Perinatal asphyxia and inadvertent neonatal intoxication from local an
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《英国医生杂志》
1 Department of Paediatrics, Anna Meyer Children's Hospital, Via L Giordano 13, 50132 Florence, Italy, 2 Laboratory of Toxicology, Careggi Hospital, Via Pieraccini 17, Florence, Italy
Correspondence to: Maria Serenella Pignotti m.pignotti@meyer.it
Introduction
Local infiltration of the perineum and cream application to the skin around the perivaginal skin are simple and common techniques for pain relief from episiotomy. Small amounts of the anaesthetic are thought to reach the fetus because of the short interval between local infiltration and delivery.2
Intoxication of newborns by lidocaine given to the mother during delivery was first described by Sinclair and colleagues in 1965.3 Detailed clinical features including apnoea, hypotonia, seizures, and cardiac symptoms such as bradycardia or ventricular tachycardia were reported in 1991.4 Other specific typical signs are dilated pupils fixed to light and eyes fixed in the "doll's eye manoeuvre" (oculocephalic reflex).5 Such toxic effects have been described with lidocaine levels as low as 3μ/ml,6 which are very close to the levels found in cord blood of normal neonates.2 6 Diagnosis is confirmed by determining anaesthetic levels in liquor, blood, and urine.
In our two cases the neonates developed symptoms of intoxication at different times, probably because of different types of absorption. In the first case the blood specimen showed high lidocaine levels and the urine specimens showed growing levels of lidocaine and prilocaine over the next two days, with the appearance of metabolites. As no lidocaine injections were reported in the medical record we assume that the drug was absorbed transcutaneously. This kind of absorption was indisputable for prilocaine because this drug is available in Italy only as a cream. In the second case the first blood specimen showed high levels of mepivacaine, which could have reached the fetus via placental transfer or via injection inadvertently directed into the fetal scalp, with levels decreasing over the next three days.
In both cases the clinical pictures were not typical for intrapartum asphyxia. The slight acidosis soon after birth or later, after cardiorespiratory resuscitation, was not a sufficient basis for an experienced clinician to justify the seizures. Hypoxic-ischaemic encephalopathy is not usually associated with a period without symptoms soon after birth in a neonate with a high Apgar score (case 1) before the onset of hypotonia, tonic seizures, arrest of spontaneous respiration, or with fixed dilated pupils and eyes fixed in the oculocephalic reflex.4 All these signs can be assumed to be caused by intoxication from local anaesthetic.
Both neonates arrived at our neonatal intensive care unit with a diagnosis of acute perinatal asphyxia, which was not consistent with the clinical picture above. Only the suspicion of involvement of other pathogenetic factors (such as neonatal intoxication) led us to make a correct diagnosis. Delay of appropriate treatment may worsen the outcome, and the medicolegal aspect of "unexplained perinatal asphyxias" can be ruled out with appropriate diagnosis. High levels of anaesthetic in blood, urine, and cerebrospinal fluid are essential for the diagnosis. If neonatal intoxication is suspected, an early urine specimen for toxicology screening is the cheapest and easiest way to secure a correct diagnosis. More studies are needed to understand how often this kind of aetiology occurs in neonatal encephalopathy.
More information about the toxicology screening used is on bmj.com
Do not assume that every case of neonatal encephalopathy is due to perinatal asphyxia
Contributors: MSP conceived, analysed, and drafted the paper. GI drafted the paper and discussed core ideas. RC performed laboratory tests and took part in discussions about data. GD supervised the clinical research, coordinated and drafted the paper, and discussed the results; he is also the guarantor.
Funding: None.
Competing interests: None declared.
References
Edwards AD, Nelson KB. Neonatal encephalopathies. BMJ 1998;317: 1537-8.
Philipson EH, Kuhnert BR, Syracuse CD. Maternal, foetal and neonatal lidocaine levels following local perineal infiltration. Am J Obstet Gynecol 1984;149: 403-7.
Sinclair JC, Fox HA, Lentz JF, Murphy J. Intoxication of the fetus by a local anesthetic. A newly recognized complication of maternal caudal anesthesia. N Engl J Med 1965;273: 1173-7.
De Praeter C, Vanhaesebrouck P, de Praeter N, Govaert P, Bogaert M, Leroy J. Episiotomy and neonatal lidocaine intoxication. Eur J Pediatr 1991;150: 685-6.
Volpe JJ. Neonatal seizures. Neurology of the newborn. 4th ed. Philadelphia: Saunders, 2001: 178-214.
