Pharmacodynamics & Kinetics
A major risk with administering drugs in pediatric patients due to decreased levels of protein binding
What is drug overdose and toxicity?
FYI...
• Decreased protein binding of drugs in the newborn period
• Decreased concentration of plasma proteins, persistence of fetal albumin, acidotic pH, and increased free fatty acids alter binding properties of plasma proteins and drugs
• Example: Thiopental is highly protein bound, so the fraction of unbound drug is 2x greater in the neonate than the adult (neonate > adult > child)
The reason as to why reduced doses are frequently required in pediatric patients
What is reduced metabolism & delayed elimination?
FYI...
• Neonatal concentration & activity of many microsomal enzymes are reduced/absent! (CYP450 <50% as in adults)
• GFR is reduced until about 5-7 months
In pediatrics patients, this induction agent may increase salivation, precipitate seizures, and increase IOP & ICP.
What is Ketamine?
Three drugs that you should always have prepared and ready for pediatric procedures
What is...
Succinylcholine (IM & IV doses)
Atropine (0.02mg/kg IV)
Epinephrine (consideration concentrations from 1-100mcg/mL available depending on patient...10mcg/kg for resuscitation!)
IV doses of propofol for infants & children
What is...
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
In infants, an immature BBB increases sensitivity to this class of medications, raising the risk of respiratory depression.
What are opioids?
FYI...
• Increased permeability to sedatives, opioids, and hypnotics
• Their immature BBB can affect onset time as well as duration of response
IV & IM induction dose for Ketamine in pediatric patients
What is...
IV: 1-3mg/kg
IM: 5-10mg/kg
FYI...
• Repeat/rescue dose 0.5-1mg/kg PRN.
• Onset: 30 seconds; DOA 5-8 minutes
• Elimination half-life 2.5-3hrs
• PONV 33% in children!
The 2 major side effects that are possible after giving a pediatric patient succinylcholine
What is bradycardia & asystole?
FYI...
• Can give atropine 0.02mg/kg IV prior to administration
These two anesthetic agents are most commonly used for an inhalational induction
What is...Sevoflurane & Nitrous
FYI...
• Uptake & elimination is more rapid in pediatric patients!
• Greater alveolar ventilation to FRC ratio and fraction of CO going 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
What is...
PO: 0.5-1 mg/kg (MAX dose of 20 mg)
IV: 0.1mg/kg
FYI...
• PO dose given ~30 min before procedure
• Bolus in preterm/term neonates can lead to profound hypotension (especially with concurrent fentanyl administration)!
These neuromuscular blockers do NOT have decreased clearance in neonates/infants.... and WHY
What is Atracurium, Cisatracurium, and Mivacurium?
Hoffman's elimination!
FYI...
• Duration of action in infants is typically longer because of immature hepatic & renal function
NSAID IV doses in pediatric patients: Ketorolac & Acetaminophen
What is...
Ketorolac 0.5 mg/kg IV
Acetaminophen 15 mg/kg IV (max 60mg/kg per day)
This NMB is good for high-dose opioid anesthesia (like CV & high risk cases) because it increases HR and decreases opioid induced chest wall & glottis rigidity
What is pancuronium?
FYI...
• ALL NMBs must be reversed!
• Atropine 20mcg/kg + 1mg edrophonium
• Glycopyrrolate 10mcg/kg + 50mcg/kg neostigmine
• Sugammadex can be used with same dosing as adults
The reason why infants & children experience a faster distribution of drugs & onset of action
What is cardiac output?
FYI...
• Pharmacokinetic principle of distribution is also affected by protein binding in pediatric populations
• Infants & children have less circulating albumin & a1 acid glycoprotein which can lead to toxicity with highly protein bound drugs
MAC value of sevoflurane for fullterm neonates
What is 3.3%?
FYI...
• MAC of sevoflurane is the greatest in full term neonates and slowly decreases after
• MAC of isoflurane is the greatest in 1-6 month olds (1.87%) and decreases thereafter
• Uptake of volatile anesthetics is increased in neonates and infants due to increased cardiac output
The reason why NMBD doses are the same in adult & pediatric pateints, despite pediatric patients having a larger Vd (ECF)
A lower plasma concentration is needed to reach effect! Also, 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 due to hepatic & renal function
IV dose of morphine in pediatric patients AND the age group it should be used with caution
What is...
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
• Concentration in the neonate's brain is 2-3x higher due to their immature BBB and the high water solubility of morphine
This anesthetic complication is characterized by metabolic acidosis, rhabdomyolysis, and CV collapse after high-dose infusions
What is Propofol Related Infusion Syndrome (PRIS)?
The treatment for succinylcholine induced cardiac arrest
What is 10 mg/kg IV calcium chloride OR 30 mg/kg IV calcium gluconate
FYI...
• There is no upper limit on dose of calcium! Repeat until conversion to NSR!
• Defibrillation is NOT effective!
• High mortality rate when treated as MH without calcium administration
Doses for thiopental in pediatric patients for healthy neonates, infants, & children
What is...
Healthy neonate 4-5mg/kg
Infants 7-8mg/kg
Children 5-6mg/kg
The reasons why pediatric patients have unique pharmacokinetic considerations compared to adults (4)
What is...
Altered protein binding
Large Vd (ECF)
Smaller fat/muscle stores
Immature organ (renal & hepatic) function
Intralipid dose for local anesthetic toxicity in pediatric patients
What is 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 dose for neonates <6 months is also reduced to 0.5-1.5mg/kg
Three adverse events pediatric patients are at a greater risk for during an inhalational induction
What is bradycardia, hypotension, and cardiac arrest?
Four drugs thought to cause neuronal apoptosis
*BONUS*: What IV anesthetic agent is thought to mitigate neuronal apoptosis?
What is...
Ketamine
Isoflurane
Midazolam
Nitrous
*BONUS ANSWER*: Dexmedetomidine
Succinylcholine doses for infants, children, laryngospasm treatment, and IM administration :)
What is...
Infants: 3 mg/kg IV
Children: 2 mg/kg IV
Laryngospasm: 0.1 mg/kg IV
4 mg/kg IM
FYI...
• Remember, fasciculations will not be observed in infants!
• BLACK BOX warning for pediatric/adolescent patients (except emergency airway) due to hyperkalemic arrest