psd-502 and Methemoglobinemia

Lidocaine and prilocaine are local anesthetics, a class of medications which are frequently used in clinical medicine to minimize pain in a variety of procedures. They are commonly found in over-the-counter products such as topical anesthetic creams advertised to relieve localized muscle and joint pain. While safe and well-tolerated when used appropriately, an overdose of these anesthetics increases the risk for local anesthetic systemic toxicity (LAST), which in severe cases can present with seizures, cardiac dysrhythmias, and ultimately cardiovascular collapse. The reduced muscle mass of pediatric patients puts them at an increased risk of LAST due to the depot effect of the systemically absorbed anesthetic. Methemoglobinemia may also be associated with local anesthetic toxicity. Our case involves a previously healthy 15-month-old female who presented to one of our networks' emergency departments in status epilepticus following an accidental ingestion of a tube of 2.5% lidocaine/2.5% prilocaine cream. Her seizure activity was initially resistant to intraosseous benzodiazepine administration, but ultimately resolved following administration of lipid emulsion and sodium bicarbonate. Additionally, the patient had refractory hypoxia on the monitor which resolved shortly after administration of methylene blue. After stabilization, the patient was transferred to the Pediatric ICU and ultimately made a complete recovery. LAST is a life-threatening presentation which requires early recognition by clinicians, as well as an understanding of the appropriate treatment modalities. We review the assessment and management of LAST, with special focus on the pediatric patient.

Topics: Anesthetics, Local; Child; Female; Humans; Infant; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Prilocaine

With growing awareness of the importance of pain control in all procedures, the use of lidocaine-prilocaine cream (EMLA) for all ages is increasing. Lidocaine-prilocaine cream has been implicated as a cause of methemoglobinemia. Diagnostic clues may be oxygen-resistant cyanosis and an oxygen "saturation gap" between arterial blood saturation and pulse oximetry. Treatment with intravenous methylene blue is often effective. Since EMLA is often mistakenly considered risk-free it is routinely applied by medical staff in the emergency room. Subsequent to the case of EMLA-induced methemoglobinemia in an 8 year old girl we wish to alert the medical community to this phenomenon, and in this work review the relevant literature.

Topics: Anesthetics, Combined; Anesthetics, Local; Child; Cyanosis; Enzyme Inhibitors; Female; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Methylene Blue; Oximetry; Oxygen; Prilocaine

Dentistry has two medications in its pain management armamentarium that may cause the potentially life-threatening disorder methemoglobinemia. The first medications are the topical local anesthetics benzocaine and prilocaine. The second medication is the injectable local anesthetic prilocaine. Acquired methemoglobinemia remains a source of morbidity and mortality in dental and medical patients despite the fact that it is better understood now than it was even a decade ago. It is in the interest of all dental patients that their treating dentists review this disorder. The safety of dental patients mandates professional awareness.

Topics: Anesthesia, Dental; Anesthetics, Combined; Anesthetics, Local; Benzocaine; Enzyme Inhibitors; Hemoglobins; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobin; Methemoglobinemia; Methylene Blue; Nitrous Oxide; Oxidation-Reduction; Oximetry; Prilocaine

Hospitalized preterm infants undergo multiple painful heel lances. A two-phase, randomized, controlled trial was undertaken to determine the safety and efficacy of lidocaine-prilocaine 5% cream (EMLA, Astra Pharmaceuticals, L.P, Westborough, MA) for relieving pain from heel lance. One hundred twenty infants were randomly assigned to receive 0.5 g of EMLA or placebo cream for 30 minutes (Phase 1) or 60 minutes (Phase 2) before a routine heel lance. Efficacy was assessed using the Premature Infant Pain Profile (PIPP). Safety was determined by methemoglobin concentration 8 hours after EMLA application and by clinical signs of methemoglobinemia. No significant differences existed on PIPP scores between EMLA and placebo groups in Phase 1 (p < .480) or Phase 2 (p < .831). No infant had any clinical signs of methemoglobinemia. The mean methemoglobin concentration was 1.19% (.47). Approximately 10% of infants had minor skin reactions, and approximately 20% of EMLA-treated infants had blanching at the application site. The authors conclude that EMLA is safe but not efficacious for relieving pain from heel lance in preterm infants.

