Sedation

Sedating Drugs (IV Anesthesia):

Guidelines: Scheduled bolus injections or continuous infusions of morphine or lorazepam should be administered in pt’s receiving propofol for >72h. The level of sedation should be monitored using the Ramsay Scale. Pt’s should be awakened from sedation qd to asses respiratory and neurologic function. Morphine for analgesia should be used in any pt with perceived agitation secondary to pain. A telephone study on 110 pt’s found that the vast majority of pt’s who undergo procedural sedation in the ED have no recall of the event (Emerg Med J 2007;24:322-4) (a grimace or groan was observed in 49% of pt’s, but only 7.4% had immediate recall and 4.5% had delayed [72 hours] recall).

Ramsay Scale for Assessment of Sedation:

Level/score: 1 –> anxious and agitated.

2 –> cooperative, oriented, tranquil.

3 –> responds only to verbal commands.

4 –> asleep with brisk response to light stimulation.

5 –> Asleep with sluggish response to stimulation.

6 –> Asleep w/o response to stimulation.

The Sedation-Agitation Scale (SAS):

1. –> Unarousable – deep hypnosis, non-arousable, no spontaneous movement, no coughing.

2. –> Very sedated – rousable with strong tactile stimulus, occasional spontaneous and non-purposeful movements, does not respond to commands.

3. –> Sedated – Asleep/sedated but rousable with tactile stimulus and displays purposeful movements and follows simple commands.

4. –> Calm cooperative – Calm, awakens easily, follows commands.

5. –> Agitated – Anxious or mildly agitated, attempting to sit up, calms down to verbal instructions.

6. –> Very agitated – Does not calm despite frequent verbal remind; requires physical restraints, biting ET tube.

7. –> Dangerous agitation – Severe anxiety, diaphoresis, frequent vigorous movements, pulling on ET tube , trying to remove catheters, climbing over bed rails, striking at staff, thrashing side to side.

Goals of Sedation:

Non-ventilated pt’s –> SAS 3-4.

Ventilated pts: AC, SIMV, PS –> SAS 2-4.

Ventilated pts: PCV, low TV AC –> SAS 1-2.

Bispectral Index (BIS) Monitor: Uses EEG leads. A simple EEG-based device that provides a single number, ranging from zero (corresponding to an isoelectric ECG) to 100 (full, normal consciousness). BIS monitoring has shown promise for assessing depth of sedation in adults and children (Anesth Analg 2006;102:380-8). BIS units are inexpensive and easy to use with disposable skin leads.

Confusion Assessment Method:

1. Acute onset or fluctuating course: Is there evidence of an acute mental status change from baseline. Did the abnormal behavior fluctuate in the past 24hrs. Based on GCS, prior delirium assessment or Richmond Agitation-Sedation Scale (RASS).

2. Inattention: did the pt have difficulty focusing attention. Based on the Attention Screening Exam (ASE).

3. Disorganized Thinking: evidence of incoherent thinking if incorrectly answer 2 of the following 4 Q’s.

Will a stone float on water (will a leaf float on water)?

Are there fish in the sea (are there elephants in the sea)?

Does 1 pound (kilogram) weigh more than 2 pounds (do 2 pounds weigh more than 1 pound)?

Can you use a hammer to pound a nail (can you use a hammer to cut wood)?

4. Altered level of consciousness: Is the pt anything other than alert, such as vigilant, lethargic, or stupor?

Positive: features 1 & 2 and either feature 3 or 4 (Primary Psychiatry 2004;11:59-64).

Ddx of ICU Agitation: hypoxia, hypercarbia, hypoglycemia, encephalopathy, drug/ ETOH withdrawal, CNS catastrophes, ICU psychosis, pain, anxiety or disorientation. Pt’s in the ICU who develop delirium while mechanically ventilated have a 3-fold increased risk of death compared with similarly treated pt’s who do not develop delirium, even after controlling for pre-existing comorbidities, coma, illness severity, and sedative or analgesic medications (JAMA 2004;291:1753-1762).

Conscious Sedation: Fentanyl (~50 mcg) + Midazolam (3mg) or Demerol (25-75mg) + Midazolam are the most commonly used meds.

Indications for Sedation in ICU:

Pt is danger to self/ others, anxiety is worsening the underlying pathology, initial ETT tolerance, NMB, part of program to restore day/night cycling, protection from withdrawal syndromes. See Weaning Trials & Sedation with Intubation |

Contra: respiratory insufficiency, CV instability, specific drug intolerance, need for “barnacle therapy (unwanted meds).

ICU psychosis: The stressful ICU environment leads to sleep deprivation, increased arousal, mechanical ventilation, and social isolation. This often combines with pre- and postsurgical anxiety states, metabolic derangements and polypharmacy.

Sedative/Hypnotic Agents of Choice:

Based on cost, efficacy, tolerance, pharmacokinetics and pharmacodynamics and side-effects.

Analgesic: Morphine.

Sedation: Lorazepam (Ativan) if long-term (>24hr). Midazolam (Versed) or Propofol if short-term.

Long term sedation –> Lorazepam is the drug of choice for non-intubated pt’s and pt’s who will require long term sedation/hypnosis in the ICU (> 48 hours). Benzodiazepines should be avoided in pt’s with liver disease. Lorazepam and propofol act synergistically; the addition of propofol should be considered to prevent oversedation and long waking time. The daily interruption of sedative-drug infusions is recommended in pt’s receiving mechanical ventilation. This approach allows daily assessment of neurological function that would otherwise not be possible and prevents oversedation and reduction of total sedative dosages.

Short term sedation, neurological/neurosurgical pt’s –> Propofol is the drug of choice due to the rapid emergence once discontinued.

Deep hypnosis to facilitate “lung protective ventilation” –> This may be achieved with propofol alone. However, propofol and lorazepam have synergistic effects and the combination may achieve the desired level of hypnosis at a lower cost.

Tx of Delirium or sedation without respiratory depression –> Haloperidol.

Sedation for invasive procedures –> Midazolam alone or in combination with fentanyl.

Sedation Protocols:

1. To treat SAS 7, sedation for PCV, neurosurgical/neurology pt’s , pt’s with hepatic dysfunction and short term sedation (< 24 hours):

Propofol: Start IV drip at 10ug/kg/min, titrate dose by increments of 5-10 mcg/kg/min at 10 minute intervals.

Lorazepam 2-4 mg IV Q4 hour; hold if pt requiring < 50 mcg/kg/min Propofol.

Hold propofol drip Q AM to assess neuro status, restart drip at previous level. Propofol should only be used in intubated pt’s.

Weaning Propofol: Decrease propofol by 10ug/kg/min q 2 hour. Check triglyceride Monday and Thursday: if >400 mg/dl halve propofol dose and start lorazepam infusion at XX mg/hr (if > 600 mg/dl stop propfol).

2. To treat SAS 5 or 6 or for any pt for whom sedation is required:

Non Intubated pt: Lorazepam 2-4 mg IV Q 6 hours. Hold for SAS < 3.

