Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| British Columbia Emergency Health Services | UNKNOWN |
Not provided
Not provided
Not provided
Not provided
Acute painful conditions make-up a large proportion of pre-hospital transports in British Columbia (BC) yet Basic Life Support (BLS) paramedics have limited options to provide analgesia and therefore adequate and timely pain relief is often significantly delayed.
Inhaled nitrous oxide is commonly used as a pre-hospital analgesic and is considered "usual care" for pre-hospital providers in BC, but its utility in severe pain is uncertain. Moreover, nitrous oxide is limited in its effectiveness by a short duration of action, nausea, vomiting, and the necessity for patient cooperation.
IN Ketamine has been shown to provide rapid, easily-administered, and well-tolerated analgesia in many settings. The investigators believe that the addition of IN ketamine to usual care with nitrous oxide inhalation for adults experiencing moderate to severe intensity acute pain in the pre-hospital setting will result in improved pain severity, improved patient-reported comfort, and improved patient satisfaction.
Purpose:
The purpose of this study is to see whether intra-nasal (IN) Ketamine (50 mg / ml) solution (Sandoz; Drug Identification Number (DIN) 02246796) administered via mucosal atomization device (LMA MAD300 Nasal TM; Wolfe Tory Medical Inc., San Diego, CA), in addition to usual care with nitrous oxide inhalation, to pre-hospital patients being transported by British Columbia Emergency Health Services (BC EHS) Basic Life Support (BLS) paramedics with moderate to severe pain (pain > 5/10 on a validated numerical rating scale or NRS) will improve pain relative to usual care plus placebo.
Hypothesis:
It is hypothesized that the addition of IN ketamine to usual care with nitrous oxide inhalation for adults experiencing moderate to severe intensity acute pain in the pre-hospital setting will result in a greater proportion of patients experiencing a 2-point or more reduction in verbal numerical rating scale (VNRS) pain score within 30 minutes, as well as improved patient-reported comfort, reduced nitrous oxide requirements, and improved patient and provider satisfaction compared to usual care alone.
Background:
Acute painful conditions make-up a large proportion of pre-hospital transports yet BLS paramedics have limited options to provide analgesia, and therefore, adequate and timely pain relief is often significantly delayed. Inhaled nitrous oxide is commonly used as a pre-hospital analgesic and is considered "usual care" for BLS pre-hospital providers. Nitrous oxide has been shown to be effective for analgesia in patients with moderate pain but its utility in severe pain is uncertain. No alternative treatments exist for BLS providers in the pre-hospital setting. Intra-nasal ketamine is a safe, well-tolerated means of providing analgesia and has been proven to work in the pre-hospital setting without the need for cardio-respiratory monitoring.
Objectives:
The objective of this study is to collect pilot data to compare the addition of intranasal Ketamine or an intranasal placebo in terms of efficacy and effectiveness in patients receiving usual care with nitrous oxide for moderate to severe pain.
Secondary objectives will be to assess subjective improvement in pain, effect on nitrous oxide requirements, incidence of adverse effects, patient and provider satisfaction, and study recruitment potential. These data will inform future large-scale trial designs and will be used to validate a proposed 7-point patient-reported pain improvement scale.
Research Methods:
This will be a randomized double-blind pilot trial conducted in the pre-hospital setting in the lower mainland. The pilot series will constitute 40 patients (20 per group). The sample size for a larger randomized controlled trial will then be calculated using the effect size and variance of the accrued data.
