Toxic Additives in Medications for Preterm Infants
To date, we have had little information regarding the extent to which preterm infants are exposed to excipients via oral medications. Pharmaceutical excipients are inactive substances, such as binders, fillers, solvents, flavorings, colorings, or preservatives, that are included in the manufacturing process or contained in the finished product. These sometimes toxic additives are commonplace in liquid formulations of medications administered to preterm infants.
A recent exploratory study from the United Kingdom1 quantified excipient exposure in 38 preterm infants younger than 30 weeks' gestational age and birth weight of less than 1500 g. Throughout their NICU stay, these infants were exposed to more than 20 different excipients, including ethanol and propylene glycol (chemicals associated with neurotoxicity in humans), and concentrations of sorbitol in excess of recommended guidelines for maximum exposure in adults. Infants with chronic lung disease were exposed to higher concentrations of these toxic additives.
Iron, vitamin, and mineral supplements, along with drugs such as furosemide and dexamethasone, were among the agents that produced either chronic, low-level exposure, or episodic, high-level exposure to toxins such as ethanol. Although this investigation did not establish a clinical link between outcomes and excipient exposure, it does have important clinical implications. Toxic excipients could be a factor in the adverse neurological outcomes often seen in this population. The toxicity of an active drug could be exacerbated by the concurrent administration of ethanol in the oral formulation.
The article offers no immediate solutions but is thought-provoking and defines an issue of importance to neonatal caregivers.
Reference
1. Whittaker A, Currie AE, Turner MA, Field DJ, Mulla H, Pandya HC. Toxic additives in medications for preterm infants. Arch Dis Child Fetal Neonatal Ed. 2009;94:F236-F240. [Context Link]
Forgoing Nutrition and Hydration in Children at the End of Life
When the burdens associated with artificial means to sustain life-ventilators, resuscitation, and critical care medications-outweigh the benefits to the child near the end of life, there is a consensus that withdrawing or withholding these interventions is morally permissible. In adults, this consensus extends to the withholding of medically administered nutrition and hydration when it no longer benefits the patient.
In terminally ill children, however, the decision to withhold or withdraw nutrition or fluids can be more difficult to accept because of the emotional power and symbolism associated with feeding as a basic element in the care of a child. Healthcare providers may be uncertain about the ethical and legal ramifications of such a decision.
A recent report from the Committee on Bioethics of the American Academy of Pediatrics1 summarizes the medical, social, ethical, and legal issues involved in decisions to withhold or withdraw medically provided nutrition and hydration from children who lack decision-making capacity. The focus is on children who depend on fluids and nutrition delivered through medical means for survival, not on children who are hungry and thirsty and are capable of eating and drinking.
The bottom line is that medically provided fluids and nutrition represent medical interventions similar to other types of support and have the same potential for adverse effects and discomfort. The report concludes that it is ethically permissible to withdraw medically provided fluids and nutrition from children in selected circumstances. Consideration of burdens and benefits is the correct approach to determine the appropriateness of continuing to provide nutrition and hydration. The report provides several scenarios in which the burdens of treatment outweigh the benefits. The roles of both parents and healthcare providers in the decision-making process are described.
Reference
1. Diekema DS, Botkin JR, The Committee on Bioethics. Clinical report-forgoing medically provided nutrition and hydration in children. Pediatrics. 2009;124:813-822. [Context Link]
Platelet Transfusions in the NICU
Neonatal thrombocytopenia is a common problem, and in the absence of symptoms (bleeding, oozing, and bruising), it is often managed with prophylactic platelet transfusions. Although platelet transfusions are clearly of benefit to the neonate who is actively bleeding, the need for frequent prophylactic platelet transfusions in stable, nonbleeding infants has been questioned. Platelet transfusions, which do carry risks, are usually given when an infant's platelet count falls to a predetermined low level, such as 20 x 109/L in a stable infant, a figure based not on evidence, but on expert consensus.1
A study by Gerday and colleagues,1 published in the journal Transfusion, considered the possibility of using platelet mass (platelet count multiplied by platelet volume) rather than platelet count alone to determine the need for a transfusion. Platelet mass confers the ability to stop bleeding by generating a platelet plug, possibly because larger platelets are younger and qualitatively superior.