Intubated Pt:

SAS 6. Lorazepam infusion – start at 2mg/hr and then titrate to SAS level XX increasing by 2mg/hr no more frequently than every 15 minutes.

SAS <6. Lorazepam 2-4 mg Q 4 hourly IV. If poor response change to an infusion of lorazepam at 2mg/hr and then titrate to SAS level XX increasing by 1mg/hr no more frequently than every 15 minutes. Hold lorazepam drip Q AM to assess neuro status, restart drip at previous level.

3. Delerium: Haloperidol 5-25 mg IV Q 10 minutes PRN for SAS 6 or 7. Do not exceed 80 mg over 2 hours.

Haloperidol 5-25 mg IV Q 4 hours. Hold for SAS <3.

Ig SAS >4 choose from:

Lorazepam 2-4 mg IV Q 4 hours. Hold for SAS <3.

Haloperidol 10 mg IV Q 10 minutes PRN for SAS 6 or 7. Do not exceed 80 mg over 2 hours.

Haloperidol 5 mg IV Q 4 hours. Hold for SAS <3.

Drugs of Choice for ICU Sedation:

Ultrashort-acting Barbiturates: Can be used as an anesthetic induction agent.

Thiopental (Pentothal): 2-5mg/kg over 30-45s. Onset 45s, DUO 5-10min. SE: myocardial/respiratory depression, peripheral vasodilation. Decreases cerebral blood flow and ICP. Use cautiously if CAD or shock.

Methohexital (Brevital): 1mg/kg. Immediate onset, used for induction and intubation. SE: myocardial depression, hypotension.

Contra: porphyria.

Etomidate (Amidate): 0.3 mg/kg IV. An ultrashort-acting nonbarbiturate hypnotic agent used as an anesthesia induction agent. A potentially significant benefit of etomidate in the emergency setting is its lack of cardiodepressant effects. The drug rapidly accumulates in vascular organs, reaching peak brain concentrations within 1 minute of IV infusion. There is virtually no accumulation of the drug, and anesthesia may be maintained through repeated or continuous dosing. The most common side effects of etomidate are N/V, pain on injection, and myoclonic jerks. Etomidate’s excellent hemodynamic stability and short duration of action make it an important induction agent for emergent intubation.

Induction anesthesia @ 0.3 (0.2-0.4) mg/kg IV. Onset in 30-90sec. For induction and intubation. Minimal BP effects.

SE: incr/decr BP, adrenocortical suppression. Propofol and etomidate are equally safe sedatives for ER procedures, but etomidate carries a lower procedure success rate (97.2% & 88.6%) and is more likely to induce myoclonus (1.8% & 20%) (Ann Emerg Med 2007;49:15-22). Although etomidate’s use in pt’s with septic shock has been questioned because it can interfere with adrenal function for 24 to 72 hours after intubation through inhibition of 11-beta-hydroxylase, the clinical significance does not appear to affect outcomes (Crit Care 2007;11:R56;e-pub ahead of print). No credible evidence supports the assertion that etomidate should be avoided in patients with septic shock (Journal Watch Emergency Medicine February 1, 2008)…..Etomidate and ketamine are the two induction agents known to have the least potential to induce or worsen hypotension. Etomidate appears to be safe in patients with septic shock (Intensive Care Med 2009;35:1868)…..showed no difference in mortality and had no effect on Sequential Organ Failure Assessment (SOFA) scores. Outcomes did not differ significantly with either midazolam (0.1 mg/kg) or etomidate (0.3 mg/kg) for induction in 122 adult patients with suspected sepsis (Ann Emerg Med 2010;56:481)…..Etomidate is an ideal induction agent because of its predictable dosing, rapid onset, short duration of action, and excellent hemodynamic stability……This report adds to a growing body of well-designed studies that refute the assertion that etomidate should not be used in patients with sepsis.

Narcotics:

Naloxone (Narcan): to reverse –> 0.1-2mg IV, titrate to response, may repeat in 2-3min intervals to max of 10mg. Always consider opiate OD if see a low respirator rate with constricted [miotic = pinpoint] pupils).

Fentanyl (Sublimaze): 0.4mg/kg IV. Load at 2ug.kg (25-100 mcg), the infuse at 1-2 mcg/kg/hr (25-100 mcg/hr). 50-75X more potent than morphine. Minimal myocardial effects. Duration of analgesia is ~1h. SE: respiratory depression, muscle rigidity, hypotension, bradycardia, truncal rigidity (“wooden chest”). Reverse with Naloxone (0.4mg/kg IVP). Analgesic dose @0.05-0.1mg (2-10ug/kg) (1-2ml). No histamine release as with MS. Can accumulate in the peripheral compartment to incr the T-½ from 45min to 16hrs. May be preferred if pt has hemodynamic instability.

Morphine Sulfate (MSO4 = MS): 2.5-15mg IV. Inexpensive. SE: hypotension (incr venous & arterial capacitance), bradycardia, biliary tract spasms, pruritus, urinary retention, respiratory depression, constipation. Incr concentrations if renal failure. T-½ of 2hrs. Give a bolus dose of 0.05mg/kg, then infuse at 2-10mg/hr. A sedation protocol that included morphine only as needed was associated with fewer ventilator (14 vs. 10) and intensive care unit days (13 vs. 22) and no excess complications in critically ill patients (Lancet 2010;375:475)…..The control group received continuous infusions of propofol followed by midazolam, along with as-needed morphine boluses (5 mg), and were awakened daily…..Intervention patients received as-needed morphine boluses only……Intervention patients also required more attention from nurses and other caregivers, and about 15% received one-on-one comfort from dedicated caregivers…..About 18% of intervention patients were persistently uncomfortable and required episodes of continuous sedation (although such patients were evaluated with the intervention group in the intent-to-treat analysis).

Pt Controlled Analgesia (PCA) Morphine: 1 mg/ml usual concentration. 5 mg/ml high concentration. Loading Dose 0.04 mg/kg (may repeat q10 min X 3 PRN). Maintenance PCA Dose 0.02 mg/kg. Lockout Interval 8-15 minutes. 4 hour limit 0.3 mg/kg lean body wt or up to 30 mg max, adjust according to need (up to max 150 mg opioid tolerance). Continuous Infusion (only if opioid tolerance or high need): ~ one-third of the average hourly usage. e.g. 0.01-0.04 mg/kg/hr. Age > 65 years decrease dose 25%. Debilitated pt decrease dose 25-50%. Opioid tolerance increase dose 25-50%. Inadequate analgesia increase PCA dose 25%.

Adjunct Therapy: Ketorolac x 48 hours; 30 mg q6h if > 50 kg and < 65 y/o; 15 mg q6h if < 50 kg or > 65 y/o. Celebrex 200-400 mg q12h PO. Ativan 0.25-0.5 mg IV q6h PRN.

