sign in sign up
<<
Home , Methoxyflurane, Sedation

NEW

Advancing Acute Pain Management

At last, PENTHROX® is here... A guide to Fast, effective pain management designed for fast, efficient patient management. Inhaled patient-controlled analgesia

PENTHROX is indicated for the emergency relief of moderate to severe pain in conscious adult patients with trauma and associated pain

What is inhaled patient-controlled analgesia? Inhaled patient-controlled analgesia allows fully conscious patients to self-administer analgesia by inhaling a through a facemask or mouthpiece. The patient determines the concentration of drug delivered. Although various inhalational anaesthetics have been used for inhaled patient-controlled analgesia (examples include and ) there are currently only two drugs licensed for this purpose in the UK: 50% combined with 50% (N2O/O2) and . Inhaled patient-controlled analgesia has the advantage over oral and parenteral drugs in that it is non-narcotic, with minimal side effects. It allows the patient to regulate the dose he/she receives while requiring relatively little training for the clinician. Table 1 outlines some indications for inhaled analgesia. Penthrox is indicated for the emergency relief of moderate to severe pain in conscious adult patients with Adverse events should be reported. On the other hand, inhaled patient-controlled trauma and associated pain. Please consult the Summary Reporting forms and information can be analgesia has to be used with the same caution of Product Characteristics before prescribing. Information found at www.mhra.gov.uk/yellowcard. Dr John Wright is Consultant in Emergency about this product, including adverse reactions, Adverse events should also be reported to as other forms of analgesia in some cases, such Galen Limited on 028 3833 4974 and select Medicine, Royal Victoria Infirmary, Newcastle- precautions, contra-indications and method of use can as patients with head injury, while it is uniquely be found at www.medicines.org.uk/emc. Legal category: the customer services option, or e-mail upon-Tyne NE1 4LP ([email protected]) POM. Further information is available on request from [email protected]. contraindicated (in the case of N2O/O2) in the Medical information enquiries should also Dr Will Passmore is Specialist Registrar in Galen Limited, Seagoe Industrial Estate, Craigavon, BT63 be directed to Galen Limited. presence of pathological air-containing spaces such 5UA, United Kingdom. Emergency Medicine, Royal Victoria Infirmary, Newcastle-upon-Tyne as pneumothorax. Penthrox Educational materials and training on its administration are available from Galen on request. Date of preparation: January 2016. PMR-JAN-2016-0042.

Untitled-3PEN-15-075 1 A5 Abbreviated ED Ad.indd 1 01/02/2016 17:0616:41 There are many options in the of inhaled patient-controlled analgesia. The 50:50 management of acute pain episodes (Figure 1). Oral mix of nitrous oxide and oxygen is commonly analgesia is often limited by the latency of onset known as Entonox and also Nitronox or Equanox, of therapeutic effect. Acute pain episodes require and is colloquially known as ‘gas and air’. N2O/ rapid and effective pain relief. In these situations O2 is inhaled and exhaled from a portable cylinder clinicians will use more than one route of analgesic through a mouthpiece or facemask, via a regulator. drug administration to achieve rapid analgesia. Indications

Prescribing inhaled N2O/O2 is a popular option because of its rapid patient-controlled analgesia onset and recovery characteristics combined Nitrous oxide 50% and oxygen 50% (N2O/O2) with predictable and reliable analgesic properties Until recently, doctors and allied health professionals (O’Sullivan and Benger, 2003). The analgesic only had this gas as the sole readily available choice effect is reported to be equivalent to a dose of Table 1. Indications for inhaled analgesia Medical* Surgical* Trauma Breakthrough pain, Postoperative pain Fracture reduction palliative patients Splint or plaster application Acute on chronic pain in Renal colic dressings application and changes patients where intravenous access is not possible Obstetric labour pain from Procedural Injured patient without intravenous access in contractions Flexible sigmoidoscopy acute pain Venepuncture Dental procedures Procedural sedation, e.g. joint reduction Tooth extraction Minor surgical procedures: Distressed and in pain, injured paediatric suturing, incision and drainage patient not tolerating intramuscular or intravenous drug administration

*Inhaled methoxyflurane is only licensed in the UK for use in trauma pain, not medical or surgical pain

Figure 1. Analgesic options in acute pain.

