Opioids & Their Use in Anaesthesia

1. Presented by:
Dr. Md. Zareer Tafadar
Post Graduate Student
Deptt. Of Anaesthesiology &Critical Care
Silchar Medical College & Hospital.

2.  Opioids have been the mainstay of pain treatment for thousands
of years, and they remain so today.
 The word opium is derived from the Greek word for juice “opios”.
 Opium is a dark brown, resinous material obtained from the
capsule of the poppy plant (Papaver somniferum).
 There are 20 natural alkaloids derived from the juice of poppy
plant.
 The term “opioid” is used to denote all exogenous substances
natural and synthetic, that bind to any of the several sub-
populations of opioid receptors and produce at least some agonist
effects.
 Opiate is the term used for drugs derived from opium.

3.  Opioids are among the world's oldest known drugs and the
therapeutic use of the opium predates recorded history.
 Hippocrates and Galen, two of the most prominent Greek
physicians, employed opium to battle headaches, coughing,
asthma and melancholy
 1805- German chemist Friedrich Serturner isolated the pure active
ingredient in opium. He named this chemical “morphine”, after
Morpheus, the Greek god of dreams
 1874: German chemists invented heroin by adding two acetyl
groups to morphine .
 1939: Meperidine the first opiate with a structure altogether
different from that of morphine.

4.  1942: Weijlard and Erikson produced nalorphine (N-
allylnormorphine), the first opiate antagonist.
 1959:Fentanyl was first synthesized by Paul Janssen
 1973: Candace Pert and Solomon Snyder discovered that opioids
act by attaching to specific receptors within the brain. These
receptors were called the opiate receptors.
 1975: Scottish neuroscientists John Hughes and Hans Kosterlitz
discovered two neurotransmitters that activate the opiate
receptors.- “endorphins”.
 1974 to 1976: Other fentanyl congeners like alfentanyl, sufentanyl
were synthesized.

5. On the basis of source
 Naturally occuring
 Phenanthrene :Morphine, Codeine ,Thebaine
 Benzylisoquinoline: Papaverine ,Noscapine ,Narcine
 Semisynthetic
 Heroin
 Dihydromorphone/morphinone
 Thebaine derivatives: Etorphine, Buprenorphine.
 Synthetic
 Phenylpiperidines: Meperidine, Fentanyl, Sufentanil,
Alfentanil, Remifentanil.
 Morphinan compounds:Levorphanol, Butorphanol.
 Phenyl-heptylmines: Methadone,
Propoxyphene,Dextropropoxyphene Diphenylpropylamine.
 Benzomorphans: Pentazocine

6.  On the basis of action
Opioid Agonists
 Morphine
 Meperidine
 Fentanyl
 Sufentanyl
 Remifentanyl
 Alfentanyl
 Codeine
 Hydromorphone
 Oxymorphone
 Oxycodone
 Propoxyphene
 Methadone
 Tramadol
 Heroin
Opiod Agonist- Antagonist
 Pentazocine
 Butorphanol
 Nalbuphine
 Buprenorphine
 Nalorphene
 Bremazocine
 Dezocine
 Opiod Antagonist
 Naloxone
 Naltrexone
 Nalmefene

7.  Endorphins:
 Derived from POMC
 ß-endorphins: 2 Types - ß-endorphin1 and ß-endorphin-2
 Primarily μ agonist and also has δ action
 Enkephalins:
 Derive from Proenkephalin
 Met-ENK and leu-ENK
 Met-ENK - Primarily μ and δ agonist and leu-ENK – δ agonist
 Dynorphins:
 Derive from Prodynorphin: DYN-A and DYN-B
 Potent κ agonist and also have μ and δ action
 Endomorphins:
 Binds to the µ-receptor with high affinity and high selectivity.