PCA Pediatric Morphine: If inadequate analgesia increase PCA dose 10-15%. Loading Dose 0.05-0.10 mg/kg. Maintenance PCA Dose 0.015-0.02 mg/kg. Lockout Interval 8-15 minutes. 4 hour limit 0.25+ mg/kg, adjust according to need. Continuous Infusion 0.004-0.02 mg/kg/hr.

Adjunct Therapy: Acetaminophen 15 mg/kg PO (or 30 mg/kg PR X 1 then 15 mg/kg) q4h X 24, then q4-6h PRN.

Alfentanil (Alfenta): Sedation 5-7 mcg/kg IV bolus, maintenance 0.25-0.5 mcg/kg/min, with ~ a 2.5 mg total depending on length of case. General Anesthesia: 50-75 mcg/kg (2-3 divided doses) + reduced dose (1-3 mg/kg) thiopental or other agent for induction. For pure narcotic induction, ~ 75-250 (average 150) mcg/kg divided doses, maintenance 0.5-3 mcg/kg/min with 5-7 mcg/kg bolus PRN (02/N20/+ PRN inhalational agent). Average infusion rate 1-1.5 mcg/kg/min. In procedures < 60 minutes or high risk pt’s, induction dose reduced to 10-50 mcg/kg (+ thiopental). High intrasubject variability in dose.

Sufentanil (Sufenta): 2.5-10 mcg IV PRN perioperative analgesia or intraoperative supplementation. General Anesthesia: 1-3 mcg/kg IV total or 1 (or less) mcg/kg/hr of surgery, with 50-75% up front (0.5 mcg/kg/hr elderly/high risk/balanced). Maintenance 0.1-0.5 mcg/kg/hr with 5-10 mcg bolus PRN (02/N20/+ PRN inhalational agent). Major cardiovascular: induction 5-10 mcg/kg slowly, maintenance 1-3 mcg/kg/hr or 3-5 mcg/kg bolus PRN. Up to 30 mcg/kg with 02/Air can be used for major procedures and require extended post-op ventilation.

Nalbuphine (Nubain): Balanced anesthesia: 0.3-3.0 mg/kg IV over 10-15 minutes, maintenance doses 0.25-0.50 mg/kg in single IV administrations.

Remifentanil (Ultiva): Sedation/Analgesia LD 1 mcg/kg over 60 sec, maintenance 0.025-0.25 mcg/kg/min titrated. Induction/intubation with hypnotic agents: 0.5-1.0 mcg/kg/min. Maintenance: N20 66% — 0.4 (0.1-2.0) mcg/kg/min. Isoflurane 0.4-1.5 MAC or propofol 100-200 mcg/kg/min — 0.25 (0.05-2.0) mcg/kg/min. PRN supplemental bolus 1 mcg/kg. Post-op pain 0.1 (0.025-0.2) mcg/kg/min.

Hydromorphone: 5-10X more potent than MS with minimal hemodynamic effects. Bolus at 0.5-1mg, then infuse at 0.5-2mg/h.

Meperidine (Demerol): 0.5-2mg/kg IV/IM/PO. Poor choice in the ICU or for >48hrs use as risk of sz.

Benzodiazepines: Good amnesia.

Mortality rates are significantly higher when a benzodiazepine is the sedating agent used in a mechanically ventilated patient, and hospital and ICU length of stay is more than a day longer (Society of Critical Care Medicine (SCCM) 38th Critical Care Congress: Abstract 674. Presented February 3, 2009).

Diazepam (Valium): Sedation @ 0.1-0.2 mg/kg q3-4hrs. Onset of action in 1-3 min. 10mg IM 1-2hr pre-op or 5-10mg slow IVP for sedation. Give 5-10mg q2-4h. Onset in 1-5 min. with caution in elderly.

SE: respiratory depression, disorientation, unpredictable IM absorption. Inexpensive, but long T-½.

Midazolam (Versed): Sedation @ 0.025-0.35 mg/kg q1-4 hr. Onset of action in 1-3 min. Sedation in ICU by continuous infusion via loading dose @ 0.1-0.2 mg/kg IV (1-5mg), then infuse at 0.01-0.2mg/kg/hr. Light sedation @ 0.03-0.04 mg/kg/hr. Deep sedation @ 0.06-0.15 mg/kg/hr. IM/IV 1-2hr for pre-op for sedation. Can give constant infusion of 50-100mg/100ml D5W or NS. 1-5mg/hr. DOC for short-term (<24hr) ICU sedation. Short DUO, predictable IM absorption, anterograde amnesia. Reduce dose 50% in elderly. Short-term use in ICU only as get unpredictable awakening times.

SE: hypotension, respiratory and CV depression, especially if hypovolemia.

Lorazepam (Ativan): Sedation @ 0.04 mg/kg q6-12 hr. Onset of action in 5-15 min. Bolus at 0.5-2mg, then infuse at 0.01-0.1mg/kg/hr, peak effect in 15-30min. Surgery give 0.05mg/kg (max 4mg) IM 2hr pre-op. DOC for long-term (>24hr) ICU sedation or liver failure. Contra: egg allergy. 1-4mg IV push q1-6h. No active metabolites, expensive. In 11/06 the FDA advise that it be used with caution in pediatric pt’s who may exhibit sensitivity to constituents of the injection, including polyethylene glycol, propylene glycol, and the preservative benzyl alcohol (linked to gasping syndrome = CNS depression).

Be Alert for Metabolic Acidosis in Patients on Lorazepam Drips: One of the carrier molecules of lorazepam is propylene glycol. This has been implicated as the cause of hyperosmolar metabolic acidosis in ICU patients on continuous infusions of lorazepam. About 12% to 45% of propylene glycol is excreted unchanged in the urine, with the remainder metabolized by the liver. Therefore, caution should be exerted when administering lorazepam in patients with renal or hepatic dysfunction. Toxicity from propylene glycol has also been seen with administration of other drugs that use it as a carrier or solvent such as phenytoin, etomidate, nitroglycerin, and diazepam. Other effects of propylene glycol include renal dysfunction, intravascular hemolysis, cardiac arrhythmias, seizures, and CNS depression. Fortunately, these metabolic derangements appear to correct after discontinuing the infusion of lorazepam. It is important to note that the upper limit of lorazepam dosing is 0.1 mg/kg/hr, which is about 7 to 10 mg/hr as an infusion for a 70- to 100-kg patient. Each milliliter of lorazepam contains about 0.8 mL (830 mg) of propylene glycol, which has a recommended daily allowance of 25 mg/kg/day. The dose of propylene glycol required for toxicity has not been well established and accumulation has been described over a wide range of lorazepam doses. Also, toxicity has been seen with serum propylene glycol concentrations of 12 to 130 mg/dL and infusion periods ranging from 2 to 24 days. The main factors that appear to be related to toxicity are rate of infusion, length of infusion, and degree of osmolar gap. Alternative sedative drugs to lorazepam include midazolam, propofol, and haloperidol.

