Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more…...
Transcript of Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more…...
![Page 1: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/1.jpg)
Emily Rodman, PharmD, BCPPSClinical Pharmacy Specialist - Neonatology
Growing Pains –Neonatal Analgesia
![Page 2: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/2.jpg)
Page 1
xxx00.#####.ppt 10/24/19 1:43:33 PMPage 1
Objectives• Recall how physiological differences affect pharmacokinetic parameters (absorption, distribution, metabolism, elimination) of medications in the neonate - with a focus on medications used in pain
•Apply developmental pharmacology concepts to medication dosing in the neonate
![Page 3: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/3.jpg)
Page 2
xxx00.#####.ppt 10/24/19 1:43:34 PMPage 2
Pain in Neonates•Increased sensitivity to pain
•Pain sensitivity may not be clinically evident in premature neonates and critically ill neonates
•Neonates exhibit greater hormonal, metabolic, and cardiovascular responses to procedures compared with older children (short term physiologic instability)
•Changes in white matter microstructure and altered cognitive development
Page GG. J Perinat Educ. 2004;13(3):10-7.Lago P. Acta Paediatrica. 2009; 932-9.
![Page 4: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/4.jpg)
Page 3
xxx00.#####.ppt 10/24/19 1:43:34 PMPage 3
Conditions of Pain• Diagnostic
- Arterial puncture
- Bronchoscopy
- Endoscopy
- Heel lancing
- Lumbar puncture
- Retinopathy of prematurity examination
- Suprapubic bladder puncture
- Venipuncture
• Therapeutic- Bladder cath
- Central line placement
- Chest tube insertion
- Dressing change
- Gavage tube insertion
- Intramuscular injections
- Removal of adhesive tape
- Suture removal
- Tracheal intubation/extubation
- Tracheal suctioning
• Surgical- Circumcision
- Incision and drainage of abscess
- Venous and arterial cutdown
- Patent ductus arteriosusligation
- Bowel resection
- Tracheoesophageal fistula repair
- Many more…
Khurana S, Whit Hall R, Anand KJS. NeoReviews Feb 2005, 6 (2) e76-e86
![Page 5: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/5.jpg)
Page 4
xxx00.#####.ppt 10/24/19 1:43:35 PMPage 4
Nonpharmacologic Treatment•Environmental
- Decrease bright lights
- Avoid loud noises
- Cluster care- Undisturbed rest
•Positioning- Swaddling/containment
- Facilitated tucking
•Touch- Stroking/caressing
- Massaging
- Holding- Kangaroo care
•Distraction- Music
- Rhythmic rocking
- Soft, smoothing voice
•Nonnutritive sucking- Pacifier
- Nonlactating nipple
- + sucrose
Khurana S, Whit Hall R, Anand KJS. NeoReviews Feb 2005, 6 (2) e76-e86Committee on Fetus and Newborn. Pediatrics. 2016 Feb;137(2):e20154271.
![Page 6: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/6.jpg)
Page 5
xxx00.#####.ppt 10/24/19 1:43:35 PMPage 5
Pharmacotherapy•Neonatal Challenges -
-Over 90% of FDA approved drugs DO NOT have neonatal labeling
-Results of tragic lessons from the past
• Grey baby syndrome (Chloramphenicol)
• Kernicterus (Trimethoprim/Sulfamethoxazole)
- Lack of safety and efficacy data
•Lack of neonatal dosing guidelines
•Lack of commercially available formulations
![Page 7: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/7.jpg)
Page 6
xxx00.#####.ppt 10/24/19 1:43:35 PMPage 6
Developmental Pharmacokinetics•Most dramatic changes occur during the first 12 months of life•Ongoing process throughout infancy, childhood and adolescence
Adapted from Kearns GL, et al. N Engl J Med 2003
![Page 8: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/8.jpg)
Page 7
xxx00.#####.ppt 10/24/19 1:43:36 PMPage 7
Absorption
![Page 9: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/9.jpg)
Page 8
xxx00.#####.ppt 10/24/19 1:43:36 PMPage 8
Gastric Emptying Time•Absorption at the small intestine
