1. Opioid Free Anesthesia
Tom Baribeault MSN CRNA

2. What is Opioid Free Anesthesia
New technique of anesthesia administration
Opioid-free intra-operatively
Maintain hemodynamics with medications that protect the nervous system
Acute surgical pain management
Treat the cause of the pain .
Pain is more than a number and treatment needs to be based on an understanding of how pain works. Surgical pain complex phenomenon that we have to better understand and treat as a pathological condition
Sisyphus effect, Other side effects, Addiction/Dependence

3. Why Safer anesthetic Acute surgical pain control
Less respiratory depression
Acute surgical pain control
Prevent chronic pain
Avoid side effects of opioids
Patient satisfaction
Shorter hospital stay $$$
Reduce opioid addiction/dependence
1) Less respiratory depression.
2) Pain is under controlled in a large % of surgical patients, as our patients get older, sicker and larger our ability to give opioids decreases. First hours pain control is crucial to stop possibility of chronic pain
3) PONV, pruritus, Cognitive/Sleep Dysfunction, Ileus, Constipation, Urinary Retention, Immune Suppression. ERAS literature shows that these things prolong hospital stays
4) 1:15 surgical patients develop opioid dependence or addiction

4. Preconceptions Opioids are:
Necessary: hemodynamic control and pain management
Beneficial: improve the patient experience
Safe: respiratory depression and other side effects can be safely managed
Adequate: pain is well controlled
Balanced anesthesia has been the primary technique since We were taught to maintain HR and BP using opioids, and departing what we’ve been taught can be scary especially outside of a traditional learning environment.
We have to unlink the ideas that opioids=pain management. Before we had our current medications, opioids were beneficial because they lowered the amount of anesthetic agent necessary while providing a more hemodynamically stable anesthetic. Current medications can do the same thing, provide beneficial effects and avoid the negative side effects of opioids.
We use opioids so extensively that we become good at mitigating their side effects, and in time begin to forget that they are one of the most dangerous classes of medications. Using opioids as a first line treatment instead of last sets the patient up for respiratory depression or arrest, addiction or dependence, and other side effects.
Since balanced anesthesia has been the primary technique for so long, many people begin to believe that the results they get from it are GOOD and ADEQUATE. But we know that our BEST efforts with balanced anesthesia leads to poor post operative pain management, unavoidable side effects, and prolonged hospital stays.

5. Special Populations Respiratory Complex Pain Management PONV Cancer
Opioid users/abusers
Recovery
High risk chronic pain
PONV
Cancer
Elderly
Patients that benefit the most vs penalizing health patients by giving inferior anesthetic because they are healthy?
1. COPD, obese, sleep apnea, elderly or young
2. Pain management
A. Long term opioid therapy/heroin
B. methadone suboxone, do not want opioids risk relapse
C. most at risk surgeries for chronic pain sternotomy, thoracotomy, breast, amputation
3. Opioids more likely to cause PONV than Anesthesia
4. questionable at this point
5. cognitive dysfunction sleep disturbance

6. Anatomy Peripheral Nerves Spinal Nerves A Beta A Delta C
Rexed Lamina I
Rexed Lamina V
Peripheral nerves first order neurons
1A. Touch low threshold
1B. fast pain high threshold
1C.slow pain high threshold Majority of pain nerves (B & C release Glutamate and Substance P)
Second order neurons
2A. A Delta and C Nociceptive specific Midbrain/Limbic system Periaqueductal Grey, Rostral Ventromedial Medulla.
2B. A Beta, A delta, and C Wide Dynamic Range Neuron. Thalamus, Pain matrix

7. Anatomy
Rexed Lamina I. A Delta and C Nociceptive specific Midbrain/Limbic system Periaqueductal Grey, Rostral Ventromedial Medulla.
Rexed Lamina V. A Beta, delta, and C Wide Dynamic Range Neuron. Thalamus, Pain matrix