Nitrous Oxide: provides anxiolysis and moderate analgesia when inhaled. Typically given as a 50:50 mix at or near sea level or a maximum of 60:40 at higher elevations. In this concentration alone, general anesthesia cannot be provided. In its pure form, nitrous oxide is colorless, sweet smelling, heavier than air, and nonflammable. When mixed with O2 , however, it supports combustion. Nitrous oxide is highly soluble in plasma (30 times > nitrogen) and quickly diffuses across biologic membranes. This accounts for its rapid onset of action (30 to 60 seconds). Maximum effect occurs after about 5 minutes. Cortical function is depressed rapidly, and basically all sensations are affected. These include decreases in taste, smell, hearing, and sensation to touch, pain, and temperature. The cardiovascular system, as well as the respiratory system and airway reflexes, are not significantly altered. Inhalation of a 50:50 nitrous oxide-O2 mixture has been reported to produce analgesia equivalent to 10 to 20 mg of morphine. However, pt’s experience a wide range of levels of relief. About 25% report marked pain relief, with 40 to 50% reporting mild to moderate relief, and the remaining 15 to 25% experiencing no relief. Because of this variable response, when extremely painful procedures are performed, carefully titrated doses of an opioid may be required to supplement analgesia. Conversely, nitrous oxide may be used as a means to reduce the amount of opioid analgesics required for procedures. The use of nitrous oxide is helpful as an adjunct during local or regional anesthesia administration prior to repair of a variety of soft tissue and orthopedic injuries. It may also be administered during difficult pelvic examinations, for cardiac- and noncardiac-related chest pain, during attempts at difficult IV access, and as initial pain tx of sickle cell pain crisis and renal colic. In general, nitrous oxide is ideal for procedures or conditions that are associated with a continuous baseline pain level, but it may afford insufficient analgesia when a particularly painful procedure (e.g., abscess drainage) is performed. As mentioned above, the addition of an opioid may be required for pt’s who do not receive moderate relief with nitrous oxide, or for more prolonged procedures.

Equipment: self-administered via a hand-held mask or mouthpiece attached to a demand valve. A negative pressure of 3 to 5 cm H2 O must be produced within the mask or mouthpiece to activate the flow of gas. This provides for pt-controlled delivery in cooperative adults or children above the age of 8 years and acts as a fail-safe control, because if the pt becomes too somnolent, delivery will not continue. A double-tank system is used to deliver the nitrous oxide and O2 mixture. The system relies on a mixing valve preset to deliver a fixed 50:50 ratio and will only deliver gas when O2 is flowing. The double-tank system contains a fail-safe device that automatically stops the flow of nitrous oxide when the O2 supply is depleted. In addition, through special reference pressures, the unit provides automatic O2 enrichment at very shallow breathing rates. Scavenging devices can be placed in line with the delivery system to collect exhaled nitrous oxide.

SE’s: Drowsiness, dizziness or vertigo, giddiness, dysphoria or panic, nausea, voice change, amnesia, inappropriate laughing out loud, paraesthesias.

Toxicity 3 stages: Of the five principal oxides of nitrogen, nitrous oxide is comparatively harmless. Initially there may be mild irritation of the upper respiratory tract, cough, sore throat, conjunctivitis, dyspnoea, H-A, vertigo, and tightness of the chest. After a latent period of 3 to 30 hours, inflammation of the lungs, pulmonary oedema, dyspnoea, wheezing and cyanosis resulting in severe respiratory failure. ~50% who survive pulmonary edema develop bronchiolitis obliterans within a few weeks. Early sx’s are often mild, even in cases where there is serious late toxicity. At levels of 100 to 150 ppm toxicity occurs within 30 to 60 minutes and at levels of 200 to 700 ppm fatalities result after short exposure (Ellenhorn & Barceloux, 1988). Chest discomfort occurs after exposure to 15 ppm for 1 hour and the sensation becomes unpleasant at 25 ppm. After 1 minute at 50 ppm subjects feel substernal pain. Longer exposure at this concentration causes reversible inflammatory changes in the lungs. No adverse effects were found in workers exposed for several years at 30 to 35 ppm oxides of nitrogen (ACGIH, 1986). 13 cases of polyneuropathy (numbness, paresthesia, ataxia and clumsiness) reports with substance-abuse in which dentists self-administered 300,000 to 800,000 ppm (30-80%) nitrous oxide, 30 to 60 minutes/day, 2-7 days/week, for periods ranging from 3 mo’s to several years (Lancet 1978;8102:1227-1230).

Dx: ABG studies may show hypoxia, hypercapnia and acidosis. Pulmonary function tests may show obstructive, restrictive and diffusion defects.

Other Agents:

Ketamine (Ketalar): [10mg/ml, 50mg/ml, 100mg/ml] 1.5-5mg/kg (max 13mg/kg) IM, onset 4-10min. 0.5-1mg slow IVP (max 0.5mg/kg). Peds @ 1mg/kg slow ivp OR 4mg/kg im OR 6mg/kg pr. Onset 45s-7min. The half-life of redistribution from plasma to peripheral tissues is 7-11 minutes, and the half-life of elimination is 2-3 hours. Unique among sedatives in that it provides both analgesia and sedation without respiratory depression. Serious adverse events are rare. Dissociative anesthetic with good analgesia and amnesia despite the appearance of wakefulness as unlike other anesthetic agents that depress the reticular activating system, ketamine acts by interrupting association pathways between the thalamocortical and limbic systems. An attractive agent for procedural sedation because it maintains airway protective reflexes while providing both analgesic and sedative effects. Maintains hypoxic pulmonary vasoconstrictor reflexes. Does not relieve visceral sensation. Useful in burn, peds, thoracic surgery. Has bronchodilator effect (safe is asthma). Use of ketamine (0.3 mg/kg) as an adjunct analgesic agent (during Propofol sedation, 0.4 mg/kg) was associated with fewer adverse events, especially desaturation compared to Fentanyl (1.5 µg/kg) use (Acad Emerg Med 2008;15:877).

SE: tachycardia, HTN, incr ICP, incr CO and myocardial O2 demand. Increases saliva. Respiratory depression. Hallucinations can be avoided by pre-tx with benzo. 20% have unpleasant dreams on waking. Use of ketamine as a single agent is limited by emergence phenomena and the concern of inducing vomiting or laryngospasm.

Contra: ischemic heart disease, congestive heart failure, previous psychotic illness, eclampsia, incr ICP. Ketamine is a unique drug giving complete anesthesia and analgesia with preservation of vital brain stem functions. This “dissociative” state has been described as “a functional and neuro-physiological dissociation between the neocortical and limbic systems”. IV Ketamine was effective for procedural sedation in adults according to a study with 92 pt’s (Emerg Med J 2008;25:498)….The procedure was successfully completed in 98% of patients. Overall, 22% of patients had adverse events, including vomiting (4%), clonic movements (4%), and agitation (13%)……Midazolam successfully treated agitation in all 7 of the 12 agitated patients who required treatment…..During sedation, heart rate increased by a mean of 30.2 beats per minute, and systolic blood pressure increased by a mean of 25.4 mm Hg.

