The inwardly
rectifying K+ channels and mitogen activated protein kinase (MAPK) cascade are activated.
MECHANISM cont…
•δ-opioid receptor, DOP (named after the tissue it was first isolated from, vas Deferens)
•κ-opioid receptor, KOP (named after the first ligand, Ketocyclazine)
•μ-opioid receptor, MOP (named after Morphine, proposed 1976,cloned 1993)
•NOP: nociceptin/orphanin FQ (N/OFQ) or orphanin like receptors (ORL1)
MECHANISM cont…
Remifentanil is a selective μ-opioid receptor agonist
STRUCTURE
 Like alfentanil and sufentanil, is based on its
parent drug fentanyl(Piperidine derivative).
 The crucial difference is the addition of an
ester group allowing it to be rapidly
metabolized by non-specific plasma and
tissue esterases.
 This gives rise to its characteristic ultra-fast
offset and allows for rapid titration.
PHARMACOKINETICS
ABSORPTION
 Only IV formulation
 Rapid onset of action (within 1–1.5 minutes)
and peak analgesic effect (within 1–3
minutes). Remifentanil has a faster onset of
action than fentanyl or sufentanil.
DISTRIBUTION
 Rapidly distributed throughout blood and highly perfused
tissues; subsequently distributed into peripheral tissues;
unlike other opiate agonists, remifentanil does not
accumulate at high doses or with prolonged administration.
 Initial Vd: 100ml/kg. Vd steady state: 260-415ml/kg
 Rapidly equilibrates across blood-brain barrier.
 Crosses placenta; average maternal remifentanil
concentrations are about twice those observed in fetus.
 Plasma Protein Binding: 70–92% (primarily α1-acid
glycoprotein).
BLOOD CONCENTRATION – MINTO MODEL
 Linear response
 Blood-brain equilibration half-time = 1 ± 1 minutes
 Rapid titration
METABOLISM
 Broken down by esterases, can be used safely in patients with pseudocholinesterase deficiency.
 Major metabolite: remifentanil acid → renal excretion
 Metabolite accumulates in patients with reduced renal function. Despite this, dosing does not
need to be adjusted for renal dysfunction as its almost entirely inactive
 Clearance was reduced by ≈20% during hypothermia (28-30 O C).
ELIMINATION
 Self-reversal
Short Elimination
Half life
(3-10 mins)
High clearance (amount
of plasma cleared of the
drug/min) 40mls/min/kg
Small volume of
Distribution (Vd)
CONTEXT-SENSITIVE HALF TIME
 Time it takes for the concentration of a drug in
the plasma to decrease by half after an infusion
is terminated.
 The context-sensitive half-time often cannot be
predicted by the elimination half-life (a measure
of the time needed for actual drug metabolism or
elimination) because it also depends on drug
distribution. It is a useful concept because it
helps explain the duration of action of a drug
given by infusion after stopping the infusion.
 For remifentanil both elimination and context
half life is 3min.
CONTEXT-SENSITIVE HALF TIME cont…
Half-lives of Remifentanil Value
(minutes)
Significance
Rapid distribution half-
life
1 Immediate onset of action
Slower distribution half-
life
6 Easier titration of dose
Terminal elimination
half-life
10-20 Rapid clearance reduces
accumulation
Effective biological half-
life
3-10 Rapid recovery
Context -sensitive half-
life
3-6 Independent of duration of
infusion
PHARMACOKINETICS IN SPECIAL POPULATION
 Elderly: Between 20 to 85 years of age, Vdc and CL values decrease by ≈25% and 33% in
healthy adult volunteers, requiring a 50% reduction in the initial and subsequent doses of
remifentanil in those >65 years of age.
 Paediatric patients: The elimination half-life in neonates is not significantly different from that
of young healthy adults. Changes in analgesic effect after changes in infusion rate of
remifentanil should be rapid and similar to those seen in young healthy adults. The
pharmacokinetics of the carboxylic acid metabolite in paediatric patients 2 to 17 years of age
are similar to those seen in adults after correcting for differences in body weight.
PHARMACOKINETICS IN SPECIAL POPULATION cont….
 Gender: No clinically relevant differences seen in pharmacokinetc profile based on gender.
 Hepatic or Renal impairment: No clinically relevant differences in PK profile of drug
 Body mass (Obesity): Pharmacokinetic parameters are reduced by about one-third in obese
versus lean patients. Dose reduction in obese patients should be based on the patient’s ideal
body weight
PHARMACODYNAMICS
POTENCY OF OPIOIDS COMPARED
Most potent: Crafentanil>>Sufentanil>>Fentanyl≥Remifentanyl>>Alfentanyl
THERAPEUTIC INDEX
 Therapeutic index = ED50/LD50
 Very high therapeutic index (33,000)
 Thus wide therapeutic window (Dose range between minimum effective
concentration and minimum toxic concentration)
ADVERSE EFFECTS
CVS
 Hypotension: Hypotension potentiated with other anaesthetics, so titrate accordingly.
Vassopressors kept ready
 Bradycardia, rarely asystole: Use glycopyrrolate premedication
 No histamine release unlike other opioids on rapid administration (anaphylactoid reaction)
RS
 Respiratory depression and apnoea
 Transient, always plan for securing airway to be there (trained staff)
GIT
 Nausea and vomiting: same risk as that of other opioids
 Constipation
CNS
 Delirium
SKIN
 Pruritus
MUSCULOSKELETAL
 Post op Shivering: twice the risk as compared
 Muscle Rigidity: wooden chest syndrome, common with bolus dose and high doses.
Management: simultaneous injection of muscle relaxant/induction agent like propofol/thio. In
spontaneous patients stop infusion/naloxone/muscle relaxant. Prevention: slow injection 30-
90sec
WITHDRAWAL
 Hyperalgesia (even after short infusions): morphine (0.15–0.3mg.kg-1) or alternative, should be
given at least 30 minutes before stopping remifentanil to allow it time to reach peak effect
 After prolonged use (>3 days):
 Hypertension
 Tachycardia
 Agitation
DRUG INTERACTIONS
 Risk of serotonin syndrome
 Potentiate sedative drug
CLINICAL USES
INTUBATION WITHOUT MUSCLE RELAXANT
 Obtunds airway reflexes and under most circumstances allows tracheal intubation without the
use of muscle relaxants in both adults and children.
 Benefits in certain situations: e.g.
1. In those with abnormal sensitivity to muscle relaxants e.g. allergy, myasthenia gravis,
malignant hyperthermia etc.
2. Where assistance of nerve stimulators is desirable e.g. for monitoring facial nerve function
during mastoid/parotid surgery or if planning a regional block immediately after induction
