Case Studies in Toxicology: A Common Procedure, an Uncommon Complication

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.