Topics: Anesthetics, Combined; Anesthetics, Local; Heel; Humans; Infant, Newborn; Infant, Premature; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Pain; Prilocaine; Punctures

Topics: Anesthetics, Local; Drug Combinations; Drug Eruptions; Drug Hypersensitivity; Hospital Departments; Humans; Infant, Newborn; Infant, Premature; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Ointments; Prilocaine; Punctures

This is the case of a 23-year-old female with a past medical history of ADHD and Depression who was evaluated in the emergency department for perioral cyanosis and hypoxia after application of the eutectic mixture of lidocaine and prilocaine (EMLA) local anesthetic prior to a laser-assisted hair removal procedure. This report illustrates a case of methemoglobinemia which is a rare but significant complication of topical anesthetic use.

Topics: Anesthetics, Local; Female; Hair Removal; Humans; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Young Adult

Prilocaine/lidocaine is widely used as local anesthetic in children for cannulation and minor surgical procedures. Usually it is unproblematic but it is important to adhere to recommended dose to avoid serious complications. Excessive amount of prilocaine/lidocaine, large application area, prolonged application time or repeated application can, especially in infants, cause methemoglobinemia with clinical symptoms. In severe cases intensive care and antidote treatment with Methylene blue may be required. We report three infants who were overdosed with prilocaine/lidocaine, two of them due to incorrect use after circumcision and one premature baby where prilocaine/lidocaine was not removed in time. Two of the babies had MetHb levels > 33% and were seriously affected with hypoxia, tachycardia and fatigue. After Methylene blue was given the infants recovered within 15 minutes and MetHb levels returned to normal.

Topics: Anesthetics, Combined; Anesthetics, Local; Blood Gas Analysis; Drug Overdose; Enzyme Inhibitors; Humans; Infant, Newborn; Lidocaine, Prilocaine Drug Combination; Male; Methemoglobinemia; Methylene Blue

Eutectic mixtures of lidocaine and prilocaine are used during painful dermatological procedures. Poisoning is rarely reported in adults.. We report three cases of women who experienced lidocaine and prilocaine poisoning after laser-assisted hair removal. Plasma levels of local anesthetics were assayed by a fully validated liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method.. The rules of application of the anesthetic cream were observed apart from the maximum dose and/or maximum surface area. One patient applied a higher dose than the maximum recommended dose (140 instead of 60 g) and all patients failed to comply with the maximum recommended surface area (600 cm. Health authorities should publish explicit recommendations targeting users and prescribers with particular emphasis on the maximal surface area of application.

Topics: Anesthetics, Local; Chromatography, Liquid; Female; Hair Removal; Humans; Laser Therapy; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Self Medication; Tandem Mass Spectrometry

A eutectic mixture of lidocaine and prilocaine (EMLA) is used topically to provide local anesthesia for a variety of painful superficial procedures. Although the side effects of EMLA are usually mild and transient local reactions, potentially life-threatening complications can occur. We report a case of generalized seizures and methemoglobinemia after topical application of EMLA for curettage of molluscum contagiosum lesions in a 3.5-year-old girl with atopic dermatitis.

Topics: Administration, Topical; Anesthetics, Local; Child, Preschool; Dermatitis, Atopic; Female; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Molluscum Contagiosum; Prilocaine; Seizures

Topical anesthetics are commonly used in many health care settings and for many clinical conditions. However, there are a number of potential adverse effects associated with their use. Their widespread administration can convey a false sense of security and failure to appreciate possible complications. We present the case of an infant with extensive vascular malformations treated with EMLA cream who developed seizures and methemoglobinemia from lidocaine and prilocaine toxicity. We describe the pathophysiology of these morbidities, the use of pulse oximetry in this setting, and the clinical presentation and treatment of methemoglobinemia.

