NDMS Conference 2007 Pediatric Pharmacy and Disaster Medicine

1. NDMS Conference 2007Pediatric Pharmacy and Disaster Medicine Shannon Manzi, PharmD MA-1 DMAT Children’s Hospital Boston

2. Objectives • Perform weight based dosing calculations. • List the commonly encountered vaccines in a disaster scenario and the appropriate administration sites. • Describe the treatment options available for routinely encountered pediatric illnesses.

3. Disclaimer - FDA non-approved uses • Nearly 70% of the treatments we use every day in children as standard of care are not approved by the FDA. This workshop will inevitably touch upon non-labeled uses for several of the therapies that will be discussed. If you would like a notation of the off-label indications, please contact me after the workshop. Thank you.

4. Workshop schedule • Hour 1 – Pediatric dosing considerations • Hour 2 – Vaccines and common pediatric illnesses Break • Hour 3 – Continue common pediatric illnesses • Hour 4 – Code and RSI medications

5. Pediatric Dosing • Weight based dosing • kg vs. lbs • Broselow tape • Advantages • Disadvantages • BSA • Age based dosing • Utilized for multi-ingredient preparations or medications that do not require precise measurements. • Miralax, Milk of Magnesia, Colace

6. Pediatric Dosing • Derived from adult dosing • Young’s Rule (age based) • Pediatric Dose = Adult Dose (years of age /12) • Clark’s Rule (weight based) • Pediatric Dose = Adult Dose ( # kg / 70 kg) • Body Surface Area • Pediatric Dose = Adult Dose (Child’s BSA m2/1.73)

7. Preterm Neonate < 36 weeks gestation Term Neonate ≥ 36 weeks gestation Neonate 1 to 30 days old Infant 1 month to 1 year Child 1 to 12 years of age Adolescent 12 to 18 years of age Gestational Age Age from conception to birth Postnatal Age Time from birth Postconceptual Age Time from conception Definition of Age

8. Absorption of Oral Medications • Bioavailability influenced by: • pH-dependent passive diffusion • gastric pH • motility of the stomach & small intestine • gastric emptying time • gastrointestinal perfusion

10. Absorption of Parenterals • Intramuscular & Subcutaneous • reduced absorption in preterm infants • lower regional blood flow and reservoir mass • Percutaneous Drug Absorption • preterm infant lacks a mature stratum corneum • higher degree of skin hydration and ratio of surface area per kilogram of weight

11. Absorption of Parenterals • Rectal drug absorption • physical position of drug • superior vs. lower rectum • Superior drug placement • subject to hepatic first-pass metabolism • reduced bioavailability • Lower rectum drug placement • bypass the liver

13. Neonates Gentamicin Vd = 0.48 L/kg ECW: 57% Total Body Water ECW: 44% Body Weight Less adipose tissue, but higher [H2O] in that tissue Adults Gentamicin Vd = 0.2 L/kg ECW: 32% Total Body Water ECW: 19% Body Weight Volume of Distribution

14. More Volume of Distribution • Decreased volume of distribution for fat soluble drugs • decreased amounts of adipose tissue • high water content in neonatal fat • Diazepam • Vd: • Neonate = 1.4 - 1.8 L/kg • Adult = 2.2 - 2.6 L/kg

15. Distribution • Newborns have altered tissue affinity and membrane permeability • can result in an increased volume of distribution. • Increased permeability of the CNS to certain drugs (e.g. phenytoin) • due to the lower myelin content and increased cerebral blood flow

16. Distribution • Neonates have decreased plasma protein binding • higher free fraction for many drugs • higher apparent volume of distribution • Decreased concentrations of total plasma proteins • approximately 80 % of the serum proteins vs. adults • decreased affinity for drugs by fetal albumin • lower plasma pH • endogenous interfering substances

17. Metabolism

18. Cytochrome P450 Considerations • Full-term and preterm neonates have significantly reduced activity • 20 to 70% of adult levels • Activity reaches or surpasses adult levels within several months as postnatal age  • Older children show greater metabolism of theophylline, phenytoin, carbamazepine, quinidine, and procainamide vs. adults

19. Elimination • Nephrogenesis occurs through 35 weeks postconceptional age with increasing renal mass occurring throughout gestation & continuing after birth • Glomerular filtration, tubular secretion and tubular reabsorption are all decreased at birth vs. adults • Renal function matures in the following order: • first glomerular filtration, then tubular secretion, and finally tubular reabsorption

20. Glomerular Filtration • Gestational age is the primary factor controlling the development of GFR • Preterm-neonate • GFR at birth is approximately 0.7 - 0.8 mL/min • Term-neonate • GFR at birth is approximately 2-4 mL/min (10-20 ml/min/1.73m2).