Statistical Analysis:
A statistician will be contracted to independently oversee the analysis of study results. The intention-to-treat principal will be used to analyze all data. Data will be analyzed using descriptive statistics. Categorical data will be presented as frequency and percentage frequency of occurrence. Continuous data will be presented as medians with ranges and interquartile ranges (IQRs). Adverse effects will be described as frequency of occurrence with 95% confidence intervals. A p-value of 0.05 will be considered statistically significant.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intranasal Ketamine | Experimental | Ketamine dosing will be weight-based as follows: 30mg of IN ketamine for patients weighing 50 kg or less; 50 mg of IN ketamine for patients weighing 50 kg to 100 kg; and 75 mg of IN ketamine for patients weighing greater than 100 kg (i.e. 0.5 mg/kg to 1.0 mg/kg of intranasal ketamine). Syringes containing ketamine will be prepared from the intravenous formulation of Ketamine (50 mg / ml) solution (Sandoz; DIN 02246796) and stored in pre-filled 5 ml syringes. Ketamine will be administered to patients through a mucosal atomization device. One-half of the pre-specified volume will be administered into each nare. No repeat doses will be administered. |
|
| Placebo | Placebo Comparator | Syringes containing normal saline will be prepared such that the volume of normal saline in 5 ml syringes matches that of the ketamine for each of the weight based groups previously specified in the Treatment Arm Description. Syringes containing normal saline will also be labeled "Study Drug". The normal saline will also be administered to patients through a mucosal atomization device. One-half of the pre-specified volume will be administered into each nare. No repeat doses of placebo will be administered. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketamine | Drug | Intranasal Ketamine administered via mucosal atomization device at 0.5 - 1 mg / kg IN. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion experiencing 2-point or more pain score reduction at 30 minutes | The proportion of patients experiencing a 2-point or more reduction in NRS pain score at 30 minutes. | 30 minutes. |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion experiencing 2-point or more pain score reduction at 15 minutes | The proportion of patients experiencing a 2-point or more reduction in NRS pain score at 15 minutes. | 15 minutes |
| The proportion of patients feeling "a lot better" or "moderately better" at 30 minutes post medication delivery or hospital at hospital arrival |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Gary Andolfatto | University of British Columbia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| British Columbia Emergency Health Services Station 249 | Surrey | British Columbia | V3V 1Z2 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26024309 | Background | Murphy A, McCoy S, O'Reilly K, Fogarty E, Dietz J, Crispino G, Wakai A, O'Sullivan R. A Prevalence and Management Study of Acute Pain in Children Attending Emergency Departments by Ambulance. Prehosp Emerg Care. 2016;20(1):52-8. doi: 10.3109/10903127.2015.1037478. Epub 2015 May 29. | |
| 12385606 | Background | McLean SA, Maio RF, Domeier RM. The epidemiology of pain in the prehospital setting. Prehosp Emerg Care. 2002 Oct-Dec;6(4):402-5. doi: 10.1080/10903120290938021. |
| Label | URL |
|---|---|
| British Columbia Ambulance Service information page. | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D010146 | Pain |
| D059787 | Acute Pain |
| D000377 | Agnosia |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010468 | Perceptual Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D007649 | Ketamine |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Normal Saline | Drug | Intranasal Normal Saline administered via mucosal atomization device. |
|
|
The proportion of patients feeling "a lot better" or "moderately better" at 30 minutes post medication delivery or hospital at hospital arrival |
| 30 minutes |
| The proportion of patients feeling "a lot better" or "moderately better" at 15 minutes. | The proportion of patients feeling "a lot better" or "moderately better" at 15 minutes. | 15 minutes |
| The proportion of patients feeling "a lot better", "moderately better" or "a little better" at 15 minutes and at 30 minutes. | The proportion of patients feeling "a lot better", "moderately better" or "a little better" at 15 minutes and at 30 minutes. | 15 minutes, 30 minutes |
