Procedural Sedation and Analgesia Education Package for Registrars

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1 Procedural Sedation and Analgesia Education Package for Registrars Emergency Department, Royal Hobart Hospital Dr Ray Siauw Updated January 2015 Scope This document accompanies the Procedural Sedation and Analgesia Policy. It is intended to assist emergency medicine trainees to achieve the necessary competence to safely and effectively administer procedural sedation and analgesia for diagnostic or interventional procedures within the Royal Hobart Hospital Emergency Department. Aims 1. Optimise patient safety 2. Optimise patient comfort by minimising procedural pain, distress and the need for physical immobilisation or restraint 3. Achieve an optimal match between desired and achieved levels of sedation 4. Facilitate timely completion of the planned procedure Definitions Procedural sedation and analgesia (PSA) the technique, by use of drugs, of inducing tolerance of painful or distressing procedures. Lack of response to painful stimulation is not assured. Nevertheless, minimisation of pain is a desired outcome, therefore procedural analgesia, not just sedation, is emphasised. Mild sedation (sometimes known as anxiolysis ) amelioration of distress or anxiety, without depression of consciousness. Typically the result of one standard dose of midazolam alone, or of breathing nitrous oxide (inspired concentration 50%) alone. Higher doses, other drugs, or combinations of drugs are likely to produce deeper levels of sedation see below. Moderate sedation (previously known as conscious sedation ) depression of consciousness during which patients are able to respond purposefully to verbal commands or light tactile stimulation. Deep sedation consciousness is lost and patients respond only to painful stimulation. Associated with loss of the ability to maintain a patent airway, inadequate spontaneous ventilation and/or impaired cardiovascular function. General anaesthesia a drug induced state characterised by absence of purposeful response to any stimulus, loss of protective airway reflexes, depression of respiration and disturbance of circulatory reflexes. Depth of sedation can be regarded as a continuum from mild sedation, through moderate and deep sedation to general anaesthesia. Most sedative agents produce a dose- dependent progression along this continuum.

2 Analgesia reduction or elimination of pain perception Dissociative sedation (an effect produced by the drug ketamine) a trancelike cataleptic state characterized by profound analgesia and amnesia, with retention of protective airway reflexes, spontaneous respirations, and cardiopulmonary stability 1. These effects of ketamine are not consistent with the sedation continuum outlined above (see Appendix). Procedures for which PSA may be indicated include, but are not limited to: - Wound repair - Reduction of fractures or dislocations - Incision and drainage of cutaneous abscesses - Insertion of an intercostal catheter - Insertion of a central venous catheter - Electrical cardioversion - Lumbar puncture Risks The transition from complete consciousness through the various depths of sedation to general anaesthesia is a continuum and not a set of discrete, well- defined stages. The margin of safety of drugs used to achieve sedation and/or analgesia varies widely between patients and loss of consciousness and/or loss of protective reflexes may occur rapidly and unexpectedly. Therefore doctors who administer PSA must be prepared to manage the following potential complications: - A: depression of protective airway reflexes, leading to airway obstruction; - B: depression of respiration, leading to critical hypercapnia or hypoxaemia; - C: depression of the cardiovascular system, leading to hypotension or cardiac arrest; - individual variations in response to the drugs used, particularly in children, the elderly, and those with pre- existing medical disease. This includes unexpected extreme sensitivity to the drugs used which may result in unintentional loss of consciousness, and the above complications. - drug interactions or adverse reactions, including anaphylaxis. Over- sedation, airway obstruction, respiratory or cardiovascular complications may occur at any time. Consent Informed consent should be obtained, both for the procedure and for the PSA. Ideally, written information should be provided to the patient or the patient s guardian, prior to PSA, outlining the nature of the proposed sedation and potential risks. The patient or guardian should be allowed time to read this and to ask questions. Relevant information sheets are available on the RHH ED Infosite. Patient Assessment Prior to PSA, patient assessment should include the following:

