Jeffrey L. Segar, MD, Danielle R. Rios MD, MS, John M. Dagle, MD, PhD, and Sarah B. Tierney PharmD
Peer Review Status: Internally Peer Reviewed
Analgesics and Sedatives
Jeffrey L. Segar, MD, Danielle R. Rios MD, MS, Elizabeth W. Amelon, Pharm.D., BCPS, Sarah B. Tierney, Pharm.D.
Peer Review Status: Internally Peer Reviewed (6/19/2014)
Systemic narcotics are the most commonly used agents for management of pain in the post-operative patient. They are also the most frequently used agents given to ventilated children, particularly when paralyzed with neuromuscular blockers, or those with bronchopulmonary dysplasia.
Jeffrey L. Segar, MD and Sarah B. Tierney, PharmD
Peer Review Status: Internally Peer Reviewed 12/19/12
Agents should always be used in concert with adequate sedatives and analgesics
Non-depolarizing Agents | Initial Dose (mg/kg) | Onset of paralysis after administration (minutes) | Pharmacokinetics (Duration, dosing interval, protein binding) |
Remarks |
---|---|---|---|---|
Vecuronium | IV: 0.1 (0.1 mg/kg/h for continuous infusion) |
1-3 | Duration (dose-dependent): 30-40 minutes Dosing interval: 60-120 minutes Protein binding: 60-80% |
|
Pancuronium | IV: 0.15 | 1-5 | Duration (dose-dependent): 24 minutes Dosing interval: 60-120 minutes Protein binding: 87% |
|
Rocuronium | IV: 0.4 – 0.6 Do not give IM |
0.5-1.0 | Duration: 20-120 minutes Dosing interval: 10-30 minutes Protein binding: 30% |
|
*Depolarizing agents are not routinely recommended because they persist for a longer duration due to their resistance to acetylcholinesterase.
*Reversal of neuromuscular blockade: Neostigmine 0.04 – 0.08 mg/kg IV and atropine 0.02 mg/kg.
References:
- Feltman DM, Weiss MG, Nicoski P, and Sinacore J. Rocuronium for nonemergent intubation of term and preterm infants. Journal of Perinatology 2011; 31: 38-43.
- Lexi-Comp, Inc. Pediatric Drug Information. Accessed online. Updated annually.
- Johnson PN, Miller J, Gormley AK. Continuous-infusion neuromuscular blocking agents in critically ill neonates and children. Pharmacotherapy 2011; 31 (6): 609-620.
- Thomas Reuters. Neofax. 24th Edition. 2011.
Anticonvulsants
Jeffrey L. Segar, MD and Sarah B. Tierney, PharmD
Peer Review Status: Internally Peer Reviewed 3/13/12
Drug | Recommended Dosage | Therapeutic Serum Level | Onset Duration | Toxicity/Remarks |
---|---|---|---|---|
Phenobarbitial | 1Loading 15-20 mg/kg IV over 15 - 20 min. 2Maintenance: 3-5 mg/kg IV, IM , POq 12 - 24 hr. (first dose given 12 to 24 hours after loading) |
15-40 mg/L | IV: Within 5 minutes PO: Within 20-60 minutes Max IV effect within 30 minutes Duration: 5-10 hours |
Sedation, respiratory arrest, hypotension, T1/2 96 h / increase 1st two wk of life; induces drug metabolism(interactions), sensitivity reactions IV push < 1 mg/kg/min. |
3Phenytoin | Loading: 15 - 20 mg/kg IV *Maintenance: 5 - 8 mg/kg/d q 8 - 12 hr IV (first maintenance dose 24 hours after loading) |
10-20 mg/L4 | Large patient variability in onset and duration | Extravasation risk due to high pH. *If >1 week old, may need to increase dosage to ³ 8 mg/kg IV q12 h or q 8h to maintain therapeutic effect / levels IV push < 0.5 mg/kg/min. Ø IM |
Fosphenytoin (prodrug of phenytoin) |
Dosing the same as for phenytoin; however, doses are expressed in phenytoin sodium equivalents (PEs). 1 PE = 1 mg phenytoin | Same as for phenytoin | Conversion of fosphenytoin to phenytoin is 7-15 minutes then phenytoin kinetics take over | Rapidly absorbed via IV and IM route. Can give intraosseously. Fosphenytoin is preferred product for pediatrics. |
Levetiracetam (Keppra) |
Loading dose5 10 mg/kg IV over 15 minutes. Up to 50 mg/kg loading dose has been used. PO can also be used. Maintenance dose 10 – 30 mg/kg/dose q 24 hours in neonatal period and q12 hours in infancy. |
10-40 mcg/mL However, not routinely monitored. |
IV/PO: Rapid Max effects within 60 minutes. Duration: not specified t1/2 = 9 hours |
Must dilute to a concentration of 5 mg/ml in D5W or NS prior to IV administration. No drug-drug interactions. PO rapidly and completely absorbed. IV:PO conversion is 1:1. Well-tolerated even at a loading dose of 50 mg/kg. Adverse effects reported are some sedation and irritability at 24 hours after initial dose. |
Lorazepam | 0.05 - 0.1 mg/kg/dose slow IV push over 2 - 3 min. | IV: Within 5 minutes Duration: 3-24 hours. |
May increase phenobarbital level. May cause respiratory depression. | |
Diazepam | 50.2 to 0.75 mg/kg slow IV push. Give in maximum increments of 0.2 mg/kg q 2 min. If seizures stop before completion of dosing, discontinue infusion. Rectal dose: 0.5-1.0 mg/kg. |
0.15-0.3mcg/ml | IV: Within 1-3 minutes Rectal: Within 2-10 minutes |
CNS depression, respiratory depression including apnea, phlebitis. Doses may be repeated q 15 - 30 min. x 2 to 3 doses total |
Footnotes:
- If seizures are noted to continue after the initial phenobarbital loading dose, an additional 5 mg/kg bolus dose can be given every 15 - 30 minutes (total load dose should not exceed 35 mg/kg). Sedation occurs at serum concentrations above 40 mg/L. Respiratory depression may develop with larger loading doses (serum concentrations above 60 mg/L) or if given in conjunction with diazepam.
