Skip to main content
Top
Published in: BMC Pregnancy and Childbirth 1/2021

Open Access 01-12-2021 | Sectio Ceasarea | Research article

Pruritus after continuous administration of epidural morphine for post-cesarean delivery analgesia: a case control study

Authors: Xinyi Tian, Kaifan Niu, Hong Cao, Gonghao Zhan, Yan Zhang, Feng Xu, Wangning Shangguan, Ye Gao

Published in: BMC Pregnancy and Childbirth | Issue 1/2021

Login to get access

Abstract

Background

Pruritus is one of the most common side effects of epidural morphine administered for post-surgery analgesia, and pregnant women tend to be highly susceptible. The relative contributions of morphine concentration, local anesthetics, and level of pain to pruritus after epidural morphine for post-cesarean delivery analgesia remain unclear. Accordingly, the present study aimed to identify risk factors for pruritus after continuous administration of epidural morphine for post-cesarean delivery analgesia.

Methods

This case control study was based on routinely collected clinical data. Participants included women who had undergone cesarean section and adopted a patient-controlled analgesia pump for postoperative analgesia. A series of logistic regression analyses were performed. Interaction terms were added to explore the moderation effects of combined local anesthetics and pain level on associations between morphine concentration and pruritus. Robustness of the results was checked through sensitivity analysis using propensity scores matching approach.

Results

Higher morphine concentration, assisted reproductive treatment, and multipara and cesarean section history were significantly more prevalent in the pruritus group than in the control group. The probabilities of pruritus at morphine concentrations of 10, 15, 20, 25, 30 and 40 μg/mL increased sequentially from 0.05, 0.1, 0.2, 0.35, 0.54 to 0.84, respectively. The trend remained steep in the ropivacaine stratum and became flatter when combined with levobupivacaine. At mild pain combined with levobupivacaine, the incidence of pruritus increased from 0.33 (95% confidence interval [CI] 0.1–0.68) in the 10 μg/mL morphine group to 0.48 (95% CI 0.1–0.88) in the 40 μg/mL morphine group. In the stratum of moderate pain combined with levobupivacaine, the incidence increased from 0.4 (95% CI 0.04–0.92) to 0.56 (95% CI 0.03–0.98). The results in the sensitivity analysis were in consistent with above findings.

