Pharma Voice

Administering drugs in neonates

Deepak Patra and Chanchal Mishra enumerate neonatal routes of drug administration.

The choice of the appropriate route for administering drugs in any situation depends on the drug as well as on the doctors. Common sense, feasibility and convenience dictate the route to be used.

Factors governing choice of route

The ability of the neonate to digest, absorb and metabolise foods is similar to that of the older child but there are some differences in the route of administration. Some factors which govern the choice of route are:

• The physical and chemical properties of the drug (such as whether it is in a solid, liquid and gaseous state, its solubility, stability, pH and irritancy)
• Whether the site of desired action is localised and approachable or generalised and not approachable
• The rate and extent of absorption of the drug from different routes
• The effect of digestive juices and first pass metabolism of the drug
• The rapidity with which the response is desired (routine treatment or emergency)
• The accuracy of dosage required (IV and inhalation routes can offer fine tuning)
• The condition of the patient (if he is unconscious or vomiting)

Local routes

Local routes are used only for localised lesions at accessible sites. Thus high concentrations are attained at the desired site without exposing the rest of the body. These include:

Topical: External application of the drug to the surface for localised action. This route is convenient as well as encouraging to the patients.

Deeper tissues: Certain deep areas can be approached by using a syringe and needle, but the drug should be such that systemic absorption is slow. This method comprises intra-articular injection, intrathecal injection and retrobulbar injection.

Arterial supply: Close intra-arterial injection is used for contrast media in angiography; anti-cancer drugs can be infused in femoral or brachial artery for limb malignancies.

Systemic routes

Systemic routes are used when the drug is intended to be absorbed into blood and distributed all over, including the site of action, through circulation.

Oral route: Oral medication is clearly unsuitable for babies who are shocked, acidotic or otherwise obviously unwell because there is a real risk of paralytic ileus and delayed absorption.

Antibiotics can be given orally to any baby who is well enough to take milk feed without detrimental effects. Recommended drugs include amoxicillin, ampicillin, Cephalexin, chloramphenicol, ciprafloxacin, erythromycin, flucloxacillin, fluconazole, flucytosine, isoniazid, metronidazole, rifampicin, sodium fusidate and trimethoprim.

This administration is much more easily managed on postnatal wards. Small quantities are best given from a dropper bottle (avoiding touching the tongue with the pipette) or dropped on to the back of the tongue from the nozzle of a syringe.

Rectal administration: This is a useful way of giving a drug that is normally given orally, to a baby who is not being fed. Choral hydrate, cisapride, codeine phosphate and paracetamol are sometimes given this way. Suppositories have usually been used in the past (merely because that is how rectal drugs are normally given to adults) but liquid formulations are more appropriate here, as absorption is always more rapid and often more complete when a liquid formulation is used. Along with sub-lingual or buccal routes, cutaneous, inhalation and nasal approaches are also systemic routes but they are less or negligibly used in neonatal administration. Parenteral IV drugs should be given slowly and, where possible, through a secure established IV line containing dextrose or sodium chloride.

Procedures for parenterals

Parenteral preparations may be given by various routes like intravenous, intraspinal, intramuscular, subcutaneous and intradermal. Intravenous and intraspinal preparations are rarely given in a form other than aqueous solutions. The chemical and physical properties of a drug must be determined, its drug interactions and desired excipients, and the effect of each step of the process on its stability must be studied and understood.

Continuous IV infusions: Drugs for continuous infusion such as adrenaline, diamorphine, dobutamine, dopamine, doxapram, glyceryl trinitrate, hydrocortisone, insulin, isoprenaline, labetalol, lidocaine, magnesium sulphate, morphine, noradrenaline, nitroprusside, streptokinase and tolazoline should be administered from a second carefully labelled infusion pump connected by a three-way tap into the main infusion line.

Remember to readjust the total fluid intake. Great care is needed to ensure that patients never receive even accidentally a brief surge of one of the vasoactive drugs and the same is true of many inotropes.

Never load the syringe or burette with more of the drug than is likely to be needed in 12-24 hours, to limit the risk of accidental over-infusion.

Intra muscular administration: This is more reliable than oral medications in a baby who is unwell but drug release from the IM "depot" is sometimes slow (a property that is used to advantage during treatment with naloxone, procaine, penicillin and vitamin K). It may also be unreliable if there is circulatory shock. The anterior aspect of the quadriceps muscle in the thigh is the only safe site in a small-waisted baby and only this side should be used.

The main hazard of IM medications is the risk that the injection will accidentally damage a major nerve. Small babies have little muscle bulk and the sciatic nerve is easily damaged when drugs are given into the buttock.

IM injection should be avoided in any patient with a severe bleeding tendency. With certain drugs, such as bupivacaine, the accidental injection of drug into a blood vessel during deep tissue infiltration is toxic to the heart.

Intrathecal and intra-ventricular routes: Streptomycin was the first effective anti-tuberculous drug because it does not cross the blood-brain very well. A policy of repeated intrathecal injection soon evolved to cope with the scourge of tuberculous meningitis.

The intrathecal dose is always much smaller than the IV or IM dose because of the smaller volume of distribution. Gentamycin is still sometimes given to the cerebral ventricles, but the only published controlled trial suggests that children so treated actually did worse than those given standard IV treatment. Many antibiotics are irritant and preservatives even more so. Dilute the preparation before use and check there is free flow of CSF before injecting the drug.

Intraosseous administration: This can be a valuable way of providing fluids in an emergency. Drugs that can be given intravenously can also be given by this route. Insert the needle into the upper end of the tibia a little below the tuberosity, using a slight screwing action, until marrow is entered.

Point the needle obliquely and away from the knee joint. An 18-gauge bone marrow needle is best, but success can be achieved with a 21-gauge lumbar puncture needle and stylet. The only common complication is osteomyelitis.

Final choice

Each route of drug administration has its pros and cons. Oral medication is suitable for neonates and IM administration is reliable but in some cases it cannot be used. Rectal administration is a useful way of giving a drug that is normally given orally to a baby. Parenteral IV drugs should be given slowly; and intraosseous administration provides fluid in emergencies.

(The writers are from the Ranchi College of Pharmacy, Hatia, Ranchi)