Stanford PICU Sedation Protocol v2.0- Continuous Sedation (see below for intermittent)
|
Class |
Name (Trade Name) |
Onset (sec) |
Duration (min) |
Metabolism/ Clearance |
Dose Cost (U of M) |
Comments |
Depolarizing |
succinylcholine (Anectine) |
30-60 |
5-7 |
Plasma cholinesterases |
1-2 mg/kg $1.53/200 mg |
Quickest onset of all NMB’s. Contraindicated in muscular dystrophies, multiple sclerosis, spinal cord injuries, encephalitis, glaucoma, malignant hyperthermia, burns, and crush injuries. Pseudocholinesterase deficiency results in prolonged NMB. Will raise serum K+ levels. Has been associated with bradyarrhythmia/cardiac arrest. May be given IM: 3-5 mg/kg (max 150 mg). |
Nondepolarizing |
pancuronium (Pavulon) |
120-180 |
45-60 |
1○ Renal Hepatic |
0.1 mg/kg Infusion: 1-2 mcg/kg/min $1.02/10 mg |
Causes tachycardia from sympathomimetic effect. |
|
vecuronium (Norcuron) |
120-180 |
30-40 |
1○ Hepatic Renal |
0.1 mg/kg Infusion: 1-3 mcg/kg/min $3.84/10 mg |
Minimal CV effects. Can use 0.3 mg/kg dose for more rapid onset (60-90 sec). 1/3 of a dose is metabolized to 3-, 17-, and 3,17-descetylvecuronium. (Relative potency is 1:2:20:60, respectively). |
|
rocuronium (Zemuron) |
60-90 |
30-40 |
1○ Hepatic Renal |
0.6-1.2 mg/kg Infusion: 10-12 mcg/kg/min (generally not done in PICU). $3.85/50 mg |
Quickest onset of nondepolarizing NMB’s. Minimal CV effects. Should be stored under refrigeration. 17-desacetyl rocuronium metabolite has 1/20th the activity of the parent drug. |
|
cis-atracurium (Nimbex) |
180-300 |
35-45 |
Hoffman degradation Renal |
0.1-0.2 mg/kg Infusion: 1-3 mcg/kg/min $22.5/20 mg |
“Cis” isomer of atracurium. More potent than atracurium, so less used and less laudanosine accumulation. Histamine release. |
Neuromuscular Blockers not on Formulary:
Analgesics:
Class |
Name (Trade Name) |
Duration of Action (hr) |
Relative Potency |
Dose Cost (U of M) |
Comments |
Opioids |
morphine (Duramorph) |
2-4 |
1 |
0.1-0.2 mg/kg Infusion: 25-200 mcg/kg/hr $0.85/10 mg |
Histamine release. Onset of action is not as quick as fentanyl (Peak iv effect ~5 min vs 2 min for fentanyl). |
|
fentanyl (Sublimaze) |
1-2 |
100 |
1-2 mcg/kg Infusion: 1-5 mcg/kg/hr $0.89/250 mcg |
No histamine release. Minimal CV effects. Developed for less sedating effects. Intubating doses are 5-10 mcg/kg, if used as sole agent. “Anesthestic” doses are 25-150 mcg/kg. Rapid, high doses are associated with “rigid chest syndrome”. Generally avoided on ECMO due to membrane binding concerns. |
|
hydromorphone (Dilaudid) |
4-5 |
7.5 |
0.015 mg/kg Infusion: 0.002-0.004 mg/kg/hr $6.60/6 mg (PCA) |
Histamine release. Often used as PCA. |
|
methadone (Dolophine) |
6-8 |
1 |
0.1-0.2 mg/kg $0.33/1 mg (IV) $0.06/1 mg (PO) |
Histamine release. Very sedating. Oral form has ~50% bioavailability. Duration of action increases to 24-48 hrs with repeated doses. Typically used to control narcotic withdrawal. |
|
meperidine (Demerol) |
2-4 |
0.1 |
1 mg/kg $0.65/25 mg |
Histamine release. Do not use with MAO inhibitors. Normeperidine metabolite can cause seizures, hallucinations, and agitation. Less association with biliary tract spasm. Has been used for fevers caused by excessive shivering. |
|
sufentanil (Sufenta) |
1 |
500 |
10-25 mcg/kg $10.84/250 mcg |
Fentanyl derivative. Typically used during cardiac surgery. |
|
alfentanil (Alfenta) |
15-45 min |
10 |
10-50 mcg/kg $3.44/1000 mcg |
Fentanyl derivative. Should be given as a continuous infusion. |
|
remifentanil (Ultiva) |
3-10 min |
200 |
0.25 mcg/kg/min $8.05/1000 mcg |
Fentanyl derivative. Metabolized by blood and non-specific tissue esterases. Should be given as a continuous infusion. |
