PEM Board Review Chapter 23: Procedural Sedation Different types of agents are used for procedural sedation and analgesia for pediatric patients in the emergency department. These include the dissociative agent ketamine, opioids, benzodiazepines, and two newer agents, propofol and etomidate. Ketamine, a phencyclidine derivative that produces dissociative anesthesia and amnesia, has been well researched in the pediatric setting. It can induce a trancelike state in which the child may appear to be awake and may retain some purposeful movement. Ketamine has intrinsic analgesic and amnestic properties, making it an ideal choice for procedural sedation and analgesia. In addition, it has bronchodilator properties that make it a potential agent for rapid sequence induction (RSI) in patients who have asthma exacerbations. Ketamine is associated with increased airway reflexes, including hypersalivation and laryngospasm. Fortunately, laryngospasm and subsequent obstructive apnea are relatively rare events. Some factors that seem to increase the risk of laryngospasm are manipulation of the pharynx, laryngeal stimulation, and upper respiratory infections. In a pediatric study, laryngospasm occurred in 9% of children undergoing upper gastrointestinal endoscopy compared with none of those undergoing lower gastrointestinal endoscopy. In most cases, laryngospasm associated with ketamine use can be treated effectively with airway repositioning and gentle bag-valve-mask ventilation. Occasionally, administration of a neuromuscular blocking agent and subsequent endotracheal intubation are required. Opioids commonly used in procedural sedation and analgesia include morphine and fentanyl. As with other opioids, common adverse effects include respiratory depression, hypotension, nausea, and vomiting, but laryngospasm is not seen. Fentanyl has the advantage of being relatively short-acting. However, it is associated with apnea, bradycardia, and chest wall rigidity and laryngospasm, which occurs primarily with rapid infusion and high doses (>5 mcg/kg). Morphine has a slower onset and longer duration of action. Benzodiazepines such as midazolam function as sedatives, anxiolytics, and amnestics by potentiating the inhibitory effects of gamma-aminobutyric acid (GABA). They also are used to relieve musculoskeletal spasticity and short-term insomnia. It is important to remember that benzodiazepines have no analgesic properties and generally are used in concert with another agent for painful procedures. Common adverse effects include respiratory depression and hypotension but not laryngospasm. Etomidate is a nonbarbiturate sedative hypnotic agent that is being used with increasing frequency in children. The advantages of etomidate include rapid onset and short duration of action as well as minimal hemodynamic effects. Adverse effects include myoclonus and adrenal suppression (with prolonged use). Laryngospasm is not an associated adverse effect. Some common indications for etomidate use include relatively short procedures, such as reduction of shoulder/hip dislocation and RSI. Doses range 0.1 to 0.3 mg/kg. 1 Propofol is a general anesthetic agent that causes dose-dependent sedation. The usual bolus dose is 1 mg/kg over 2 minutes, followed by an infusion at 50 to 100 mcg/kg per minute. This medication has a very fast onset of action (0.5 to 1 minutes), a short duration of action (5 to 10 minutes), and minimal residual sedation. Long-term administration rarely is associated with refractory metabolic acidosis. Compared with ketamine, propofol is associated with increased incidences of apnea. Compared with etomidate, propofol more frequently causes hypotension. However, propofol use is not associated with laryngospasm. Common indications for propofol use include sedation for cross-sectional imaging. Administration of an analgesic agent is required for painful procedures because propofol has no analgesic properties. Maximum local dose of Lido without Epi per procedure= 5mg/kg Maximum local dose of Lido with Epi per procedure=7mg/kg Calculating appropriate Lido dose: 1% Lido=1g/100cc, therefore, 1000mg/100cc, therefore 10mg/cc; if the child weighs 10kg and the max dose is 5mg/kg, the max dose for that child would be 50mg, which would be 5cc. Signs of Lido toxicity: develops in an orderly progression from CNS effects to CV involvement. Early signs are numbness of tongue and mouth, metallic taste, lightheadedness, tinnitus, visual disturbance, nystagmus, and slurring of speech. This may progress to muscle twitching, confusion, unconsciousness, and seizures. Cardiac effects include ectopy, AV conduction disturbances, hypotension, dysrhythmias, and cardiac arrest. If a patient doesn’t inform the physician of the early symptoms—especially