Glycine: Mechanism of Action, Uses, Side Effects

Mechanism of action

Glycine functions as an irrigating solution rather than a pharmacologically active drug. During endoscopic urologic procedures, it distends the operative field and provides optical clarity by maintaining a transparent medium that does not conduct electrical current. This non-conductive property is essential during monopolar electrosurgical resection.

When systemically absorbed through opened venous sinuses during surgery, glycine undergoes hepatic metabolism. It is deaminated primarily to ammonia and glyoxylate, with subsequent conversion to oxalate and glycolic acid. This metabolic pathway is clinically significant because ammonia accumulation can cause neurotoxicity. Glycine also acts as an inhibitory neurotransmitter in the central nervous system, particularly in the spinal cord and brainstem, binding to glycine receptors and causing neuronal hyperpolarization through chloride influx.

The hypotonic nature of glycine solutions (1.5% glycine is approximately 200 mOsm/L) means that excessive absorption leads to dilutional hyponatremia and hypoosmolality, contributing to the constellation of findings known as TURP syndrome.

High-yield for exams

Glycine 1.5% irrigation is hypotonic (~200 mOsm/L) and non-conductive, required for monopolar electrosurgery during TURP
TURP syndrome: hyponatremia + hyperammonemia + volume overload from glycine absorption through prostatic venous sinuses
Glycine metabolizes to ammonia (causing encephalopathy) and glyoxylate/oxalate (rare crystal nephropathy)
Classic TURP syndrome triad: altered mental status, cardiovascular instability, visual disturbances (including transient blindness)
Risk factors: prolonged surgery >90 min, large resection >45g, high irrigation pressure, baseline hyponatremia or liver disease
Bipolar TURP with saline irrigation eliminates glycine toxicity while still allowing TURP syndrome from fluid absorption
Treatment: stop surgery, hypertonic saline (3%) for symptomatic Na <120 mEq/L, furosemide for volume overload, supportive care
Glycine acts as inhibitory neurotransmitter at spinal glycine receptors, contributing to CNS depression in toxicity

Indications

Glycine irrigation solution is indicated for:

Transurethral resection of the prostate (TURP): The primary indication, providing distention and visualization during monopolar electrosurgical resection
Transurethral resection of bladder tumors: When monopolar electrocautery is used
Other endoscopic urologic procedures: Including ureteroscopy and nephroscopy when a non-electrolyte solution is required

Glycine has largely been replaced by normal saline in institutions using bipolar resection technology, which permits the use of isotonic electrolyte solutions. The choice of irrigant depends on the type of electrosurgical equipment available.

Pharmacokinetics

Glycine is administered as a continuous irrigation solution during surgical procedures and is not systemically administered by design. However, inadvertent systemic absorption occurs through opened venous sinuses in the prostatic bed or bladder wall.

Absorption: The volume absorbed depends on the duration of surgery, intravesical pressure, number and size of opened venous channels, and patient positioning. Absorption can range from negligible amounts to several liters in complicated cases.

Distribution: Once absorbed, glycine distributes throughout total body water. The hypotonic solution causes fluid shift into cells and dilutional effects on serum sodium and other electrolytes.

Metabolism: Glycine undergoes rapid hepatic metabolism. The primary pathway involves deamination by glycine cleavage enzyme system, producing ammonia, carbon dioxide, and a methylene group. Secondary pathways convert glycine to glyoxylate (via glycine oxidase) and subsequently to oxalate and glycolic acid.

Excretion: Unmetabolized glycine and its metabolites (including ammonia, oxalate, and glycolic acid) are renally excreted. The elimination half-life of glycine itself is approximately 1-2 hours, but ammonia clearance depends on hepatic function and may be prolonged in patients with liver disease.

Adverse effects

The most clinically significant adverse effect is TURP syndrome, which occurs when large volumes of glycine are absorbed systemically during prolonged resection procedures.