|
codeine (Tylenol w/ codeine) |
4-6 |
0.08 |
1 mg/kg (PO) $0.39/12 mg (5 mL elixir) |
Minor route of metabolism forms morphine. IV formulation does exists but is not on formulary. |
|
oxycodone (Oxycontin) (Percocet [Tylenol], Percodan [aspirin]) |
4-6 |
0.5 |
0.1 mg/kg (PO) $1.87/5 mg (5 mL solution) $0.33/5 mg (tablet) |
Must be given enterally. |
|
hydrocodone (Vicodin [Tylenol]) |
4-6 |
|
0.135 mg/kg (PO) $2.36/7.5 mg (15 mL elixir) $0.31/5 mg (tablet) |
Must be given enterally. |
As a class, all opioids can cause respiratory depression, slow gut motility, sedation, and dysphoria. Most cause histamine release. Remember: Naloxone (Narcan) can be used in case of opioid overdose (Use 5-10 mcg/kg/dose [max 200 mcg/dose]). |
Analgesics (cont.):
Class |
Name (Trade Name) |
Comments |
Non-opioids |
|
|
NSAID |
ibuprofen (Motrin) |
Must be given enterally. Can cause renal insufficiency in setting of marginal renal blood flow. Avoid in patients with calcineurin inhibitor immunosuppressants (tacrolimus, cyclosporine). |
|
ketorolac (Toradol) |
IV formulation. Associated with increased post-operative bleeding. Dose: 0.5-1 mg/kg; Cost: $1.76/60 mg. |
Non-NSAID |
acetaminophen (Tylenol) |
Must be given enterally. |
Sedatives/Hypnotics/Anesthetics:
Class |
Name (Trade Name) |
Duration of Action |
Dose Cost (U of M) |
Comments |
Benzodiazepines |
diazepam (Valium) |
Long |
0.1-0.3 mg/kg $2.29/10 mg $1.58/5 mg (5 mL solution PO) |
Has active metabolite. Excellent enteral bioavailability. May be given IM. May be given rectally for seizures. |
|
lorazepam (Ativan) |
Moderate |
0.1 mg/kg Infusion: 10-100 mcg/kg/hr $6.38/20 mg |
No active metabolite. Infusion can cause metabolic acidosis due to propylene glycol carrier, especially with renal insufficiency. Although not commonly done here, it can be given enterally. May be given IM. |
|
midazolam (Versed) |
Short |
0.1 mg/kg Infusion: 25-300 mcg/kg/hr $1.09/5 mg |
Has active metabolite. IV form does not need alcohol carrier. Powerful amnestic. Associated with ataxic movements. May be given IM or intranasally. Poor enteral bioavailability due to extensive liver 1st pass metabolism. |
As a class, all benzodiazepines produce anxiolysis, amnesia, and muscle relaxation; they can all depress respiration and cause hypotension. Remember: Flumazenil (Romazicon) can be used in case of benzodiazepine overdose (Use 5-10 mcg/kg/dose [max 200 mcg/dose]). |
||||
Barbiturates |
thiopental (Pentothal) *supplies disappearing in USA |
Very short |
5 mg/kg Infuse: 2-10 mg/kg/hr $1.58/50 mg |
Onset of action in 30-60 secs. Lowers ICP. Causes myocardial/circulatory depression. Use continuous EEG if on infusion. Pentobarbital is a metabolite. |
|
pentobarbital (Nembutal) |
Short to Moderate |
1-3 mg/kg Infusion: 1-4 mg/kg/hr $6.61/50 mg |
Causes myocardial/circulatory depression. Lowers ICP. Can impair immune function. May be given IM: 2-6 mg/kg (max 100 mg). Use continuous EEG if on infusion. Has propylene glycol carrier that can cause metabolic acidosis. |
Intravenous Anesthetics |
ketamine (Ketalar) |
Short to Moderate |
0.5-1 mg/kg $0.80/10 mg $4.76/500 mg |
PCP derivative. Generally does not blunt respiratory drive. Contraindicated for increased ICP. Causes release of endogenous norepinephrine. Causes bronchodilation. May cause bronchorrhea, excessive salivation, and larynospasm. Associated with “emergence reactions”. May be given IM. |
|
propofol (Diprivan) (chemical name: 2,6-diisopropylphenol)
|
Very short |
2-4 mg/kg Infusion: 20-200 mcg/kg/min $4.00/200 mg $10.00/500 mg |