- Maintenance phenobarbital doses of 5 mg/kg/day may occasionally result in accumulation of serum levels to >30 mg/L in the neonate less than 1 week of age. Unless undue sedation occurs (monitoring of serum phenobarbital levels will be of assistance in identifying and managing such patients) little adverse consequences should be anticipated from the higher serum levels. Therapeutic levels may be > 45 mg/L and require very careful respiratory monitoring.
- Phenytoin is contraindicated in patients with heart block or sinus bradycardia. FDA Alert (11/24/08): Potential increased risk of serious skin reactions including Stevens Johnson syndrome and toxic epidermal necrolysis in Asian patients positive for HLA allele, HLA-B*1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including Han Chinese, Filipinos, Malaysians, South Asian Indians, and Thais.
- Maintenance doses of phenytoin are impossible to accurately establish because of marked individual variation. Frequent plasma phenytoin concentration measurements are essential, particularly in the rapidly changing period of the first 3 weeks of age. Drug is highly protein bound; free fraction of drug may be increased in patients with hypoalbuminemia and/or hyperbilirubinemia. If the therapeutic range is based on the premise that in the neonate there is a greater concentration of unbound phenytoin in plasma at any given total plasma concentration, then a total plasma phenytoin concentration of 6-14 mcg/ml will provide the same concentration of unbound phenytoin as a 10-20 mcg/ml total concentration in an adult (Loughnan et al, 1977). However, the actual relationship between serum levels and anticonvulsant activity of phenytoin (alone) has not been demonstrated in the neonate. The plasma level 8 hr. after dosing should be the most representative of the average phenytoin concentration.
- Levetiracetam can be used as monotherapy or adjunctive therapy for neonatal seizures. In a retrospective case review of 22 neonates ≥ 37 weeks (Khan et al 2011); 20 patients received a loading dose of 50 mg/kg, 1 patient a loading dose of 20 mg/kg, and 1 patient a loading dose of 10 mg/kg. The patients’ were then maintained on 25 mg/kg q 12 hours, 20 mg/kg q 12 hours, and 10 mg/kg q 12 hours, respectively. Of the 22 patients, 19 (86%) demonstrated immediate seizure cessation at 1 hour. Furthermore, 7/22 (32%) achieved complete seizure cessation after administration of the loading dose, 14 (64%) achieved seizure cessation by 24 hours, 19 (86%) by 48 hours, and all 22 (100%) by 72 hours. Outcomes were confirmed by electroencephalographic correlation. Follow-up at 6 months after initiation of therapy demonstrated no new adverse effects. When used as 2nd or 3rd line therapy phenobarbital and phenobarbital and phenytoin/fosphenytoin where the first-line agents, respectively.
- The total acute IV dose of diazepam necessary to control neonatal seizures has ranged from less than 0.1 mg/kg to 2.7 mg/kg. Based on the proposed therapeutic serum level of diazepam, a dose of 0.5 mg/kg should produce levels in excess of that ordinarily necessary. Only in very unusual circumstances should alternate routes of administration be considered. Evidence does exist to support the efficacy of rectal administration. The parenteral injection form is used in conjunction with a syringe and catheter inserted 5 cm into the rectum. It is important to note that there is no evident advantage in using diazepam instead of phenobarbital, but to maintain anticonvulsant effect, a longer acting anticonvulsant such as phenobarbital is generally used following diazepam or lorazepam (as this combination often produces respiratory depression, close monitoring of the patient is essential).
References:
- Abend NS, Gutierrez-Colina AM, Monk, HM, et al. Levetiracetam for Treatment of Neonatal Seizures. J Child Neurol 2011; 26(4): 465-470.
- Khan O, Chang E, Cipriani C, et al. Use of Intravenous Levetiracetam for Management of Acute Seizures in Neonates. Pediatr Neurol 2011; 44: 265-269.
- Lexi-Comp, Inc. Pediatric Drug Information. Accessed online. Updated annually.
- Merhar SL, Schibler KR, Sherwin CM, et al. Pharmacokinetics of Levetiracetam in Neonates with Seizures. J Pediatr 2011; 159: 152-4.
- Thomas Reuters. Neofax. 23rd Edition. 2010.
