Intranasal Ketamine Versus Subcutaneous Ketamine for Treatment of Post-traumatic Acute Pain in the Emergency Department ( INVESCK )

Acute Pain Clinical Trial

Official title:

Intranasal Ketamine Versus Subcutaneous Ketamine for Treatment of Post Traumatic Acute Pain in the Emergency Department

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05229055
• Other study ID #: Intranasal ketamine
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: April 15, 2023
• Est. completion date: December 1, 2025

Study information

• Verified date: May 2023
• Source: University of Monastir
• Contact: Nouira Semir, Professor
• Phone: 73106046
• Email: semir.nouira[@]rns.tn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Pain is the most common complaint for emergency department (ED) visit. Intranasal ketamine has been shown to provide rapid, well-tolerated, effective analgesia to emergency department (ED) patients with acute pain. few trials have studied ketamine infusion subcutaneously for pain management in trauma patients.

Description:

Materials and methods :

Study design It is a randomized, prospective, double blind, controlled, multicentric trial.

Study setting and selection of participants :

The trial is conducted in three community teaching hospitals :

• Emergency department, fattouma bourgiba university hospital, monastir, tunisia.

• Emergency department, sahloul university hospital, sousse, tunisia.

• Emergency department, farhat hached university hospital, sousse, tunisia.

Inculsion criteria :

The study includes patients aged 18 to 60 years who presented to the ED with acute limb trauma pain with a visual analgesic scale (VAS) of 5 or more on a standard 11 point (0-10). An informed consent is necessary. Pain was considered traumatic if it is reported as appearing immediately after the trauma and no anterior pain was described in the same limb.

The intranasal route Ketamine solution 250 mg/5ml was used. It was applied intranasally using a nasal spray pump where each spray delivered approximately 0.4 ml of solution corresponding to 20 mg of ketamine. After initial evaluation, each patient having the inclusion criteria receives one pulverisation (0.4 ml) per nostril of ketamine corresponding to a total dose of 20 mg of ketamine. Ketamine dosing was based on previous reports of intranasal ketamine use in ED patients, doses ranged from 0.45mg/kg to 1.25mg/kg.

The subcutaneous route :

Ketamine dosing by subcutanous route was based on previous reports use for post operative pain management. . The results of these reports revealed that low-dose ketamine 20-60 mg (0.5mg/kg for patients weighing 40-120 kg) showed an over all decrease in either the amount of opioid used or the amount of pain experienced. the investigators decided to chose a dose of 20mg of ketamine for all patients administered via 1ml insulin syringe once subcutaneously.

Protocol :

After initial medical evaluation, every patient who meet the inclusion criteria, will receive randomly either subcutaneous or intanasal dose of ketamine as detailed above according to the predetermined randomization. To ensure a double-blind administration of ketamine ; patients enrolled in the intranasal ketamine group will receive concomitantly 1ml of normal saline solution subcutaneously, and patients enrolled in the subcutaneous ketamine group will receive concomitantly a spray of normal saline solution in each nostril. None of the treating physician or nurses are aware about the medication received. The included patients were followed and monitored until their discharge from the ED. All enrolled patients underwent close supervision of study staff to ensure safety. Study investigators record VAS, and adverse effects at 15, 30, 60, 90, and 120 minutes and at ED discharge. During ED stay, patients were monitored in order to evaluate the need for rescue analgesic treatment. At 30 minutes, if patients report a pain numeric rating scale score of 5 or greater and request additional pain relief, titrated morphine is adminstered as a rescue analgesic with a dose of 0.1mg/kg repeated every 3 to 5 minutes if the pain numeric rating scale score is still greater or equal to 3.

. Patients's informed consent is obtained.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 1, 2025
• Est. primary completion date: May 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• • Patients who presented to the ED with acute limb trauma pain with a visual analgesic scale (VAS) of 5 or more on a standard 11 point (0-10).

• Pain was considered traumatic if it is reported as appearing immediately after the trauma and no anterior pain was described in the same limb.

Exclusion Criteria:

• Pregnancy/Breastfeeding

• altered mental status (GCS<15)

• Allergy to ketamine or morphine

• Weight less than 40 kg or greater than 100kg

• Unstable vital signs (systolic blood pressure <90 or > 180mmHg, pulse rate<50 or >150bpm, and respiration rate <10 or >30 breath/min)

• Medical history of acute head or eye injury

• Medical history of seizure

• Medical history of intracranial hypertension,

• Medical history of chronic pain,

• Medical history of severe renal or hepatic insufficiency.

