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GLYCINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Glycine is a nonessential, simple amino acid that makes up many proteins. Glycine is used as an irrigation solution in surgical procedures, especially genitourinary procedures such as transurethral resection of the prostate (TURP). Glycine is also used to treat peptic ulcer disease and for correction of acute isovaleric acidemia. Topical application of glycine has been used to promote wound healing of leg ulcerations.

Specific Substances

    1) Aminoacetic acid
    2) Aminoethanoic acid
    3) Gly
    4) Sucre de gelatine

Available Forms Sources

    A) FORMS
    1) Glycine is mainly used as a 1.5% to 2% nonconductive irrigation solution. Ethanol is sometimes incorporated into the solution to facilitate monitoring of irrigant absorption via breath ethanol analysis.
    2) Oral preparations of glycine, sometimes in conjunction with calcium carbonate, are available.
    B) USES
    1) Glycine is used as a nonconductive surgical irrigation solution in genitourinary surgical procedures. Glycine is used orally for the treatment of peptic ulcer disease and correction of isovaleric acidemia, and topically for the treatment of wound healing.

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH THERAPEUTIC USE
    1) Absorption of hypotonic glycine irrigation solution, especially during genitourinary surgical procedures such as transurethral resection of the prostate (TURP), has been reported to cause visual disturbances, transient blindness and hyponatremia, which can be fatal. These effects have been described as the TURP syndrome or the post-prostatectomy (PPS) syndrome. Other reported effects include hypotension, hyperammonemia, metabolic acidosis, increased osmolal gap, hypocalcemia, hemolytic anemia, ECG changes, headache, coma, seizures, dyspnea, and cerebral edema.
    B) WITH POISONING/EXPOSURE
    1) Experience with human overdose is limited. A woman received 6 L of 1.5% glycine irrigation solution inadvertently via the intravenous route and developed altered mental status, electrolyte abnormalities and cerebral edema; she recovered completely with supportive care. In another case a man was inadvertently given 1 L of 1.5% glycine irrigation solution via the intravenous route. Confusion, vomiting, hypotension, tachycardia, ECG changes, dyspnea, anemia, thrombocytopenia, hyponatremia, and hypocalcemia were reported.
    0.2.5) CARDIOVASCULAR
    A) WITH THERAPEUTIC USE
    1) Systemic absorption of glycine irrigation solutions during genitourinary surgical procedures may result in bradycardia, tachycardia, hypotension, and ECG changes.
    B) WITH POISONING/EXPOSURE
    1) Hypotension, tachycardia, and ECG changes have been reported after an accidental intravenous infusion of a glycine irrigation solution.
    0.2.7) NEUROLOGIC
    A) WITH THERAPEUTIC USE
    1) Mental status changes, cerebral edema, seizures, and coma have been reported following systemic absorption of glycine irrigation solutions.
    B) WITH POISONING/EXPOSURE
    1) Mental status changes and confusion have been reported following an accidental intravenous infusion of a glycine irrigation solution.
    0.2.12) FLUID-ELECTROLYTE
    A) WITH THERAPEUTIC USE
    1) Electrolyte disturbances, including profound hyponatremia which has been fatal, have been reported after systemic absorption of glycine irrigation solutions.
    B) WITH POISONING/EXPOSURE
    1) Electrolyte abnormalities, including hyponatremia and hypocalcemia, have been reported after an accidental intravenous infusion of a glycine irrigation solution.
    0.2.13) HEMATOLOGIC
    A) WITH THERAPEUTIC USE
    1) Thrombocytopenia and hemolytic anemia have been reported after systemic absorption of glycine irrigation solutions.
    B) WITH POISONING/EXPOSURE
    1) Thrombocytopenia and anemia have been reported after an accidental intravenous infusion of a glycine irrigation solution.