- Warner A, Privitera M, Bates D. Standards of laboratory practice: antiepileptic drug monitoring. Clinical Chemistry 1998; 44: 1085-1095.
Antimicrobials
Sarah Tierney, Pharm.D. and Jonathan Klein, MD
Peer Review Status: Internally Peer Reviewed 12/20/12
Goals | When to draw level | |
---|---|---|
Initial trough | 0.3-1.0 | Just prior to 2nd dose |
Late troughs | 0.3-1.0 | Obtain on day 7 if continuing therapy >7 days and then weekly thereafter. Draw earlier and/or more frequent if there is decreased urine output or other changes in renal function. |
Peaks | 5-12 | IV: 30 minutes after the end of the infusion |
Gentamicin is a concentration-dependent, bactericidal antibiotic used for the treatment of gram-negative organisms including Pseudomonas, Escherichia coli, Proteus, and Serratia. It is also used in combination with ampicillin for treatment of gram-positive group B Streptococcus species and Listeria monocytogenes. The rationale for using the extended-interval dosing protocol for gentamicin is based on the concentration-dependent bactericidal activity of aminoglycosides, the extended post-antibiotic effect, and the possibility of reduced nephrotoxicity and ototoxicity.1,2
Bactericidal effects
The current gentamicin dosing protocol (Neofax) achieves an early and high peak gentamicin plasma concentration for optimal bactericidal effect about 94% of the time.3,4 In vitro, aminoglycosides eradicate bacteria at a rate proportional to the peak concentration attained. Therefore, a high peak level results in a more rapid and efficient bactericidal effect against susceptible organisms. In addition, aminoglycosides have an extended post-antibiotic effect (PAE) which is defined as the time period that surviving bacteria, following exposure to an antibiotic, cannot metabolize or multiply even though extracellular antibiotic is no longer present. The duration of PAE is approximately 8-12 hours in the immunocompromised patient.1
Potential toxicity
The uptake of aminoglycosides occurs in the renal tubular cells and is a saturable process; therefore, larger doses would not be expected to be any more nephrotoxic than smaller doses. Both animal and human studies have shown that the concentration in the renal cortex is significantly lower when administered as a single daily dose than when divided and administered more frequently. Animal data supports an accumulation threshold in the organ of Corti as well, so there is the potential for less ototoxicity.1,5 Although neonates are believed to experience a lower risk for ototoxicity and nephrotoxicity than adults;5 sustained elevated peak (>12 mg/L) or trough (>2 mg/L) concentrations may cause these toxicities in neonates.3
References
- Behm-Dillon, DM. Appropriate Use of Antibiotics: The Antibiotic Advisory Subcommittee and You. UIHC P&T News; Jan/Feb 2000. Accessed 10/28/2009.
- Gentamicin. Pediatric Dosage Handbook. 15 Edition. 2008: 819-823.
- Hoff DS, et al. Pharmacokinetic Outcomes of a Simplified, Weight-Based, Extended-Interval Gentamicin Dosing Protocol in Critically Ill Neonates. Pharmacotherapy 2009; 29 (11): 1297-1305.
- Gentamicin. Neofax. 2008: 42-43.
- Haughey DB, et al. Two-compartment gentamicin pharmacokinetics in premature neonates: a comparison to adults with decreased glomerular filtration rates. J Pediatr 1980; 96:325-30.
Edward F. Bell, MD and Jeffrey L. Segar, MD
Peer Review Status: Internally Peer Reviewed
This nomogram is for use only in term neonates (<30 days old) receiving gentamicin or tobramycin 2.5 mg/kg given IV every 12 hours.
Illustration of the upper and lower range of acceptable gentamicin serum concentrations (heavy dashed and solid parallel lines). The mean + S.D. for the peak serum gentamicin concentrations of 81 neonates is shown as well as individual gentamicin disappearance curves for 31 neonates who required dosing adjustment (Zone I = required increased dosage; Zone II = required decreased dosage). A single blood sample is drawn between 8 and 12 hours after the start of drug infusion. Any value falling within the Normal Zone is bordered by the following: upper 8 and 12 hour serum values = 3.5 and 2 mcg/ml; lower 8 and 12 hour serum values = 1.8 and 1 mcg/ml.
Dosage adjustment
Zone I: | If 8 to 12 hour level is below the Normal Zone, the dosing interval should be shortened to every 8 hours. Recheck the drug level 1 to 2 hours prior to dosing. Acceptable level would be between 1 and 2 mcg/ml. |
Zone II: | If 8 to 12 hour level is above the Normal Zone, perform the following calculation (%RDR = percent required dose reduction): |
%RDR= | observed conc. - maximum acceptable conc. x 100 |
observed conc. |
If the %RDR calculated is <25%, then reduce the dose by the calculated percent and continue dosing every 12 hours. If the %RDR calculated is > 25%, then increase the dosing interval to every 24 hours while keeping the dose at 2.5 mg/kg per dose. Recheck drug levels 1 to 2 hours prior to dosing. Acceptable levels would be between 1 and 2 mcg/ml.
Reference
Leff RD, Andersen RD, Roberts RJ. Simplified gentamicin dosing in neonates: a time- and cost-efficient approach. Pediatr Infect Dis 1984;3:208-212.