Methoxyflurane (Penthrox) Nitrous oxide/oxygen Intranasal , (Entonox) e.g. , sulfentanyl

Options Intravenous analgesia

Intranasal , e.g. , , Intranasal Intranasal diamorphine 15 mg subcutaneous (Chapman et al, There are a number of restrictions to its use. 1943). It has proved to be a very safe agent with Nitrous oxide inhalation is contraindicated in the minimal side effects and is particularly useful for presence of pathological air-containing spaces. managing transient acute pain caused by short- These spaces may expand as the nitrous oxide term procedures such as wound dressings. Its poor diffuses into them faster than diffuses out. solubility in blood allows rapid achievement of The manufacturers explicitly warn against use in analgesia, with an effect usually apparent within conditions such as gross abdominal distension, bowel 60 seconds. When the patient inhales, gas first obstruction, pneumothorax, middle ear and sinus enters the lungs then the pulmonary and systemic disease (BOC Healthcare, 2015). N2O/O2 should circulations. It takes 1–2 minutes to build up be used with caution in patients with significant head reasonable concentrations of nitrous oxide in the injury or decreased levels of consciousness. Since brain. It is also fast to washout of the system (the nitrous oxide affects white blood cell production effects begin to wane after about 30 seconds; Latto et and function if it is used for several hours, it has al, 1973), which is excellent for its safety profile, but been recommended that N2O/O2 should not be also means patients need to have a constant supply administered to immunosuppressed patients or at hand available for adequate analgesia. to patients requiring multiple general anaesthetics (Lazyer, 1978; Brodsky and Cohen, 1986). Clinical management The contraindications to using 2N O/O2 can In most UK clinical settings, N2O/O2 is supplied be limiting in the pre-hospital environment and as an Entonox cylinder, which is white with blue for many patients who attend the emergency and white shoulders (Figure 2). The additional department requiring pain relief. An unusual feature equipment required consists of a demand valve, of this analgesia is that at temperatures below -7°C inhalation tubing, an individual patient filter and the two constituent separate, resulting in the either a mask or individual patient mouthpiece potential outcome of hypoxia because an oxygen-rich (Figure 3). The demand valve ensures that the gas mixture is inhaled initially (Litwin, 2010). Another does not flow unless a negative pressure is achieved, disadvantage of having to have a constant supply of i.e. the patient inhales through the closed circuit. N2O/O2 available is that when a patient is required to move from one department to another, e.g. Figure 2. Entonox cylinder. to radiology, he/she has to be escorted by a porter who also has to transport a large cylinder of gas. Similarly, storage and replacement Figure 3. Mouthpiece used to deliver Entonox. of these large cylinders can be a logistical problem A single dose of 3 ml of methoxyflurane provides for many emergency departments. approximately 25–30 minutes of effective analgesia if used continuously and up to 1 hour if used Methoxyflurane intermittently. An additional dose of 3 ml (total of The alternative inhaled patient-controlled analgesia 6 ml) can be administered subsequently, providing up is methoxyflurane. Methoxyflurane is an almost to 2 hours of effective analgesia (Galen Ltd, 2016). It colourless belonging to the fluorinated is self-administered under observation (with assistance hydrocarbon group of volatile anaesthetic agents. if necessary) using the hand-held Penthrox . It has the characteristic pungent but not unpleasant At the recommended dose, anaesthesia cannot occur. odour of the halogenated anaesthetics (Coffey et The Penthrox inhaler is a small, lightweight, al, 2014). Initially used as an anaesthetic agent, it cylindrical device, approximately fell out of favour with the introduction of newer, 15 cm long. It has a distinctive green colour and non-gaseous anaesthetic techniques and because of effectively looks like a large green whistle. At one concerns about renal toxicity (Crandell et al, 1966). end is a mouthpiece, near which is sited an activated However, methoxyflurane has analgesic properties carbon chamber which has a dilutor hole on top not shared by other halogenated anaesthetics. At which, when covered with the patient’s index finger, sub-anaesthetic levels it is a safe and very effective allows a higher concentration of methoxyflurane analgesic (Tomi et al, 1993). to be inhaled. Internally, the device contains a S-shaped wick which absorbs the Indications liquid methoxyflurane. An internal one-way valve Methoxyflurane has been used effectively and safely near the base allows air and methoxyflurane vapour in Australia, since the 1970s, as an inhalational to be inhaled through the wick. The valve closes analgesic in many areas including trauma, for on expiration to prevent exhalations passing into postoperative analgesia and as analgesia during the atmosphere. A tape is attached to the inhaler burns dressing changes (Grindlay and Babl, 2009). Figure 4. Penthrox delivery system for In the UK it is indicated for emergency relief of methoxyflurane. moderate to severe pain in conscious adult patients with trauma and associated pain. It has the unique ability of causing rapid and profound analgesia at low concentrations. The pain relief produced is equivalent to 10 mg intramuscular morphine (Yakaitis et al, 1972). It is therefore excellent in situations requiring easy and safe administration to achieve rapid relief of pain with minimal side effects.