• Nurses independently administered sedation for 191 procedures in 118 patients in resource-poor settings with no serious adverse events (Ann Emerg Med 2012;59:268)…Procedures included abscess drainage (36%), orthopedic procedures (20%), and burn care (18%). Half the patients were younger than 18 years and 18% were younger than 2 years. Ketamine was administered intravenously in 90% of cases and intramuscularly in 10%. There were 39 minor adverse events in 35 patients. These included hypoxia without physiological consequences, vomiting, emergence phenomena, and hypersalivation. No serious adverse events occurred.

• Neither intramuscular atropine (0.01 mg/kg) nor metoclopramide (0.04 mg/kg) reduced the incidence of IM (4 mg/kg) ketamine-associated vomiting (Acad Emerg Med 2012;19:1128).

Propofol (Diprivan): Start at 5 mcg/kg/min infusion, titrate by 5-10 mcg q5-10min to maintenance infusion of 5-50 mcg/kg/min (up to 150 mcg/kg/min). Sedation by continuous infusion in ICU @ Loading dose 0.25-1 mg/kg, then maintenance infusion: Light sedation @ 1-3 mg/kg/hr. Deep sedation @ 3-6 mg/kg/hr

Surgery induction adult @ 2-3 mg/kg, peds @ 3-6 mg/kg, this will induce unconsciousness in 30 sec. Lacks analgesic and amnestic properties. Need to add analgesic such as MS if used in ICU for sedation. Hypnotic, onset in 45s. Very short acting (may awaken in 8-15 min, Vs 60-90 min with Midazolam). Pharmacokinetics not changed by chronic hepatic or renal failure.

SE: profound hypotension, may be painful to inject unless preceded by IV lidocaine (max dose of 4mg/kg), best via central line. Should be used for no longer than 72h. “Milk of Amnesia”. Has 1.1 fat cal/ml. Do not use for pediatric ICU sedation. Has enough Vit-K to reverse the effects of Warfarin. The propofol vials and prefilled syringes contain an ingredient that slows microbial growth but does not eliminate it completely, each unit should be reserved for a single pt and used immediately after opening for a maximum of 6 hours (general/procedural anesthesia) or 12 hours (intensive care unit).

Propofol infusion syndrome: Researchers warn that the sedative propofol can cause propofol infusion syndrome, an irreversible chain of events associated with significant morbidity and mortality, in the treatment of refractory status epilepticus (CHEST 2008: Abstract AP2328. Presented October 28, 2008). Propofol was infused for a median of 63 hours (range, 2 – 391 hours) with a median cumulative dosage of 12,750 mg (range, 336 – 57,545 mg). The median peak infusion rate was 67 µg/kg/minute (range, 19 – 200 µg/kg/minute). This was an average of 150 – 300 mg an hour. Propofol infusion syndrome is defined as the unexplained presence of 1 or more of the following symptoms: bradycardia, metabolic acidosis, renal failure, rhabdomyolysis, cardiac failure, and cardiopulmonary arrest. Once the symptoms have started, it is usually quite aggressive in its course and is usually irreversible.

Check Triglyceride Level in Patients on Propofol Drips: There is an association with increased levels of triglycerides of up to 500 to 600 mg/dL in some studies, which may predispose patients to acute pancreatitis. If propofol is used at high dosages or for prolonged periods, triglyceride levels should be monitored. The lipid carrier may also predispose to thrombosis by interfering with prothrombin times, but information about this complication is limited.

There have been reported cases of blood-stream infections secondary to the infusion of contaminated propofol. Propofol preparations are now available with a choice of preservatives like ethylenediaminetetraacetic acid (EDTA) and metabisulfite (Pharmacotherapy 2005;25:8-18).

Anesthesia in healthy adult < 55 y/o: 40 mg q10 seconds until induction (2-2.5 mg/kg). Maintenance infusion: 200 mcg/kg/min (6-12 mg/kg/hr). Intermittent bolus 20-50 mg PRN.

If Elderly/ASA III+ use 20 mg q10 seconds until induction (1-1.5 mg/kg). Maintenance infusion: 50-100 mcg/kg/min (3-6 mg/kg/hr).

ED / Procedure Sedation: 1 mg/kg as an initial IV bolus, with supplemental doses of 0.5 mg/kg IV as needed. A study of 790 ED pt’s found that the average initial dose was 1.2 mg/kg. Most received the drug for dislocation reduction (38%) or fx reduction (35%); other indications included cardioversion (10%), CT scanning (2%), and tube thoracostomy (1%). The overall rate of oxygen desaturation was 7.7%, with 3.9% of pt’s requiring brief bag-valve-mask ventilation. No pt required intubation. Hypotension (defined as a systolic blood pressure <100 mm Hg) occurred in 3.5% of pt’s (Acad Emerg Med 2006;13:24-30). Propofol is safe even when it is administered by a non-anesthetist during endoscopy, as long as skilled and trained individuals are involved (Gastrointest Endosc 2007;66:443)(mean dose of propofol was 161 mg for upper endoscopy and 116 mg for colonoscopy, the colonoscopy pt’s also received 25 mg of meperidine), only rare pt’s requiredmask ventilation, most lasted for <30 seconds, and no endotracheal intubation was required. Oxygen administered at a rate of 3 L per minute did not reduce the incidence of hypoxia compared with administration of room air during propofol sedation (Ann Emerg Med 2008;52:1)…..Hypoxia occurred in 18% patients in the supplemental oxygen group and in 28% in the room air group; the difference of 10% was not statistically significant……These findings highlight the role of capnography in the early detection of respiratory depression during deep sedation. Titrated sedation with propofol, performed by a non-anesthesiologist physician, provides faster recovery and better tolerance than midazolam in patients undergoing flexible bronchoscopy (Eur Respir J 2009;34:1277-1283)…..recovery time was significantly shorter in the propofol group (5.4 minutes) than in the midazolam group (11.7 minutes).

Ketofol (0.75 mL/kg ketamine + 0.75 mL/kg propofol): 1:1 mixture of ketamine 10 mg/mL and propofol 10 mg/mL mixed together in a 10- or 20-mL syringe) given IV in 1- to 3-mL aliquots and titrated at the physician’s discretion aiming to attain deep or dissociative sedation. Some pt’s can be given reprocedure opioid analgesia. Supplemental oxygen by nasal cannula (2 – 5 L/minute) is recommended. Recovery times range from 5 to 45 minutes (median, 15 minutes), with more than 80% of pt’s recovering within 20 minutes.