3 - History of the current problem, past medical history, history of previous anaesthetics or PSA, current medications, allergies, fasting status. - History of recently administered analgesic or sedative medications (eg. opiates or benzodiazepines) take particular note of drugs given pre- hospital, or in ED prior to PSA. Recent intake of alcohol or illicit substances is also relevant. - Examination including that relevant to the current problem, of the airway, respiratory and cardiovascular status. - Results of relevant laboratory investigations and imaging. Careful patient assessment is critical to identifying those patients at increased risk of airway, respiratory or cardiovascular complications during PSA. Such patients include: - Elderly - ASA grades Morbid obesity - Significant obstructive sleep apnoea - Known or suspected difficult intubation - Acute respiratory or cardiovascular compromise - Potential for aspiration of stomach contents (particular caution is recommended for a patient who has recently consumed alcohol) - Previous adverse events related to PSA or general anaesthesia Fasting Commonly cited fasting times were originally developed for elective general anaesthesia. Clinically significant emesis and pulmonary aspiration is an extremely rare occurrence and it is important to note that the periods of greatest risk during general anaesthesia are when the airway is manipulated during intubation and extubation, which are not performed during PSA. There is no evidence that fasting has any impact on the incidence of complications during PSA. There is insufficient evidence to recommend any specific fasting time prior to PSA and no evidence that fasting guidelines intended for general anaesthesia should be applied to PSA 2,3,4,5. The Australasian College for Emergency Medicine does not give a specific recommendation on pre- PSA fasting 6. The American College of Emergency Physicians policy gives the following Level B recommendation: - Do not delay procedural sedation in adults or paediatrics in the ED based on fasting time. Preprocedural fasting for any duration has not demonstrated a reduction in the risk of emesis or aspiration when administering procedural sedation and analgesia. 7

4 The risks of vomiting and aspiration must be weighed carefully against the urgency of the procedure within the context of the patient s condition. Based on this risk assessment, it may be appropriate to choose one of the following courses of action: - Delay the procedure until the patient is fasted - Proceed with PSA - Facilitate transfer to operating theatre for general anaesthesia Traditional fasting times for elective general anaesthesia are 6 hours from solids, 4 hours from breast milk and 2 hours from clear fluids. Seriously ill or injured patients should be assumed to be un- fasted. Any uncertainty about the safety of PSA should be referred to the on- call ED consultant. Risk factors for aspiration include: advanced age, greater underlying illness (ie. higher ASA status classification), and conditions predisposing to gastro- oesophageal reflux (oesophageal disease, hiatus hernia, peptic ulcer disease, gastritis, bowel obstruction, ileus, elevated intracranial pressure, age less than 6 months). Patients with potential for difficult intubation or difficult bag- mask ventilation, should an airway emergency occur, are also considered high risk. Examples of procedures which may need to be urgently performed in an un- fasted patient include: reduction of a fracture or dislocation with associated neurological or circulatory compromise to the distal limb, or electrical cardioversion of an arrhythmia associated with haemodynamic instability. Staffing A minimum of three staff members are required for PSA. This must include: - the proceduralist (where appropriate, this may be a non- ED member of staff eg. surgical or orthopaedic registrar) - the sedationist : a doctor solely dedicated to administering PSA and monitoring the patient; this doctor is not to be distracted from this duty by being asked to assist with the procedure. This doctor is to be an ED registrar or consultant, or where appropriate, a registrar or consultant from Anaesthetics or ICU. - a third medical or nursing staff member to assist One of the three staff must be an ED registrar or consultant skilled in airway management and cardiopulmonary resuscitation. An ED Consultant (at night, the ED consultant on call) must be notified prior to any PSA being administered. Where appropriate, the Emergency Medical Unit (EMU) consultant or registrar should also be notified prior to PSA, to facilitate timely transfer to EMU for post- PSA recovery.