can be the case in the pediatric patient—the first sign of toxicity may be a seizure. Give IV Lorazepam. Bupivacaine-induced cardiac toxicity carries a high mortality—benzo’s may prolong the half-life and even preferentially raise cardiac levels!! Therefore, use Phenytoin for treatment of bupivacaine-induced seizures or cardiac dysrhythmias. Ketamine provides analgesia as well as sedation and can be used as a single agent. Benzos, chloral hydrate, pentobarbital, and propofol are all sedatives but provide no analgesia and should be combined with an analgesic (such as fentanyl) to achieve appropriate PS&A. Minimal sedation: responds normally to verbal commands, not asleep Moderate sedation: should not require repeated painful stimulation to be aroused and should not require intervention to maintain a patent airway. Deep sedation: patient cannot be easily aroused but responds purposefully after repeated verbal or painful stimulation. The ability to independently maintain ventilatory function may be impaired. 2 Dissociative Sedation: a trancelike cataleptic state induced by the dissociative agent ketamine, characterized by profound analgesia and amnesia, with retention of protective airway reflexes, spontaneous respirations, and cardiopulmonary stability. Anesthesia: patient not arousable, even by painful stimulation. Flumazenil reverses the CNS and respiratory depression associated with Benzo’s. Dose=0.01-0.02 mg/kg/dose IV/IM (maximum initial dose of 0.2mg) Dose may be repeated every minute to a maximum cumulative dose of 1 mg. Because of the risk of seizures, it should not be used in patients receiving long-term benzos, cyclosporine, INH, Lithium, propoxyphene, theophylline, or TCA’s. The onset of action is 1 minute and the duration between 30-60 minutes. Pentobarbital is a barbiturate, and there are no approved reversal agents for barbiturates. Ketamine possesses catecholamine-like properties, thus inducing bronchodilatiion and hypertension. Its side effects include laryngospasm, apnea, respiratory depression, increased ICP, increased IOP, emergence reactions, and hypersalivation; because it increases ICP and IOP, it should not be used in patients with head injury, increased ICP, glaucoma, or acute globe injury. The initial step in the patient who has apnea during procedural sedation is to stimulate the patient with a sternal rub. Then try repositioning the airway, then O2, then consider reversal agents. Patients are at highest risk for respiratory depression during 2 separate periods: 1) during the first 5-10 min after IV administration of meds, and 2) during the immediate post-procedure period, when painful procedural stimuli have ceased. Chest wall rigidity, known as “wooden chest syndrome” is a side effect best known to be associated with the use of fentanyl. It is most often associated with doses greater than 15mcg/kg but may also be seen with rapid infusions of smaller doses. It has not been reported in the low bolus doses of 1-2mcg/kg recommended for procedural sedation. If chest wall rigidity occurs, it is not usually reversible with naloxone. Neuromuscular paralysis and intubation may be required to achieve adequate ventilation. The usual duration of action from intermittent IV dosing of Etomidate is 4-10 minutes. Onset of action is less than 1 minute. It is critical to provide additional sedatives if the noxious stimuli is anticipated to last longer than 4-10 minutes. Propofol possesses inherent antiemetic and euphoric properties. The most serious adverse effect of it is potent respiratory depression and apnea, which can occur suddenly and without warning. It can also produce hypotension by direct negative inotropy as well as arterial and venodilation. 3 ETCO2 detection via side-stream capnography is the most reliable method of monitoring adequate ventilation during sedation in non-intubated patients. Absent ET CO2 waveforms and levels indicate apnea, laryngospasm, or complete airway obstruction. Rising levels of ETCO2 and change in shape of the CO2 waveform indicate hypoventilation. With an obstructed airway, chest excursions may occur without air movement. Chloral hydrate is metabolized in the liver to the active metabolite 2,2,2-trichlorethanol. This active metabolite has a long half-life in neonates (24 hrs) and children (12 hours). It is a pure sedative-hypnotic agent without analgesic properties. When given orally, the average time to peak sedation is 30 minutes, with an additional recovery time of 2 hours. Despite a wide margin of safety, chloral hydrate can cause airway obstruction and respiratory depression, especially at high doses (75-100mg/kg). Benzos lack analgesic properties. Pentobarbital can lead to respiratory depression and hypotension as it is a negative