• Ketofol provides effective and safe sedation and analgesia for painful emergency room procedures (Ann Emerg Med. 2007;49:23-30)….”A good option in the emergency department setting for a short procedure requiring significant analgesia (fx reduction or incision/drainage), while preserving a short recovery time (the main drawback to fentanyl/midazolam combination).” The median dose of ketofol administered was 0.75 mg/kg each of propofol and ketamine (range, 0.20 – 2.05 mg/kg). Occasionally pt’s develope hypoxia that may require bag-valve-mask-assisted ventilation for 2 minutes. If note agitation give some IV midazolam. Different combinations of ketamine and propofol (e.g., k/p 30:70) can provide good sedation with fewer psychomimetic side effects, while avoiding hypotension and minimizing respiratory depression.

• Ketofol compared favorably to Midazolam/Fentanyl for procedural sedation, but pain was better controlled with ketofol according to a prospective randomized trial, 62 adults (age range, 20–37) (Acad Emerg Med 2011;18:800)……Median doses were 1.125 mg/kg of ketofol and 0.04 mg/kg of midazolam with 2 µg/kg of fentanyl…..Mean total sedation times were similar in the two groups (25.1 and 26.1 minutes).

• Adding ketamine to propofol (ketofol =0.75 mg/kg ketamine plus 1.5 mg/kg propofol) substantially reduced the incidence of significant hypotension in a healthy general anesthesia population (J Trauma Acute Care Surg 2012;73:94)….The main outcome — a decrease in systolic blood pressure of >20% from baseline — occurred in significantly more propofol than ketofol recipients at 5 minutes (49% vs. 12%) and at 10 minutes (67% vs. 39%). No significant difference was noted at 30 minutes. No emergence reactions were observed, and nausea was similar in both groups.

Thiopental (Pentothal): Induction anesthesia @ 5 mg/kg. Infusion @ 50 mcg/kg/min.

Neuroleptic Analgesia:

Combo of tranquilizer and narcotic analgesia.

Droperidol + Fentanyl (Innovar): 50:1. A preanesthetic, causes amnesia, analgesia, somnolence w/o unconsciousness.

Haloperidol (Haldol): Can be given IM/PO/IV. Start at 0.5-2 mg IV push if mild agitation, 2-5mg if moderate agitation or 10-20mg if severe. Increase by 5mg q20min until agitation subsides. Repeat doses q4-6h around the clock.

If mild agitation or elderly start @ 0.5-2mg.

If severe agitation start @5-10mg, and if after 30 minutes pt has continued agitation double the dose. After the 2^nd dose and if partial response give 0.5-1mg Lorazepam IV concurrently or alternate lorazepam with Haldol q30min. If no response after 3 doses, switch to another agent. Onset: in minutes IV, 10min IM, 2-3h PO. Once pt is calm, add the total mg of Haldol and administer the same mg divided q6 over the next 24hrs, if the pt remains cam, then reduce the dose by 50% every 24hrs. Has antiemetic properties. Good for delirium. A butyrophenone, DA agonist-antagonist. Causes CNS depression at subcortical levels (midbrain and RAS). SE: QT prolongation, reduce sz threshold, extrapyramidal such as: can rarely cause tardive dyskinesia, NMS, dystonic reactions. T-½ of 18-54h. Can write order “Haloperidol 10mg IV q10 minutes PRN for sedation-agitation score (SAS) of 6 or 7, do not exceed 80 mg over 2 hours, Hold for SAS <3”. Check an ECG for Long Qt Interval Before Giving Haloperidol: Along QT can be inherited or acquired; the acquired form is usually induced by drugs or electrolyte abnormalities like hypokalemia and hypomagnesaemia. Drugs commonly used in the ICU that potentiate this effect are haldol, amiodarone, metoclopramide, ibutilide, procainamide, azithromycin, clarithromycin, cisapride, erythromycin, methadone, and pentamidine. When using these drugs, an ECG should be checked to ensure a normal QT. If the patient does develop a long QT interval, strong consideration should be given to stopping the medicine and correcting any electrolyte abnormalities. Experienced practitioners will give empiric magnesium in the setting of normal renal function. If the patient develops torsades de pointes, overdrive pacing, isoproterenol, and magnesium are the standard of care. The goal is to increase heart rate to shorten ventricular repolarization. Overdrive pacings is to a rate of 100 to 120 beats per minute either transvenously or externally. Isoproterenol may also be effective to this end (NEJM 2004;350:1013-22).

Scopolamine: 3-6ug/kg. Onset in seconds, last 2-3h, hepatic metabolism. A natural antimuscarinic from belladonna plant. A mydriatic, antisialagogue, bronchodilator, vagolytic, anhidrotic. No cardiac depression. Can be used as ICU sedation.

Sedation with Midazolam & Opioids: Used for analgesia and sedation during painful procedures. Must have continuous pulse ox and a secure IV. A resuscitation cart with a bag-valve-mask, oral and nasal airways, endotracheal tubes, and a functioning laryngoscope must be nearby. Suction equipment and naloxone and flumazenil should be at the bedside.

Step #1: the opioid agent is titrated to light sedation. Generally, morphine sulfate is administered in 1- to 2-mg increments every 3 to 5 minutes until the pt is comfortable and eyelids are heavy or speech is slightly affected (“thick”). Another 15 to 20 minutes are allowed to pass for peak opioid effect to occur.

Step #2: just prior to the procedure, midazolam in 1- to 2-mg increments is used to supplement the sedation until the pt is somnolent or speech is slurred. Asking the pt to count backward from 100 is a useful tool. Often the pt will begin to skip numbers or count repetitively when the appropriate degree of sedation is reached.

Dexmedetomidine (Precedex): Start @ 1mcg/kg IV over 10min, then 0.2-0.7mcg/kg/hr IV. An alpha-2 agonist is a sedative with analgesic and anxiolytic properties. FDA approved in 12/99 for use in pt’s in intensive care settings. Can be used as a single agent, no loading dose needed. Often used in combination with propofol, opioids, and anxiolytic agents. Advantages of respiratory stability and easy rousability, no need to discontinue prior to extubation. It may slow the heart rate and the hemodynamic response is predictable, thus avoid if hypovolemia or heart block. Drug interactions via CYP 2A6 substrate. Half life 2hr. Compared with midazolam, Dexmedetomidine (a 2-adrenergic–receptor agonist) showed equal efficacy and better safety (JAMA 2009;301:489)…..Sedation efficacy was similar between groups, but delirium prevalence was significantly lower in the dexmedetomidine group (54% vs. 77%). Dexmedetomidine patients were extubated sooner (3.7 vs. 5.6 days) and were discharged from the ICU sooner (5.9 vs. 7.6 days). All-cause 30-day mortality was the same in both groups. Bradycardia was more common with dexmedetomidine, and tachycardia and hypertension were more common with midazolam. In a small pilot study, the alpha-2 agonist dexmedetomidine showed advantages over haloperidol in the treatment of delirious, agitated, intubated patients (Crit Care. 2009;Published online May 19)….they were extubated, on average, a day earlier, and their post intervention ICU length of stay fell from 6.5 to 1.5 days.”

Post sedation and Analgesia Disposition Criteria:

1. Return to baseline verbal skills.

2. Return to age- and condition-appropriate vital signs.

3. Return to baseline muscular control function (infants able to sit unattended; child or adult able to walk unassisted).