Laboratory Monitoring

    A) Monitor fluid, electrolytes (sodium), and urine output in patients with symptoms of hyponatremia or water intoxication.
    B) Monitor vital signs.
    C) Monitor neurologic state, ammonia level and visual status as indicated.
    D) Central venous or pulmonary artery pressure monitoring may be indicated to guide fluid therapy in patient's that develop significant alterations in fluid balance.
    E) Obtain an ECG and institute continuous cardiac monitoring.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) The role of gastric decontamination in glycine poisoning is unknown. Most cases of glycine toxicity occur through absorption of glycine during surgical procedures, rendering gastric decontamination ineffective. However, in cases of large glycine ingestion, gastric decontamination may play a role in overdose.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.

Range Of Toxicity

    A) A minimum human toxic dose has not been established. A woman inadvertently received 6 L of 1.5% glycine irrigation as an intravenous infusion and developed severe mental status depression, significant electrolyte abnormalities and cerebral edema; she recovered with supportive care including loop diuretics and desmopressin. Toxicity has been reported after intraoperative absorption of less than one liter of 1.5% glycine irrigation solution. Toxicity is more common after intraoperative absorption of more than 3000 mL of 1.5% irrigation solution, or if extravasation occurs.

Clinical Effects

Summary Of Exposure

    A) WITH THERAPEUTIC USE
    1) Absorption of hypotonic glycine irrigation solution, especially during genitourinary surgical procedures such as transurethral resection of the prostate (TURP), has been reported to cause visual disturbances, transient blindness and hyponatremia, which can be fatal. These effects have been described as the TURP syndrome or the post-prostatectomy (PPS) syndrome. Other reported effects include hypotension, hyperammonemia, metabolic acidosis, increased osmolal gap, hypocalcemia, hemolytic anemia, ECG changes, headache, coma, seizures, dyspnea, and cerebral edema.
    B) WITH POISONING/EXPOSURE
    1) Experience with human overdose is limited. A woman received 6 L of 1.5% glycine irrigation solution inadvertently via the intravenous route and developed altered mental status, electrolyte abnormalities and cerebral edema; she recovered completely with supportive care. In another case a man was inadvertently given 1 L of 1.5% glycine irrigation solution via the intravenous route. Confusion, vomiting, hypotension, tachycardia, ECG changes, dyspnea, anemia, thrombocytopenia, hyponatremia, and hypocalcemia were reported.

Vital Signs

    3.3.4) BLOOD PRESSURE
    A) WITH THERAPEUTIC USE
    1) HYPOTENSION: Hypotension has occurred following bladder irrigation with glycine solution during bladder cytoscopy, transurethral resection of the prostate, and transurethral resection of bladder tumors (Thomas & Hales, 1984; Hahn & Essen, 1994; Hahn, 1995).
    B) WITH POISONING/EXPOSURE
    1) HYPOTENSION: A 52-year-old man experienced hypotension and tachycardia, with systolic blood pressure dropping to 82 mm Hg, after accidently receiving 1 L of a 1.5% glycine irrigation solution intravenously. The patient made a full recovery in 48 hours with supportive care (Ahmed et al, 2008).
    3.3.5) PULSE
    A) WITH THERAPEUTIC USE
    1) BRADYCARDIA: Bradycardia has been reported following bladder irrigation with glycine solution during transurethral resection of the prostate (Thomas & Hales, 1984).
    B) WITH POISONING/EXPOSURE
    1) TACHYCARDIA: A 52-year-old man became tachycardic (heart rate 108 beats/minute) after inadvertently receiving 1 L of a 1.5% glycine irrigation solution intravenously. The patient made a complete recovery in 48 hours with supportive care (Ahmed et al, 2008).

