Methods of Pain Relief in Children - Literature review Example

A Review of the Available Pharmacological Options for the Relief of Procedural Pain in Children in the Accident and Emergency Department Introduction Pain is a symptom of injury or illness in the part of the body from where the pain arises. Pain may be defined as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage".1 Acute pain in a very common experience in paediatric emergency departments.2 Besides pain arising due to accidents and injuries, pain can also occur due to procedures performed for therapeutic and diagnostic purposes like venipuncture, burns dressings, and fracture reduction.3,4,5,6 Research has shown that management of pain in children and infants is more often than not inadequate, despite evidence that pain in these age groups can be management effectively and safely through proper dose adjustment and safe clinical practices.7,8 It is important to control pain in infants and children because of the, unwanted and devastating consequences they have. Some evidence has shown that procedures performed in neonatal period without proper control of pain can increase distress during future procedures like immunizations.9 In children, the memory of a bad experience on the first occasion of a procedure can increase the amount of pain and distress in subsequent procedures due to anxiety and anticipatory fear. Pain during procedures can lead to stress which can contribute to negative cognitive, social, physiological, psychological and emotional outcomes not only for their children, but also for their family members.9,10,11,40 According to the American Academy of Paediatrics11, "the concepts of pain and suffering go well beyond that of a simple sensory experience. It has emotional, cognitive and behavioral components as well as developmental, environmental and socio-cultural.” Thus, it is very important to manage pain in infants and children adequately and appropriately. Such an effective clinical practice is possible through "thorough current knowledge of analgesics, age-specific doses, appropriate routes of administration and possible side effects."11 Another important aspect of pain management in children is that only pharmacological pain management is ineffective and for successful pain relief, "a family centred approach combining pharmacological methods with psychological and behavioural methods is needed for the optimum comfort of children."6 It is possible to manage pain in children safely through use of non-invasive monitoring devices and short active sedatives and analgesics. Several years of research in the management of pain in children has formulated some best practice guidelines, especially during procedures, and these include "comprehensive pre-procedural evaluation", "informed consent", adequate documentation and "assessment of pain".6 Thus it is very important to assess pain adequately in infants and children and scales for assessment are different for different age groups.6 Assessment of pain is very important and is a crucial step in the management of paediatric pain. This is difficult in infants and children. Employment of pain assessment tools tailor made for paediatric population is useful to ascertain the level of pain.34 In infants and small children, who are unable to express pain verbally, the "Faces Pain Rating Scale" is useful. In older children, the "Visual Analogue Scale" is useful.2 It essential to assess pain properly to facilitate effective management. Assessment of pain involves appropriate pain history, detailed physical examination and specific diagnostic tests.12 There is no 'gold standard' scale for pain assessment in neonates. The immature nervous system of the neonates responds in a different manner to pain and analgesia43. More often than not, pharmacological strategies are employed for relief of procedural pain in children.4 In this essay, various pharmacological options for relief of pain in an emergency room will be discussed through review of literature and critical analysis. The pharmacological options which will be emphasized are oral analgesics like paracetamol, non-steroidal anti-inflammatory drugs and opioids and systemic drugs like opioids and entonox. Literature review Several pain reduction strategies have been developed to manage pain in children. These can be categorized into pharmacological and non-pharmacological. Pharmacological interventions can be oral or systemic. The most commonly used oral medications are paracetamol, ibuprofen and opioids like codeine.15 Medications used through systemic routes include opioids and diclofenac.16 Locally applied anaesthetics like amethocaine and Eutectic Mixture of Local Anesthetics EMLA are useful to provide analgesia for venipuncture and other such simple procedures.6 Non-pharmacological interventions include hypnosis, music, distraction and other psychological interventions like cognitive-behavioural therapies.13 Research has shown that non-pharmacological interventions can only be used as adjuvants to pharmacological treatments and have limited role in the