Bupivacaine in Postoperative Pain Management

Buprenorphine's versatility in acute pain is gaining traction, particularly where there’s a need to reduce opioid-related risks.

"Buprenorphine in Postoperative Pain Management"
"An Old One But a Good One!

1. Microdosing and Low-Dose Buprenorphine
2. Sublingual and Buccal Administration in Acute Settings
3. Buprenorphine for Opioid-Naïve Patients in the ER
4. Combination with Other Analgesics
5. Role in Opioid-Tolerant Patients
6. Use in Enhanced Recovery After Surgery (ERAS) Protocols

1. Buprenorphine In Postoperative Pain Management An Overview of Clinical Applications and Efficacy Dr. Saeid Safari Anaesthetic fellow, ANZCA, Australia Assistant Prof. of Shahid Beheshti University of Medical Sciences

2. Outline This presentation explores the efficacy of buprenorphine in preoperative and postoperative settings, highlighting its benefits, challenges, and strategies for effective use. Buprenorphine offers a unique pharmacological profile that may address these challenges while minimizing the risk of opioid misuse.

3. Buprenorphine: “An old one but a good one”

4. Introduction Buprenorphine is not entirely new for postoperative pain management, but its use has evolved and gained more attention in recent years, particularly in specific patient populations . Traditionally, buprenorphine has been primarily recognized for its role in treating opioid use disorder (OUD) due to its safety profile and lower potential for abuse compared to full opioid agonists.

5. “An old one but a good one”

6. “An old one but a good one”

7. Clinical Application of Buprenorphine as Analgesia

8. Mechanism of Action Buprenorphine has a distinctive and complicated pharmacological profile and is an effective therapy for opioid dependence. Buprenorphine is a partial mu-opioid agonist with low intrinsic activity and strong receptor affinity. Buprenorphine's high affinity allows it to effectively bind to mu receptors , while its lower intrinsic activity means it activates these receptors less intensely than full agonists, resulting in a unique profile that can be advantageous in pain management and reducing the risk of overdose.

9. Classification of Opioids This table categorizes opioids based on their mechanism of action, highlighting buprenorphine's role as a partial agonist, which provides analgesia with a lower risk of addiction. Classification Description Full Agonists Bind fully to mu-opioid receptors (e.g., morphine, fentanyl) Partial Agonists Bind partially to mu-opioid receptors (e.g., buprenorphine) Antagonists Block opioid receptors (e.g., naloxone) Mixed Agonist/Antagonist Activate some receptors while blocking others (e.g., pentazocine)

10. Mechanism of Action Buprenorphine works by binding to the mu-opioid receptor, producing analgesic effects while simultaneously acting as an antagonist at the kappa-opioid receptor. This dual action helps to alleviate pain while reducing the potential for abuse and dependence associated with full agonist opioids. Buprenorphine's ceiling effect limits the risk of respiratory depression, making it a safer alternative for patients with a history of substance use disorders.

11. Mechanism of Action The maximum effect that buprenorphine can have as a partial mu-opioid agonist will always be less than what a full mu-opioid agonist can have. Furthermore, compared to an opioid agonist with higher intrinsic activity like morphine, buprenorphine requires the occupancy of a greater proportion of receptors to exert a given effect. Buprenorphine has a high affinity for the receptor, which increases the possibility that it will be bound as opposed to unbound and makes it challenging to remove from the receptor.

12. Pharmacokinetics of Buprenorphine Buprenorphine's pharmacokinetics are characterized by its high lipophilicity , allowing for rapid penetration of the blood-brain barrier. The drug has a long half-life , which can lead to sustained analgesic effects but also means that it remains in the system longer, potentially complicating postoperative pain management. The onset of action varies by route of administration: intravenous administration provides rapid relief (5-15 minutes), while sublingual and transdermal routes have delayed effects. Understanding these pharmacokinetic properties is crucial for optimizing pain control in postoperative patients.