21. Influence of Age on ClearanceRitschel WA. Handbook of Basic Pharmacokinetics. Table 14.6

22. Estimating Renal Clearance • Pediatrics • Schwartz Method • Creatinine and body length • More specific constant based on age classification (1 week to 18 years) CrCl (ml/min)=  [length (cm) x k] / Scrk = 0.45 for infants 1 to 52 weeks old k = 0.55 for children 1 to 13 years old k = 0.55 for adolescent females 13-18 years old k = 0.7 for adolescent males 13-18 years old • Traub Method • Creatinine and body length • One constant for all age classifications (k =0.28) (1 – 16 years) CLcr = 0.28 x H x BSA SCr

23. IV fluid calculations • Maintenance • 4 mL/kg for first 10 kg • 2 mL/kg for next 10 kg • 1 mL/kg for every kg over 20 kg • Example: “Please run D5 1/2NS at 1.5x maintenance” • Patient is 45 kg

24. IV fluid calculations Answer • 10 kg x 4 mL/kg = 40 mL • 10 kg x 2 mL/kg = 20 mL • 25 kg x 1 mL/kg = 25 mL 45 kg 85 mL/hr

25. Dosage forms • Oral • (N)G-tube, (N)J-tube • Intravenous • Intramuscular • Subcutaneous • Rectal • Transdermal

26. Manipulation of dosage forms • May include • Pre-cutting tablets and suppositories to an appropriate dose • Serial dilutions of an injectable medication to obtain a measurable dose for a newborn or infant. Must avoid excessive free water (i.e. dilution in D5W or < 0.45% NaCl). • Using suspensions for rectal dosing when a patient cannot take anything by mouth • Dilute 1:1 with tap water (sorbitol will induce explusion) • Often used for anti-epileptic medications • Using injectable form PO • Dexamethasone, benzodiazepines

27. Vaccines and schedules • Vaccines available in the cache • Hepatitis A • Hepatitis B • MMR • Tetanus • Vaccines that might be used in a pandemic/epidemic • Influenza/Avian influenza • Smallpox • Vaccine administration • Subcutaneous • Intramuscular • Intradermal • Nasal

28. Immunization sites • < 1 year • Vastus lateralis (anteriolateral thigh) is the preferred site • Deltoid muscle does not have adequate mass • Gluteus maximus does not have adequate mass and there is danger of hitting the sciatic nerve • > 1 year • Deltoid preferred • May use vastus lateralis as alternative

29. Vaccine Administration • Needle length (IM) • < 1 year = 5/8” • > 1 year = 1” • Adolescents and adults (if obese) = 1 1/2” • Bore size (IM) • < 1 year = 25 gauge • > 1 year = 23 gauge • Route • Majority are IM • Most live vaccines are given SC such as MMR and varicella

30. Vaccines and Schedules • MMWR 2007 schedules and catch up schedules • Downloads available for handheld devices • Recent news • Universal influenza vaccination for children 6 mos – 18 years • Rotavirus (Rotateq®) vaccine concerns

31. 2007 vaccine schedule

32. Vaccine Case • Present case Influenza pandemic – A family presents to the clinic consisting of two adults, a 6 month old, 3 year old, and 9 year old child. • Handout scenario cards to the groups • Collate answers and responses to the different challenges presented

33. Commonly encountered pediatric illnesses post-disaster • Allergic reactions/Anaphylaxis • Asthma/Status Asthmaticus • Bronchiolitis • Croup • Gastroenteritis • New onset diabetes/DKA • Overdose/toxic exposure • Psychois, acute • Seizures/Status Epilepticus • Sepsis/meningitis • Trauma-related

34. Allergic reactions/Anaphylaxis • Unfamiliar environment • Lack of access to emergency medications • General approach • Epinephrine IM • Diphenhydramine 1 mg/kg IV/PO • Steroids (methylprednisolone 2 mg/kg IV or PO prednisone/prednisolone) • albuterol • H2 antagonists • Cache treatment options (all of the above are available) • Epi-pen (0.3 mg) – if < 30 kg use epinephrine 1:1000 injection • Famotidine PO only