Clinical management The ‘green whistle’ delivery system Figure( 4) (Penthrox™ inhaler – Medical Developments International) has been in use for almost 40 years. This device delivers a small dose (3 ml) of methoxyfluorane which provides strong and long- lasting analgesia in a variety of settings. It is used by ambulance services, the military, first aid officers, in ski-fields and mines, and in the emergency departments of several major hospitals. to provide support around the patient’s wrist. The What evidence there is suggests that methoxyflurane inhaler is a single-patient use device which prevents compares well to N2O/O2 (Tomlin et al, 1973; cross contamination between patients and is easily Abdullah et al, 2011). Furthermore, a review disposed of after use. article assessing the efficacy of methoxyflurane in The major concern with methoxyflurane is the pre-hospital and emergency department setting , which has only been reported concluded that it was an efficacious analgesic with no following anaesthetic use (large doses for several significant adverse effects (Grindlay and Babl, 2009). hours) and has been attributed to the breakdown A UK-based multicentre double-blind, randomized, product, inorganic fluoride ions (Kharasch et al, controlled clinical study was conducted to investigate 1995). There is no evidence of nephrotoxicity the safety and efficacy of methoxyflurane at analgesic associated with subanaesthetic doses. There doses vs placebo in patients aged ≥12 years presenting have been reported cases of hepatitis, thought to the emergency department with pain associated to be an idiosyncratic response resulting from a with minor to moderate trauma. The authors hypersensitivity reaction. concluded that ‘methoxyflurane administered via the Penthrox inhaler is an efficacious, safe, and Comparing N2O/O2 and rapidly acting analgesic’ (Coffey et al, 2014). In 2015 methoxyflurane Penthrox received regulatory approval in Europe, Effective use of N2O/O2 requires a tight fit between including the UK. the patient’s face and the mask or a constant seal with the mouthpiece to ensure that any demand valve Managing inhaled patient-controlled system functions correctly. The weight and bulk of analgesia the equipment presents a storage, transport and usage N2O/O2 problem, and excludes its use in many circumstances. Staff instructions Clinicians need to ensure that the gases do not Although rules vary within the UK NHS, in general, separate in cold conditions and care is always staff who have undergone in-service training in the required during cleaning and decontamination use of N2O/O2 and have achieved competencies in to eliminate the possible transmission of the locally agreed clinical procedure can administer microorganisms between patients. When N2O/O2 N2O/O2 without a prescription. Examples of is used continuously over 1 hour, up to 250 litres of professionals who can administer N2O/O2 include nitrous oxide can be excreted into the atmosphere, doctors, and ambulance technicians, a potential hazard to operators chronically exposed nurses, midwives, physiotherapists, radiographers to nitrous oxide (Koulaouzos, 2004). On the other and operating department practitioners. Students hand, methoxyflurane is single-patient use, easily may administer N2O/O2 under the supervision of administered with a rapid onset but gradual offset. a qualified member of staff. The operator does not have to worry about the The patient’s suitability should be assessed to potential expansion of gas-filled cavities and the ensure that he/she understands the use of N2O/O2 potential pollution factor is 200 times less than and has the manual dexterity to hold the hand piece N2O/O2. The main concern clinicians need to keep or facemask unaided. An Entonox cylinder is white in mind is to avoid administering methoxyflurane in colour with blue and white shoulders. ‘Entonox’ to patients with renal disease. should be clearly written on the side of the cylinder. There have been few studies directly comparing Additional equipment includes a demand valve, the efficacy of the two main options for inhaled inhalation tubing, individual patient filter and patient-controlled analgesia, and there is a either a mask or individual patient mouthpiece. compelling argument that a randomized controlled The cylinder should be stored at room temperature trial comparing the two drugs should be done. for at least 24 hours before use and should be stored with the valve in the ‘off’ position. The tap on the patient will then be inhaling pure nitrous oxide, Entonox cylinder should be turned in an anti- which will result in loss of consciousness. Therefore clockwise direction to open the demand valve. The check for any signs of frost on the lower half of gauge should be examined to determine how much the cylinder or a ‘sloshing’ sound when moving the gas is in the cylinder and ensure there is enough to cylinder, which indicates that separation of gases complete the procedure. The effectiveness of2 N O/ has occurred. The cylinder may need to be inverted O2 should be assessed by questioning the patient three times to ensure adequate mixing of the gases. throughout and following the procedure to ensure If excessive sedation or loss of consciousness that adequate levels of analgesia are being achieved. occurs, remove the facemask or mouthpiece from the patient and clear the airway. Support Patient instructions respiration if necessary. Administer oxygen and The patient should be shown the equipment and contact the medical team. If treatment exceeds asked to select for use the mouthpiece or facemask. 4 days, twice-weekly blood cell counts should be If the patient chooses to use the mask, explain that performed looking for evidence of bone marrow he/she should hold it over his/her mouth and nose, suppression (megaloblastic changes in red cells or maintaining an airtight seal, and that he/she should hypersegmentation of neutrophils). breathe normally. If the patient chooses to use the mouthpiece, explain that he/she should hold the After care mouthpiece between the teeth and should breathe Observe the patient until the effects of the gas through the mouth only. Explain how N2O/O2 is have worn off. Turn off the2 N O/O2 supply by used while the clinical procedure is being carried turning the tap in a clockwise direction. Depress out, and describe possible side effects. the diaphragm under the valve. Decontaminate Only the patient should apply and hold the the hand piece, demand valve and facemask in hot apparatus in position. Encourage the patient to soapy water. If the patient has tested positive for practice the technique of N2O/O2 inhalation, by meticillin-resistant Staphylococcus aureus, discuss this self-demand, before the procedure starts. Allow the with the infection control team. Document the use patient to practice using the apparatus for at least of Entonox in the patient’s notes. 30 seconds, ideally 1–2 minutes, before commencing any painful procedure. Encourage the patient to Methoxyflurane breathe normally throughout the procedure and Staff instructions to inform staff if he/she experiences pain. If the Penthrox is a prescription-only drug, but non- patient hyperventilates he/she should be encouraged medical prescribing is permitted. It should to exhale slowly. If the patient experiences any N2O/ therefore be possible for the same groups of health O2-related side effects reassure the patient and cease professionals permitted to administer N2O/O2 to inhalation until the side effects have worn off and administer methoxyflurane via the Penthrox inhaler. the sensation of pain starts to return. Inform the The patient’s suitability should be assessed to ensure patient not to walk around unaided until dizziness that he/she understands the use of methoxyflurane or disorientation has subsided. and has the manual dexterity to hold the inhaler. Inappropriate inhalation of N2O/O2 will Ensure that the patient does not have renal disease cause light-headedness, euphoria and intoxication, or any of the other contraindications before ultimately leading to unconsciousness. Be aware that using. The Penthrox inhaler is a cylindrical green if N2O/O2 has been stored at temperatures below polyethylene device (Figure 3), approximately 15 cm -7°C separation of gases may occur. This will initially long. An activated carbon chamber is inserted into result in lack of analgesia as the patient inhales pure the dilution hole on the top of the inhaler. Then, oxygen. However, once the oxygen is consumed, the while holding the inhaler upright, the base can be NEW used to begin unscrewing the cap with a half turn. Aust Dent J 56: 296–301 BOC Healthcare (2015) ENTONOX® – The Essential The bottle is then separated from the inhaler and Guide. www.bochealthcare.co.uk/internet.lh.lh.gbr/ the cap completely unscrewed. The inhaler is then en/images/entonox_essential_guide_hlc401955_ turned upside down at a 45° angle and the contents Sep10409_64836.pdf (accessed 27 January 2016) of one 3 ml bottle are poured in while rotating and Brodsky JB, Cohen EN (1986) Adverse effects of nitrous oxide. Med Toxicol 5: 362–74 shaking the inhaler lightly. The wrist loop is placed Chapman WP, Arrowhead JG, Beecher HK (1943) The over the patient’s wrist and the patient inhales and analgesic effects of low concentrations of nitrous Advancing Acute Pain Management exhales through the mouthpiece. oxide compared in man with morphine sulphate. J Clin Invest 22: 871–5 If stronger analgesia is required, the patient Coffey F, Wright J, Hartshorn S, et al (2014) STOP!: a can cover the diluter hole on the activated carbon randomised, double-blind, placebo-controlled study ® chamber with the index finger, allowing a higher of the efficacy and safety of methoxyflurane for the At last, PENTHROX is here... treatment of acute pain. Emerg Med J 31: 613–18 concentration of methoxyflurane to be inhaled. A Crandell WB, Pappas SG, Macdonald A (1966) Fast, effective pain management designed second dose of 3 ml can be administered, if necessary. Nephrotoxicity associated with methoxyflurane for fast, efficient patient management. Up to 6 ml can be used per day. The total weekly anaesthesia. 