-Motility is irregular à difficult to predict the extent or time for peak drug absorption
•Factors affecting gastric emptying time
-Gestational age, disease states
• Reaches adult values at 6-8 months of age
![Page 10: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/10.jpg)
Page 9
xxx00.#####.ppt 10/24/19 1:43:36 PMPage 9
Intestinal Integrity•Immature or altered permeability of intestinal mucosa ↑
drug absorption
•GI integrity is influenced by drug osmolality
-Can cause diarrhea, cramping, abdominal distension and
vomiting
-↑ Osmolality destroys GI integrity
-↑ Risk of necrotizing enterocolitis
![Page 11: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/11.jpg)
Page 10
xxx00.#####.ppt 10/24/19 1:43:37 PMPage 10
Absorption: Morphine •Oral bioavailability is 35% in adults due to first-pass effect
•Adults require higher mg/kg/dose for oral vs IV route
•Neonates believed to not need as high of a conversion as older children
Pediatric Dosing:
Neonatal Dosing:
![Page 12: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/12.jpg)
Page 11
xxx00.#####.ppt 10/24/19 1:43:37 PMPage 11
IM Administration•Factors influencing absorption
-Skeletal muscle blood flow
-Muscle size
-Muscle activity
•IM fentanyl-Longer onset and duration of action
•IV is preferred over IMTayman C, et al. J Pediatr Pharmacol Ther. 2011 Jul;16(3):170-84. http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/appdx-full-d.pdf
![Page 13: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/13.jpg)
Page 12
xxx00.#####.ppt 10/24/19 1:43:37 PMPage 12
Transdermal Administration•Factors influencing absorption
-Skin thickness, skin hydration, surface area of skin, skin damage
•Concern for increased absorption
-Newborn’s ratio of skin surface area to body weight is approximately 3 times that of an adult
•Possible systemic toxicity -Fentanyl, corticosteroids, alcohol, diphenhydramine
![Page 14: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/14.jpg)
Page 13
xxx00.#####.ppt 10/24/19 1:43:38 PMPage 13
Distribution
![Page 15: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/15.jpg)
Page 14
xxx00.#####.ppt 10/24/19 1:43:38 PMPage 14
Distribution•Volume of distribution (Vd) is a concept used to explain the drug concentrations in the blood stream
•Magnitude of Vd provides insight into drug distribution
![Page 16: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/16.jpg)
Page 15
xxx00.#####.ppt 10/24/19 1:43:38 PMPage 15
Fluid Compartments
Age TBW (%)Extracellular Water (%)
Adipose Tissue
(%)
Preterm 87 50 1-5
Term 77 45 12-16
3 months
73 33
1 year 59 28
Adult 55 20 20
Adapted from Clinical Pharmacy 1987; 6: 549
and Clinical Therapeutics 1991; 13: 526
DECR
EASE
INCR
EASE
![Page 17: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/17.jpg)
Page 16
xxx00.#####.ppt 10/24/19 1:43:39 PMPage 16
What does this mean?•Increased %TBW and extracellular water in pediatric patients
•Larger doses of hydrophilic and smaller doses of lipophilic drugs are required in neonates
C = dose
volume
![Page 18: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/18.jpg)
Page 17
xxx00.#####.ppt 10/24/19 1:43:39 PMPage 17
Gentamicin: Volume of Distribution
Stolk LM, Ther Drug Monit. 2002;24:27-31.Van den Anker J. Red Book: 2018 Report of the Committee on Infectious Diseases. 31th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2018.
![Page 19: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/19.jpg)
Page 18
xxx00.#####.ppt 10/24/19 1:43:40 PMPage 18
Lorazepam: Volume of Distribution
Age Vd (L/kg)Neonates 0.76 ± 0.37 (range: 0.14 to 1.3)
5 months to < 3 years 1.62 (range: 0.67 to 3.4)
3 to <13 years 1.5 (range: 0.49 to 3)
13 to <18 years 1.27 (range: 1 to 1.54)
Adults 1.3
McDermott CA, et al. J Pediatr. 1992 Mar;120(3):479-83. Chamberlain JM, et al. J Pediatr. 2012 Apr;160(4):667-672.e2.