Walson PD, Ott MA, Carter DE. Lidocaine and mepivacaine in cord blood. Pediatr Pharmacol 1982;2: 341-8. (Accepted 8 September 2004)(Maria Serenella Pignotti, neonatologist1)
Correspondence to: Maria Serenella Pignotti m.pignotti@meyer.it
Introduction
Local infiltration of the perineum and cream application to the skin around the perivaginal skin are simple and common techniques for pain relief from episiotomy. Small amounts of the anaesthetic are thought to reach the fetus because of the short interval between local infiltration and delivery.2
Intoxication of newborns by lidocaine given to the mother during delivery was first described by Sinclair and colleagues in 1965.3 Detailed clinical features including apnoea, hypotonia, seizures, and cardiac symptoms such as bradycardia or ventricular tachycardia were reported in 1991.4 Other specific typical signs are dilated pupils fixed to light and eyes fixed in the "doll's eye manoeuvre" (oculocephalic reflex).5 Such toxic effects have been described with lidocaine levels as low as 3μ/ml,6 which are very close to the levels found in cord blood of normal neonates.2 6 Diagnosis is confirmed by determining anaesthetic levels in liquor, blood, and urine.
In our two cases the neonates developed symptoms of intoxication at different times, probably because of different types of absorption. In the first case the blood specimen showed high lidocaine levels and the urine specimens showed growing levels of lidocaine and prilocaine over the next two days, with the appearance of metabolites. As no lidocaine injections were reported in the medical record we assume that the drug was absorbed transcutaneously. This kind of absorption was indisputable for prilocaine because this drug is available in Italy only as a cream. In the second case the first blood specimen showed high levels of mepivacaine, which could have reached the fetus via placental transfer or via injection inadvertently directed into the fetal scalp, with levels decreasing over the next three days.
In both cases the clinical pictures were not typical for intrapartum asphyxia. The slight acidosis soon after birth or later, after cardiorespiratory resuscitation, was not a sufficient basis for an experienced clinician to justify the seizures. Hypoxic-ischaemic encephalopathy is not usually associated with a period without symptoms soon after birth in a neonate with a high Apgar score (case 1) before the onset of hypotonia, tonic seizures, arrest of spontaneous respiration, or with fixed dilated pupils and eyes fixed in the oculocephalic reflex.4 All these signs can be assumed to be caused by intoxication from local anaesthetic.
Both neonates arrived at our neonatal intensive care unit with a diagnosis of acute perinatal asphyxia, which was not consistent with the clinical picture above. Only the suspicion of involvement of other pathogenetic factors (such as neonatal intoxication) led us to make a correct diagnosis. Delay of appropriate treatment may worsen the outcome, and the medicolegal aspect of "unexplained perinatal asphyxias" can be ruled out with appropriate diagnosis. High levels of anaesthetic in blood, urine, and cerebrospinal fluid are essential for the diagnosis. If neonatal intoxication is suspected, an early urine specimen for toxicology screening is the cheapest and easiest way to secure a correct diagnosis. More studies are needed to understand how often this kind of aetiology occurs in neonatal encephalopathy.
More information about the toxicology screening used is on bmj.com
Do not assume that every case of neonatal encephalopathy is due to perinatal asphyxia
Contributors: MSP conceived, analysed, and drafted the paper. GI drafted the paper and discussed core ideas. RC performed laboratory tests and took part in discussions about data. GD supervised the clinical research, coordinated and drafted the paper, and discussed the results; he is also the guarantor.
Funding: None.
Competing interests: None declared.
References
Edwards AD, Nelson KB. Neonatal encephalopathies. BMJ 1998;317: 1537-8.
Philipson EH, Kuhnert BR, Syracuse CD. Maternal, foetal and neonatal lidocaine levels following local perineal infiltration. Am J Obstet Gynecol 1984;149: 403-7.
Sinclair JC, Fox HA, Lentz JF, Murphy J. Intoxication of the fetus by a local anesthetic. A newly recognized complication of maternal caudal anesthesia. N Engl J Med 1965;273: 1173-7.
De Praeter C, Vanhaesebrouck P, de Praeter N, Govaert P, Bogaert M, Leroy J. Episiotomy and neonatal lidocaine intoxication. Eur J Pediatr 1991;150: 685-6.
Volpe JJ. Neonatal seizures. Neurology of the newborn. 4th ed. Philadelphia: Saunders, 2001: 178-214.
Walson PD, Ott MA, Carter DE. Lidocaine and mepivacaine in cord blood. Pediatr Pharmacol 1982;2: 341-8. (Accepted 8 September 2004)(Maria Serenella Pignotti, neonatologist1)