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) SUMMARY: Visual disturbances and transient blindness have been reported following glycine absorption during genitourinary surgical procedures such as transurethral resection of the prostate (TURP). The exact mechanism remains unknown.
    2) VISUAL DISTURBANCES: A 73-year-old man complained of visual disturbances including dark vision through both eyes and the appearance of seeing through a color photographic negative immediately after a TURP procedure using glycine 1.5% as an irrigant. Pupils showed mydriasis and reacted poorly to light. Symptoms completely subsided after 2.5 hours (Radziwill et al, 1997).
    3) TRANSIENT BLINDNESS: Transient blindness was reported after a 3-hour TURP procedure in a 78-year-old man. Glycine 1.5% plus ethanol 1% was used for bladder irrigation; breath ethanol measurements indicated that 1600 mL +/- 350 mL glycine solution had been absorbed. The patient had small unreactive pupils (probably fentanyl-related) and vital signs that were otherwise normal. Vision returned to normal over the next day (Adejumo & Davies, 1996).
    a) Approximately 75 minutes into a TURP procedure, a 65-year-old man experienced blurred vision and temporary blindness after absorption of a glycine irrigation solution. After termination of the surgery and provision of fluids and other supportive care, the patient's vision returned to normal over the next 16 hours (Khan-Ghori et al, 1998).
    b) Transient blindness occurred 1 hour after recovery from anesthesia in a 38-year-old woman following a hysteroscopic procedure using glycine irrigation. Vision slowly returned to normal approximately 30 hours after surgery (Levin & Ben-David, 1995).
    c) A 74-year-old man complained of facial warmth, swelling around the eyes, and frontal headache 45 minutes into a TURP procedure using glycine irrigation. During recovery, he stated that he was completely blind. Funduscopic exam was normal. Vision began to return 2 hours postoperatively, with complete return of sight within 24 hours (Russell, 1990).
    4) PROSPECTIVE STUDY: Mizutani et al (1990) studied visual acuity in 18 patients undergoing transurethral prostatectomies. Four patients (22%) experienced significant changes in visual acuity. All patients had elevated serum glycine, but there was no correlation between glycine concentrations and severity of visual symptoms (Mizutani et al, 1990).
    5) PROSPECTIVE STUDY: In a study of 12 TURP patients, visual evoked potentials (p100 latency) significantly increased postoperatively from baseline values. No changes were noted in visual acuity (Mantha et al, 1991).