27: 591–607 Galen Ltd (2016) PENTHROX 3mL inhalation dose should not exceed 15 ml and administration vapour, liquid summary of product characteristics. PENTHROX is indicated for the emergency relief of moderate to severe pain in on consecutive days is not recommended. www.medicines.org.uk/emc/medicine/31391 conscious adult patients with trauma and associated pain (accessed 27 January 2016) Grindlay J, Babl FE (2009) Review article: efficacy and Patient instructions safety of methoxyflurane analgesia in the emergency The patient should be shown the inhaler. It should department and prehospital setting. Emerg Med be explained that he/she breathes normally but Australas 21: 4–11 Kharasch ED, Hankins DC, Thummel KE (1995) inhales and exhales through the mouthpiece. The Human kidney methoxyflurane and sevoflurane patient should be instructed to start breathing in metabolism. Anesthesiology 82: 689–99 and out of the mouthpiece, gently initially and then Koulaouzos A (2004) Application for inclusion of normally. Explain that the patient can occlude the methoxyflurane in the WHO model list of essential medicines. http://archives.who.int/eml/expcom/ dilution hole for stronger analgesia if required. The expcom14/methoxyflurane/methoxyflurane_ patient should be instructed to inhale and exhale meddevelopmentsint-ltd_application.pdf (accessed through the mouthpiece intermittently to achieve 27 January 2016) Latto IP, Molloy MJ, Rosen M (1973) Arterial adequate analgesia. Continuous administration will concentration of nitrous oxide during intermittent reduce the time of analgesia. Patients should self- patient controlled inhalation of 50% nitrous oxide administer the minimum dose required. in oxygen (ENTONOX) during the first stage of labour. Br J Anaesth 45: 1029–34 Lazyer RB (1978) Myeloneuropathy after prolonged After care exposure to nitrous oxide. Lancet ii: 1227–30 Observe the patient until the effects of Litwin PD (2010) The effects of temperature on nitrous oxide and oxygen mixture homogeneity and methoxyflurane have worn off. The cap should be stability. BMC Anesthesiology 10: 19 replaced on the 3 ml bottle and both the inhaler and O’Sullivan I, Benger J (2003) Nitrous oxide in bottle should be placed in the plastic bag provided. emergency medicine. Emerg Med J 20: 214–17 Tomi K, Mashimo T, Tashiro C et al (1993) Alterations in The bag is sealed and the bag and contents should pain threshold and psychomotor response associated be disposed of in the clinical waste. Document the with subanaesthetic concentrations of inhalation Penthrox is indicated for the emergency relief of use of the Penthrox inhaler in the patient’s notes. anaesthetics in humans. Br J Anaesth 70: 684–6 Adverse events should be reported. Tomlin PJ, Jones BC, Edwards R et al (1973) Subjective moderate to severe pain in conscious adult patients with trauma and associated pain. Please consult the Summary Reporting forms and information can be The publication of this guide has been supported by an and objective sensory responses to inhalation of of Product Characteristics before prescribing. Information found at www.mhra.gov.uk/yellowcard. unrestricted educational grant from Galen Ltd. Galen Ltd nitrous oxide and methoxyflurane.Br J Anaesth 45: about this product, including adverse reactions, Adverse events should also be reported to 719–25 precautions, contra-indications and method of use can Galen Limited on 028 3833 4974 and select has not had any editorial input into this publication. the customer services option, or e-mail Yakaitis RW, Cooke JE, Redding JS (1972) Self- be found at www.medicines.org.uk/emc. Legal category: POM. Further information is available on request from [email protected]. Abdullah WA, Sheta SA, Nooh NS (2011) Inhaled administered methoxyflurane for postoperative pain: Medical information enquiries should also methoxyflurane (Penthrox) sedation for third molar effectiveness and patient acceptance.Anesth Analg Galen Limited, Seagoe Industrial Estate, Craigavon, BT63 be directed to Galen Limited. extraction: a comparison to nitrous oxide sedation. 51: 208–12 5UA, United Kingdom. Penthrox Educational materials and training on its administration are available from Galen on request. Date of preparation: January 2016. PMR-JAN-2016-0042.