13. Pharmacokinetics of Buprenorphine This table summarizes the pharmacokinetic properties of buprenorphine, illustrating its absorption, distribution, metabolism, and excretion characteristics, which are essential for understanding its clinical use. Bioavailability 30-50% (sublingual) Peak Plasma Concentration 1-4 hours Half-Life 24-60 hours Metabolism Hepatic (CYP3A4) Excretion Urine (as metabolites) Onset of action 15 - 45 minutes (varies by route)

14. interactions of buprenorphine with various medications: Interaction Type Medication Class Examples Effect on Buprenorphine CYP3A4 Inhibitors Antifungals Ketoconazole Increases buprenorphine levels, risk of side effects Antibiotics Erythromycin, Clarithromycin Increases buprenorphine levels, risk of side effects HIV Protease Inhibitors Ritonavir Increases buprenorphine levels, risk of side effects Other Grapefruit Juice Increases buprenorphine levels, risk of side effects CYP3A4 Inducers Anticonvulsants Carbamazepine, Phenytoin Decreases buprenorphine levels, reduced efficacy Antibiotics Rifampin Decreases buprenorphine levels, reduced efficacy Herbal Supplements St. John's Wort Decreases buprenorphine levels, reduced efficacy Benzodiazepines Sedatives Alprazolam, Diazepam, Lorazepam Increased risk of sedation and respiratory depression Other Opioids Opioid Analgesics Morphine, Oxycodone Increased sedation, risk of respiratory depression CNS Depressants Various Alcohol, Barbiturates, Muscle Relaxants Enhanced sedative effects, increased respiratory depression

15. Routes of Administration Buprenorphine can be administered via multiple routes: parenteral, sublingual, intramuscular, intrathecal, epidural, and transdermal. Each route offers unique benefits and challenges in pain management . The choice of route may depend on patient needs and clinical settings.

16. Buprenorphine: pharmaceutics

17. Efficacy in Postoperative Pain Studies show buprenorphine effectively manages postoperative pain. Comparable efficacy to traditional opioids like morphine. Johnson et al. demonstrated effective pain control in non-dependent patients "no ceiling for analgesia" means that buprenorphine can provide continuous pain relief with increasing doses, making it a useful option in managing pain, particularly in chronic or severe cases, while still maintaining a safety profile due to its partial agonist properties.

18. Dosing Guidelines Table 1: Dosing Guidelines for Buprenorphine Route Dose Range Equivalent to Morphine Parenteral 0.3 mg/mL 10 mg Sublingual 0.2 - 0.4 mg Varies Intramuscular 5 - 15 mg/kg Varies Intrathecal 0.03 - 0.045 mg Varies Epidural 30 mg/hour (subcutaneous) Varies

19. Buprenorphine: acute pain

20. Dosage Buprenorphine does not have a ceiling dose for analgesia and does not decrease the analgesic effect of other full opioid agonists when used in combination. Patch Apply topically ONCE a week (on the same day each week) If initiating treatment, use one 5 MICROg /hr patch Allow a minimum of three days to attain steady state before titrating dose A maximum of two patches may be applied at a time to attain required dose Maximum dose of 40 MICROg /hr Sublingual tablet 200 - 400 MICROg sublingually every FOUR to SIX hours when required, to a maximum dose of 1200 MICROg in 24 hours Titrate to effect in consultation with APS Elderly patients may require lower starting doses Sublingual buprenorphine has 50% bioavailability when compared to intravenous buprenorphinel e.g. 100 MICROg IV approximately equivalent to 200 MICROg sublingual Intravenous injection For intraoperative, PACU and ICU use only Seek guidance from Specialist Pain Medicine Physician for dosage. Intermittent intravenous boluses must not be administered concurrently with a PCA or sublingual tablet

21. intrathecal and epidural Feature Intrathecal Buprenorphine Epidural Buprenorphine Administration Route Directly into the cerebrospinal fluid (CSF) Into the epidural space Mechanism of Action Acts on mu-opioid receptors in the spinal cord Absorbed into systemic circulation, acts centrally Onset of Action Rapid onset due to direct delivery Moderate onset, slower than intrathecal Duration of Analgesia Prolonged pain relief, longer pain-free intervals Effective pain control, duration varies with dose Clinical Applications Major orthopedic and abdominal surgeries, cesarean sections Coronary artery bypass, thoracic and abdominal surgeries Typical Dosing Dose-dependent; higher doses yield longer effects Ranges from 4 to 8 mg per hour, adjustable based on needs Advantages - Prolonged analgesia- Reduced systemic side effects - Effective pain control- Flexibility in dosing Potential Side Effects - Respiratory depression, Nausea- Pruritus - Sedation- Nausea- Urinary retention- Risk of catheter-related complications Monitoring Requirements Close monitoring for respiratory depression and side effects Monitoring for side effects and catheter complications