Cardiovascular

    3.5.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Systemic absorption of glycine irrigation solutions during genitourinary surgical procedures may result in bradycardia, tachycardia, hypotension, and ECG changes.
    B) WITH POISONING/EXPOSURE
    1) Hypotension, tachycardia, and ECG changes have been reported after an accidental intravenous infusion of a glycine irrigation solution.
    3.5.2) CLINICAL EFFECTS
    A) BRADYCARDIA
    1) WITH THERAPEUTIC USE
    a) In an study of 273 patients who underwent transurethral resection of the prostate (TURP), the incidence of bradycardia and hypotension was 20% in patients with low grade glycine irrigation solution absorption. However, patients who absorbed greater than 2,000 mL had a 50% to 80% incidence. Extravascular absorption of glycine also increased the risk of bradycardia and hypotension (Olsson et al, 1995).
    b) CASE REPORT: Thirty minutes following bladder irrigation with 1.5% glycine during transurethral resection of the prostate, a 75-year-old man experienced hyponatremia (109 mmol/L), hypotension, and bradycardia. Bradycardia and hypotension did not respond to atropine; after an isoproterenol infusion, the patient recovered. Past medical history was significant for atrial fibrillation, chronic obstructive pulmonary disease, myocardial infarction, and mild congestive heart failure (Thomas & Hales, 1984).
    B) TACHYCARDIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 52-year-old man became tachycardic (108 BPM) after inadvertently receiving 1 liter of a 1.5% glycine irrigation solution intravenously. The patient made a complete recovery in 48 hours with supportive care (Ahmed et al, 2008).
    C) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypotension has been reported after systemic absorption of glycine irrigation solutions (Yende & Wunderink, 1999; Hahn, 1995; Thomas & Hales, 1984).
    b) CASE REPORT: A 69-year-old man experienced hypotension and hypovolemic shock, with a drop in systolic blood pressure from 160 mm Hg to 80 mm Hg, during a TURP procedure. Measured breath ethanol levels (0.15 mg/mL) did not indicate significant glycine absorption during the procedure. The authors determined that absorption occurred by the extravascular route (Hahn, 1995).
    c) CASE REPORT: Hypotension, hyponatremia, and bradycardia were reported 30 minutes following bladder irrigation with 1.5% glycine during a TURP procedure. Bradycardia and hypotension did not respond to atropine; after an isoproterenol infusion, the patient recovered. Past medical history was significant for atrial fibrillation, chronic obstructive pulmonary disease, myocardial infarction, and mild congestive heart failure (Thomas & Hales, 1984).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 52-year-old man experienced hypotension and tachycardia, with systolic blood pressure dropping to 82 mm Hg, after accidently receiving 1 L of a 1.5% glycine irrigation solution intravenously. The patient made a full recovery in 48 hours with supportive care (Ahmed et al, 2008).
    D) ELECTROCARDIOGRAM ABNORMAL
    1) WITH THERAPEUTIC USE
    a) A study of 22 patients undergoing TURP showed that 82% of patients absorbing greater than 1 L of a 1.5% glycine and 1% ethanol solution had ECG changes 24 hours after surgery. Abnormalities consisted primarily of flattened T waves. One patient had inversion of the T wave and another patient had atrial fibrillation. Only 1 patient absorbing less than 1,000 mL glycine solution had ECG changes (Hahn & Essen, 1994).
    b) CASE REPORT: A 65-year-old man developed QRS complex widening and ST segment depression associated with electrolyte abnormalities after absorption of a glycine irrigation solution during a TURP procedure. After termination of surgery, the ECG showed left bundle branch block. The patient recovered over the next day with supportive care (Khan-Ghori et al, 1998).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 52-year-old man had ECG findings of nonspecific ST wave changes after accidently receiving 1 L of a 1.5% glycine irrigation solution intravenously. The patient recovered in 48 hours with supportive care (Ahmed et al, 2008).
    E) CARDIAC ARREST
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 72-year-old man experienced sudden cardiac arrest following absorption of 1.5% glycine irrigation solution during a TURP procedure. Blood pressure became unrecordable with ECG showing nodal rhythm with U waves and a rate of 30 per minute. Normal sinus rhythm returned 1 to 2 hours later after correction of electrolyte abnormalities (Charlton, 1980).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) DYSPNEA
    1) WITH THERAPEUTIC USE
    a) Dyspnea has been reported with the TURP syndrome (Barletta et al, 1994; Cashman, 1990)
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 52-year-old man became dyspneic, with a respiratory rate ranging 26-30/minute and an arterial oxygen saturation of 85-90% on room air after accidentally receiving 1 L of a 1.5% glycine irrigation solution intravenously. The patient's respiratory status was managed with noninvasive positive pressure ventilation, and he made a full recovery in 48 hours (Ahmed et al, 2008).