![Page 20: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/20.jpg)
Page 19
xxx00.#####.ppt 10/24/19 1:43:40 PMPage 19
Plasma Protein Binding•Only unbound drug is pharmacologically active
•Neonatal patients have qualitative and quantitative differences in protein binding
![Page 21: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/21.jpg)
Page 20
xxx00.#####.ppt 10/24/19 1:43:40 PMPage 20
What does this mean?↓ Protein Binding = ↑ Free Drug
% Protein Bound
Drug Neonates Adults
Morphine 18-22 33-37
Phenobarbital 28-43 45-50
Phenytoin 70-90 89-93
![Page 22: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/22.jpg)
Page 21
xxx00.#####.ppt 10/24/19 1:43:41 PMPage 21
Blood Brain Barrier•Medication uptake dependent on lipid solubility and blood flow
-However, may be easier to cross in the newborn period
![Page 23: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/23.jpg)
Page 22
xxx00.#####.ppt 10/24/19 1:43:41 PMPage 22
Metabolism & Elimination
![Page 24: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/24.jpg)
Page 23
xxx00.#####.ppt 10/24/19 1:43:41 PMPage 23
Phase I Reactions: Oxidation•Cytochrome P450 system
•Different developmental patternsKearns GL, et al. N Engl J Med. 2003 Sep 18;349(12):1157-67. Review.
![Page 25: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/25.jpg)
Page 24
xxx00.#####.ppt 10/24/19 1:43:42 PMPage 24
Metabolism: Fentanyl •Metabolized by CYP3A4 into nor-fentanyl
•Only a small percentage is eliminated unchanged
•Other drugs metabolized by CYP3A4 may compete for clearance and increase fentanyl plasma concentrations
Pacifici GM. Pediatr Neonatol. 2015 Jun;56(3):143-8.
![Page 26: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/26.jpg)
Page 25
xxx00.#####.ppt 10/24/19 1:43:42 PMPage 25
Phase II Reactions: Glucuronidation•Uridine diphosphate (UDP)-glucuronosyltransferase (UGT)
- Activity reduced at birth- Reached adult levels around 6 – 18 months
•Bilirubin, morphine, APAP, corticosteroids and lorazepamundergo glucuronidation
•Historical example: Chloramphenicol tragedy
Tayman C, et al. J Pediatr Pharmacol Ther. 2011 Jul;16(3):170-84.
![Page 27: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/27.jpg)
Page 26
xxx00.#####.ppt 10/24/19 1:43:42 PMPage 26
Metabolism: Morphine •M3G: opioid antagonist, respiratory stimulant, contributes to development of tolerance
•M6G: potent opioid agonist, respiratory depressant
![Page 28: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/28.jpg)
Page 27
xxx00.#####.ppt 10/24/19 1:43:43 PMPage 27
Phase II Reactions: Glycine Conjugation•Decreased in newborns
•Increases to adult levels by approximately 8 weeks of age
•Historical example: Neonatal gasping syndrome
Tayman C, et al. J Pediatr Pharmacol Ther. 2011 Jul;16(3):170-84.
