Acute Pain Management

Transcription

1 Acute Pain Management Dr Zamil Karim MBBS, FANZCA,FFPMANZCA, FIPP

2 The journey to Acute pain management begins in the perioperative period. The evaluation and assessment occurs in the perioperative period and begins with the assessment of the patient. Patient expectation, beliefs - history- pain, opiate use, analgesic use Anaesthesia-LA, GA, Regional Procedure- minor, major, day stay, multistay Footer Text 2

3 The focus today will be predominantly on the use of opiates, orals and systemically in the management of acute postoperative pain. As the public becomes more aware of the incredible techniques that are now available to manage acute, chronic and cancer pain, the expectation that there will be painless surgery and postoperative recovery increases. We have a potent arsenal of modalities that can effectively minimize the patients postoperative pain Doing so prevents unnecessary patient discomfort, lengthy hospital stays, undue medical expenses, poor clinical outcomes and extensive utilization of already overburdened health care resources. Footer Text 3

4 Pathophysiology of Postoperative Pain Surgery represents a form of premediated injury to the body Provokes changes in the peripheral and central nervous system that must be dealt with therapeutically to define effective care and to positively influence outcome. The physical process of incision, traction, and cutting of tissues stimulates free nerve endings and specific nociceptors. The threshold for activation and the activity of these receptors is modified by the local release of chemical mediators of inflammation and sympathetic amines released within the surgical stress response. Substances such as bradykinin, serotonin and histamine both sensitize and stimulate the receptors whereas arachidonic acid derivatives only sensitize them. Footer Text 4

5 Inflammatory cascade Footer Text 5

6 Multimodal approach The multimodal approach of pain management utilizes the WHO ladder whereby there are three steps to the pain management triangle Simple analgesics NSAIDS opiates Footer Text 6

7 Some of the sites where these medication act on Footer Text 7

8 Today I will focus on the following Paracetamol NSAIDs and opioids Footer Text 8

9 Paracetamol Acetaminophen Only para-aminophenol in clinical use Does not inhibit the function of the cyclooxygenase enzyme outside the central nervous system. Selective COX inhibition in the CNS Reduces the COX oxidization, and so reduces function. May modulate the endogenous cannabinoid system through one of its metabolite AM404 Which inhibits the reuptake of the endogenous cannabinoid anandamide by neurons making it more available to reduce pain. Footer Text 9

10 Has a spectrum of action similar to that of the NSAIDs and resembles particularly the COX-2 selective inhibitors Inhibits the peroxidase function of the isoenzymes of the cyclooxygenases Inhibition of the phenoxyl radical formation from a critical tyrosine residue essential for the cyclooxygenase activity of the COX-1 and COX 2 and prostaglandin synthesis Footer Text 10

11 Paracetamol Pharmacokinetics Oral,iv and rectal Oral bioavailability % Hepatic metabolism Renal excretion Over dose hepatic toxicity Dose Footer Text 11

12 Nonsteroidal anti-inflammatory drugs Selective and non selective Spectrum of analgesic, anti- inflammatory and anti pyretic effects Effects mediation by the inhibition of prostaglandin synthesis in the peripheral tissues, nerves and the CNS NSAIDs exert their effect by the inhibition of the enzyme cyclooxygenase, the enzyme that makes PGs There are two types of COXs COX1- constitutive- physiologic function inflammation - COX 2 inducible made during Footer Text 12

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14 Nonselective antiiflammaotory medication Brufen Voltaren Footer Text 14

15 Selective COX 2 Inhibitors Celecoxib Paracoxib Meloxicam Footer Text 15

16 Opiates Morphine Pethidine Fentanyl Hydromorphone Onynorm Oxycontin Targin Tramadol immediate and sustained release Tapentadol Buprenorphine Footer Text 16

17 Morphine Gold standard opiate Agonist at mu and kappa receptor Increase intracellular calcium concentrations, which increases potassium conductance and hyperpolarization, which inturn decreases membrance excitability. Footer Text 17

18 Morphine Well absorbed orally Bioavailability 15-20% (extensive first pass metabolism 20-40% protein bounding Hepatic metabolism Morphine3- glucuronide and morphine6- glucuronide M-6-G active metabolite Urinary excretion of the glucuronides Not removed by hemodialysis or peritoneal dialysis Footer Text 18

19 Fentanyl Tertiary amine which is a synthetic phenyl piperdine Highly selective mu agonists 80 times more potent than morphine Highly lipid soluble Action within 2-3 minutes Duration minutes but higher dose up to 6 hours High protein binding 94% Short duration of action after single dose is due to redistribution not metabolism Metabolism due to N-dealkylation to norfentanyl 10 % excreted unchanged in urine Footer Text 19