5 Facilities and Equipment PSA should be performed in a resuscitation bay, thereby allowing rapid access to equipment necessary for managing airway obstruction, respiratory depression or cardiovascular collapse. In particular, consider having the following emergency equipment prepared and immediately to hand, as these will be required first in an emergency: - Appropriately sized bag- valve- mask connected to oxygen supply - Appropriately sized Guedel airway - Yankauer suction catheter connected to suction supply - Crystalloid (Normal saline or Hartmann s) connected via hand- pump set to the patient s IV cannula. Intravenous Access Reliable venous access should be established for any PSA. Care should be taken to secure venous access against accidental dislodgement unexpected patient movement can occur during PSA. When intramuscular ketamine is chosen as PSA, it may be appropriate to establish venous access after sedation is achieved (see Appendix). Monitoring Vital signs must be recorded before and at regular intervals during PSA. All patients must have continuous monitoring by pulse oximetry. Continuous ECG monitoring and regular non- invasive BP monitoring is desired in most patients. It may be more practical or less distressing in some patients to commence monitoring after sedation is achieved, eg. young children. All patients must have their depth of sedation carefully monitored. This is usually done by assessing the patient s response to verbal or tactile stimulation. All patients must have their rate and depth of respiration carefully monitored. End- tidal CO 2 monitoring is a recommended technique for detecting hypopnoea. Oxygenation Preoxygenation and continuous supplemental oxygen during PSA is preferred. The rationale for this is that in the rare event of laryngospasm or airway obstruction, preoxygenation will delay the onset of critical hypoxaemia and there will be more time to perform airway rescue manoeuvres. It is recognised however, that supplemental oxygen removes the ability of pulse oximetry to provide an early warning of respiratory depression, that is, critical hypercapnia may occur before desaturation. End- tidal CO2 monitoring is therefore recommended whenever supplemental oxygen is used. Medication Doses of drugs should be kept to the minimum required for patient comfort.

6 Drugs must be selected that are most appropriate for the patient, the procedure and the clinical situation. It is therefore essential that doctors administering PSA be familiar with the pharmacodynamics, pharmacokinetics and side- effect profile of the agents available (see Appendix). It is recognised that although the drugs commonly used for PSA each have an excellent safety record when used alone, combinations of agents, especially of more than two agents, are associated with a greatly increased risk of complications 8. For similar reasons it is important to take into account all medications administered to the patient prior to PSA (such as pre- hospital analgesia) and any consumption of alcohol or other sedative drugs of abuse. N 2 0 Mixer The N 2 0 mixer in the paediatric procedure room allows inhalation of N 2 0 with titration of the inhaled concentration up to a maximum of 70% N 2 0 (See Appendix). Documentation The Emergency Department Procedural Sedation Form must be completed. This provides a record of the staff involved, the patient assessment, consent, drugs and their doses, observations and complications. Recovery and Discharge, use of EMU Recovery should take place in the resuscitation bay, monitored by a dedicated member of staff. Return to routine observations and transfer out of the resuscitation bay is safe when vital signs are within normal limits and the patient has regained responsiveness to voice, eg. able to obey commands. Typically, this will only be a matter of minutes following PSA with a single IV dose of ketamine or propofol. Unnecessarily prolonged observation in a resuscitation area is a significant drain on ED resources. The Emergency Medical Unit (EMU) is the preferred place to transfer patients for recovery after PSA, if it is anticipated they will be discharged home subsequently, and there is an EMU bed available. The patient may be discharged home once he/she has returned to his/her pre- PSA level of consciousness. The patient must be discharged into the care of a responsible adult to whom clear instructions should be given, including advice about eating and drinking, pain relief, and resumption of normal activities, as well as about making legally- binding decisions, driving or operating machinery. PSA Competency Assessment ED Registrars are required to fulfil the following competency requirements to be permitted to administer PSA (by the use of intravenous or intramuscular agents) without direct consultant supervision. Competency will be assessed on a three- level basis as follows. Level 1 permitted to administer PSA under direct consultant supervision (An ED consultant must be notified prior to administering PSA and must directly supervise the registrar) Read and understand this clinical policy and associated documents Complete the PSA competency MCQ test Be credentialed in basic airway manoeuvres (suction, airway positioning, airway adjuncts, bag- valve- mask ventilation)