TURP Syndrome

TURP syndrome is characterized by a constellation of signs and symptoms resulting from fluid overload, dilutional hyponatremia, and glycine toxicity:

Cardiovascular: Hypertension initially (from fluid overload), followed by hypotension, bradycardia, arrhythmias, and potential cardiovascular collapse
Neurological: Confusion, restlessness, visual disturbances (transient blindness reported), seizures, and altered mental status; glycine's inhibitory neurotransmitter effects contribute to CNS depression
Metabolic: Hyponatremia (often <120 mEq/L), hypoosmolality, hyperammonemia with potential encephalopathy
Pulmonary: Pulmonary edema from volume overload
Nausea and vomiting: Early signs of hyponatremia

Other Adverse Effects

Hyperammonemia: Can cause encephalopathy, particularly in patients with underlying hepatic dysfunction; ammonia levels may remain elevated for 12-24 hours post-procedure
Oxalate nephropathy: Rare complication from glycine metabolism to oxalate, potentially causing acute kidney injury with calcium oxalate crystal deposition
Visual disturbances: Transient blindness lasting minutes to hours, attributed to direct glycine effects on retinal neurotransmission or cerebral edema
Hemolysis: Rare, due to hypotonic solution causing osmotic red blood cell lysis
Hypothermia: From large volumes of room-temperature irrigant

The incidence of clinically significant TURP syndrome ranges from 1-8% of procedures, with higher risk in prolonged operations (>90 minutes) and large prostate resections (>45 g tissue removed).

Contraindications and warnings

Contraindications

Anuria or severe renal impairment: Inability to excrete absorbed fluid and metabolites increases toxicity risk

Warnings and Precautions

Hepatic impairment: Impaired glycine metabolism leads to prolonged hyperammonemia and increased neurotoxicity risk; use with extreme caution or consider alternative irrigants
Cardiovascular disease: Patients with congestive heart failure, coronary artery disease, or severe hypertension are at increased risk for complications from fluid absorption and electrolyte disturbances
Hyponatremia: Patients with baseline hyponatremia are at higher risk for severe neurological complications if further sodium dilution occurs
Prolonged procedures: Limit operative time when possible; consider switching to bipolar technology with saline irrigation for large resections
Elderly patients: Age-related decreases in cardiac and renal reserve increase vulnerability to TURP syndrome

Monitoring

Intraoperative and immediate postoperative monitoring should include:

Volume of irrigant used and estimated absorption (input-output balance)
Serum sodium and osmolality
Mental status and neurological examination
Cardiovascular status (blood pressure, heart rate, rhythm)
Consider ammonia levels if encephalopathy develops
Fluid balance and signs of volume overload

Early recognition of TURP syndrome is critical. A high index of suspicion should be maintained when operative time exceeds 60 minutes or when clinical signs suggest fluid absorption.

Drug interactions

Glycine irrigation solution has limited systemic drug interactions when used appropriately, but several considerations exist:

Diuretics: Patients on chronic diuretic therapy may have baseline volume contraction or electrolyte abnormalities that complicate management if TURP syndrome develops. However, loop diuretics (furosemide) are often used therapeutically to manage fluid overload if significant absorption occurs.

Antihypertensive medications: Chronic antihypertensive therapy may mask early hypertensive signs of fluid absorption or exacerbate hypotension in later stages of TURP syndrome.

Medications affecting ammonia metabolism: Drugs that impair hepatic function or increase ammonia production theoretically increase hyperammonemia risk, though clinical significance is not well established. These include valproic acid, certain chemotherapy agents, and medications causing hepatotoxicity.

Anesthetic agents: General anesthesia may mask early neurological signs of hyponatremia or ammonia toxicity. Regional anesthesia (spinal or epidural) allows better monitoring of mental status changes but does not prevent the syndrome.

No direct pharmacokinetic interactions occur because glycine is not absorbed through normal gastrointestinal or transdermal routes when used as an irrigant. Interactions are primarily physiological consequences of excessive absorption rather than drug-drug interactions in the traditional sense.

