Opioids in anesthesia,uses,side effects.

About opioids use in anesthesia

1. Moderator : Dr. Sobia SR Presented by: Dr. S haik Abdul Rahman PGT , First year, Department of Anaesthesiology . OPIOID ANALGESIA

2. Introduction 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-population of opioid receptors and produce at least some agonist effects. Opiate is the term used for drugs derived from opium.

3. History The first undisputed reference to opium is found in the writings of Theophratus in the third century. Arabian physicians were well versed in its uses and introduced the plant to the Orient. In 18 th century opium smoking became popular in the orient and its availability in europe led to considerable abuse. In 1806, Serturner isolated a pure substance in opium, which he named morphine, after Morphus the Greek god of dreams. By the middle of the 19 th century, the use of pure alkaloids, rather than crude opium preparations, began to spread throughout the medical world.

4. Classification On the basis of source Naturally occuring Phenanthrene : morphine, codein , thebaine Benzylisoquinoline : papaverine , noscapine , narcine . Semisynthetic Heroin Dihydromorphone , morphinone . Thebain derivatives : etorphine , buprenorphine . Synthetic Phenylpiperidine : meperidine , fentanyl , sufentanyl , alfentanyl , remifentanyl . Morphinan compounds : levorphanol , butorphanol . Diphenylpropylamines : methadone Benzomorphans : pentazocine .

5. classification On the basis of action Opioid Agonist Morphine Meperidine Fentanyl Sufentanyl Remifentanyl Alfentanyl Codeine Hydromorphone Oxymorphone Oxycodone Propoxyphene Methadone Tramadol Heroin Opioid agonist- antagonist Pentazocine Butorphanol Nalbuphine Buprenorphine Nalorphine Bremazocine Dezocine Opioid antagonist Naloxone Naltrexone nalmefene

6. Endogenous opioid peptides Endorphins: Primarily μ -agonist and also has δ -action. Enkaphalins : Derived from proenkephalin . Met-ENK and leu -ENK. Met-ENK- primarily μ and δ agonist and lue -ENK- δ agonist. Dynorphins : Potent κ agonist also have μ and δ action. Endomorphins : Binds to the μ receptor with high affinity and high selectivity

7. Opioid Receptors μ receptor κ receptor δ receptor Location μ 1- supraspinal μ2- spinal κ 1- spinal κ2- supraspinal Spinal supraspinal Effects Analgesia Respiratory depression Sedation Euphoria Miosis Bradycardia Hypothermia Physical dependence Spinal analgesia Dysphoria Sedation psychomimetic Spinal analgesia Affective behaviour( supraspinal ) Respiratory depression Agonist Morphine , Codeine, Fentanyl , Pentazocine ( weak), Endorphins Pentazocine , Dynorphins Enkephalins

8. Mechanism of opioid induced analgesia Supraspinal level : Opioids bind with receptors in rostroventral region of medulla and cause stimulation of off cells present there, thereby blocking nociceptive stimuli transmission. Spinal level : Opioid act with their receptors present in substantia gelatinosa of dorsal horn cells and inhibit the release of exitatory transmission. Cellular level : Opioids bind to receptors to stimulate G protien synthesis and inhibit adenylate cyclase thereby subsequent reduction of intracellular cAMP which causes opening of K+ channels producing hyperpolarization of membrane and suppression of N-type Ca 2+ channels decreasing exitability . At high concentration they can directly inhibit NMDA receptors.

9. Mechanism of action of μ -agonist in the spinal cord Presynaptic neurons Activation of opioid receptor decreases Ca2+ influx in response to incoming AP. Decrease in the level of neuroexcitatory transmitters like glutamate,NA,DA,5-HT. Post-synaptic neurons Increase in K+ efflux Resultant hyperpolarisation prevents propagation of AP

10. Terminology

11. Agonist

12. Morphine – The prototype opioid Pharmacological action Analgesia Produce strong analgesia without loss of conciousness . 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. Viceral pain is relieved better than somatic pain.

13. Sedation Drowsiness and indifference to surroundings. Inability to concentrate and extravagant imagination- colorful day dream. Apparent exitement . 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 and addicts sense of wellbeing, pleasurable floating feelings- euphoria In normal persons these sensations may be unpleasant in absence of pain- dysphoria .

14. Depression Pontine and medullary ventilatory centre- Both rate and depth of respiration is diminised . 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).

15. 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 corticosterioids , but no infertility. Increase ADH release- oliguria . CVS No direct action on the myocardium. Histamine release, depression of vasomotor centre and decrease in sympathetic tone of blood vessels may cause vasodilatation leading to hypotension. Cardiac work reduction due to consistent vasodilatation.

