Pharmacodynamics & Kinetics
Changes in protein binding in pediatric patients put them at risk for...
Drug overdose and toxicity
FYI...
• Decreased protein binding of drugs in the newborn period
• Decreased concentration of plasma proteins, persistence of fetal albumin, and increased free fatty acids alter binding properties
Reduced doses are frequently required in pediatric patients due to...
Reduced metabolism and delayed elimination
FYI...
• Neonatal concentration & activity of many microsomal enzymes are reduced/absent! (CYP 450 <50% as in adults)
• GFR is reduced until about 5-7 months
2 major side effects after giving a pediatric patient succinylcholine
Bradycardia & asystole
FYI...
• Can give atropine 0.02mg/kg IV prior to administration
Three drugs that you should always have prepared and ready for pediatric procedures are
Succinylcholine (IM & IV doses)
Atropine (0.02mg/kg IV)
Epinephrine (consideration concentrations from 1-100mcg/mL available...10mcg/kg for resuscitation!)
Doses of propofol for infants & children
Infants 4 mg/kg IV
Children 3 mg/kg IV
FYI...
• Bolus doses are typically increased due to the large Vd in pediatric patients
• Clearance is similar to adults
• Prolonged recovery in neonates
IV & IM induction dose for Ketamine in pediatric patients
1-3mg/kg IV or 5-10mg/kg IM
FYI...
• Repeat/rescue dose 0.5-1mg/kg PRN
• DOA 5-8 minutes
• Elimination half-life 2.5-3hrs
• PONV 33% in children!
Anesthetic agents are most commonly used for inhalational induction
Sevoflurane & Nitrous
FYI...
• Uptake & elimination is more rapid in pediatric patients!
• Greater alveolar ventilation to FRC ratio and fraction of CO to the VRG
• Reduced blood:gas & tissue:blood solubility
• Sevo MAC: 3.3% neonates, 3.2% 1-6months, decreases to 2.5% at 10y/o, then continues to drop
IV & PO dose of midazolam for pediatric patients
0.5-1 mg/kg PO (MAX dose of 20 mg)
0.1mg/kg IV
FYI...
• PO dose given ~30 min before procedure
• Bolus in preterm/term neonates can lead to profound hypotension!
Clearance of neuromuscular blockades are decreased in neonates/infants except.... and WHY
Atracurium, Cisatracurium, and Mivacurium
Hoffman's elimination
NSAID doses in pediatric patients: ketorolac & acetaminophen
ketorolac 0.5 mg/kg IV
acetaminophen 15 mg/kg IV (max 60mg/kg per day)
Despite pediatric patients having a larger Vd, adult and infant NMBD doses are the SAME because...
Lower plasma concnetration to reach effect! Infants have immature neuromuscular transmission until 2 months with increased sensitivity
FYI...
• Children 2-12y/o have increased dose requirements compared to adults
• Inhalational agents will prolong DOA
• DOA is longer in infants d/t hepatic & renal function
Dose of morphine in pediatric patients and the age group it should be used cautiously in
0.1-0.2mg/kg IV
< 1 year of age
FYI...
• Term & preterm infants have decreased clearance & prolonged elimination half-life
• Clearance increases to adult values by 3-6months
Pediatric patients are at a greater risk for _______ during inhalational induction (3)
Bradycardia
Hypotension
Cardiac arrest
The treatment for succinylcholine induced cardiac arrest
10 mg/kg IV calcium chloride OR 30 mg/kg IV calcium gluconate
FYI...
• There is no upper limit! Continue to repeat until conversion to NSR!
• Defibrillation is NOT effective!
• High mortality rate when treated as MH without calcium administration
Doses for thiopental in pediatric pateints for healthy neonates, infants, & children
Healthy neonate 4-5mg/kg
Infants 7-8mg/kg
Children 5-6mg/kg
Physiologic reasons why pediatric patients have different pharmacokinetic considerations than adults (4)
Altered protein binding
Large Vd (ECF)
Smaller fat/muscle stores
Immature organ (renal & hepatic) function
Intralipid dose for local anesthetic toxicity in pediatric patients
1.5mL/kg bolus followed by 0.5-1mL/kg/min
FYI...
• Pediatric patients have a lower concentration of a1-acid glycoproteins AND reduced CYP450 system!
• Increased risk of CNS & cardiovascular toxicity
• Bupivacaine max dose for neonates <6 months is reduced to 1.5mg/kg
• Ropivicaine max does for neonates <6 months is also reduce to 0.5-1.5mg/kg
Four drugs thought to cause neuronal apoptosis
Ketamine
Sevoflurane
Midazolam
Nitrous
Succinylcholine doses for IM administration, infants, children, AND laryngospasm treatment :)
4 mg/kg IM
Infants 3 mg/kg IV
Children 2 mg/kg IV
Laryngospasm 0.1 mg/kg IV
FYI...
• Remember, fasciculations will not be observed in infants!
• BLACK BOX warning for pediatric patients (except emergency airway) due to hyperkalemic arrest