This presentation will cover several areas starting theoretically and moving through to practical application



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Tramadol:

  • Moderate affinity ì receptor agonist.

  • Acts on spinal modulating pathways

    • Inhibition of neuronal NA and Serotonin uptake

    • Stimulation of presynaptic serotonin release

  • Adverse Effects:

    • Nausea & Vomiting

    • Ondansetron interferes with analgesic effect

  • Non addictive, less sedation

  • Dose: 3 mg/kg IM/IV/PO for moderate to severe pain



Buprenorphine:

  • Semisynthetic, Agonist-Antagonist

  • Routes of administration:

      • IV, IM, Neuraxial, SC, SL, Trasdermal

  • Useful in morphine intolerant patient

  • Ceiling effect for respiratory depression, but not for analgesia.

  • Antiflammatory action

      • Useful in intra-articular injections

  • Prolongs duration of analgesia in peripheral nerve blocks with LA

Methadone:

  • Synthetic broad spectrum opioid

      • Mu receptor agonist

      • NMDA antagonist

      • Inhibitor of monoamine transmitters

  • Useful in treatment of neuropathic pain

  • Orally well absorbed

  • No dose adjustment in renal disease

  • Drug most commonly used for opioid rotation

NSAIDs


Mechanism of Action

Inhibition of Cyclo-oxygenase enzymes (type 1 & 2)

Reduce concentrations of PGE2 :

Sensitise peripheral nociceptors to histamine and bradykinin

Centally Increase Substance P and Glutamate Increase sensitivity of second order neurons Decrease

NTs from descending pathway



Benefits:

  • Opioid Sparing

  • Reduced incidence of opioid side effects

  • Anti-inflammatory effects

Adverse Effects:

  • Platelet Dysfunction

  • Gastrointestinal Ulceration

  • Nephrotoxicity

  • Impaired bone healing

  • Hypersensitivity


α2 Adrenergic Agonists

Primarily preoperative and intraoperative use



Clonidine:

  • α2 agonist, α2: α1 biding 220:1

  • PO, IV, TD, Neuraxial routs

  • Reduced postoperative opioid requirement

  • SE: Sedation, Bradycardia, hypotension



Dexmedetomedine:

  • Superselective α2 agonist: α2:α1 binding 1620:1

  • Supraspinal, Spinal & Peripheral action

  • No respiratory depression

NMDA Antagonists

Ketamine:

  • NMDA receptor antagonism theoretically reduces central sensitisation, hyperalgesia and opioid tolreance

  • Currently role in postoperative pain relief is uncertain

    • Insignificant difference in pain

    • Clinically insignificant opioid sparing

    • Psychomimetic side effects – hallucination, nighmares

Neuraxial Analgesia: Epidural Analgesia

  • Superior to systemic opioids

  • Efficacy determined by

    • Catheter-incision site congruency

    • Choice of analgesic drugs

      • LA+Opioid

    • Rates of infusion

    • Duration of epidural analgesia

      • At least 2-4 days

    • Type of pain assessment

      • Dynamic Vs Rest






Recommended catheter insertion sites




Location of incision

Examples of surgical procedure

Congruent epidural placement

Thoracic

Lung reduction, Radical mastectomy

Toracotomy, thymectomy



T4-T8

Upper Abdominal

Cholycystectomy, esophagectomy, gastrectomy, hepatic resection, whipple’s

T6-8

Middle Abdominal

Cystoprostatectomy, nephrectomy

T7-T10

Lower Abdominal

AAA repair, Colectomy, TAH, Radical prostatectomy

T8-T11

Lower Extremity

Femoral-Popliteal bypass, THR, TKR

L1-L4


Local Anaesthetics comparison Opioids:

Local Anaesthetics

  • Act on spinal nerve roots,dorsal root ganglion or spinalcord itself.