7 o This may be at DEMT s discretion or, o Assessment of skills may be performed during registrar teaching (dates TBA) Level 2 permitted to administer PSA with on- site consultant support (An ED consultant must be notified prior to administering PSA and must be on- site to assist if necessary) - Fulfil the requirements of level 1 - Administer PSA to a minimum of five patients under direct consultant supervision and submit a log of these cases (the Observed PSA form can be used). Registrars are encouraged to seek supervision for more than five if they wish. Level 3 permitted to administer PSA independently, without ED consultant on site. (An ED consultant must be notified prior to administering PSA, including the on- call consultant during night shift). - Fulfil the requirements of level 2 - Sufficient experience in advanced airway management: o This will be at DEMT s discretion and will take into account level of training and previous critical care rotations. Appendix: Pharmacologic Agents for PSA Nitrous Oxide N 2 O is an inhaled anaesthetic gas with a long history of use in general anaesthesia and as an analgesic for childbirth and dental procedures. It has mild analgesic, anxiolytic, sedative and amnestic properties with minimal respiratory or cardiovascular depression. It may be administered as a 50:50 mixture with oxygen ( Entonox ) via a demand- valve and mouthpiece, or as a continuous flow via the N 2 O/O 2 mixer (in the paediatric procedure room) with its concentration titratable from 0% to 70%. It is suitable, in concentrations of 50-70%, as a sole agent for PSA for brief and distressing or mildly painful procedures, eg. - IV cannulation - Burns care - Infiltration of local anaesthetic - Distressing examination (eg. corneal exam in a toddler) It may be appropriate to use N 2 O in combination with a more potent analgesic (eg. intranasal fentanyl), for more painful procedures such as fracture reduction. Such a strategy may be advantageous in allowing more timely completion of the procedure and faster recovery than PSA with IV agents. However, such combinations greatly increase the risk of adverse events such as emesis and respiratory depression compared with N 2 O alone. Emesis is the most commonly reported adverse event (around 7-10%). Others include nausea, dizziness, euphoria and dysphoria, which are usually transient.

8 Diffusion hypoxia there is a theoretical risk of alveolar hypoxia occurring following the cessation of N 2 O administration, as residual N 2 O diffuses from tissues into the alveoli, displacing the available alveolar oxygen. It is therefore standard practice to administer 100% oxygen for 3-5 minutes at the conclusion of PSA with N 2 O. Expansion of trapped gas N 2 O diffuses from tissues into airspaces and will cause expansion of gas trapped in an enclosed space. The presence of pneumothorax, middle ear obstruction or bowel obstruction is therefore a contraindication to N 2 O. Patients who have recently had retinal surgery or craniotomy may have trapped intraocular gas, or intracranial gas respectively, and also should not be exposed to N 2 O. Environmental exposure there are epidemiological reports of impaired fertility and increased risk of spontaneous abortion in female dental assistants working with unscavenged N 2 O. This nosocomial risk is likely to be extremely small with occasional exposure to scavenged N 2 O as used in our ED. Nevertheless, patients, relatives and staff who are in early pregnancy should be warned of this risk and ideally should not be given N 2 O or be present when N 2 O is used. Interference with methionine synthase activity N 2 O oxidises vitamin B 12, eliminating this important coenzyme for methionine synthase, essential for the synthesis of DNA and RNA in rapidly dividing tissues such as bone marrow, and for myelin synthesis. Accordingly, there are case reports of N 2 O- associated bone marrow toxicity leading to megaloblastic anaemia, and of severe myeloneuropathy (subacute combined degeneration of the spinal cord). Inactivation of methionine synthase can also result in elevation of plasma homocysteine (a known risk factor for coronary artery and cerebrovascular disease). Based on these rare complications, N 2 O is relatively contraindicated in patients with known vitamin B 12 deficiency. 9 Ketamine 1 Ketamine is a NMDA receptor antagonist with potent sedative, analgesia and amnestic properties. It is said to exert its effect by disconnecting the thalamoneocortical and limbic systems, thereby dissociating the central nervous system from external stimuli. Its dissociative action puts ketamine in its own class, distinct from other agents in that it does not display a dose- dependent continuum of effect. That is, ketamine does not exhibit moderate sedation or deep sedation depending on dose. Dissociative sedation is either present or absent, and once dissociated, further administration of ketamine does not deepen sedation. Titration of ketamine is however required to maintain the dissociative state over time. Characteristics of dissociative sedation include: a trance- like state unresponsive but with eyes open; normal or slightly enhanced muscle tone, muscular clonus or spontaneous, random limb movement; nystagmus; hypersalivation; substantial or complete analgesia; total amnesia; maintenance of airway reflexes and maintenance of cardiovascular stability heart rate and blood pressure may be increased. Route of administration Both the intravenous and intramuscular routes are effective and safe and the choice of route is dependent on practical factors such as the ease with which IV access can be obtained. For many young children, intramuscular administration is effective, and mitigates the distress caused by the physical restraint necessary to obtain IV access. With IM administration, it is still recommended that IV access be secured once sedation is achieved, as a safety measure. A single IM injection provides a duration of effect (20-30 minutes) sufficient for most procedures, however, additional doses are sometimes required. These are most effectively given by the IV route. Intravenous dosing mg/kg by slow IV injection. Further IV doses of 0.5 to 1.0 mg/kg may be required. Time to peak effect: 1 min. Duration of effect: 5-10 min.

