Lewis Nelson, MD

Case

A 50-year-old man ingests two handfuls of small, red berries that he picked from a shrub in front of his apartment building, with the belief that they would have medicinal value. Two hours later, he developed abdominal cramping and vomited multiple times, followed shortly thereafter by profuse diaphoresis, lethargy, and ataxia. His concerned family brought him to the ED where his vital signs on presentation were: blood pressure (BP), 78/43 mm Hg; heart rate (HR), 50 beats/minute; respiratory rate (RR), 12 breaths/minute; temperature (T), 97.8°F. With the exception of bradycardia, the patient’s cardiac, pulmonary, and abdominal examinations were normal. His skin was diaphoretic, and he had no focal motor or sensory deficits or tremor. Initial laboratory values were: hemoglobin, 12.6 g/dL; sodium, 137 mEq/L; potassium, 4.6 mEq/L; bicarbonate, 20 mEq/L; blood urea nitrogen, 17 mg/dL; creatinine, 2.2 mg/dL; glucose, 288 mg/dL. The patient’s troponin I level was slightly elevated at 0.06 ng/mL; electrocardiogram (ECG) results are shown in Figure 1.

Why do plant poisonings occur?

There is the general belief that what is natural is not only healthful but also safe. This is clearly not true: cyanide, uranium, and king cobras are all natural but hardly safe. While most plants chosen for their purported medicinal properties are generally harmless in most patients when taken in low doses, there are plants that are sufficiently poisonous to be consequential with even relatively small exposures. Some people, often unknowingly vulnerable due to genetic or other causes, are uniquely susceptible to even minute doses.

Humans probably learned about plant toxicity early on—most likely the hard way. To this day, however, the Internet is replete with traditional and avant-garde natural healing remedies involving the use of naturally-derived plant products. These numerous bioactive compounds are often sold in plant form or as extracts, the latter being more concerning given their more concentrated formulation.

Plant misidentification is a common cause of poisoning, whether the intended use is for food or medicine. For example, some mistake “deadly nightshade” (Atropa belladonna) berries, which are deep blue, for blueberries, or pokeweed roots for horseradish roots due to their similar appearances.¹

Alternatively, even when a plant is correctly identified, patients may experience adverse effects if they exceed the “therapeutic dose” (eg, dysrhythmia from aconite roots used in traditional Chinese medicine) or if the plant is improperly prepared (eg, hypoglycemia from consuming unripe ackee fruit).² In addition, a toxic plant such as Jimson weed (Datura stramonium) or coca leaf extract may be intentionally ingested for its psychoactive hallucinatory effects.² Although rare in the United States, in certain parts of Asia, persons intent on self-harm may consume toxic plants.¹

When ingested, what plants cause bradycardia and hypotension, and why do these effects occur?

The two broad classes of plant-derived toxins that can cause these findings are cardioactive steroids and sodium channel active agents.

Cardioactive Steroids
There are numerous botanical sources of cardioactive steroids (sometimes called cardiac glycosides) such as Digitalis lanata, from which digoxin is derived; and Digitalis purpurea, the source of digitoxin. Poisoning by Digitalis spp, squill, lily of the valley, oleander, yellow oleander, and Cerbera manghas are clinically similar. Cardioactive steroids act pharmacologically to block the sodium-potassium ATPase pump on the myocardial cell membrane. This in turn increases intracellular sodium, which subsequently inhibits the exchange of extracellular sodium for intracellular calcium, leading to inotropy. Clinical manifestations of toxicity include nausea, vomiting, hyperkalemia, bradycardia, cardiac dysrhythmias, and occasionally hypotension—some of which can be life-threatening.

Sodium Channel Active Agents
Several plant toxins affect the flow of sodium by blocking or activating the sodium channel. Both effects alter the rate and strength of cardiac contraction, causing cardiac dysrhythmias.

Aconite is often used in traditional Chinese medicine. In North America, it is mainly derived from Aconitinum napellus, commonly called monkshood, helmet flower, or wolfsbane. It effectively holds open the voltage-dependent sodium channel, increasing cellular excitability. By prolonging the sodium current influx, neuronal and cardiac repolarization eventually slow due to sodium overload, leading to bradycardia and hypotension, as well as neurological effects. Its cardiotoxicity resembles that caused by cardiac glycosides, though a history of paresthesias or muscle weakness may help to differentiate the two toxins.

Veratrum spp include false hellebore, Indian poke, and California hellebore. These plants are occasionally mistaken for leeks (ramps) and can cause vomiting, bradycardia, and hypotension by a mechanism of action similar to aconitine.

Grayanotoxins, a group of diterpenoid toxins found in death camas, azalea, Rhododendron spp, and mountain laurel, can become concentrated in honey made from these plants. Depending on the specific toxin, they variably open or close the sodium channel. In addition to causing bradycardia and hypotension, patients may exhibit mental status changes (“mad honey” poisoning) and seizures.²

Case Continuation

After rapid infusion of 1-liter of normal saline, the patient’s BP was 80/63 mm Hg and HR was 52 beats/minute. His wife arrived to the ED 30-minutes later with a plastic bag containing the red berries the patient had ingested. The emergency physician identified them as Taxus baccata, or more commonly, yew berries. The patient stated that he ingested both the red fleshy aril and chewed the hard central seed. 

How is cardiotoxicity from yew berries treated?

Within hours of ingestion, toxicity progresses from nausea, abdominal pain, paresthesias, and ataxia, to bradycardia, cardiac conduction delays, wide-complex ventricular dysrhythmias and mental status changes.³ Although toxicity of Taxus has been known since antiquity, no antidote exists. Ventricular dysrhythmias causing hemodynamic instability should be electrically cardioverted, although there is no evidence to support the safety or efficacy of such therapy. Since the serum, and therefore cardiac concentration of taxine will be identical after cardioversion to its value prior, recurrent dysrhythmias are common.¹ Sodium bicarbonate has been inconsistently effective in the treatment of wide-complex tachydysrhythmias,⁴ but its use seems counterintuitive for most cases. There may be merit to raising the sodium gradient on an already sodium overloaded myocyte, but short-term gain may lead to unintended consequences. Success with antidysrhythmics has been limited: although amiodarone is often used to treat wide-complex tachydysrhythmias, its efficacy in Taxus toxicity has been conflicting.^4-6

There have been a few reported cases of yew alkaloid crossreactivity with digoxin assays, suggesting that digoxin-specific antibody fragments may bind taxine.⁷ There is no evidence, however, that cardioactive steroids are present in yew, and empiric use of antidigoxin Fab-fragments cannot be recommended. A single case report demonstrated that hemodialysis was ineffective in the removal of taxines, likely due to the toxin’s large volume of distribution.⁸ As a last resort, extracorporeal life support with membrane oxygenation is described favorably in two cases of yew berry poisoning refractory to conventional therapy.^9,10

Case Conclusion

The patient’s ECGs showed a morphologically abnormal rhythm, possibly with a Brugada pattern, which are representative of the dysrhythmias caused by taxine’s inhibitory effects on the sodium and calcium channels. Despite an attempt at electrical cardioversion, the dysrhythmia persisted. He was given intravenous boluses of fluids and started on an amiodarone infusion. The patient’s BP gradually improved over the following 2 hours, and the dysrhythmia resolved with hemodynamic improvement. The amiodarone infusion was then discontinued, and he was admitted to the hospital for further testing. Echocardiography, electrophysiology studies, and cardiac catheterization were all normal. The absence of structural, dysrhythmogenic, and ischemic abnormalities supported the toxic etiology of his hemodynamic aberrations. He was discharged from the hospital 3 days later without report of sequelae.

Dr Nguyen is a medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

Case

A 50-year-old man ingests two handfuls of small, red berries that he picked from a shrub in front of his apartment building, with the belief that they would have medicinal value. Two hours later, he developed abdominal cramping and vomited multiple times, followed shortly thereafter by profuse diaphoresis, lethargy, and ataxia. His concerned family brought him to the ED where his vital signs on presentation were: blood pressure (BP), 78/43 mm Hg; heart rate (HR), 50 beats/minute; respiratory rate (RR), 12 breaths/minute; temperature (T), 97.8°F. With the exception of bradycardia, the patient’s cardiac, pulmonary, and abdominal examinations were normal. His skin was diaphoretic, and he had no focal motor or sensory deficits or tremor. Initial laboratory values were: hemoglobin, 12.6 g/dL; sodium, 137 mEq/L; potassium, 4.6 mEq/L; bicarbonate, 20 mEq/L; blood urea nitrogen, 17 mg/dL; creatinine, 2.2 mg/dL; glucose, 288 mg/dL. The patient’s troponin I level was slightly elevated at 0.06 ng/mL; electrocardiogram (ECG) results are shown in Figure 1.