Diuretic Agents
Jeffrey L. Segar, MD
Peer Review Status: Internally Peer Reviewed
Drug | Dosage | Toxicity |
---|---|---|
Furosemide (Lasix) Inhibits chloride reabsorption in the ascending limb of the loop of Henle, inhibits tubular sodium transport |
Initial dose: 1 mg/kg dose IV slow push, IM, or PO. May increase dose as required to a maximum of 2 mg/kg/dose IV or IM and 6 mg/kg/dose PO. For oliguria, repeat max. effective dose as required, but no more often than every 12 hr (fullterm) or 24 hr (premature) 1 |
Causes major urinary loss of sodium and chloride; also potassium and calcium. Increases prostaglandin secretion and renal blood flow. Peak effect 1 - 3 hr after IV dose; duration 6 hr. Monitor for dehydration and electrolyte (Na, Cl, K) imbalances, ototoxicity, metabolic alkalosis, renal nephrocalcinosis. |
Spironolactone (Aldactone) antagonist of aldosterone |
Oral: 1 to 3 mg/kg/d ÷ q 12 - 24 hr |
increased Urine Ca++, Mg++, Na+, Cl-; decreased Urine K+; clinical effect usu. seen 2 -3 days after start therapy. Monitor for hyperkalemia, drowsiness, GI upset, masculinization, rash |
Chlorothiazide (Diuril, Diurigen) decreased sodium reabsorption in the distal nephron |
PO or IV: 10 - 20 mg/kg ÷ q 12 hr. 2 |
increased Urine Na+, K+, Mg++, Cl-, HCO3-, phosphorus; Urine Ca++ . Monitor for dehydration and electrolyte imbalances, metabolic alkalosis, hypercalcemia ,hyperglycemia, hyperuricemia; Donít use in pts w/ sig. liver / renal disease |
Metolazone decreased Na+ reabsortion in distal nephron |
Oral: 0.2 - 0.4 mg/kg /day divided q 12 - 24 hr. |
Same as chlorothiazide; hypokalemia is major electrolyte imbalance |
Footnotes
- The plasma clearance of furosemide varies considerably in the neonate (Aranda et al 1980, Chemtob et al 1987). Since the diuretic effect occurs subsequent to renal tubular secretion, the excessive plasma concentration is more likely to result in displacement of bilirubin or ototoxicity than enhanced diuretic effect. Avoiding an excessive plasma concentration of drug by appropriate dose and dosing intervals is prudent. Attention to the duration of diuretic response along with frequent assessment of diuretic needs (particularly when initiating therapy) will assist in determining the appropriate dose and dosing interval (as opposed to an arbitrary every 12 or 24 hour routine) (Vert et al 1982).
- The thiazides have a relatively flat dose response curve indicting that significant increases in dose are not associated with comparable increases in diuretic or antihypertensive effects. Because of the dependence of diuretic effect on renal elimination, an increase in dosing interval is recommended with renal failure (give every 24 hours with 50 percent or less of normal creatinine clearance).
Effects of Drugs on the Fetus or Newborn
Download Effects of Drugs on the Fetus or Newborn
Identifying Neonatal Abstinence Syndrome (NAS) and Treatment Guidelines
University of Iowa Stead Family Children’s Hospital -11/2014
What is Neonatal Abstinence Syndrome?
• Neonatal withdrawal after intrauterine exposure to certain drugs (illicit or prescription)
• Occurs with the abrupt cessation of the drug exposure at birth
• Most commonly seen with opioid exposure, but also seen after exposure to sedatives, selective serotonin reuptake inhibitors (SSRI), polysubstance abuse, and occasionally barbiturates and alcohol • Develops in 55-94% of opioid drug-exposed infants and 28-30% of SSRI-exposed infants
Screening
-
Maternal history
-
Meconium drug testing
-
Urine drug screen
-
Umbilical cord testing
Jeffrey L. Segar, MD
Peer Review Status: Internally Peer Reviewed
It has been reported that women account for approximately 30% of the drug-addicted population and the majority of them are of childbearing age. Thus, drug abuse not only affects the mother but may harm the fetus and child.
Clinical manifestations
A. Signs of heroin withdrawal occur in 50-75% of infants born to addicted mothers and usually begin within the first 24-72 h of life.
The incidence of withdrawal depends on several factors, including dosage, duration of addiction, and time of last maternal dose.
Heroin use may be associated with delayed symptomatology up to 7 days, signs from methadone may occur even later.
B. The signs of drug withdrawal may be subtle or overt, consisting of a combination of any of the following:
- Gastrointestinal: Diarrhea, vomiting, ravenous appetite, poor feeding.
- Neurologic: Irritability, jitteriness, restlessness (rubbed knees, rubbed nose), erratic sleeping, fist-sucking, shrill cry, hypertonia, hyperreflexia, myoclonus and less often seizures. The incidence of seizures is higher in methadone-maintained mothers (10-15%) than in those abusing heroin.
- Urinary and/or meconium drug testing should be performed for any baby with signs consistent with neonatal withdrawal.