Conclusions

Higher concentrations of morphine, multipara, and assisted reproductive treatment were factors associated with a higher probability of pruritus. Pain level or combined local anesthetics could moderate the association between morphine concentration and pruritus.
Literature
1.
go back to reference Bonnet MPB, Mignon A, Mazoit JX, Ozier, Marret E. Analgesic efficacy and adverse effects of epidural morphine compared to parenteral opioids after elective caesarean section: a systematic review. Eur J Pain. 2010;14(9):894 e891–899.CrossRef Bonnet MPB, Mignon A, Mazoit JX, Ozier, Marret E. Analgesic efficacy and adverse effects of epidural morphine compared to parenteral opioids after elective caesarean section: a systematic review. Eur J Pain. 2010;14(9):894 e891–899.CrossRef
2.
go back to reference Lavand hmme P. Postcesarean analgesia: effective strategies and association with chronic pain. Curr Opin Anaesthesiol. 2006;19(3):244–8.CrossRef Lavand hmme P. Postcesarean analgesia: effective strategies and association with chronic pain. Curr Opin Anaesthesiol. 2006;19(3):244–8.CrossRef
3.
go back to reference Wilson MJ, Macarthur C, Shennan A, Group CS. Urinary catheterization in labour with high-dose vs mobile epidural analgesia: a randomized controlled trial. Br J Anaesth. 2009;102(1):97–103.CrossRef Wilson MJ, Macarthur C, Shennan A, Group CS. Urinary catheterization in labour with high-dose vs mobile epidural analgesia: a randomized controlled trial. Br J Anaesth. 2009;102(1):97–103.CrossRef
4.
go back to reference Szarvas S, Harmon D, Murphy D. Neuraxial opioid-induced pruritus: a review. J Clin Anesth. 2003;15(3):234–9.CrossRef Szarvas S, Harmon D, Murphy D. Neuraxial opioid-induced pruritus: a review. J Clin Anesth. 2003;15(3):234–9.CrossRef
5.
go back to reference Kumar K, Singh SI. Neuraxial opioid-induced pruritus: An update. J Anaesthesiol Clin Pharmacol. 2013;29(3):303–7.CrossRef Kumar K, Singh SI. Neuraxial opioid-induced pruritus: An update. J Anaesthesiol Clin Pharmacol. 2013;29(3):303–7.CrossRef
6.
go back to reference Mulroy MF, Larkin KL, Siddiqui A. Intrathecal fentanyl-induced pruritus is more severe in combination with procaine than with lidocaine or bupivacaine. Reg Anesth Pain Med. 2001;26(3):252–6.CrossRef Mulroy MF, Larkin KL, Siddiqui A. Intrathecal fentanyl-induced pruritus is more severe in combination with procaine than with lidocaine or bupivacaine. Reg Anesth Pain Med. 2001;26(3):252–6.CrossRef
7.
go back to reference Reich A, Szepietowski JC. Opioid-induced pruritus: an update. Clin Exp Dermatol. 2010;35(1):2–6.CrossRef Reich A, Szepietowski JC. Opioid-induced pruritus: an update. Clin Exp Dermatol. 2010;35(1):2–6.CrossRef
8.
go back to reference Simmons SW, Taghizadeh N, Dennis AT, Hughes D, Cyna AM. Combined spinal-epidural versus epidural analgesia in labour. Cochrane Database Syst Rev. 2012;10:CD003401.PubMed Simmons SW, Taghizadeh N, Dennis AT, Hughes D, Cyna AM. Combined spinal-epidural versus epidural analgesia in labour. Cochrane Database Syst Rev. 2012;10:CD003401.PubMed
9.
go back to reference Armstrong S, Fernando R. Side effects and efficacy of Neuraxial opioids in pregnant patients at delivery: a comprehensive review. Drug Saf. 2016;39(5):381–99.CrossRef Armstrong S, Fernando R. Side effects and efficacy of Neuraxial opioids in pregnant patients at delivery: a comprehensive review. Drug Saf. 2016;39(5):381–99.CrossRef
10.
go back to reference Ganesh A, Maxwell LG. Pathophysiology and management of opioid-induced pruritus. Drugs. 2007;67(16):2323–33.CrossRef Ganesh A, Maxwell LG. Pathophysiology and management of opioid-induced pruritus. Drugs. 2007;67(16):2323–33.CrossRef
11.
go back to reference Stumpf A, Stander S, Warlich B, Fritz F, Bruland P, Pfleiderer B, et al. Relations between the characteristics and psychological comorbidities of chronic pruritus differ between men and women: women are more anxious than men. Br J Dermatol. 2015;172(5):1323–8.CrossRef Stumpf A, Stander S, Warlich B, Fritz F, Bruland P, Pfleiderer B, et al. Relations between the characteristics and psychological comorbidities of chronic pruritus differ between men and women: women are more anxious than men. Br J Dermatol. 2015;172(5):1323–8.CrossRef
12.
go back to reference Verhoeven EW, de Klerk S, Kraaimaat FW, van de Kerkhof PC, de Jong EM, Evers AW. Biopsychosocial mechanisms of chronic itch in patients with skin diseases: a review. Acta Derm Venereol. 2008;88(3):211–8.PubMed Verhoeven EW, de Klerk S, Kraaimaat FW, van de Kerkhof PC, de Jong EM, Evers AW. Biopsychosocial mechanisms of chronic itch in patients with skin diseases: a review. Acta Derm Venereol. 2008;88(3):211–8.PubMed