  • High incidence of motor block

  • Hypotension

  • Sign

Significant failure rate due to regression and inadequate analgesia

Opioids:

  • Site of action:Lipophilic: systemicHydrophilic: spinal

  • Cathetre-Site congruencynot essential

  • No motor blockade

  • No hypotension

  • Analgesia superior to systemic opioids




Differences between lipophilic and hydrophilic opioids




Property

Lipophilic Opioids

Hydrophilic Opioids

Common Drugs

Fentayl, Sufentanyl

Morphine, Hydromorphone

Onset of analgesia

Rapid (5-10 min)

Delayed (30-60min)

Duration of analgesia

Shorter (2-4 Hrs)

Longer (6-24 hrs)

CSF Spread

Minimal

Extensive

Site of action

Spinal ± Systemic

Spinal

Side Effects

Lower nausea and vomiting, pruritus

Early respiratory depression



Nausea & vomiting, pruritus

Early (<6 Hr) and Delayed (> 6 Hr) respiratory depression



Local Anaesthetic-Opioid Combinations

  • Additive Effect

  • Superior analgesia, including dynamic pain relief

  • Limits regression of sensory blockade

  • Decreased LA dose requirement

  • Analgesia superior to IV PCA with opioids

Adjuvants:

  • Clonidine: 5-20 μg/Hr Dose dependent hypotension, bradycardia

  • Epinephrine conc. Of 2.5 μg/ml

  • Ketamine Theoretically useful in attenuating central sensitisation



Hypotension

0.7 – 3 % with epidural LAs




Epidural Analgesia: Adverse Effects

Motor Block

2 – 3 % with epidural LAs

More with cathetre-incision incongruence

Resolves within 2 hours of stopping infusion

If persistant, think of Spinal hematoma/abscess, cathetre migration



Nausea & vomiting

20 – 50 % with single dose neuraxial opioid

45 – 80 % with continuous opioid infusion

Dose depdndent. Due to cephalad migration

Less with fentanyl than morphine

Treated with Naloxone, Ondansetrone, Droperidol, Metoclopramide, Dexamethasone


Pruritus

60% with Opioids; 15-18 % with LAs

Due to cephalad migration and activation of trigeminal nucleus. ?? Itch centre

Treated with Naloxone, Droperidol


Respiratory Depression

Incidence 0.1 – 0.9 % with opioids

Equivalent to systemic administration of opioid

Early < 6 hr, Delayed > 6 hr

Delayed depression with Morphine. Due to cephalad spread

Risk Factors: Increasing dose, increasing age, concomitant sedatives, prolonged and extensive surgery, thoracic surgery

Treatment: Naloxone 0.5 – 5 μg/kg/hr



Urinary Retention

Higher than with systemic opioids

10 – 30% with epidural Las

Higher with higher infusion rates of LA


Benefits: (LA based epidurals)

  • Better attenuation of stress response to surgery

  • Earlier return of GI function without contributing to bowel dehiscence

  • Decreased postoperative pulmonary complications

  • Decreased incidence of postop MI with thoracic epidural

  • Better postop analgesia

Risks:

  • Higher incidence of spinal hematoma with LMWHs

  • Infections: Meningitis, Spinal Abscess (1/10000 with catheter < 4 days)