3. Where avoidance of incomplete reversal or recurarisation is desirable
4. Less risk of awareness.
CONSCIOUS SEDATION
 NORA and Day-care procedures: Rapid recovery with clear head
 Simple dental extractions
 Hysteroscopy
 Joint / fracture reductions
 Burns dressing changes
 Awake tracheostomy
 Bronchoscopy, Endoscopy
 Adjunct-rescue to partially failed regional block or regional block that is wearing off
CONSCIOUS SEDATION cont….
 not suitable for any patient that has a potentially difficult airway, is morbidly obese, is not
starved, or for a potentially prolonged procedure.
 It also needs to be carried out in a location that is equipped to deal with any complications and
have full AAGBI monitoring and resuscitation kit available
ROLE IN OBSTETRICS
 While epidural analgesia remains the gold standard for labour pain, remifentanil patient
controlled analgesia (PCA) has now been cautiously accepted as an alternative in circumstances
where epidurals are contraindicated.
 Crosses the placental barrier however it is rapidly metabolized and redistributed by the foetus,
even in the pre-term.
 Has a greater depressant effect on maternal respiratory function and consciousness than other
opioids; this needs to be explained to parturients and must be vigilantly monitored.
 Useful during emergency Caesarian sections to avoid laryngoscopy-induced pressor response in
eclamptic patients
ROLE IN NEURO-ANAESTHESIA
 Awake craniotomy: help in brain mapping
 Wake up test: spine surgery: gold standard test for nerve injury
 Does not effect SSEP (becoz of short effect)
ROLE IN CARDIAC-ANAESTHESIA
 Blunts response to hemodynamic stress
 Rapid recovery post-op
BENEFITS IN ICU
 Rapid offset allowing for earlier neurological assessment during sedation holds.
 Profound respiratory depression helping to avoid patient-ventilator dysynchrony .
 Very short context-sensitive half-life and minimal accumulation – ideal for resuming
spontaneous breathing rapidly.
 No need to dose-adjust in chronic or acute kidney injury (AKI) – offset times are approximately
twice as long in moderate-severe renal impairment however as the difference is only 16.5 mins
this is not usually significant.
 More predictable offset times particularly in patients with multi-organ dysfunction.
ISSUES IN ICU
 Potential for hyperalgesia and withdrawal following cessation of infusion, warranting the use of
post-remifentanil analgesia/opiate to be in place prior to dose reduction.
 Potential risk of apnoea and/or chest wall rigidity (in high doses) which may make ventilation
more difficult.
 The apnoea risk needs to be taken seriously, particularly when using in patients who are not
intubated. Staff need to remain vigilant of this potential complication when in use and have a
plan in place if apnoeas were to occur.
 Cardiovascular instability (namely hypotension/bradycardia) may increase a patient’s
vasopressor/inotrope requirement.
NEURAXIAL USES
 Contraindicated
 Contains glycine(acidic buffer): an
inhibitory neurotransmitter.
DOSING
PREPARATION
 Lyophilised Powder form: 1mg/vial or 2mg/vial
 Preparation: 1mg in 20ml or 2mg in 40ml NS: 50mcg/ml
 Care should be taken to avoid inadverant injection of drug in infusion set.
 Diluents: 5 % glucose solution, 5 % glucose and 0.9 % sodium chloride solution, 0.9 % sodium
chloride solution, 0.45 % sodium chloride solution, sterilised water for Injection
DOSING
 The pharmacokinetics are more closely associated with lean body weight (LBW) rather than
actual body weight (ABW).
 Although obese patients do require a larger dose than their LBW would suggest, it is far less
than their ABW dose; this would put them at risk of cardiovascular depression
DOSING
 Minto Model TCI pump: By Dr. Charles Minto. Predicting the concentration of remifentanil in
plasma and the effect site.
 Input of patient sex, age, weight (kg) and height (cm). Age more than 12years.
Purpose Cet (effect site conc.)
GA 2.5ng/ml
RSI 8ng/ml
Awake fiberoptic/Conscious sedation 2ng/ml
DOSING
DOSING
DOSING: PEDIATRICS >1YEAR
DOSING: MAC
MANUAL INFUSION USING 50MCG/ML CONCEN
DOSAGE IN ELDERLY
 The clearance of remifentanil is slightly reduced in
older people ( > 65 years) compared to that in young
patients.
 The pharmacodynamic activity increases with
increasing age.
 The initial dose should be reduced by 50% in older
people and then carefully titrated to meet the
individual patient need
EC50 is a measure of brain
sensitivity. Decreased EC50
means increased sensitivity.
PHARMACEUTICAL PARTICULARS
 Remifentanil should not be mixed with propofol in the same intravenous admixture
solution.
 Remifentanil has been shown to be compatible with propofol when administered into a
running IV catheter.
PHARMACOECONOMICS
PHYSICOCHEMICAL PROPERTIES
PHARMACOKINETICS COMPARISION
PHARMACOKINETICS COMPARISION
Agent Route of administration
Onset of
action
Tmax Duration of
action
Fentanyl i.v 1-2min 3-4min 30min
Remifentanil i.v 30s 1min 5-10min
Agent metabolize excretion
Protein
binding rate
(%)
Distribution
volume
(L/kg)
Half life
Plasma clearance
(ml/kg.min)
Fentanyl liver kidney 84 4.1 3-4h 13.3
Remifentanil Plasma kidney 70 0.39 9.1min 2800
CONCLUSION
 Desirable features: rapid onset, rapid offset, rapid titration
 Undesirable: Muscle rigidity, apnea, hemodynamic instability ( can be managed well if careful
drug titration and availability of vigilant anesthetist)
REFERENCES
1. Atterton B, Lobaz S, Konstantatos A. Remifentanil use in anaesthesia and critical care. Anaesthesia.
2016 Nov 29;342:1-9.
2. Opioids-NYSORA
3. Basic Pharmacologic Principles-NYSORA
4. Correll DJ, Rosow CE. Opioids. In: Vacanti C, Segal S, Sikka P, Urman R, eds. Essential Clinical
Anesthesia. Cambridge University Press; 2011:242-250.
5. Trivedi M, Shaikh S, Gwinnutt C. Pharmacology of opioids-part 1 anaesthesia tutorial of the week 64.
6. Gupta DK, Krejcie TC, Avram MJ. Pharmacokinetics of opioids. In: Evers AS, Maze M, Kharasch ED,
eds. Anesthetic Pharmacology: Basic Principles and Clinical Practice. Cambridge University Press;
2011:509-530.
7. Servin FS, Billard V. Remifentanil and other opioids. Handb Exp Pharmacol. 2008;(182):283-311. doi:
10.1007/978-3-540-74806-9_14. PMID: 18175097.
8. Beers, R., Camporesi, E. Remifentanil Update. CNS Drugs 18, 1085–1104 (2004).
https://doi.org/10.2165/00023210-200418150-00004
9. REMITHEM Monograph
THANK YOU