Clinical pearls

TURP syndrome recognition: The classic triad is mental status changes, cardiovascular instability, and visual disturbances during or immediately after transurethral resection. Suspect it when serum sodium drops below 125 mEq/L or when more than 2 liters of irrigant absorption is estimated.

Ammonia as the culprit: While hyponatremia contributes to TURP syndrome symptoms, hyperammonemia from glycine metabolism causes much of the neurotoxicity. This explains why symptoms may persist even after sodium correction and why encephalopathy can occur with relatively modest hyponatremia.

Bipolar technology advantage: Modern bipolar resection systems allow use of normal saline irrigation, eliminating glycine-specific toxicity and reducing (though not eliminating) TURP syndrome risk. This represents the standard of care in many centers.

Treatment of TURP syndrome: Management includes stopping surgery promptly, supportive care, judicious hypertonic saline (3%) for symptomatic severe hyponatremia (typically if Na <120 mEq/L with neurological symptoms), and loop diuretics for volume overload. Avoid overly rapid sodium correction (risk of osmotic demyelination syndrome); target 4-6 mEq/L increase in first few hours.

Visual symptoms are unique: Transient blindness associated with glycine (not seen with other irrigants) is thought to result from glycine's inhibitory effects on retinal neurotransmission, particularly affecting retinal ganglion cells. It typically resolves within 24 hours but is distressing to patients.

Limit irrigation pressure: Keeping intravesical pressure below 60 cm H₂O reduces venous absorption. Surgeons should position the irrigation bag no more than 60 cm above the patient.

Exam tip for serum markers: In TURP syndrome, expect low serum sodium, low serum osmolality, elevated ammonia, and potentially elevated glycolic acid. Ethylene glycol toxicity is a distractor that presents with high anion gap metabolic acidosis, oxalate crystals, and no recent surgical history.

Practice questions

1. A 72-year-old man undergoes transurethral resection of the prostate for benign prostatic hyperplasia. The procedure lasts 105 minutes using monopolar electrocautery with glycine 1.5% irrigation. Thirty minutes after surgery, he becomes confused and reports blurred vision. Vital signs show BP 160/95 mmHg, pulse 58/min. Laboratory studies reveal serum sodium 118 mEq/L (normal 135-145) and serum osmolality 248 mOsm/kg (normal 275-295). Which of the following best explains his visual symptoms?

Answer: B. This patient has TURP syndrome with characteristic transient visual disturbances unique to glycine irrigation. Glycine acts as an inhibitory neurotransmitter and directly affects retinal ganglion cells, causing temporary blindness or blurred vision that typically resolves within 24 hours. While cerebral edema from hyponatremia contributes to overall neurological symptoms, it does not specifically explain the visual changes that are pathognomonic for glycine toxicity. The patient is actually hypertensive (not hypotensive), making ischemia unlikely.

2. A 68-year-old man with cirrhosis undergoes transurethral resection of a bladder tumor using glycine irrigation. The 90-minute procedure is uncomplicated with estimated blood loss of 200 mL. Two hours postoperatively, he is increasingly lethargic and difficult to arouse. Blood pressure is 145/88 mmHg, pulse 62/min. Laboratory results show sodium 128 mEq/L, ammonia 185 mcg/dL (normal 15-45), and creatinine 1.1 mg/dL. Which underlying condition most increases this patient's risk for his current presentation?

Answer: C. This patient's encephalopathy is primarily driven by severe hyperammonemia (185 mcg/dL, nearly 4 times normal), which results from impaired hepatic metabolism of absorbed glycine. His cirrhosis severely limits the liver's ability to clear ammonia produced from glycine breakdown via the glycine cleavage enzyme system. While his mild hyponatremia contributes, the marked ammonia elevation in the setting of known liver disease is the key pathophysiologic factor. Patients with cirrhosis should ideally avoid glycine irrigation or have surgery with bipolar technology using saline instead.

3. During a transurethral resection of the prostate, the anesthesiologist notes that the patient has become restless and confused 75 minutes into the procedure. The irrigation fluid reservoir shows 18 L used with only 14 L recovered in the collection bag. Blood pressure is 168/96 mmHg. Which of the following interventions is most appropriate as the immediate next step?