Topics: Administration, Topical; Anesthetics, Local; Diagnosis, Differential; Female; Humans; Infant; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Port-Wine Stain; Prilocaine; Seizures

The use of creams is considered to be generally safe. However, systemic side effects can occur.. A 22-year-old woman came to the emergency department with dyspnea, confusion and 'blue' skin after laser treatment of the upper legs for excessive hair. She had used three tubes of a eutectic mixture of local anaesthetics (EMLA) cream containing lidocaine/prilocaine for analgesia. Her oxygen saturation was 87%, measured with pulse oximetry. Blood gas analysis showed a concentration of oxy-Hb of 79% and a met-Hb of 19%. Our working diagnosis was methaemoglobinaemia as a result of using excessive amounts of EMLA cream. Because the met-Hb concentration decreased spontaneously and the oxy-Hb concentration consequently normalised, we did not administer methylene blue. The patient was discharged symptom-free after several hours of observation.. An overdose of EMLA cream, whether or not in combination with laser-induced skin damage, can produce a high systemic o-toluidine concentration. This can lead to methaemoglobinaemia. In such cases, the pulse oximeter is not reliable for measuring the oxygen saturation; therefore, blood gas analysis is necessary for making a diagnosis.

Topics: Analgesics; Anesthetics, Combined; Anesthetics, Local; Blood Gas Analysis; Female; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Pain; Prilocaine; Young Adult

Emla(®) cream, a mixture of two local anaesthetics (prilocaine 2.5%, lidocaine 2.5%) has a good benefit-risk profile. However, methaemoglobinaemia can occur, especially when the cream is applied in excessive amounts or over long periods.. The authors report a case of seizure and respiratory disturbances (MetHb=20.1%) after excessive application of Emla(®) (30g) for curettage of molluscum contagiosum in a young girl with eczema. The patient's clinical condition improved after withdrawal of the cream and administration of methylene blue, and she returned home on day two.. This new case of methaemoglobinaemia in a child following application of Emla(®) cream highlights the importance of strict compliance with the instructions for use of this medicinal product.

Topics: Anesthetics, Combined; Child, Preschool; Dosage Forms; Drug Overdose; Female; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Prilocaine

The case of an infant who had received EMLA(R) for local pain therapy after scalding to 5% of the body surface with boiling water is reported. Due to the application of EMLA(R) on the injured skin and exceeding the recommended doses of prilocaine and lidocaine the child developed symptomatic methemoglobinemia. During surgical wound dressing the boy showed cyanosis, decreased peripheral oxygen saturation and potentially suffered a general seizure. With a symptomatic therapy including mechanical ventilation and anticonvulsive drugs the methemoglobinemia normalized within 9 h. The child recovered without any neurological impairment after wound treatment was completed.

Topics: Administration, Topical; Anesthetics, Local; Bandages; Burns; Cyanosis; Diagnosis, Differential; Humans; Iatrogenic Disease; Infant; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Methemoglobinemia; Ointments; Oxygen; Prilocaine; Respiration, Artificial; Tolonium Chloride

To reduce the overall time spent in the ED, triage nurses are encouraged to treat patients with a topical anesthetic cream, eutectic mixture of local anesthetics (EMLA). We present a case in which a 28-day-old neonate who was treated with EMLA cream in triage developed severe methemoglobinemia 18 hours post admission to the pediatric ward. This case demonstrates that there may be some risks associated with this approach, and that protocols for the use of EMLA at triage should include not only the indications for its use, but also need to ensure that there is a process to have the EMLA removed before patient discharge or transfer.