8. μ receptor κ receptor δ receptor
Location μ1 – supraspinal
µ2 - spinal
κ1 – spinal
κ3 –supraspinal
Spinal
Supra-spinal
Effects Analgesia
Respiratory depression
Sedation
Euphoria
Miosis
Bradycardia,
Hypothermia
Physical dependence
Spinal analgesia
Dysphoria
Sedation
Psychomimetic
Spinal analgesia
Affective behaviour
(Supraspinal)
Respiratory depression
Agonists Morphine, Codeine,
Fentanyl
Pentazocine(weak)
Endorphins
Pentazocine,
Dynorphins
Enkephalins

9. 1. Brainstem: mediating
respiration, cough, nausea
& vomiting, maintenance
of BP, pupillary diameter
and control of GI
secretion.
2. Medial thalamus:
mediating poorly
localized deep pain
3. Spinal cord: receptors
located in the substantia
gelatinosa are involved in
the receipt & integration
on sensory input leading
to the attenuation of
painful afferent stimuli

10. 4. Hypothalamus:
mediating
neuroendocrine
secretion.
5. Limbic system:
receptors in the
amygdala play a
major role in
emotional behavior
& response and little
analgesic effect.
6. Peripheral nerve
fibers

12.  Opioid receptors belong to a super family of G-protein coupled
receptors.
 All three opioid receptor classes couple to G-proteins and inhibit
adenyl-cyclase. The subsequent reduction of intracellular cAMP
results in opening of K+ channels and supression of N type of Ca2+
channels.
 The resultant hyperpolarization prevents excitation and
propagation of action potential.
 The reduced intracellular Ca2+ leads to suppression of
neurotransmitter release – NA, DA, 5-HT, GABA and Glutamate.
 Opioid receptors may regulate the function of other ion channels
including excitatory post synaptic currents evoked by NMDA
receptors.

14. Mechanism Of Action Of μ-
Agonists In The Spinal Cord
Pre-synaptic Neuron
•Activation of opioid receptor decreases
Ca2+ influx in response to incoming AP
•Decrease in level of neuroexcitatory
transmitters like Glutamate NA, DA, 5-
HT.
Post-synaptic Neuron
• Increase in the K+ efflux
• Resultant hyperpolarization prevents
propagation of action potential

15. Pharmacological Actions
 Analgesia
 Produces strong analgesia without
loss of consciousness.
 Other sensory modalities are not
affected.
 Increases the threshold of pain and modifies `
the perception of noxious stimuli.
 Associated reactions to pain -apprehension, fear and autonomic
effects are also relieved .
 Nociceptive pain is better relieved than neuritic pain.
 Visceral pain is relieved better than somatic pain.

16.  Sedation:
 Drowsiness and indifference to surroundings.
 Inability to concentrate and extravagant imagination
– colorful day dream.
 Apparent excitement.
 Larger doses produce sleep – EEG resembles normal
sleep
 Mood effects:
 Opioids produce euphoria, tranquility, and other
alterations of mood including rewarding properties.
 In persons with pain & addicts sense of wellbeing,
pleasurable floating feelings – euphoria.
 In normal persons these sensations may be
unpleasant in absence of pain – dysphoria.

17.  Depression
 Pontine and medullary ventilatory centre – Both rate
and depth of respiration is diminished.
 Medullary cough centre .
 Temperature regulating centre.
 Vasomotor centre – High doses cause fall in BP.
 Stimulation
 CTZ – sensitize CTZ to vestibular and other
impulses.
 Edinger Westphal Nucleus – miosis .
 Vagal centre – Bradycardia .
 Hippocampal cells – convulsions (inhibition of
GABA release).

18.  Neuro-endocrine:
 GnRH and CRH are inhibited – FSH, LH and ACTH
levels are lowered. Only short term tolerance
develops.
 Decrease in levels of Sex hormone and
corticosteroids, but no infertility.
 Increases ADH release – oliguria..
 CVS:
 No direct action on the myocardium.
 Histamine release, depression of vasomotor centre
and decrease in the sympathetic tone of blood
vessels may cause vasodilatation leading to
hypotension.
 Cardiac work reduction due to consistent
vasodilatation.