• Medical history of glaucoma

• Alcohol or drug abuse

• Psychiatric illness,

• Recent (4 hours before) analgesic agent use.

Related Conditions & MeSH terms

• Acute Pain
• Emergencies

Intervention

Drug:
• Ketamine
giving ketamine intranasal

Locations

Country	Name	City	State
Tunisia	university of Monastir	Monastir

Sponsors (1)

Lead Sponsor	Collaborator
University of Monastir

Country where clinical trial is conducted

Tunisia, 

References & Publications (11)

Andolfatto G, Innes K, Dick W, Jenneson S, Willman E, Stenstrom R, Zed PJ, Benoit G. Prehospital Analgesia With Intranasal Ketamine (PAIN-K): A Randomized Double-Blind Trial in Adults. Ann Emerg Med. 2019 Aug;74(2):241-250. doi: 10.1016/j.annemergmed.2019.01.048. Epub 2019 Mar 27. — View Citation

Andolfatto G, Willman E, Joo D, Miller P, Wong WB, Koehn M, Dobson R, Angus E, Moadebi S. Intranasal ketamine for analgesia in the emergency department: a prospective observational series. Acad Emerg Med. 2013 Oct;20(10):1050-4. doi: 10.1111/acem.12229. — View Citation

Elia N, Tramer MR. Ketamine and postoperative pain--a quantitative systematic review of randomised trials. Pain. 2005 Jan;113(1-2):61-70. doi: 10.1016/j.pain.2004.09.036. — View Citation

Galinski M, Dolveck F, Combes X, Limoges V, Smail N, Pommier V, Templier F, Catineau J, Lapostolle F, Adnet F. Management of severe acute pain in emergency settings: ketamine reduces morphine consumption. Am J Emerg Med. 2007 May;25(4):385-90. doi: 10.1016/j.ajem.2006.11.016. — View Citation

Guirimand F, Dupont X, Brasseur L, Chauvin M, Bouhassira D. The effects of ketamine on the temporal summation (wind-up) of the R(III) nociceptive flexion reflex and pain in humans. Anesth Analg. 2000 Feb;90(2):408-14. doi: 10.1097/00000539-200002000-00031. — View Citation

Schmid RL, Sandler AN, Katz J. Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes. Pain. 1999 Aug;82(2):111-125. doi: 10.1016/S0304-3959(99)00044-5. — View Citation

Shrestha R, Pant S, Shrestha A, Batajoo KH, Thapa R, Vaidya S. Intranasal ketamine for the treatment of patients with acute pain in the emergency department. World J Emerg Med. 2016;7(1):19-24. doi: 10.5847/wjem.j.1920-8642.2016.01.003. — View Citation

Smith DC, Mader TJ, Smithline HA. Low dose intravenous ketamine as an analgesic: a pilot study using an experimental model of acute pain. Am J Emerg Med. 2001 Oct;19(6):531-2. doi: 10.1053/ajem.2001.27152. No abstract available. — View Citation

Strigo IA, Duncan GH, Bushnell CM, Boivin M, Wainer I, Rodriguez Rosas EM, Persson J. The effects of racemic ketamine on painful stimulation of skin and viscera in human subjects. Pain. 2005 Feb;113(3):255-264. doi: 10.1016/j.pain.2004.10.023. — View Citation

Todd KH, Ducharme J, Choiniere M, Crandall CS, Fosnocht DE, Homel P, Tanabe P; PEMI Study Group. Pain in the emergency department: results of the pain and emergency medicine initiative (PEMI) multicenter study. J Pain. 2007 Jun;8(6):460-6. doi: 10.1016/j.jpain.2006.12.005. Epub 2007 Feb 15. — View Citation

Tuchscherer J, McKay WP, Twagirumugabe T. Low-dose subcutaneous ketamine for postoperative pain management in Rwanda: a dose-finding study. Can J Anaesth. 2017 Sep;64(9):928-934. doi: 10.1007/s12630-017-0914-0. Epub 2017 Jun 19. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	VAS decrease of more than 50% comparing to initial value at 30 minutes following analgesia administration	resolution of pain with decrease of VAS more than 50% comparing to initial value	30 minutes
Primary	rate of severe adverse events	occurence of severe adverse events	120 minutes
Secondary	rate of rescue analgesia 1 doses of morphine required to reach efficient analgesia	The need for rescue analgesia	30 minutes
Secondary	rate of rescue analgesia 2 doses of morphine required to reach efficient analgesia	The need for rescue analgesia	120 minutes