9 Intramuscular dosing 4-5 mg/kg. Further IM doses of 2-4 mg/kg may be required. Time to peak effect: 5 min. Duration of effect: min. Care must be taken to avoid rapid IV administration, which is associated with respiratory depression and apnoea. Ketamine should be injected slowly, over 1-2 minutes. This will usually require dilution of the standard IV formulation (100 mg/ml) to a more useable volume eg. 10 mg/ml. Adjunctive agents Routine, prophylactic co- administration of ondansetron may slightly reduce the rate of vomiting. Ketamine produces such profound analgesia that local anaesthesia is often unnecessary for procedures. Routine use of anticholinergic agents is no longer recommended to prevent hypersalivation. Routine pre- treatment with benzodiazepines is not required and is associated with an increased risk of respiratory depression. Should unpleasant emergence reactions occur they are readily treated with titrated benzodiazepines, typically IV midazolam. Adverse Effects Emesis occurs in 5 to 15% of patients. It usually occurs late during the recovery phase, when the patient has regained alertness and is able to protect the airway independently. Emesis appears more common in young adolescents than in younger or older children. Emergence reactions so called emergence delirium (causing clinically significant distress or requiring physical or chemical restraint) is rare and historically associated with large, general anaesthetic doses. Much more common emergence phenomena are mild, transient and rarely require medical treatment. Some disorientation or visual hallucinations are common, and some children become teary, but gentle reassurance and/or parental presence is usually all that is required. Respiratory depression uncommon, and usually associated with rapid IV administration or co- administration with other sedative agents. Laryngospasm a rare (0.3% of children in a large meta- analysis), but life- threatening complication. Risk factors include: upper respiratory tract infection, active pulmonary disease including asthma, age less than 3 months, and procedures which may stimulate the gag reflex, either by instrumentation or secretions. Reported occurrences have almost always responded to bag- mask ventilation and oxygen. Paralysis and intubation are rarely required. Propofol 10 Propofol is a highly lipid- soluble, potent, pure sedative agent. Due to its potency it is unsuitable when only mild- moderate sedation is required as it very readily produces deeper levels of sedation. It has no analgesic properties, although due to its potency it has been used alone for painful procedures. More commonly it is combined with a short- acting opiate such as fentanyl. Unlike midazolam and fentanyl which are usually titrated together, propofol because of its ultra- short half- life, should be titrated as a sole agent, after desired analgesia has been achieved with an opiate. Time to peak effect: seconds. Duration of effect: 6 minutes Suggested intravenous dosing: mg/kg initial bolus. Further boluses of mg/kg every 3 minutes as required to achieve or maintain sedation.