19. Pharmacokinetics
 Absorption and Distribution:
 Well absorbed after IM administration with onset of action in 15 -30
min. Duration of action is about 4 hrs. Variable absorption orally.
 IV administration results in wide distribution in the visceral
circulation. However CNS penetration is poor.
 Readily crosses placental barrier – causing hypoxia and apnoea in
fetus.
 Metabolism:
 The principal pathway of metabolism is conjugation with
glucuronic acid in hepatic and extra hepatic sites esp. the kidneys to
produce water soluble metabolites.
 Morphine-3-glucuronide (70-80%): Pharmacologically inactive.
 Morphine-6-glucuronide (5-10%): Agonist action at µ–receptors
produces analgesia and depression of ventilation.
 Excretion:
 Via Urine, Plasma t1/2 = 2-3 hrs
 Completely eliminated in 24 hrs.
 Elimination of morphine glucuronides may be impaired in patients
with renal failure.

20. all µ-receptor agonists
 dose dependent depression
of respiration,
• brainstem sensitivity to CO2
• slope of the CO2-ventilation response curve
• apnoeic threshold
• hypoxic drive to respiration
•carotid body chemoreception is virtually
abolished
• pontine & medullary centres involved in
rhythmic respiration
Signs :
Oxygen desaturation .
Obstructive apnea.
Periodic breathing resembling
Cheyne- Stokes breathing.
Slow respiratory rate.

21.  The stimulatory effect of hypercapnoea on ventilation is blunted.
 Apnoeic threshold and resting EtPCO2 are increased .
 However voluntary control of respiration is not lost.
 Effect is increased during co-administration with other CNS
depressants like inhalational anesthetics, BZDs, and most of the
sedative-hypnotics.
 Standard therapy is Naloxone.

22. CVS: Orthostatic hypotension. Bradycardia may be due to stimulation of
vagal nuclei in medulla or direct depressant effect of morphine on the SA node.
 CNS: Sedation, mental clouding – sometimes dysphoria. Skeletal muscle
rigidity and myoclonus. Raised ICT
Smooth Muscle contraction: Biliary colic, urinary retention and
bronchospasm.
Nausea and vomiting.
Idiosyncrasy and allergy.
Tolerance and dependence:
 Tolerance and dependence is the most common problem with morphine.
Exhibited in most actions except constipation and miosis.
 It produces psychological and physical dependence.
 Withdrawal may lead to drug seeking behaviour and may turn to
morphine withdrawal syndrome. It is characterized by anxiety, fear,
restlesness, diarrhoea, abdominal colic, delirium and convulsion.
Treatment is methadone

23. Acute Morphine Poisoning:
 Occurs if >50 mg (Lethal dose – 250 mg) is administered.
 Manifested as depression of ventilation which may progress to
apnoea.
 The triad of miosis, hypoventilation and coma should suggest
overdose with an opioid.
 Gastric lavage with KMnO4. Specific antidote: Naloxone: 0.4 to 0.8
mg IV repeatedly in 2-3 minutes till respiration picks up.

24. Therapeutic Uses
Analgesic:
 Surgical analgesia, post operative analgesia, long bone fracture,
burns.
 Myocardial infarction.
 Palliative therapy in cancer.
 Visceral pains – pulmonary embolism, pleurisy, acute
pericarditis.
Other Uses
 Pre-anaesthetic medication
 Acute left ventricular failure – Cardiac asthma
 Congeners of morphine such as loperamide and diphenoxylate
may be used in severe intractable diarrhoea.

25. Contraindications
 Head Injury
 Bronchial asthma
 Respiratory insufficiency - emphysema
 Shock – Hypotension
 Undiagnosed acute abdomen
 Renal Failure, Liver diseases and hypothyroidism
 Unstable personalities

26.  Phenylepiperidine derivative
having structural similarities
with that of local anaesthetics.
Pharmacokinetics
 1/10th as potent as morphine, but efficacy is similar.
 Rapid but short duration of action (2-3 Hrs)
 In equal analgesic dose it produces as much sedation, euphoria
and respiratory depression as morphine.
 Less spasmodic action in smooth muscles – less miosis,
constipation and urinary retention
 Not useful in diarrhoea and is devoid of antitussive action.
 Less histamine release – safer in asthmatics.
 Better oral absorption.