16. Pharmacokinetics Absorbtion and Distribution Well absorbed after IM administration with onset of actionin 15-30 min. Duration of action is about 4hrs. Variable absorbtion orally. IV administration results in wide distribution in visceral circulation. However CNS penetration is poor. Readilly crosses placental barrier- causing hypoxia and apnea 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 mu receptors produces analgesia and depression of ventilation. Excretion Via urine, plasma half life= 2-3 hrs Completely eliminated in 24 hrs. Elimination of morphine glucuronides may be impaired in patients with renal failure.

17. Therapeutic uses Analgesia Surgical analgesia, post operative analgesia, long bone fracture, burns. Myocardial infarction Palliative therapy in cancer. Viceral pains- pulmonary embolism, pleurisy, acute pericarditis . Other uses Pre anaesthetic medication. Acute left ventricular failure – cardiac asthma

18. Adverse effects Ventilatory depression- all μ receptor agonists cause dose dependent depression. Decrease brainstem sensitivity to co2 Decrease slope of the co2-ventilation response curve Increrase apnoeic thresold Decrease hypoxic drive to respiration Carotid body chemoreceptors are virtually abolised . Decrease in pontine and medullary centres involved in rhythmic respiration Signs Oxygen desaturation Obstructive apnea Periodic breathing resembling Cheyne -Stokes breathing. Slow respiratory rate

19. Cardiovascular system Orthostatic hypotension Bradycardia may be due to stimulation of vagal nuclei in medulla or direct depressant effect of morphine on the SA node. Central nervous system Sedation and mental clouding- sometimes dysphoria . skeletal muscle rigidity. Myoclonus Raised ICT Smooth muscle contraction Biliary colic Urinary retention bronchospasm

20. Nausea and vomiting Idiosyncrasy and allergy Tolerance and dependence Tolerance and dependance is the most common problem with morphine. Exhibited in most actions except constipation and miosis . It produces psychological and physical dependence. Withrawal may lead to drug seeking behaviour and may turn to morphine withrawal syndrome. It is characterised by anxiety, fear ,restlessness, diarrhoea, abdominal colic, delirium and convulsion. Treatment is methadone.

21. Meperidine ( Pethedine ) Phenylepiperidine derivative having structural similarities with that of local anaesthetic. Pharmakokinetics 1/10 th 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 muscle- less miosis , constipation and urinary retention. Less hitamine release – safer in asthmatics. Better oral absorption.

22. Clinical use: For labor analgesia and post operative analgesia. Effective for supression of post operative shivering. Adverse effect: 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 MAO inhibitors.

23. Fentanyl Phenylpiperidine derivative synthetic opioid structurally related to meperidine . Pharmacokinetics 75 to 125 times as potent as morphine. Rapid onset(2-5min) and shorter duration(1-2hrs) due to greater lipid solubility. Rapidly redristributed to inactive strorage sites such as fat and skeletal muscles. 75% of the initial dose undergoes first-pass pulmonary uptake

24. Clinical uses Analgesia : low IV dose 1-2 mcg/kg. Adjuvant to anaesthesia : (2-20 mcg/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 mcg/kg. Intrathecal fentanyl may be used to provide labour analgesia and as an adjuvant for spinal and epidural anaesthesia. Oral transmucosal fentanyl 5-20 mcg/kg may be used to decrease pre-operative anxiety and facilitate induction. Transdermal fentanyl patch delivering 75-100 mcg/hr may be used for treatment of chronic pain in cancer patients.

25. Adverse effects Similar to morphine. Persistent / recurrent respiratory depression. Carotid sinus baroreceptor reflex control is makedly 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 .

26. Fentanyl as a sole Anaesthetic Agent Advantages Lack of direct myocardial depressant effects. Absence of histamine release. Suppression of stress response to surgery. Disadvantages Failure to prevent sympathetic response to surgical stimulation. Possible patient awareness. Post operative ventilatory depression.

27. Sufentanil Pharmacokinetics Potency is 5-10 times that of fentanyl . Lipophilic nature permits rapid penetration into BBB and onset of CNS effects. Approx. 60% of the drug undergoes first pass pulmonary uptake. Extensive protein binding – mainly α 1 acid glycoprotein. Metabolism N – dealkylation - inactive metabolite. O – demethylation – desmethyl sufentanyl has 10% activity sufentanil . Extensively metabolised by hepatic microsomal enzymes. Context – sensitive half time is shorter than of alfentanyl for continous infusion upto 8 hrs due to large Vd .

28. Sufentanyl vs Fentanyl Longer analgesia and less ventilatory depression. More rapid induction. Earlier emergence and earlier tracheal extubation .

29. Alfentanyl Fentanyl analogue with lesser potency and short duration of action. Despite its lower lipid solubility it has a more rapid onset of action due to the higher degree of non-ionisation. It used to provide analgesia when the noxious stimulation is acute but transient as in laryngoscopy , tracheal intubation and performance of a retrobulbur block. Associated with a lower incidence of post operative nausea and vomiting. It is less preferred because of higher incidence of muscle rigidity.