20 Pethidine Synthetic phenylpiperidine derivate Less in use now Mu and kappa agonist Oral bioavailability 45-75% Extensive first pass metabolism High bioavalabilty when administered IM into the deltoid (100%) Used more in Labour Metabolism by N-demethylation to norpethidine and then hydrolysis to pethidinic acid Norpethidine may accumulate in renal failure and has a 50% analgesic activity and convulsant properties Urinary excretion May precipitate severe hypertensive crisis in patients who are receiving MAOIs Footer Text 20

21 Hydromorphone Hydrogenated, semisynthetic potent mu opioid receptor agonist Weak kappa activity 5-10 times more potent than morphine Altered chemical structure so that enhanced distribution in the CNS Control release formulation Constant plasma concentration throughout the 24 hour period Controlled release from a matrix so minimal effects from food and alcohol Good oral absorption Faster onset of action than morphine Same side effect profile as morphine Footer Text 21

22 Oxycodone semisynthetic analgesic derived form the opium alkaloid thebaine Mu and kappa activity High oral bioavailability Twice as potent as morphine Immediate release and slow release formulation Parent drug is the active component Onset of analgesia within 15 minutes after ingestion so a good oral choice in Acute pain management Plasma half life is 3-5 hours Stable levels are reached in 24 hours Effect lasts for three to four hours Footer Text 22

23 Oxycodone Oral bioavailability 60-87% Protein binding 45 % Hepatic metabolism and renal excertion 2 main metabolites- oxymorphone potent analgesic And noroxycodone weak analgesic Structurally different form morphine so less first pass metabolism so greater bioavailability Less immunosuppression than other opiates Antinociceptive thru kappa receptor Footer Text 23

24 Oxycontin Prolonged release formulation that can be taken 12 hourly Onset of analgesia within 1 hour of consumption Hepatic metabolism and renal excretion Should not be crushed as it may result in a toxic dose because of the rapid release of the drug Dose should be reduced and adjusted in patients with impaired renal function( creatinine clearance < 60ml/minute ) Dose also reduced in hepatic dysfunction Footer Text 24

25 Targin Oxycontin combined with naloxone Ratio 2:1 Oral sustained release formulation Naloxone component is hepatically extracted during first pass metabolism (>97%) Naloxone binds to the gut mu receptor hence reducing the GIT side effects Similar onset and offset to Oxycontin but the formulation has constant release of the opiate during transit along the large intestine Can be used like Oxycontin once return of bowel function Footer Text 25

26 Tramadol Centrally acting analgesic that is structurally related to codine and morphine Two enantiomers that contribute to analgesia via different mechanisms + Tramadol and the metabolite O-desmethyl tramadol are agonist at the mu receptor + Tramadol inhibits serotonin reuptake and - tramadol inhibits noradrenaline reuptake enhancing the inhibitory effects on pain transmission in the spinal cord. After oral administration it is rapidly and almost completely absorbed Sustained release formulation release drug over 12 hours and have a bioavialaibility of 87-90% Footer Text 26

27 Tramadol Metabolised by O and N demethylation and by conjugation reaction forming glucuronides and sulfates Mainly renal excretion Half life 6 hours Analgesic potency of about 10% of morphine Footer Text 27

28 Buprenorphine Semi synthetic oripavine alkaloid derived from thebaine Partial opioid receptor agonist Binds to the mu receptor with great affinity but has a low intrinsic activity ( the rate of dissociation from the mu receptor slow) Kappa receptor binding This results in an antagonistic effect on any other opioid that may be coadministered with buprenorphine Analgesic activity at 5-10% receptor occupancy Onset within 5-15 minutes after iv administration minutes after sublinguinal Uses analgesia, opiate tolerant patient, opioid dependence treatment and chronic pain Footer Text 28

29 Buprenorphine Hepatic and gut metabolism and the majority of the dose is excreted by the gut 15 % of the original is excreted in the urine Buprenorphine also transdermal patches High potency Low molecular weight Lipophilic drug Patch provides steady delivery for 7 days, steady state achieved during the first application After removal of the patch the concentrations decline approximately 50% in 12 hours Ceiling effect with respiratory depressant effect Footer Text 29

30 Buprenorphine Sublinguinal PCA Intramuscular Transdermal patches Doses SL 200 to 400micrograms 2-4 hourly PCA 1800mg in 94 ml saline with 20 microgram boluses Footer Text 30

31 Tapentadol Central acting mu opioid agonist and noradrenaline reuptake inhibitor Two formulation- immediate release and sustained release formulations The mu opioid receptor agonism of the afferent pain fibers inhibits the release of excitatory neurotransmitters and reduces the upward transmission of the pain signals The effects on the brain include an influence on the release of neurotransmitters by the descending pain pathways providing further inhibition of pain The noradrenaline reuptake inhibition has an antinociceptive effect via the descending pain pathways by reducing pain signals to the brainvia effects on the alpha 2 receptors Footer Text 31

