Neonatal Drug Therapy Manual


Disclaimer: Official controlled document is the CHEO and Ottawa Hospital online copy. It is the responsibility of user to ensure that any paper copy version is the same as the online version before use.

Alternate Name(s): 
General Anesthetic
Original Date: 
February 2010
Revised Date: 
Nov 2023
  • Adjunct therapy for sedation and analgesia in the neonatal intensive care unit
  • Moderate sedation for diagnostic and therapeutic procedures
  • IV direct: over 3-5 minutes.
    • Maximum rate* (for urgent use, such as RSI): 0.5 mg/kg/min,  maximum 2 mg/min
  • IV continuous infusion
  • Subcutaneous
  • IM
  • Intranasal (IN)

    Administer injection solution intranasally using Mucosal Atomization Device (MAD).  Larger volumes should be divided between both nostrils.  

    Ensure to account for the deadspace volume in the MAD (approx 0.06 mL for the MAD300 model). Either draw up extra medication for this volume, OR draw back on the syringe after administration of dose and then empty the air into the nostril so no drug remains in the MAD.

*adverse effects include laryngospasm, apnea, dysphoria, nystagmus and emergence agitation. Rapid IV administration/higher doses may increase risk of these effects. 

  • IV direct, SC, IM: 0.5 - 2 mg/kg/dose

Ketamine Equivalents

1 mg 1000 mcg
1 mg/mL


1000 mcg/mL


  • IV/SC continuous infusion:
    • Preterm neonates:  100 - 500 mcg/kg/hour
    • Term neonates: 100 - 900 mcg/kg/hour
    • Titrate dose according to effect/side effects. A maximum dose has not been established, but one report in mechanically ventilated children used a maximum dose of up to 3600 mcg/kg/hour. Several tapering protocol can be implemented, one approach would be to decrease by 10% every 6 to 8 hours.
  • Intranasal: 1 - 4 mg/kg/dose; higher doses have been used in pediatric studies for intubation, though aren't as well documented in neonate literature.  
    • Additional dose may be repeated after 7 minutes if adequate sedation not obtained.

MIST Protocol:

Gestational Age Premedication
Less than 29 weeks

Sucrose according to policy

Atropine 20 mcg/kg IV

Optional: Fentanyl 0.5-1 mcg/kg over 3-5 minutes

OR ketamine 0.5 mg/kg IV over 2 minutes

29 weeks or greater

Sucrose according to policy

Atropine 20 mcg/kg IV

Optional: Fentanyl 0.5-1 mcg/kg over 3-5 minutes

OR ketamine 1 mg/kg IV over 2 minutes


Side Effects: 
  • CNS: tonic-clonic movements, elevated intracranial pressure, hallucinations
    • Controversy exists with regard to the anesthetic neurotoxicity caused by Ketamine. Repeated high Ketamine doses (20 mg/kg) and other N-methyl-D-Asparate (NMDA) antagonists have been associated with increased neuroapoptosis in the developing brain on animal models. Both brain immaturity and prolong exposures were necessary to produce neuroapoptotic  cell death. Clinical applicability of these findings is limited since the development age of the rodent models in these studies corresponded to 16-22-weeks-old-fetus.
  • CVS: tachycardia and hypertension (dose-dependent)
  • GI: hypersalivation
  • Opthalmic: nystagmus
Parameters to Monitor: 
  • Cardiovascular effects; HR, BP, RR, oxygen saturation
Reconstitution and Stability: 


IV direct:

- Use Ketamine 1 mg/mL (1000 mcg/mL) - 3 mL prefilled syringe prepared by pharmacy

- If patient receiving Ketamine by continuous infusion, use appropriate setting on pump to administer bolus dose

IV continuous infusion:

- Use 1 mg/mL (1000 mcg/mL) prefilled syringe prepared by pharmacy.

** Ketamine 5 mg/mL (5000 mcg/mL) prefilled syringe can also be dispensed by pharmacy if required

SC continuous infusion:

- Use Ketamine 5 mg/mL (5000 mcg/mL) prefilled syringe prepared by pharmacy


- Use Ketamine 10 mg/mL or 50 mg/mL vial.  Ideal volume is 0.3 to 0.5 mL per nostril,  (maximum 1 mL per nostril)


Instructions for mixing from vials:

  • Ketamine 10 mg/mL
    • Add 2 mL (20 mg) to 18 mL of 0.9% NaCl
    • Final concentration: 1 mg/mL (equivalent to 1000 mcg/mL)
  • Ketamine 10 mg/mL
    • Add 10 mL (100 mg) to 10 mL of 0.9% NaCl
    • Final concentration: 5 mg/mL (equivalent to 5000 mcg/ml)



IV direct:

- Use Ketamine 1 mg/mL (1,000 mcg/mL) in NaCl 0.9% - vials prepared by pharmacy

IV continuous infusion: 

Ketamine 10 mg/mL 

• Add 2 mL (20 mg) to 18 mL of D5W 

• Final concentration: 1 mg/mL (equivalent to 1,000 mcg/mL)


- Solutions Compatible: D5W, 0.9% NaCl

- Y-site Compatible: fentanyl, hydromorphone, midazolam, morphine, SMOF. Ketamine at concentrations < 10 mg/mL is compatible with heparin 0.5-1 unit/mL. 

  • Onset of action for :
    • intranasal route : up to 10 minutes
    • subcutaneous route: within 15-30 minutes

- Golding CL, Miller JL, Gessouroun MR, Johnson PN. Ketamine Continuous Infusions in Critically Ill Infants and Children.  Annals of Pharmacotherapy 2016, Vol. 50 (3) 234-41

- Milesi C, Baleine J, Mura T, Benito-Castro F, Ferragu F, Thiriez G, et al.  Nasal midazolam vs ketamine for neonatal intubation in the delivery room: a randomised trial.  Archives of disease in childhood Fetal and neontal edition 2018 May; 103 (3):F221-F226

- Yan J, Jiang H. Dual effects of Ketamine: neurotoxicity versus neuroprotection in anesthesia for the developing brain. Journal of neurosurgical anesthesiology 2014 Apr;26 (2):155-60

- American Society on Health-System Pharmacists (ASHP). Handbook on Injectable Drugs. 19th Edition. Bethesda: ASHP 2017

- Diaz.Intranasal ketamine preinduction of paediatric outpatients.  Paediatr Anaesth. 1997;7(4):273-8.

- Weksler, N., Ovadia, L., Muati, G. et al. Nasal ketamine for paediatric premedication. Can J Anaesth 40, 119–121 (1993).

- McPherson, C. (2018). Premedication for Endotracheal Intubation in the Neonate. Neonatal Network : NN., 37(4), 238–247.

-Poonai N, Canton K, Ali S, Hendrikx S, Shah A, Miller M, Joubert G, Rieder M, Hartling L. Intranasal ketamine for procedural sedation and analgesia in children: A systematic review. PLoS One. 2017 Mar 20;12(3):e0173253. 

- Diane Snyers, Sophie Tribolet, Vincent Rigo; Intranasal Analgosedation for Infants in the Neonatal Intensive Care Unit: A Systematic Review. Neonatology 17 May 2022; 119 (3): 273–284






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