management of acute pain in emergency department6. According to the British Association for Emergency Medicine (2005)16, pain in children in the emergency room must be managed using psychological strategies, non-pharmacological adjuncts and pharmacological agents.16 "Pain assessment forms an integral part of the National Triage Scale” 16 and pain management is based on the assessment16. For mild pain of scores 1-2, oral or rectal paracetamol at doses 20mg/kg or oral ibuprofen at 10mg/kg may be used, for moderate pain of scores 4-6, oral or rectal diclofenac of 1mg per kg or oral codeine phosphate of 1mg/kg are recommended and for severe pain of scores beyond 6, entonox, or intranasal diamorphine at doses 0.1mg per kg, and or, IV morphine 0.1- 0.2 mg/kg are suitable16. Paracetamol, also known as acetaminophen, is both an antipyretic and analgesic. It acts by inhibiting synthesis of prostaglandin. It is given in doses of 10-15mg per kg either orally, rectally or intramuscularly, every 4-6 hours. In the emergency department, there is not much role for this drug for control of pain6. It may be given for pain management after the procedure, but not for relief of pain during the procedure. The drug can be administered even in neonates because of limited side effects. Another class of oral analgesics are non-steroidal anti-inflammatory drugs (NSAIDS). Examples of drugs belonging to this category are ibuprofen and diclofenac sodium. These drugs provide relief of pain by nonselective inhibition of cyclo-oxygenase which inhibits cyclo-oxygenase-1 and 2 isoenzymes, thus decreasing the synthesis of important inflammatory mediators, the prostaglandins.17 NSAIDS are excellent analgesics, but when given orally or intramuscularly, the onset of action is prolonged and hence not suitable for procedural pain management in emergency. They can however be administered for relief of pain from simple injuries and post-procedural pain. The dosage of ibuprofen is 5-8mg/kg/dose and the drug can be given once is 6-8 hours. Diclofenac sodium can be given intravenously, but is not recommended in children because of associated side effects, the worst of which is acute renal failure. Other side effects include headache, dizziness, bronchospasm, and gastritis.17 Due to these possible adverse reactions, NSAIDS avoided in children, especially in those less than 9 months of age.18 Other than paracetamol and NSAIDS, the next class of oral analgesics are opioid analgesics like codeine, oxycodone, hydrocodone and tramadol. Opioid analgesics act by binding to the opioid receptors, mainly in the central nervous system.17 Even these drugs have limited role in the relief of pain in emergency department of pain when given orally because of delayed onset of action. Opioid analgesics are useful for relief of pain in emergency department when given through systemic routes. Opioids suitable for such purposes are morphine, hydromorphine, tramadol and fentanyl. Intravenous administration of these drugs causes instant relief of pain, but must be administered with caution because of associated side effects like respiratory depression and sedation and hence children given these medications must be monitored constsntly.17 Sedation may infact be an advantage for procedural pain. The most commonly used opioid analgesic in emergency is morphine35. The drug interacts mainly with μ-opioid receptors which are rampantly distributed in various parts of the brain like hypothalamus, posterior amygdala, nuclei caudatus and putamen and some parts of the cortex, in parts of spinal cord and in the gastrointestinal tract17. Morphine, which mimics endogenous endorphins, binds to and activates the receptors and thus exerts various pharmacological actions like relief of pain, sleepiness and pleasurable feelings. Morphine can be given through any route, although, analgesics benefits are best noted when given through systemic routes. Other opioid analgesics like hydromorphine, tramadol and fentanyl exert analgesia through similar mechanisms and are useful in the emergency department for management of procedural pain and pain caused due to musculoskeletal injuries in children. The dosage of morphine varies based on the mode of administration. When given through intravenous route for the purpose of relief of pain in an emergency setting, the dose is 0.05mg- 0.1mg given slowly over one minute, after dilution with atleast 5ml of normal saline. Intravenous morphine can be given in incremental small doses, but it is difficult to tailor the drug dosing individual analgesic requirements because of delayed onset of action of atleast 10 minutes45. The dose of fentanyl is for intravenous purpose 20-50 mcg/kg/dose and that of tramadol is 1mg/kg/dose16. Of recent interest in the management of pain in children in an emergency setting is intranasal administration of opioids. The drug studied and used for this purpose is diamorphine or diacetyl morphine, a semi-synthetic, water soluble opioid analgesic.6 Intranasal diamorphine has drawn lot of attention because of absence of respiratory depression and prolonged