13.
14.
go back to reference Toomey M, Biddle C. Update for nurse anesthetists--pt 4. Itching, the "little" big problem as an orphan symptom. AANA J. 2006;74(5):379–84.PubMed Toomey M, Biddle C. Update for nurse anesthetists--pt 4. Itching, the "little" big problem as an orphan symptom. AANA J. 2006;74(5):379–84.PubMed
15.
go back to reference Girgin NK, Gurbet A, Turker G, Aksu H, Gulhan N. Intrathecal morphine in anesthesia for cesarean delivery: dose-response relationship for combinations of low-dose intrathecal morphine and spinal bupivacaine. J Clin Anesth. 2008;20(3):180–5.CrossRef Girgin NK, Gurbet A, Turker G, Aksu H, Gulhan N. Intrathecal morphine in anesthesia for cesarean delivery: dose-response relationship for combinations of low-dose intrathecal morphine and spinal bupivacaine. J Clin Anesth. 2008;20(3):180–5.CrossRef
16.
go back to reference Palmer CM, Emerson S, Volgoropolous D, Alves D. Dose-response relationship of intrathecal morphine for postcesarean analgesia. Anesthesiology. 1999;90(2):437–44.CrossRef Palmer CM, Emerson S, Volgoropolous D, Alves D. Dose-response relationship of intrathecal morphine for postcesarean analgesia. Anesthesiology. 1999;90(2):437–44.CrossRef
17.
go back to reference Chinachoti T, Nilrat P, Samarnpiboonphol P. Nausea, vomiting and pruritus induced by intrathecal morphine. J Med Assoc Thail. 2013;96(5):589–94. Chinachoti T, Nilrat P, Samarnpiboonphol P. Nausea, vomiting and pruritus induced by intrathecal morphine. J Med Assoc Thail. 2013;96(5):589–94.
18.
go back to reference Jiang C, Liu C, Wu T, Sun W-Z, Lin S, Huang F, et al. Mini-dose intrathecal morphine for post-cesarean section analgesia. Ma Zui Xue Za Zhi. 1992;29:683–9. Jiang C, Liu C, Wu T, Sun W-Z, Lin S, Huang F, et al. Mini-dose intrathecal morphine for post-cesarean section analgesia. Ma Zui Xue Za Zhi. 1992;29:683–9.
19.
go back to reference Cottrell BH. A review of opioid-induced itching after cesarean birth. Nurs Womens Health. 2015;19(2):154–63.CrossRef Cottrell BH. A review of opioid-induced itching after cesarean birth. Nurs Womens Health. 2015;19(2):154–63.CrossRef
20.
go back to reference Gail MH, Haneuse S. Power and sample size for multivariate logistic modeling of unmatched case-control studies. Stat Methods Med Res. 2019;28(3):822–34.CrossRef Gail MH, Haneuse S. Power and sample size for multivariate logistic modeling of unmatched case-control studies. Stat Methods Med Res. 2019;28(3):822–34.CrossRef
21.
go back to reference Hayes AF. Introduction to mediation, moderation, and conditional process analysis: a regression-based approach. New York, NY, US: Guilford Press; 2013. Hayes AF. Introduction to mediation, moderation, and conditional process analysis: a regression-based approach. New York, NY, US: Guilford Press; 2013.
22.
go back to reference Fuller JG, McMorland GH, Douglas MJ, Palmer L. Epidural morphine for analgesia after caesarean section: a report of 4880 patients. Can J Anaesth. 1990;37(6):636–40.CrossRef Fuller JG, McMorland GH, Douglas MJ, Palmer L. Epidural morphine for analgesia after caesarean section: a report of 4880 patients. Can J Anaesth. 1990;37(6):636–40.CrossRef
23.
go back to reference Singh SI, Rehou S, Marmai KL, Jones PM. The efficacy of 2 doses of epidural morphine for postcesarean delivery analgesia: a randomized noninferiority trial. Anesth Analg. 2013;117(3):677–85.CrossRef Singh SI, Rehou S, Marmai KL, Jones PM. The efficacy of 2 doses of epidural morphine for postcesarean delivery analgesia: a randomized noninferiority trial. Anesth Analg. 2013;117(3):677–85.CrossRef
24.
go back to reference Kissin I. Patient-controlled-analgesia analgesimetry and its problems. Anesth Analg. 2009;108(6):1945–9.CrossRef Kissin I. Patient-controlled-analgesia analgesimetry and its problems. Anesth Analg. 2009;108(6):1945–9.CrossRef
25.
go back to reference Patel KN, Dong X. Itch: cells, molecules, and circuits. ACS Chem Neurosci. 2011;2(1):17–25.CrossRef Patel KN, Dong X. Itch: cells, molecules, and circuits. ACS Chem Neurosci. 2011;2(1):17–25.CrossRef
26.
go back to reference Miyamoto T, Patapoutian A. Why does morphine make you itch? Cell. 2011;147(2):261–2.CrossRef Miyamoto T, Patapoutian A. Why does morphine make you itch? Cell. 2011;147(2):261–2.CrossRef
27.
