Vince Nguyen, MD

Case

A 35-year-old woman underwent an elective hysteroscopic myomectomy to remove a symptomatic 2.7-cm uterine leiomyoma. The procedure was uncomplicated, and the patient awoke in the postanesthesia care unit (PACU) in good condition. Two hours later, however, she developed severe shortness of breath and required bilevel positive airway pressure ventilation. Her vital signs in the PACU were: blood pressure (BP), 110/70 mm Hg; heart rate, 90 beats/minute; respiratory rate, 12 breaths/minute; temperature, 98.4°F. Oxygen saturation was 94% on room air. She was diaphoretic and tachycardic on physical examination, but her pulmonary, abdominal, and gynecologic examinations were normal. During the examination, she complained of nausea, vomited, and then became increasingly lethargic and confused. 

How can this patient’s clinical presentation be explained?

Uterine fibroids are the most common pelvic tumor in women.¹ Hysteroscopic myomectomy is a minimally invasive surgical procedure commonly performed to resect submucosal fibroids. The procedure takes about 60 minutes, and is often performed on an outpatient basis under general anesthesia. During the procedure, an electrosurgery device called a resectoscope is inserted through the cervix. The uterine cavity is then distended with a large volume of irrigating solution. Maneuvering the resectoscope, the surgeon then shaves the protruding fibroid layer-by-layer until it aligns with the surrounding myometrium.

Surgical complications of hysteroscopic myomectomy may produce life-threatening effects. Excessive resection of the myometrium may increase blood loss, which can cause chest pain, shortness of breath, diaphoresis, lethargy, and confusion. Uterine perforation may produce hypotension, abdominal pain and distention, infection, and vaginal bleeding.

Venous Thromboembolism

Venous thromboembolism (VTE) is a common postoperative complication, with pulmonary embolism accounting for the most common preventable cause of hospital death in the United States.² Gynecologic surgery, especially brief procedures, are associated with among the lowest rates of VTE, however, making this an unlikely explanation in this case.³ Additionally, VTE is not expected to produce the neurological findings observed in this patient.

Negative Pressure Pulmonary Edema

An uncommon but life-threatening complication for patients undergoing general anesthesia is negative pressure pulmonary edema, or “postextubation pulmonary edema,” which is estimated to occur in up to 1 in 1,000 procedures involving mechanical ventilation. During extubation, forced inspiration against a closed glottis causes intravascular fluid to be drawn into the interstitial space leading to pulmonary edema.⁴

Hyponatremia

An unusual but well described complication of endoscopic surgery is hyponatremia from systemic absorption of the irrigating fluid. Fluid overload may result in pulmonary edema, and dilutional hyponatremia may cause altered mental status or seizures.

Case Continuation

A chest X-ray performed after the patient became symptomatic revealed mild bilateral pulmonary edema. Her postoperative laboratory values were: sodium, 112 mEq/L; potassium, 3.3 mEq/L; chloride, 81 mEq/L; bicarbonate, 25 mEq/L; blood urea nitrogen, 18 mg/dL; creatinine, 0.6 mg/dL. Her ammonia level was 24 mmol/L (normal range, 11-35 mmol/L). An endotracheal tube was placed after her level of consciousness declined further. Her neurological examination revealed bilateral fixed and dilated pupils. An emergent computed tomography (CT) scan of the brain revealed severe generalized swelling of the brain.

What is the cause of this patient’s hyponatremia?

Monopolar electrosurgical devices such as the resectoscope cannot be used with electrolyte-containing irrigation fluids (eg, isotonic saline or lactated Ringer’s solution).  Nonconductive, nonelectrolyte solutions such as glycine 1.5%, sorbitol 3%, or mannitol 5%, are the most common irrigating fluids employed to dilate the operating field and to wash away debris and blood.⁵

A dilutional hyponatremia can occur when the irrigating fluid is absorbed systemically. As it was first described following transurethral resection of the prostate procedures in the 1950s, the syndrome is referred to as “TURP” syndrome. Since then, several hundred life-threatening and even fatal cases of TURP syndrome have been reported.⁶ The syndrome occurs with other operations including transcervical resection of the endometrium (TCRE).⁵ The irrigating fluid is most frequently absorbed directly into the vascular system when a vein has been severed during the electrosurgery, particularly when the infusion pressure exceeds the venous pressure.⁶ Additionally, extravasation of the irrigating fluid into the intraperitoneal space can occur after instrument perforation of the uterine wall in TCRE, or via the fallopian tubes.⁶

What are the signs and symptoms of TURP syndrome?

Mild-to-moderate TURP syndrome occurs in 1% to 8% of TURP procedures performed.  Fluid absorption is slightly more common during TCRE, and occurs more often during the resection of fibroids.⁶ The dilutional hyponatremia can result in brain edema, as well as pharmacological effects specific to the irrigant solutes. 

Symptoms of TURP syndrome are primarily neurological, with nausea being the earliest sign of a mild syndrome. A “mini” mental-status test may show transient confusion with smaller absorption volumes.⁷ As the fluid absorption increases, the hyponatremia worsens, resulting in cerebral edema. This manifests as encephalopathy, which includes disorientation, twitching, and seizures. Hypotension is uncommon, since the fluid is being absorbed intravascularly.⁶ Shortness of breath, uneasiness, chest pain, and pulmonary edema may develop from systemic fluid overload. The intra-abdominal extravasation of fluid can result in abdominal pain. Other symptoms are specific to the irrigant.

Glycine

Glycine 1.5% is the most common irrigant solution used; as such, it produces the highest incidence of TURP syndrome.⁸ This solution is hypoosmotic (osmolality of 200 mosm/kg) compared with the normal serum (osmolality of 280 to 296 mosm/kg).⁵ In addition, glycine may cause visual disturbances.⁸ The metabolism of glycine produces ammonia, serine, and oxalate (Figure), and 10% of patients who absorb glycine show a marked hyperammonemia, further exacerbating the neurological effects^.9,10

Sorbitol and mannitol

Sorbitol and mannitol irrigation fluids are used less frequently than glycine. Sorbitol 3% is metabolized to fructose and glucose, and has an osmolality of 165 mosm/kg.⁶ When absorbed systemically, sorbitol’s effects are similar to those of glycine, except that it does not induce visual symptoms. Mannitol 5% solution has the advantage of being isosmotic (275 mosm/kg). It is not metabolized and is excreted entirely in the urine. The excretion of mannitol creates an osmotic diuresis, thereby preventing hyponatremia from occurring.⁹Sorbitol and Mannitol

What are the treatment options for TURP Syndrome? Can it be prevented?

Patients with TURP syndrome in its mildest form can be asymptomatic, but severe cases can be life threatening or fatal. Unlike the treatment for hyponatremia caused by psychogenic polydipsia or the syndrome of inappropriate antidiuretic hormone, which calls for fluid restriction, plasma volume expansion is indicated in TURP syndrome, as hypovolemia and low-cardiac output develop as soon as irrigation is discontinued.

Hypertonic saline is indicated for neurological symptoms, or if the serum sodium concentration is <120mEq/L.⁶ Although furosemide has been used to treat acute pulmonary edema, no studies support its routine use in the treatment of fluid absorption,⁶ and its use may aggravate hyponatremia and hypovolemia. 

Bipolar electrosurgical systems, unlike monopolar systems, permit the use of electrolyte solutions such as isotonic saline, thereby significantly reducing the risk of hyponatremia. For hysteroscopic procedures, the American College of Obstetricians and Gynecologists recommends the use of an automated fluid pump and monitoring system, thus minimizing the fluid pressure and halting or terminating the procedure before absorption thresholds are exceeded.¹¹

Case Conclusion

The patient was immediately given a 1 mL/kg bolus of hypertonic saline. Two hours later, her serum sodium improved to 114 mEq/L and serum sodium concentration normalized over the next 24 hours. Her cardiovascular and neurological examinations worsened, however, and she required vasopressors. Her pupils remained fixed and dilated, and she lost her corneal and gag reflexes. A repeat CT of the brain showed persistent cerebral edema with signs of herniation, and she did not recover.

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 35-year-old woman underwent an elective hysteroscopic myomectomy to remove a symptomatic 2.7-cm uterine leiomyoma. The procedure was uncomplicated, and the patient awoke in the postanesthesia care unit (PACU) in good condition. Two hours later, however, she developed severe shortness of breath and required bilevel positive airway pressure ventilation. Her vital signs in the PACU were: blood pressure (BP), 110/70 mm Hg; heart rate, 90 beats/minute; respiratory rate, 12 breaths/minute; temperature, 98.4°F. Oxygen saturation was 94% on room air. She was diaphoretic and tachycardic on physical examination, but her pulmonary, abdominal, and gynecologic examinations were normal. During the examination, she complained of nausea, vomited, and then became increasingly lethargic and confused. 

How can this patient’s clinical presentation be explained?

Uterine fibroids are the most common pelvic tumor in women.¹ Hysteroscopic myomectomy is a minimally invasive surgical procedure commonly performed to resect submucosal fibroids. The procedure takes about 60 minutes, and is often performed on an outpatient basis under general anesthesia. During the procedure, an electrosurgery device called a resectoscope is inserted through the cervix. The uterine cavity is then distended with a large volume of irrigating solution. Maneuvering the resectoscope, the surgeon then shaves the protruding fibroid layer-by-layer until it aligns with the surrounding myometrium.

Surgical complications of hysteroscopic myomectomy may produce life-threatening effects. Excessive resection of the myometrium may increase blood loss, which can cause chest pain, shortness of breath, diaphoresis, lethargy, and confusion. Uterine perforation may produce hypotension, abdominal pain and distention, infection, and vaginal bleeding.

Venous Thromboembolism

Venous thromboembolism (VTE) is a common postoperative complication, with pulmonary embolism accounting for the most common preventable cause of hospital death in the United States.² Gynecologic surgery, especially brief procedures, are associated with among the lowest rates of VTE, however, making this an unlikely explanation in this case.³ Additionally, VTE is not expected to produce the neurological findings observed in this patient.

Negative Pressure Pulmonary Edema

An uncommon but life-threatening complication for patients undergoing general anesthesia is negative pressure pulmonary edema, or “postextubation pulmonary edema,” which is estimated to occur in up to 1 in 1,000 procedures involving mechanical ventilation. During extubation, forced inspiration against a closed glottis causes intravascular fluid to be drawn into the interstitial space leading to pulmonary edema.⁴

Hyponatremia

An unusual but well described complication of endoscopic surgery is hyponatremia from systemic absorption of the irrigating fluid. Fluid overload may result in pulmonary edema, and dilutional hyponatremia may cause altered mental status or seizures.

Case Continuation

A chest X-ray performed after the patient became symptomatic revealed mild bilateral pulmonary edema. Her postoperative laboratory values were: sodium, 112 mEq/L; potassium, 3.3 mEq/L; chloride, 81 mEq/L; bicarbonate, 25 mEq/L; blood urea nitrogen, 18 mg/dL; creatinine, 0.6 mg/dL. Her ammonia level was 24 mmol/L (normal range, 11-35 mmol/L). An endotracheal tube was placed after her level of consciousness declined further. Her neurological examination revealed bilateral fixed and dilated pupils. An emergent computed tomography (CT) scan of the brain revealed severe generalized swelling of the brain.

What is the cause of this patient’s hyponatremia?

Monopolar electrosurgical devices such as the resectoscope cannot be used with electrolyte-containing irrigation fluids (eg, isotonic saline or lactated Ringer’s solution).  Nonconductive, nonelectrolyte solutions such as glycine 1.5%, sorbitol 3%, or mannitol 5%, are the most common irrigating fluids employed to dilate the operating field and to wash away debris and blood.⁵

A dilutional hyponatremia can occur when the irrigating fluid is absorbed systemically. As it was first described following transurethral resection of the prostate procedures in the 1950s, the syndrome is referred to as “TURP” syndrome. Since then, several hundred life-threatening and even fatal cases of TURP syndrome have been reported.⁶ The syndrome occurs with other operations including transcervical resection of the endometrium (TCRE).⁵ The irrigating fluid is most frequently absorbed directly into the vascular system when a vein has been severed during the electrosurgery, particularly when the infusion pressure exceeds the venous pressure.⁶ Additionally, extravasation of the irrigating fluid into the intraperitoneal space can occur after instrument perforation of the uterine wall in TCRE, or via the fallopian tubes.⁶

What are the signs and symptoms of TURP syndrome?

Mild-to-moderate TURP syndrome occurs in 1% to 8% of TURP procedures performed.  Fluid absorption is slightly more common during TCRE, and occurs more often during the resection of fibroids.⁶ The dilutional hyponatremia can result in brain edema, as well as pharmacological effects specific to the irrigant solutes. 

Symptoms of TURP syndrome are primarily neurological, with nausea being the earliest sign of a mild syndrome. A “mini” mental-status test may show transient confusion with smaller absorption volumes.⁷ As the fluid absorption increases, the hyponatremia worsens, resulting in cerebral edema. This manifests as encephalopathy, which includes disorientation, twitching, and seizures. Hypotension is uncommon, since the fluid is being absorbed intravascularly.⁶ Shortness of breath, uneasiness, chest pain, and pulmonary edema may develop from systemic fluid overload. The intra-abdominal extravasation of fluid can result in abdominal pain. Other symptoms are specific to the irrigant.

Glycine

Glycine 1.5% is the most common irrigant solution used; as such, it produces the highest incidence of TURP syndrome.⁸ This solution is hypoosmotic (osmolality of 200 mosm/kg) compared with the normal serum (osmolality of 280 to 296 mosm/kg).⁵ In addition, glycine may cause visual disturbances.⁸ The metabolism of glycine produces ammonia, serine, and oxalate (Figure), and 10% of patients who absorb glycine show a marked hyperammonemia, further exacerbating the neurological effects^.9,10

Sorbitol and mannitol

Sorbitol and mannitol irrigation fluids are used less frequently than glycine. Sorbitol 3% is metabolized to fructose and glucose, and has an osmolality of 165 mosm/kg.⁶ When absorbed systemically, sorbitol’s effects are similar to those of glycine, except that it does not induce visual symptoms. Mannitol 5% solution has the advantage of being isosmotic (275 mosm/kg). It is not metabolized and is excreted entirely in the urine. The excretion of mannitol creates an osmotic diuresis, thereby preventing hyponatremia from occurring.⁹Sorbitol and Mannitol

What are the treatment options for TURP Syndrome? Can it be prevented?

Patients with TURP syndrome in its mildest form can be asymptomatic, but severe cases can be life threatening or fatal. Unlike the treatment for hyponatremia caused by psychogenic polydipsia or the syndrome of inappropriate antidiuretic hormone, which calls for fluid restriction, plasma volume expansion is indicated in TURP syndrome, as hypovolemia and low-cardiac output develop as soon as irrigation is discontinued.

Hypertonic saline is indicated for neurological symptoms, or if the serum sodium concentration is <120mEq/L.⁶ Although furosemide has been used to treat acute pulmonary edema, no studies support its routine use in the treatment of fluid absorption,⁶ and its use may aggravate hyponatremia and hypovolemia. 

Bipolar electrosurgical systems, unlike monopolar systems, permit the use of electrolyte solutions such as isotonic saline, thereby significantly reducing the risk of hyponatremia. For hysteroscopic procedures, the American College of Obstetricians and Gynecologists recommends the use of an automated fluid pump and monitoring system, thus minimizing the fluid pressure and halting or terminating the procedure before absorption thresholds are exceeded.¹¹

Case Conclusion

The patient was immediately given a 1 mL/kg bolus of hypertonic saline. Two hours later, her serum sodium improved to 114 mEq/L and serum sodium concentration normalized over the next 24 hours. Her cardiovascular and neurological examinations worsened, however, and she required vasopressors. Her pupils remained fixed and dilated, and she lost her corneal and gag reflexes. A repeat CT of the brain showed persistent cerebral edema with signs of herniation, and she did not recover.

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 35-year-old woman underwent an elective hysteroscopic myomectomy to remove a symptomatic 2.7-cm uterine leiomyoma. The procedure was uncomplicated, and the patient awoke in the postanesthesia care unit (PACU) in good condition. Two hours later, however, she developed severe shortness of breath and required bilevel positive airway pressure ventilation. Her vital signs in the PACU were: blood pressure (BP), 110/70 mm Hg; heart rate, 90 beats/minute; respiratory rate, 12 breaths/minute; temperature, 98.4°F. Oxygen saturation was 94% on room air. She was diaphoretic and tachycardic on physical examination, but her pulmonary, abdominal, and gynecologic examinations were normal. During the examination, she complained of nausea, vomited, and then became increasingly lethargic and confused. 

How can this patient’s clinical presentation be explained?

Uterine fibroids are the most common pelvic tumor in women.¹ Hysteroscopic myomectomy is a minimally invasive surgical procedure commonly performed to resect submucosal fibroids. The procedure takes about 60 minutes, and is often performed on an outpatient basis under general anesthesia. During the procedure, an electrosurgery device called a resectoscope is inserted through the cervix. The uterine cavity is then distended with a large volume of irrigating solution. Maneuvering the resectoscope, the surgeon then shaves the protruding fibroid layer-by-layer until it aligns with the surrounding myometrium.

Surgical complications of hysteroscopic myomectomy may produce life-threatening effects. Excessive resection of the myometrium may increase blood loss, which can cause chest pain, shortness of breath, diaphoresis, lethargy, and confusion. Uterine perforation may produce hypotension, abdominal pain and distention, infection, and vaginal bleeding.

Venous Thromboembolism

Venous thromboembolism (VTE) is a common postoperative complication, with pulmonary embolism accounting for the most common preventable cause of hospital death in the United States.² Gynecologic surgery, especially brief procedures, are associated with among the lowest rates of VTE, however, making this an unlikely explanation in this case.³ Additionally, VTE is not expected to produce the neurological findings observed in this patient.

Negative Pressure Pulmonary Edema

An uncommon but life-threatening complication for patients undergoing general anesthesia is negative pressure pulmonary edema, or “postextubation pulmonary edema,” which is estimated to occur in up to 1 in 1,000 procedures involving mechanical ventilation. During extubation, forced inspiration against a closed glottis causes intravascular fluid to be drawn into the interstitial space leading to pulmonary edema.⁴

Hyponatremia

An unusual but well described complication of endoscopic surgery is hyponatremia from systemic absorption of the irrigating fluid. Fluid overload may result in pulmonary edema, and dilutional hyponatremia may cause altered mental status or seizures.

Case Continuation

A chest X-ray performed after the patient became symptomatic revealed mild bilateral pulmonary edema. Her postoperative laboratory values were: sodium, 112 mEq/L; potassium, 3.3 mEq/L; chloride, 81 mEq/L; bicarbonate, 25 mEq/L; blood urea nitrogen, 18 mg/dL; creatinine, 0.6 mg/dL. Her ammonia level was 24 mmol/L (normal range, 11-35 mmol/L). An endotracheal tube was placed after her level of consciousness declined further. Her neurological examination revealed bilateral fixed and dilated pupils. An emergent computed tomography (CT) scan of the brain revealed severe generalized swelling of the brain.

What is the cause of this patient’s hyponatremia?

Monopolar electrosurgical devices such as the resectoscope cannot be used with electrolyte-containing irrigation fluids (eg, isotonic saline or lactated Ringer’s solution).  Nonconductive, nonelectrolyte solutions such as glycine 1.5%, sorbitol 3%, or mannitol 5%, are the most common irrigating fluids employed to dilate the operating field and to wash away debris and blood.⁵

A dilutional hyponatremia can occur when the irrigating fluid is absorbed systemically. As it was first described following transurethral resection of the prostate procedures in the 1950s, the syndrome is referred to as “TURP” syndrome. Since then, several hundred life-threatening and even fatal cases of TURP syndrome have been reported.⁶ The syndrome occurs with other operations including transcervical resection of the endometrium (TCRE).⁵ The irrigating fluid is most frequently absorbed directly into the vascular system when a vein has been severed during the electrosurgery, particularly when the infusion pressure exceeds the venous pressure.⁶ Additionally, extravasation of the irrigating fluid into the intraperitoneal space can occur after instrument perforation of the uterine wall in TCRE, or via the fallopian tubes.⁶

What are the signs and symptoms of TURP syndrome?

Mild-to-moderate TURP syndrome occurs in 1% to 8% of TURP procedures performed.  Fluid absorption is slightly more common during TCRE, and occurs more often during the resection of fibroids.⁶ The dilutional hyponatremia can result in brain edema, as well as pharmacological effects specific to the irrigant solutes. 

Symptoms of TURP syndrome are primarily neurological, with nausea being the earliest sign of a mild syndrome. A “mini” mental-status test may show transient confusion with smaller absorption volumes.⁷ As the fluid absorption increases, the hyponatremia worsens, resulting in cerebral edema. This manifests as encephalopathy, which includes disorientation, twitching, and seizures. Hypotension is uncommon, since the fluid is being absorbed intravascularly.⁶ Shortness of breath, uneasiness, chest pain, and pulmonary edema may develop from systemic fluid overload. The intra-abdominal extravasation of fluid can result in abdominal pain. Other symptoms are specific to the irrigant.

Glycine

Glycine 1.5% is the most common irrigant solution used; as such, it produces the highest incidence of TURP syndrome.⁸ This solution is hypoosmotic (osmolality of 200 mosm/kg) compared with the normal serum (osmolality of 280 to 296 mosm/kg).⁵ In addition, glycine may cause visual disturbances.⁸ The metabolism of glycine produces ammonia, serine, and oxalate (Figure), and 10% of patients who absorb glycine show a marked hyperammonemia, further exacerbating the neurological effects^.9,10

Sorbitol and mannitol

Sorbitol and mannitol irrigation fluids are used less frequently than glycine. Sorbitol 3% is metabolized to fructose and glucose, and has an osmolality of 165 mosm/kg.⁶ When absorbed systemically, sorbitol’s effects are similar to those of glycine, except that it does not induce visual symptoms. Mannitol 5% solution has the advantage of being isosmotic (275 mosm/kg). It is not metabolized and is excreted entirely in the urine. The excretion of mannitol creates an osmotic diuresis, thereby preventing hyponatremia from occurring.⁹Sorbitol and Mannitol

What are the treatment options for TURP Syndrome? Can it be prevented?

Patients with TURP syndrome in its mildest form can be asymptomatic, but severe cases can be life threatening or fatal. Unlike the treatment for hyponatremia caused by psychogenic polydipsia or the syndrome of inappropriate antidiuretic hormone, which calls for fluid restriction, plasma volume expansion is indicated in TURP syndrome, as hypovolemia and low-cardiac output develop as soon as irrigation is discontinued.

Hypertonic saline is indicated for neurological symptoms, or if the serum sodium concentration is <120mEq/L.⁶ Although furosemide has been used to treat acute pulmonary edema, no studies support its routine use in the treatment of fluid absorption,⁶ and its use may aggravate hyponatremia and hypovolemia. 

Bipolar electrosurgical systems, unlike monopolar systems, permit the use of electrolyte solutions such as isotonic saline, thereby significantly reducing the risk of hyponatremia. For hysteroscopic procedures, the American College of Obstetricians and Gynecologists recommends the use of an automated fluid pump and monitoring system, thus minimizing the fluid pressure and halting or terminating the procedure before absorption thresholds are exceeded.¹¹

Case Conclusion

The patient was immediately given a 1 mL/kg bolus of hypertonic saline. Two hours later, her serum sodium improved to 114 mEq/L and serum sodium concentration normalized over the next 24 hours. Her cardiovascular and neurological examinations worsened, however, and she required vasopressors. Her pupils remained fixed and dilated, and she lost her corneal and gag reflexes. A repeat CT of the brain showed persistent cerebral edema with signs of herniation, and she did not recover.

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.

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.