Topics: Administration, Topical; Anesthetics, Local; Emergency Nursing; Enzyme Inhibitors; Female; Humans; Infant, Newborn; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Methylene Blue; Prilocaine; Triage

Topics: Administration, Topical; Adult; Anesthetics, Local; Arrhythmias, Cardiac; Cardiovascular System; Female; Hair Removal; Heart Arrest; Humans; Laser Therapy; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Prilocaine

Topics: Anesthetics, Local; Child; Female; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Prilocaine

This case report illustrates an adult presenting with the simultaneous occurrence of both methemoglobinemia (MetHb) and systemic toxicity from the topical application of local anesthetics while undergoing laser epilation therapy of the legs. The concurrent development of both is considered uncommon in this setting and may have been related to several factors, including her recent previous treatment, increased absorption secondary to abraded skin with the addition of occlusive dressing, and possible alteration of protein binding and drug metabolism due to the use of medications. The clinical manifestations and mechanisms of MetHb and systemic local anesthetic toxicity are discussed.

Topics: Adult; Anesthetics, Local; Female; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Ointments; Prilocaine

High levels of methemoglobinemia can cause tissue hypoxia and cyanosis. We report the case of a 7-month-old girl with pulmonary dysplasia receiving inhaled nitric oxide who had cyanosis caused by methemoglobinemia after prolonged use of a eutectic mixture of local anesthetics cream.

Topics: Administration, Inhalation; Anesthetics, Combined; Anesthetics, Local; Female; Humans; Infant; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Nitric Oxide; Prilocaine; Treatment Failure

We describe a 3-year-old child with mollusca contagiosa whose caregiver applied a eutectic mixture of 5% lidocaine and prilocaine (EMLA) in excessive amounts with the subsequent development of adverse reactions, including methemoglobinemia and hypoxemia. Because of the significant systemic absorption of lidocaine and prilocaine, the patient required overnight admission to the pediatric intensive care unit for close monitoring. A brief description of the proper dosing, pharmacokinetics, and possible side effects of EMLA cream are reviewed.

Topics: Administration, Topical; Anesthetics, Combined; Child, Preschool; Female; Follow-Up Studies; Humans; Hypoxia; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Molluscum Contagiosum; Prilocaine; Risk Assessment

Topical anesthetics remain a powerful, new advance for pain relief prior to cutaneous procedures. They are frequently used by dermatologists to decrease the pain associated with laser pulses, surgical procedures, or soft tissue augmentation. EMLA is the most commonly used agent, however, several new topical anesthetic agents have been released recently that claim increased efficacy and a faster onset of action.. We review and compare the efficacy of several commonly used topical anesthetics and provide a look into the future.. EMLA remains the most widely used topical anesthetic given its proven efficacy and safety by several clinical trials. There has been a recent release of several new topical anesthetic agents with some demonstrating efficacy after a 30-minute application time. A reservoir of anesthetic is located and stored in the upper skin layers during application, providing additional anesthetic benefit 30 minutes after removal. As the options for the practitioner continue to grow, the demand for faster onset, comparative efficacy, and safety trials will continue to be of paramount importance.

Topics: Anesthetics, Local; Drug Combinations; Drug Costs; Gels; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Liposomes; Methemoglobinemia; Ointments; Prilocaine; Tetracaine; Vasoconstrictor Agents