27. Clinical Uses:
 For labour analgesia and post operative analgesia.
 Effective for suppression of post operative shivering.
Adverse Effects:
 Similar to morphine.
 Atropine like effects – dry mouth, blurred vision,
tachycardia.
 Overdose – tremors, mydriasis, delirium and
convulsion due to norpethidine accumulation.
 Serotonin syndrome in patients receiving MAOs

28.  Phenylpiperidine derivative
synthetic opioid structurally
related to meperidine
 Pharmacokinetics
 75 to 125 times as potent as morphine.
 Rapid onset and shorter duration due to greater lipid
solubility.
 Rapidly redistributed to inactive storage sites such
as fat and skeletal muscles.
 75% of the initial dose undergoes first-pass
pulmonary uptake.

29. Clinical Uses
 Analgesia: Low IV dose 1-2 µg/kg
 Adjuvant to anaesthetics (2-20 µg/kg) to blunt
circulatory response to Intubation of the trachea and
to decrease requirement of inhalational agents.
 As a component of Total Intravenous Anaesthesia
(TIVA) – Dose 50-150 µg/kg.
 Intrathecal fentanyl may be used to provide labour
analgesia and as an adjuvant for spinal and epidural
anaesthesia.
 Oral transmucosal fentanyl 5- 20 µg/kg may be used
to decrease pre-operative anxiety and facilitate
induction.
 Transdermal fentanyl patch delivering 75 - 100 µg/hr
may be used for treatment of chronic pain in cancer
patients.

30. Adverse Effects:
 Similar to morphine
 Persistent/ recurrent respiratory depression
 Carotid sinus baroreceptor reflex control is
markedly depressed- caution in neonates.
 Bradycardia is more prominent than in
morphine.
 Allergic reactions are rare.
 Myoclonus may produce clinical picture of
seizure activity in the absence of EEG
changes
 Modest increases in ICP in head injury
patients inspite of an unchanged PaCO2
.

31. Fentanyl As a Sole Anaesthetic Agent
Advantages
 Lack of direct myocardial depressant effects.
 Absence of histamine release.
 Suppression of stress respone to surgery.
Disadvantages
 Failure to prevent sympathetic response to
surgical stimulation.
 Possible patient awareness.
 Postoperative ventilatory depression

32.  Thienyl analogue of fentanyl.
 Pharmacokinetics:
 Potency is 5 to 10 times that of fentanyl..
 Lipophilic nature permits rapid penetration into the BBB and onset of
CNS effects.
 Approx. 60% of the drug undergoes first pass pulmonary uptake.
 Extensive protein binding - mainly α1 acid glycoprotein.
 Enhanced effect in neonates probably due to α1 acid glycoprotein.
 Metabolism :
 N-dealkylation→ inactive metabolite
 O-demethylation→ desmethyl sufentanyl has10% activity of
sufentanyl.
 Extensively metabolised by hepatic microsomal enzymes.
 Hepatic clearance sensitive to hepatic blood flow.
 Context-sensitive half time is shorter than that of alfentanyl for
continuous infusion up to 8 hrs due to the large Vd.

33.  Sufentanyl Vs Fentanyl:
 Longer analgesia and less ventilatory depression.
 More rapid induction.
 Earlier emergence and earlier tracheal extubation

34.  Fentanyl analogue with lesser potency and shorter duration of
action.
 Despite its lower lipid solubilty it has a more rapid onset of
action due to the higher degree of non-ionisation.
 It is used to provide analgesia when the noxious stimulation is
acute but transient as in laryngoscopy, tracheal intubation and
performance of a retrobulbar block.
 Associated with a lower incidence of PONV.
 Acute dystonia has been described in patients with untreated
Parkinson’s disease.

35.  Selective μ agonist with potency similar to fentanyl.
 Predictable onset and termination of effect because of
 Rapid clearance
 Smaller Vd
 No significant redistribution to inactive storage sites
.
 Unique ester-linkage
 Metabolised by non-specific plasma and tissue
esterases. Safe in hepatic and renal failure.
 Not a substrate of pseudo-cholinesterase.
 Blood-brain equilibration time similar to alfentanil.

36. Clinical Uses
 Short intense analgesia
 Suppressing transient sympathetic response to laryngoscopy of at risk
patients.
 Intermittent administration as PCA during labour and delivery.
 Sedation in mechanically ventilated patients.
 Sedation and analgesia during monitored anaesthesia.
 To attenuate haemodynamic response to electroconvulsive therapy.
Side effects:.
 Termination of analgesic effect on accidental stoppage of infusion.
 Induce seizure like activity
 Nausea and vomiting
 Depression of ventillation
 Decrease in B.P and H.R.
 Acute opoid tolerance.

