Intranasal ketamine an effective alternative to IV morphine for acute analgesia in EDs
Intranasal ketamine for acute traumatic pain in the Emergency Department: a prospective, randomized clinical trial of efficacy and safetyBMC Emerg Med. 2016 Nov 9;16(1):43
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90 patients presenting to the emergency department with moderate to severe pain due to mild or moderate blunt trauma were randomized to be managed with either intranasal (IN) ketamine, intravenous (IV) morphine, or intramuscular (IM) morphine. Patients were assessed for pain every 5 minutes for the first 60 minutes after administration. Results demonstrated significantly earlier onset of clinically relevant pain reduction in the IN ketamine and IV morphine groups compared to the IM morphine group. Adverse events related to confusion, dizziness, and difficulty concentrating were more frequent following IN ketamine administration, while morphine administration was associated with a greater incidence of dry mouth.
Was the allocation sequence adequately generated?
Was allocation adequately concealed?
Blinding Treatment Providers: Was knowledge of the allocated interventions adequately prevented?
Blinding Outcome Assessors: Was knowledge of the allocated interventions adequately prevented?
Blinding Patients: Was knowledge of the allocated interventions adequately prevented?
Was loss to follow-up (missing outcome data) infrequent?
Are reports of the study free of suggestion of selective outcome reporting?
Were outcomes objective, patient-important and assessed in a manner to limit bias (ie. duplicate assessors, Independent assessors)?
Was the sample size sufficiently large to assure a balance of prognosis and sufficiently large number of outcome events?
Was investigator expertise/experience with both treatment and control techniques likely the same (ie.were criteria for surgeon participation/expertise provided)?
Yes = 1
Uncertain = 0.5
Not Relevant = 0
No = 0
The Reporting Criteria Assessment evaluates the transparency with which authors report the methodological and trial characteristics of the trial within the publication. The assessment is divided into five categories which are presented below.
Inclusion / Exclusion
Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA. J Clin Epidemiol. 1992;45:255-65
The Fragility Index is a tool that aids in the interpretation of significant findings, providing a measure of strength for a result. The Fragility Index represents the number of consecutive events that need to be added to a dichotomous outcome to make the finding no longer significant. A small number represents a weaker finding and a large number represents a stronger finding.
Why was this study needed now?
Patients presenting to the orthopaedic emergency department are often in a significant amount of pain. Opiates have traditionally been used as a form of analgesia in these patients. The use of these drugs often requires close monitoring of patients, as hemodynamic or respiratory complications can be quite common. Interest has increased in the possible use of intranasal ketamine in the treatment of these patients, avoiding not only the need for the monitoring associated with opioids, but also avoiding the administration of injections. There is a paucity of evidence evaluating the use of intranasal ketamine in this setting; hence, the need for this study.
What was the principal research question?
In the management of pain for patients presenting to the ED with traumatic limb or spine injuries, what is the efficacy and safety of intranasal ketamine, compared to either intravenous morphine or intramuscular morphine, when assessed over the first 60 minutes after admittance?
What were the important findings?
- Time to clinically relevant pain reduction was significantly shorter in the IN ketamine group (14.3min [95%CI 9.8-18.8]) and the IV morphine group (8.9min [95%CI 6.6-11.2]) compared to the IM morphine group (26.0min [95%CI 20.3-31.7]) (p=0.003 and 0.000, respectively); there was no significant difference between the IN ketamine group and the IV morphine group (p=0.300).
- Overall maximum VAS pain reduction within the first 60 minutes did not significantly differ between the IN ketamine group (56mm), IV morphine group (59mm), and the IM morphine group (48mm) (p=0.300).
- No significant differences in the percentage of patients who did not demonstrate a clinically relevant pain reduction were observed between groups.
- Adverse event monitoring demonstrated a significantly higher incidence of difficulty concentrating in the IN ketamine group compared to the two morphine groups. The was also a significantly higher incidence of confusion in the IN ketamine group compared to the IV morphine group, and a significantly higher incidence of dizziness in the IN ketamine group compared to the IM morphine group. Adverse events related to dry mouth were significantly more frequent in the morphine groups compared to the IN ketamine group.
- Overall, no significant difference in the degree of patient satisfaction was observed between the IN ketamine group (58.7mm [95%CI 45.3-72.1]), IV morphine group (70.2mm [95%CI 55.2-85.2]), and IM morphine group (73.9mm [95%CI 62.9-84.9]).
- No statistically significant differences in vital signs were observed between the three groups.
What should I remember most?
In the management of pain for those presenting to emergency departments with traumatic limb or spine injuries, the use of intranasal ketamine demonstrated similar analgesic efficacy and hemodynamic/respiratory safety over 60 minutes after administration when compared to intravenous morphine. Both intranasal ketamine and intravenous morphine demonstrated significantly more rapid onset of analgesia when compared to intramuscular morphine.
How will this affect the care of my patients?
The results of this study suggest that intranasal administration of ketamine may offer an effective alternative and easier-to-administer method of acute analgesia to intravenous morphine in managing patients in emergency departments with severe pain due to blunt trauma resulting in limb and spine injuries.
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