sedation, which are a draw back with use intravenous opioids. Diamorphine, when administered through nasal route gets absorbed through the highly vascular nasal epithelium and reach the heart through the sphenopalatine and facial veins, thus bypassing first bypass metabolism37. The drug acts as a analgesic by binding to the mu-opiod receptors in the brain. Actually, the drug metabolises to morphine and 6-monoacetyl morphine which bind to the receptors. The drug has to be given systemically only, because of high first pass metabolism when given orally. The drug has not only analgesic properties, but also anxiolytic and euphoric properties.17 Another drug which merits importance in the management of pain in children in an emergency setting is entonox. Entonox is a homogenous gas mixture that contains 50% nitrous oxide and 50% oxygen.28 The nitrous oxide is in the active form and acts within 30 seconds after administration through inhalation. It has a strong analgesic effect. It is contraindicated in pneumothorax, middle ear disease, sinus problems and bowel obstruction. The drug wears off very fast28. The type of analgesia provided by this gas is known as neuroleptanalgesia in which analgesia occurs along with state of quiescence and altered awareness, thus allowing the patient to cooperate for procedures without feeling the pain. Recent research has indicated the role of this mixture in the management of procedural pain in children attending to emergency department28 because of minimal side effects, ease of administration and short duration of action. Local anesthetics have also been studied for providing local analgesia for simple procedures like venous puncture and arterial puncture. EMLA has both lignocaine and prilocaine in equal quantities and when rubbed local gets absorbed into skin and numbs the nerve endings, thus causing an analgesic effect. Amethocaine also has similar properties. 23 These topical applicants are useful only for simple procedures like needle pricks and are not useful for management of pain due to injuries and other procedures like burns dressings. Critical analysis There are limited studies to ascertain effective pain relief strategies in children because of challenges associated with pain assessment, variation in the severity of illness and developmental differences. Clark et al (2007)15 conducted a randomized controlled trial to compare, evaluate and ascertain the efficacy of acetaminophen, codeine and ibuprofen in the management of acute pain in children with musculoskeletal trauma. The study was conducted in children between the ages 6-17 years suffering from musculoskeletal trauma. Acetaminophen was used at doses of 15mg/kg, ibuprofen at 10mg/kg and codeine at 1mg/kg. The study proved that of the 3 oral analgesics, ibuprofen was the most effective in terms of relief of pain. However, pain relief with this analgesic was observed only in 60 percent of the patients, that too after one hour after administration. Thus, it can be said that oral medications have minimal role in the management of acute pain in the emergency, especially for procedural purposed where pain relief needs to be immediate. Also, concerns over detrimental effects of NSAIDS on bone metabolism and fracture healing prevents the use of these medicines as first line drug for acute pain management.22 However, the drugs are useful for multimodal pain relief management, for relief of post procedural pain and pain due to musculoskeletal injury, after emergency management is over. Research has shown that the best practice to manage acute severe pain in children is by administering opioids either through intravenous or intranasal mode38 . Of these two modes, intranasal is less distressing, less traumatizing and easy to administer. Kidd et al (2009)38 compared and evaluated the concentration time profiles of morphine following intravenous and intranasal administration of diamorphine in children. From their observational study, it was evident that intranasal administration caused delayed and attenuated levels of morphine when compared to intravenous administration, but pain control was adequate. The study by Kidd et al, was a good observational study. The author of this critical analysis agrres with the researchers that when immediate action is needed, intravenous morphine is a better option. However, recommendations from this study cannot implied for best practice guidelines because it is only an observational study. Although, in a previous study, Wilson et al (1997)39 proved the efficacy and safety of intranasal diamorphine when administered in paediatric patients undergoing various procedures in accident and emergency department. Wilson et al 39 conducted a prospective randomized clinical trial in patients between 3- 16 years age to compare between intranasal diamorphine and intramuscular diamorphine. The dosing of intranasal diamorphine used was 0.1mg/kg. The researchers concluded that intranasal diamorphine is an efficient, safe and acceptable method of administration of analgesia in paediatric population in the accident and emergency