Untitled-3PEN-15-075 1 A5 Abbreviated ED Ad.indd 1 01/02/2016 17:0616:41 NEW

Advancing Acute Pain Management

At last, PENTHROX® is here... Fast, effective pain management designed for fast, efficient patient management.

PENTHROX is indicated for the emergency relief of moderate to severe pain in conscious adult patients with trauma and associated pain

Penthrox is indicated for the emergency relief of moderate to severe pain in conscious adult patients with Adverse events should be reported. trauma and associated pain. Please consult the Summary Reporting forms and information can be of Product Characteristics before prescribing. Information found at www.mhra.gov.uk/yellowcard. about this product, including adverse reactions, Adverse events should also be reported to precautions, contra-indications and method of use can Galen Limited on 028 3833 4974 and select be found at www.medicines.org.uk/emc. Legal category: the customer services option, or e-mail POM. Further information is available on request from [email protected]. Medical information enquiries should also Galen Limited, Seagoe Industrial Estate, Craigavon, BT63 be directed to Galen Limited. 5UA, United Kingdom.

Penthrox Educational materials and training on its administration are available from Galen on request. Date of preparation: January 2016. PMR-JAN-2016-0042.

Untitled-3PEN-15-075 1 A5 Abbreviated ED Ad.indd 1 01/02/2016 17:0616:41