Neurologic

    3.7.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Mental status changes, cerebral edema, seizures, and coma have been reported following systemic absorption of glycine irrigation solutions.
    B) WITH POISONING/EXPOSURE
    1) Mental status changes and confusion have been reported following an accidental intravenous infusion of a glycine irrigation solution.
    3.7.2) CLINICAL EFFECTS
    A) COMA
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 40-year-old woman undergoing shoulder arthroscopy received glycine irrigation solution during the procedure and was found comatose (Glasgow coma score of 3) approximately 7 hours after surgery (Ichai et al, 1996). Laboratory values indicated hyponatremia (116 mmol/L), and severe diffuse cerebral edema with both ventricles and basal cisterns collapsed on brain CT. Angiography confirmed brain death with the autopsy showing cerebral edema.
    b) CASE SERIES: Two patients became deeply comatose with severe hyponatremia and hyperammonemia after TURP procedures using 1.5% glycine irrigation. In both cases, the clinical course of the coma more closely followed the patients' hyperammonemia than the hyponatremia (Ryder et al, 1984).
    B) SEIZURE
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Approximately 16 hours following glycine bladder irrigation during cystoscopy and bladder biopsy, a 79-year-old woman became confused, agitated, hyponatremic, and had 2 seizures. She remained in a post-ictal state for 4 hours. The patient recovered fully after fluid support and phenytoin were given (Siddiqui et al, 1996).
    b) CASE REPORT: Approximately 45 minutes into a transurethral prostatic resection procedure using glycine, a 61-year-old man experienced altered mental status followed by seizure activity. Electrolyte studies showed hyponatremia, which was corrected by infusion of 3% saline and administration of furosemide (Barletta et al, 1994).
    C) CLOUDED CONSCIOUSNESS
    1) WITH THERAPEUTIC USE
    a) Confusion was associated more frequently with large volume glycine absorption in a study of 273 patients undergoing transurethral resection of the prostate (Olsson et al, 1995).
    b) Tauzin-Fin et al (1997) reported 2 cases in which patients developed postoperative confusion after absorption of less than 1 L of 1.5% glycine. Despite low absorption, high serum concentrations of glycine were observed (Tauzin-Fin et al, 1997).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 52-year-old man became disoriented and confused after accidentally receiving 1 L of a 1.5% glycine irrigation solution intravenously. The patient made a full recovery in 48 hours with supportive care (Ahmed et al, 2008).
    D) CEREBRAL EDEMA
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 32-year-old woman developed severe mental status depression after an elective hysteroscopy in which she inadvertently received 6 L of 1.5% glycine irrigation as an intravenous infusion. Initially, she developed decreases in her heart rate and blood pressure and had no purposeful movements. An initial serum sodium level was undetectable (ie, less than 100 mEq/L) along with hypocalcemia, hypomagnesemia, hypoosmolality, lactate 2.95 mmol/L and ammonia 592 mcg/dL. Neuroimaging was consistent with diffuse cerebral edema. Treatment included free water restriction, loop diuretics and desmopressin; hemodialysis was not required. Her neurological function improved and neuroimaging on hospital day 3 revealed no evidence of central pontine myelinosis and resolution of cerebral edema. One month after the event, the patient's neurologic function was completely normal (Villano et al, 2015).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) In a study of 273 patients who underwent transurethral resection of the prostate, postoperative nausea and vomiting were significantly higher in patients who absorbed 1,001 mL to 2,000 mL glycine irrigation solution compared to those who had no absorption (Olsson et al, 1995).
    b) CASE SERIES: Hahn (1994) reported 4 cases of nausea, vomiting, and abdominal pain in 4 patients undergoing transurethral resection of bladder tumors. Fluid absorption likely occurred by an extravascular route in all cases.(Hahn & Essen, 1994)
    c) In a double-blind study comparing the adverse effect profile of 1.5% glycine with 3% mannitol during transurethral resection procedures, absorption of glycine was associated with significantly more nausea and vomiting compared to mannitol. In all patients, nausea lasted less than 5 minutes in approximately 50% of the patients but was prolonged up to 120 minutes in others (Hahn et al, 1998).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 52-year-old man experienced multiple bouts of vomiting after accidently receiving 1 L of a 1.5% glycine irrigation solution intravenously. The patient made a full recovery in 48 hours with supportive care (Ahmed et al, 2008).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) METABOLIC ACIDOSIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: An 87-year-old man developed confusion, coma, hyponatremia, hyperammonemia, hypocalcemia, hypotension, hemolytic anemia, and a mild metabolic acidosis without an anion gap (pH 7.26, PCO2 29 mmHg, bicarbonate 16 mEq/L) but with an associated osmolal gap of 40 mOsm/kg (Yende & Wunderink, 1999).
    B) METABOLIC ALKALOSIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 52-year-old man developed a mild metabolic alkalosis (pH 7.48) with moderate hypoxemia (PaO2 65 mmHg) after inadvertently receiving 1 liter of a 1.5% glycine irrigation solution intravenously. He also developed confusion, vomiting, hypotension, tachycardia, ECG changes, dyspnea, hyponatremia, and hypocalcemia. The patient made a complete recovery in 48 hours with supportive care (Ahmed et al, 2008).