![Page 29: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/29.jpg)
Page 28
xxx00.#####.ppt 10/24/19 1:43:43 PMPage 28
Metabolism: Benzyl Alcohol
•Caution: neonatal gasping syndrome, deathBenzyl Alcohol Metabolism. Wikimedia Commons. Website. 11 Sept 2017 <https://commons.wikimedia.org/wiki/File:Benzyl_Alcohol_Metabolism_Scheme.png>
![Page 30: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/30.jpg)
Page 29
xxx00.#####.ppt 10/24/19 1:43:43 PMPage 29
Phase II Reactions: Sulfation•Sulfotransferase system is fairly well developed at birth
•May compensate for limited function of other pathways
•Clinical example: APAP
![Page 31: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/31.jpg)
Page 30
xxx00.#####.ppt 10/24/19 1:43:44 PMPage 30
Metabolism: Acetaminophen •Metabolized via sulfation rather than glucuronidation as in adults
Age Half-life
Neonates 7 hours (range: 4 to 10 hours)
Infants ~4 hours (range: 1 to 7 hours)
Children 3 hours (range: 2 to 5 hours)
Adolescents ~3 hours (range: 2 to 4 hours)
Adults 2 hours (range: 2 to 3 hours)
Acetaminophen Metabolism. Wikimedia Commons. Website. 11 Sept 2017 <http://upload.Wikimedia.org/Wikipedia/commons/1/12/paracetamol_metabolism.svg>
![Page 32: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/32.jpg)
Page 31
xxx00.#####.ppt 10/24/19 1:43:44 PMPage 31
Elimination: Creatinine Clearance
Gallini. Pediatr Nephrol (2000) 15:119–124
![Page 33: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/33.jpg)
Page 32
xxx00.#####.ppt 10/24/19 1:43:44 PMPage 32
Elimination: Serum Creatinine
Gallini. Pediatr Nephrol (2000) 15:119–124
![Page 34: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/34.jpg)
Page 33
xxx00.#####.ppt 10/24/19 1:43:45 PMPage 33
Gabapentin•Observational evaluation
- 22 NICU pts received gabapentin
- 10.2 mg/kg/day mean starting dose
- 25.5 mg/kg/day maximum dose
- N-PASS score decreased in most patients from median of 3.1 to 0
- It also reduced the need for analgesic or sedative medications
- Well tolerated
•Highly lipophilic/penetrates well through the BBB
•Not metabolized
•PK data- Neonates: plasma half-life of 14 hours (adults 5-7 hours)
- Eliminated unchanged via the kidneys
Sacha GL, et al. J Pediatr Pharmacol Ther. 2017 May-Jun;22(3):207-211.
![Page 35: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/35.jpg)
Page 34
xxx00.#####.ppt 10/24/19 1:43:45 PMPage 34
Elimination: Morphine•Reaches 80% of adult values by 6 months of age
Age Clearance (L/h/kg)24-27 weeks 0.136
28-31 weeks 0.193
Term neonate 0.44
3 months 1.14
6 months 1.43
Age Half-life (hr)Preterm 10-20
Neonates 7.6
6 months 2.9
Anand KJ. J Perinatol. 2007 May;27 Suppl 1:S4-S11. Review.McRorie TI, et al. Am J Dis Child. 1992 Aug;146(8):972-6.
![Page 36: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/36.jpg)
Page 35
xxx00.#####.ppt 10/24/19 1:43:45 PMPage 35
Elimination: Morphine
Bouwmeester 2004.
![Page 37: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/37.jpg)
Page 36
xxx00.#####.ppt 10/24/19 1:43:46 PMPage 36
Elimination: Fentanyl
Age ClearancePreterm 2 – 85 mL/min/kgNeonates < 1 week old 7.4 mL/min/kgNeonates 7 – 14 days old 23.6 mL/min/kgInfants post abdominal surgery 0 to 9 mL/min/kgAdults 0.4 to 1.5 L/min
Saarenmaa E, et al. J Pediatr. 1999 Feb;134(2):144-50.
![Page 38: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/38.jpg)
Page 37
xxx00.#####.ppt 10/24/19 1:43:46 PMPage 37
Opioid Conversions“The potency ratio of
fentanyl compared to morphine is
different in adults (80 to 100 times) as compared to infants
(13 to 20 times).”Anand. Journal of
Perinatology (2007)27.
![Page 39: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/39.jpg)
Page 38
xxx00.#####.ppt 10/24/19 1:43:46 PMPage 38
Summary•Decreased Vd for lipophilic medications, increased for hydrophilic medications
•Decreased protein binding
•Increased blood brain barrier penetration
•Decreased metabolism
•Decreased elimination
![Page 40: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/40.jpg)
Page 39
xxx00.#####.ppt 10/24/19 1:43:47 PMPage 39
Children are NOT just small adults!
![Page 41: Growing Pains – Neonatal Analgesia€¦ · - Tracheoesophageal fistula repair - Many more… KhuranaS, Whit Hall R,AnandKJS. NeoReviewsFeb 2005,6 (2) e76-e86. Page 4 xxx00.#####.ppt](https://reader034.fdocuments.in/reader034/viewer/2022052500/5f7e6a9352d3bb09ac198d92/html5/thumbnails/41.jpg)
Page 40
xxx00.#####.ppt 10/24/19 1:43:47 PMPage 40
Questions?