Determination of Analgesic Equipotent Doses of Inhaled Metoxyflurane vs. Intravenous Fentanyl
Condition: Acute Pain; Trauma; Hypovolemia
MeSH terms: Acute Pain; Hypovolemia
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of this study is to determinate the equipotent doses of inhaled metoxyflurane vs.
      intravenous fentanyl.
    

Detailed description: 
      Traumatized patients frequently experience pain prehospital due to the fear of adverse
      cardiovascular effects (e.g. hypotension) and respiration depression of opioid treatment,
      leading to insufficient analgesia. Therefore, there is of interest to investigate other
      analgesics that do not have these adverse effects.

      In Norway, methoxyflurane has been approved for the emergency relief of moderate to severe
      trauma pain in conscious adult patients. Metoxyflurane (Penthrox®) do not have these adverse
      effects (hypotension and respiration depression). It is easy to administrate via an
      inhalator, and is therefore suitable for use prehospital. This would possible help to treat
      pain better prehospital.

      There exists no data of how effective metoxyflurane is as an analgesic compared to an opioid.
      The aim of this study is to determinate the equipotent doses of inhaled metoxyflurane vs.
      intravenous fentanyl.

      Ten healthy volunteers (18 - 64 years) will be enrolled in a randomized, double blind,
      placebo-controlled, crossover study using a standard experimental pain model: CPT- Cold
      pressor test (ice water). Our group has used this experimental pain model in earlier studies
      and a crossover study is suitable to compare different drugs.

      Possible side effects will be recorded for both metoxyflurane and fentanyl: sedation,
      dizziness, itching, nausea and vomiting. Respiration frequency and non-invasive blood
      pressure will be recorded every as possible low blood pressure or respiration depression can
      occur.

      The aim of this study is to determinate equipotent doses of inhaled metoxyflurane vs.
      intravenous fentanyl. We have chosen to compare with fentanyl (the comparator) because it is
      a well-known drug in clinical practice for acute pain treatment. In addition, both drugs have
      a fast onset (minutes) and the analgesic effect last for approximately the same time interval
      (20-30 min). Therefore, they are comparable in a clinical setting.

      There exists no exact data of equipotent doses between metoxyflurane and fentanyl, only
      retrospective clinical data. One retrospective study compared intranasal fentanyl with
      inhaled metoxyflurane for visceral pain prehospital in 1024 patients. The initial dose of
      fentanyl was 0.018 mg and the total mean dose at hospital arrival was 0.036 mg. In the
      metoxyflurane group 51.9% received 3 ml, a second dose was used in 41.9% and 6.2% received a
      third dose. Metoxyflurane produced the greatest initial pain scores reduction, and intranasal
      fentanyl provided greater pain reduction by hospital arrival.

      From these data we have chosen two doses of fentanyl to be compared with 3 ml Penthrox: 0.025
      mg and 0.05 mg intravenous. Both drugs will also be compared to placebo (NaCl 9 mg/ml).
    

Intervention name(s): Methoxyflurane (M); Fentanyl (F1); Fentanyl (F2); NaCl (C)
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs, in this intervention inhalation of metoxyflurane 3 ml and NaCl i.v. will be administered.(13,14) The CPT will be conducted using a temperature-controlled bath with circulating 3°C water (FP 45-HE Refrigerated/Heating Circulator, Julabo Labortechnic, 77960 Seelback, Germany). The subjects submerge their right hand to the wrist with fingers abducted for up to 90 s. The endpoints are NRS scores every 10 s.This test will be performed 3 times for each session.; The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs, in this intervention fentanyl 0.025 mg i.v. and NaCl for inhalation will be administered(13,14) The CPT will be conducted using a temperature-controlled bath with circulating 3°C water (FP 45-HE Refrigerated/Heating Circulator, Julabo Labortechnic, 77960 Seelback, Germany). The subjects submerge their right hand to the wrist with fingers abducted for up to 90 s. The endpoints are NRS scores every 10 s.This test will be performed 3 times for each session.; The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs, in this intervention fentanyl 0.05 mg i.v. and NaCl for inhalation will be administered.(13,14) The CPT will be conducted using a temperature-controlled bath with circulating 3°C water (FP 45-HE Refrigerated/Heating Circulator, Julabo Labortechnic, 77960 Seelback, Germany). The subjects submerge their right hand to the wrist with fingers abducted for up to 90 s. The endpoints are NRS scores every 10 s.This test will be performed 3 times for each session.; The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs, in this intervention NaCl i.v. and NaCl inhal will be used - placebo(13,14) The CPT will be conducted using a temperature-controlled bath with circulating 3°C water (FP 45-HE Refrigerated/Heating Circulator, Julabo Labortechnic, 77960 Seelback, Germany). The subjects submerge their right hand to the wrist with fingers abducted for up to 90 s. The endpoints are NRS scores every 10 s.This test will be performed 3 times for each session.
Other intervention name(s): NaCl; NaCl (C); NaCl (C)
Intervention MeSH terms: Fentanyl; Methoxyflurane
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is a randomized, double blind, placebo-controlled crossover study.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: metoxyflurane; pain; fentanyl; cold pressor test