Investigators compared the number of platelet transfusions given when clinicians used platelet count as a guideline with the number of transfusions given when platelet mass was the deciding factor. The number of transfusions given when platelet mass-based guidelines were used was significantly lower, a reduction that was accounted for by fewer prophylactic platelet transfusions. Furthermore, there was no increase in bleeding of any type when transfusions were guided by platelet mass. Fewer platelet transfusions, regardless of the reason, did not result in more bleeding episodes.
Because this study was nonrandomized and relatively small, the researchers suggest that additional evidence through replication is warranted. Fewer NICU transfusions not only are cost-effective but also signify better transfusion practice.
Reference
1. Gerday E, Baer VL, Lambert DK, et al. Testing platelet mass versus platelet count to guide platelet transfusions in the neonatal intensive care unit [published online ahead of print June 23, 2009]. Transfusion. _02253 1.6 [Context Link]
Ibuprofen Increases Bilirubin Levels
Ibuprofen, a cyclooxygenase inhibitor, is often used for medical closure of the patent ductus arteriosus in preterm infants. There are known drawbacks to the use of ibuprofen, however, including competition with unbound bilirubin for albumin binding sites, and for enzymes in the hepatic glucuronidation pathway. The result is an increase in circulating bilirubin levels, which, superimposed on the already-elevated total serum bilirubin (TSB) of the preterm infant, potentially raises the risk for bilirubin encephalopathy.
In a retrospective cohort study, Zecca and colleagues1 compared bilirubin levels in a group of preterm infants who received ibuprofen with those in a group of infants who did not. Management of jaundice was identical and consistent in the 2 groups. They found that the ibuprofen-treated infants had significantly higher peak TSB levels, more need for phototherapy, and a longer duration of phototherapy than those of the non-ibuprofen-treated infants.
The neurological effects of the ibuprofen-induced elevation of bilirubin, in conjunction with preexisting bilirubinemia, are unknown. However, the difference between safe and harmful bilirubin levels is likely to be small in preterm, very low birth-weight infants. It is conceivable that the increase in TSB (and therefore, unbound bilirubin) attributable to ibuprofen therapy could reach a threshold value associated with neurological damage. The effect of ibuprofen on bilirubin level has been compared with that of sulfisoxazole, a drug that is contraindicated in the newborn because of its ability to displace bilirubin from albumin and cause kernicterus in the newborn with hyperbilirubinemia.2
Reference
1. Zecca E, Romagnolli C, Pia De Carolis M, Costa S, Marra R, De Luca, D. Does ibuprofen increase neonatal hyperbilirubinemia? Pediatrics. 2009;124(2):480-484. [Context Link]
2. Ahlfors CE. Effect of ibuprofen on bilirubin-albumin binding. J Pediatr. 2004;144:386-388. [Context Link]
Influenza in Mothers and Newborns
Most experts predict that the 2009 to 2010 influenza season will be severe. Dr Margaret Chan of the World Health Organization estimates that one-third of the world's population could be stricken with the 2009 H1N1 virus. Although influenza-related illness in most people is expected to be mild, some individuals are at high risk of serious illness or death if they become infected.
One of these high-risk groups is pregnant women and their newborn infants. Severe illness among pregnant women and their newborn infants has been reported during the current outbreak of novel H1N1 influenza. Adverse pregnancy outcomes from previous influenza pandemics include increased rates of spontaneous abortion and preterm birth. Illness can progress rapidly in pregnant women and can be complicated by secondary bacterial infections including pneumonia. Fetal distress associated with severe maternal illness can occur. Pregnant women are a priority for influenza vaccination to protect both themselves and their unborn babies.