37.  Time taken for blood plasma concentration of a drug to
decline by one half after an infusion designed to
maintain a steady state (i.e. a constant plasma
concentration) has been stopped.
 The “context” in this case is the duration of infusion.
 During an infusion, the peripheral compartments begin
to “fill up.” After the infusion is stopped, drug will be
eliminated, but will also continue to be redistributed as
long as the concentration in a peripheral compartment.
This leads to a rapid drop in central compartment drug
concentration.
 When central compartment (plasma) concentration
drops below that of the peripheral compartment(s), the
direction of drug redistribution will reverse and will
slow the decline in plasma concentration

38. Initial Phase Late Phase
Central
Compartment
Peripheral
compartment
Central
Compartment
Peripheral
compartment

40.  Centrally acting analgesic with moderate affinity for μ receptors and
weak κ and δ activity.
 Dual mechanism of action
 Opioid agonist effect.
 5-HT and NA uptake inhibition enhancing function of spinal
inhibitory pathways.
 Effective both orally and IV (100mg = 10 mg Morphine).
 Uses
 Effective for the treatment of chronic pain.
 Can be used where NSAIDS are contraindicated.
 Short diagnostic procedures.
 Post-operative shivering.
 Disadvantages
 Seizures have been demonstrated.
 High incidence of nausea and vomiting.

41. These drugs bind to μ-
receptors where they act as
partial agonist or competitive
antagonist and exhibit partial
agonist actions at other
receptors.
Produce analgesia with
limited ventilatory
depression and low potential
for producing physical
dependence.
However they can attenuate
the efficacy of subsequently
administered opioid agonists.
Ceiling effect present.

42.  Benzomorphan derivative.
 Weak μ-receptor antagonist, but agonist of κ and δ receptor.
 One of the commonly used agents, given orally and IM.
 Ceilings in both analgesia and respiratory depression occur after
30 to 70 mg of pentazocine.
 Low abuse liability. However can precipitate withdrawal
symptoms in patients who have been administered opioids on a
regular basis.
Uses: Moderately severe pain in injury, burns, trauma and
orthopaedic manuevers .

43. Disadvantages
 Depresses myocardial contractility.
 Increases blood catecholamine levels thus increasing B.P, H.R,
SVR,PAP, and LVEDP.
 Inhibits gastric emptying and GIT transit.
 High incidence of PONV.
 Limited analgesia.
 Partially antagonizes other opioids.
 Produces psychotomimetic effects.

44.  Agonist- antagonist opioid that resembles Pentazocine.
 Compared to Pentazocine, its agonist action is 20 times greater
and antagonist activity is 15- 30 times greater.
 Rapidly and almost completely absorbed after I.M
administration.
 Respiratory depression is similar to morphine, higher doses reach
a ceiling.
 Less abuse and has less addictive potential than morphine or
fentanyl.
 Intra-operative use is limited like pentazocine.
 Transnasal butorphanol is effective in relieving migraine and
postoperative pain.

45. Side effects
 Sedation, nausea and diaphoresis.
 Ventilatory depression is similar to that produced by
morphine.
 In patients with cardiac disease, it causes significant
increases in cardiac index,left ventricular end-diastolic
pressure and pulmonary artery pressure.
 Acute biliary spasm can occur but increases in biliary
pressure are less than after equipotent doses of fentanyl or
morphine.
 Uses:
 Long lasting painful conditions – cancer
 Postoperative pain
 Myocardial infarction

46.  Buprenorphine is a thebaine derivative,
 Approximately 33 times more potent than morphine
 Has 50 times higher affinity for µ- receptor than morphine.
 Given Sublingually or parenterally but not orally – high 1st pass
metabolism
 The onset of action of is slow, peak effect takes 3 hours, and its duration
of effect is prolonged (>10 hours).
Uses
 Analgesic component in balanced anesthesia.
 Excellent analgesic for relieving pain in the post operative period, cancer,
renal colic.
 Adjuvant for spinal and epidural analgesia. High lipid solubility limits
cephalad spread and delayed depression of ventilation.