30. Remifentanyl 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. Metabolized by non-specific plasma and tissue esterases . Safe in hepatic and renal failure. Not a substrate of pseudo- choline esterase. Blood – brain equilibrium time similar to alfentanyl .

31. Clinical use Short intense analgesia. Supressing transient sympathetic response to laryngoscopy of at risk patients. Intermittent administration as PCA during labor 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 ventilation. Dcreased BP and HR. Acute opioid tolerance.

32. Context sensitive half life Time taken for blood plasma concentration of a drug to decline by 50% 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 redristributed 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 redristribution will reverse and will slow the decline in plasma concentration.

33. initial phase late phase Central compartment Central compartment Peripheral compartment Peripheral compartment

34. Context sensitive half life

35. Tramadol 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 enhacing function of spinal inhibitory pathways. Efective both orally and IV ( 100mg=10 mg) Uses Effective for treatment of chronic pain. Can be used where NSAIDS are contraindicated. Short diagnostic procedures. Post operative shivering. Disadvanteges Seizures have been demonstrated. High incidence of nausea and vomiting.

36. Opioid agonist-antagonist

37. Opioid Agonist-Antagonist These drugs are agonist at κ , μ (partial or full) and δ and thereafter becomes Antagonist at μ 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 is present.

38. Pentazocine It is agonist at κ and δ receptors and antagonist μ receptors. Ceiling occurs in both analgesia and respiratory depression occur after 30mg to 70mg of pentazocine . Low abuse liability. However can precipitate withrawal symptoms in patients who have been administered opioids on a regular basis. Uses Moderately severe pain in injury, burns, trauma, and orthopedic manuevers .

39. Disadvantages Depresses myocardial contractility. Increases blood catecholamine levels thus increasing B.P, H.R, SVR , PAP , LVEDP. Inhibits gastric emptyng and GIT transit. High incidence of post operative nausea and vomiting. Limited analgesia. Partially antagonizes other opioids . Produces psychotomimetic effects.

40. Butorphanol Agonist-Antagonist opioid that resembles pentazocine . Compared to pentazocine its agonistic action is 20 times greater and antagonistic 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 been addictive potential than morphine or fantanyl . Intra-operative use is limited. Transnasal butorphanol is effective in relieving migraine and postoperative pain.

41. Side effects Sedation, nausea, and diaphoresis. Ventilatory depression is similar to that produced by morphine. In patients with cardiac disease,it causes significant increase 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 condition- cancer. Postoperative pain. Myocardial infarction.

42. Buprenorphine Buprenorphine is agonist at μ receptors in low doses and antagonist in high doses. It has highest receptor binding potential. It is 25 times more potent than morphine. Given sublingually or parenterally but not orally- high first pass metabolism. Ceiling effect is seen beyond 1.2 mg It is long acting: The effect of single use can last for 10 hrs. Uses Analgesic component in balance anaesthesia. Its local anesthetic properties make it a useful adjuvant to local anaesthetics for nerve blocks.

43. Adverse effects Hypotension, drowsiness, nausea, vomiting. Pulmonary oedema has been observed in some patients. In addicts- precipitates withrawal syndrome. Respiratory depression ( fatal in neonates) and cannot be reversed by naloxone .

44. Nalbuphine Agonistic potency is equal to that of morphine at the κ - receptor and antagonistic 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, it also interferes with the analgesia produced by pure agonist. The onset of effect is rapid ( 5-10 minutes), and its duration is long ( 3-6 hrs) 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.

45. Uses As an analgesic supplement for consious sedation or balance anaesthesia. Can be used to reverse the respiratory depression of opioid agonists in the postoperative period while maintaining analgesia. Adverse effect Sedation is the most common side effect. Withrawal symptoms less than that of morphine but greater than that of pentazocine .

46. Antagonist

47. Opioid Antagonist Naloxone , naltrexone , nalmefene . Higher affinity for receptors results in displacement of the opioid agonists from the receptor sites.

48. Naloxone Non selective antagonist of all types of opioid receptors. Uses Treat opioid induced depression of ventilation in post-operative period and in neonates due to maternal opioid administration. Opioid overdose Diagnostic – To confirm physical opioid dependence. In hypovolemic and septic shock naloxone is useful to promote myocardial contractility and improves patient outcome. Adverse effects Severe hypertension, tachycardia or even pulmonary oedema- naloxone causes sympathetic stimulation. Cerebral metabolic rate, oxygen consumption and blood flow is increased therefore increases ICT- naloxone has non specific analeptic effect. Nausea / vomiting.