4. Return to baseline mental status.

5. Pt able to take fluids by mouth prior to release.

6. Pain controlled with oral pain medications.

7. Responsible adult present who understands specific sedation and analgesia emergency department disposition criteria.

Adult Disposition Instructions after Systemic Analgesia and Sedation:

1. Do not drive or operate heavy machinery for the next 24 hr. 2. Eat a light diet for the next 24 hr.

3. Take only your prescribed medications as needed, including any pain medication you were discharged with. Do not drink alcohol.

4. Do not make any important decisions or sign important documents for the next 24 hr. You may be forgetful due to medications that were administered.

5. If you experience any difficulty breathing or persistent N/V, call or return to the emergency department or dial 911.

6. You should have a responsible person with you for the rest of the day and during the night.

Conscious Sedation in Ped’s:

The term “conscious sedation” refers to a state of drug induced central nervous system depression, where the verbal contact is maintained with the pt, and airway and other reflexes are preserved. Sedation to a deeper level implies loss of verbal contact and response to gentle stimulation. This state of “deep sedation” risks the loss of protective reflexes, airway control, aspiration, and hypoxia. “Deep sedation” carries a requirement for a level of care consistent with general anesthesia. All conscious sedation should be done in a hospital setting under proper monitoring with anesthesiology. Asking the parents to entertain the supine child by blowing bubbles can be helpful for minor procedures. Humorous videos watched during painful procedures increase pain tolerance in children according to a study (eCAM 2007;doi:10.1093/ecam/nem097).

Indicated for: BM aspiration, cardiac cath, BAE potentials, CT, dental procedure, echo, endoscopy, EEG, laceration repair, liver Bx, LP, ortho manipulation, sexual abuse exam, wound debridement, VCG.

Goals: Alleviate anxiety. Minimize physical pain and discomfort. Minimize negative psychological responses to tx. Maximize amnesia. Control behavior to expedite performance of procedures. Maintain safety by minimizing risks. Ensure safe discharge.

Papoose: represents the example of the papoose, which is commonly used for restraint during repair of lacerations and other wounds. It is used to expose the head, face, and extremities with minimal discomfort to the child. In recent years, with child life presence many centers have narrowed the use of this tool a good deal. After explaining the procedure to the family, open the papoose across the ED stretcher. Place the child supine on the papoose and expose the body area necessary for treatment. Beginning with the midabdominal restraints, cover the child across the midline with the Velcro-lined sides. Better exposure of the extremities, such as the hand, is obtained by flexion of the area under the harness. Before starting a wound repair or other procedure, reassess for the safety and adequacy of the immobilization of the child and correct it if necessary.

Mummy Wraps: The mummy wrap is an alternative restraint to use for treating emergency problems of the head, especially minor trauma. By slight variation, it also provides access to the distal extremities. Prepare the patient and family for the procedures. Fold a bedsheet on itself so the width measures from the axillae to the heel of the child. Stand the child on the bed and place the bedsheet behind his/her back, under the axilla, and in front of the arms, with the short end of the sheet tucked behind one arm around the child’s back. With the child standing, wrap the long end of the sheet on the child’s other side, around the back to the front and across the trunk again, finishing behind the child. Lay the child supine or prone to best expose the injury to be treated. Extend several lengths of 2- or 3-in wide adhesive tape across the patient, attaching it to the sides of the stretcher to firmly hold the child’s trunk in place. In some settings, using the mummy wrap inside of a papoose without the need for adhesive tape is an excellent alternative. An injured extremity can be left out of the wrap for better exposure.

Ketamine: First line. Sedation in children @ 1-2 mg/kg IV, onset in 1 minute, lasts 10-20 minutes. IM dose = 6mo-8yo @ 2-5mg/kg IM +/- 0.01mg/kg Atropine Sulfate (IM/IV), onset in 3-5 min, lasting ~20-45 min. Or PO 6-10mg/kg or IV 0.5-1mg/kg. Get vitals q5min until discharge. Gives a dissociative, trancelike state with rare respiratory depression, usually increasing the HR and BP from catecholamine release. SE: N/V, bad dreams and hallucinations rare in children (1-2%), nystagmus, hypersecretions, agitation, emergence delirium, myoclonus, laryngospasm, cardiovascular stimulation. Ketamine sedation without atropine prophylaxis (for hypersalivation) appears to be safe in children according to an observational study (Acad Emerg Med 2008;15:314).

Contra: HTN, ischemia, increased intracranial or intraocular pressure, active respiratory infection, psychosis, infants younger than three mo’s. The incr airway secretions (hypersalivation) decreased by anticholinergics like atropine or glycopyrrolate. Excellent for burn pt’s needing dressing changes.

Compared to IM MCP: (2mg/kg meperidine, 1mg/kg promethazine, 1mg/kg chlorpromazine with respiratory depression, dystonic reaction, lowered sz threshold) (Arch Ped & Adol 1996, 150).

For IV: use 1-2mg/kg (additional 0.5-1 PRN) Ketamine and 0.05-.1mg/kg Midazolam (max 4mg) for reduced dysphoric reactions and 90% optimal sedation. (Peds 1997:99).

Chloral Hydrate (Aquachloral Supprettes, Somnote): [Syrup 500 mg/5 mL, rectal supp 500 mg. Trade only: Caps 500 mg. Rectal suppositories: 325, 650 mg] A sedative/ hypnotic, onset 15-60min, DUA: 2-8hr, dose: 50-100mg/kg (max 2000mg) PO/ PR. Peds Sedative @ 25 mg/kg/day PO/PR divided tid-qid, up to 500 mg tid. Hypnotic @ 50 mg/kg PO/PR qhs, up to maximum of 1 g. Pre-anesthetic: 25- 50 mg/kg PO/PR before procedure. Give syrup in ½ glass of fruit juice or water. A nonselective CNS depressant

SE: leukopenia, dependence, withdrawal reactions. Frequent: N/V, diarrhea, sleep walking. Paradoxical hyperactivity. Most effective for children <2yo an radiological studies. Not good for suturing or other “noxious” procedures. Best to have pulse ox as respiratory depression at high doses. Unpredictable GI absorption rate.

Nitrous Oxide: 50/50 mix of 02 and NO (Nitrox). Inhalation, short term use only. Not a good analgesic, but effective sedation. SE: N/V. 30% N2O (50% has not been tested in pediatric population). Only effective >8yo. Difficult to manage, requires close monitoring & drug scavenger system. Inspired through a demand-valve mask. This mode of delivery requires cooperation by the pt. Thus, nitrous oxide is used mainly in pt’s older than 4 years of age, although it can be used in younger children using a continuous delivery system.