35. Asthma/Status Asthmaticus • Poor air quality, environmental exposures (mold, fumes, etc) • Lack of access to controller medications, rescue inhalers • General approach • Albuterol ± ipratropium (Combivent) “3 back-to-back” • Steroids – methylprednisolone 2 mg/kg IV • O2 • If persistent/worsening symptoms - Status Asthmaticus • Continuous albuterol 0.5 mg/kg/hr • Magnesium 40 mg/kg IV in NS over 20 minutes • Epinephrine IM if impending respiratory failure • Terbutaline SC/IV 10 mCg/kg bolus over 5 minutes, continuous infusion without syringe pump would be very difficult to titrate. • All are available in the cache. However, there is a very limited supply of terbutaline (10 mg).

36. Asthma/Status Asthmaticus • MDIs vs nebulizer • Use spacer • 3 – 4 puffs emergently then 2 puffs q20min x 2 doses, reassess • Does not require electricity or compressed gas/O2 • Is equally effective, if not superior • Homemade spacers • 500 mL plastic bottle Arch Dis Child 2000;82:495-498

37. Bronchiolitis • Bronchiolitis • Lower airway obstruction • Seasonal, commonly associated with RSV • No effective pharmacotherapy • Trial of racemic epinephrine nebulized x 1 may be an option • Some practitioners try albuterol x 1 • < 10 kg = 1.25 mg • 10 – 30 kg = 2.5 mg • ≥ 30 kg = 5 mg • One 0.083% “bullet” contains 2.5 mg • Supportive care, frequent nasal suctioning

38. Croup • Croup • Upper airway obstruction • Dexamethasone 0.6 mg/kg PO/IM/IV (max 10 mg) x 1 dose, all equally effective (provided they do not vomit!) • May give the injection PO to decrease volume • Humidified O2 • Racemic epinephrine • < 5 kg = 0.25 mL • > 5 kg = 0.5 mL • Limited amount of racemic epinephrine in cache (only one box). Can use epinephrine 1:10,000 as an alternative: • < 5 kg = 2.5 mL • > 5 kg = 5 mL

39. Dehydration/Gastroenteritis • Dehydration • NS or LR 20 mL/kg IV bolus, repeat if needed Followed by • Dextrose containing fluids at 1 – 2 x maintenance rate • Gastroenteritis • Viral vs. bacterial** • Antiemetics • Avoid promethazine (Phenergan) in children < 2 years unless absolutely necessary, no small veins • Avoid prochlorperazine (Compazine) in small children if possible, use lower doses PR • May use metoclopramide (Reglan) if other alternatives not available – 0.1 mg/kg/dose, max 10 mg • Keep lobbying for ondansetron (Zofran) – it is now available as a generic! • No “pushing” any of these!

40. Gastroenteritis • IV vs. PO hydration • Pedialyte in cache • Diarrhea predominate • PO rehydration fluids • Does not reduce stool output, must tell families this is not a measure of “success” • ? Role for solutions with lower osmolality • WHO standard recipe: • 1 liter of clean drinking water • 1 teaspoon of salt • 8 teaspoonfuls of sugar

41. Diabetes/DKA • Lack of access to medications, lack of appropriate diet, stressors • Management Avoid bolus insulin IV in DKA • NS 10 – 20 mL/kg IV bolus • Ideal fluid ~3/4 NS, can bifuse NS with 1/2NS +/- dextrose as required (usual when BG < 300 mg/dL) • Only insulin that should be given IV is Regular. Humalog has been used, greater risk of precipitous hypoglycemia. • Insulin available in cache – Regular, NPH, 70/30 • Insulin infusions extremely difficult to run without syringe pump • Definitive care ASAP for DKA • Monitor for signs of cerebral edema and possible herniation

42. Overdose/toxic exposure • Unfamiliar environment, lack of supervision, accessible substances • History, history, history • No ipecac • Activated charcoal • < 50 kg = 1 gm/kg • ≥ 50 kg = 50 gm • PO is more tolerable when mixed with instant cocoa mix • Must protect airway in patients with deteriorating mental status • Is NOT effective for heavy metals, hydrocarbon, caustics or alcohols • Avoid metoclopramide (Reglan), prochlorperazine (Compazine) and promethazine (Phenergan) as antiemetic if co-ingestion of an anticholinergic substance, such as diphenhydramine (Benadryl). • “Antidotes” in cache • Sodium bicarbonate, insulin, dextrose, glucagon, calcium, naloxone