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

50. Anaesthetic techniques using opioids Analgesia Sedation Balanced Anaesthesia Neuroleptanalgesia – Neuroleptanaesthesia . TIVA High-Dose Opioid Anaesthesia for cardiac surgery. Intrathecal Infusion.

51. 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 IV) produces variable degree of pain relief and not always effective in patients with severe pain. IV opioids can produce potent and short-lasting analgesia.

52. Bolus Dose Infusion rate Fentanyl 1-3 mcg/kg 0.01-0.05mcg/kg/min Alfentanyl 10-20 mcg/kg 0.25-0.75mcg/kg/min Sufentanyl 0.1-0.3 mcg/kg 0.0015-0.01 mcg /kg/min Remifentanil ---- 0.05-0.25 mcg/kg/min

53. Sedation Morphine (0.75 mcg/ kg / min) is the most frequently used IV agent in the ICU. Remifentanil ( 0.15 mcg / kg / min) allows more rapid emergence from sedation and earlier extubation while providing comparable levels of sedation.

54. Balance Anaesthesia Opioid as a component of balance anaesthesia: Reduce pre-operative pain and anxiety. Decrease the somatic and autonomic responses to airway manipulation. Improves haemodynamic stability. Reduce the dose of sedative-hypnotic agents. Reduce the requirement of inhaled anaesthetic agents. Provide immediate post operative analgesia.

55. Loading dose Maintainance Dose Bolus Infusion Fentanyl 2-6 mcg /kg 25-50 mcg every 15-20 min 0.5-5mcg/kg/hr Alfentanyl 25-50 mcg / kg 5-10 mcg/kg 0.5-2mcg/kg/min Sufentanyl 0.25- 2 mcg / kg 0.1-0.25mcg/kg 0.5-1.5mcg/ kg/hr Remifentanyl 1- 2 mcg / kg 0.1-1.0mcg/kg/min

56. Neuroleptanalgesia -anaesthesia Introduced by De Castro and Mundeleer . Neuroleptanalgesia is characterized by- Analgesia Absence of clinically apparent motor activity. Supression of autonomic reflexes. Maintainance of cardiovascular stability. Amnesia in most patients. Neuroleptanalgesia is achieved by: major tranquilizer ( butyrophenones / phenothiazines ) potent opioid analgesic ( fantanyl ) The addition of an inhaled anaesthetic agent , usually N2O, improves amnesia and has been called neuroleptanaesthesia .

57. Total Intavenous Anaesthesia(TIVA) Useful when delivery of inhalation 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 exellent TIVA. Alfentanil : provides analgesia, haemodynamic stability and blunting of responses to noxious stimuli. Propofol : provides hypnosis and amnesia and is anti-emetic.

58. TIVA Induction Maintainance Alfentanyl 25-50 mcg / kg 0.5-1.5 mcg/ kg/ min Propofol 0.5 to 1.5 mg/ kg 80 to 120 mcg /kg/ min

59. High Dose Opioid Anaesthesia for Cardiac Surgery Introduced as a stress-free anaesthetic method for cardiac surgery. Opioids can be administered as a primary or sole anaesthetic. First performed with morphine. However, fentanyl and sufentanyl were recommended later. Advantage of providing stable haemodynamics due to Lack of myocardial depression effect. Absence of histamine release ( fentanyl congeners). Supression of stress response to surgery. Several factors have diminised the popularity Lack of evidence substantiating any significant outcome benifit . Added drug costs. Trend towards “ fast track” approaches to cardiac patients. Possible awareness. Post- operative depression of ventilation.

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

61. 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 anaesthetic. This permits the use of lower concentrations of both the 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. Newer drug delivery system. 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 to high incidence of significant respiratory depression. TTS fentanyl produces the same adverse effects as other opioids .

63. Iontophoretic Transdermal Patch Iontophoresis : Technique by which drug passage through the skin is augmented with an external electric current. When in need of pain medication, patient double clicks the button- 40mcg of fentanyl delivered over 10 mins . Advantages Avoid the risk of complications from needle –related injuries and infection. Pre-programmed electronics eliminate the potential for manual programme errors and exessive dosing. Compact size of the system enables greater patient mobility after surgery.

64. Transmucosal Drug Delivery 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 fentanyl that consist 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 operative anxiety and facilitate induction.

65. Buccal Lozenge

66. Target Controlled Infusion ( TCI) Computer controlled infusion pumps ( CCIP) Target concentration is set instead of infusion rate. CCIP calculates infusion rate from target concentration and delivers required volume. Therapeutic plasma concentration for a particular opioid for a particular effect needs to be known

67. Patient Controlled Analgesia (PCA) Combine the advantages of continuous infusion with flexibility of bolus doses according to patient’s need. Activating a switch – delivers a bolus dose. Lock interval: minimum time that would have to elapse between two activations .

68. Conclusion 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 intra- oprative and post-operatively.

69. THANK YOU