Hematologic

    3.13.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Thrombocytopenia and hemolytic anemia have been reported after systemic absorption of glycine irrigation solutions.
    B) WITH POISONING/EXPOSURE
    1) Thrombocytopenia and anemia have been reported after an accidental intravenous infusion of a glycine irrigation solution.
    3.13.2) CLINICAL EFFECTS
    A) THROMBOCYTOPENIC DISORDER
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Thrombocytopenia, with a platelet count of 81,000/mm(3), occurred in an 87-year-old man the day after undergoing bladder cystoscopy with glycine bladder irrigation. The patient developed adult respiratory distress syndrome, renal failure, and small bowel ischemia, and died 2 weeks later.
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 52-year-old man experienced thrombocytopenia after accidentally receiving 1 L of a 1.5% glycine irrigation solution intravenously. The patient made a full recovery in 48 hours with supportive care (Ahmed et al, 2008).
    B) HEMOLYTIC ANEMIA
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: The morning after undergoing bladder cystoscopy with glycine bladder irrigation, a 87-year-old man experienced hypotension, confusion, hyponatremia, elevated osmolal gap, acidosis, hypocalcemia, hyperammonemia, hemolytic anemia, and thrombocytopenia. Past medical history was significant for hypertension, nephrolithiasis, stage IIB prostate cancer status post radiation therapy, and coronary artery disease. He developed adult respiratory distress syndrome, renal failure, and small bowel ischemia, and died 2 weeks later (Yende & Wunderink, 1999).
    C) ANEMIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 52-year-old man developed anemia after accidentally receiving 1 L of a 1.5% glycine irrigation solution intravenously. Symptoms resolved in 48 hours with supportive care (Ahmed et al, 2008).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH THERAPEUTIC USE
    a) A 76-year-old man had an immunological reaction to a glycine irrigation solution during a urological procedure. The patient turned unusually red, developed edema of the lips and conjunctiva, and collapsed. The patient was ventilated and cardiac massage performed; the patient recovered following atropine, calcium chloride, promethazine, and hydrocortisone. An in vitro immunological test revealed evidence of C3 complement activation (Moskovits et al, 1987).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor fluid, electrolytes (sodium), and urine output in patients with symptoms of hyponatremia or water intoxication.
    B) Monitor vital signs.
    C) Monitor neurologic state, ammonia level and visual status as indicated.
    D) Central venous or pulmonary artery pressure monitoring may be indicated to guide fluid therapy in patient's that develop significant alterations in fluid balance.
    E) Obtain an ECG and institute continuous cardiac monitoring.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Carefully monitor serum electrolytes and osmolality.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Monitor heart rate and blood pressure, electrocardiogram, and fluid intake and output.
    b) Hemodynamic pressure monitoring may be indicated to assess the patient's fluid status and guide fluid therapy following severe exposure.
    c) Monitor visual function and mental status.
    2) BREATH ANALYSIS
    a) Ethanol monitoring of expired air has been used to monitor volume of glycine irrigation solution absorbed.
    b) Hahn & Olsson (1996) described a method in which ethanol concentrations were monitored in expired air via a breathalyzer. During a TURP procedure, a solution of glycine 1.5% plus ethanol 2% was used to irrigate the bladder, and the patient was instructed to perform a breath test every 10 minutes. The volume of irrigant absorbed was then estimated through a nomogram. In this particular case, the estimated irrigant absorbed was rapidly increasing, allowing the surgeon to terminate the case before adverse events arising from TURP syndrome occurred.
    c) However, extravascular absorption of a glycine/ethanol solution may render breath analysis inaccurate. Hahn (1995) presented a TURP case of a 69-year-old man who experienced circulatory shock despite breath ethanol monitoring. In cases of extravascular absorption of glycine, maximum breath ethanol levels may be delayed approximately 20 minutes and irrigation solution absorption may be 3 times larger than calculated by the nomogram.
    3) OTHER
    a) ANIMAL STUDY - In a sheep model, 45 grams of intravenous glycine given as a 1.5% solution resulted in elevated glycine levels in plasma, CSF, and vitreous fluid. After 7 hours, plasma and CSF glycine levels decreased whereas vitreous glycine levels remained elevated (Wright & Seggie, 1992).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Monitor fluid, electrolytes (sodium), and urine output in patients with symptoms of hyponatremia or water intoxication.
    B) Monitor vital signs.
    C) Monitor neurologic state, ammonia level and visual status as indicated.
    D) Central venous or pulmonary artery pressure monitoring may be indicated to guide fluid therapy in patient's that develop significant alterations in fluid balance.
    E) Obtain an ECG and institute continuous cardiac monitoring.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) The role of gastric decontamination in glycine poisoning is unknown. Since most cases of glycine toxicity occur through absorption of glycine during surgical procedures, gastric decontamination is ineffective. However, in cases of oral glycine ingestion, activated charcoal may play a role in overdose.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) The role of gastric decontamination in glycine poisoning is unknown. Most cases of glycine toxicity occur through absorption of glycine during surgical procedures, rendering gastric decontamination ineffective. However, in cases of large glycine ingestion, gastric decontamination may play a role in overdose.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) In cases of overdose ingestions, treatment should include recommendations listed in the TREATMENT-OTHER section as appropriate.