8. Anatomy Rexed Lamina I Rexed Lamina V Midbrain Periaqueductal Grey
Rostral Ventromedial Medulla
Descending Fibers
Rexed Lamina V
Thalamus
Pain Matrix
Peripheral nerves first order neurons
1A. Touch low threshold
1B. fast pain high threshold
1C.slow pain high threshold Majority of pain nerves (B & C release Glutamate and Substance P)
Second order neurons
2A. A Delta and C Nociceptive specific Midbrain/Limbic system Periaqueductal Grey, Rostral Ventromedial Medulla.
2B. A Beta, A delta, and C Wide Dynamic Range Neuron. Thalamus, Pain matrix

9. Anatomy
Rexed Lamina I. A Delta and C Nociceptive specific Midbrain/Limbic system Periaqueductal Grey, Rostral Ventromedial Medulla.
Rexed Lamina V. A Beta, delta, and C Wide Dynamic Range Neuron. Thalamus, Pain matrix

10. Natural Inhibition Periaqueductal Grey Rostral Ventromedial Medulla
A Beta Inhibition
releases endorphines, dynorphins, and enkephalins (endogenous opioid substances)
activates descending inhibitory nerve fibers hyperpolarize the ascending pathway Serotonin and norephinephrine
A beta interneuron inhibition gaba and glycine

11. Natural Inhibition
releases endorphines, dynorphins, and enkephalins (endogenous opioid substances)
activates descending inhibitory nerve fibers hyperpolarize the ascending pathway Serotonin and norephinephrine
A beta interneuron inhibition gaba and glycine

12. Hyperalgesia Primary (Peripheral) Sensitization
Inflammation Induced Central Sensitization
Secondary (Central) Sensitization
Allodynia
Opioid Induced Hyperalgesia
1. Sensitizing soup, Inflammatory mediators Bradykinin, Prostaglandin, Histamine, Leukotriene and others cause C fibers to become low threshold, continually fire, and have stronger response to stimuli
2. Prostaglandin E2 in CSF not understood interaction cox2 nmda receptors
3. Excess Glutamate from C fibers, NMDA receptor loses Mg plus, AMPA receptors creation.
4. Death of interneuron, loss of A Beta inhibition, touch and pressure now felt as painful.
5. Sensitization to nociception and desensitization to anti-nociception (Sisyphus effect) Mechanism not known Inflammatory or NMDA receptor. Dose, frequency and potency related

13. Peripheral Sensitization
Sensitizing soup, Inflammatory mediators Bradykinin, Prostaglandin, Histamine, Leukotriene and others cause C fibers to become low threshold, continually fire, and have stronger response to stimuli

14. Peripheral Sensitization
Sensitizing soup, Inflammatory mediators Bradykinin, Prostaglandin, Histamine, Leukotriene and others cause C fibers to become low threshold, continually fire, and have stronger response to stimuli

15. Hyperalgesia Primary (Peripheral) Sensitization
Inflammation Induced Central Sensitization
Secondary (Central) Sensitization
Allodynia
Opioid Induced Hyperalgesia
Prostaglandin E2 in CSF not understood interaction cox2 nmda receptors

16. Central Sensitization
3. Excess Glutamate from C fibers, NMDA receptor loses Mg plus, AMPA receptors creation.

17. Central Sensitization
3. Excess Glutamate from C fibers, NMDA receptor loses Mg plus, AMPA receptors creation.

18. Allodynia
Death of interneuron, loss of A Beta inhibition, touch and pressure now felt as painful.

19. Opioid Induced Hyperalgesia
Sensitization to nociception and desensitization to anti-nociception (Sisyphus effect) Mechanism not known Inflammatory or NMDA receptor. Dose, frequency and potency related.
Tolerance, morphine 8 hours infusion, 2 days round the clock bolus dosing. Remifentanil 3 hours infusion.