  • Superficial cellulitis: 4-14 %

  • Catheter migration: Intrathecal, Intravascular, subcutaneous



Drug

Dosing

Comments

Clonidine

15-45 μg

Improves quality of blockade

Epinephrine

0.1-0.6 mg

Prolongs motor block & urinary retention

Neostigmine

6.5 – 50 μg

Motor blockade

Nausea & vomiting



Opioid

Dose

Fentanyl

5-25 μg

Sufentanyl

2-10 μg

Morphine

0.1-0.3 mg

Diamorphine

1-2 mg

Pethidine

10-30 mg



Peripheral Regional Analgesia

  • Pain control superior to systemic opioids

  • Fewer side effects compared to systemic opioids

  • Fewer neurologic and infectious complications compared to neuraxial block

  • Prolonged duration

  • Single injection and continuous catheter techniques

Indications of peripheral Nerve Blocks





Pain control superior to systemic opioids

Fewer side effects compared to systemic opioids

Fewer neurologic and infectious complications compared to neuraxial block

Prolonged duration

Single injection and continuous catheter techniques

Pain control superior to systemic opioids

Fewer side effects compared to systemic opioids

Fewer neurologic and infectious complications compared to neuraxial block

Prolonged duration

Single injection and continuous catheter techniques

Pain control superior to systemic opioids

Fewer side effects compared to systemic opioids

Fewer neurologic and infectious complications compared to neuraxial block

Prolonged duration

Single injection and continuous catheter techniques


Pain control superior to systemic opioids

Fewer side effects compared to systemic opioids

Fewer neurologic and infectious complications compared to neuraxial block

Prolonged duration

Single injection and continuous catheter techniques


Peripheral Nerve Block

Indication

Lumbar plexus

Surgery of knee

Femoral Nerve

TKA, ACL repair, femoral neck fracture, saphenous vein stripping, muscle biopsy of anterior, medial or lateral thigh

Sciatic Nerve

AK amputation (combined with lumbar plexus block

Ankle replacement, arthrodesis

Calcaneal osteotomy

Achilles tendon repair



Popliteal Fossa

BK amputation (combined with saphenous nerve block)

Ankle surgery: Triple arthrodesis, Achilles tendon repair

Foot surgery: Bunion surgery, Transmetatarsal amputation


Paravertebral Block:

  • Suited for thoracic, breast surgery, VATS, cholecystectomy, nephrectomy etc

  • Used to treat rib fracture pain

  • Potential space, contains anterior and posterior ramus of the spinal nerve root with white and grey rami communicantes

  • Single injection or continuous catheter technique

  • Comparable to thoracic epidural blockade

  • No hypotension, PONV, urinary retention

Other Techniques:

  • Rectus Sheath Block

  • Transversus abdominis plane block

  • Placement of continuous wound catheter

  • Continuous intra-articular infusion of LA

  • Periarticular soft tissue injection of LA

  • Intrapleural or Intraperitoneal Analgesia



Complications:

  • Intravascular injection

  • Unintentional neuraxial spread

    • Scalene block

    • Lumbar plexus block

    • Paravertebral block

  • Nerve Damage

    • Incidence 1:10000 – 1:30000

    • Significant nerve damage 1:1 00 000

    • Direct injury, hematoma, infection, ischemia

    • >90% recover within 1 week

    • 92 -97% within 4-6 weeks, 99% within 1 year


Slide (28) 32 So what does pain management look like at BHS

The follow



  • Are statistics from our APS & Operational statistics

  • Our PACU APP

  • And a discussion of the drugs, & how they’re used currently @ BHS & those around the corner

Slide (29) 33 BHS Statistics

Slide (30) 34 Some Innovation in care

Different ways of administering L.A.



Adjunctive therapies

Old drugs used differently

    • Gabapentin : Used pre operatively: Opioid sparing effect during the first 24 hours after a single 300 to 1,200 mg dose of gabapentin, administered one to two hours preoperatively, ranged from 20 percent to 62 percent (2)

New: Adjunctives ie Capsaicin cream (used for centuries in the east)

Narcotics Different routes Topical

Old :Narcotic’s Buprenophine patch (<3D:7D/S/C Fat to metablosie Heat 25 - 50% increase/pressure increase, 3 week site rotation

APP doing

New Targin: Oxycodone/Narloxone (10/5mg) oral

Tapentadol: Oxycodone/Noradrenaline oral
Slide (31) 35 APP BHS

Slide (32) 36 Some Adjunctives Pharmogolygt

Anticonvulsants: Gabapentin

  • Ideally if anticonvulsants are considered they are best admninstered preoperatively (6)