Why do plant poisonings occur?

There is the general belief that what is natural is not only healthful but also safe. This is clearly not true: cyanide, uranium, and king cobras are all natural but hardly safe. While most plants chosen for their purported medicinal properties are generally harmless in most patients when taken in low doses, there are plants that are sufficiently poisonous to be consequential with even relatively small exposures. Some people, often unknowingly vulnerable due to genetic or other causes, are uniquely susceptible to even minute doses.

Humans probably learned about plant toxicity early on—most likely the hard way. To this day, however, the Internet is replete with traditional and avant-garde natural healing remedies involving the use of naturally-derived plant products. These numerous bioactive compounds are often sold in plant form or as extracts, the latter being more concerning given their more concentrated formulation.

Plant misidentification is a common cause of poisoning, whether the intended use is for food or medicine. For example, some mistake “deadly nightshade” (Atropa belladonna) berries, which are deep blue, for blueberries, or pokeweed roots for horseradish roots due to their similar appearances.¹

Alternatively, even when a plant is correctly identified, patients may experience adverse effects if they exceed the “therapeutic dose” (eg, dysrhythmia from aconite roots used in traditional Chinese medicine) or if the plant is improperly prepared (eg, hypoglycemia from consuming unripe ackee fruit).² In addition, a toxic plant such as Jimson weed (Datura stramonium) or coca leaf extract may be intentionally ingested for its psychoactive hallucinatory effects.² Although rare in the United States, in certain parts of Asia, persons intent on self-harm may consume toxic plants.¹

When ingested, what plants cause bradycardia and hypotension, and why do these effects occur?

The two broad classes of plant-derived toxins that can cause these findings are cardioactive steroids and sodium channel active agents.

Cardioactive Steroids
There are numerous botanical sources of cardioactive steroids (sometimes called cardiac glycosides) such as Digitalis lanata, from which digoxin is derived; and Digitalis purpurea, the source of digitoxin. Poisoning by Digitalis spp, squill, lily of the valley, oleander, yellow oleander, and Cerbera manghas are clinically similar. Cardioactive steroids act pharmacologically to block the sodium-potassium ATPase pump on the myocardial cell membrane. This in turn increases intracellular sodium, which subsequently inhibits the exchange of extracellular sodium for intracellular calcium, leading to inotropy. Clinical manifestations of toxicity include nausea, vomiting, hyperkalemia, bradycardia, cardiac dysrhythmias, and occasionally hypotension—some of which can be life-threatening.

Sodium Channel Active Agents
Several plant toxins affect the flow of sodium by blocking or activating the sodium channel. Both effects alter the rate and strength of cardiac contraction, causing cardiac dysrhythmias.

Aconite is often used in traditional Chinese medicine. In North America, it is mainly derived from Aconitinum napellus, commonly called monkshood, helmet flower, or wolfsbane. It effectively holds open the voltage-dependent sodium channel, increasing cellular excitability. By prolonging the sodium current influx, neuronal and cardiac repolarization eventually slow due to sodium overload, leading to bradycardia and hypotension, as well as neurological effects. Its cardiotoxicity resembles that caused by cardiac glycosides, though a history of paresthesias or muscle weakness may help to differentiate the two toxins.

Veratrum spp include false hellebore, Indian poke, and California hellebore. These plants are occasionally mistaken for leeks (ramps) and can cause vomiting, bradycardia, and hypotension by a mechanism of action similar to aconitine.

Grayanotoxins, a group of diterpenoid toxins found in death camas, azalea, Rhododendron spp, and mountain laurel, can become concentrated in honey made from these plants. Depending on the specific toxin, they variably open or close the sodium channel. In addition to causing bradycardia and hypotension, patients may exhibit mental status changes (“mad honey” poisoning) and seizures.²

Case Continuation

After rapid infusion of 1-liter of normal saline, the patient’s BP was 80/63 mm Hg and HR was 52 beats/minute. His wife arrived to the ED 30-minutes later with a plastic bag containing the red berries the patient had ingested. The emergency physician identified them as Taxus baccata, or more commonly, yew berries. The patient stated that he ingested both the red fleshy aril and chewed the hard central seed. 

How is cardiotoxicity from yew berries treated?

Within hours of ingestion, toxicity progresses from nausea, abdominal pain, paresthesias, and ataxia, to bradycardia, cardiac conduction delays, wide-complex ventricular dysrhythmias and mental status changes.³ Although toxicity of Taxus has been known since antiquity, no antidote exists. Ventricular dysrhythmias causing hemodynamic instability should be electrically cardioverted, although there is no evidence to support the safety or efficacy of such therapy. Since the serum, and therefore cardiac concentration of taxine will be identical after cardioversion to its value prior, recurrent dysrhythmias are common.¹ Sodium bicarbonate has been inconsistently effective in the treatment of wide-complex tachydysrhythmias,⁴ but its use seems counterintuitive for most cases. There may be merit to raising the sodium gradient on an already sodium overloaded myocyte, but short-term gain may lead to unintended consequences. Success with antidysrhythmics has been limited: although amiodarone is often used to treat wide-complex tachydysrhythmias, its efficacy in Taxus toxicity has been conflicting.^4-6

There have been a few reported cases of yew alkaloid crossreactivity with digoxin assays, suggesting that digoxin-specific antibody fragments may bind taxine.⁷ There is no evidence, however, that cardioactive steroids are present in yew, and empiric use of antidigoxin Fab-fragments cannot be recommended. A single case report demonstrated that hemodialysis was ineffective in the removal of taxines, likely due to the toxin’s large volume of distribution.⁸ As a last resort, extracorporeal life support with membrane oxygenation is described favorably in two cases of yew berry poisoning refractory to conventional therapy.^9,10

Case Conclusion

The patient’s ECGs showed a morphologically abnormal rhythm, possibly with a Brugada pattern, which are representative of the dysrhythmias caused by taxine’s inhibitory effects on the sodium and calcium channels. Despite an attempt at electrical cardioversion, the dysrhythmia persisted. He was given intravenous boluses of fluids and started on an amiodarone infusion. The patient’s BP gradually improved over the following 2 hours, and the dysrhythmia resolved with hemodynamic improvement. The amiodarone infusion was then discontinued, and he was admitted to the hospital for further testing. Echocardiography, electrophysiology studies, and cardiac catheterization were all normal. The absence of structural, dysrhythmogenic, and ischemic abnormalities supported the toxic etiology of his hemodynamic aberrations. He was discharged from the hospital 3 days later without report of sequelae.

Dr Nguyen is a medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

Case

A 50-year-old man ingests two handfuls of small, red berries that he picked from a shrub in front of his apartment building, with the belief that they would have medicinal value. Two hours later, he developed abdominal cramping and vomited multiple times, followed shortly thereafter by profuse diaphoresis, lethargy, and ataxia. His concerned family brought him to the ED where his vital signs on presentation were: blood pressure (BP), 78/43 mm Hg; heart rate (HR), 50 beats/minute; respiratory rate (RR), 12 breaths/minute; temperature (T), 97.8°F. With the exception of bradycardia, the patient’s cardiac, pulmonary, and abdominal examinations were normal. His skin was diaphoretic, and he had no focal motor or sensory deficits or tremor. Initial laboratory values were: hemoglobin, 12.6 g/dL; sodium, 137 mEq/L; potassium, 4.6 mEq/L; bicarbonate, 20 mEq/L; blood urea nitrogen, 17 mg/dL; creatinine, 2.2 mg/dL; glucose, 288 mg/dL. The patient’s troponin I level was slightly elevated at 0.06 ng/mL; electrocardiogram (ECG) results are shown in Figure 1.

Why do plant poisonings occur?

There is the general belief that what is natural is not only healthful but also safe. This is clearly not true: cyanide, uranium, and king cobras are all natural but hardly safe. While most plants chosen for their purported medicinal properties are generally harmless in most patients when taken in low doses, there are plants that are sufficiently poisonous to be consequential with even relatively small exposures. Some people, often unknowingly vulnerable due to genetic or other causes, are uniquely susceptible to even minute doses.

Humans probably learned about plant toxicity early on—most likely the hard way. To this day, however, the Internet is replete with traditional and avant-garde natural healing remedies involving the use of naturally-derived plant products. These numerous bioactive compounds are often sold in plant form or as extracts, the latter being more concerning given their more concentrated formulation.