32 Tapentadol Despite its mu opioid binding that is nearly 50 times lower than morphine its analgesic potency is only 2-3 times lower Fast oral absorption but bioavailability is 32 % due to extensive first pass metabolism 20 % protein binding Half life 5 hours, steady state in hours Extensive hepatic metabolism- uridine diphosphate glucuronosyltransferase- to tapentodol- o -glucuronide Moderate hepatic dysfunction warrants dose reduction ansd not recommended in patients with severe hepatic dysfunction. Footer Text 32

33 suboxone Combination of buprenorphine with naloxone in a combination of 4:1 Usually daily dose Buprenorphine is a partial agonist at the mu receptor with a high binding affinity There is little free receptor availability so that additional pure opioid agonists impart no additional benefit The long half life results in stable blood levels and so is better in OST In some patients better analgesia is obtained from the splitting of the medication but if patients are on Suboxone, then ideally the patient needs to stop this during hospital admission to allow receptor accessibility for opioids used in Analgesia The issue is that some patients can relapse and this approach is advised with caution Once again the preop consultation is very important- history. Rapport and a plan to do this in a structured manner All of these need to be communicated to the patients prescriber Footer Text 33

34 Methadone Synthetic opioid medication best known for its use in the treatment of opioid dependence Effective analgesia with increased efficacy in neuropathic pain,. Recaemic mixture of cis and trans Acts on th mu opioid receptors centrally and peripherally Action on the NMDA receptor Fat soluble drug with good oral bioavailability (60-70% Time to peak concentration-1-5 hours Analgesic effect within 30 minutes and may last for up to 6 hours High plasma protein bounding Widely distributed to tissues and with continuous use tissue levels may exceed levels in plama. This extensive protein and tissue binding is responsible for the long plasma half life with continuous use Footer Text 34

35 Methadone Hepatic metabolism Less than 10% extraction by first pass Parent drug and metabolites also excreted in urine and faeces. Age does not affect clearance so no dose adjustment is required in those over 65 For patients with renal disease the faecel excretion will increase and so no dose adjustment is required Footer Text 35

36 Substance use disorder Maintance opioid agonists do not provide adequate analgesia as tolerance counterbalances any analgesic effects Single daily dose does not provide an effective analgesic profile For analgesia the medication will need to be delivered every 6-8 hours Issues Opioid induced hyperalgesia Tolerance Footer Text 36

37 ketamine NoncompetItive N- methyl-d-aspartate (NMDA) receptor antagonist Attenuates central sensitization and hyperalgesia and thereby reduces postoperative tolerance Recent evidence has shown that ketamine at sub anaesthetic doses reduces postoperative opioid consumption 0 to 48 hours postoperatively and reduced pain 6 weeks after surgery in opioid dependent patients (21) Dose range in this cohort include a range from 0.1 to 0.5 mg /kg at induction and or maintaining a infusion for the duration of surgery. Infusion range from mk/kg per hour. Bolus doses can also be used in the PACU 0.1mk/kg Larger doses may result in the onset of visual hallucination and dysphoria. Footer Text 37

38 Ketamine Nielsen reported the using this regime of a bolus at induction followed by a infusion resulted in a better pain score in the PACU and that the overall morphine consumption was significantly reduced In chronic pain patients, there was a reduced pain score reporting at 6 months again demonstrating the beneficial effect of the ketamine Ketamine can be combined with a PCA to improve the analgesia in a difficult patient Ketamine also has a role in chronic pain where there are case reports of the beneficial effect of day stay infusions and multistay infusions on patients chronic pain. Side effects at these low doses are minimal and can be managed by reducing the infusion rate. Footer Text 38

39 Lignocaine Local anaesthetics are drugs that produce reversible conduction blockade of impulses along peripheral and central nerve pathways Meta-analysis by Marret et al in the British Journal of surgery 2008 looked at IV lignocaine for enhanced recovery after surgery. Conclude that IV bolus and infusions of lignocaine did the following -reduced duration of ileal dysfunction -reduced length of hospital stay -reduced post operative pain and - reduced the incidence of post operative nausea and vomiting Footer Text 39

40 Lignocaine- How IV bolus 100mg and then infusion at 2mg/kg for 24 hours Variation for the above was 1.5mg/kg for one hour post op Variation 3mg/kg for the duration of the surgery and ceasing the infusion prior to recovery. Chang published in Pain 2017, vol 17- the safety and enhanced recovery after breast surgery He looked at different protocols and different rates of infusion and duration of infusions Conclusion was that in the immediate postop period there were lower pain scores and that opioid consumption was less but the groups were not large enough so the results were not conclusive in breast surgery. Footer Text 40