| Adverse Events | Incidence of adverse events. | Every 15 minutes until care transferred to Emergency Department |
| Patient Satisfaction | Patient satisfaction with analgesia provided using a ten point numeric rating scale anchored with 0 = "not at all satisfied" and 10 = "completely satisfied" on hospital arrival. | At 30 minutes post analgesia administration. |
| Provider Satisfaction | Paramedic satisfaction with analgesia provided using a ten point numeric rating scale anchored with 0 = "not at all satisfied" and 10 = "completely satisfied" on hospital arrival. | At 30 minutes post analgesia administration. |
| Median Nitrous Oxide Consumption | Median nitrous oxide consumption in each group will be recorded and compared. | At 30 minutes post analgesia administration. |
| Median reduction in pain score at 15 minutes | Median reduction in NRS pain score at 15 minutes | 15 minutes |
| Median reduction in pain score at 30 minutes | Median reduction in NRS pain score at 30 minutes | 30 minutes |
| 19490463 | Background | Marinangeli F, Narducci C, Ursini ML, Paladini A, Pasqualucci A, Gatti A, Varrassi G. Acute pain and availability of analgesia in the prehospital emergency setting in Italy: a problem to be solved. Pain Pract. 2009 Jul-Aug;9(4):282-8. doi: 10.1111/j.1533-2500.2009.00277.x. Epub 2009 Mar 16. |
| 19497456 | Background | Lord B, Cui J, Kelly AM. The impact of patient sex on paramedic pain management in the prehospital setting. Am J Emerg Med. 2009 Jun;27(5):525-9. doi: 10.1016/j.ajem.2008.04.003. |
| 20679429 | Background | Jennings PA, Cameron P, Bernard S. Epidemiology of prehospital pain: an opportunity for improvement. Emerg Med J. 2011 Jun;28(6):530-1. doi: 10.1136/emj.2010.098954. Epub 2010 Aug 2. |
| 8216592 | Background | Chambers JA, Guly HR. The need for better pre-hospital analgesia. Arch Emerg Med. 1993 Sep;10(3):187-92. doi: 10.1136/emj.10.3.187. |
| 23406077 | Background | Ducasse JL, Siksik G, Durand-Bechu M, Couarraze S, Valle B, Lecoules N, Marco P, Lacombe T, Bounes V. Nitrous oxide for early analgesia in the emergency setting: a randomized, double-blind multicenter prehospital trial. Acad Emerg Med. 2013 Feb;20(2):178-84. doi: 10.1111/acem.12072. |
| 24779097 | Background | Oglesbee S, Selde W. Nitrous oxide. New delivery of an old drug. JEMS. 2014 Apr;39(4):34-7. No abstract available. |
| 16299211 | Background | Faddy SC, Garlick SR. A systematic review of the safety of analgesia with 50% nitrous oxide: can lay responders use analgesic gases in the prehospital setting? Emerg Med J. 2005 Dec;22(12):901-8. doi: 10.1136/emj.2004.020891. |
| 23672762 | Background | Johansson J, Sjoberg J, Nordgren M, Sandstrom E, Sjoberg F, Zetterstrom H. Prehospital analgesia using nasal administration of S-ketamine--a case series. Scand J Trauma Resusc Emerg Med. 2013 May 14;21:38. doi: 10.1186/1757-7241-21-38. |
| 12487045 | Background | Borland ML, Jacobs I, Geelhoed G. Intranasal fentanyl reduces acute pain in children in the emergency department: a safety and efficacy study. Emerg Med (Fremantle). 2002 Sep;14(3):275-80. doi: 10.1046/j.1442-2026.2002.00344.x. |
| 17067720 | Background | Borland M, Jacobs I, King B, O'Brien D. A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department. Ann Emerg Med. 2007 Mar;49(3):335-40. doi: 10.1016/j.annemergmed.2006.06.016. Epub 2006 Oct 25. |
| 19125831 | Background | Borland ML, Clark LJ, Esson A. Comparative review of the clinical use of intranasal fentanyl versus morphine in a paediatric emergency department. Emerg Med Australas. 2008 Dec;20(6):515-20. doi: 10.1111/j.1742-6723.2008.01138.x. |
| 20070272 | Background | Holdgate A, Cao A, Lo KM. The implementation of intranasal fentanyl for children in a mixed adult and pediatric emergency department reduces time to analgesic administration. Acad Emerg Med. 2010 Feb;17(2):214-7. doi: 10.1111/j.1553-2712.2009.00636.x. |
| 24268523 | Background | Karlsen AP, Pedersen DM, Trautner S, Dahl JB, Hansen MS. Safety of intranasal fentanyl in the out-of-hospital setting: a prospective observational study. Ann Emerg Med. 2014 Jun;63(6):699-703. doi: 10.1016/j.annemergmed.2013.10.025. Epub 2013 Nov 22. |
| 21574967 | Background | Jennings PA, Cameron P, Bernard S. Ketamine as an analgesic in the pre-hospital setting: a systematic review. Acta Anaesthesiol Scand. 2011 Jul;55(6):638-43. doi: 10.1111/j.1399-6576.2011.02446.x. Epub 2011 May 16. |