Plant misidentification is a common cause of poisoning, whether the intended use is for food or medicine. For example, some mistake “deadly nightshade” (Atropa belladonna) berries, which are deep blue, for blueberries, or pokeweed roots for horseradish roots due to their similar appearances.¹

Alternatively, even when a plant is correctly identified, patients may experience adverse effects if they exceed the “therapeutic dose” (eg, dysrhythmia from aconite roots used in traditional Chinese medicine) or if the plant is improperly prepared (eg, hypoglycemia from consuming unripe ackee fruit).² In addition, a toxic plant such as Jimson weed (Datura stramonium) or coca leaf extract may be intentionally ingested for its psychoactive hallucinatory effects.² Although rare in the United States, in certain parts of Asia, persons intent on self-harm may consume toxic plants.¹

When ingested, what plants cause bradycardia and hypotension, and why do these effects occur?

The two broad classes of plant-derived toxins that can cause these findings are cardioactive steroids and sodium channel active agents.

Cardioactive Steroids
There are numerous botanical sources of cardioactive steroids (sometimes called cardiac glycosides) such as Digitalis lanata, from which digoxin is derived; and Digitalis purpurea, the source of digitoxin. Poisoning by Digitalis spp, squill, lily of the valley, oleander, yellow oleander, and Cerbera manghas are clinically similar. Cardioactive steroids act pharmacologically to block the sodium-potassium ATPase pump on the myocardial cell membrane. This in turn increases intracellular sodium, which subsequently inhibits the exchange of extracellular sodium for intracellular calcium, leading to inotropy. Clinical manifestations of toxicity include nausea, vomiting, hyperkalemia, bradycardia, cardiac dysrhythmias, and occasionally hypotension—some of which can be life-threatening.

Sodium Channel Active Agents
Several plant toxins affect the flow of sodium by blocking or activating the sodium channel. Both effects alter the rate and strength of cardiac contraction, causing cardiac dysrhythmias.

Aconite is often used in traditional Chinese medicine. In North America, it is mainly derived from Aconitinum napellus, commonly called monkshood, helmet flower, or wolfsbane. It effectively holds open the voltage-dependent sodium channel, increasing cellular excitability. By prolonging the sodium current influx, neuronal and cardiac repolarization eventually slow due to sodium overload, leading to bradycardia and hypotension, as well as neurological effects. Its cardiotoxicity resembles that caused by cardiac glycosides, though a history of paresthesias or muscle weakness may help to differentiate the two toxins.

Veratrum spp include false hellebore, Indian poke, and California hellebore. These plants are occasionally mistaken for leeks (ramps) and can cause vomiting, bradycardia, and hypotension by a mechanism of action similar to aconitine.

Grayanotoxins, a group of diterpenoid toxins found in death camas, azalea, Rhododendron spp, and mountain laurel, can become concentrated in honey made from these plants. Depending on the specific toxin, they variably open or close the sodium channel. In addition to causing bradycardia and hypotension, patients may exhibit mental status changes (“mad honey” poisoning) and seizures.²

Case Continuation

After rapid infusion of 1-liter of normal saline, the patient’s BP was 80/63 mm Hg and HR was 52 beats/minute. His wife arrived to the ED 30-minutes later with a plastic bag containing the red berries the patient had ingested. The emergency physician identified them as Taxus baccata, or more commonly, yew berries. The patient stated that he ingested both the red fleshy aril and chewed the hard central seed. 

How is cardiotoxicity from yew berries treated?

Within hours of ingestion, toxicity progresses from nausea, abdominal pain, paresthesias, and ataxia, to bradycardia, cardiac conduction delays, wide-complex ventricular dysrhythmias and mental status changes.³ Although toxicity of Taxus has been known since antiquity, no antidote exists. Ventricular dysrhythmias causing hemodynamic instability should be electrically cardioverted, although there is no evidence to support the safety or efficacy of such therapy. Since the serum, and therefore cardiac concentration of taxine will be identical after cardioversion to its value prior, recurrent dysrhythmias are common.¹ Sodium bicarbonate has been inconsistently effective in the treatment of wide-complex tachydysrhythmias,⁴ but its use seems counterintuitive for most cases. There may be merit to raising the sodium gradient on an already sodium overloaded myocyte, but short-term gain may lead to unintended consequences. Success with antidysrhythmics has been limited: although amiodarone is often used to treat wide-complex tachydysrhythmias, its efficacy in Taxus toxicity has been conflicting.^4-6

There have been a few reported cases of yew alkaloid crossreactivity with digoxin assays, suggesting that digoxin-specific antibody fragments may bind taxine.⁷ There is no evidence, however, that cardioactive steroids are present in yew, and empiric use of antidigoxin Fab-fragments cannot be recommended. A single case report demonstrated that hemodialysis was ineffective in the removal of taxines, likely due to the toxin’s large volume of distribution.⁸ As a last resort, extracorporeal life support with membrane oxygenation is described favorably in two cases of yew berry poisoning refractory to conventional therapy.^9,10

Case Conclusion

The patient’s ECGs showed a morphologically abnormal rhythm, possibly with a Brugada pattern, which are representative of the dysrhythmias caused by taxine’s inhibitory effects on the sodium and calcium channels. Despite an attempt at electrical cardioversion, the dysrhythmia persisted. He was given intravenous boluses of fluids and started on an amiodarone infusion. The patient’s BP gradually improved over the following 2 hours, and the dysrhythmia resolved with hemodynamic improvement. The amiodarone infusion was then discontinued, and he was admitted to the hospital for further testing. Echocardiography, electrophysiology studies, and cardiac catheterization were all normal. The absence of structural, dysrhythmogenic, and ischemic abnormalities supported the toxic etiology of his hemodynamic aberrations. He was discharged from the hospital 3 days later without report of sequelae.

Dr Nguyen is a medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

A mother presents to the ED with her 4-day-old daughter after noting abnormal jerking movements of the neonate's upper extremities. She states the baby has had watery stools for the past day, but has been tolerating bottle formula feeds without vomiting and having appropriate urinary output. The patient was born full-term via normal spontaneous vaginal delivery, with Apgar scores of 8 at 1 minute and 9 at 5 minutes. The postdelivery course was uncomplicated, and both mother and baby were discharged home 2 days after delivery.

Initial vital signs are: heart rate, 135 beats/min; respiratory rate (RR), 48 breaths/min; and temperature, 98.7°F; blood glucose was normal. On physical examination, the baby is awake and well-appearing, with a nonbulging anterior fontanelle, soft, supple neck, and flexed and symmetrically mobile extremities. Moro, suck, rooting, and grasp reflexes are all intact. No abnormal movements are noted. The remainder of the examination is unremarkable.

Do the jerking movements indicate a focal seizure? What could cause these movements in a neonate?

As the length of the postpartum hospital stay has decreased over the past 20 years, EDs have experienced an increase in neonatal visits for conditions that traditionally manifested in newborn nurseries. While most presentations are for benign reasons (eg, issues related to feeding, irritability), patients with concerning conditions, including central nervous system (CNS) abnormalities, may also initially present to the ED. Causes of such clinical findings may be structural (eg, cerebral malformations, subdural hematomas, herpes encephalitis) and/or metabolic (eg, hypoglycemia, hypocalcemia, inborn errors). Many early-onset neonatal seizures are benign and resolve by several months of age, but it is essential to identify those that are consequential and treatable.

Case Continuation

In the evaluation of the neonatal patient with suspected seizure, it is important to take a detailed maternal and labor history, and to consider a broad differential in the face of nonspecific findings. In this case, the patient's mother disclosed a personal history of chronic pain, for which she took buprenorphine 2 mg orally in the morning and 4 mg orally at bedtime (total daily dose of 6mg/day) throughout her pregnancy.

How does drug withdrawal present in the neonate?

Neonatal abstinence syndrome (NAS) is the clinical syndrome of withdrawal in a newborn exposed in utero to drugs capable of inducing dependence. Agents associated with NAS include opioids, benzodiazepines, ethanol, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, and nicotine.^1,2

Over the past decade, there has been a 330% rise in the diagnosis of opioid-related NAS alone.³ In response to this increase, the US Food and Drug Administration recently added a black-box warning to all extended-release/long-acting opioid preparations detailing this risk.⁴

Presenting symptoms of NAS are protean, differ from patient to patient, and are a function of drug type, duration, and amount of drug exposure. NAS may mimic other severe life-threatening conditions such as those previously noted, and the inability to obtain an adequate symptom-based medical history from a neonate further complicates the diagnosis. Before making a diagnosis of NAS, other conditions should be carefully considered in the differential.

