Effect of Granisetron on Morphine Induced Pruritus in Cesarean Section

NCT03483870 | Completed Phase 2

• 1 other identifier: Granisetron in C.S
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Neuraxial anesthesia, which includes epidural anesthesia and intrathecal anesthesia, is a frequent anesthetic approach for caesarean delivery and other lower abdominal and lower limb anesthetic procedures. The addition of neuraxial morphine to local anesthetics provides an effective and prolonged postoperative analgesia. Neuraxial administration of morphine which is considered as a gold standard for analgesia has been associated with a frequent incidence of pruritus and postoperative nausea and vomiting. The incidence of neuraxial opioid induced pruritus varies widely from 30% - 60% after orthopedic surgery with intrathecal morphine injection and from 60% - 100% in pregnant women after neuraxial opioid administration. Parturients appear to be the most susceptible to neuraxial opioid-induced pruritus which probably might be due to the interaction of estrogens with opioid receptors. Although the exact mechanism of neuraxial opioid induced pruritus is unclear, the postulated mechanisms include the presence of an "itch center" in the central nervous system (CNS), medullary dorsal horn activation, antagonism of inhibitory transmitters, modulation of 5-hydroxytryptamine subtype 3 (5-HT3) or serotonergic pathways and the involvement of prostaglandins. There is dense concentration of opioid receptors and 5-HT3 receptors in the dorsal part of the spinal cord and the nucleus of the spinal tract of the trigeminal nerve in the medulla. Activation of these receptors by neuraxial opioid administration or by circulating estrogen in parturients results in neuraxial opioid induced pruritus which is usually localized to the face, neck, or upper thorax. Nalbuphine, propofol and ondansetron have been used effectively in the treatment of pruritus associated with neuraxial morphine in surgical patients. Granisetron is a potent and highly selective 5-HT3 receptor antagonist that has little or no affinity for other 5-HT receptors, or dopaminergic, adrenergic, benzodiazepine, histaminic, or opioid receptors. Its onset of action is 1-3 min, peak plasma level 30 min, plasma half-life is 4-6 h and duration of action up to 24 h. Its longer duration of action than that of ondansetron may coincide with the peak incidence of pruritus after intrathecal morphine (6-9 h). In contrast, other 5-HT3-receptor antagonists have affinities for various receptor-binding sites. For example, ondansetron has detectable binding to 5-HT1B, 5-HT1C, α1-adrenergic, and μ-opioid receptor sites. Although not proven, the binding of these agents to additional receptor subtypes other than their target receptor may underlie the inferior adverse event profile seen with ondansetron compared with granisetron.

Conditions

Pruritus

Keywords

Granisetron; Serum Serotonin; Morphine

Outcome Measures

Primary Outcomes (1)

• Incidence of pruritus during the first postoperative 24 hours.

  The effect of prophylactic intravenous (IV) administration of granisetron on incidence and severity of pruritus that occurs after intrathecal morphine in parturients undergoing cesarean section (CS).

  24 hours

Secondary Outcomes (5)

• Onset time of pruritus

  24 hours

• The pruritus grading system (PGS)

  24 hours

• Postoperative pain assessment

  24 hours

• Perioperative adverse events

  24 hours

• Participants' satisfaction after end of the delivery

  24 hours

Study Arms (2)

Morphine sulphate & Placebo

PLACEBO COMPARATOR

20 parturients under intrathecal anesthesia will receive 200 ug morphine sulphate intrathecally and 2 mL of normal saline 0.9% (placebo) IV injection preoperative.

Drug: Morphine Sulfate; Drug: Placebo

Morphine sulphate & Granisetron

ACTIVE COMPARATOR

20 parturients under intrathecal anesthesia will receive 200 ug morphine sulphate intrathecally and 2 mL of 2 mg granisetron IV injection preoperative.

Drug: Morphine Sulfate; Drug: Granisetron

Interventions

Morphine Sulfate DRUG

200 ug morphine sulphate will be injected intrathecally

Morphine sulphate & Granisetron; Morphine sulphate & Placebo

Placebo DRUG

2 mL of normal saline 0.9% IV injection

Also known as: Normal saline 0.9%

Morphine sulphate & Placebo

Granisetron DRUG

2 mL of 2 mg granisetron IV injection

Also known as: Kytril, Sancuso

Morphine sulphate & Granisetron

Eligibility Criteria

• Age: 20 Years - 40 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Parturients of American Society of Anesthesiologists (ASA) class I or II physical status.
• Age: 20-40 years.
• At term gestation (≥ 37 weeks) with a singleton uncomplicated pregnancy.
• Elective cesarean delivery under intrathecal anesthesia.

You may not qualify if:

• Parturient refusal.
• Significant organ dysfunctions (e.g., cardiac, respiratory, renal, or liver disorders).
• Morbid obesity (BMI \>35).
• Parturients with known hypersensitivity to granisetron, morphine or amide local anesthetics.
• Parturients with pruritogenic systemic disease.
• A coexisting skin disorder or preexisting pregnancy induced pruritus.
• Parturients with any contraindication for intrathecal anesthesia, e.g. coagulopathy.
• Emergency cesarean section.
• Psychiatric disorders.
• Fetal abnormalities.
• Failed or unsatisfactory intrathecal block.

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Assiut University Hospital

Asyut, Egypt

Location

Related Publications (12)

• Kumar K, Singh SI. Neuraxial opioid-induced pruritus: An update. J Anaesthesiol Clin Pharmacol. 2013 Jul;29(3):303-7. doi: 10.4103/0970-9185.117045.

  PMID: 24106351 RESULT

• Dimitriou V, Voyagis GS. Opioid-induced pruritus: repeated vs single dose ondansetron administration in preventing pruritus after intrathecal morphine. Br J Anaesth. 1999 Nov;83(5):822-3. doi: 10.1093/bja/83.5.822. No abstract available.

  PMID: 10690153 RESULT

• Koju RB, Gurung BS, Dongol Y. Prophylactic administration of ondansetron in prevention of intrathecal morphine-induced pruritus and post-operative nausea and vomiting in patients undergoing caesarean section. BMC Anesthesiol. 2015 Feb 17;15:18. doi: 10.1186/1471-2253-15-18.

  PMID: 25971957 RESULT

• Szarvas S, Harmon D, Murphy D. Neuraxial opioid-induced pruritus: a review. J Clin Anesth. 2003 May;15(3):234-9. doi: 10.1016/s0952-8180(02)00501-9.

  PMID: 12770663 RESULT

• Blower P. A pharmacologic profile of oral granisetron (Kytril tablets). Semin Oncol. 1995 Aug;22(4 Suppl 10):3-5. No abstract available.

  PMID: 7570052 RESULT

• Breen TW, Shapiro T, Glass B, Foster-Payne D, Oriol NE. Epidural anesthesia for labor in an ambulatory patient. Anesth Analg. 1993 Nov;77(5):919-24. doi: 10.1213/00000539-199311000-00008.

  PMID: 8214727 RESULT

• Reich A, Szepietowski JC. Opioid-induced pruritus: an update. Clin Exp Dermatol. 2010 Jan;35(1):2-6. doi: 10.1111/j.1365-2230.2009.03463.x. Epub 2009 Jul 29.

  PMID: 19663845 RESULT

• Charuluxananan S, Kyokong O, Somboonviboon W, Narasethakamol A, Promlok P. Nalbuphine versus ondansetron for prevention of intrathecal morphine-induced pruritus after cesarean delivery. Anesth Analg. 2003 Jun;96(6):1789-1793. doi: 10.1213/01.ANE.0000066015.21364.7D.

  PMID: 12761013 RESULT

• Wood S. Factors influencing the selection of appropriate pain assessment tools. Nurs Times. 2004 Aug 31-Sep 6;100(35):42-7.

  PMID: 15471273 RESULT

• van Wijngaarden I, Tulp MT, Soudijn W. The concept of selectivity in 5-HT receptor research. Eur J Pharmacol. 1990 Jun 12;188(6):301-12. doi: 10.1016/0922-4106(90)90190-9.

  PMID: 2164935 RESULT

• Perez EA, Hesketh P, Sandbach J, Reeves J, Chawla S, Markman M, Hainsworth J, Bushnell W, Friedman C. Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind, randomized parallel study. J Clin Oncol. 1998 Feb;16(2):754-60. doi: 10.1200/JCO.1998.16.2.754.

  PMID: 9469367 RESULT

• Slappendel R, Weber EW, Benraad B, van Limbeek J, Dirksen R. Itching after intrathecal morphine. Incidence and treatment. Eur J Anaesthesiol. 2000 Oct;17(10):616-21. doi: 10.1046/j.1365-2346.2000.00727.x.

  PMID: 11050519 RESULT

Related Links

• Using Pruritus Grading System for Measurement of Pruritus in Patients with Diseases Associated with Itch

MeSH Terms

Conditions

Pruritus

Interventions

Morphine; Saline Solution; Granisetron

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, 2-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) The trial will be planned that neither the doctors (investigator) nor the parturients will be aware of the group allocation. The study drugs will be prepared by an anesthesiologist not involved in performing the intrathecal anesthesia, patient care or in data collection.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: comparison of the effect of intravenous granisetron with the effect of using placebo on morphine induced pruritus in parturients undergoing elective cesarean section under spinal anesthesia.

Study Record Dates

• First Submitted: March 22, 2018
• First Posted: March 30, 2018
• Study Start: June 1, 2018
• Primary Completion: October 1, 2020
• Study Completion: October 30, 2020
• Last Updated: September 9, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)