Treatment
A. Obtain a Social Service consult
B. Swaddling - most infants can be managed in this manner
C. Small, frequent feedings if gastrointestinal signs present
D. Medications
Neonatal Abstinence Scoring Systems exist to assess the severity of withdrawal. However, clinical expertise, rather than a numerical score, should be used in the decision to use medications. Generally, severe irritability interfering with feeding and sleep, vomiting and diarrhea, temperature instability, severe tachypnea, and seizures are indications for treatment.
Drug | Dosage |
---|---|
Phenobarbital | 15-20 mg/kg loading dose, then 3-6 mg/kg/d maintenance |
Paragoric | 3-6 drops q4-6 h PO; if no improvement, increase dose by 1-2 drops. Begin gradual wean after 4-6 days |
Diazepam | 0.2 - 0.5 mg/kg/day dose PO q8h |
Methadone | 0.1 - 0.5 mg/kg/day PO q4-12h |
Duration of treatment in neonatal heroin withdrawal may vary from 4 days to 6 weeks, longer with methadone withdrawal.
Other drugs
Marijuana
- Crosses the placenta, slowly metabolized by fetus
- Higher incidence of tremors and altered visual responses in offspring of heavy users
- No known overt withdrawal
Cocaine
- Vasoconstrictive effects lead to neurologic complications (infarct, IVH, cystic lesions)
- Higher incidence of prematurity, LBW, abruptio placenta
- Associated with higher incidence of genitourinary tract and gastrointestinal anomalies
- Short and/or long term neurobehavioral abnormality
Alcohol
- Acute ingestion: hyperactivity, tremors for 72h, followed by lethargy for 48h
- Chronic ingestion: consider fetal alcohol ingestion and its spectrum of abnormalities including CNS, growth deficiency, facial features, cardiac and musculoskeletal anomalies
Download Neonatal Abstinence Syndrome and Treatment Guidelines
What is Neonatal Abstinence Syndrome?
-
Neonatal withdrawal after intrauterine exposure to certain drugs (illicit or prescription)
-
Occurs with the abrupt cessation of the drug exposure at birth
-
Most commonly seen with opioid exposure, but also seen after exposure to sedatives, polysubstance abuse, and occasionally barbiturates and alcohol • Develops in 55-94% of drug-exposed infants
Jeffrey L. Segar, MD
Peer Review Status: Internally Peer Reviewed
One of the most frequently asked questions of pediatricians, obstetricians and nurses concerns the effect of various drugs taken by the nursing mother on her infant. A comprehensive reference to guide you in your decision as to whether or not a mother receiving a given drug should continue to breast feed will be found in the literature. References include: Roberts, Drug Therapy in Infants (Chapter 11); Briggs, et al, Drugs in Pregnancy and Lactation, 1991; White and White, Breast feeding and Drugs in Human Milk, Vet Human Tox Suppl. I, Vol 22, 1980. There are only a few known categories of drugs which when given to the mother warrant the interruption of breast feeding.
It may be possible to minimize infant drug exposure by instructing the mother to take the medication immediately after completing breast feeding or by collecting breast milk for subsequent feeding just prior to taking medication.
If drug therapy in the mother is to be of short duration, interruption rather than complete termination of breast-feeding should be advised.
The link below leads to a comprehensive database about maternal drugs in breast milk.
Use of Drug Monitoring Levels in the NICU
Jonathan M. Klein, MD, Thomas N. George, MD, and Sarah B. Tierney, PharmD
Peer Review Status: Internally Peer Reviewed - 12/30/21
General guidelines
- Antibiotic dosing and intervals for gentamicin and theophylline should be administered as described in the Iowa Neonatology Handbook. Vancomycin should be dosed at 15mg/kg, at the same intervals as described in the Handbook.
- Antibiotics should be withheld until the level is known, and an order to that effect should be written. If the trough level is greater than acceptable, the drug should not be given and another level checked 6 hours later, and this should be repeated as needed until a safe level is obtained.
- Peak levels are not necessary for patients being treated with a course of antibiotics without an identified organism.
- If a blood culture is positive, and an organism and sensitivities are identified, both peak and trough levels should be obtained to ensure adequate dosing.
- If 10 days of antibiotics are planned, and the first trough level obtained is acceptable, consider repeating the trough levels at 4 to 6 days into therapy to ensure non-toxic levels, especially if there is evidence or concern of impaired renal function.
Gentamicin
- A gentamicin trough level should be obtained within 1 hour of the dose:
Obtain level prior to the administration of the 2nd dose.
If impaired renal function is a concern, a level should be obtained before the 2nd dose.
An acceptable trough is < 2 mcg/ml, with an optimal target ≤ 1.0. - Peak levels are not necessary for patients being treated with a course of antibiotics without an identified organism. If obtained, an acceptable peak is 5 – 12 mcg/ml and should be obtained 30 minutes after the end of a 30 minute infusion or immediately after the end of a 1-hour infusion.
Vancomycin
- A vancomycin trough level should be obtained within 1 hour of the dose:
Gestational age ≥ 30 weeks, obtain level prior to the administration of the 3rd dose.
Gestational age < 30 weeks, obtain level prior to the administration of the 2nd dose.
If impaired renal function is a concern, a level should be obtained before the 2nd dose.
An acceptable trough is < 10 mcg/ml. - Peak levels are not necessary for patients being treated with a course of antibiotics without an identified organism. If obtained, an acceptable peak is 20 – 40 mcg/ml and should be obtained 30 minutes after the infusion.