Neonatal opioid withdrawal manifests primarily with CNS and gastrointestinal (GI) effects since there are high concentrations of opioid receptors in these areas. Although clinical findings are generally similar among opioid agents, the onset and duration following abstinence varies—largely based on individual drug half-life; this helps to differentiate between opioid agents. For example, while babies exposed to heroin in utero present with signs of NAS within 24 hours of birth, those exposed to buprenorphine or methadone tend to present 2 to 6 days after delivery.¹ Between 55% to 94% of neonates with in-utero opioid exposure develop NAS.⁵

Selective Serotonin Reuptake Inhibitors

SSRIs have also been associated with a neonatal syndrome, and largely involve similar signs and symptoms as NAS. Although the specific etiology is not clear, it has been suggested that this syndrome is the result of serotonin toxicity rather than withdrawal; as such, it is often referred to as "serotonin discontinuation syndrome." Clinical findings occur from several hours to several days after birth and usually resolve within 1 to 2 weeks.⁶

Cocaine Exposure

In-utero cocaine exposure is also associated with neurobehavioral abnormalities in neonates although a withdrawal syndrome is less clearly defined. Findings, however, are consistent with NAS and include increased irritability, tremors, and high-pitched cry—most frequently occurring between 24 and 48 hours postdelivery.⁶

Neonatal Alcohol Withdrawal Syndrome

Neonatal alcohol withdrawal syndrome, particularly in fetuses exposed to alcohol during the last trimester, is distinct from fetal alcohol syndrome (FAS). The latter is associated with typical dysmorphic features, growth deficiencies, and CNS findings reflective of permanent neurologic sequelae. Neonatal alcohol withdrawal presents with CNS findings similar to those listed for other in-utero exposures—eg, increased irritability, tremors, nystagmus hyperactive reflexes.⁷

Screening for NAS: The Finnegan Scale

The Finnegan Neonatal Abstinence Scoring System is one of the most commonly employed and validated tools used to screen for NAS. It comprises a 31-item scale, listing the clinical signs and symptoms of NAS, which are scored by severity and organized by system to include neurologic, metabolic, vasomotor, respiratory, and GI disturbances (Figure). Point allocation is based on mild, moderate, or severe symptoms as follows:

• Mild findings (eg, sweating, fever <101°F mottling, nasal stuffiness) each score 1 point.

• Moderate findings (eg, high-pitched cry, hyperactive moro reflex, increased muscle tone, fever >101°F, increased RR >60 with retractions, poor feeding, loose stools) each score 2 points.

• Severe findings (eg, myoclonic jerks, generalized convulsions, projectile vomiting, watery stools) each score 3 points.

While each of the above are independently nonspecific, the constellation of findings, together with the appropriate history, provide for a clinical diagnosis. The Finnegan Scale is therefore designed not only to aid in diagnosis, but also to quantify the severity of NAS and guide management.

Screening for NAS begins at birth in neonates with known in-utero exposure (ie, when risk of NAS is high) or at the time of initial presentation in other circumstances. Scoring is performed every 4 hours; the first two or three scores will determine the need for pharmacotherapy (see below).

How is NAS treated?

The two main goals of management in the treatment of opioid-related NAS are to relieve the signs and symptoms of withdrawal and to prevent complications (eg, fever, weight loss, seizures). Therapy should begin with nonpharmacologic measures that minimize excess external stimuli, such as swaddling, gentle handling, and minimizing noise and light. To prevent weight loss, small hypercaloric feeds may be helpful. If pharmacologic treatment is indicated, oral opioid replacement with morphine is considered by many to be the drug of choice. Oral morphine dosing may be guided by NAS severity based on the Finnegan score; alternatively, initial dosing at 0.1 mg/kg orally every 4 hours has also been recommended.¹

Other agents, such methadone 0.1 mg/kg orally every 12 hours and buprenorphine 15.9 mcg/kg divided in three doses orally, may also be used. In patients whose symptoms persist despite opioid treatment, use of adjuncts such as phenobarbital and clonidine may be indicated.

Case Conclusion

The patient was admitted to the neonatal intensive care unit where she appropriately underwent a sepsis workup. Laboratory evaluation, including blood and urine cultures, was obtained. A brain ultrasound was unremarkable, and since lumbar puncture was unsuccessful, the patient was started empirically on meningitis doses of the cefotaxime, vancomycin, and acyclovir.

An initial Finnegan score was calculated. With the exception of soft stools, there were no other persistent symptoms, and patient did not achieve a score indicating a need for pharmacologic management. After 48 hours, she remained afebrile and soft stools resolved. All laboratory values, including cultures, were unremarkable. The patient was discharged on hospital day 3, with a scheduled well-baby follow-up appointment.

A mother presents to the ED with her 4-day-old daughter after noting abnormal jerking movements of the neonate's upper extremities. She states the baby has had watery stools for the past day, but has been tolerating bottle formula feeds without vomiting and having appropriate urinary output. The patient was born full-term via normal spontaneous vaginal delivery, with Apgar scores of 8 at 1 minute and 9 at 5 minutes. The postdelivery course was uncomplicated, and both mother and baby were discharged home 2 days after delivery.

Initial vital signs are: heart rate, 135 beats/min; respiratory rate (RR), 48 breaths/min; and temperature, 98.7°F; blood glucose was normal. On physical examination, the baby is awake and well-appearing, with a nonbulging anterior fontanelle, soft, supple neck, and flexed and symmetrically mobile extremities. Moro, suck, rooting, and grasp reflexes are all intact. No abnormal movements are noted. The remainder of the examination is unremarkable.

Do the jerking movements indicate a focal seizure? What could cause these movements in a neonate?

As the length of the postpartum hospital stay has decreased over the past 20 years, EDs have experienced an increase in neonatal visits for conditions that traditionally manifested in newborn nurseries. While most presentations are for benign reasons (eg, issues related to feeding, irritability), patients with concerning conditions, including central nervous system (CNS) abnormalities, may also initially present to the ED. Causes of such clinical findings may be structural (eg, cerebral malformations, subdural hematomas, herpes encephalitis) and/or metabolic (eg, hypoglycemia, hypocalcemia, inborn errors). Many early-onset neonatal seizures are benign and resolve by several months of age, but it is essential to identify those that are consequential and treatable.

Case Continuation

In the evaluation of the neonatal patient with suspected seizure, it is important to take a detailed maternal and labor history, and to consider a broad differential in the face of nonspecific findings. In this case, the patient's mother disclosed a personal history of chronic pain, for which she took buprenorphine 2 mg orally in the morning and 4 mg orally at bedtime (total daily dose of 6mg/day) throughout her pregnancy.

How does drug withdrawal present in the neonate?

Neonatal abstinence syndrome (NAS) is the clinical syndrome of withdrawal in a newborn exposed in utero to drugs capable of inducing dependence. Agents associated with NAS include opioids, benzodiazepines, ethanol, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, and nicotine.^1,2

Over the past decade, there has been a 330% rise in the diagnosis of opioid-related NAS alone.³ In response to this increase, the US Food and Drug Administration recently added a black-box warning to all extended-release/long-acting opioid preparations detailing this risk.⁴

Presenting symptoms of NAS are protean, differ from patient to patient, and are a function of drug type, duration, and amount of drug exposure. NAS may mimic other severe life-threatening conditions such as those previously noted, and the inability to obtain an adequate symptom-based medical history from a neonate further complicates the diagnosis. Before making a diagnosis of NAS, other conditions should be carefully considered in the differential.