inotrope. The usual duration of dissociation provided by typical IV doses of ketamine (1-2mg/kg IV) is 10-15 minutes. Using IM Ketamine at 4mg/kg can increase the duration to 30-60 minutes. The most common side effect of fentanyl is facial pruitis and nasal itching. It may also induce hypotension in high doses (uncommon). Thiopental has a side effect of inducing bronchospasm so would be contraindicated in intubating an asthmatic. Paradoxical excitation and agitation following administration of midazolam is a common side effect. This usually resolves without specific therapy within 20 minutes. There is no need to administer additional sedatives or reversal agents. Moderate sedation (formerly “conscious sedation”) is defined as a drug-induced depression of consciousness during which patients respond purposefully to verbal commands either alone or accompanied by light tactile stimulation. With moderate sedation, no intervention is required to maintain a patent airway and cardiovascular function is usually maintained. A child who is minimally sedated would respond normally to verbal commands and would not be asleep. 4 Laryngospasm following use of ketamine is <1% of ketamine sedations in the ED; it is classically described as stridulous (stridorous) and high-pitched. Stertorous (sonorous) respirations are more typically lower pitched and help identify the site of the airway obstruction as the oro or naso-pharynx. The first step here would be airway repositioning. If the patient truly had laryngospasm then the first step would be PPV with bag-valve-mask in an attempt to overcome the laryngospasm. If this fails, then neuromuscular paralysis and emergency ET intubation should be performed. Propofol is a pure sedative-hypnotic. It provides no analgesia and should be combined with an agent with analgesic properties such as ketamine (aka “ketofol”) when used with painful procedures. Propofol has been touted as an ideal drug for ED based procedural sedation because of its reliability, rapid onset, short duration, easy titratability, and intrinsic antiemetic properties. However, its use has been limited due to concerns for respiratory and cardiovascular depression. Etomidate’s adverse effects include respiratory depression, myoclonus, nausea, and vomiting as well as transient adrenal suppression. Barbiturates (thiopental and methohexital) frequently can cause hypotension at typical IV doses so their use should be avoided in patients with volume depletion or cardiovascular compromise. Inhaled Nitrous oxide (40%) provides anxiolysis and only mild analgesia so for procedures would need to be combined with an IV opioid or local analgesia; safest route of administration is via a self-administered demand-valve mask; should be avoided in patients with potential closed-space diseases such as bowel obstruction, middle ear disease, pneumothorax, or pneumocephaly; it is also a known teratogen and mutagen. LET is the only agent designed for use on non-intact skin (lacs). Ethyl chloride and fluoromethane are topical sprays that are used to anesthetize intact skin by rapid evaporative cooling. EMLA is a topical cream that is only approved for use on intact skin; LET is contraindicated in areas of end arterial supply (penis, digits, pinna, tip of nose) because it contains Epi. ASA Physical Status Classes: Class I: normal healthy patient Class II: patient with mild systemic illness without functional limitation (a child with history of well controlled asthma with no active wheezing) Class III: patient with severe systemic disease with definite functional limitation Class IV: patient with severe systemic disease that is a constant threat to life. Class V: moribund patient not expected to survive without the procedure Initial doses of fentanyl used IV for procedural sedation is 1-2mcg/kg. Subsequent doses of 0.5-1mcg/kg are used to titrate to effect. 5 Nitrous oxide can provide both sedation and analgesia. However, since the analgesic qualities are weak in the concentrations administered in the ED setting, compared to the OR, its use has been largely limited to procedures that: 1) require minimal sedation; 2) are of very short duration; or 3) combine the use of regional or local anesthetics, such as lidocaine in hematoma blocks. Because flumazenil and naloxone may have a shorter duration of action than the medications they are reversing, patients must be carefully monitored for the possibility of resedation. Reported side-effects of naloxone include hypertension, ventricular tachyarrhythmias, cardiac arrest, and vomiting. There are no approved reversal agents for barbiturates. The decision to perform procedural sedation and analgesia (PSA) to facilitate fracture manipulation must be balanced against the risks of sedation in