22. PCA (Intravenous use) default prescription: Bolus Dose Lockout Concentration Syringe 30 MICROg 10 minutes 30 MICROg /mL 1500 MICROg /50 rnL Bolus Dose Frequency Maximum Cumulative Dos Syringe 15 to 30 MICROg Every 10 minutes 300 MICROg 300 MICROg /10 mL PACU (Intravenous use) default prescription:

23. Postoperative Pain Management in Oral and Maxillofacial Surgery Buprenorphine has high analgesic potential, good safety profile, ease of opioids switches and reversibility by μ- antagonist. Transdermal route is cost effective and has increased patient compliance and ease of handling with less adverse effects. Thus, the efficacy of transdermal buprenorphine in postoperative pain management was good

24. Barriers to Use These include underutilization due to a lack of awareness among healthcare providers, regulatory challenges, and stigma associated with its use in treating OUD. Additionally, the complex pharmacological profile of buprenorphine can lead to hesitancy in prescribing, particularly in acute care settings. Addressing these barriers is essential for optimizing pain management strategies for patients with chronic pain and OUD.

25. Challenges in Postoperative Pain Management One major concern is the potential for reduced analgesic efficacy due to the partial agonist nature of buprenorphine, which can lead to a ceiling effect on pain relief. Furthermore, the presence of buprenorphine in the system can complicate the use of full opioid agonists , as they may not provide the expected level of pain relief. Clinicians must balance the need for effective analgesia with the risk of respiratory depression and other side effects associated with opioid use.

26. Antihyperalgesic Properties

27. Safety and Side Effects Common side effects include sedation, respiratory depression, and nausea. Caution is advised when used with other CNS depressants . Monitoring is essential to prevent adverse effects, especially in vulnerable populations.

28. Strategies for Improvement To enhance postoperative pain management, a multimodal analgesic approach is recommended. This involves combining buprenorphine with other analgesics, such as acetaminophen and gabapentinoids , to reduce reliance on opioids and improve overall pain control. Continuing buprenorphine during the perioperative period is also crucial. This practice helps prevent withdrawal symptoms and enhances the analgesic effects of other medications, leading to better patient outcomes and satisfaction.

29. buprenorphine is being increasingly considered for several reasons:

30. Benefits Benefit Description Effective Analgesia Provides significant pain relief for moderate to severe postoperative pain. Lower Abuse Potential Partial agonist properties reduce the risk of addiction compared to full agonists. Long Duration of Action Extended half-life allows for sustained pain control, reducing the need for frequent dosing. Antihyperalgesic Properties May help prevent central sensitization and chronic pain development post-surgery. Ceiling Effect on Respiratory Depression Lower risk of respiratory depression compared to full agonists, enhancing safety in postoperative settings. Flexibility in Administration Available in multiple forms (sublingual, transdermal, IV), allowing for tailored pain management strategies.

31. Considerations Consideration Description Patient History Important to assess the patient's history of opioid use and dependence. Monitoring for Efficacy Continuous assessment of pain control is necessary to adjust dosages as needed. Potential for Partial Agonism May require higher doses of full agonists for adequate pain relief in some patients. Drug Interactions Awareness of potential interactions with other medications, especially those metabolized by CYP3A4. Withdrawal Symptoms Patients on long-term buprenorphine may experience withdrawal if not managed properly. Individualized Pain Management Treatment plans should be tailored to the individual patient's needs and surgical procedure.

32. Conclusion Buprenorphine presents a unique option for postoperative pain management due to its pharmacological properties and lower abuse potential. However, its use in patients on maintenance therapy requires careful consideration of its pharmacokinetics and potential challenges in achieving adequate pain control. Understanding these factors will help clinicians provide better care for patients requiring pain management after surgery.

33. Thank You