To investigate the effects of the association of inhaled nitric oxide (iNO) and oxidant drugs (acetaminophen, phytomenadione, and EMLA cream) on methemoglobinemia during the neonatal period.. Prospective, randomized, experimental study.. University Experimental Pharmacology laboratory.. Sixty newborn piglets weighing 1.5-2.0 Kg.. Twelve groups of five piglets were anaesthetized, mechanically ventilated, and studied for 3 hrs. Eight groups received iNO (40 ppm or 80 ppm) alone or in association with a single intravenous dose of acetaminophen (120 mg/kg propacetamol), phytomenadione (5 mg vitamin K1) or EMLA cream (2.5 g) applied to the ventral lower abdomen for 3 hrs. Three other groups received, respectively, acetaminophen, phytomenadione, or EMLA cream without iNO. The last group (control group) received neither drugs nor iNO.. Methemoglobinemia was measured before the beginning of each experiment, 30 mins later, and every hour for 3 hrs. There was no significant difference in methemoglobinemia at any time between groups receiving acetaminophen (0.90%+/-0.12%), phytomenadione (0.88%+/-0.11%), or EMLA cream alone (0.97%+/-0.11%) and the control group (0.92%+/-0.12%). At 3 hrs, methemoglobinemia was slightly but significantly increased in group receiving iNO alone (1.04%+/-0.17% at 40 ppm iNO and 1.14%+/-0.16% at 80 ppm iNO; p < .05). Conversely, methemoglobinemia increased as a function of time in groups in which iNO was associated to drug administration and was significantly greater than the control group at 3 hrs (80 ppm iNO + acetaminophen, 2.80%+/-0.47%; 80 ppm iNO + phytomenadione, 2.38%+/-0.45%; 80 ppm iNO + EMLA cream, 2.33%+/-046%; p < .001).. These results demonstrate that if oxidant drugs (acetaminophen, phytomenadione, or EMLA cream) did not increase blood methemoglobinemia in neonatal piglets, their association with iNO caused an increase in methemoglobin. Special care should be taken to monitor methemoglobinemia when iNO is combined to such drugs in newborn infants.

Topics: Acetaminophen; Administration, Inhalation; Animals; Animals, Newborn; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobin; Methemoglobinemia; Nitric Oxide; Ointments; Oxidants; Prilocaine; Prospective Studies; Random Allocation; Swine; Time Factors; Vasodilator Agents; Vitamin K 1

The use of topical lignocaine/prilocaine (EMLA, Astra Pharmaceuticals, North Ryde, NSW, Australia) for pain relief for neonatal circumcision is becoming more prevalent. Because of immaturity of the methaemoglobin reductase pathway, the neonate is vulnerable to methaemoglobinaemia which is a recognized complication of prilocaine therapy. This is the second report of methaemoglobinaemia due to the use of EMLA in association with circumcision during the newborn period.

Topics: Anesthetics, Combined; Anesthetics, Local; Circumcision, Male; Humans; Infant, Newborn; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Methemoglobinemia; Prilocaine

We report on a retrospective analysis of eight episodes of toxic methaemoglobinaemia in seven premature infants after the combined exposure to prilocaine by EMLA cream (12.5 mg prilocaine) and caudal anaesthesia (5.4-6.7 mg/kg prilocaine). The causative relationship between prilocaine and the infants' deterioration came to our attention through an anonymous voluntary incident-reporting system. The highest methaemoglobin concentration found was 30.6% (5.5 h after anaesthesia). All infants were symptomatic (mottled skin, paleness, cyanosis, poor peripheral perfusion) and two were exposed to unnecessary diagnostic and therapeutic procedures for unspecified deterioration in their conditions. Pharmacokinetic evaluation indicated a single compartment first-order elimination with a methaemoglobin half-life of 8 h. Normal levels (<1%) were reached 36 h after exposure to prilocaine.. Whereas local skin application of prilocaine to premature babies is safe, peridural administration is not because premature infants are more sensitive to methaemoglobin inducing agents and tolerate methaemoglobinaemia less well.

Topics: Anesthesia, Caudal; Anesthetics, Local; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Prilocaine; Retrospective Studies; Time Factors

Topics: Anesthetics, Combined; Anesthetics, Local; Child, Preschool; Eczema; Female; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Prilocaine; Seizures

Topics: Anesthetics, Local; Circumcision, Male; Drug Combinations; Humans; Infant, Newborn; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Methemoglobinemia; Ointments; Prilocaine

Topics: Anesthesia, Local; Anesthetics, Combined; Female; Hemangioma; Humans; Infant, Newborn; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Prilocaine; Skin Neoplasms

EMLA cream is an acronym for eutectic mixture of local anesthetics. It contains lidocaine and prilocaine creams. A eutectic preparation, applied topically, penetrates into the dermis after an application period of 1 to 2 hours. This case report describes the successful treatment with EMLA cream of post-herpetic neuralgia, which was resistant to other modes of therapy, and briefly discusses the pharmacology of EMLA cream.