41 Preempetive analgesia Defined as an antinociceptive treatment that prevents the establishment of altered central processing of afferent inputs which amplifies postoperative pain By decreasing the altered central sensory processing, preemptive analgesia is thought to consequently decreases the incidence of hyperalgesia and allodynia after surgery Metaanalysis by Ong in Anaesthesia and Analagesia 2005 concluded that preemptive analgesia showed an overall beneficial effect in selective analgesic regimes that was most pronounced after epidural analgesia, local wound infiltration and systemic NSAID administration Footer Text 41

42 The overall reduction in the case of supplemental analgesia in this group was reported to be og the magnitude of up to % Also with the use of preemptive analgesia techniques the time to first analgesia use was also significantly prolonged The use of NMDA agonists and opiates did not yield results that was consistent enough to draw a positive conclusion for the favorable effect of the preemptive analgesia. Prolonging the time to the first analgesia request meant that the analgesic duration had outlasted the pharmacological duration of the action of the drug This is the technique of increasing the duration of the analgesia without increasing the dosage or dosing frequency. Footer Text 42

43 This then would translate to less pain, less total analgesic consumption and better patient comfort The difference in the efficacy of the individual analgesic intervention for a preemeptive effect maybe due to a degree of sufficiency of the afferent blockade, the nature of the pain and its inflammatory component. Preemptive analgesia cannot be effective if the analgesic intervention is not adequate The analgesic intervention needs to produce sufficiently dense and prolonged duration of blockade for them to block the transmission of noxious afferent information from the periphery to the spinal cord and brain. In this respect it appears that systemic opiates do not provide a sufficiently dense and long duration of blockade od spinal nociception to prevent central sensitization. Epidural on the hand can hence their role in preemeptive analgesia. Footer Text 43

44 What are some techniques to decrease opioid use Dexmedetomidine- alpha 2 adrenoreceptor agonist that possesses sedative and anxiolytic properties Stimulation of the alpha 2 adrenoreceptors located at the dorsal horns of the spinal cord and locus coeruleus Dose microgram /kg Footer Text 44

45 Clonidine- alpha 2 adrenoreceptor agonist, 8 times less selective than demedetomide Multiple formulations that can be used Ketamnie Dextromethorphan- NMDA receptor antagonist Oral or IM preoperative Dose in mg oral, mg im Footer Text 45

46 Gabapentonoids- alpha 2 delta subunits of the calcium channels, decreasing the release of the excitatory neurotransmitters Reduce postop pain and opioid consumption However recent metanalysis concluded that the effect of this was over estimated There was no difference in the opioid consumption following single or repeated dosing with the use of pregablin Footer Text 46

47 Duloxetine- oral serotonin and noradrenaline reuptake inhibitor Analgesic effect derived from the modulating effect on descending inhibitory pain pathways in the brain and spinal cord Dose 60mg /day TCA- effect by suppressing the central pain sensitization through the inhibition of reuptake of noradrenaline and serotonin as well as antagonism of peripheral sodium channels and spinal NMDA receptors. Footer Text 47

48 My View:Acute Pain Management Move beyond the pain score Multimodal analgesia is at least two non opioid agents with opioids as adjuncts Reconsider the role of opioids Enhanced Recovery Pathways should be standard practice when possible Footer Text 48

49 So what should the plan be with regards to postoperative Paracetamol NSAID if no contraindication Opiate oral if appropriate, choice doesn t matter LA if possible Footer Text 49

50 So what do I do? Caesarean section Knee and hip joint replacement Fractured ribs Upper limb fractures Shoulder surgery Lap choles Footer Text 50

51 What do I do? Opiate tolerant patient illicit drug use for acute surgery Methadone maintance patient Footer Text 51

52 College statement regarding long acting opioids? MY VIEW There is a place but one needs to choose where There needs to be a weaning plan and this needs to be communicated to the relevant care providers The role of assessment in the context of analgesia will in my opinion reduce the risk associated with the use of long acting opiates in pain management. Footer Text 52

53 So in conclusion the Acute pain management cycle commences in the preoperative period and continues in the postoperative period The choice of analgesia, many as they are is best decided by factoring in the mentioned issues including surgery type, patient characteristics and the expected duration of noxious stimulation. The multimodal approach provides the best evidence available for good and effective postoperative analgesia. I conclude with the remarke that a poorly responsive nociceptive pain could have components of neuropathic pain and that this is not a patient who is just seeking more opiates. Footer Text 53

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