Should be given as a continuous infusion. Does not have analgesic properties. Prolonged use is associated with fatal metabolic acidosis. Mixed in oil/lipid mixture with egg derived substances; susceptible to microbial contamination. Can cause brief period of apnea during induction and hypotension/bradycardia with higher infusion rates. |
|
etomidate (Amidate) |
Very short |
0.3 mg/kg $4.73/20 mg |
Very quick onset of action. Believed to lower ICP but with no cardiovascular depression. Associated with suppression of hypothalamic-adrenal axis. Associated with myoclonus. |
Hypnotics |
dexmedetomidine (Precedex) |
Very short |
0.2-0.7 mcg/kg/hr $63.90/200 mcg |
Selective a2-adrenegic receptor agonist. Related to clonidine. Can cause hypotension and bradycardia. Paradoxical hypertension reported with high doses. |
|
chloral hydrate (Nortec) |
Moderate |
25-50 mg/kg $0.50/500 mg (5 mL syrup PO) |
Must be given enterally. Active metabolite is trichloroethanol. Chronic use may be associated with cardiac dysfunction. Usually does not blunt respiratory drive. Seems to work well in patients with Trisomy 21. |
Antihistamines |
diphenhydramine (Benadryl) |
Moderate |
0.5-1 mg/kg $0.82/50 mg (IV) |
Has anticholinergic properties (e.g. dry mouth, dry eyes, etc.) |
Antipsychotics |
haloperidol (Haldol) |
Moderate |
0.05 mg/kg/dose or 1-5 mg/dose $0.85/5 mg |
Has anticholinergic properties. May cause extrapyramidal effects (acute dystonic reaction and pseudoparkinsonian symptoms) and rarely, malignant hyperthermia. IV administration may cause hypotension. |
|
droperidol (Inapsin) |
Moderate |
0.03-0.1 mg/kg/dose (max 2.5 mg/dose) $0.08/0.25 mg |
Similar to haloperidol. Less risk for extrapyramidal effects. Has black box warning for prolonged QT/torsades de point risk. |
Cases:
1) 9 month old infant with jaundice and liver failure requiring percutaneous liver biopsy.
2) Same patient 2 hours later, tachycardic, appearing pale and mottled.
3) Same patient 24 hours later, on HFOV for ARDS, requiring epinephrine infusion, no urine for past 8 hours.
4) 10 year old s/p MVA, initially following commands but now becoming unresponsive after arrival into the trauma room.
5) 6 year old initially admitted for septic shock/ARDS/MODS, continuing to require moderate amounts of support and increasing sedative doses for “agitation”; seems somewhat “wild” at times.
Evidence
- RESTORE by Curley et al demonstrated no difference in length of mechanical ventilation when utilizing a protocol for sedation vs. usual care in pediatric patients with acute respiratory failure
Withdrawal
- Generally consider WAT-1 score >4 consistent with withdrawal
- Risk of withdrawal related to cumulative dose and duration of opioid and benzodiazepene exposure
- Often start methadone/valium if patient has been on moderate/high dose benzodiazepenes and narcotics for 5+ days
- Initial description of the WAT-1 score
References
1) Curley MA, Wypij D, Watson RS, Grant MJ, Asaro LA, Cheifetz IM, Dodson BL,Franck LS, Gedeit RG, Angus DC, Matthay MA; RESTORE Study Investigators and the
Pediatric Acute Lung Injury and Sepsis Investigators Network. Protocolized sedation vs usual care in pediatric patients mechanically ventilated for acute
respiratory failure: a randomized clinical trial. JAMA. 2015 Jan 27;313(4):379-89. doi: 10.1001/jama.2014.18399. PubMed PMID: 25602358.
2) Franck LS, Harris SK, Soetenga DJ, Amling JK, Curley MA. The Withdrawal Assessment Tool-1 (WAT-1): an assessment instrument for monitoring opioid andbenzodiazepine withdrawal symptoms in pediatric patients. Pediatr Crit Care Med. 2008 Nov;9(6):573-80.
3) Adult CPG for Pain, Sedation, Delirium, Mobility, CCM 2018