More Related Content

Similar to REMIFENTANIL: An Ultra short acting opioid.pptx

pediaric PSA
pediaric PSApediaric PSA
pediaric PSA
Noha El-Anwar
 
Intravenous Induction Agents by Dr. Animesh
Intravenous Induction Agents by Dr. AnimeshIntravenous Induction Agents by Dr. Animesh
Intravenous Induction Agents by Dr. Animesh
19anisingh
 
Tiva in 21st century by prof. minnu m. panditrao
Tiva in 21st century by prof. minnu m. panditraoTiva in 21st century by prof. minnu m. panditrao
Tiva in 21st century by prof. minnu m. panditrao
Minnu Panditrao
 
General Anestheics.pptx
General Anestheics.pptxGeneral Anestheics.pptx
General Anestheics.pptx
FarazaJaved
 
Antiemetics and prokinetics by dr.roohna
Antiemetics and prokinetics by dr.roohnaAntiemetics and prokinetics by dr.roohna
Antiemetics and prokinetics by dr.roohna
Dr Roohana Hasan
 
Remifentanil presentation
Remifentanil presentationRemifentanil presentation
Pharmacology of obstretic drugs
Pharmacology of obstretic drugsPharmacology of obstretic drugs
Pharmacology of obstretic drugs
SREEJITH HARIHARAN
 
ivanaesthetics-160916154203 (1).pptx
ivanaesthetics-160916154203 (1).pptxivanaesthetics-160916154203 (1).pptx
ivanaesthetics-160916154203 (1).pptx
Keerthy Unnikrishnan
 
Intravenous Induction agents
Intravenous Induction agentsIntravenous Induction agents
Intravenous Induction agents
sumanth reddy
 
ivanaesthetics-160916154203 (1).pdf
ivanaesthetics-160916154203 (1).pdfivanaesthetics-160916154203 (1).pdf
ivanaesthetics-160916154203 (1).pdf
ssuser814a33
 
status epilepticus...
status epilepticus...status epilepticus...
status epilepticus...
NeurologyKota
 
Sedative analgesic presentation
Sedative analgesic presentation  Sedative analgesic presentation
Sedative analgesic presentation
Muhammad Umar Hafeez
 
Tramadol
TramadolTramadol
Haemodynamic effects piasecki
Haemodynamic effects piaseckiHaemodynamic effects piasecki
Haemodynamic effects piasecki
Polanest
 
Total Intravenous Anaesthesia
Total Intravenous AnaesthesiaTotal Intravenous Anaesthesia
Total Intravenous Anaesthesia
Brijesh Savidhan
 
Post Operative Nausea & Vomiting
Post Operative Nausea & VomitingPost Operative Nausea & Vomiting
Post Operative Nausea & Vomiting
Kiran Rajagopal
 
Introduction, Classification, general mechanism of action and pharmacology of...
Introduction, Classification, general mechanism of action and pharmacology of...Introduction, Classification, general mechanism of action and pharmacology of...
Introduction, Classification, general mechanism of action and pharmacology of...
Chalapathi institute of pharmaceutical sciences
 
Labour analgesia - ajay
Labour analgesia - ajayLabour analgesia - ajay
Labour analgesia - ajay
Ajay Aggarwal
 
Labour analgesia - ajay
Labour analgesia - ajayLabour analgesia - ajay
Labour analgesia - ajay
Ajay Aggarwal
 
Pharmacokinetics
PharmacokineticsPharmacokinetics
Pharmacokinetics
Simran Khanijo
 

Similar to REMIFENTANIL: An Ultra short acting opioid.pptx (20)

pediaric PSA
pediaric PSApediaric PSA
pediaric PSA
 
Intravenous Induction Agents by Dr. Animesh
Intravenous Induction Agents by Dr. AnimeshIntravenous Induction Agents by Dr. Animesh
Intravenous Induction Agents by Dr. Animesh
 
Tiva in 21st century by prof. minnu m. panditrao
Tiva in 21st century by prof. minnu m. panditraoTiva in 21st century by prof. minnu m. panditrao
Tiva in 21st century by prof. minnu m. panditrao
 
General Anestheics.pptx
General Anestheics.pptxGeneral Anestheics.pptx
General Anestheics.pptx
 
Antiemetics and prokinetics by dr.roohna
Antiemetics and prokinetics by dr.roohnaAntiemetics and prokinetics by dr.roohna
Antiemetics and prokinetics by dr.roohna
 
Remifentanil presentation
Remifentanil presentationRemifentanil presentation
Remifentanil presentation
 
Pharmacology of obstretic drugs
Pharmacology of obstretic drugsPharmacology of obstretic drugs
Pharmacology of obstretic drugs
 
ivanaesthetics-160916154203 (1).pptx
ivanaesthetics-160916154203 (1).pptxivanaesthetics-160916154203 (1).pptx
ivanaesthetics-160916154203 (1).pptx
 
Intravenous Induction agents
Intravenous Induction agentsIntravenous Induction agents
Intravenous Induction agents
 
ivanaesthetics-160916154203 (1).pdf
ivanaesthetics-160916154203 (1).pdfivanaesthetics-160916154203 (1).pdf
ivanaesthetics-160916154203 (1).pdf
 
status epilepticus...
status epilepticus...status epilepticus...
status epilepticus...
 
Sedative analgesic presentation
Sedative analgesic presentation  Sedative analgesic presentation
Sedative analgesic presentation
 
Tramadol
TramadolTramadol
Tramadol
 
Haemodynamic effects piasecki
Haemodynamic effects piaseckiHaemodynamic effects piasecki
Haemodynamic effects piasecki
 
Total Intravenous Anaesthesia
Total Intravenous AnaesthesiaTotal Intravenous Anaesthesia
Total Intravenous Anaesthesia
 
Post Operative Nausea & Vomiting
Post Operative Nausea & VomitingPost Operative Nausea & Vomiting
Post Operative Nausea & Vomiting
 
Introduction, Classification, general mechanism of action and pharmacology of...
Introduction, Classification, general mechanism of action and pharmacology of...Introduction, Classification, general mechanism of action and pharmacology of...
Introduction, Classification, general mechanism of action and pharmacology of...
 