  • Gabapentin binds to the alpha-2 delta sub-unit of the presynaptic voltage gated-calcium channels responsible for the inhibition of the calcium influx.(2)prevents release of excitatory neurotransmitters in Pain Pathway

Pregablin is similar to gabapentin but has a superior pharmacokinetic profile its many potential actions such as reducing opioid requirements, prevention & reduction of opioid tolerance, improvement of the quality of opioid analgesia, decreased respiratory depression, relief of anxiety, and gastric sparing make it an attractive drug to consider for control of pain in the post operative period



Slide (33) 37

Magnesium :30–50 mg/kg,

    • followed by 7–15 mg/kg/h IV

    • In the Peripheral Nervous System it interferes with the release of neurotransmitters at all synaptic junctions & potentiates the action of local anesthetics(3)

  • Peripheral nervous system: interferes with the release of neurotransmitters at all synaptic

  • junctions & potentiates the action of local anesthetics.[40]

  • At the neuromuscular junction, magnesium concentrations of 5 mmol/L cause significant

  • presynaptic neuromuscular blockade and enhance the action of the nondepolarizing muscle relaxants.[40]

  • It can precipitate severe muscle weakness in patients with Eaton-Lambert syndrome, patients with myasthenia gravis, or patients pretreated with a small dose of a defasciculating agent.[40] Magnesium prolongs the action of depolarizing neuromuscular blocker drugs (e.g., succinylcholine); administration before the use of succinylcholine prevents the release of potassium provoked by the neuromuscular blocking drug (see  Chapter 29).

  • Magnesium has several important pharmacologic actions.

  • Its route of elimination is renal, and any patient who is oliguric or in a reduced urine output state requires downward dosing adjustment of magnesium therapy.

  • Magnesium should be regarded as a cardiovascular drug, first and foremost, with calcium antagonistic and antiadrenergic properties that may be accompanied by minimal myocardial depression.[40] (millers)

Slide (34) 38

NSAID’s Cox 2 :

Recent research indicates that, in addition to peripheral blockade of prostaglandin synthesis, central inhibition of cyclooxygenase-2 may play an important role in modulating nociception. Although nonspecific NSAIDs provide analgesic efficacy similar to coxibs, their use has been limited in the perioperative setting because of platelet dysfunction and gastrointestinal toxicity. Coxibs may be a safer alternative in that setting. Both coxibs and traditional NSAIDs may contribute to a dose-dependent increase in cardiovascular toxicity and impaired osteogenesis benefits of coxibs include improved quality of analgesia; reduced incidence of GI side effects & no platelet inhibition (note Cox 1 & 2: Ketorolac )



Paracetamol

Is antipyretic & analgesic but has little, if any, anti-inflammatory action.

Its analgesic action is believed to be inhibit COX-3. At the spinal cord level, it also antagonize neurotransmission by NMDA, substance P, and nitric oxide pathways IV 100 ml: 10 mg/ml @ 15/60min; Onset of action <5 -10/60, peak at 1- 2hrs (6hrly order)


Slide (35) 39

Central alpha2 agonist Clonidine: Its sedative, pro-anesthetic, and pro-analgesic effects ability to blunt the central sympathetic response by as yet unknown mechanism(s). It also minimizes opioid-induced muscle rigidity, lessens postoperative shivering, causes minimal respiratory depression, and has hemodynamic stabilizing effects(2)
Slide (36) 40 L.A. Some innovations in care

Different ways of administering: Intavenous LA: acts a membrane stabilizer (reversibly block the Na channels of the lipid membranes & prevent sudden influx of sodium ions into the axon, blocking depolarization & the action potential. (2009 Mosby: Marx: Rosen’s emergency medicine)


Increase Regional LA use: continuous or intermittent bolusing (new research suggest higher efficacy than continuous infusion Epidural PCA & TAP; femoral; wound; elastomeric pump e.t.c

PAIN BUSTER device elastomeric pump. An elastomeric pump is a device that has a distensible bulb inside a protective bulb with a built-in filling port, delivery tube, and bacterial filter LA and anti inflammatory medication use