each patient. Careful presedation assessment begins with a focused history and physical examination. Most organizations follow the classification published by the ASA (Table 1). The MP classification system can be used to identify patients at risk for having difficult airways (Fig. 2). The adequacy of seeing the posterior oropharynx has been shown to correlate with glottic exposure during direct laryngoscopy. The patient described in the vignette, who has poorly controlled asthma, obesity, and OSAS, should be classified as ASA level 3 (ie, having moderate systemic disease that may limit his activity but is not incapacitating). His oropharyngeal examination findings suggest an MP class 2 airway. An ASA level 3 or greater and MP class 3 or greater have been shown to correlate with an increased risk of sedation-related adverse events and unexpected difficult airway, respectively. Although these data have been extrapolated from the adult anesthesiology literature, the American Academy of Pediatrics encourages practitioners to consult with appropriate subspecialists or anesthesiology about patients deemed to be at high risk for procedural sedation (Table 2). In such cases, the practitioner may defer PSA in the emergency setting and opt for complete control of the airway with general anesthesia outside the emergency department or use alternative techniques such as local or regional block anesthesia with minimal sedation. The key steps prior to performing PSA in the emergency department are: 1. Risk stratification based on the ASA physical status classification. 6 2. A focused presedation history and physical examination (Table 3). 3. Documentation of the time of last oral intake. 4. Preparation and set up; the acronym SOAPME may be used to review the preparatory steps (Table 4). 5. Selection of the appropriate agents based on desired depth of sedation to best facilitate the procedure. Preoperative and elective procedure NPO guidelines have limited applicability in the emergency setting. Adverse events are more related to depth of sedation, type of procedure, and age of patients than to NPO status. Therefore, the emergency physician should weigh the risks and benefits of the procedure and sedation for each patient in deciding duration of preprocedural fasting. The indications for PSA include any procedure that is likely to invoke significant pain or distress or one that requires a relatively motionless state, such as advanced imaging studies or complex laceration repair (Table 5). The choice of agent usually involves a combination of a sedativehypnotic (or dissociative) agent and narcotic analgesic for painful procedures. Other factors that may determine the type of medication include familiarity with a particular class of agent, institutional preference, or clinician credentialing for sedation in the emergency department. Table 6 lists the properties of the various pharmacologic agents and their major adverse effects. Airway complications are the most common adverse events during PSA. They include hypoventilation, apnea, airway obstruction, aspiration, bronchospasm, and rarely laryngospasm. Respiratory depression can be a consequence of a deeper level of sedation than anticipated or an adverse effect of the sedative-hypnotic agent used. It may be enhanced by concomitant use of narcotic analgesia. The clinician administering sedation must be proficient in early recognition of airway obstruction or hypoventilation and be prepared to intervene to secure an adequate airway. Interventions might include airway realignment, bag-mask ventilation, and intubation, if necessary. Severe laryngospasm requiring neuromuscular blockade and intubation is an infrequent complication in procedural sedation cases in the pediatric emergency department. It is precipitated by incomplete or complete closure of the true vocal cords. It is defined as absence of air exchange in the presence of chest wall movement with or without stridor, not responsive to airway repositioning and routine bag-valvemask ventilation. Occluding the pop-off valve to generate higher 7 pressures with bag-mask ventilation and attempting the “laryngospasm maneuver” may be temporizing measures before administering a neuromuscular blocking agent and endotracheally intubating the patient. The laryngospasm maneuver is performed by applying firm pressure in the notch located between the angle of the mandible anteriorly, the mastoid posteriorly, and the base of the skull superiorly. The purported mechanism is pressure in the notch surpassing the patient’s pain threshold that causes the vocal cords to relax. It is similar to the jaw thrust maneuver, but the pressure is directed toward the mandibular condyles rather than to the angles of the mandible. Table 6: Overview of Medications Agent Pediatric Dosing Onset (min) Duration (min) Comments Choral hydrate PO: 25 to 100 mg/kg, after 30 min can repeat 25 to 50 mg/kg. Maximum total dose: 2 g or 100 mg/kg (whichever is less). Single use only in neonates 15 to 30 60 to 120 Effects unreliable if age <3 years Diazepam IV: initial 0.05 to 0.1 mg/kg, then titrate slowly to maximum 0.25 mg/kg 4 to 5 60 to 120 Reduce dose when used in combination with opioids Sedativehypnotics 8 Etomidate IV: 0.1 mg/kg; repeat if inadequate response <1 5 to 15 Adverse effects include respiratory depression, myoclonus, nausea, emesis Midazolam IV (0.5 to 5 years): initial 0.05 to 0.1 mg/kg, then titrated to maximum 0.6 mg/kg IV (6 to 12 years): initial 0.025 to 0.05 mg/kg, then titrated to maximum 0.4 mg/kg 2 to 3 45 to 60 Reduce dose when used in combination with opioids; may produce paradoxic excitement IM: 0.1 to 0.15 mg/kg 10 to 20 60 to 120 PO: 0.5 to 0.75 mg/kg 15 to 30 60 to 90 IN: 0.2 to 0.5 mg/kg 10 to 15 60 PR: 0.25 to 0.5 mg/kg 10 to 30 60 to 90 PR: 25 mg/kg 10 to 15 60 Avoid if temporal lobe epilepsy or porphyria IV: 1 to 6 mg/kg, titrated in 1- to 2mg/kg increments every 3 to 5 min to desired effect 3 to 5 15 to 45 May produce paradoxic excitement; avoid in patients who have porphyria IM: 2 to 6 mg/kg, maximum 100 mg 10 to 15 60 to 120 PO/PR (<4 yrs): 3 to 6 15 to 60 mg/kg, maximum 100 mg PO/PR (>4 yrs): 1.5 to 3 mg/kg, 60 to 240 Methohexital IV: 0.5 to 1.0 mg/kg Pentobarbital 9 maximum 100 mg Propofol IV: 1.0 mg/kg, followed by 0.5 mg/kg repeat doses as needed <1 5 to 15 Frequent hypotension and respiratory depression; avoid with egg or soy allergies Thiopental PR: 25 mg/kg 10 to 15 60 to 120 Avoid in patients with porphyria Fentanyl IV: initial 1.0 mcg/kg up to 50 mcg/dose, may repeat every 3 min, titrate to effect 3 to 5 30 to 60 Reduce dosing when combined with benzodiazepines Morphine IV: initial 0.05 to 0.15 mg/kg up to 3 mg/dose, may repeat every 5 min, titrate to effect 5 to 10 120 to 180 Reduce dosing when combined with benzodiazepines IV: 1 to 1.5 mg/kg slowly over 1 min, may repeat every 10 min as needed 1 Dissociation: 15 Recover y: 60 Multiple contraindications. Unpleasant dreams or hallucinations rare in kids. Dissociation: 15 to 30 Often given with concurrently atropine or glycopyrrolate to counter hypersalivation Analgesics Dissociative Drug Ketamine IM: 4 to 5 mg/kg, may 3 to 5 repeat (2 to 4 mg/kg) after 10 min Recovery: 90 to 150 Inhalational Drug 10 Nitrous oxide Preset mixture with minimum 30% oxygen self-administered by demand valve mask (requires cooperative child); continuous flow nasal mask in uncooperative child with close monitoring <5 <5 following discontinuati on Requires specialized apparatus and gas scavenger capability; several contraindications Reversal Drugs Naloxone IV/IM: 0.1 IV: 2 mg/kg/dose up to maximum of 2 mg/dose, may repeat every 2 min as needed IV: 20 to 40 IM: 60 to 90 If shorter acting than the reversed drug, serial doses may be required Flumazenil IV: 0.02 mg/kg/dose, may repeat every 1 min up to 1 mg 30 to 60 If shorter acting than the reversed drug, serial doses may be required 1–2 Alterations in dosing may be indicated depending on the clinical situation and the practitioner’s experience with the drugs. Individual doses may vary when used in combination with other drugs, especially when benzodiazepines are combined with opiates. Ketamine is absolutely contraindicated in patients <3 months (airway risk) or when known psychosis (may exacerbate). Relative contraindications include age <12 months, procedures involving stimulation of posterior pharynx, history of tracheal surgery or stenosis, active pulmonary infection or disease (including upper respiratory tract infection), known or suspected cardiovascular disease, suspected raised intracranial or intraocular pressure, globe injury, porphyria or thyroid dysfunction. IM=intramuscular, IN=intranasal, IV=intravenous, PO=oral, PR=rectal Reprinted from Pershad J, Kost S. Emergency department based sedation services. Clin Pediatr Emerg Med. 2007;8:253-261. Copyright © 2007, Elsevier close 11 Table 1: American Society of Anesthesiologists (ASA) Risk Classification Class I A normal, healthy patient. Class II A patient who has mild systemic disease (no functional limitation). Class III A patient who has moderate or severe systemic disease that limits activity but is not incapacitating. Class IV A patient who has an incapacitating systemic disease that is a constant threat to life. Class V A moribund patient who is not expected to survive 24 hours with or without the procedure. Reprinted from Pershad J, Kost S. Emergency department based sedation services. Clin Pediatr Emerg Med. 2007;8:253-261. Copyright © 2007, Elsevier 12