47.  Adverse Effects:
 Hypotension,drowsiness, nausea, vomiting
 Pulmonary oedema has been observed in some patients
 In addicts – precipitates withdrawal syndrome.
 Respiratory depression (fatal in neonates) and cannot be reversed
by Naloxone

48.  Nalbuphine is an agonist-antagonist opioid structurally
related to oxymorphone and naloxone
 Agonist potency is equal to that of morphine at the κ-
receptor and antagonist potency at the µ-receptor is one-
fourth as much as nalorphine.
 Activation of supraspinal and spinal κ-receptors results
in limited analgesia, respiratory depression and sedation.
 Like other agonist-antagonist compounds, interferes with
the analgesia produced by pure µ-agonists.
 The onset of effect is rapid (5 to 10 minutes), and its
duration is long (3 to 6 hours).
 In contrast to pentazocine and butorphanol it causes no
significant changes in systemic, pulmonary arterial, and
pulmonary capillary wedge pressure. Hence can be used
for sedation and analgesia in patients with heart disease.

49. Uses
 As an analgesic supplement for conscious
sedation or balanced anesthesia
 Can be used to reverse the respiratory depression
of opioid agonists in the postoperative period
while maintaining analgesia.
Adverse Effects
 Sedation is the most common side effect.
 Withdrawal symptoms less than that of morphine
but greater than that of pentazocine.

50.  Naloxone , naltrexone, nalmefene
 Higher affinity for μ-receptors results in
displacement of the opioid agonists from the
receptor sites.

51.  Non-selective antagonist of all types of opioid receptors
Uses
 Treat opioid induced depression of ventilation in post-
operative peiod and in neonates due to maternal opioid
administration.
 Opioid overdose.
 Diagnostic- To confirm physical opioid dependence.
 In hypovolaemic and septic shock naloxone is useful to
promote myocardial contractility and inproves patient
outcome.
Adverse Effects
 Antagonizes analgesic actions of opioids.
 Nausea/ vomiting .
 Increased sympathetic nervous system activity- tachycardia,
hypertension, pulmonary oedema and cardiac
dysrhythmias.
 Administration of naloxone to an opioid dependent
parturient may produce acute withdrawal in the neonate.
 Antagonizes the depressant effect of inhaled anaesthetics.

52.  Highly effective orally and duration of action is
as long as 24 hrs.
Nalmefene
 6-methylene analogue of naltrexone.
 Equipotent to naloxone.
 Primary advantage is its longer duration of
action as compared to naloxone – as long as 24
hrs.
 Prophylactic administration decreases the need
for anti-emetics and anti-pruritic medications
in patients receiving opioid analgesics.

53. Analgesia
Sedation
Balanced Anaesthesia
Neuroleptanalgesia-Neuroleptanaesthesia
TIVA
High-Dose Opioid Anaesthesia for Cardiac Surgery
Monday, March 9, 2015 53
DEPT OF ANAESTHESIA MKCG
MEDICAL COLLEGE
Intrathecal Infusion

54. 1.Analgesia
 PCA using opioids is now the cornerstone of post-operative
analgesia.
 Morphine remains a rational choice for PCA therapy. However it
is slow in onset and does not allow rapid titration of effect.
 Meperidine (50-100) mg produces variable degree of pain relief
and not always effective in patients with severe pain.
 IV opioids can produce potent and short-lasting analgesia.
Bolus Dose Infusion Rate
Fentanyl 1-3 µg/kg 0.01-0.05 µg/kg/min
Alfentanil 10-20 µg/kg 0.25-0.75 µg/kg/min
Sufentanil 0.1-0.3 µg/kg 0.0015-0.01µg/kg/min
Remifentanil - 0.05-0.25µg/kg/min

55. 2.Sedation
 Morphine (0.75 µg/kg/min) is the most frequently used IV agent
in the ICU.
 Remifentanil (0.15 µg/kg/min) allows more rapid emergence
from sedation and earlier extubation while providing comparable
level of sedation.
3.Balanced Anaesthesia
 Opioid as a component of balanced anesthesia:
 Reduce post-operative pain and anxiety.
 Decrease the somatic and autonomic responses to airway
stimulation.
 Improve haemodynamic stability.
 Reduce the dose of sedative –hypnotic agents.
 Reduce the requirement of inhalational agents.
 Provide immediate post-operative analgesia.