Neonatal opioid withdrawal manifests primarily with CNS and gastrointestinal (GI) effects since there are high concentrations of opioid receptors in these areas. Although clinical findings are generally similar among opioid agents, the onset and duration following abstinence varies—largely based on individual drug half-life; this helps to differentiate between opioid agents. For example, while babies exposed to heroin in utero present with signs of NAS within 24 hours of birth, those exposed to buprenorphine or methadone tend to present 2 to 6 days after delivery.¹ Between 55% to 94% of neonates with in-utero opioid exposure develop NAS.⁵

Selective Serotonin Reuptake Inhibitors

SSRIs have also been associated with a neonatal syndrome, and largely involve similar signs and symptoms as NAS. Although the specific etiology is not clear, it has been suggested that this syndrome is the result of serotonin toxicity rather than withdrawal; as such, it is often referred to as "serotonin discontinuation syndrome." Clinical findings occur from several hours to several days after birth and usually resolve within 1 to 2 weeks.⁶

Cocaine Exposure

In-utero cocaine exposure is also associated with neurobehavioral abnormalities in neonates although a withdrawal syndrome is less clearly defined. Findings, however, are consistent with NAS and include increased irritability, tremors, and high-pitched cry—most frequently occurring between 24 and 48 hours postdelivery.⁶

Neonatal Alcohol Withdrawal Syndrome

Neonatal alcohol withdrawal syndrome, particularly in fetuses exposed to alcohol during the last trimester, is distinct from fetal alcohol syndrome (FAS). The latter is associated with typical dysmorphic features, growth deficiencies, and CNS findings reflective of permanent neurologic sequelae. Neonatal alcohol withdrawal presents with CNS findings similar to those listed for other in-utero exposures—eg, increased irritability, tremors, nystagmus hyperactive reflexes.⁷

Screening for NAS: The Finnegan Scale

The Finnegan Neonatal Abstinence Scoring System is one of the most commonly employed and validated tools used to screen for NAS. It comprises a 31-item scale, listing the clinical signs and symptoms of NAS, which are scored by severity and organized by system to include neurologic, metabolic, vasomotor, respiratory, and GI disturbances (Figure). Point allocation is based on mild, moderate, or severe symptoms as follows:

• Mild findings (eg, sweating, fever <101°F mottling, nasal stuffiness) each score 1 point.

• Moderate findings (eg, high-pitched cry, hyperactive moro reflex, increased muscle tone, fever >101°F, increased RR >60 with retractions, poor feeding, loose stools) each score 2 points.

• Severe findings (eg, myoclonic jerks, generalized convulsions, projectile vomiting, watery stools) each score 3 points.

While each of the above are independently nonspecific, the constellation of findings, together with the appropriate history, provide for a clinical diagnosis. The Finnegan Scale is therefore designed not only to aid in diagnosis, but also to quantify the severity of NAS and guide management.

Screening for NAS begins at birth in neonates with known in-utero exposure (ie, when risk of NAS is high) or at the time of initial presentation in other circumstances. Scoring is performed every 4 hours; the first two or three scores will determine the need for pharmacotherapy (see below).

How is NAS treated?

The two main goals of management in the treatment of opioid-related NAS are to relieve the signs and symptoms of withdrawal and to prevent complications (eg, fever, weight loss, seizures). Therapy should begin with nonpharmacologic measures that minimize excess external stimuli, such as swaddling, gentle handling, and minimizing noise and light. To prevent weight loss, small hypercaloric feeds may be helpful. If pharmacologic treatment is indicated, oral opioid replacement with morphine is considered by many to be the drug of choice. Oral morphine dosing may be guided by NAS severity based on the Finnegan score; alternatively, initial dosing at 0.1 mg/kg orally every 4 hours has also been recommended.¹

Other agents, such methadone 0.1 mg/kg orally every 12 hours and buprenorphine 15.9 mcg/kg divided in three doses orally, may also be used. In patients whose symptoms persist despite opioid treatment, use of adjuncts such as phenobarbital and clonidine may be indicated.

Case Conclusion

The patient was admitted to the neonatal intensive care unit where she appropriately underwent a sepsis workup. Laboratory evaluation, including blood and urine cultures, was obtained. A brain ultrasound was unremarkable, and since lumbar puncture was unsuccessful, the patient was started empirically on meningitis doses of the cefotaxime, vancomycin, and acyclovir.

An initial Finnegan score was calculated. With the exception of soft stools, there were no other persistent symptoms, and patient did not achieve a score indicating a need for pharmacologic management. After 48 hours, she remained afebrile and soft stools resolved. All laboratory values, including cultures, were unremarkable. The patient was discharged on hospital day 3, with a scheduled well-baby follow-up appointment.

A mother presents to the ED with her 4-day-old daughter after noting abnormal jerking movements of the neonate's upper extremities. She states the baby has had watery stools for the past day, but has been tolerating bottle formula feeds without vomiting and having appropriate urinary output. The patient was born full-term via normal spontaneous vaginal delivery, with Apgar scores of 8 at 1 minute and 9 at 5 minutes. The postdelivery course was uncomplicated, and both mother and baby were discharged home 2 days after delivery.

Initial vital signs are: heart rate, 135 beats/min; respiratory rate (RR), 48 breaths/min; and temperature, 98.7°F; blood glucose was normal. On physical examination, the baby is awake and well-appearing, with a nonbulging anterior fontanelle, soft, supple neck, and flexed and symmetrically mobile extremities. Moro, suck, rooting, and grasp reflexes are all intact. No abnormal movements are noted. The remainder of the examination is unremarkable.

Do the jerking movements indicate a focal seizure? What could cause these movements in a neonate?

As the length of the postpartum hospital stay has decreased over the past 20 years, EDs have experienced an increase in neonatal visits for conditions that traditionally manifested in newborn nurseries. While most presentations are for benign reasons (eg, issues related to feeding, irritability), patients with concerning conditions, including central nervous system (CNS) abnormalities, may also initially present to the ED. Causes of such clinical findings may be structural (eg, cerebral malformations, subdural hematomas, herpes encephalitis) and/or metabolic (eg, hypoglycemia, hypocalcemia, inborn errors). Many early-onset neonatal seizures are benign and resolve by several months of age, but it is essential to identify those that are consequential and treatable.

Case Continuation

In the evaluation of the neonatal patient with suspected seizure, it is important to take a detailed maternal and labor history, and to consider a broad differential in the face of nonspecific findings. In this case, the patient's mother disclosed a personal history of chronic pain, for which she took buprenorphine 2 mg orally in the morning and 4 mg orally at bedtime (total daily dose of 6mg/day) throughout her pregnancy.

How does drug withdrawal present in the neonate?

Neonatal abstinence syndrome (NAS) is the clinical syndrome of withdrawal in a newborn exposed in utero to drugs capable of inducing dependence. Agents associated with NAS include opioids, benzodiazepines, ethanol, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, and nicotine.^1,2

Over the past decade, there has been a 330% rise in the diagnosis of opioid-related NAS alone.³ In response to this increase, the US Food and Drug Administration recently added a black-box warning to all extended-release/long-acting opioid preparations detailing this risk.⁴

Presenting symptoms of NAS are protean, differ from patient to patient, and are a function of drug type, duration, and amount of drug exposure. NAS may mimic other severe life-threatening conditions such as those previously noted, and the inability to obtain an adequate symptom-based medical history from a neonate further complicates the diagnosis. Before making a diagnosis of NAS, other conditions should be carefully considered in the differential.

Neonatal opioid withdrawal manifests primarily with CNS and gastrointestinal (GI) effects since there are high concentrations of opioid receptors in these areas. Although clinical findings are generally similar among opioid agents, the onset and duration following abstinence varies—largely based on individual drug half-life; this helps to differentiate between opioid agents. For example, while babies exposed to heroin in utero present with signs of NAS within 24 hours of birth, those exposed to buprenorphine or methadone tend to present 2 to 6 days after delivery.¹ Between 55% to 94% of neonates with in-utero opioid exposure develop NAS.⁵

Selective Serotonin Reuptake Inhibitors

SSRIs have also been associated with a neonatal syndrome, and largely involve similar signs and symptoms as NAS. Although the specific etiology is not clear, it has been suggested that this syndrome is the result of serotonin toxicity rather than withdrawal; as such, it is often referred to as "serotonin discontinuation syndrome." Clinical findings occur from several hours to several days after birth and usually resolve within 1 to 2 weeks.⁶

Cocaine Exposure

In-utero cocaine exposure is also associated with neurobehavioral abnormalities in neonates although a withdrawal syndrome is less clearly defined. Findings, however, are consistent with NAS and include increased irritability, tremors, and high-pitched cry—most frequently occurring between 24 and 48 hours postdelivery.⁶

Neonatal Alcohol Withdrawal Syndrome

Neonatal alcohol withdrawal syndrome, particularly in fetuses exposed to alcohol during the last trimester, is distinct from fetal alcohol syndrome (FAS). The latter is associated with typical dysmorphic features, growth deficiencies, and CNS findings reflective of permanent neurologic sequelae. Neonatal alcohol withdrawal presents with CNS findings similar to those listed for other in-utero exposures—eg, increased irritability, tremors, nystagmus hyperactive reflexes.⁷

Screening for NAS: The Finnegan Scale

The Finnegan Neonatal Abstinence Scoring System is one of the most commonly employed and validated tools used to screen for NAS. It comprises a 31-item scale, listing the clinical signs and symptoms of NAS, which are scored by severity and organized by system to include neurologic, metabolic, vasomotor, respiratory, and GI disturbances (Figure). Point allocation is based on mild, moderate, or severe symptoms as follows:

• Mild findings (eg, sweating, fever <101°F mottling, nasal stuffiness) each score 1 point.

• Moderate findings (eg, high-pitched cry, hyperactive moro reflex, increased muscle tone, fever >101°F, increased RR >60 with retractions, poor feeding, loose stools) each score 2 points.

• Severe findings (eg, myoclonic jerks, generalized convulsions, projectile vomiting, watery stools) each score 3 points.

While each of the above are independently nonspecific, the constellation of findings, together with the appropriate history, provide for a clinical diagnosis. The Finnegan Scale is therefore designed not only to aid in diagnosis, but also to quantify the severity of NAS and guide management.

Screening for NAS begins at birth in neonates with known in-utero exposure (ie, when risk of NAS is high) or at the time of initial presentation in other circumstances. Scoring is performed every 4 hours; the first two or three scores will determine the need for pharmacotherapy (see below).

How is NAS treated?

The two main goals of management in the treatment of opioid-related NAS are to relieve the signs and symptoms of withdrawal and to prevent complications (eg, fever, weight loss, seizures). Therapy should begin with nonpharmacologic measures that minimize excess external stimuli, such as swaddling, gentle handling, and minimizing noise and light. To prevent weight loss, small hypercaloric feeds may be helpful. If pharmacologic treatment is indicated, oral opioid replacement with morphine is considered by many to be the drug of choice. Oral morphine dosing may be guided by NAS severity based on the Finnegan score; alternatively, initial dosing at 0.1 mg/kg orally every 4 hours has also been recommended.¹

Other agents, such methadone 0.1 mg/kg orally every 12 hours and buprenorphine 15.9 mcg/kg divided in three doses orally, may also be used. In patients whose symptoms persist despite opioid treatment, use of adjuncts such as phenobarbital and clonidine may be indicated.

Case Conclusion

The patient was admitted to the neonatal intensive care unit where she appropriately underwent a sepsis workup. Laboratory evaluation, including blood and urine cultures, was obtained. A brain ultrasound was unremarkable, and since lumbar puncture was unsuccessful, the patient was started empirically on meningitis doses of the cefotaxime, vancomycin, and acyclovir.

An initial Finnegan score was calculated. With the exception of soft stools, there were no other persistent symptoms, and patient did not achieve a score indicating a need for pharmacologic management. After 48 hours, she remained afebrile and soft stools resolved. All laboratory values, including cultures, were unremarkable. The patient was discharged on hospital day 3, with a scheduled well-baby follow-up appointment.

A mother presents to the ED with her 4-day-old daughter after noting abnormal jerking movements of the neonate's upper extremities. She states the baby has had watery stools for the past day, but has been tolerating bottle formula feeds without vomiting and having appropriate urinary output. The patient was born full-term via normal spontaneous vaginal delivery, with Apgar scores of 8 at 1 minute and 9 at 5 minutes. The postdelivery course was uncomplicated, and both mother and baby were discharged home 2 days after delivery.

Initial vital signs are: heart rate, 135 beats/min; respiratory rate (RR), 48 breaths/min; and temperature, 98.7°F; blood glucose was normal. On physical examination, the baby is awake and well-appearing, with a nonbulging anterior fontanelle, soft, supple neck, and flexed and symmetrically mobile extremities. Moro, suck, rooting, and grasp reflexes are all intact. No abnormal movements are noted. The remainder of the examination is unremarkable.

Do the jerking movements indicate a focal seizure? What could cause these movements in a neonate?

As the length of the postpartum hospital stay has decreased over the past 20 years, EDs have experienced an increase in neonatal visits for conditions that traditionally manifested in newborn nurseries. While most presentations are for benign reasons (eg, issues related to feeding, irritability), patients with concerning conditions, including central nervous system (CNS) abnormalities, may also initially present to the ED. Causes of such clinical findings may be structural (eg, cerebral malformations, subdural hematomas, herpes encephalitis) and/or metabolic (eg, hypoglycemia, hypocalcemia, inborn errors). Many early-onset neonatal seizures are benign and resolve by several months of age, but it is essential to identify those that are consequential and treatable.

Case Continuation

In the evaluation of the neonatal patient with suspected seizure, it is important to take a detailed maternal and labor history, and to consider a broad differential in the face of nonspecific findings. In this case, the patient's mother disclosed a personal history of chronic pain, for which she took buprenorphine 2 mg orally in the morning and 4 mg orally at bedtime (total daily dose of 6mg/day) throughout her pregnancy.

How does drug withdrawal present in the neonate?

Neonatal abstinence syndrome (NAS) is the clinical syndrome of withdrawal in a newborn exposed in utero to drugs capable of inducing dependence. Agents associated with NAS include opioids, benzodiazepines, ethanol, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, and nicotine.1,2

Over the past decade, there has been a 330% rise in the diagnosis of opioid-related NAS alone.3 In response to this increase, the US Food and Drug Administration recently added a black-box warning to all extended-release/long-acting opioid preparations detailing this risk.4

Presenting symptoms of NAS are protean, differ from patient to patient, and are a function of drug type, duration, and amount of drug exposure. NAS may mimic other severe life-threatening conditions such as those previously noted, and the inability to obtain an adequate symptom-based medical history from a neonate further complicates the diagnosis. Before making a diagnosis of NAS, other conditions should be carefully considered in the differential.

Neonatal opioid withdrawal manifests primarily with CNS and gastrointestinal (GI) effects since there are high concentrations of opioid receptors in these areas. Although clinical findings are generally similar among opioid agents, the onset and duration following abstinence varies—largely based on individual drug half-life; this helps to differentiate between opioid agents. For example, while babies exposed to heroin in utero present with signs of NAS within 24 hours of birth, those exposed to buprenorphine or methadone tend to present 2 to 6 days after delivery.1 Between 55% to 94% of neonates with in-utero opioid exposure develop NAS.5

Select Serotonin Reuptake Inhibitors

SSRIs have also been associated with a neonatal syndrome, and largely involve similar signs and symptoms as NAS. Although the specific etiology is not clear, it has been suggested that this syndrome is the result of serotonin toxicity rather than withdrawal; as such, it is often referred to as "serotonin discontinuation syndrome." Clinical findings occur from several hours to several days after birth and usually resolve within 1 to 2 weeks.6

Cocaine Exposure

In-utero cocaine exposure is also associated with neurobehavioral abnormalities in neonates although a withdrawal syndrome is less clearly defined. Findings, however, are consistent with NAS and include increased irritability, tremors, and high-pitched cry—most frequently occurring between 24 and 48 hours postdelivery.6

Neonatal Alcohol Withdrawal Syndrome

Neonatal alcohol withdrawal syndrome, particularly in fetuses exposed to alcohol during the last trimester, is distinct from fetal alcohol syndrome (FAS). The latter is associated with typical dysmorphic features, growth deficiencies, and CNS findings reflective of permanent neurologic sequelae. Neonatal alcohol withdrawal presents with CNS findings similar to those listed for other in-utero exposures—eg, increased irritability, tremors, nystagmus hyperactive reflexes.7

Screening for NAS: The Finnegan Scale

The Finnegan Neonatal Abstinence Scoring System is one of the most commonly employed and validated tools used to screen for NAS. It comprises a 31-item scale, listing the clinical signs and symptoms of NAS, which are scored by severity and organized by system to include neurologic, metabolic, vasomotor, respiratory, and GI disturbances (Figure). Point allocation is based on mild, moderate, or severe symptoms as follows:

• Mild findings (eg, sweating, fever <101°F mottling, nasal stuffiness) each score 1 point.

• Moderate findings (eg, high-pitched cry, hyperactive moro reflex, increased muscle tone, fever >101°F, increased RR >60 with retractions, poor feeding, loose stools) each score 2 points.

• Severe findings (eg, myoclonic jerks, generalized convulsions, projectile vomiting, watery stools) each score 3 points.

While each of the above are independently nonspecific, the constellation of findings, together with the appropriate history, provide for a clinical diagnosis. The Finnegan Scale is therefore designed not only to aid in diagnosis, but also to quantify the severity of NAS and guide management.

Screening for NAS begins at birth in neonates with known in-utero exposure (ie, when risk of NAS is high) or at the time of initial presentation in other circumstances. Scoring is performed every 4 hours; the first two or three scores will determine the need for pharmacotherapy (see Table).

How is NAS treated?

The two main goals of management in the treatment of opioid-related NAS are to relieve the signs and symptoms of withdrawal and to prevent complications (eg, fever, weight loss, seizures). Therapy should begin with nonpharmacologic measures that minimize excess external stimuli, such as swaddling, gentle handling, and minimizing noise and light. To prevent weight loss, small hypercaloric feeds may be helpful. If pharmacologic treatment is indicated, oral opioid replacement with morphine is considered by many to be the drug of choice. Oral morphine dosing may be guided by NAS severity based on the Finnegan score; alternatively, initial dosing at 0.1 mg/kg orally every 4 hours has also been recommended.1

Other agents, such methadone 0.1 mg/kg orally every 12 hours and buprenorphine 15.9 mcg/kg divided in three doses orally, may also be used. In patients whose symptoms persist despite opioid treatment, use of adjuncts such as phenobarbital and clonidine may be indicated.

Case Conclusion

The patient was admitted to the neonatal intensive care unit where she appropriately underwent a sepsis workup. Laboratory evaluation, including blood and urine cultures, was obtained. A brain ultrasound was unremarkable, and since lumbar puncture was unsuccessful, the patient was started empirically on meningitis doses of the cefotaxime, vancomycin, and acyclovir.

An initial Finnegan score was calculated. With the exception of soft stools, there were no other persistent symptoms, and patient did not achieve a score indicating a need for pharmacologic management. After 48 hours, she remained afebrile and soft stools resolved. All laboratory values, including cultures, were unremarkable. The patient was discharged on hospital day 3, with a scheduled well-baby follow-up appointment.

Dr Laskowski is a medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of "Case Studies in Toxicology," is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

A mother presents to the ED with her 4-day-old daughter after noting abnormal jerking movements of the neonate's upper extremities. She states the baby has had watery stools for the past day, but has been tolerating bottle formula feeds without vomiting and having appropriate urinary output. The patient was born full-term via normal spontaneous vaginal delivery, with Apgar scores of 8 at 1 minute and 9 at 5 minutes. The postdelivery course was uncomplicated, and both mother and baby were discharged home 2 days after delivery.

Initial vital signs are: heart rate, 135 beats/min; respiratory rate (RR), 48 breaths/min; and temperature, 98.7°F; blood glucose was normal. On physical examination, the baby is awake and well-appearing, with a nonbulging anterior fontanelle, soft, supple neck, and flexed and symmetrically mobile extremities. Moro, suck, rooting, and grasp reflexes are all intact. No abnormal movements are noted. The remainder of the examination is unremarkable.

Do the jerking movements indicate a focal seizure? What could cause these movements in a neonate?

As the length of the postpartum hospital stay has decreased over the past 20 years, EDs have experienced an increase in neonatal visits for conditions that traditionally manifested in newborn nurseries. While most presentations are for benign reasons (eg, issues related to feeding, irritability), patients with concerning conditions, including central nervous system (CNS) abnormalities, may also initially present to the ED. Causes of such clinical findings may be structural (eg, cerebral malformations, subdural hematomas, herpes encephalitis) and/or metabolic (eg, hypoglycemia, hypocalcemia, inborn errors). Many early-onset neonatal seizures are benign and resolve by several months of age, but it is essential to identify those that are consequential and treatable.

Case Continuation

In the evaluation of the neonatal patient with suspected seizure, it is important to take a detailed maternal and labor history, and to consider a broad differential in the face of nonspecific findings. In this case, the patient's mother disclosed a personal history of chronic pain, for which she took buprenorphine 2 mg orally in the morning and 4 mg orally at bedtime (total daily dose of 6mg/day) throughout her pregnancy.

How does drug withdrawal present in the neonate?

Neonatal abstinence syndrome (NAS) is the clinical syndrome of withdrawal in a newborn exposed in utero to drugs capable of inducing dependence. Agents associated with NAS include opioids, benzodiazepines, ethanol, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, and nicotine.1,2

Over the past decade, there has been a 330% rise in the diagnosis of opioid-related NAS alone.3 In response to this increase, the US Food and Drug Administration recently added a black-box warning to all extended-release/long-acting opioid preparations detailing this risk.4

Presenting symptoms of NAS are protean, differ from patient to patient, and are a function of drug type, duration, and amount of drug exposure. NAS may mimic other severe life-threatening conditions such as those previously noted, and the inability to obtain an adequate symptom-based medical history from a neonate further complicates the diagnosis. Before making a diagnosis of NAS, other conditions should be carefully considered in the differential.

Neonatal opioid withdrawal manifests primarily with CNS and gastrointestinal (GI) effects since there are high concentrations of opioid receptors in these areas. Although clinical findings are generally similar among opioid agents, the onset and duration following abstinence varies—largely based on individual drug half-life; this helps to differentiate between opioid agents. For example, while babies exposed to heroin in utero present with signs of NAS within 24 hours of birth, those exposed to buprenorphine or methadone tend to present 2 to 6 days after delivery.1 Between 55% to 94% of neonates with in-utero opioid exposure develop NAS.5

Select Serotonin Reuptake Inhibitors

SSRIs have also been associated with a neonatal syndrome, and largely involve similar signs and symptoms as NAS. Although the specific etiology is not clear, it has been suggested that this syndrome is the result of serotonin toxicity rather than withdrawal; as such, it is often referred to as "serotonin discontinuation syndrome." Clinical findings occur from several hours to several days after birth and usually resolve within 1 to 2 weeks.6

Cocaine Exposure

In-utero cocaine exposure is also associated with neurobehavioral abnormalities in neonates although a withdrawal syndrome is less clearly defined. Findings, however, are consistent with NAS and include increased irritability, tremors, and high-pitched cry—most frequently occurring between 24 and 48 hours postdelivery.6

Neonatal Alcohol Withdrawal Syndrome

Neonatal alcohol withdrawal syndrome, particularly in fetuses exposed to alcohol during the last trimester, is distinct from fetal alcohol syndrome (FAS). The latter is associated with typical dysmorphic features, growth deficiencies, and CNS findings reflective of permanent neurologic sequelae. Neonatal alcohol withdrawal presents with CNS findings similar to those listed for other in-utero exposures—eg, increased irritability, tremors, nystagmus hyperactive reflexes.7

Screening for NAS: The Finnegan Scale

The Finnegan Neonatal Abstinence Scoring System is one of the most commonly employed and validated tools used to screen for NAS. It comprises a 31-item scale, listing the clinical signs and symptoms of NAS, which are scored by severity and organized by system to include neurologic, metabolic, vasomotor, respiratory, and GI disturbances (Figure). Point allocation is based on mild, moderate, or severe symptoms as follows:

• Mild findings (eg, sweating, fever <101°F mottling, nasal stuffiness) each score 1 point.

• Moderate findings (eg, high-pitched cry, hyperactive moro reflex, increased muscle tone, fever >101°F, increased RR >60 with retractions, poor feeding, loose stools) each score 2 points.

• Severe findings (eg, myoclonic jerks, generalized convulsions, projectile vomiting, watery stools) each score 3 points.

While each of the above are independently nonspecific, the constellation of findings, together with the appropriate history, provide for a clinical diagnosis. The Finnegan Scale is therefore designed not only to aid in diagnosis, but also to quantify the severity of NAS and guide management.

Screening for NAS begins at birth in neonates with known in-utero exposure (ie, when risk of NAS is high) or at the time of initial presentation in other circumstances. Scoring is performed every 4 hours; the first two or three scores will determine the need for pharmacotherapy (see Table).

How is NAS treated?

The two main goals of management in the treatment of opioid-related NAS are to relieve the signs and symptoms of withdrawal and to prevent complications (eg, fever, weight loss, seizures). Therapy should begin with nonpharmacologic measures that minimize excess external stimuli, such as swaddling, gentle handling, and minimizing noise and light. To prevent weight loss, small hypercaloric feeds may be helpful. If pharmacologic treatment is indicated, oral opioid replacement with morphine is considered by many to be the drug of choice. Oral morphine dosing may be guided by NAS severity based on the Finnegan score; alternatively, initial dosing at 0.1 mg/kg orally every 4 hours has also been recommended.1

Other agents, such methadone 0.1 mg/kg orally every 12 hours and buprenorphine 15.9 mcg/kg divided in three doses orally, may also be used. In patients whose symptoms persist despite opioid treatment, use of adjuncts such as phenobarbital and clonidine may be indicated.

Case Conclusion

The patient was admitted to the neonatal intensive care unit where she appropriately underwent a sepsis workup. Laboratory evaluation, including blood and urine cultures, was obtained. A brain ultrasound was unremarkable, and since lumbar puncture was unsuccessful, the patient was started empirically on meningitis doses of the cefotaxime, vancomycin, and acyclovir.

An initial Finnegan score was calculated. With the exception of soft stools, there were no other persistent symptoms, and patient did not achieve a score indicating a need for pharmacologic management. After 48 hours, she remained afebrile and soft stools resolved. All laboratory values, including cultures, were unremarkable. The patient was discharged on hospital day 3, with a scheduled well-baby follow-up appointment.

Dr Laskowski is a medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of "Case Studies in Toxicology," is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.

A mother presents to the ED with her 4-day-old daughter after noting abnormal jerking movements of the neonate's upper extremities. She states the baby has had watery stools for the past day, but has been tolerating bottle formula feeds without vomiting and having appropriate urinary output. The patient was born full-term via normal spontaneous vaginal delivery, with Apgar scores of 8 at 1 minute and 9 at 5 minutes. The postdelivery course was uncomplicated, and both mother and baby were discharged home 2 days after delivery.

Initial vital signs are: heart rate, 135 beats/min; respiratory rate (RR), 48 breaths/min; and temperature, 98.7°F; blood glucose was normal. On physical examination, the baby is awake and well-appearing, with a nonbulging anterior fontanelle, soft, supple neck, and flexed and symmetrically mobile extremities. Moro, suck, rooting, and grasp reflexes are all intact. No abnormal movements are noted. The remainder of the examination is unremarkable.

Do the jerking movements indicate a focal seizure? What could cause these movements in a neonate?

As the length of the postpartum hospital stay has decreased over the past 20 years, EDs have experienced an increase in neonatal visits for conditions that traditionally manifested in newborn nurseries. While most presentations are for benign reasons (eg, issues related to feeding, irritability), patients with concerning conditions, including central nervous system (CNS) abnormalities, may also initially present to the ED. Causes of such clinical findings may be structural (eg, cerebral malformations, subdural hematomas, herpes encephalitis) and/or metabolic (eg, hypoglycemia, hypocalcemia, inborn errors). Many early-onset neonatal seizures are benign and resolve by several months of age, but it is essential to identify those that are consequential and treatable.

Case Continuation

In the evaluation of the neonatal patient with suspected seizure, it is important to take a detailed maternal and labor history, and to consider a broad differential in the face of nonspecific findings. In this case, the patient's mother disclosed a personal history of chronic pain, for which she took buprenorphine 2 mg orally in the morning and 4 mg orally at bedtime (total daily dose of 6mg/day) throughout her pregnancy.

How does drug withdrawal present in the neonate?

Neonatal abstinence syndrome (NAS) is the clinical syndrome of withdrawal in a newborn exposed in utero to drugs capable of inducing dependence. Agents associated with NAS include opioids, benzodiazepines, ethanol, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, and nicotine.1,2

Over the past decade, there has been a 330% rise in the diagnosis of opioid-related NAS alone.3 In response to this increase, the US Food and Drug Administration recently added a black-box warning to all extended-release/long-acting opioid preparations detailing this risk.4

Presenting symptoms of NAS are protean, differ from patient to patient, and are a function of drug type, duration, and amount of drug exposure. NAS may mimic other severe life-threatening conditions such as those previously noted, and the inability to obtain an adequate symptom-based medical history from a neonate further complicates the diagnosis. Before making a diagnosis of NAS, other conditions should be carefully considered in the differential.

Neonatal opioid withdrawal manifests primarily with CNS and gastrointestinal (GI) effects since there are high concentrations of opioid receptors in these areas. Although clinical findings are generally similar among opioid agents, the onset and duration following abstinence varies—largely based on individual drug half-life; this helps to differentiate between opioid agents. For example, while babies exposed to heroin in utero present with signs of NAS within 24 hours of birth, those exposed to buprenorphine or methadone tend to present 2 to 6 days after delivery.1 Between 55% to 94% of neonates with in-utero opioid exposure develop NAS.5

Select Serotonin Reuptake Inhibitors

SSRIs have also been associated with a neonatal syndrome, and largely involve similar signs and symptoms as NAS. Although the specific etiology is not clear, it has been suggested that this syndrome is the result of serotonin toxicity rather than withdrawal; as such, it is often referred to as "serotonin discontinuation syndrome." Clinical findings occur from several hours to several days after birth and usually resolve within 1 to 2 weeks.6

Cocaine Exposure

In-utero cocaine exposure is also associated with neurobehavioral abnormalities in neonates although a withdrawal syndrome is less clearly defined. Findings, however, are consistent with NAS and include increased irritability, tremors, and high-pitched cry—most frequently occurring between 24 and 48 hours postdelivery.6

Neonatal Alcohol Withdrawal Syndrome

Neonatal alcohol withdrawal syndrome, particularly in fetuses exposed to alcohol during the last trimester, is distinct from fetal alcohol syndrome (FAS). The latter is associated with typical dysmorphic features, growth deficiencies, and CNS findings reflective of permanent neurologic sequelae. Neonatal alcohol withdrawal presents with CNS findings similar to those listed for other in-utero exposures—eg, increased irritability, tremors, nystagmus hyperactive reflexes.7

Screening for NAS: The Finnegan Scale

The Finnegan Neonatal Abstinence Scoring System is one of the most commonly employed and validated tools used to screen for NAS. It comprises a 31-item scale, listing the clinical signs and symptoms of NAS, which are scored by severity and organized by system to include neurologic, metabolic, vasomotor, respiratory, and GI disturbances (Figure). Point allocation is based on mild, moderate, or severe symptoms as follows:

• Mild findings (eg, sweating, fever <101°F mottling, nasal stuffiness) each score 1 point.

• Moderate findings (eg, high-pitched cry, hyperactive moro reflex, increased muscle tone, fever >101°F, increased RR >60 with retractions, poor feeding, loose stools) each score 2 points.

• Severe findings (eg, myoclonic jerks, generalized convulsions, projectile vomiting, watery stools) each score 3 points.

While each of the above are independently nonspecific, the constellation of findings, together with the appropriate history, provide for a clinical diagnosis. The Finnegan Scale is therefore designed not only to aid in diagnosis, but also to quantify the severity of NAS and guide management.

Screening for NAS begins at birth in neonates with known in-utero exposure (ie, when risk of NAS is high) or at the time of initial presentation in other circumstances. Scoring is performed every 4 hours; the first two or three scores will determine the need for pharmacotherapy (see Table).

How is NAS treated?

The two main goals of management in the treatment of opioid-related NAS are to relieve the signs and symptoms of withdrawal and to prevent complications (eg, fever, weight loss, seizures). Therapy should begin with nonpharmacologic measures that minimize excess external stimuli, such as swaddling, gentle handling, and minimizing noise and light. To prevent weight loss, small hypercaloric feeds may be helpful. If pharmacologic treatment is indicated, oral opioid replacement with morphine is considered by many to be the drug of choice. Oral morphine dosing may be guided by NAS severity based on the Finnegan score; alternatively, initial dosing at 0.1 mg/kg orally every 4 hours has also been recommended.1

Other agents, such methadone 0.1 mg/kg orally every 12 hours and buprenorphine 15.9 mcg/kg divided in three doses orally, may also be used. In patients whose symptoms persist despite opioid treatment, use of adjuncts such as phenobarbital and clonidine may be indicated.

Case Conclusion

The patient was admitted to the neonatal intensive care unit where she appropriately underwent a sepsis workup. Laboratory evaluation, including blood and urine cultures, was obtained. A brain ultrasound was unremarkable, and since lumbar puncture was unsuccessful, the patient was started empirically on meningitis doses of the cefotaxime, vancomycin, and acyclovir.

An initial Finnegan score was calculated. With the exception of soft stools, there were no other persistent symptoms, and patient did not achieve a score indicating a need for pharmacologic management. After 48 hours, she remained afebrile and soft stools resolved. All laboratory values, including cultures, were unremarkable. The patient was discharged on hospital day 3, with a scheduled well-baby follow-up appointment.

Dr Laskowski is a medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of "Case Studies in Toxicology," is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.