Topics: Administration, Topical; Aged; Anesthetics, Local; Drug Combinations; Female; Herpesviridae Infections; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Neuralgia; Pain Measurement; Prilocaine

Cyanosis associated to low oxygen saturation may reveal hemoglobin pathology.. A 3 year-old child had a nephroblastoma with pleural effusion. He suddenly developed persistent cyanosis despite pleural effusion drainage; transcutaneous and measured oxygen saturations were low and PaO2 on arterial blood gases was high. Methemoglobinemia was diagnosed, due to prilocaine-lignocaine cream used for local anesthesia, associated to partial G6PD deficiency. The methemoglobinemia disappeared after methylene blue treatment.. Cyanosis with low oxygen saturation and high or normal PaO2 should lead to the search of a hemoglobin pathology, especially methemoglobinemia, by appropriate methods.

Topics: Anesthetics, Local; Blood Gas Monitoring, Transcutaneous; Child, Preschool; Drug Combinations; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Methemoglobinemia; Oximetry; Prilocaine

There are insufficient data to support the use of Emla cream for circumcision in newborn infants at this time. There are no studies that adequately address safety or efficacy. Before efficacy studies can be evaluated, pharmacodynamic studies need to be completed. These studies are in progress and are closed (personal communication, Vivian Broach BSPharm, Astra Pharmaceutical Product Information Service, Astra Pharmaceutical, Westborough, MA, June 8, 1995). Subsequent studies should be performed within the first 72 hours of birth and assess the following parameters: (1) serum concentrations of metHb, lidocaine, and prilocaine and its metabolites from time zero to at least 24 hours after application of the cream; (2) application time and dose applied should be varied to assess differences in absorption, as well as onset and duration of analgesia; (3) application technique could be varied to assess the depth of analgesia, that is, application to the inner and outer surface of the prepuce versus the outer surface only. Until these studies are completed, routine use of Emla cream for local anesthesia during circumcision cannot be recommended.

Topics: Anesthetics, Local; Circumcision, Male; Drug Combinations; Humans; Infant, Newborn; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Methemoglobinemia; Prilocaine

A statistically significant (p = 0.049) increase in methemoglobin (MetHb), which did not exceed normal values, was noted 8 h after application of 1 g of EMLA (Eutectic Mixture of Local Anesthetics) to the foreskin of 10 normal newborns to reduce pain associated with circumcision. The highest MetHb concentration observed was 3 g/l (toxic > 50 g/l). No infant showed clinical signs of methemoglobinemia. We conclude that EMLA is safe to use as a local anesthetic in term neonates.

Topics: Analgesia; Anesthetics, Local; Circumcision, Male; Drug Combinations; Humans; Infant, Newborn; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Methemoglobinemia; Prilocaine

Topics: Anesthetics, Local; Drug Combinations; Humans; Infant, Newborn; Infant, Premature; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Ointments; Prilocaine; Risk

Topics: Anesthetics, Local; Drug Combinations; Humans; Infant; Infant, Newborn; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Ointments; Prilocaine

Mild methemoglobinemia is a known side-effect of one of the constituents of EMLA cream, this topical local anesthetic is used with great caution in neonates.. One hundred and sixteen neonates admitted from January to July 1994 in an intensive care unit were included in the study. All required skin punctures which were performed 1 h 30-2 hours after EMLA had been applied on the skin. A reaction score (0 to 5) to skin puncture was established 157 times (120 after and 37 without local anesthesia); methemoglobin (Met Hb) concentrations were measured in 47 blood samples, 18-24 hours (40.4% of samples) or 2-3 days (36.2%) after application of EMLA.. Ninety-four neonates were quiet before puncture (score 0-1). Among them, 57% of those who were given EMLA had a low score (2 or less) vs 18% without EMLA. A low reaction was observed in 65% when the dressings had been kept in place for at least 90 minutes vs 15% with a shorter application. A lower reaction was noted in 78.8% of cases after venopuncture (41% after arterial puncture). No Met Hb level was above 5% and 7 (15%), in five neonates, were between 3 and 5%. There was no clear relationship between methemoglobinemia and gestational age or duration of dressing.. EMLA cream is effective and safe in neonates including preterms, when it is applied in a small amount once a day.