56. Loading
Dose
Maintenance Dose Comments
Bolus Infusion
Fentanyl 2-6 µg/kg 25-50 µg/kg 0.5-5.0
µg/kg/hr
Risk of significant
depression of
spontaneous ventilation
Alfentanil 25-50 µg/kg 5-10 µg/kg 0.5-2
µg/kg/min
Propofol decreases
elimination clearance
and distribution
Sufentanil 0.25 -
2µg/kg
0.1 - 0.25
µg/kg
0.5-
1.5 µg/kg/hr
Remifentanil 1 - 2 µg/kg 0.1-1.0
µg/kg/min
During emergence and
post-operatively
alternative analgesia
should be administered
or low-dose infusion
continued

57. 4.Neuroleptanalgesia- anaesthesia
 Introduced by De Castro and Mundeleer.
 Neuroleptanalgesia is characterized by
 analgesia,
 absence of clinically apparent motor activity.
 suppression of autonomic reflexes.
 maintenance of cardiovascular stability.
 amnesia in most patients.
 Neuroleptanalgesia is achieved by:
 Major tranquilizer ( butyrophenone /phenothiazines) and
 Potent opioid analgesic (fentanyl)
 The addition of an inhaled agent, usually N2O, improves
amnesia and has been called Neuroleptanaesthesia.

58. 5.Total Intravenous Anaesthesia (TIVA)
 Useful when delivery of inhalational agents are compromised or
contraindicated.
 Most commonly an opioid is combined with another drug more
likely to provide hypnosis and amnesia.
 Combination of alfentanil and propofol produces excellent TIVA.
 Alfentanil: Provides analgesia, haemodynamic stability and blunting
of responses to noxious stimuli.
 Propofol: Provides hypnosis and amnesia and is anti-emetic.
Induction Maintenance
Alfentanil 25 to 50 µg/kg 0.5 - 1.5 µg/kg/min
Propofol 0.5 to 1.5 mg/kg 80 to 120 µg/kg/min

59. 6.High-Dose Opioid Anesthesia for Cardiac
Surgery
 Introduced as a stress-free anesthetic method for cardiac surgery.
 Opioids can be administered as the primary or sole anesthetic.
 First performed with morphine. However, fentanyl and sufentanil
were recommended later.
 Advantage of providing stable haemodynamics due to
 Lack of myocardial depressant effect.
 Absence of histamine release (fentanyl congeners)
 Supression of stress response to surgery.
 Several factors have diminished the popularity
 Lack of evidence substantiating any significant outcome benefit
 added drug costs.
 Trend toward “fast-track” approaches to cardiac patients.
 Possible awareness.
 Postoperative depression of ventilation.

60. Induction
Dose
Infusion Comments
Fentanyl 5-75 µg/kg 0.1 -1.0
µg/kg/min
Naloxone infusion with
individual dose titration is
needed for reversal.
Alfentanil 150 µg/kg
(+/-
thiopental)
2 to 12 µg/kg/min Associated with more
cardiovascular adverse
effects than is the case with
fentanyl and sufentanil.
Sufentanil 2 to 20 µg/kg 1.0 to 2.0 µg/kg/hr More rapid induction and
more stable haemodynamics
intraoperatively and
postoperatively.
Remifentanil 2 µg/kg
(+Propofol)
0.25 -0.5 µg/kg/min
(+ propofol,
3 mg/kg/hr)
Appropriate anaesthesia for
minimally invasive coronary
artery bypass surgery.
High incidence of muscle
rigidity.

61. 7.Intrathecal Infusion
 Administration of opioids into the epidural or intrathecal space
provides more direct access to the substantia gelatinosa of dorsal
horn of the spinal cord.
 Dose is substantially lowered than those required for oral or
parenteral administration.
 Intraspinal narcotics often are combined with local anesthetics.
This permits the use of lower concentrations of both agents.
 Produce dose-dependent side effects, such as itching, nausea,
vomiting, respiratory depression, and urinary retention.
 Use of lipophilic opioids reduces risk of delayed respiratory
depression .