Contra: nausea and vomiting, trapped gas (eg, bowel obstruction, pneumothorax, middle ear infection), and pregnancy. Rebound pulmonary hypertension can be safely and effectively prevented in infants being withdrawn from inhaled nitric oxide (NO) therapy by administration of a single dose of enteral Sildenafil (0.4 mg/kg) at the final stage of the weaning process (Am J Respir Crit Care Med 2006;174:1042-1047). Nitrous oxide plus a lidocaine hematoma block is an effective alternative to deep sedation induced by IV ketamine plus midazolam for closed forearm fx reduction in children seen in the emergency department (Pediatrics 2006;118:e1078-e1086). Children who received inhaled nitrous oxide had significantly less pain and anxiety during painful diagnostic or therapeutic procedures than those who received placebo (Pediatrics 2011;127:e1464)……Nitrous oxide — particularly given its anxiolytic effects — might be a good choice for simple and short procedures that would not otherwise warrant deep sedation.

Fentanyl (Sublimaze): 1-2ug/kg IV (max 5uf-kg), onset in 2-3 min, DUA: 45-60min. SE: respiratory depression, chest wall rigidity. Lollipop: 200, 300, 400ug doses. Great for BM Bx’s.

Midazolam (Versed): 0.05-0.15mg/kg IV onset in 3-5min, DUA: 1-2 hr. Can also add to juice @0.5-1mg/kg PO or slowly drip into nostrils @0.2-0.5mg/kg or give IM. SE: respiratory depression if used in combination with opiates.

PO: e6 mo: 0.25–0.5 mg/kg/dose x 1; max. dose: 20 mg. Younger pt’s (6 mo–5 yr) may require higher doses of 1 mg/kg/dose whereas, older pt’s (6–15 yr) may require only 0.25 mg/kg/dose. Use 0.25 mg/kg/dose for pt’s with cardiac or respiratory compromise, concurrent CNS depressive drug, or high-risk surgery.

6 mo–5 yr: 0.05–0.1 mg/kg/dose IV over 2–3 min. May repeat dose PRN in 2–3 min intervals up to a max. total dose of 6 mg. A total dose up to 0.6 mg/kg may be necessary for desired effect.

6–12 yr: 0.025–0.05 mg/kg/dose IV over 2–3 min. May repeat dose PRN in 2–3 min intervals up to a max. total dose of 10 mg. A total dose up to 0.4 mg/kg may be necessary for desired effect.

>12–16 yr: Use adult dose; up to max. total dose of 10 mg. When a child who needs to be sedated can’t or won’t take oral midazolam, intranasal or buccal delivery via aerosol is a useful alternative (Ann Emerg Med 2011;online June 21)……sedation onset was faster with intranasal administration and more patients in this group achieved adequate sedation (85.5%) than with oral delivery (66.7%) or buccal administration (59.6%).

Pentobarbital: [900mg cap, Elixir 18.2mg/5ml. 50mg/ml inj].

Onset of action: PO: 15–60 min; IM: 10–15 min; IV: 1 min. Duration of action: PO: 1–4 hr; IV: 15 min.

Hypnotic – Child: PO: <4 yr: 3–6 mg/kg/dose QHS. e4 yr: 1.5–3 mg/kg/dose QHS. IM: 2–6 mg/kg/dose. Max. dose: 100 mg.

Preprocedure sedation – Child: PO/IM: 2–6 mg/kg/dose. Max. dose: 150 mg. IV: 1–3 mg/kg/dose. Max. dose: 150 mg.

Barbiturate coma – Child and adult: IV: Load: 10–15 mg/kg given slowly over 1–2 hr. Maintenance: Begin at 1 mg/kg/hr. Dose range: 1–3 mg/kg/hr as needed. Therapeutic serum levels: Sedation: 1–5 mg/L; Hypnosis: 5–15 mg/L; Coma: 20–40 mg/L (steady state is achieved after 4–5 days of continuous IV dosing).

Methohexital (Brevital): [2 mg/mL elixer. 1, 5 mg/mL inj] 1-1.5mg/kg IV lasts 5 min. Can be given rectally via an 8F feeding tube at dose of 25mg/kg (max 500mg) 15 min before a procedure such as CT scan. Methohexital (initial IV dose, 1 mg/kg) was superior to pentobarbital (initial IV dose, 2 mg/kg) for sedation of children during head CT (Pediatr Emerg Care 2009;25:648)…… If sedation was inadequate after the first dose, subsequent doses of 0.5 mg/kg of methohexital (up to 2.0 mg/kg) or 2.0 mg/kg of pentobarbital (up to 6.0 mg/kg) were given at 5-minute intervals. Outcome measures were adequacy of sedation, time to completion of CT, total duration of sedation monitoring, and adverse events during sedation……The proportion of patients who required redosing did not differ significantly between the methohexital and pentobarbital groups (33% and 55%).

Etomidate: Sedation in adults @ 0.2 mg/kg over 30-60 seconds. Onset <1 minute, lasts 3-5 minutes. Advantages: single agent, reliable, no cardiovascular or respiratory depression. Has been shown to reduce intracranial pressure (ICP) and improve cerebral perfusion pressure in adults and children (Pediatr Emerg Care 2006;22:90-3). Disadvantages: action too short for some procedures. Etomidate (median dose, 0.33 mg/kg IV) for CT scan sedation was safe and effective and produced a shorter duration of sedation than pentobarbital (median dose, 4 mg/kg) in healthy children (Pediatr Emerg Care 2007;23:690).

Reversal: Flumazenil (Romazicon) @0.01 mg/kg or 0.2mg IV –> Benzo’s.

Narcan (Naloxone) @ 0.1mg/kg (max 2mg) IV/ IM –> Opioids. Always consider opiate OD if see a low respirator rate with constricted [miotic = pinpoint] pupils).

Demerol-Phenergan-Thorazine (DPT): IM, unpredictable. Not recommended because of unreliable efficacy, the potential for respiratory depression, and an exceedingly long (7 hours) half-life.

Discharge criteria: Monitoring should continue until the child meets criteria for safe discharge.

Airway patency and stable cardiovascular function. Easy arousability with intact protective reflexes. Ability to talk (if age-appropriate). Ability to sit up unaided (if age-appropriate). Adequate hydration. Young infants or children who are handicapped should return to the level of responsiveness observed before sedation.

**Ref: (Mechanical ventilation. Hosp Med 1999;12:26-36) (Weaning from mechanical ventilation–the team approach and beyond. Intensive Care Med. 1994;20:317-8) (Issues in ventilator weaning. Chest. 1999;115:1215-6) (Clinical management of weaning from mechanical ventilation. Intensive Care Med. 1998;24:999-1008) (Weaning from mechanical ventilation. NEJM. 1991;324:1496-8) (Hospital Medicine, by Wachter, 2000, Lippincott, p108-112) (Sedation in the intensive care unit, a systematic review. JAMA 2000;283:11) (Prolonged sedation with midazolam or propofol. Crit Care Med. 1997;25:556-7) (Mechanical ventilation. Hosp Med 1999;12:26-36) (Analgesia and sedation. J Crit Illness 2001;16:10)