43. Agitation and/or Psychosis, acute • Unfamiliar environment, situational stress, lack of availability of usual care sites/medications • Limited options in cache • Haloperidol IM/IV/PO • 0.075 mg/kg IV/IM (< 12 years max 3 mg/dose, ≥ 12 years max 5 mg/dose) • In adults, some use up to 10 mg (use with caution, consider diphenhydramine co-adminstration) • Diazepam IM/IV/PO • 0.1 mg/kg IV/IM, usual max 5 mg • 0.2 mg/kg PO, max 10 mg • Diphenhydramine IV/PO • 1 mg/kg/dose IV/PO, may give IM but is very painful • Risperidone PO • Especially helpful if patient is already on baseline • 0.05 mg/kg PO, max generally is 2 mg/dose

44. Seizures • Lack of access to medications, toxic ingestions, infectious • Cache options • Benzodiazepines are first line • Lorazepam IV preferred in children, not available in cache • Diazepam IV 0.1 – 0.2 mg/kg, < 5 years = max 5 mg, ≥ 5 years = max 10 mg, give over 3 – 5 minutes • May repeat every 10 – 15 minutes, up to 3 doses • Diazepam may be given PR if no IV or IO access • 0.5 mg/kg of the injectable form

45. Seizures • Dependent upon age and antiepileptic drug history, phenytoin/fosphenytoin is the second line choice • Fosphenytoin now in cache, may give IM • Dose is 10 – 20 mgPE/kg (max 1500 mg) IV/IM • Give over 7 minutes, hypotension common, slow rate and give fluid • Perineal itching secondary to phosphate deposition – will abate in ~ 15 minutes • If using phenytoin injection, do NOT give IM and run very slowly (not greater than 1-3 mg/kg/min or 50 mg/min whichever is less) • Phenobarbital is generally used third line (second line for neonates) • 10 – 20 mg/kg IV (max 1000mg) slowly over 3 – 5 min, max 30 mg/min for children, 60 mg/min for adults • Be prepared to control airway • Look for reversible causes, particularly hypoglycemia

46. Status Epilepticus Case • Present case A 7 year old male is brought to your acute mobile DMAT hospital from a local shelter. By report, he has been seizing for ~ 20 minutes. His grandmother is with him and tells you that he has a seizure disorder and has been on medication since he was 4 years old. She does not have the prescription bottle or any of the tablets, but as you run down the list of possible antiepileptics, she says that “Dilantin” sounds familiar. • Handout scenario cards to the groups • Collate answers and responses to the different challenges presented

47. Sepsis/Meningitis • Neonatal • Ampicillin 100 – 150 mg/kg/dose (total up to 300 mg/kg/day, use higher end if meningitis suspected) IV/IM q12h PLUS • Gentamicin several different dosing schemas – first dose can be 2.5 – 5 mg/kg IV/IM given over 30 minutes • Infant/child • Ceftriaxone 50 mg/kg/dose IV/IM q12 – 24h for sepsis • Ceftriaxone 100 mg/kg x 1 dose IV/IM for suspected meningitis, followed by 50 mg/kg/dose q12h • Add vancomycin if suspected Gram positive infection (catheter related, Gram positive meningitis, etc) • Vancomycin 10 – 20 mg/kg/dose IV q6 – 12 hr (depends on age), run very slowly over an hour, treat “Redman’s syndrome” with diphenhydramine and slow rate to 2 hours

48. Trauma • Unfamiliar environment, lack of supervision, debris and dangerous materials • Head • Accounts for majority of deaths secondary to trauma • Late presenting signs due to pliability of skull and expansion of sutures • Be prepared to control airway, premed with lidocaine 1 mg/kg IV prior to intubation to ameliorate ICP spikes • For signs of herniation, mannitol 0.5 grams/kg IV • Thoracic/intraabdominal • Second most common cause of death • Ribs are pliable – may not see fractures despite thoracic trauma • Extremities • Likely to be bony injuries, less likely to be tendons or ligaments

49. Chronic Pediatric Conditions to consider • Asthma • Bleeding disorders • Complex care children • Cystic fibrosis • Diabetes • Mood stabilization/ADHD • End-stage renal disease • Oncologic processes/fever & neutropenia • Transplant recipients • HIV/AIDS

50. Emergency Medications • Think outside the box • Learn how to manipulate existing adult dosage forms (HANDS ON exercise) • Use standardized concentrations • Review pharmacology of PALS and RSI medications