When monitoring for aminoglycoside toxicity, the nurse pays special attention to the:

Analgesics and Sedatives

Jeffrey L. Segar, MD, 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.

Analgesics and Sedatives

*Treatment of withdrawal (abstinence) from narcotics:

• See [[{"fid":"1866","view_mode":"default","fields":{"format":"default"},"type":"media","link_text":"Neonatal Abstinence Syndrome and Treatment Guidelines under Effects of Drugs on the Fetus or Newborn","field_deltas":{"1":{"format":"default"}},"attributes":{"class":"file media-element file-default","data-delta":"1"}}]]

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

*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

Footnotes:

1. 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.
2. 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.
3. 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.   
4. 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.
5. 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.    
6. 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

Gentamicin peak and trough guidelines1

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

1. Behm-Dillon, DM.  Appropriate Use of Antibiotics: The Antibiotic Advisory Subcommittee and You.  UIHC P&T News; Jan/Feb 2000.  Accessed 10/28/2009. 
2. Gentamicin.  Pediatric Dosage Handbook.  15 Edition. 2008: 819-823.
3. 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.
4. Gentamicin.  Neofax.  2008: 42-43.
5. 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

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

Footnotes

1. 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).
2. 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:

1. Gastrointestinal: Diarrhea, vomiting, ravenous appetite, poor feeding.
2. 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.
3. 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.

Schedule for Treatment of Infant in Withdrawal

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.

https://www.ncbi.nlm.nih.gov/books/NBK501922/?report=classic

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.

A. Determination of T1/2: (First Order)

B. Optimal Dosing Schedule (T):

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.

TABLE 1: RECOMMENDED SINGLE BLOOD LEVEL SAMPLING TIMES

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.

TABLE 2: RECOMMENDED T 1/2 SAMPLING TIMES

*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.

TABLE 3: USUAL THERAPEUTIC RANGE

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.

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 and Sarah B. Tierney, PharmD
Peer Review Status: Internally Peer Reviewed 12/19/12

Footnotes:

• Monitoring serum levels is required.  See “Use of Drug Monitoring Levels in the NICU” for more information. 

References:

• Lexi-Comp, Inc. Pediatric Drug Information.  Accessed online.  Updated annually.
• Thomas Reuters.  Neofax.  24th Edition. 2011. 

Jeffrey L. Segar, MD and Sarah B. Tierney, PharmD
Peer Review Status: Internally Peer Reviewed

Emergency Drug Doses

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.

Pharmacologic Therapy for Neonatal Systemic Hypertension