Abstracts

Case Reports

    A) ADULT
    1) A 61-year-old man, undergoing transurethral prostatic resection where a 1.5% glycine irrigation solution was used, experienced a sudden onset of blindness, nausea/vomiting, and altered mental status followed by seizure activity. Electrolyte studies revealed that serum sodium had decreased from 138 mEq/L to 120 mEq/L, with serum ammonia rising to 708 micromoles/L. Treatment included hypertonic saline (3%) and furosemide for hyponatremia in addition to pyridoxine and L-arginine for hyperammonemia. The patient recovered, with normal vision returning after 24 hours (Barletta et al, 1994).
    2) A 52-year-old man accidently received 1 L of a 1.5% glycine irrigation solution intravenously. He became confused and developed multiple bouts of vomiting, hypotension, tachycardia, ECG changes, dyspnea, hyponatremia and hypocalcemia. Treatment mainly consisted of noninvasive positive pressure ventilation and a calculated sodium repletion with 0.9% normal saline. The patient made a full recovery in 48 hours (Ahmed et al, 2008).

Range Of Toxicity

Summary

    A) A minimum human toxic dose has not been established. A woman inadvertently received 6 L of 1.5% glycine irrigation as an intravenous infusion and developed severe mental status depression, significant electrolyte abnormalities and cerebral edema; she recovered with supportive care including loop diuretics and desmopressin. Toxicity has been reported after intraoperative absorption of less than one liter of 1.5% glycine irrigation solution. Toxicity is more common after intraoperative absorption of more than 3000 mL of 1.5% irrigation solution, or if extravasation occurs.

