Ashley Hawrylyshyn PACU Presentation October 2011

Opiate Induced Pruritis (OIP)

Pruritis is a common sensation after the

administration of opioids Defined as: sensation that provokes the desire to scratch and can be aroused by a variety of mechanical, electrical and chemical stimuli Most clinicians cite concerns of post operative pain, nausea and vomiting and shivering above itching However, for some patients pruritis may be more unpleasant than pain itself (Ballantyne et al)

What is the incidence of OIP?

Method of Opiate Administration and Procedure Frequency Neuraxial Opioids Systemic Opioids Parturients with Neuraxial Opioids Major Orthopedic Surgery with Intrathecal Opioids 30-100% 2-10% 60-100% 30-60%

Does opiate type or dose influence the incidence of pruritis?

Generally, there is a lack of correlation between the

dose and type of opioids administered and the intensity with which pruritis is perceived
Method of Opiate Administration
Intrathecal Morphine Epidural Morphine Intrathecal Fentanyl Epidural Fentanyl Intrathecal Sufentanyl

Frequency
62-85% 65-70% 67-100% 67% 80%

Epidural Sufentanyl

55%

What causes OIP?

Exact mechanism unclear, may be several
Itch sensation arises from superficial skin, where nerve

endings cluster in itch points; C fibers mediate afferent sensation transmission Likely mu opioid receptor mediated in part (based on IT induced morphine scratching in monkeys) ? Presence of itch center in CNS medulla oblongata Serotonin and Prostglandin also implicated

Why is pruritis typically in the nose and upper face?

Facial area innervated by the trigeminal (TG) nerve is

predominantly affected Likely due to cephalad spread of opioids in the CSF and subsequent interaction with TG nucleus and nerve roots; spinal nucleus of TG nerve is rich in opioid receptors Ophthalmic division of spinal sensory nucleus is most inferior , supports observation pruritis following intrathecal opioids typically in nose and upper face

- Current therapeutic strategies for OIP are unsatisfactory - No drug agent proved to be totally effective

Prevention and Treatment of OIP

AntiHistamines In Neuraxial OIP, histamine is not released and does not appear to be causative Histamine mediator of itching is however produced by orally and intravenous administered opioids Sedative side effect of antihistamines may interrupt itch scratch cycle, without relieving itch sensation Typical doses studied: Promethazine 50mg, Hydroxyzine 50mg

Prevention and Treatment of OIP

NSAIDs (inhibit COX and formation of PGE1/PGE2) Tenoxicam and diclofenac significantly decrease pruritis scores associated with epidural and IT OIP(Colbert et al) Ondansetron Prophylactic treatment with ondansetron reduced the prevalence of IT morhine induced pruritis vs placebo; 34% response vs 66% placebo (Iatrou et al) Ondansetron 8mg effective for established OIP in patients who received IT morphine for postoperative analgesia for ortho procedures (Borgeat et al)

Prevention and Treatment of OIP

Propofol
Borgeat et al: IV propofol 10mg vs placebo following IT morphine.

Absence of positive treatment response, second treatment 5 mins later. Treatment success rate 84% propofol, placebo 16% and 90% of placebo failures treated by supplemental propofol dose Charuluxananan: compared nalbuphine and propofol after IT morphine for C-section; treatment success rate higher in nalbuphine 3mg IV compared with propofol 20mg IV (83 vs 61%); both superior to placebo Proposed mechanism: marked depression of posterior horn transmission in spinal cord

Prevention and Treatment of OIP

Opioid Antagonists Kjellberg et al: systematic review of randomized trials with IV naloxone, oral naltrexone and IV nalbuphine Naloxone infusion: NNT to prevent pruritus 3.5, no evidence of dose responsiveness; with increasing doses, number of patients who required rescue analgesia increased Oral nalxtrexone: 3mg not effective, 6-9mg efficacious (NNT < 2), but analgesia duration decreased Nalbuphine: 40mg IV bolus, efficacious, not associated with decreased pain, but risk of drowsiness doubled

Conclusion
Pruritis after opioids is a common side effect, that is usually self-

limiting and non life threatening Currently, no established role for prophylactic treatment Overall treatment recommendations:
Minimal analgesic doses of opioids to provide pain relief Addition of local anesthetics to neuraxial infusion as tolerated Use combination therapy (likely multiple pathways involved) Opioid antagonists probably most potent antipruritic agents, but

remember they may also decrease analgesia Conflicting evidence re subhypnotic doses of propofol Serotonin antagonists appear good choice (no effect on analgesia and PONV benefit) NSAIDs possible prophylactic therapy for OIP

References
Kjellber, F. and M.R. Tramer. (2001) Pharmacological control of opioid-induced pruritus: a quantitative systematic review of randomized trials. European Journal of Anesthesiology, 18, 346-357.
Waxler, B. et al. (2005) Primer of Postoperative Pruritis for Anesthesiologists. Anesthesiology, 103, 168-78. Ganesh, A. and L. Maxwell. (2007) Pathophysiology and Management of Opioid-Induced Pruritis. Drugs, 67, 2323-33. Szarvas, S. et al. (2002) Neuraxial Opioid-Induced Pruritus: A Review. Journal of Clinical Anesthesia, 15, 234-9. Reich, A. and J.C. Szepietowski (2009) Opioid-induced Pruritis: an update. Clinical Dermatology, 35, 2-6.