Answer: C. This patient has developed TURP syndrome with an estimated 4-liter absorption of glycine solution, manifested by confusion and hypertension. The most critical immediate step is to terminate surgery to prevent further fluid absorption and worsening toxicity. While obtaining labs and giving furosemide are appropriate subsequent steps, they should not delay stopping the procedure. Hypertonic saline is reserved for severe symptomatic hyponatremia (typically sodium <120 mEq/L with seizures or severe mental status changes) and is premature before lab confirmation. Increasing irrigation would worsen absorption.

Frequently asked questions

How does glycine work as an irrigation solution?

Glycine provides a clear, non-conductive medium for visualization during monopolar electrosurgical procedures. It distends the operative field and does not conduct electricity, which is essential when using monopolar cautery. The 1.5% solution is hypotonic and transparent, allowing optimal endoscopic visualization during transurethral resection of the prostate or bladder. Unlike saline, it will not disperse electrical current and cause burns to surrounding tissue during monopolar resection.

What are the side effects of glycine irrigation?

The main adverse effect is TURP syndrome, which occurs when large volumes are absorbed systemically. This causes dilutional hyponatremia (often sodium <120 mEq/L), hyperammonemia leading to encephalopathy, cardiovascular instability with initial hypertension then hypotension, and volume overload with potential pulmonary edema. Unique to glycine is transient blindness from its effects on retinal neurotransmission. Other effects include nausea, confusion, seizures, and rarely acute kidney injury from oxalate crystal deposition. Most complications occur during prolonged procedures exceeding 90 minutes.

What is TURP syndrome and how is it treated?

TURP syndrome results from excessive systemic absorption of irrigation fluid during transurethral prostate resection, causing hyponatremia, hyperammonemia, and fluid overload. Symptoms include confusion, visual disturbances, nausea, bradycardia, hypertension then hypotension, and potentially seizures or cardiovascular collapse. Treatment includes immediately stopping surgery, administering hypertonic saline (3%) if sodium is below 120 mEq/L with neurological symptoms, giving loop diuretics like furosemide for volume overload, and providing supportive care. Sodium should be corrected slowly (4-6 mEq/L over first few hours) to avoid osmotic demyelination syndrome.

Why does glycine cause hyperammonemia?

Glycine undergoes hepatic metabolism via the glycine cleavage enzyme system, which breaks it down through deamination. This process releases ammonia as a byproduct, along with carbon dioxide. When large volumes of glycine are absorbed during surgery, the liver cannot process all the glycine quickly enough, leading to accumulation of ammonia in the bloodstream. Hyperammonemia causes encephalopathy with confusion, lethargy, and altered mental status. Patients with pre-existing liver disease are at particularly high risk because their impaired hepatic function further limits ammonia clearance.

Glycine vs saline irrigation—what is the difference?

Glycine 1.5% is hypotonic and non-conductive, required for monopolar electrosurgery but carries risk of TURP syndrome with hyponatremia and glycine-specific toxicity (hyperammonemia, transient blindness). Normal saline is isotonic and conductive, used with bipolar electrosurgery technology. Saline eliminates glycine-specific toxicity but can still cause TURP syndrome from fluid absorption, though typically less severe due to isotonicity. Modern practice increasingly favors bipolar technology with saline when available. Glycine remains necessary only when monopolar equipment is used, which is becoming less common in well-resourced settings.

Conditions it is used for

irrigation for transurethral resection of prostateirrigation for transurethral resection of bladder tumorirrigation for endoscopic urologic surgery

mannitolsorbitolsterile waternormal saline

Sources and further reading

DailyMed (FDA labels)StatPearls (NCBI Bookshelf)MedlinePlus WHO ATC/DDD index: B05CX03

Educational content for medical students, prepared by the WhiteCoat Pro editorial team with AI assistance; every page is reviewed by a second AI model for factual errors. It is not medical advice and does not replace the product label, local guidelines or a clinician.

Glycine