ENTONOX - BOC

1 The essential guideBOC: Living healthcareENTONOX BOC: Living healthcare 2 IndexIntroduction3 Pharmacology of analgesic action4 Safety and efficacy5 ENTONOX and clinical therapy 7 Obstetrics 7 Emergency care 7 Colonoscopy 9 Paediatrics9 Painful procedures10 Dentistry10 Effect of ENTONOX on other systems 11 Respiratory system 11 Gastro-intestinal system 11 Considerations for use 13 Contraindications 13 Side-effects13 Safety and the environment 14 Summary 15 Abbreviated prescribing information 16 References 18 IntroductionBOC: Living healthcare 3 ENTONOX is the 50:50 mixture of nitrous oxide(N2O) and oxygen (O2). It is a very effective analgesic agent with rapid onset and offset characteristics. Extensive use of ENTONOX and nitrous oxide has shown that its effects are predictable and reliable and it has proved to be a very safe agent with minimal side-effects. Nitrous oxide was discovered and purified byPriestley, Mayow and Hales in the mid 1700 s.

2 The American dentist Horace Wells first used itmedically in 1844 to reduce the pain of tooth extraction. During the late 1800 s the use of nitrous oxide became popular in the USA and was introduced into Europe, in 1867, by Quincy Coulton1. Interestingly, until the late 1800 s nitrous oxidewas used alone and without any supplemental airor oxygen, therefore some of the sedative andanalgesic effects of the gas could have been dueto hypoxia. In 1881 nitrous oxide was introduced for pain relief in childbirth and in 1911 Guedel describedan analgesic technique (possibly the first patientcontrolled analgesia ) in which patients self-administered a mixture of air and nitrous oxideduring childbirth and minor surgery2. BOC Healthcare studied the nitrous oxide/oxygensystem after a suggestion from Tunstall in 1961. It was found that it was possible to store a pressurised homogeneous gas mixture containingnitrous oxide at ambient temperature. This led to the BOC pre-mixed gas patent and to the ENTONOX product.

3 Since the introduction of ENTONOX into obstetricpractice by Tunstall in 19613and into the ambulance service by Baskett in 19704, ENTONOXhas become the mainstay of analgesia for childbirth and pain relief in acute situations. Today nitrous oxide is an essential ingredient inanaesthesia. As ENTONOX it is a vital part of analgesia for childbirth and is uniquely placed asan ideal agent for the treatment of short-term paindue to almost any cause. Pharmacology of analgesic actionENTONOX is a gaseous analgesic agent that is composed of nitrous oxide and oxygen in equalproportions. It is supplied in cylinders that have awhite and blue shoulder. The gas is contained at a pressure of either 137bar or 217bar and is delivered to the patient by connecting the cylinderto a demand valve via an integral or external pressure regulator. The patient will self-administer the gas, under the supervision of an appropriatehealthcare professional, by using a mouthpiece orfacemask attached to a demand valve.

4 How ENTONOX worksENTONOX is widely used as an analgesic agent but its mechanism of action has not yet been fullyexplained. It is known that the effects of ENTONOX take place within the pain centres of the brain andspinal cord and are related to the release ofendogenous neurotransmitters such as opioidpeptides5and serotonin6,7and the activation ofcertain opioid receptors8,9. Also, Jevtovic-Todorovicet that N-methyl-D-aspartate (NMDA)receptor currents were inhibited by nitrous oxideand it is known that the NMDA receptor is involvedin many CNS pathways, that control sensations,such as pain and euphoria. Whilst many of theanaesthetic effects of nitrous oxide remainunknown, there is increasing clarity as to theanalgesic affects of this gas. A hypothesis by Maze et. al.,11suggests thatENTONOX has its analgesic effects by the activationof descending noradrenergic pathways due to therelease of opioid peptides in the peri-aqueductalgrey area of the midbrain.

5 These descending pathways are thought to modulate pain throughthe activation of alpha-2 adrenoceptors in the dorsal horn of the spinal cord. Due to the physical properties of nitrous oxide(namely its blood/gas solubility) ENTONOX worksvery quickly and analgesia is maximal within 2-3 minutes of inhaling the gas but its effects are apparent within a matter of breaths. Rapid recoveryRecovery from the effects of ENTONOX are veryrapid12. Once inhalation of ENTONOX has stopped,there is a fall of 35% in the arterial concentration within 30 seconds13. Studies have shown psychomotor recovery, after 30 minutes of exposure. This was shown in a clinical trial undertaken at the HPRU medical research centreusing 50% nitrous a study by Zacny , there was a subjective feeling of complete recovery, within 5 minutes15, in individuals who breathed 40% nitrous oxide for 30 minutes. A study by Martin et , used a technique shown tobe the most sensitive test for detecting impairment ofdriving ability due to drugs to assess the effect ofENTONOX on simulated driving ability following its useduring screening flexible sigmoidoscopy.

6 The groupconcluded that ENTONOX did not impair driving abilitywhen used for this application. The patient can drive home just 30 minutes afterENTONOX administration, provided a healthcare professional has judged them competent and thepatient agrees that they feel able to care is needed when ENTONOX is administered to a patient who has been given concomitant : Living healthcare 4 BOC: Living healthcare 5 Safety and efficacyThe level of analgesia has been compared with the effects of opiates. Chapman et that20-30% nitrous oxide had a comparable pain relieving effect to 15mg of subcutaneous morphineand Dundee and Moore18showed that 50% nitrousoxide ( ENTONOX ) was equivalent to approximately 100mg to the low fat solubility of nitrous oxide, it doesnot accumulate to any great extent within thebody. In addition, nitrous oxide is not metabolisedby the body and will be eliminated completely by the lungs.

7 The pharmacological profile of ENTONOX offers rapidonset of potent analgesia with speedy reversal ofeffects when required. This fast offset of action offers a clear advantage over all other analgesicagents, and if used in combination for pain reliefallows a reduction in the doses of the other agentsused ( morphine, pethidine), thus reducing theoften serious side-effects associated with them. BOC: Living healthcare 6 BOC: Living healthcare 7 ENTONOX and clinical therapyThe reduction and elimination of pain and anxietyis extremely important to healthcare professionalsand patients alike. ENTONOX has proved to be auseful analgesic and sedative agent that is fast,safe and easy to is widely used in many clinical areas in hospitals and in the ambulance service. The benefits of ENTONOX for the relief of acute painand discomfort due to short procedures in accidentand emergency departments, hospital wards andclinics are now increasingly recognised by healthcare professionals.

8 This reflects the enthusiasm and eagerness shown by many hospital staff in their use of ENTONOX for the benefit of providing pain relief for patients. ObstetricsDuring childbirth, ENTONOX analgesia can help torelieve the pain experienced by women as theyundergo labour . It does not completely eliminatethe sensation associated with contractions, but reduces the level of pain and anxiety to make themmore is used during early labour to help mothers copewith the pain during contractions and, if required,for uncomfortable vaginal examinations and suturing. It is generally used towards the end ofthe first stage of labour . The gas mixture allows, as near as possible, the mother to experience thesensation of a natural is an effective method of pain relief for motherswho want to remain in control during is self-administered under the supervision of midwives, allowing mothers to adjust their intake to suit their own individual pain thresholds and comfort levels.

9 ENTONOX is known to cross the placenta but has no known negative effects on the baby duringchildbirth. In fact, the oxygen component will increase the levels of oxygen in the bloodstream,which ultimately will pass via the placenta to thebaby. This is good for the baby, especially duringlabour contractions19. ENTONOX and emergency careIn 1970 Baskett first used ENTONOX as part of theimmediate care given by the ambulance then many studies have reported on the beneficial effects of ENTONOX . Donan et , in 240 patients with traumatic chest, abdominal or back pain, over 90% experienced relief of their pain and apart from drowsiness, noside-effects were reported. Stewart et the safety of ENTONOX inpre-hospital care in a 1983 study of over 1,000 patients. They found no serious complications, but reported the following minor side-effects: dizziness - excitation nausea - numbness became drowsy or fell into a light sleep but all could be readily roused by verbal command, all could cough and swallow on request and no cardiovascular side-effects were noted.

10 Today ENTONOX forms an integral part of the immediate care offered by ambulance staff andfirst responders. ENTONOX has the benefit of a non-invasive mechanism of delivery, few side-effects or contraindications and is simple to properties make ENTONOX an ideal analgesicfor treating patients in the pre-hospital setting aswell as accident and emergency : Living healthcare 8 ENTONOX for painful proceduresBOC: Living healthcare 9 ENTONOX has been used widely in the treatment ofpain due to injury and also pain caused by medicalintervention, investigation and treatment. ColonoscopyENTONOX is used during colonoscopy because of itsbenefits over intravenous, intramuscular and oralsedation. Saunders et effective sedation with ENTONOX compared with pethidineand midazolam. They reported fewer episodes ofarterial desaturation as well as faster recovery andreduced time to discharge in the ENTONOX group. In another study by Lindblom et , recovery timeafter colonoscopy was reduced by 37 minutes inthe ENTONOX group compared with the intravenousketobemidone and midazolam group, with similarlevels of relief from discomfort in both groups.