room. Since this is a randomised controlled trial, inferences from this study can be applied for best practice. A similar study was conducted by Kendall et al (2001)4 in children and teenagers and the authors opined that "nasal diamorphine spray should be the preferred method of pain relief in children and teenagers presenting to emergency departments in acute pain with clinical fractures. The diamorphine spray should be used in place of intramuscular morphine." The study by Kendall et al 4 was also a randomised controlled study with good number of children involved in the study and from all the above 3 studies it can be inferred that intranasal diamorphine is useful for management of pain in children in emergency room. Studies by Wilson et al and Kendall et al compared intranasal diamorphine, as against intramuscular morphine, but Kidds et al studied intranasal diamorphine against intravenous morphine. From the critical analysis of these 3 studies, the author infers that intranasal diamorphine is more effective in the management of acute pain in children an emergency setting when compared to intramuscular morphine. Intravenous morphine has quicker onset of action than intranasal diamorphine and must be considered in conditions where immediate pain relief is required and considering the side effects associated with intravenous mophine, adequating monitoring is mandatory while administering the drug. For topical analgesia, two topical anaesthetics have been studied, EMLA and amethocaine. Lander et al (2009)23 compared the efficacy between these two pain-relieving strategies with reference to venipuncture. The authors found that amethocaine was much better in producting pain relief. However, some researchers argue the effectiveness of topical analgesia in the management of acute pain in children in an emergency spectrum. The researchers who condemn the use of topical anaesthetics for local analgesia argue that pain relief from this strategy is similar to or less effective than non-pharmacological strategies like distraction.24, 25 These anaesthetics do not effectively block the intensive nociceptive stimulus caused by prick, though the stimulus is brief and due to differences in the penetration depth and stimulus intensities, the drugs are more effective for venepuncture than heel prick42. The author opines that the benefits of local analgesia strategies are limited only to needle pricks and when the child is able to be distracted, this strategy need not be applied. There is not much consensus on the ideal drug for immediate pain management in procedures conducted in an emergency setting like for example intubation. While intubating a child in emergency, the onset of action has to be in seconds. Recent studies have pointed to the usefulness of fentanyl for such an application. Shah and Ohlsson (2002)27 conducted a systematic review of seven randomized controlled trials and a couple of cohort studies and opined that fentanyl was a good drug for analgesia during intubation. They however opined that further research is warranted to ascertain the benefits of opioid analgesia in terms of validated pain scales, because none of the studies ascertained the analgesic effect with reference to a validated pain scale. Also, in very small babies, like neonates and preterm babies, where sedation needs to be provided by weighing the benefits of analgesia as against the negative outcomes of the drug administered, the usefulness of intravenous opioid analgesia is controversial. Analgesic management in neonates and preterm babies is difficult due to unpredictable pharmacokinetics and outcomes43. Neonates and small children, are more sensitive to the side effects of opiod analgesics and use of these drugs must be done with caution44. Bellu et al (2008)26 conducted a systematic review to ascertain the effectiveness of opioids as analgesics in preterm and term infants undergoing intubation. The researchers found that the doses and types of opioids were heterogenous and the outcomes were unpredictable, based on which they deferred to recommend opioids for pain reduction in neonatal age group. Thus, it can be inferred that intravenous opioids like fentanyl, are useful for immediate pain reduction in situations like emergency intubation, but the use of these drugs must be applied with caution, especially in small age groups like neonates and preterms. Entonox has been studied and used widely in children undergoing dressing for burns. Another procedure for which entonox is widely studied is gastrointestinal endoscopy. Michaud et al (1999)29 conducted a prospective pilot study to ascertain the usefulness of entonox in gastrointestinal procedures. From the results of the study it was evident that the gas mixture provided effective and rapid analgesia without heavy sedation, facilitating adequate cooperation, relaxation and efficiency of the procedure. The analgesic effect was associated with minimal ignorable side effects, implying the usefulness of this method of analgesia for control of pain in gastrointestinal endoscopy. There is some research