| 25245275 | Background | Green SM, Andolfatto G, Krauss BS. Ketamine and intracranial pressure: no contraindication except hydrocephalus. Ann Emerg Med. 2015 Jan;65(1):52-4. doi: 10.1016/j.annemergmed.2014.08.025. Epub 2014 Sep 20. No abstract available. |
| 25447557 | Background | Graudins A, Meek R, Egerton-Warburton D, Oakley E, Seith R. The PICHFORK (Pain in Children Fentanyl or Ketamine) trial: a randomized controlled trial comparing intranasal ketamine and fentanyl for the relief of moderate to severe pain in children with limb injuries. Ann Emerg Med. 2015 Mar;65(3):248-254.e1. doi: 10.1016/j.annemergmed.2014.09.024. Epub 2014 Nov 18. |
| 20961685 | Background | Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011 Mar;152(3 Suppl):S2-S15. doi: 10.1016/j.pain.2010.09.030. Epub 2010 Oct 18. |
| 9708149 | Background | Kulbe J. The use of ketamine nasal spray for short-term analgesia. Home Healthc Nurse. 1998 Jun;16(6):367-70. No abstract available. |
| 24654665 | Background | Plunkett A, Turabi A, Wilkinson I. Battlefield analgesia: a brief review of current trends and concepts in the treatment of pain in US military casualties from the conflicts in Iraq and Afghanistan. Pain Manag. 2012 May;2(3):231-8. doi: 10.2217/pmt.12.18. |
| 21292791 | Background | Reid C, Hatton R, Middleton P. Case report: prehospital use of intranasal ketamine for paediatric burn injury. Emerg Med J. 2011 Apr;28(4):328-9. doi: 10.1136/emj.2010.092825. Epub 2011 Feb 3. |
| 24127709 | Background | 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. |
| 15109503 | Background | Carr DB, Goudas LC, Denman WT, Brookoff D, Staats PS, Brennen L, Green G, Albin R, Hamilton D, Rogers MC, Firestone L, Lavin PT, Mermelstein F. Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain: a randomized, double-blind, placebo-controlled, crossover study. Pain. 2004 Mar;108(1-2):17-27. doi: 10.1016/j.pain.2003.07.001. |
| 17499654 | Background | 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. |
| 23521979 | Background | Marland S, Ellerton J, Andolfatto G, Strapazzon G, Thomassen O, Brandner B, Weatherall A, Paal P. Ketamine: use in anesthesia. CNS Neurosci Ther. 2013 Jun;19(6):381-9. doi: 10.1111/cns.12072. Epub 2013 Mar 22. |
| 8881626 | Background | Malinovsky JM, Servin F, Cozian A, Lepage JY, Pinaud M. Ketamine and norketamine plasma concentrations after i.v., nasal and rectal administration in children. Br J Anaesth. 1996 Aug;77(2):203-7. doi: 10.1093/bja/77.2.203. |
| 12516077 | Background | Yanagihara Y, Ohtani M, Kariya S, Uchino K, Hiraishi T, Ashizawa N, Aoyama T, Yamamura Y, Yamada Y, Iga T. Plasma concentration profiles of ketamine and norketamine after administration of various ketamine preparations to healthy Japanese volunteers. Biopharm Drug Dispos. 2003 Jan;24(1):37-43. doi: 10.1002/bdd.336. |
| 15601346 | Background | Weber F, Wulf H, Gruber M, Biallas R. S-ketamine and s-norketamine plasma concentrations after nasal and i.v. administration in anesthetized children. Paediatr Anaesth. 2004 Dec;14(12):983-8. doi: 10.1111/j.1460-9592.2004.01358.x. |
| 19733106 | Background | Huge V, Lauchart M, Magerl W, Schelling G, Beyer A, Thieme D, Azad SC. Effects of low-dose intranasal (S)-ketamine in patients with neuropathic pain. Eur J Pain. 2010 Apr;14(4):387-94. doi: 10.1016/j.ejpain.2009.08.002. Epub 2009 Sep 3. |
| 24712757 | Background | Yeaman F, Meek R, Egerton-Warburton D, Rosengarten P, Graudins A. Sub-dissociative-dose intranasal ketamine for moderate to severe pain in adult emergency department patients. Emerg Med Australas. 2014 Jun;26(3):237-42. doi: 10.1111/1742-6723.12173. Epub 2014 Apr 8. |
| 15943962 | Background | Jensen MP, Martin SA, Cheung R. The meaning of pain relief in a clinical trial. J Pain. 2005 Jun;6(6):400-6. doi: 10.1016/j.jpain.2005.01.360. |
| 21856077 | Background | Ferreira-Valente MA, Pais-Ribeiro JL, Jensen MP. Validity of four pain intensity rating scales. Pain. 2011 Oct;152(10):2399-2404. doi: 10.1016/j.pain.2011.07.005. |
| 25271179 | Background | Bahreini M, Jalili M, Moradi-Lakeh M. A comparison of three self-report pain scales in adults with acute pain. J Emerg Med. 2015 Jan;48(1):10-8. doi: 10.1016/j.jemermed.2014.07.039. Epub 2014 Sep 27. |
| 30926189 | Derived | 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. |
| D019954 | Neurobehavioral Manifestations |
| D009422 | Nervous System Diseases |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |