Topical use of local anesthetics in neonates.

INTRODUCTION: Various local anesthetics as in lidocaine ointment, amethocaine cream and EMLA cream are used topically for minor invasive interventions, such as venipuncture, both in children and adults. Since neonates have a nervous system that, albeit immature, enables them to feel pain, analgesia for these procedures is also indicated. Several studies in neonates have been carried out to establish effectiveness and safety of topically applied local anesthetics. These studies are reviewed in order to assess effectiveness and safety. METHODS: A Medline search was made in order to review all studies on effectiveness and safety of topical use of local anesthetics in neonates. Effectivity or safety studies using local anesthetics for circumcision were rejected. RESULTS: Seven studies on effectiveness were found: Three studies examined lidocaine ointment and four examined EMLA cream. Effectiveness of lidocaine ointment was questionable in two studies and negative in one. Effectiveness of EMLA cream was positive in two studies and negative in the other two. Four studies were found on safety of EMLA cream. All studies indicated that use of EMLA cream was safe. DISCUSSION: The poor effectiveness found in the reviewed studies is possibly due to too long an application time, a lipophilic carrier used and difficulties in assessing pain. The time of application is often based upon studies in children. Since the skin of neonates acts more as a mucosa than as mature skin the local anesthetics are able to cross this barrier more rapidly. Also a high bloodflow in the heel enhances the uptake of the drug. The application time in neonates should therefore be reduced compared to children. The use of a lipophilic carrier should be avoided since a lipophilic carrier impedes the local anesthetic to be absorbed, leading to reduced effect. Various methods of pain assessment were being used. Since not all methods used are validated it is difficult to obtain an objective end point. CONCLUSION AND RECOMMENDATION: The articles reviewed are non conclusive in their results of effective analgesia. Due to a lipophilic base form and a hydrophilic matrix EMLA cream is most effective. An application time of 30 minutes is recommended. In spite of the present precautions due to fear of methemoglobinemia, use of EMLA cream proved to be safe when used once a day. Since the clinical situation often requires more than one application a day, more research is needed to establish a safe and effective local anesthetic which can be applied topically several times a day in the neonate.

Long-term stability of morphine and bupivacaine mixture for spinal use.

From clinical studies it has been proven that morphine in combination with bupivacaine is applicable in cancer pain. The availability of a ready to use parental dosage form of morphine and bupivacaine is comfortable for health care workers. Stability of a morphine or a bupivacaine preparation or a combination of both in a PVC cassette or polypropylene syringe for spinal use is examined in several studies. Apart from one study no data on long-term stability of morphine-bupivacaine mixture is available. A forced degradation study and a shelf-life study at room temperature (20-25 degrees C) were started on morphine hydrochloride 0.2 mg/ml and bupivacaine hydrochloride 7.5 mg/ml in 50 ml sterilized glass bottles type II. The results of the stability study showed that this mixture was stable up to 18 months at room temperature, whereafter morphine showed a slight degradation (5%) and bupivacaine remained stable.