into the usefulness of high concentration entonox which contains upto 70 percent nitrous oxide. Babl et al (2008)31 conducted a prospective observational study for analgesia in paediatric emergency department. The study revealed that, high concentration nitrous oxide is effective for procedural analgesia and sedation in children, even in those between 1-3 years age. The most common side effect noted was vomiting. The side effects are not dependent on preprocedural fasting state, which means that the gas can be administered to even to those without fasting.32 There is not much literature to ascertain the benefits of entonox as against intravenous or intranasal diamorphine, in an emergency setting. However, one study 28 compared entonox with intravenous morphine in children undergoing intrapleural tube removal. Though the participants of the study are not homogenous with pediatric patients in an emergency setting, inferences from this study imply that entonox is not useful for such procedures. Thus, it can be said that entonox is suitable only for some procedures like burns dressings and gastrointestinal endoscopy and more research is warranted to ascertain the benefits of this gas as against other strategies of pain management. Future recommendations Morphine "works through the body's natural pain-killing machinery, preventing pain messages from reaching the brain."33 Researchers are trying to develop morphine-like drug with analgesic effect similar to morphine, but without side effects like respiratory depression and sedation.33 A combination of sedation and analgesia may be the most useful strategy for moderate to severe pain relief in children undergoing procedures in emergency room. Otley and Nguyen (2000)30 assessed the effectiveness of administering a combination of benzodiazepines and inhalational nitrous oxide for paediatric patients undergoing minor surgical procedures. From their study, it was evident that such a strategy to manage pain was not only effective, but also safe. Conclusion Pain is a very common concern in paediatric emergency and accident department. Children either come to the department with painful conditions like injuries, lacerations and fractures, or need to be subjected to various painful therapeutic and diagnostic procedures. In any case, pain in children needs to be managed appropriately and adequately, because of the short term and long term consequences it is associated with like distress, anxiety for future procedures and cognitive and behavioral changes. However, there is evidence to show that pain in paediatric population is managed poorly. One of the main reasons for such inadequate pain management in neonates, infants and children is the lack of reliable and age-appropriate pain assessment tools. As such pain assessment is a critical step in the management of pain. Several strategies have been used to manage pain in children in an emergency setting. These include both pharmacological and non-pharmacological. This literature review and critical analysis has concentrated on pharmacological strategies to relieve pain. While for simple causes of pain like wounds, oral medicaions like paracetamol and NSAIDS may suffice, for pain related to procedures, these drugs are not suitable because of their duration of onset of action. In such conditions, systemic drugs are the best. Of all the systemic analgesic used and studied, the most popular drugs are opioids, that too morphine, because it can be given by any route. However, opioids are associated with many side effects, the worst being respiratory depression. This side effect can be prevented by administering the drug intranasally. The drug useful for this purpose is diamorphine, because of its water soluble attributes. Intranasal diamorphine is effective, reliable and safe method of analgesia for pain in children in an emergency setting. Another effective approach, other than opioids is entonox. But this strategy has limited value, especially in procedures like pleural aspiration. For simple procedures like venepuncture, local anaesthetics are useful. From this literature review and critical analysis, it is evident that there is no single drug which can be called “first line drug” in the pain management of children in emergency setting. While in most cases diamorphine is useful, through intranasal route, other pharmacological options may be employed based on the case. More research is warranted in the area of pain management of children in an acute setting like accident and emergency. References 1.NHS Best Practice Statement (2006) Management of chronic pain in adults. Accessed on 10th July, 2010 from www.nhshealthquality.org. 2. Shavit, I., and Hershman, E. Management of Children Undergoing Painful Procedures in the Emergency Department by Non-Anesthesiologists. IMAJ 2004; 6: 350- 355 3. Sacchetti, A., Baren, J., Carraccio, C. Total procedural requirements as indication for emergency department sedation. Pediatr Emerg Care 2010; 26: 209- 11 4. Kendall, J.M., Reeves, B.C., and latter, V.S. 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