Pregnant women who have symptoms compatible with influenza (fever, cough, sore throat, and headache) should be tested for influenza. However, treatment should not be delayed pending results of testing, because antiviral treatment is most effective within 48 hours after onset of symptoms. Treatment with antiviral medications is recommended for pregnant women with suspected influenza. The currently circulating novel influenza A (H1N1) virus is sensitive to the neuraminidase inhibitor antiviral medications zanamivir (Relenza) and oseltamivir (Tamiflu). Oseltamivir is given orally and results in systemic absorption; thus, it is the drug of choice for treatment of influenza in pregnant women. By contrast, zanamivir is given by inhalation and results in lower systemic absorption, making it the drug of choice for prophylaxis in the influenza-exposed pregnant woman. In addition, fever should be treated in pregnant women because of potential harm to the fetus.
Infants are thought to be at higher risk for severe illness from novel influenza A (H1N1) infection, and little is known about prevention of novel H1N1 flu infection in infants. There is no guarantee that the newborn will not become infected, but the risk can be reduced by following these guidelines1:
* Isolate the ill mother following delivery.
* The mother should avoid close contact with the infant until she has received antiviral medication for 48 hours, fever has resolved, and secretions can be controlled.
* The mother can pump her breast milk, which is fed by a healthy individual to the newborn by bottle. Antiviral medication is not a contraindication to breastfeeding.
* After 48 hours (and all conditions are met), the mother can hold or feed the infant while wearing a facemask and clean gown, and observing strict cough etiquette and hand hygiene. These precautions should be continued for 7 days and until the mother is symptom-free for 24 hours.
* The newborn is potentially infected if delivery occurs during the 2 days before through 7 days after illness onset in the mother. Observe the newborn closely for signs of influenza.
* If the newborn tests positive for influenza, treatment should be considered. Oseltamivir is approved for prevention of influenza in patients 1 year of age and older; however, an emergency use authorization has been issued for oseltamivir for influenza treatment and prevention in patients younger than 1 year.2
Reference
1. Centers for Disease Control and Prevention. Pregnant women and novel influenza A (H1N1) virus: considerations for clinicians. http://www.cdc.gov/h1n1flu/clinician_pregnant.htm. Published June 30, 2009. Accessed September 16, 2009. [Context Link]
2. Centers for Disease Control and Prevention. Emergency use authorization review oseltamivir phosphate for swine influenza A. http://www.cdc.gov/h1n1flu/eua/tamiflu.htm. Accessed September 16, 2009. [Context Link]
An Online Healthcare Innovations Exchange
Despite being connected more than ever before, new ideas can travel slowly and sometimes even fail to go beyond the walls of the institution where they were born.1 That is why the Association for Healthcare Research and Quality's "Innovations Exchange" is such a valuable resource for busy clinicians.
Based on the concept that we should not waste our time "reinventing the wheel," the Innovations Exchange is a central repository of solutions to clinical problems and successful approaches in the delivery of healthcare, but it is far more than a list of great ideas. The innovations are searchable by subject and healthcare setting and include complete profiles of successful (and attempted) approaches, their impact, and how the innovators developed and implemented them. Other resources include expert commentaries, articles, perspectives, quality tools, and opportunities to network with other healthcare professionals.
The Innovations Exchange is used by a variety of healthcare professionals, from nurses and physicians to educators, researchers, and policy makers. More than one-third of its users are nurses. Detailed information about how to submit an innovation is provided at the Web site.1 Here are some recent submissions to the Innovations Exchange:
* Remote viewing of NICU babies by mother promotes bonding, potentially improves infants' long-term outcomes.
* Nurse Home Visitation Program reduces readmissions, emergency department visits, child abuse, and foster home placements for medically fragile infants.
* Noise alert system helps staff and visitors to reduce decibel levels in neonatal intensive care unit.
* Standardized protocol reduces likelihood of pneumothorax and death in low birth-weight infants.
Reference
1. Association for Healthcare Research and Quality. Innovations Exchange. http://www.innovations.ahrq.gov/index.aspx. Accessed September 20, 2009. [Context Link]