Topics: Administration, Cutaneous; Anesthetics, Local; Dose-Response Relationship, Drug; Drug Combinations; Drug Tolerance; Humans; Infant, Newborn; Infant, Premature; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Ointments; Prilocaine

EMLA (eutectic mixture of lidocaine and prilocaine) cream is currently not recommended for use in infants < 1 month of age because of the potential risk of methemoglobinemia as a result of the o-toluidine metabolite of prilocaine. We studied bioavailability and changes in methemoglobin levels following topical penile exposure to 1 g of EMLA cream for 1 hour in piglets. Lidocaine, prilocaine, and o-toluidine concentrations were measured simultaneously using a high-performance liquid chromatography method. The systemic bioavailability of EMLA was low: 4.0 +/- (SD) 4.7% for lidocaine (range 0-13.6; n = 8) and 7.2 +/- 5.7% for prilocaine (range 0-14.5; n = 8). The ratio between exposure to o-toluidine with EMLA versus intravenous administration (i.e., AUCEMLA/AUCIV; see text) was also low: 4.2 +/- 9.3% (range 0-28.6; n = 9). The mean maximum methemoglobin value after intravenous administration was 1.23 +/- 0.64% (range 0.5-3.0; n = 12) and after penile application 0.99 +/- 0.36% (range 0.5-2.0; n = 12). The methemoglobin value was elevated significantly above baseline after intravenous administration (p = 0.03), but not after penile application of EMLA. These findings suggest that penile administration of 1 g of EMLA may be safe for neonatal circumcision, but further study is required.

Topics: Absorption; Anesthetics, Local; Animals; Animals, Newborn; Circumcision, Male; Cross-Over Studies; Drug Combinations; Injections, Intravenous; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Methemoglobinemia; Ointments; Penis; Prilocaine; Swine; Toluidines

We have measured plasma concentrations of local anaesthetics, and the substance fraction of methaemoglobin (MetHb), in infants less than 3 months of age, after application of a lignocaine-prilocaine cream (EMLA). A total of EMLA 2 g was applied over four different skin areas, totalling 16 cm2, for 4 h before anaesthesia for a minor surgical procedure. Sampling was carried out before and 4, 8 and 12 h after application. Maximum MetHb values (median = 2.24%) were obtained usually at 8 h and were significantly (P less than 0.001) higher than before application (median 1.32%). The plasma concentrations of local anaesthetics were low (maximum values: prilocaine 78 ng ml-1, lignocaine 412 ng ml-1). The activity of erythrocyte MetHb reductase (cytochrome b5 reductase) was analysed. Data from a previously studied group of infants aged 3-12 months were included also. Enzyme activity did not reach adult levels until after the age of 3 months. It showed a good inverse correlation with the maximum MetHb values after application of EMLA. Although the MetHb concentrations in the infants younger than 3 months were small, the enzyme capacity may be overloaded when EMLA is administered at the same time as other MetHb-inducing agents. It is concluded that the use of EMLA should be restricted in this age group.

Topics: Age Factors; Anesthetics, Local; Cytochrome-B(5) Reductase; Drug Combinations; Erythrocytes; Female; Humans; Infant; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Methemoglobinemia; NADH, NADPH Oxidoreductases; Prilocaine

Topics: Anesthetics, Local; Child; Child, Preschool; Drug Combinations; Humans; Infant; Lidocaine; Lidocaine, Prilocaine Drug Combination; Methemoglobinemia; Prilocaine; Time Factors