Acupuncture (2) perioperative acupuncture might be a useful adjunct for acute postoperative pain management. However, there are issues with

applicability and generalizability of the procedure



Different ways of administering
R&D LA: basically two overarching approaches for prolongation of local anesthetic action. One is the use of novel delivery techniques for existing drugs. In an endeavor to “make old drugs new” [51], liposome or polymer encapsulation of local anesthetics are being formulated. The second approach is the development of novel, extremely long-acting local anesthetics; road toward achieving this goal may be long and winding, due to problems of these drug delivery systems, such as shelf life,aggregation, leakage, and toxicity (2)

Slide (37) 41 New Narcotics preparations

Targin: Oxycodone/Narloxone (10/5mg)

Tapentadol: Narcotic (oxycondone/ tramadol):centrally acting analgesic; an agonist at μ-opioid receptor & a norepinephrine reuptake inhibitor

18-fold affinity- μ opioid receptor compared to morphine;

2 -3 less potent than morphine improved

G/I tolerability compared to classical opioids.



Dose unchanged in renal impairment. No Hepatoxicity IR oral: 50, 75 & 100 mg 4-6/24
Contraindicated: severe bronchial asthma, paralytic ileus,pt’s on (MAOI): SSRI’s, selective norepinephrine reuptake inhibitor SNRI, tryptans or, tricyclic antidepressants

Side effect: Serotonin syndrome include:mental status changes such as hallucinations, coma, autonomic instability such as tachycardia, hyperthermia, and neuromuscular abnormalities such as hyperreflexia and incoordination.
.Slide (38) 42 Narcotics used topically

  • Different routes Topical

    • Old :Narcotic’s Buprenorphine /fentanyl patch


Slide (39) 43 New Adjunctive drugs

Capsaicin (8-methyl-N-vanillyl-6-nonenamide) acts as a TRPV-1 agonist TRPV1 receptor markedly reduced in inflammatory conditions & is present on unmyelinated C fiber endings in the periphery.

Activation of the TRPV receptors releases high intensity impulses & releases substance P, which results in the initial phase of burning. Continued release of substance P in the presence of capsaicin leads to the depletion of capsaicin and a subsequent decrease in C fiber activation.


Slide (40) 44 Latest research Adjunctive not seen in action

Neostigmine (2,4), & recently, adenosine

Neostigmine, a cholinesterase inhibitor, has been reported to possess analgesic properties when doses of 10–200 g were administered in the subarachnoid (not seen used)

or epidural spaces epidurally administered neostigmine(1 g/kg) produced more than 5 h of pain relief after knee surgery (249). Neostigmine (10 g/kg) also enhanced epidural local analgesia (4)



Drugs on the horizon:Prialt,(ziconotide) IT only non opioid (used Uk & USA),

IT only non opioid (used Uk & USA),



Prialt,(ziconotide) (used in UK/ USA 2007), Rx pain associated with cancer, AIDS and neuropathies. Based on a compound found in the poison of the South Pacific cone snail, it controls pain in a new way -- by blocking the calcium channels in nerve cells that transmit pain signals -- & may have broad implications for the future of pain management. Benefits; Non narcotic +/- 1000 stronger than morphine, non addictive Side Effects: ONLY Intrathecal high risk of side effecting, hallucinations and even psychosis in vulnerable people.

Slide (41 45 Advances In Organisational Aspects Of Post operative Pain Control

    • Surgery Type i.e.Laparoscopic surgery, anterior hip replacement

    • Pre/interoperatively maximized use of L.A. & NMDA receptor antagonists agents

    • CBT pre hospitalization education

    • Early rehabilitation

    • Use of alternative therapies i.e. Acupuncture, meditation, mindfulness concepts(although presently not strongly supported – research occurring in this area)

Slide (42) 46 Just to mention any thing not already mentioned in summary

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