Theophylline
- Either a trough or peak level will provide adequate information regarding dosing. A theophylline trough level should be obtained 0 - 2 hours before the scheduled dose, and the dose administered without awaiting the result. An acceptable theophylline trough level is 6 – 12 mcg/ml. If obtained, an acceptable peak level is 10 - 20 mcg/ml, and should be obtained between 2 and 4 hours after drug administration.
- Consider writing the theophylline order to reflect times of administration to be at 4 am, 12 pm and 8 pm. This would allow the peak level to be drawn with morning labs if the patient is on a q 8 h schedule.
- When initiating theophylline therapy, serum theophylline levels should be obtained 48-72 hours after the first dose and then weekly for routine levels. This will allow steady-state serum levels to be obtained.
- If concern for toxicity, serum levels may be drawn prior to steady-state to assess the patient’s current progress or evaluate potential toxicity.
Phenobarbital
- A serum concentration should be obtained 30-60 minutes after IV loading dose
- Additional levels should be obtained:
- 4-7 days into therapy (once steady state has been reached) on an unchanged dose
- 2-3 weeks into therapy to verify the concentration is not continuing to increase slowly, leading to delayed toxicity.
- As a control measurement after a change in dose.
- After adding a second drug with a potential for interaction (i.e. valproic acid)
- On-going levels can be drawn any time during dosing interval after steady state due to long half-life.
- If concern for toxicity, serum levels may be drawn prior to steady-state to assess the patient’s current progress or evaluate potential toxicity
- Therapeutic ranges for this drug should be a guide and a therapeutic concentration is one that stops seizure or decreases seizure frequency with acceptable side effects:
- Therapeutic: 15-40 mcg/mL (SI: 65-172 micromoles/L)
- Potentially toxic: >40 mcg/mL (SI: >172 micromoles/L)
Phenytoin/fosphenytoin
- A serum concentration should be obtained 2 hours after IV loading dose.
- Additional levels should be obtained:
- 1-5 days into therapy (once steady state has been reached) on an unchanged dose
- 2-3 weeks into therapy to verify the concentration is not continuing to increase slowly, leading to delayed toxicity
- As a control measurement after a change in dose
- After adding a second drug with a potential for interaction (i.e. amiodarone, azole antifungals, benzodiazepines, calcium channel blockers, PPIs, theophylline derivatives, valproic acid),
- On-going levels should be drawn as follows:
- Oral: pre-dose
- IV: 2 hours post dose
- IM: 4 hours post dose
- A “free-drug” concentration may be clinically useful in neonates with malnutrition, chronic renal failure, or hyperbilirubinemia as more free drug may be available and produce a greater effect than expected.
- If concern for toxicity, serum levels may be drawn prior to steady-state to assess the patient’s current progress or evaluate potential toxicity
- Therapeutic ranges for this drug should be a guide and a therapeutic concentration is one that stops seizure or decreases seizure frequency with acceptable side effects:
- Therapeutic: neonates 8-15 mcg/mL; 10-20 mcg/mL (SI: 40-79 micromoles/L)
- Free (unbound): 1-2 mcg/mL
References:
Lexi-Comp, Inc. Pediatric Drug Information. Accessed online. Updated annually.
Warner A, Privitera M, Bates D. Standards of laboratory practice: antiepileptic drug monitoring. Clinical Chemistry 44:5 (1998) 1085-1095.
Jeffrey L. Segar, MD
Peer Review Status: Internally Peer Reviewed
Purpose: To Determine Patient Drug Kinetic Parameters Enabling Optimal Dosage Selection
When to use:
Drug half-life studies are most valuable in cases of:
A. drug with narrow therapeutic index (little difference between therapeutic and toxic blood levels).B. unpredictable variations in individual pharmacokinetics (i.e., aminoglycosides in neonates).
C. suspected alteration of drug metabolism and/or elimination (renal disease, liver disease, shock, etc.)
How to accomplish accurate T1/2 determination:
In most situations, half-life studies should be done rather than single "peak" or "trough" studies - particularly in situations I.A - I.C above.
A. Blood sampling times should be selected to assure maximum accuracy. This means that one should avoid sampling "too close to the time of administration" (drug still being infused) yet not sample at a time when the concentration of drug may be too low to chemically detect.B. The time interval between sampling should be sufficient to allow the drug concentration to decrease by one-half (i.e., T 1/2). This will avoid errors in "extrapolation". If the patient is known or suspected of having a prolonged T 1/2, the draw times should be greater in interval than the prolonged T 1/2, but not greater than the dosing interval (see recommendation in Table 2).
C. Two or preferably three blood samples should be drawn to assure greatest accuracy.
All information regarding patient's weight, drug dose, dosing interval, time of administration, route of administration, and time blood samples were drawn should be provided. This information will then appear in the chart record and will allow accurate pharmacokinetic calculations to be made.
kel = | ln Co - ln Ct t |
( Co: initial concentration; Ct: concentration after time = t) | |
t 1/2 = | 0.693 kel |
T= log (Cmax/Cmin) x 3.3 x t 1/2 |
(Cmax: maximum concentration after dose) |
Cmin: trough concentration) |
When to do T1/2 studies vs. single time blood level studies
Single blood level determinations have only limited utility since they can be used for dosage adjustment only on a very limited scale. They are useful as a screening procedure to assure that adequate dosing is being accomplished. Drugs with relatively longer half-lives (very little difference in peak and trough levels) can ordinarily be followed by single blood levels determinations.