10 High- Risk Patients Lower doses are required to achieve sedation (and also to induce adverse effects) in the elderly or debilitated patients. Additionally, the time to reach peak effect may be longer in these patients. Accordingly, restraint and patience ( start low, go slow ) should be exercised in titrating propofol in the elderly, to avoid inadvertent over- sedation. Adverse Effects Propofol produces deeper levels of sedation and also depression of airway reflexes and respiratory and cardiovascular function in a dose- dependent fashion. Hypoventilation and apnoea the use of bag- mask ventilation is required in 3.0 to 9.4% of patients. Hypotension due to decreased peripheral vascular resistance. This effect is usually transient, with a duration similar to the drug s sedative effect. Systolic blood pressure has been shown to fall by 10.5 to 21 mmhg in healthy volunteers and hypotension can be pronounced in patients with depleted intravascular volume. Pain on injection occurs in a minority of ED patients and is rarely clinically significant. This adverse effect may be minimised by a number of described techniques. Lignocaine 0.5mg/kg may be injected with a tourniquet in situ seconds prior to propofol, or the same dose of lignocaine may be mixed in the syringe with the propofol bolus. Propofol is contraindicated in patients with allergies to propofol, eggs or soy products. Fentanyl & Midazolam This combination of potent, relatively short- acting opioid analgesic (fentanyl) and sedative- anxiolytic (midazolam) is commonly used for PSA where mild to moderate sedation is required. They are favoured because of familiarity and the availability of reversal agents. It has been shown however, that the majority of ED procedures require deeper levels of sedation 11 and although this is possible to achieve with these agents, it is practically difficult to achieve safely. Though they are relatively short- acting, it is difficult to titrate these agents to achieve deep sedation in a timely manner without significant risk of unintentional over- sedation, unnecessarily prolonged sedation, and adverse effects. Nevertheless, a single dose each of fentanyl and midazolam may be appropriate for mildly painful and/or anxiety- provoking procedures eg. lumbar puncture. These drugs should be titrated slowly and carefully (see below). The onset of action is slow relative to propofol or ketamine, in the range of 2-3 minutes, as is the time to peak: 5-15 minutes. Total duration of effect: minutes. Additional caution is required in the elderly and opioid- naïve patients. It has been suggested that due to the greater propensity of fentanyl for respiratory depression, it should be given first, and midazolam titrated subsequently 4. In children, these agents may be given intranasally for PSA using an atomiser and syringe. Dosage: Fentanyl: adults: mcg IV, children: 1-2 mcg/kg IV or IN. Subsequent doses (adult mcg, children mcg/kg) every 5 minutes to a total of 200mcg (adult) / 2.0 mcg/kg (child). Midazolam: adults: mg IV, children: mg/kg IV, mg/kg IN. Subsequent doses (adult mg, children mg/kg) every 5 minutes until sedated. Adult doses in excess of 5mg are rarely required. Many elderly patients will respond to mg.

11 Adverse Effects Though each agent has a good safety profile used alone, the combination of fentanyl and midazolam produces a synergistic response of not only the desired effect but also adverse effects, principally respiratory depression and apnoea. Again, the addition of other sedative agents, including alcohol and recreational drugs will further increase the risk of respiratory depression. Other adverse effects include: hypotension, nausea, vomiting, pruritus, chest wall rigidity (fentanyl), paradoxical agitation (midazolam). Reversal: Naloxone (for fentanyl): mg IV (child 10 mcg/kg IV), repeat every 1-2 minutes as required. Flumazenil (for midazolam): mg IV (child 10 mcg/kg IV), repeat every 1-2 minutes as required. References Anon. Previous RHH Procedural Sedation Policy ACEM Policy P09 - Guidelines on Sedation and/or Analgesia for Diagnostic and Interventional Medical, Dental or Surgical Procedure, acem.org.au (accessed Jan 2013) 1 Green et al. Clinical Practice Guideline for Emergency Department Ketamine Dissociative Sedation: 2011 Update. Ann Emerg Med (10) 2 Green SM et al. Fasting and Emergency Department Procedural Sedation and Analgesia: A Consensus- Based Clinical Practice Advisory. Ann Emerg Med 2007;49(4): ACEP Clinical Policy: Critical Issues in the Sedation of Pediatric Patients in the Emergency Department. Ann Emerg Med 2008;51: Molina JA, Lobo CA, Goh HK et al. Review of studies and guidelines on fasting and procedural sedation at the emergency department. Int J Evid Based Healthc 2010;8: Thorpe RJ, Benger J. Pre-procedural fasting in emergency sedation. Emerg Med J. 2010;27: ACEM Policy P09 - Guidelines on Sedation and/or Analgesia for Diagnostic and Interventional Medical, Dental or Surgical Procedure, acem.org.au (accessed Jan 2013) 7 ACEP Clinical Policy: Procedural Sedation and Analgesia in the Emergency Department. Ann Emerg Med 2014;63: Cote CJ et al. Adverse Sedations Events in Pediatrics: Analysis of Medications Used for Sedation. Pediatrics 2000;106(4): Macintyre PE, Schug SA, Scott DA, Visser EJ, Walker SM; APM:SE Working Group of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine (2010), Acute Pain Management: Scientific Evidence (3rd edition), ANZCA & FPM, Melbourne. 10 Miner JR, Burton JH. Clinical Practice Advisory: Emergency Department Procedural Sedation With Propofol. Ann Emerg Med 2007;50(2): Leroy PLJM et al. Professional Skills and Competence for Safe and Effective Procedural Sedation in Children: Recommendations Based on a Systematic Review of the Literature Int J Ped 2010: 1-16