Neonates illness

Drug absorption is highly variable in neonates and infants [21,22]. Older children appear to have absorption patterns similar to adults unless chronic illness or surgical procedures alter absorption. Differences in bile excretion, bowel length, and surface area probably contribute to the reduced bioavailability of cyclosporine seen in pediatric liver transplant patients [22a]. Impaired absorption has also been observed in severely malnourished children [22b]. A rapid GI transit time may contribute to the malabsorption of carbamazepine tablets, which has been reported in a child [23]. Selection of a more readily available bioavailable dosage form, such as chewable tablets or liquids, should be promoted for pediatric patients. 

Ornithine transcarbamylase deficiency. This is the most common of the urea cycle defects. Presentation is variable, ranging from a fulminant, fatal disorder of neonates to a schizophrenic-like illness in an otherwise healthy adult. Males characteristically fare more poorly than do females with this X-linked disorder because of random inactivation (lyonization) of the X chromosome. If inactivation affects primarily the X chromosome bearing the mutant OTC gene, then a more favorable outcome can be anticipated. Conversely, the unfavorably lyonized female has a more active disease. 

Franck L, Vilardi J. (1995). Assessment and management of opioid withdrawal in ill neonates. 

Storosum JG, van Zwieten BJ, Vermeulen HDB, Wohlfarth T et al (2001) Relapse and recurrence in major depression a critical review of placebo-controUed efficacy studies with special emphasis on methodological issues European Psychiatry, 16, ill- i iS Stutchfield P, Whitaker R and Russell I, on behalf of the Antenatal Steroids for Term Elective Caesarean Section (ASTECS) Research Team (2005) Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section pragmatic randomised trial British Medical Journal, 331, 662-667... 

The amount of sample available is very often limited when the patient, often a young child or neonate, is ill. 

Figure 1-2 Transmission electron micrograph of a dividing cell of Escherichia coli 0157 H7 attached to the intestinal epithelium of a neonatal calf. These bacteria, which are able to efface the intestinal microvilli, form characteristic attachments, and secrete shiga toxins, are responsible for -73,000 illnesses and 60 deaths per year in the U. S.10a After embedding, the glutaraldehyde-fixed tissue section was immuno-stained with goat anti-0157 IgG followed by protein A conjugated to 10-nm gold particles. These are seen around the periphery of the cell bound to the O-antigen (see Fig. 8-28). Notice the two microvilli of the epithelium. Courtesy of Evelyn A. Dean-Nystrom, National Animal Disease Center, USD A, Agricultural Research Service, Ames, IA.

E. sakazakii is an opportunistic pathogen that has been associated with food-borne illness in neonates. Only two major serotypes - Ol and 02 have been identified. The two O antigen gene clusters are located between the galF and gnd genes, and both have the Wzx/Wzy pathway (Mullane et al., 2008). 

The safety of benzodiazepines in neonates has been assessed in a retrospective chart review of 63 infants who received benzodiazepines (lorazepam and/or midazolam) as sedatives or anticonvulsants (57). Five infants had hypotension and three had respiratory depression. In all cases of respiratory depression, ventilatory support was initiated or increased. Significant hypotension was treated with positive inotropic drugs in two cases. Thus, respiratory depression and hypotension are relatively common when benzodiazepines are prescribed in these patients. However, both depression and hypotension could also have been due to the severe underlying illnesses and concomitant medications. Matched controls were not studied. 

Seriously ill neonates have reduced clearance and longer elimination half-life... 

Cheung P-Y, Salas E, Etches PC, Phillipos E, Schulz R, Radomski MW (1998) Inhaled nitric oxide and inhibition ofplateletaggr ation in criticdly ill neonates. The Lancet 351 1181-1182. 

Absorption of i.m. administered medications depends on the injection site because perfusion of individual muscle groups differs. For example, drug absorption from the deltoid muscle is faster than that from the vastus lateralis that is more rapid than from the glu-teus. In addition, lower perfusion or hemostatic decompensation, frequently observed in ill neonates and young infants, may reduce i.m. absorption. It may also be decreased in neonates who receive a skeletal muscle-paralyzing agent such as pancuronium because of decreased muscle contraction. In addition, the smaller muscle mass of neonates and young infants provides a small absorptive area. 

A neonate who needed a tracheostomy 10 days after a tracheoesophageal fistula repair was given intravenous lidocaine, 1 mg/kg followed 15-20 minutes later by 0.7 mg/kg. Immediately after, tonic-clonic seizures developed. The child recovered, with no observable ill effects at 6 months. 

Significant hyperbilirubinemia has been reported to occur more frequently in critically ill neonates given pancuronium than in a control group (24). The hyperbilirubinemia increased in the 4 days after withdrawal of pancuronium, whereas during the administration period the hyperbilirubinemia was less in the pancuronium group. 

In newborn infants the benefit of accurate assessment of gestational age by examination of the anterior vascular capsule of the lens and the value of funduscopic examination in ill premature babies must be weighed against the possible risks of the associated increase in blood pressure produced by the pupillary dilators. Since there is no increase in mydriatic effect with repeated instillation or increasing concentration, and their small body mass places premature neonates at increased risk of phenylephrine overdose, it is prudent to use the lowest possible concentration, as well as the most effective combination of mydriatics for indirect ophthalmoscopy in premature infants when such examination is absolutely necessary. The hypertensive effect is likely to be maximal at some time within the first 20 minutes, and whenever possible (or when risk factors are present) the blood pressure should be monitored. 

Rigby-Jones AE, Nolan JA, Priston MJ, Wright PM, Sneyd JR, Wolf AR. Pharmacokinetics of propofol infusions in critically ill neonates, infants, and children in an intensive care unit. Anesthesiology 2002 97(6) 1393-400. 

Premature neonates are reported to have a relative deficiency of vitamin E at birth, which has been associated with hemolytic anemia (16). Since there was an increased incidence of necrotizing enterocolitis when oral tocopherol was given to such infants (7,8,17,18), parenteral tocopherol was for a while recommended for use in very ill neonates (19,20). 

Adland-Davenport, P., Brown, M.P., Robinson, J.D. Derendorf, H.C. (1990) Pharmacokinetics of amikacin in critically ill neonatal foals treated for presumed or confirmed sepsis. Equine Veterinary Journal, 22, 18-22. 

Discordance between total and free magnesium measurements has been reported in selected patient populations, including those with cardiovascular disorders, diabetes meUitus, alcoholism, migraine headaches, asthma, renal transplants, head trauma, and in pregnant women. Interferences, such as that from thiocyanate, in measurement of fr ee magnesium may explain some of these discrepencies. Free magnesium determinations may be helpfiil in others of these disorders and in critically ill patients and during cardiopulmonary bypass, preeclampsia, neonatal distress, and therapy with a number of... 

Limited information on drug action in critically ill and premature neonates... 

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