ESKetamine Low-dose vs Ketamine Low-dose for Severe Acute Pain in Emergency Units, Comparison of PsychodyslEptic Effects

About This Study

Almost 30% of painful patients in emergency departments (ED) describe their pain as severe (i.e. a Verbal Numerical Rating Score VNRS ≥ 6 on a scale ranging from 0 to 10). The management of such severe pain needs to be rapid and safe, and for this purpose intravenous (IV) morphine titration is still the gold-standard. However, morphine titration takes up considerable caregiver time, as patients need to be monitored and treated progressively with small quantities of morphine every 5 minutes until analgesia. This is sometimes difficult to reconcile with a saturating flow of patients, and overcrowding in ED is proven to significantly delay time-to-analgesia, and even lead to deleterious under-treatment. Finally, the opioid crisis is a major concern, explaining why strategies are being advocated to develop other ways of managing severe acute pain in the ED and to limit the use of opioids. Recent studies show that ketamine administered in small IV doses ("low-dose" ketamine LDK: 0.2 to 0.3 mg/kg) possesses potent analgesic activity as well as interesting anti-hyperalgesic and anti-allodynic properties. Compared with morphine, LDK does not induce respiratory depression, but can sometimes induce disturbing psychodysleptic effects. These may include a sensation of unreality, fatigue, anxiety, dizziness or hallucinations. According to studies, 30-80% of LDK-treated patients experience psychodysleptic effects. However, two recent studies suggest that slow IV injections of LDK (over 10 minutes) may improve patient tolerance, although these slow infusions do not totally reduce this discomfort. Pharmacologically, ketamine is a racemic mixture of 2 isomers: esketamine S(+), which is dextrorotatory, and arketamine R(-), which is levorotatory. In recent years, a new formulation containing only esketamine has been made available to hospitals in some northern European countries, and more recently in France. Esketamine appears to have twice the analgesic efficacy of racemic ketamine, and studies on healthy volunteers or in peri-operative settings suggest that it is also better tolerated psychologically than ketamine. For the moment, however, scientific data are lacking, and no comparative trial has yet been conducted in the ED setting. The investigators plan to conduct in their ED a prospective, single-center, randomized, double-blind study aiming to compare the tolerance and efficacy of esketamine versus racemic LDK in patients presenting with severe acute pain (VNRS ≥ 6/10).

Conditions Studied

Interventions

• •Esketamine
• •Ketamine

Eligibility

Inclusion Criteria:

* Adult patients aged 18 or over,
* consulting our emergency department for a medical or traumatic pathology responsible for acute (less than 7 days old) and severe pain (greater than or equal to 6 on the Verbal Numerical Rating Scale, which has 11 levels from 0 = no pain to 10 = maximum imaginable pain).
* Free and informed consent given before the start of the trial.
* Patients affiliated to social security system.

Exclusion Criteria:

* Inability to quantify pain score ;
* proven or suspected intoxication (drug or alcohol) leading to consciousness disorders (Glasgow score less than or equal to 15) ;
* person under legal protection or deprived of liberty ;
* pregnant or breast-feeding patients ;
* known allergy to ketamine or esketamine ;
* history of drug addiction or dependence ;
* insufficiently controlled hyperthyroidism ;
* history of cerebral of myocardial infarction ;
* known severe heart failure ;
* existence of intracranial hypertension, glaucoma or ocular trauma ;
* unstable vital signs (systolic blood pressure \< 90 mmHg or \> 180, heart rate \< 50 per minute or \> 150, respiratory rate \< 10 per minute or \> 30) ;
* chronic treatment with aminophylline, theophylline or methylergometrine ;
* administration of morphine or another opioid within one hour of inclusion ;
* ongoing simultaneous participation in another study that could interfere with the treatment studied or the results of statistical analysis.

Study Locations (1)