The Effect of Adding Low-Dose Naloxone to Intrathecal Morphine on Postoperative Pain and Morphine Related Side Effects after Cesarean Section: A Double-Blind, Randomized, Clinical Trial

Saloumeh Peivandi; Mohammad Reza  Habibi; Afshin Gholipour  Baradari; Abdolmajid  Gholinataj; Ali  Habibi; Mohammad  Khademloo; Foad  Foladi

doi:10.3889/oamjms.2019.852

Authors

Saloumeh Peivandi Department of Gynecology and Obstetrics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Mohammad Reza Habibi Department of Anesthesiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Afshin Gholipour Baradari Department of Anesthesiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Abdolmajid Gholinataj Department of Anesthesiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Ali Habibi Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Mohammad Khademloo Department of Community Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Foad Foladi Department of Community Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

DOI:

https://doi.org/10.3889/oamjms.2019.852

Keywords:

Naloxone, Morphine, Cesarean Section, Anesthesia, Spinal, Pain, Postoperative

Abstract

BACKGROUND: Nowadays, spinal anaesthesia is a suitable choice for most elective and emergency cesarean section (C-section) deliveries.

AIM: This study aimed to determine the effect of adding low-dose naloxone to intrathecal morphine on postoperative pain and morphine related side effects after C-section.

MATERIAL AND METHODS: In the present double-blind, randomised clinical trial, 70 women aged over 18 years, who were candidates for elective medical C-section under spinal anaesthesia were selected and randomly assigned to either the study group or the control group. For spinal anaesthesia, 10 mg of Bupivacaine plus 100 Î¼g of morphine was administered for all patients. However, patients in the study group received 20 Âµg of naloxone intrathecally; but the patients in the control group only received normal saline as a placebo. After surgery, patient-controlled analgesia (PCA) pump with paracetamol (ApotelÂ®) was connected to each patient. The intensity of postoperative pain in the patients was evaluated and recorded using Visual Acuity Screening (VAS) at 2, 4, 6 and 24 hours after the surgery. The patients were also examined for postoperative nausea and pruritus.

RESULTS: Regardless of the groups to which the patients were assigned, a significant difference in pain intensity was observed during the study period (time effect; p < 0.001). Although the intensity of pain was lower in the study group, the difference was not statistically significant (group effect; p = 0.84). Also, there was no group time interaction between pain intensity and the times studied (p = 0.61). The incidence rates of postoperative nausea and pruritus were significantly lower in the study group compared to the control group (p < 0.001).

CONCLUSION: According to the results of this study, adding low dose naloxone to intrathecal morphine did not significantly change postoperative pain intensity in the patients undergone elective C-section using spinal anaesthesia; however, significantly decreased the severity of postoperative nausea and pruritus.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Lavand'homme P. Postoperative cesarean pain: real but is it preventable? Curr Opin Anaesthesiol. 2018; 31(3):262-267. https://doi.org/10.1097/ACO.0000000000000585 PMid:29521684

Gholipour Baradari A, Firouzian A, Hasanzadeh Kiabi F, Emami Zeydi A, Khademloo M, Nazari Z, et al. Bolus administration of intravenous lidocaine reduces pain after an elective caesarean section: Findings from a randomised, double-blind, placebo-controlled trial. J Obstet Gynaecol. 2017; 37(5):566-570. https://doi.org/10.1080/01443615.2016.1264071 PMid:28604179

Habibi A, Alipour A, Baradari AG, Gholinataj A, Habibi MR, Peivandi S. The Effect of Adding Lidocaine to Patient Controlled Analgesia with Morphine on Pain Intensity after Caesarean Section with Spinal Anesthesia: A Double-Blind, Randomized, Clinical Trial. Open Access Maced J Med Sci. 2019; 7(12):1946-1950. https://doi.org/10.3889/oamjms.2019.545 PMid:31406534 PMCid:PMC6684416

Borges NC, Pereira LV, de Moura LA, Silva TC, Pedroso CF. Predictors for Moderate to Severe Acute Postoperative Pain after Cesarean Section. Pain Res Manag. 2016; 2016:5783817. https://doi.org/10.1155/2016/5783817 PMid:27956847 PMCid:PMC5121467

Kintu A, Abdulla S, Lubikire A, Nabukenya MT, Igaga E, Bulamba F, et al. Postoperative pain after cesarean section: assessment and management in a tertiary hospital in a low-income country. BMC Health Serv Res. 2019; 19(1):68. https://doi.org/10.1186/s12913-019-3911-x PMid:30683083 PMCid:PMC6347795

Siddiqi R, Jafri SA. Maternal satisfaction after spinal anaesthesia for caesarean deliveries. J Coll Physicians Surg Pak. 2009; 19(2):77-80.

Sutton CD, Carvalho B. Optimal Pain Management After Cesarean Delivery. Anesthesiol Clin. 2017; 35(1):107-124. https://doi.org/10.1016/j.anclin.2016.09.010 PMid:28131114

Dongare PA, Nataraj MS. Anaesthetic management of obstetric emergencies. Indian J Anaesth. 2018; 62(9):704-709. https://doi.org/10.4103/ija.IJA_590_18 PMid:30237596 PMCid:PMC6144558

Gandhi KA, Jain K. Management of anaesthesia for elective, low-risk (Category 4) caesarean section. Indian J Anaesth. 2018; 62(9):667-674. https://doi.org/10.4103/ija.IJA_459_18 PMid:30237591 PMCid:PMC6144555

Bujedo BM. Current evidence for spinal opioid selection in postoperative pain. Korean J Pain. 2014; 27(3):200-9. https://doi.org/10.3344/kjp.2014.27.3.200 PMid:25031805 PMCid:PMC4099232

Shin YD, Park SH, Kim HT, Park CJ, Lee JH, Choi YJ. The effect of anaesthesia technique on caesarean section. Pak J Med Sci. 2016; 32(1):147-50. https://doi.org/10.12669/pjms.321.9028 PMid:27022364 PMCid:PMC4795857

Bujedo BM, Santos SG, Azpiazu AU. A review of epidural and intrathecal opioids used in the management of postoperative pain. J Opioid Manag. 2012; 8(3):177-92. https://doi.org/10.5055/jom.2012.0114 PMid:22798178

KjÃ¸lhede P, Bergdahl O, Borendal Wodlin N, Nilsson L. Effect of intrathecal morphine and epidural analgesia on postoperative recovery after abdominal surgery for gynecologic malignancy: an open-label randomised trial. BMJ Open. 2019; 9(3):e024484.

Toljan K, Vrooman B. Low-Dose Naltrexone (LDN)-Review of Therapeutic Utilization. Med Sci (Basel). 2018; 6(4). https://doi.org/10.3390/medsci6040082 PMid:30248938 PMCid:PMC6313374

Block L, Lundborg C, Bjersing J, Dahm P, Hansson E, Biber B. Ultralow Dose of Naloxone as an Adjuvant to Intrathecal Morphine Infusion Improves Perceived Quality of Sleep but Fails to Alter Persistent Pain: A Randomized, Double-blind, Controlled Study. Clin J Pain. 2015; 31(11):968-75. https://doi.org/10.1097/AJP.0000000000000200 PMid:25629634 PMCid:PMC4894772

Sartain JB, Barry JJ, Richardson CA, et al. Effect of combining naloxone and morphine for intravenous patient-controlled analgesia. Anesthesiology. 2003; 99:148-151. https://doi.org/10.1097/00000542-200307000-00024 PMid:12826854

Yeh YC, Lin TF, Wang CH, Wang YP, Lin CJ, Sun WZ. Effect of combining ultralowdose naloxone with morphine in intravenous patient-controlled analgesia: the cut-off ratio of naloxone to morphine for antiemesis after gynecologic surgery. J Formos Med Assoc. 2008; 107:478-484. https://doi.org/10.1016/S0929-6646(08)60156-4

Cepeda MS, Africano JM, Manrique AM, Fragoso W, Carr DB. The combination of low dose of naloxone and morphine in PCA does not decrease opioid requirements in the postoperative period. Pain. 2002; 96(1-2):73-9. https://doi.org/10.1016/S0304-3959(01)00425-0

Firouzian A, Gholipour Baradari A, Alipour A, Emami Zeydi A, Zamani Kiasari A, Emadi SA, et al. Ultra-low-dose Naloxone as an Adjuvant to Patient Controlled Analgesia (PCA) With Morphine for Postoperative Pain Relief Following Lumber Discectomy: A Double-blind, Randomized, Placebo-controlled Trial. J Neurosurg Anesthesiol. 2018; 30(1):26-31. https://doi.org/10.1097/ANA.0000000000000374 PMid:27673505

Cepeda MS, Alvarez H, Morales O, Carr DB. Addition of ultralow dose naloxone to postoperative morphine PCA: unchanged analgesia and opioid requirement but decreased incidence of opioid side effects. Pain. 2004; 107(1-2):41-6. https://doi.org/10.1016/j.pain.2003.09.011 PMid:14715387

Bijur PE, Schechter C, Esses D, Chang AK, Gallagher EJ. Intravenous bolus of ultra-low-dose naloxone added to morphine does not enhance analgesia in emergency department patients. J Pain. 2006; 7(2):75-81. https://doi.org/10.1016/j.jpain.2005.08.008 PMid:16459272

Koo CH, Yoon S, Kim BR, Cho YJ, Kim TK, Jeon Y, et al. Intraoperative naloxone reduces remifentanil-induced postoperative hyperalgesia but not pain: a randomized controlled trial. Br J Anaesth. 2017; 119(6):1161-1168. https://doi.org/10.1093/bja/aex253 PMid:29029049

Nekoui A, Eldufani J, Mayer P, Blaise G. The Effect of Epidural Morphine-Bupivacaine Combined with a Low Dose of Naloxone on Respiratory Function and Analgesia in Patients with Chronic Low-Back Pain. J Health Med Informat. 2018, Vol 9(1): 298. https://doi.org/10.4172/2157-7420.1000298

Rebel A1, Sloan P, Andrykowski M. Postoperative analgesia after radical prostatectomy with high-dose intrathecal morphine and intravenous naloxone: a retrospective review. J Opioid Manag. 2009; 5(6):331-9. https://doi.org/10.5055/jom.2009.0033 PMid:20073407

Song S. The dual effects of naloxone on morphine analgesia: Dose-related different responses on formalin-induced nociception. The Journal of Pain. 2005; 6(3):S21. https://doi.org/10.1016/j.jpain.2005.01.081

Firouzian A, Gholipour Baradari A, Ehteshami S, Zamani Kiasari A, Shafizad M, Shafiei S, et al. The effect of ultra-low-dose intrathecal naloxone on pain intensity after lumbar laminectomy with spinal fusion: A randomized controlled trial. J Neurosurg Anesthesiol. 2018.

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. https://doi.org/10.1213/ANE.0000000000001255 PMid:27089000

Barrons RW, Woods JA. Low-Dose Naloxone for Prophylaxis of Postoperative Nausea and Vomiting: A Systematic Review and Meta-analysis. Pharmacotherapy. 2017; 37(5):546-554. https://doi.org/10.1002/phar.1930 PMid:28349575

He F, Jiang Y, Li L. The effect of naloxone treatment on opioid-induced side effects: A meta-analysis of randomized and controlled trails. Medicine (Baltimore). 2016; 95(37):e4729. https://doi.org/10.1097/MD.0000000000004729 PMid:27631221 PMCid:PMC5402564