go back to reference Sultan P, Halpern SH, Pushpanathan E, Patel S, Carvalho B. The effect of Intrathecal morphine dose on outcomes after elective cesarean delivery: a meta-analysis. Anesth Analg. 2016;123(1):154–64.CrossRef Sultan P, Halpern SH, Pushpanathan E, Patel S, Carvalho B. The effect of Intrathecal morphine dose on outcomes after elective cesarean delivery: a meta-analysis. Anesth Analg. 2016;123(1):154–64.CrossRef
28.
go back to reference Li Y, Hu C, Fan Y, Wang H, Xu H. Epidural analgesia with amide local anesthetics, bupivacaine, and ropivacaine in combination with fentanyl for labor pain relief: a meta-analysis. Med Sci Monit. 2015;21:921–8.CrossRef Li Y, Hu C, Fan Y, Wang H, Xu H. Epidural analgesia with amide local anesthetics, bupivacaine, and ropivacaine in combination with fentanyl for labor pain relief: a meta-analysis. Med Sci Monit. 2015;21:921–8.CrossRef
29.
go back to reference Cheng Q, Zhang W, Lu Y, Chen J, Tian H. Ropivacaine vs. levobupivacaine: analgesic effect of combined spinal-epidural anesthesia during childbirth and effects on neonatal Apgar scores, as well as maternal vital signs. Exp Ther Med. 2019;18(3):2307–13.PubMedPubMedCentral Cheng Q, Zhang W, Lu Y, Chen J, Tian H. Ropivacaine vs. levobupivacaine: analgesic effect of combined spinal-epidural anesthesia during childbirth and effects on neonatal Apgar scores, as well as maternal vital signs. Exp Ther Med. 2019;18(3):2307–13.PubMedPubMedCentral
30.
go back to reference Whiteside JB, Wildsmith JA. Developments in local anaesthetic drugs. Br J Anaesth. 2001;87(1):27–35.CrossRef Whiteside JB, Wildsmith JA. Developments in local anaesthetic drugs. Br J Anaesth. 2001;87(1):27–35.CrossRef
31.
go back to reference Sanford M, Keating GM. Levobupivacaine: a review of its use in regional anaesthesia and pain management. Drugs. 2010;70(6):761–91.CrossRef Sanford M, Keating GM. Levobupivacaine: a review of its use in regional anaesthesia and pain management. Drugs. 2010;70(6):761–91.CrossRef
32.
go back to reference Sheiner E, Ohel I, Levy A, Katz M. Pregnancy outcome in women with pruritus gravidarum. J Reprod Med. 2006;51:394–8.PubMed Sheiner E, Ohel I, Levy A, Katz M. Pregnancy outcome in women with pruritus gravidarum. J Reprod Med. 2006;51:394–8.PubMed
33.
go back to reference Bolukbas Filiz F, Cengiz B, Hatice YB, et al. vs in vitroIntrahepatic Cholestasis of Pregnancy: Spontaneous Fertilization. Euroasian J Hepatogastroenterol. 2017;7:126–9.CrossRef Bolukbas Filiz F, Cengiz B, Hatice YB, et al. vs in vitroIntrahepatic Cholestasis of Pregnancy: Spontaneous Fertilization. Euroasian J Hepatogastroenterol. 2017;7:126–9.CrossRef
34.
go back to reference Marco A, Macias Rocio IR, Oscar B, et al. Molecular pathogenesis of intrahepatic cholestasis of pregnancy. Expert Rev Mol Med. 2008;10:e9.CrossRef Marco A, Macias Rocio IR, Oscar B, et al. Molecular pathogenesis of intrahepatic cholestasis of pregnancy. Expert Rev Mol Med. 2008;10:e9.CrossRef
35.
go back to reference Tan X, Shen L, Wang L, Labaciren, Zhang Y, Zhang X, et al. Incidence and risk factors for epidural morphine induced pruritus in parturients receiving cesarean section: A prospective multicenter observational study. Medicine. 2019;98(40):e17366.CrossRef Tan X, Shen L, Wang L, Labaciren, Zhang Y, Zhang X, et al. Incidence and risk factors for epidural morphine induced pruritus in parturients receiving cesarean section: A prospective multicenter observational study. Medicine. 2019;98(40):e17366.CrossRef
36.
go back to reference Xiong Y-H, Yuan Z, He L. Effects of estrogen on CD4+ CD25+ regulatory T cell in peripheral blood during pregnancy. Asian Pac J Trop Med. 2013;6(9):748–52.CrossRef Xiong Y-H, Yuan Z, He L. Effects of estrogen on CD4+ CD25+ regulatory T cell in peripheral blood during pregnancy. Asian Pac J Trop Med. 2013;6(9):748–52.CrossRef
37.
go back to reference LaBella FS, Kim RS, Templeton J. Opiate receptor binding activity of 17-alpha estrogenic steroids. Life Sci. 1978;23(17–18):1797–804.CrossRef LaBella FS, Kim RS, Templeton J. Opiate receptor binding activity of 17-alpha estrogenic steroids. Life Sci. 1978;23(17–18):1797–804.CrossRef
Metadata
Title
Pruritus after continuous administration of epidural morphine for post-cesarean delivery analgesia: a case control study
Authors
Xinyi Tian
Kaifan Niu
Hong Cao
Gonghao Zhan
Yan Zhang
Feng Xu
Wangning Shangguan
Ye Gao
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Pregnancy and Childbirth / Issue 1/2021
Electronic ISSN: 1471-2393
DOI
https://doi.org/10.1186/s12884-020-03522-6

Other articles of this Issue 1/2021

BMC Pregnancy and Childbirth 1/2021 Go to the issue