Introduction to Penthrox (Methoxyflurane)
Penthrox, commonly known as the "green whistle," is a self-administered, inhaled analgesic used for the short-term relief of moderate to severe pain in conscious adults [1.3.3, 1.9.5]. The active ingredient is methoxyflurane, a volatile anaesthetic agent that provides pain relief at sub-anaesthetic doses [1.4.4]. Its portability and rapid onset make it a valuable tool in emergency departments, for minor surgical procedures, and in pre-hospital settings like ambulance services [1.3.3, 1.9.2]. Historically, methoxyflurane was used as a general anaesthetic in the 1960s but was withdrawn from the market in the US in 2005 due to risks of kidney and liver toxicity at high doses [1.3.3]. The modern Penthrox inhaler uses a much lower dose (3mL), which has been found to be safe and effective for analgesia without the significant adverse effects associated with higher anaesthetic doses [1.3.3, 1.4.4].
Onset and Duration of Analgesic Effects
The primary question for both clinicians and patients is, how long do the effects of Penthrox last? The duration is dependent on the method of inhalation.
- Onset of Action: Pain relief begins very rapidly, typically after just 6 to 10 breaths [1.2.3, 1.2.4]. The median time to first pain relief has been reported to be as short as 3 to 4 minutes [1.6.3, 1.6.4].
- Duration with Continuous Use: A single 3mL vial of Penthrox provides analgesia for approximately 25 to 30 minutes if inhaled continuously [1.3.1, 1.3.5].
- Duration with Intermittent Use: If the patient inhales intermittently, as needed for pain, the duration of relief from a single 3mL vial can be extended to about 60 minutes [1.2.4, 1.3.4].
- Post-Inhalation Effect: After ceasing inhalation, the pain-relieving effect continues for several minutes [1.2.1, 1.2.3]. The effects are quickly reversible, which is an advantage as it does not limit subsequent treatment options [1.3.1].
If pain persists, a second 3mL dose can be administered. However, the total dose should not exceed 6mL in a single day [1.3.2]. The maximum recommended weekly dose is 15mL, and it is advised not to use Penthrox on consecutive days to minimize any potential risks [1.3.3].
Pharmacokinetics: How the Body Processes Penthrox
The duration of Penthrox is governed by its pharmacokinetics. Methoxyflurane has high lipid solubility, meaning it is readily absorbed into fatty tissues [1.4.2].
- Absorption: The drug is rapidly absorbed into the bloodstream via the lungs upon inhalation [1.4.3].
- Metabolism: About 50-75% of the absorbed methoxyflurane is metabolized by the liver [1.8.5]. This process produces metabolites, including fluoride and dichloroacetic acid [1.4.2, 1.8.4]. At the low doses used for analgesia, serum fluoride levels remain well below the known toxic threshold associated with kidney damage [1.3.2, 1.4.4].
- Elimination: The remaining drug is cleared from the body primarily through exhalation [1.4.3]. Because of its high lipid solubility, elimination can be slow as the drug diffuses out of fat tissues over time. However, the analgesic effects diminish quickly once inhalation stops [1.8.2, 1.2.2]. Full recovery is generally rapid, and patients typically do not require a formal recovery process or post-treatment monitoring, although they are advised not to drive [1.5.2, 1.5.5].
Comparison with Other Short-Acting Analgesics
Penthrox offers several advantages over other common analgesics used in emergency and procedural settings. Its efficacy and speed are often compared to nitrous oxide (Entonox) and intravenous opioids like morphine.
| Feature | Penthrox (Methoxyflurane) | Entonox (Nitrous Oxide) | IV Morphine |
|---|---|---|---|
| Onset of Action | 3-5 minutes [1.6.3, 1.6.6] | Rapid, within minutes | 5-10 minutes [1.4.6] |
| Administration | Self-administered inhaler [1.3.3] | Inhaled via mask/mouthpiece | IV injection by clinician |
| Portability | Highly portable, lightweight [1.3.3] | Requires large, heavy cylinders | Requires IV setup |
| Time to Max Relief | ~26 minutes [1.6.2] | ~44 minutes [1.6.2] | ~42 minutes [1.6.2] |
| Recovery | Rapid, no formal monitoring needed [1.5.2] | Very rapid | Longer recovery, potential for sedation |
Studies have shown that Penthrox provides a significantly faster time to first pain relief compared to standard analgesic treatments, including IV paracetamol and ketoprofen (3 minutes vs. 10 minutes) [1.6.3, 1.6.4]. Compared to IV morphine, Penthrox also demonstrates a faster onset of action [1.6.6]. This makes it an excellent bridging agent until other pain management can be administered [1.3.1].
Safety, Side Effects, and Contraindications
While generally safe at analgesic doses, Penthrox is not suitable for everyone.
Common Side Effects
Common side effects are typically mild and transient. These can include [1.7.5, 1.9.2]:
- Dizziness or drowsiness
- Headache
- Nausea
- A feeling of being drunk or euphoric
- Cough
The inhaler contains an activated charcoal chamber to adsorb exhaled methoxyflurane, reducing occupational exposure for healthcare providers [1.3.2].
Contraindications
Patients should not use Penthrox if they have [1.7.5]:
- Clinically significant kidney or liver impairment.
- A personal or family history of malignant hyperthermia.
- Cardiovascular instability or severe respiratory depression.
- Altered consciousness (e.g., from head injury, drugs, or alcohol).
It should be used with caution in the elderly and should not be administered with certain nephrotoxic drugs like tetracycline antibiotics [1.3.3]. Patients are advised not to drive or operate machinery after use if they feel drowsy or dizzy [1.2.2, 1.7.4].
Conclusion
The effects of a standard 3mL dose of Penthrox last for approximately 25-30 minutes with continuous inhalation and up to an hour with intermittent use [1.2.4, 1.3.4]. Its rapid onset within 6-10 breaths provides fast and effective relief for acute, moderate-to-severe pain [1.2.3]. While its historical use at high anaesthetic doses was associated with significant toxicity, the modern low-dose Penthrox inhaler has a strong safety profile, offering a convenient, non-opioid alternative for patient-controlled analgesia in a variety of clinical settings [1.3.3, 1.4.6]. The quick recovery and minimal side effects further solidify its role as a valuable tool in modern pain management.
For more information, consult the official patient medical information leaflet. An example can be found at medicines.org.uk [1.7.4].