Labour analgesia - ajay
Labour analgesia - ajayLabour analgesia - ajay
Labour analgesia - ajay
 
Labour analgesia - ajay
Labour analgesia - ajayLabour analgesia - ajay
Labour analgesia - ajay
 
Pharmacokinetics
PharmacokineticsPharmacokinetics
Pharmacokinetics
 

More from Dr. Ravikiran H M Gowda

Simulation in anesthesia and medicine. pptx
Simulation in anesthesia and medicine. pptxSimulation in anesthesia and medicine. pptx
Simulation in anesthesia and medicine. pptx
Dr. Ravikiran H M Gowda
 
Oncoanesthesia.pptx
Oncoanesthesia.pptxOncoanesthesia.pptx
Oncoanesthesia.pptx
Dr. Ravikiran H M Gowda
 
OVERVIEW OF SURGICAL SITE INFECTION copy.pptx
OVERVIEW OF SURGICAL SITE INFECTION copy.pptxOVERVIEW OF SURGICAL SITE INFECTION copy.pptx
OVERVIEW OF SURGICAL SITE INFECTION copy.pptx
Dr. Ravikiran H M Gowda
 
ETHICAL CONSIDERATION PEDIATRIC RESEARCH.docx
ETHICAL CONSIDERATION PEDIATRIC RESEARCH.docxETHICAL CONSIDERATION PEDIATRIC RESEARCH.docx
ETHICAL CONSIDERATION PEDIATRIC RESEARCH.docx
Dr. Ravikiran H M Gowda
 
Medication safety.pptx
Medication safety.pptxMedication safety.pptx
Medication safety.pptx
Dr. Ravikiran H M Gowda
 
REMOTE MONITORING- A RECENT ADVANCE.pptx
REMOTE MONITORING- A RECENT ADVANCE.pptxREMOTE MONITORING- A RECENT ADVANCE.pptx
REMOTE MONITORING- A RECENT ADVANCE.pptx
Dr. Ravikiran H M Gowda
 
BASIC LIFE SUPPORT AHA 2020-1.pptx
BASIC LIFE SUPPORT AHA 2020-1.pptxBASIC LIFE SUPPORT AHA 2020-1.pptx
BASIC LIFE SUPPORT AHA 2020-1.pptx
Dr. Ravikiran H M Gowda
 
Npo kannada
Npo kannadaNpo kannada
Journal club
Journal clubJournal club
Bmw management
Bmw managementBmw management
Bmw management
Dr. Ravikiran H M Gowda
 
Computer based patient record for anaesthesia
Computer based patient record for anaesthesiaComputer based patient record for anaesthesia
Computer based patient record for anaesthesia
Dr. Ravikiran H M Gowda
 
Quality improvement and patient safety in anesthesia
Quality improvement and patient safety in anesthesiaQuality improvement and patient safety in anesthesia
Quality improvement and patient safety in anesthesia
Dr. Ravikiran H M Gowda
 
Crisis resource management
Crisis resource managementCrisis resource management
Crisis resource management
Dr. Ravikiran H M Gowda
 
Audit in anaesthesia
Audit in anaesthesiaAudit in anaesthesia
Audit in anaesthesia
Dr. Ravikiran H M Gowda
 
Ethical aspects of anesthesia care and euthanasia
Ethical aspects of anesthesia care and euthanasiaEthical aspects of anesthesia care and euthanasia
Ethical aspects of anesthesia care and euthanasia
Dr. Ravikiran H M Gowda
 
Informed consent, professional negligence and vicarous liability
Informed consent, professional negligence and vicarous liabilityInformed consent, professional negligence and vicarous liability
Informed consent, professional negligence and vicarous liability
Dr. Ravikiran H M Gowda
 
Triage, natural disaster, biowar, pandemic: Role of anesthesiologist
Triage, natural disaster, biowar, pandemic: Role of anesthesiologist Triage, natural disaster, biowar, pandemic: Role of anesthesiologist
Triage, natural disaster, biowar, pandemic: Role of anesthesiologist
Dr. Ravikiran H M Gowda
 
Sleep and anesthesia
Sleep and anesthesiaSleep and anesthesia
Sleep and anesthesia
Dr. Ravikiran H M Gowda
 
Genomic basis of perioperative medicine
Genomic basis of perioperative medicineGenomic basis of perioperative medicine
Genomic basis of perioperative medicine
Dr. Ravikiran H M Gowda
 
Nitric oxide
Nitric  oxide Nitric  oxide

More from Dr. Ravikiran H M Gowda (20)

Simulation in anesthesia and medicine. pptx
Simulation in anesthesia and medicine. pptxSimulation in anesthesia and medicine. pptx
Simulation in anesthesia and medicine. pptx
 
Oncoanesthesia.pptx
Oncoanesthesia.pptxOncoanesthesia.pptx
Oncoanesthesia.pptx
 
OVERVIEW OF SURGICAL SITE INFECTION copy.pptx
OVERVIEW OF SURGICAL SITE INFECTION copy.pptxOVERVIEW OF SURGICAL SITE INFECTION copy.pptx
OVERVIEW OF SURGICAL SITE INFECTION copy.pptx
 
ETHICAL CONSIDERATION PEDIATRIC RESEARCH.docx
ETHICAL CONSIDERATION PEDIATRIC RESEARCH.docxETHICAL CONSIDERATION PEDIATRIC RESEARCH.docx
ETHICAL CONSIDERATION PEDIATRIC RESEARCH.docx
 
Medication safety.pptx
Medication safety.pptxMedication safety.pptx
Medication safety.pptx
 
REMOTE MONITORING- A RECENT ADVANCE.pptx
REMOTE MONITORING- A RECENT ADVANCE.pptxREMOTE MONITORING- A RECENT ADVANCE.pptx
REMOTE MONITORING- A RECENT ADVANCE.pptx
 
BASIC LIFE SUPPORT AHA 2020-1.pptx
BASIC LIFE SUPPORT AHA 2020-1.pptxBASIC LIFE SUPPORT AHA 2020-1.pptx
BASIC LIFE SUPPORT AHA 2020-1.pptx
 
Npo kannada
Npo kannadaNpo kannada
Npo kannada
 
Journal club
Journal clubJournal club
Journal club
 
Bmw management
Bmw managementBmw management
Bmw management
 
Computer based patient record for anaesthesia
Computer based patient record for anaesthesiaComputer based patient record for anaesthesia
Computer based patient record for anaesthesia
 
Quality improvement and patient safety in anesthesia
Quality improvement and patient safety in anesthesiaQuality improvement and patient safety in anesthesia
Quality improvement and patient safety in anesthesia
 
Crisis resource management
Crisis resource managementCrisis resource management
Crisis resource management
 
Audit in anaesthesia
Audit in anaesthesiaAudit in anaesthesia
Audit in anaesthesia
 
Ethical aspects of anesthesia care and euthanasia
Ethical aspects of anesthesia care and euthanasiaEthical aspects of anesthesia care and euthanasia
Ethical aspects of anesthesia care and euthanasia
 
Informed consent, professional negligence and vicarous liability
Informed consent, professional negligence and vicarous liabilityInformed consent, professional negligence and vicarous liability
Informed consent, professional negligence and vicarous liability
 
Triage, natural disaster, biowar, pandemic: Role of anesthesiologist
Triage, natural disaster, biowar, pandemic: Role of anesthesiologist Triage, natural disaster, biowar, pandemic: Role of anesthesiologist
Triage, natural disaster, biowar, pandemic: Role of anesthesiologist
 
Sleep and anesthesia
Sleep and anesthesiaSleep and anesthesia
Sleep and anesthesia
 
Genomic basis of perioperative medicine
Genomic basis of perioperative medicineGenomic basis of perioperative medicine
Genomic basis of perioperative medicine
 
Nitric oxide
Nitric  oxide Nitric  oxide
Nitric oxide
 

Recently uploaded

Level 3 NCEA - NZ: A Nation In the Making 1872 - 1900 SML.ppt
Level 3 NCEA - NZ: A  Nation In the Making 1872 - 1900 SML.pptLevel 3 NCEA - NZ: A  Nation In the Making 1872 - 1900 SML.ppt
Level 3 NCEA - NZ: A Nation In the Making 1872 - 1900 SML.ppt
Henry Hollis
 
Beyond Degrees - Empowering the Workforce in the Context of Skills-First.pptx
Beyond Degrees - Empowering the Workforce in the Context of Skills-First.pptxBeyond Degrees - Empowering the Workforce in the Context of Skills-First.pptx
Beyond Degrees - Empowering the Workforce in the Context of Skills-First.pptx
EduSkills OECD
 
NEWSPAPERS - QUESTION 1 - REVISION POWERPOINT.pptx
NEWSPAPERS - QUESTION 1 - REVISION POWERPOINT.pptxNEWSPAPERS - QUESTION 1 - REVISION POWERPOINT.pptx
NEWSPAPERS - QUESTION 1 - REVISION POWERPOINT.pptx
iammrhaywood
 
مصحف القراءات العشر أعد أحرف الخلاف سمير بسيوني.pdf
مصحف القراءات العشر   أعد أحرف الخلاف سمير بسيوني.pdfمصحف القراءات العشر   أعد أحرف الخلاف سمير بسيوني.pdf
مصحف القراءات العشر أعد أحرف الخلاف سمير بسيوني.pdf
سمير بسيوني
 
A Visual Guide to 1 Samuel | A Tale of Two Hearts
A Visual Guide to 1 Samuel | A Tale of Two HeartsA Visual Guide to 1 Samuel | A Tale of Two Hearts
A Visual Guide to 1 Samuel | A Tale of Two Hearts
Steve Thomason
 
REASIGNACION 2024 UGEL CHUPACA 2024 UGEL CHUPACA.pdf
REASIGNACION 2024 UGEL CHUPACA 2024 UGEL CHUPACA.pdfREASIGNACION 2024 UGEL CHUPACA 2024 UGEL CHUPACA.pdf
REASIGNACION 2024 UGEL CHUPACA 2024 UGEL CHUPACA.pdf
giancarloi8888
 
BIOLOGY NATIONAL EXAMINATION COUNCIL (NECO) 2024 PRACTICAL MANUAL.pptx
BIOLOGY NATIONAL EXAMINATION COUNCIL (NECO) 2024 PRACTICAL MANUAL.pptxBIOLOGY NATIONAL EXAMINATION COUNCIL (NECO) 2024 PRACTICAL MANUAL.pptx
BIOLOGY NATIONAL EXAMINATION COUNCIL (NECO) 2024 PRACTICAL MANUAL.pptx
RidwanHassanYusuf
 
HYPERTENSION - SLIDE SHARE PRESENTATION.
HYPERTENSION - SLIDE SHARE PRESENTATION.HYPERTENSION - SLIDE SHARE PRESENTATION.
HYPERTENSION - SLIDE SHARE PRESENTATION.
deepaannamalai16
 
Bossa N’ Roll Records by Ismael Vazquez.
Bossa N’ Roll Records by Ismael Vazquez.Bossa N’ Roll Records by Ismael Vazquez.
Bossa N’ Roll Records by Ismael Vazquez.
IsmaelVazquez38
 
Traditional Musical Instruments of Arunachal Pradesh and Uttar Pradesh - RAYH...
Traditional Musical Instruments of Arunachal Pradesh and Uttar Pradesh - RAYH...Traditional Musical Instruments of Arunachal Pradesh and Uttar Pradesh - RAYH...
Traditional Musical Instruments of Arunachal Pradesh and Uttar Pradesh - RAYH...
imrankhan141184
 
The basics of sentences session 7pptx.pptx
The basics of sentences session 7pptx.pptxThe basics of sentences session 7pptx.pptx
The basics of sentences session 7pptx.pptx
heathfieldcps1
 
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
GeorgeMilliken2
 
Educational Technology in the Health Sciences
Educational Technology in the Health SciencesEducational Technology in the Health Sciences
Educational Technology in the Health Sciences
Iris Thiele Isip-Tan
 
Gender and Mental Health - Counselling and Family Therapy Applications and In...
Gender and Mental Health - Counselling and Family Therapy Applications and In...Gender and Mental Health - Counselling and Family Therapy Applications and In...
Gender and Mental Health - Counselling and Family Therapy Applications and In...
PsychoTech Services
 
BÀI TẬP BỔ TRỢ TIẾNG ANH LỚP 9 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2024-2025 - ...
BÀI TẬP BỔ TRỢ TIẾNG ANH LỚP 9 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2024-2025 - ...BÀI TẬP BỔ TRỢ TIẾNG ANH LỚP 9 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2024-2025 - ...
BÀI TẬP BỔ TRỢ TIẾNG ANH LỚP 9 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2024-2025 - ...
Nguyen Thanh Tu Collection
 
THE SACRIFICE HOW PRO-PALESTINE PROTESTS STUDENTS ARE SACRIFICING TO CHANGE T...
THE SACRIFICE HOW PRO-PALESTINE PROTESTS STUDENTS ARE SACRIFICING TO CHANGE T...THE SACRIFICE HOW PRO-PALESTINE PROTESTS STUDENTS ARE SACRIFICING TO CHANGE T...
THE SACRIFICE HOW PRO-PALESTINE PROTESTS STUDENTS ARE SACRIFICING TO CHANGE T...
indexPub
 
RHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem students
RHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem studentsRHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem students
RHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem students
Himanshu Rai
 
Pharmaceutics Pharmaceuticals best of brub
Pharmaceutics Pharmaceuticals best of brubPharmaceutics Pharmaceuticals best of brub
Pharmaceutics Pharmaceuticals best of brub
danielkiash986
 
Temple of Asclepius in Thrace. Excavation results
Temple of Asclepius in Thrace. Excavation resultsTemple of Asclepius in Thrace. Excavation results
Temple of Asclepius in Thrace. Excavation results
Krassimira Luka
 
skeleton System.pdf (skeleton system wow)
skeleton System.pdf (skeleton system wow)skeleton System.pdf (skeleton system wow)
skeleton System.pdf (skeleton system wow)
Mohammad Al-Dhahabi
 

Recently uploaded (20)

Level 3 NCEA - NZ: A Nation In the Making 1872 - 1900 SML.ppt
Level 3 NCEA - NZ: A  Nation In the Making 1872 - 1900 SML.pptLevel 3 NCEA - NZ: A  Nation In the Making 1872 - 1900 SML.ppt
Level 3 NCEA - NZ: A Nation In the Making 1872 - 1900 SML.ppt
 
Beyond Degrees - Empowering the Workforce in the Context of Skills-First.pptx
Beyond Degrees - Empowering the Workforce in the Context of Skills-First.pptxBeyond Degrees - Empowering the Workforce in the Context of Skills-First.pptx
Beyond Degrees - Empowering the Workforce in the Context of Skills-First.pptx
 
NEWSPAPERS - QUESTION 1 - REVISION POWERPOINT.pptx
NEWSPAPERS - QUESTION 1 - REVISION POWERPOINT.pptxNEWSPAPERS - QUESTION 1 - REVISION POWERPOINT.pptx
NEWSPAPERS - QUESTION 1 - REVISION POWERPOINT.pptx
 
مصحف القراءات العشر أعد أحرف الخلاف سمير بسيوني.pdf
مصحف القراءات العشر   أعد أحرف الخلاف سمير بسيوني.pdfمصحف القراءات العشر   أعد أحرف الخلاف سمير بسيوني.pdf
مصحف القراءات العشر أعد أحرف الخلاف سمير بسيوني.pdf
 
A Visual Guide to 1 Samuel | A Tale of Two Hearts
A Visual Guide to 1 Samuel | A Tale of Two HeartsA Visual Guide to 1 Samuel | A Tale of Two Hearts
A Visual Guide to 1 Samuel | A Tale of Two Hearts
 
REASIGNACION 2024 UGEL CHUPACA 2024 UGEL CHUPACA.pdf
REASIGNACION 2024 UGEL CHUPACA 2024 UGEL CHUPACA.pdfREASIGNACION 2024 UGEL CHUPACA 2024 UGEL CHUPACA.pdf
REASIGNACION 2024 UGEL CHUPACA 2024 UGEL CHUPACA.pdf
 
BIOLOGY NATIONAL EXAMINATION COUNCIL (NECO) 2024 PRACTICAL MANUAL.pptx
BIOLOGY NATIONAL EXAMINATION COUNCIL (NECO) 2024 PRACTICAL MANUAL.pptxBIOLOGY NATIONAL EXAMINATION COUNCIL (NECO) 2024 PRACTICAL MANUAL.pptx
BIOLOGY NATIONAL EXAMINATION COUNCIL (NECO) 2024 PRACTICAL MANUAL.pptx
 
HYPERTENSION - SLIDE SHARE PRESENTATION.
HYPERTENSION - SLIDE SHARE PRESENTATION.HYPERTENSION - SLIDE SHARE PRESENTATION.
HYPERTENSION - SLIDE SHARE PRESENTATION.
 
Bossa N’ Roll Records by Ismael Vazquez.
Bossa N’ Roll Records by Ismael Vazquez.Bossa N’ Roll Records by Ismael Vazquez.
Bossa N’ Roll Records by Ismael Vazquez.
 
Traditional Musical Instruments of Arunachal Pradesh and Uttar Pradesh - RAYH...
Traditional Musical Instruments of Arunachal Pradesh and Uttar Pradesh - RAYH...Traditional Musical Instruments of Arunachal Pradesh and Uttar Pradesh - RAYH...
Traditional Musical Instruments of Arunachal Pradesh and Uttar Pradesh - RAYH...
 
The basics of sentences session 7pptx.pptx
The basics of sentences session 7pptx.pptxThe basics of sentences session 7pptx.pptx
The basics of sentences session 7pptx.pptx
 
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
What is Digital Literacy? A guest blog from Andy McLaughlin, University of Ab...
 
Educational Technology in the Health Sciences
Educational Technology in the Health SciencesEducational Technology in the Health Sciences
Educational Technology in the Health Sciences
 
Gender and Mental Health - Counselling and Family Therapy Applications and In...
Gender and Mental Health - Counselling and Family Therapy Applications and In...Gender and Mental Health - Counselling and Family Therapy Applications and In...
Gender and Mental Health - Counselling and Family Therapy Applications and In...
 
BÀI TẬP BỔ TRỢ TIẾNG ANH LỚP 9 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2024-2025 - ...
BÀI TẬP BỔ TRỢ TIẾNG ANH LỚP 9 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2024-2025 - ...BÀI TẬP BỔ TRỢ TIẾNG ANH LỚP 9 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2024-2025 - ...
BÀI TẬP BỔ TRỢ TIẾNG ANH LỚP 9 CẢ NĂM - GLOBAL SUCCESS - NĂM HỌC 2024-2025 - ...
 
THE SACRIFICE HOW PRO-PALESTINE PROTESTS STUDENTS ARE SACRIFICING TO CHANGE T...
THE SACRIFICE HOW PRO-PALESTINE PROTESTS STUDENTS ARE SACRIFICING TO CHANGE T...THE SACRIFICE HOW PRO-PALESTINE PROTESTS STUDENTS ARE SACRIFICING TO CHANGE T...
THE SACRIFICE HOW PRO-PALESTINE PROTESTS STUDENTS ARE SACRIFICING TO CHANGE T...
 
RHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem students
RHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem studentsRHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem students
RHEOLOGY Physical pharmaceutics-II notes for B.pharm 4th sem students
 
Pharmaceutics Pharmaceuticals best of brub
Pharmaceutics Pharmaceuticals best of brubPharmaceutics Pharmaceuticals best of brub
Pharmaceutics Pharmaceuticals best of brub
 
Temple of Asclepius in Thrace. Excavation results
Temple of Asclepius in Thrace. Excavation resultsTemple of Asclepius in Thrace. Excavation results
Temple of Asclepius in Thrace. Excavation results
 
skeleton System.pdf (skeleton system wow)
skeleton System.pdf (skeleton system wow)skeleton System.pdf (skeleton system wow)
skeleton System.pdf (skeleton system wow)
 

REMIFENTANIL: An Ultra short acting opioid.pptx

  • 1. REMIFENTANIL: AN ULTRA-SHORT ACTING OPIOID Dr. Ravikiran HM MBBS,DNB ADMO/CH/MLG Department of Anaesthesiology and Critical care Central Hospital, NF Railway, Maligaon, GHY-11
  • 2. INDEX  Introduction  Opioids classification  Mechanism of action of opioids  Structure  Pharmacokinetics  Pharmacodynamics  Adverse effects  Uses  Dosing  Pharmacoceutics  Pharmacoeconomics  Conclusion
  • 3. INTRODUCTION  Short acting drugs are desirable in modern clinical anesthesia practice.  They allow rapid recovery, minimal residual effects.  Preserve cognitive function for rapid discharge, better patient satisfaction.  Day care procedures, rapid turn over of case load.  Ex: Methohexital, Etomidate, Remimazolam, Remifentanil, Gantacurium, Esmolol…
  • 4. INTRODUCTION cont…  Balanced / multimodal anesthesia: Administered with combinations of synergestic agents to induce desired state.  Components: 7A 1. Anesthesia: loss of awareness 2. Analgesia: most important 3. Anxiolysis 4. Areflexia: muscle relaxation 5. Autonomic attenuation 6. Amnesia 7. Avoidance of side effects  Research continues for ideal agents
  • 5. INTRODUCTION cont…  Remifentanil is a pure μ-opioid receptor agonist.  Introduced in the early 1990s  Its rapid onset and offset coupled with its synergistic effects with other general anaesthetic agents make it an ideal option for anaesthesia and conscious sedation.
  • 7. MECHANISM The endogenous ligand or drug binds to the opioid receptor and activates the G protein, resulting in multiple effects that are primarily inhibitory. The activities of adenylate cyclase and the voltage-dependent Ca2+ channels are depressed. The inwardly rectifying K+ channels and mitogen activated protein kinase (MAPK) cascade are activated.
  • 8. MECHANISM cont… •δ-opioid receptor, DOP (named after the tissue it was first isolated from, vas Deferens) •κ-opioid receptor, KOP (named after the first ligand, Ketocyclazine) •μ-opioid receptor, MOP (named after Morphine, proposed 1976,cloned 1993) •NOP: nociceptin/orphanin FQ (N/OFQ) or orphanin like receptors (ORL1)
  • 9. MECHANISM cont… Remifentanil is a selective μ-opioid receptor agonist
  • 10. STRUCTURE  Like alfentanil and sufentanil, is based on its parent drug fentanyl(Piperidine derivative).  The crucial difference is the addition of an ester group allowing it to be rapidly metabolized by non-specific plasma and tissue esterases.  This gives rise to its characteristic ultra-fast offset and allows for rapid titration.
  • 12. ABSORPTION  Only IV formulation  Rapid onset of action (within 1–1.5 minutes) and peak analgesic effect (within 1–3 minutes). Remifentanil has a faster onset of action than fentanyl or sufentanil.
  • 13. DISTRIBUTION  Rapidly distributed throughout blood and highly perfused tissues; subsequently distributed into peripheral tissues; unlike other opiate agonists, remifentanil does not accumulate at high doses or with prolonged administration.  Initial Vd: 100ml/kg. Vd steady state: 260-415ml/kg  Rapidly equilibrates across blood-brain barrier.  Crosses placenta; average maternal remifentanil concentrations are about twice those observed in fetus.  Plasma Protein Binding: 70–92% (primarily α1-acid glycoprotein).
  • 14. BLOOD CONCENTRATION – MINTO MODEL  Linear response  Blood-brain equilibration half-time = 1 ± 1 minutes  Rapid titration
  • 15. METABOLISM  Broken down by esterases, can be used safely in patients with pseudocholinesterase deficiency.  Major metabolite: remifentanil acid → renal excretion  Metabolite accumulates in patients with reduced renal function. Despite this, dosing does not need to be adjusted for renal dysfunction as its almost entirely inactive  Clearance was reduced by ≈20% during hypothermia (28-30 O C).
  • 16. ELIMINATION  Self-reversal Short Elimination Half life (3-10 mins) High clearance (amount of plasma cleared of the drug/min) 40mls/min/kg Small volume of Distribution (Vd)
  • 17. CONTEXT-SENSITIVE HALF TIME  Time it takes for the concentration of a drug in the plasma to decrease by half after an infusion is terminated.  The context-sensitive half-time often cannot be predicted by the elimination half-life (a measure of the time needed for actual drug metabolism or elimination) because it also depends on drug distribution. It is a useful concept because it helps explain the duration of action of a drug given by infusion after stopping the infusion.  For remifentanil both elimination and context half life is 3min.
  • 18. CONTEXT-SENSITIVE HALF TIME cont… Half-lives of Remifentanil Value (minutes) Significance Rapid distribution half- life 1 Immediate onset of action Slower distribution half- life 6 Easier titration of dose Terminal elimination half-life 10-20 Rapid clearance reduces accumulation Effective biological half- life 3-10 Rapid recovery Context -sensitive half- life 3-6 Independent of duration of infusion
  • 19. PHARMACOKINETICS IN SPECIAL POPULATION  Elderly: Between 20 to 85 years of age, Vdc and CL values decrease by ≈25% and 33% in healthy adult volunteers, requiring a 50% reduction in the initial and subsequent doses of remifentanil in those >65 years of age.  Paediatric patients: The elimination half-life in neonates is not significantly different from that of young healthy adults. Changes in analgesic effect after changes in infusion rate of remifentanil should be rapid and similar to those seen in young healthy adults. The pharmacokinetics of the carboxylic acid metabolite in paediatric patients 2 to 17 years of age are similar to those seen in adults after correcting for differences in body weight.
  • 20. PHARMACOKINETICS IN SPECIAL POPULATION cont….  Gender: No clinically relevant differences seen in pharmacokinetc profile based on gender.  Hepatic or Renal impairment: No clinically relevant differences in PK profile of drug  Body mass (Obesity): Pharmacokinetic parameters are reduced by about one-third in obese versus lean patients. Dose reduction in obese patients should be based on the patient’s ideal body weight
  • 22. POTENCY OF OPIOIDS COMPARED Most potent: Crafentanil>>Sufentanil>>Fentanyl≥Remifentanyl>>Alfentanyl
  • 23. THERAPEUTIC INDEX  Therapeutic index = ED50/LD50  Very high therapeutic index (33,000)  Thus wide therapeutic window (Dose range between minimum effective concentration and minimum toxic concentration)
  • 25. CVS  Hypotension: Hypotension potentiated with other anaesthetics, so titrate accordingly. Vassopressors kept ready  Bradycardia, rarely asystole: Use glycopyrrolate premedication  No histamine release unlike other opioids on rapid administration (anaphylactoid reaction)
  • 26. RS  Respiratory depression and apnoea  Transient, always plan for securing airway to be there (trained staff)
  • 27. GIT  Nausea and vomiting: same risk as that of other opioids  Constipation
  • 30. MUSCULOSKELETAL  Post op Shivering: twice the risk as compared  Muscle Rigidity: wooden chest syndrome, common with bolus dose and high doses. Management: simultaneous injection of muscle relaxant/induction agent like propofol/thio. In spontaneous patients stop infusion/naloxone/muscle relaxant. Prevention: slow injection 30- 90sec
  • 31. WITHDRAWAL  Hyperalgesia (even after short infusions): morphine (0.15–0.3mg.kg-1) or alternative, should be given at least 30 minutes before stopping remifentanil to allow it time to reach peak effect  After prolonged use (>3 days):  Hypertension  Tachycardia  Agitation
  • 32. DRUG INTERACTIONS  Risk of serotonin syndrome  Potentiate sedative drug
  • 34. INTUBATION WITHOUT MUSCLE RELAXANT  Obtunds airway reflexes and under most circumstances allows tracheal intubation without the use of muscle relaxants in both adults and children.  Benefits in certain situations: e.g. 1. In those with abnormal sensitivity to muscle relaxants e.g. allergy, myasthenia gravis, malignant hyperthermia etc. 2. Where assistance of nerve stimulators is desirable e.g. for monitoring facial nerve function during mastoid/parotid surgery or if planning a regional block immediately after induction 3. Where avoidance of incomplete reversal or recurarisation is desirable 4. Less risk of awareness.
  • 35. CONSCIOUS SEDATION  NORA and Day-care procedures: Rapid recovery with clear head  Simple dental extractions  Hysteroscopy  Joint / fracture reductions  Burns dressing changes  Awake tracheostomy  Bronchoscopy, Endoscopy  Adjunct-rescue to partially failed regional block or regional block that is wearing off
  • 36. CONSCIOUS SEDATION cont….  not suitable for any patient that has a potentially difficult airway, is morbidly obese, is not starved, or for a potentially prolonged procedure.  It also needs to be carried out in a location that is equipped to deal with any complications and have full AAGBI monitoring and resuscitation kit available
  • 37. ROLE IN OBSTETRICS  While epidural analgesia remains the gold standard for labour pain, remifentanil patient controlled analgesia (PCA) has now been cautiously accepted as an alternative in circumstances where epidurals are contraindicated.  Crosses the placental barrier however it is rapidly metabolized and redistributed by the foetus, even in the pre-term.  Has a greater depressant effect on maternal respiratory function and consciousness than other opioids; this needs to be explained to parturients and must be vigilantly monitored.  Useful during emergency Caesarian sections to avoid laryngoscopy-induced pressor response in eclamptic patients
  • 38. ROLE IN NEURO-ANAESTHESIA  Awake craniotomy: help in brain mapping  Wake up test: spine surgery: gold standard test for nerve injury  Does not effect SSEP (becoz of short effect)
  • 39. ROLE IN CARDIAC-ANAESTHESIA  Blunts response to hemodynamic stress  Rapid recovery post-op
  • 40. BENEFITS IN ICU  Rapid offset allowing for earlier neurological assessment during sedation holds.  Profound respiratory depression helping to avoid patient-ventilator dysynchrony .  Very short context-sensitive half-life and minimal accumulation – ideal for resuming spontaneous breathing rapidly.  No need to dose-adjust in chronic or acute kidney injury (AKI) – offset times are approximately twice as long in moderate-severe renal impairment however as the difference is only 16.5 mins this is not usually significant.  More predictable offset times particularly in patients with multi-organ dysfunction.
  • 41. ISSUES IN ICU  Potential for hyperalgesia and withdrawal following cessation of infusion, warranting the use of post-remifentanil analgesia/opiate to be in place prior to dose reduction.  Potential risk of apnoea and/or chest wall rigidity (in high doses) which may make ventilation more difficult.  The apnoea risk needs to be taken seriously, particularly when using in patients who are not intubated. Staff need to remain vigilant of this potential complication when in use and have a plan in place if apnoeas were to occur.  Cardiovascular instability (namely hypotension/bradycardia) may increase a patient’s vasopressor/inotrope requirement.
  • 42. NEURAXIAL USES  Contraindicated  Contains glycine(acidic buffer): an inhibitory neurotransmitter.
  • 44. PREPARATION  Lyophilised Powder form: 1mg/vial or 2mg/vial  Preparation: 1mg in 20ml or 2mg in 40ml NS: 50mcg/ml  Care should be taken to avoid inadverant injection of drug in infusion set.  Diluents: 5 % glucose solution, 5 % glucose and 0.9 % sodium chloride solution, 0.9 % sodium chloride solution, 0.45 % sodium chloride solution, sterilised water for Injection
  • 45. DOSING  The pharmacokinetics are more closely associated with lean body weight (LBW) rather than actual body weight (ABW).  Although obese patients do require a larger dose than their LBW would suggest, it is far less than their ABW dose; this would put them at risk of cardiovascular depression
  • 46. DOSING  Minto Model TCI pump: By Dr. Charles Minto. Predicting the concentration of remifentanil in plasma and the effect site.  Input of patient sex, age, weight (kg) and height (cm). Age more than 12years. Purpose Cet (effect site conc.) GA 2.5ng/ml RSI 8ng/ml Awake fiberoptic/Conscious sedation 2ng/ml
  • 51. MANUAL INFUSION USING 50MCG/ML CONCEN
  • 52. DOSAGE IN ELDERLY  The clearance of remifentanil is slightly reduced in older people ( > 65 years) compared to that in young patients.  The pharmacodynamic activity increases with increasing age.  The initial dose should be reduced by 50% in older people and then carefully titrated to meet the individual patient need EC50 is a measure of brain sensitivity. Decreased EC50 means increased sensitivity.
  • 53. PHARMACEUTICAL PARTICULARS  Remifentanil should not be mixed with propofol in the same intravenous admixture solution.  Remifentanil has been shown to be compatible with propofol when administered into a running IV catheter.
  • 57. PHARMACOKINETICS COMPARISION Agent Route of administration Onset of action Tmax Duration of action Fentanyl i.v 1-2min 3-4min 30min Remifentanil i.v 30s 1min 5-10min Agent metabolize excretion Protein binding rate (%) Distribution volume (L/kg) Half life Plasma clearance (ml/kg.min) Fentanyl liver kidney 84 4.1 3-4h 13.3 Remifentanil Plasma kidney 70 0.39 9.1min 2800
  • 58. CONCLUSION  Desirable features: rapid onset, rapid offset, rapid titration  Undesirable: Muscle rigidity, apnea, hemodynamic instability ( can be managed well if careful drug titration and availability of vigilant anesthetist)
  • 59. REFERENCES 1. Atterton B, Lobaz S, Konstantatos A. Remifentanil use in anaesthesia and critical care. Anaesthesia. 2016 Nov 29;342:1-9. 2. Opioids-NYSORA 3. Basic Pharmacologic Principles-NYSORA 4. Correll DJ, Rosow CE. Opioids. In: Vacanti C, Segal S, Sikka P, Urman R, eds. Essential Clinical Anesthesia. Cambridge University Press; 2011:242-250. 5. Trivedi M, Shaikh S, Gwinnutt C. Pharmacology of opioids-part 1 anaesthesia tutorial of the week 64. 6. Gupta DK, Krejcie TC, Avram MJ. Pharmacokinetics of opioids. In: Evers AS, Maze M, Kharasch ED, eds. Anesthetic Pharmacology: Basic Principles and Clinical Practice. Cambridge University Press; 2011:509-530. 7. Servin FS, Billard V. Remifentanil and other opioids. Handb Exp Pharmacol. 2008;(182):283-311. doi: 10.1007/978-3-540-74806-9_14. PMID: 18175097. 8. Beers, R., Camporesi, E. Remifentanil Update. CNS Drugs 18, 1085–1104 (2004). https://doi.org/10.2165/00023210-200418150-00004 9. REMITHEM Monograph

Editor's Notes

  1. Citation F S Servin 1, V Billard; Remifentanil and other opioids; Handb Exp Pharmacol. 2008:(182):283-311.