When a single blood level is used for monitoring the progress of the patient, be sure to select a time which avoids problems of IV delivery time. Generally, a -2-3 hour single time point- following IV administration is best.
Drug | Sampling Time | |
---|---|---|
Digoxin | (1) | 6-8 hrs. post dose |
Phenobarbital | (2) | Time consistent with previous levels (if any) |
Phenytoin | (2) | Depends on formulation |
Theophylline | (3) | 2 hrs. post dose (rapidly dissolving tablet or liquid) |
In general, T 1/2 studies are not absolutely needed until several doses of the drug have been given (1 to 2 days). The exception is the patient with severe organ dysfunction who will require repeated blood level determinations to adjust dosage. In these compromised patients, T 1/2 studies should be done after the first dose and before subsequent dosing. T 1/2 studies only need to be repeated if a marked change occurs in the patient's organ function status.
Selected Dosing Interval (hr.) | Recommended T 1/2 Sampling Times (hr.) | ||
---|---|---|---|
*#1 | #2 | #3 | |
6 | 2 | 3 | 4 |
8 | 2 | 3 | 4-6 |
12 | 2 | 4 | 6 |
*Sampling within 1 hr. of drug administration is likely to be confusing because some drug may still be in the process of being infused or absorbed.
Peak (ug/ml) | Through (ug/ml) | |
---|---|---|
Gentamicin | 5-8 | 1-2 |
Tobramycin | 5-8 | 1-2 |
Kanamycin | 20-25 | 5-10 |
Amikacin | 20-25 | 5-10 |
Chloramphenicol | 20 | 5-15 |
Vancomycin | 25-40 | 5-1 |
Other Resources
Jeffrey L. Segar, MD
Peer Review Status: Internally Peer Reviewed
The cause of apnea should be thoroughly investigated (see Pulmonary section). Only if no treatable cause can be found, the diagnosis of apnea of prematurity can be considered (diagnosis of exclusion). If necessary, central apnea of prematurity may be treated using one of the following drugs.
Agent | Dose | Plasma Concentration (mcg/ml) | Toxicity |
---|---|---|---|
Caffeine citrate | 20 mg/kg IV/PO followed by 5 mg/kg/day may need up to 7.5 mg/kg/d | 5-20 | > 50 mcg/ml (see Theophylline) |
*Theophylline | 5 mg/kg IV followed by 2 mg/kg q 8 - 12 h | 5 - 15 | > 20 mcg/ml Irritability, tachycardia, arrhythmia, seizures |
Doxapram1 | 1 - 2 mg/kg/h IV 12 - 24 mg/kg q 6 h PO |
1-2 | > 5 mcg/ml Hypertension, feeding intolerance, seizures. Contains benzyl alcohol |
1 Further studies needed on bioavailability, toxicity, and long term efficacy. Potential toxicity with vehicle which contains benzyl alcohol. The drug of choice caffeine. If apnea persists despite appropriate doses, doxapram may replace caffeine. If response is still inadequate, both drugs may be combined.
Jeffrey L. Segar, MD, Danielle R. Rios MD, MS, and Sarah B. Tierney, PharmD
Peer Review Status: Internally Peer Reviewed 12/2022
Jeffrey L. Segar, MD and Sarah B. Tierney, PharmD
Peer Review Status: Internally Peer Reviewed
Drug (concentration) and Indication | Dose | Administration / Remarks |
---|---|---|
Adenosine (3 mg/ml) Acute treatment of supraventricular tachycardia |
|
Rapid IV push over 1-2 seconds Flush line immediately with 5-20 ml NS Infuse as close to IV site as possible IO administration also successful |
Atropine (0.1 mg/ml) Bradycardia |
0.02 mg/kg/dose IV | May repeat x 1 dose in 3 minutes |
Calcium gluconate (100 mg/ml)= 9.4 mg elemental calcium /ml Cardia arrest Hypocalcemia |
100 mg/kg/dose IV Not for IM or SQ use |
May repeat x 1 dose, then dose per ionized calcium results Administer by slow IV push for cardiac arrest, infuse over 30-60 minutes for other indications. Stop infusion if HR is greater than 100 bpm. Do not give intra-arterially. |
Dextrose 10% (0.1 Gm/ml) Hypoglycemia Hyperkalemia in combination with insulin |
0.2 Gm/kg/dose IV as D10W Then continuous infusion of D10W at a GIR of 4-8 mg/kg/min. Titrate to attain normoglycemia. | 2 ml/kg of Dextrose 10% Hyperkalemia: Continuous infusion of 0.5 g/kg/hr dextrose and 0.1-0.2 units/kg/hr regular insulin. Dextrose and insulin dosages are adjusted based on serum glucose and potassium concentrations. Abrupt discontinuation of dextrose infusion is not recommended due to the risk of rebound hypoglycemia. Glucose concentrations less than D15 should be administered via a central vein to minimize risk of phlebitis and thrombosis. |