20. History Balanced Anesthesia Multimodal Therapy Pre-emptive Analgesia
Fentanyl
Multimodal Therapy
Pre-emptive Analgesia
Preventative Analgesia
1a. Discovered in 1960 balanced anesthesia cardiovascularly stable, autonomic control, no ceiling effect, limited by side effects.
2. Use other analgesics to minimize the side effects of opioids. Concept behind ERAS, side effects are what keep people in the hospital
3. Blocking pain receptors prior to stimulation prevents hyperalgesia unable to be proven.
4. Using medications that block the harmful changes to the neurologic system prevents hyperalgesia

21. Peripheral and Central Inflammation
Steroids
Nsaids/Coxibs
Cannabinoids?
Local Anesthetics
1A. Decadron inhibits prostaglandin, histamine, and leukotrienes. Dose dependent 4-12 mg. Reduces pain, sore throat, and difficulty sleeping. Increases blood glucose in diabetics and non the same %.
1B. Inhibits prostaglandin, histamine, and bradykinin. Weak anti-inflammatory effect, contra-indications renal failure, gi bleed, thrombotic event, CABG, age >60
Toradol has greatest analgesic effect but most nephrotoxic. Celebrex has no bleeding issues, inhibits inflammatory process before it happens, and has few side effects than Nsaids including less cardiovascular risk. IV COX2 Parecoxib in europe
1C. 2x anti-inflammatory effect of Decadron 10x Nsaids, inhibits interleukin and prostaglandin release. Also blocks c1 and c2 pain receptors. No good studies in surgical patients. THC Cannabidiol
1D local anesthetics have weak anti-inflammatory effect by blocking prostaglandins

22. Central Sensitization
Glutamate
Ketamine
N2O
Magnesium
Gabapentinoids
Substance P
Clonidine
Dexmedetomidine
Tizanidine
1A Ketamine blocks NMDA glutamate receptor. Only drug to reverse opioid tolerance and opioid induced hyperalgesia. If mg/kg or 2-10 mcg/kg/min do not need benzo. Can continue on floor or mix 1:1 in PCA with morphine. Causes bronchodilation and being used to treat ptsd, mdd, and SI. 48 hours
1B N2O very similar mechanism to Ketamine, 75 minute 50% exposure reduced hyperalgesia for 1 month.
1C Mag bolus 10 mg/kg/hr changes concentration gradient to prevent loss of Mg plug in NMDA receptor. Dose and analgesia not correlated. 24 hours
1D Gabapentin Pregabalin (Lyrica) Blocks pre-synaptic release of glutamate and substance P. Post-op sedation? Lyrica faster absorption more consistent plasma levels rare side effects.
2A IV vs PO 2-5 vs hour half life. Anxiolysis and post-op shivering. Bradycardia and hypotension
2B Less bradycardia/hypotension than clonidine, does not last as long post-op. may be continued as an infusion on the floor

23. Central Sensitization
Anti-depressants
Duloxetine
Trazodone
Tramadol
Cyclobenzaprine
Amitriptyline
3 Duloxetine (cymbalta). Reductions in chronic pain at 3-6 months when taken week before/after. Contraindications concurrent use MAOI, methylene blue, linezolid and no use in kids.

24. Analgesics Local Anesthetics Acetaminophen Beta Blocker Opioids
Regional/Neuraxial
Lidocaine infusion
Acetaminophen
Beta Blocker
Opioids
1A Gold standard.
1B if no regional, better for tissue than bone hour effect. Plasma concentration 2-3 mcg/ml toxicity 8-10 mcg/ml, watch out for hx seizures and AV malformation. Can be continued Post-op.
2. Unknown MOA. IV vs PO and cost. 25% reduction in pain/opioid consumption. Schedule q6-8h post-op and use hydro/oxycodone.
3. Esmolol when used to eliminate intraoperative opioids patients had reduction in pain/opioid consumption for 24 hours postop.
4. Agonist/Antagonists Nubain and Buprenorphine for moderate pain. do not cause Sisyphus effect. Long acting with little respiratory depression. Smaller doses of dilaudid needed for severe pain.

25. Plan Intra-operative Local Anesthetics A2 agonist NMDA antagonist
Beta Blockers

26. Plan Post-operative Acetaminophen NSAID/Cox 2 Gabapentinoid
Anti-depressant
Opioid
Infusions
Lidocaine A2
Ketamine

27. OFA Expectations Normotensive Increased respiratory rate
Initial wake up slower
Less pain/more responsive to opioids

28. Resources
Goopioidfree.com