62. Preoperative
1. Evaluation: Evaluation should include early recognition and
high index of suspicion.
2. Identification: Identify factors such as total opioid dose
requirement and previous surgery/trauma resulting in
undermedication, inadequate analgesia, or relapse episodes.
3. Consultation: Meet with addiction specialists and pain
specialists with regard to perioperative planning.
4. Reassurance: Discuss patient concerns related to pain
control, anxiety, and risk of relapse.
5. Medication: Calculate opioid dose requirement and modes
of administration; provide anxiolytics or other medications as
clinically indicated.

63. Intraoperative
1. Maintain baseline opioids (oral, transdermal, intravenous).
2. Increase intraoperative and postoperative opioid dose to
compensate for tolerance.
3. Provide peripheral neural or plexus blockade; consider neuraxial
analgesic techniques when clinically indicated.
4. Use nonopioids as analgesic adjuncts.
Postoperative
1. Plan preoperatively for postoperative analgesia; formulate
primary strategy as well as suitable alternatives.
2. Maintain baseline opioids.
3. Use multimodal analgesic techniques.
4. Patient-controlled analgesia: Use as primary therapy or as
supplementation for epidural or regional techniques.
5. Continue neuraxial opioids: intrathecal or epidural analgesia.
6. Continue continuous neural blockade.

64. After discharge
7. If surgery provides complete pain relief, opioids should
be slowly tapered, rather than abruptly discontinued.
8. Develop a pain management plan before hospital
discharge.Provide adequate doses of opioid and
nonopioid analgesics.
9. Arrange for a timely outpatient pain clinic follow-up or
a visit with the patient’s addiction specialist.

65. Transdermal Therapeutic System
 Fentanyl is available in a transdermal therapeutic
system.
 Advantages include no first-pass drug metabolism
by the liver; improved patient compliance,
convenience, and comfort; and consistent analgesia.
 In cancer pain, TTS fentanyl offers an alternative to
oral morphine.
 Use for postoperative analgesia is not recommended
due a high incidence of significant respiratory
depression.
 TTS fentanyl produces the same adverse effects as
other opioids.

66.  Iontophoresis: Technique by which drug
passage through the skin is augumented
with an external electric current.
 When in need of pain medication,patient
double clicks the button – 40 mcg of
fentanyl delivered over 10 minutes.
 Advantages
 Avoids the risk of complications from needle-related injuries and
infection.
 Pre-programmed electronics eliminate the potential for manual
programming errors and excessive dosing.
 Compact size of the system enables greater patient mobility after
surgery.

67.  Eliminates hepatic first-pass
metabolism and improves patient
comfort, convenience, and compliance.
 Opioids with high lipid solubility,
such as buprenorphine, fentanyl,
and methadone are readily absorbed
from sublingual mucosal tissues.
 Oral transmucosal fentanyl citrate
(OTFC) is a solid dosage form of Buccal Lozenge
fentanyl that consists of fentanyl
incorporated into a sweetened lozenge on a stick.
 OTFC may be ideally suited to treat breakthrough cancer pain
 In children it may be used to decrease pre op anxiety and
facilitate induction.

68.  Computer controlled
infusion pumps
(CCIP)
 Target conc. Set
instead of infusion
rate
 CCIP calculates
infusion rate from
target concentration
and delivers required
volume
 Therapeutic pl. conc
for a particular opioid
for a particular effect
needs to be known

69.  Combine the advantages
of continuous infusion with
flexibility of bolus doses
according to patient’s need.
 Activating a switch –
delivers bolus dose. Disposable PCA Pump with a switch
 Lockout interval:
Minimum time that would have to elapse
between two activations

70.  Administration of
background infusion
superimposed on
patient controlled
boluses.
 Help to maintain
plasma concentration
in between boluses.

71.  Opioids are widely used in the practice of
anaesthesia for pre-anaesthetic medication,
systemic and spinal analgesia and
supplementation of general anaesthetic agents.
 A proper understanding of the
pharmacokinetic and pharmacodynamic
properties of opioids, is essential for their
judicious use.
 New opioid delivery systems are continually
being developed. Such systems allow more
flexibility in providing analgesia, both inside
and outside the operating room.