Dopamine To give 10 mcg/kg/min. @ 1 ml/hr : weight x 30 = mg of dopamine (in kg) in 50 ml D5W/NS Hypotension |
Begin at 5 mcg/kg/min. May increase in increments of 2.5 - 5 mcg/kg/min. as needed up to 20 mcg/kg/min. |
Consider if poor peripheral perfusion, evidence of shock, or thready pulses after epinephrine and volume expansion (and bicarbonate) Administer into a central vein when possible. Phentolamine used for treatment of IV infiltrates. |
Epinephrine 1 : 10,000 (0.1 mg/ml) Resuscitation Severe bradycardia Short term use for systemic hypotension |
0.1 - 0.3 ml/kg/dose IV, IO (0.01 – 0.03 mg/kg), - For continuous infusion - start at 0.05 mcg/kg/min to a maximum of 1 mcg/kg/min. |
Rapid IV push followed by 0.5-1 ml NS flush May repeat every 3-5 minutes ALWAYS use the diluted 1:10,000 (0.1 mg/ml) concentration for individual doses. Only use the 1:1,000 (1 mg/ml) for continuous infusion solutions NEVER inject into an artery Do not mix with bicarbonate Effectiveness of drug increases if acidosis is corrected May mix dose volume with 3-5 ml NS Follow ET administration with several positive pressure ventilations. Do NOT administer these higher doses intravenously. |
Fentanyl (50 mcg/ml) Analgesia Sedation Anesthesia |
1 mcg/kg | Consider 10 mcg/ml for doses less than 5 mcg |
Hydralazine (20 mg/ ml) Hypertension by vasodilation |
0.1-0.5 mg/kg | Doses greater than 2 mg; consider 0.4 mg/ml |
Lorazepam (2 mg/ml) Sedation Seizures |
0.05-01 mg/kg | Slow IV push Seizures, may repeat q 10-15 minutes |
Morphine (1 mg/ml) Pain Sedation |
0.05-0.1 mg/kg | Slow IV push over 5-10 minutes, IM, SQ |
Naloxone (1 mg/ml) Narcotic antagonist |
0.1 ml/kg rapid IV push, IM | May repeat in 3 - 5 minutes if no response during resuscitation. Duration of reversal is brief; may need repeated doses. |
Phenobarbital (65 mg/ml) Anticonvulsant |
15 - 20 mg/kg -For refractory seizures- Additional 5 mg/kg doses, up to a total of 40 mg/kg can be given. |
IV push over 10-15 minutes, no faster than 1 mg/min. Drug can be administered by slow IV push, IM, PR, or PO. Diluted IV product can be used orally. |
Sodium Bicarbonate 4.2% (0.5 mEq/ml) Metabolic acidosis |
1 - 2 mEq/kg | Slow IV push over 30 minutes. Use only 0.5 mEq/ml solution for infants Infuse 1 mEq/kg over ≥ 1 minute CAUSTIC; don’t infuse faster than 2 ml/kg/minute. NOT routinely given for resuscitation. Can also be given by continuous infusion, IO, or PO |
Vecuronium ( 1mg/ml) Paralysis Rapid Sequence Intubation* |
0.1 mg/kg | IV push over less than 1 minute |
Volume Expanders RBCs, NS Hypotension Hypovolemia With evidence of acute blood loss or a decrease in effective volume |
RBCs: 15 ml/kg IV NS: 10 ml/kg IV |
RBCs: Infuse over 4 hours NS: Infuse over at least 10 minutes, but preferably over 30-60 minutes. Consider if poor response to resuscitative efforts or weak pulses with a good heart rate |
Jeffrey L. Segar, MD
Peer Review Status: Internally Peer Reviewed
Definition (not fully clear):
- Term infants: > 90/65 mm Hg
- Preterm infants: > 80/45 mm Hg (Liberman)
Management should be directed towards correcting the underlying etiology. It is uncertain whether moderate hypertension associated with bronchopulmonary dysplasia requires therapy, since it is mostly transient. Renovascular hypertension can be managed pharmacologically.
Agent | Dosage | Toxicity |
---|---|---|
Hydralazine | 0.1-0.5 mg/kg/dose q 4-6 h IV | hypotension |
Propranolol | 0.25 - 1.0 mg/kg/day q 6-12 h PO | hypoglycemia, hypotension |
Captopril | 0.05 -0.1 mg/kg/dose q 6-8 h PO | neutropenia, proteinuria, renal failure |
Methyldopa | 10 mg/kg/day q 6-12 h, followed by increments of 5-10 mg/kg/day every 2-4 days up to 65 mg/kg/day | hepatitis, leukopenia |
- Iowa Neonatology Handbook Home
- Cardiology: NICU Handbook
- Feeding: NICU Handbook
- Fluid management: NICU Handbook
- Gastrointestinal: NICU Handbook
- General: NICU Handbook
- Hematology: NICU Handbook
- Infection: NICU Handbook
- Jaundice: NICU Handbook
- Metabolic: NICU Handbook
- Neurology: NICU Handbook
- Pharmacology: NICU Handbook
- Procedures: NICU Handbook
- Pulmonary: NICU Handbook
- Temperature: NICU Handbook