Maximum Tolerated Exposure

    A) CASE REPORTS
    1) CASE REPORT: A 32-year-old woman developed severe mental status depression after an elective hysteroscopy in which she inadvertently received 6 L of 1.5% glycine irrigation as an intravenous infusion. Initially, she developed decreases in her heart rate and blood pressure and had no purposeful movements. An initial serum sodium level was undetectable (ie, less than 100 mEq/L) along with hypocalcemia, hypomagnesemia, hypoosmolality, lactate 2.95 mmol/L and ammonia 592 mcg/dL. Neuroimaging was consistent with diffuse cerebral edema. Treatment included free water restriction, loop diuretics and desmopressin; hemodialysis was not required. Her neurological function improved and neuroimaging on hospital day 3 revealed no evidence of central pontine myelinosis and resolution of cerebral edema. One month after the event, the patient's neurologic function was completely normal (Villano et al, 2015).
    2) CASE REPORT: A 52-year-old man was accidentally administered 1 L of 1.5% glycine irrigation solution intravenously following a prostatectomy. The patient experienced vomiting, became disorientated, hypotensive and dyspneic. Tests and labs revealed nonspecific ST wave changes on ECG, a mild metabolic alkalosis (pH 7.48), hyponatremia, and hypocalcemia. Symptoms resolved in approximately 48 hours with supportive care (Ahmed et al, 2008).
    B) CASE SERIES
    1) In a series of 273 patients undergoing transurethral prostate resection using an irrigating solution containing 1.5% or 2.2% glycine, patients who absorbed more irrigation solution were more likely to develop affects attributable to the TURP syndrome. Toxic effects were most common in patients who absorbed more than 2000 milliliters of fluid and included blurred vision, confusion, chest pain, tiredness, nausea, prickling, uneasiness, hypertension, bradycardia and hypotension. Extravasation was associated with a greater risk of hypotension and bradycardia (Olsson et al, 1995).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 4450 mg/kg (RTECS, 2000)
    2) LD50- (ORAL)MOUSE:
    a) 4920 mg/kg (RTECS, 2000)
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 5060 mg/kg (RTECS, 2000)
    4) LD50- (ORAL)RAT:
    a) 7930 mg/kg (RTECS, 2000)
    5) LD50- (SUBCUTANEOUS)RAT:
    a) 5200 mg/kg (RTECS, 2000)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Glycine, commonly as a 1.5% or 2% solution, is used primarily in transurethral resection of the prostate, other genitourinary procedures, or arthroscopy as a non-conductive irrigation solution which can be used safely during cautery.

Toxicologic Mechanism

    A) A well-documented group of symptoms has been reported following procedures utilizing glycine irrigation solutions, especially during transurethral resection of the prostate (TURP). This group of symptoms has been termed the TUR syndrome, the TURP syndrome, or the post-prostatectomy (PPS) syndrome.
    1) Symptoms observed during the TURP syndrome have included headache, visual disturbances, transient blindness, seizures, ECG changes, hypotension, coma, hyponatremia, cerebral edema, and death (Ichai et al, 1996; Hahn & Olsson, 1996) Olsson et al, 1995).
    2) The syndrome occurs during rapid absorption of glycine, possibly through open prostatic sinuses. This causes a dramatic increase in intravascular volume, which may lead to acute hyponatremia and possible cerebral edema (Siddiqui et al, 1996). Extravascular absorption may also be a mechanism of toxicity in some cases (Hahn, 1995).
    3) The mechanism of toxicity of absorbed glycine is a topic of debate. Glycine toxicity may occur via acute water intoxication, with absorption of hypotonic glycine resulting in hyponatremia, which may progress to cerebral edema. However, toxic symptoms of glycine absorption have been observed without hyponatremia, indicating a direct toxic effect of glycine. Some authors have postulated an indirect effect, implicating glycine metabolites such as ammonia, serine, or glyoxylic/glycolic acids in causing toxicity (Ichai et al, 1996; Anandaciva, 1991).
    4) A retrospective study showed that glycine-induced hyponatremia was associated with hypo-osmolality of the plasma, unlike hyponatremia caused by mannitol (Ayus & Arieff, 1997).

Physicochemical

Molecular Weight

    A) 75.08 (RTECS , 2000)
    B) Glycine is a white odorless crystalline powder with solubility in water (RTECS , 2000).

References

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