Philip J. Dorsey, Jr., MD, MPH
Raju Thomas, MD, MHA, FACS
BASICS
DESCRIPTION
• Transurethral resection (TUR) syndrome is classically associated with TUR of the prostate (TURP) and is characterized by confusion, hypertension (HTN), bradycardia, and visual disturbances.
• Symptoms are caused by hypervolemia, dilutional hyponatremia, and solute effects from irrigant absorption during resection.
• While traditionally associated with prostate resection, it can also be seen in TUR of bladder tumor (TURBT) and has also been described for procedures such as hysteroscopy.
• Use of bipolar TURP and laser TURP techniques with normal saline irrigant has led to decreased incidence of TUR syndrome.
• Synonym(s): TURP syndrome
EPIDEMIOLOGY
Incidence
• 0.3–2% incidence (1)[B]
• Can occur as early as 15 min into resection or up to 24 hr after a TUR procedure
• Higher risk when hypotonic irrigation is used
• The declining use of TURP, because of medical management options, for the management of benign prostatic hypertrophy (BPH) has led to a reduction in the incidence of this syndrome
Prevalence
N/A
RISK FACTORS
• Resection time >60 min
• Gland size >45 g
• Intravesical pressures >30 mm Hg
• Operative technique (open venous sinuses, capsular perforations increase risk)
• Sympathetic blockade associated with spinal anesthesia may contribute to late hypotension.
Genetics
N/A
PATHOPHYSIOLOGY
• Irrigants used are osmotically active.
• Osmolarity of TUR irrigant solutions:
– Normal serum: 280–310 mOsm/L
– 5% mannitol: 275 mOsm/L
– 1.5% glycine: 200 mOsm/L
– 2.7% sorbitol/0.5% mannitol: 178 mOsm/L
– 3% sorbitol: 165 mOsm/L
• Irrigant is absorbed by venous sinuses opened during resection or by slow absorption from the periprostatic and perivesical spaces in case of capsular perforation.
• As osmotically active solute enters the intravascular space, the plasma sodium concentration drops, leading to hypo-osmolality.
Volume effects:
• Increase in intravascular volume initially leads to hypervolemia, HTN, and reflex bradycardia; later hypotension can occur.
• Volume overload of the left ventricle may also lead to PE and respiratory failure.
ALERT
After 30–40 min of resection, flow from the intravascular space to peripheral tissues increases and can cause hypovolemia and hypotension (2)[B].
• Hyponatremia:
– Caused by loading the intravascular space with nonelectrolyte solution
– Contributes to CNS disturbances
– If serum sodium levels rapidly decrease to <120 mEq/L, negative inotropic effects are manifested as hypotension and ECG changes of widened QRS complexes, ventricular ectopy, ST-segment depression, or T-wave inversions
• Hypo-osmolality:
– Blood–brain barrier is basically impermeable to sodium, but water crosses freely.
– Osmotic gradient causes uptake of water by CNS tissue.
– Resulting cerebral edema can exacerbate HTN and bradycardia via the Cushing reflex.
• Hypo-osmolar plasma results in RBCs taking on water, causing hemolysis.
• Renal failure secondary to hypotension and hemoglobinemia
• Hyperglycemia:
– Glycine is a GABA-like inhibitory neurotransmitter.
– Serum levels of glycine 17 times that of normal adults have been recorded in patients after TURP using glycine irrigant.
ALERT
Signs of glycine toxicity mimic the hyponatremic symptoms of the TUR syndrome (visual disturbances, nausea, vomiting, headache, malaise, and weakness) (3)[B].
• Glycine can cause visual disturbances and even transient blindness independent of hyponatremic or hypo-osmolar effects.
• Glycine may also have direct toxic effects on the kidney, possibly via metabolism to oxalate.
• Hyperammonemia:
– Glycine is metabolized by the liver and kidneys to 2 potential toxins, glyoxylic acid and ammonia.
– Elevated serum ammonia may contribute to CNS derangement.
ASSOCIATED CONDITIONS
• BPH
• Bladder tumors
GENERAL PREVENTION
• Using irrigants such as glycine, sorbitol, and mannitol solutions reduces the hemolytic effects associated with sterile water irrigation.
– Glycine is no longer recommended as an irrigation fluid.
• Intravesical pressure can be reduced by using continuous-flow equipment, draining the bladder with a suprapubic tube, or lowering the fluid height to <60 cm.
• If a significant extraperitoneal perforation occurs during the TURP or TURBT, it may be best to abandon the procedure after achieving hemostasis to prevent excessive fluid absorption.
• Appropriate selection of patients for TURP is based on gland size:
– Limit resection time to <60–90 min.
– Consider open prostatectomy, or other appropriate options, for adenoma >100 g measured by imaging studies.
• Judicious use of IV diuretics
• Use of bipolar resectoscopes to perform TURP allows for saline irrigation:
– Reduces the hypo-osmotic effect of the absorbed fluid
• Use of laser energy sources for TUR management also decreases occurrence of TUR syndrome.
DIAGNOSIS
A patient who is slow to awaken from anesthesia or complains of visual disturbances should be considered to have the TUR syndrome following TURP.
HISTORY
• During TUR procedure: HTN and brachycardia may be a prodrome to rapid reduction in BP
• Postoperatively: No classic presentation, but patient may complain of any of the following:
– Chest pain
– Confusion
– Headache
– Itching
– Lethargy
– Nausea and vomiting
– Shortness of breath
PHYSICAL EXAM
• Nonspecific physical findings: Although skin may be clammy
• Neurologic exam will reveal altered sensorium and confusion, but no focal signs
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Serum sodium <125 mEq/L
• Serum ammonia and glycine may be elevated if glycine solution is used
• Determine measured and calculated plasma osmolality:
– Posm = 2 × plasma Na + (glucose)/18 + BUN/2.8
– The difference between measured osmolality and calculated osmolality is known as the osmolality gap.
– Normal osmolality gap: <5–10 mOsm/kg
– Clinically significant gap is usually >14 and may be due to the presence of substances such as ethanol, ethylene glycol, or in this case irrigating solutions.
– Osmolality gap can be >30–60 mOsm/kg following TUR due to the accumulation of glycine or sorbitol.
Imaging
• Cystogram or computed tomography (CT) cystogram in cases where perforation suspected to be cause of excess fluid absorption
• CT/MRI of brain to r/o cerebrovascular accident when other causes have been excluded
Diagnostic Procedures/Surgery
• ECG changes as noted above
• Arterial blood gas (ABG)
Pathologic Findings
N/A
DIFFERENTIAL DIAGNOSIS
• Cerebrovascular accident
• Myocardial infarction
• Narcotic overdose
• Pulmonary embolism (PE)
• Seizure
TREATMENT
GENERAL MEASURES
• No specific therapy is necessary in the absence of symptomatology.
• Patients with normal renal function need no intervention to correct mild hyponatremia.
• Hemodynamic and cardiopulmonary support should be provided as needed.
• Vasoactive agents may be required to increase systemic vascular resistance in case of severe hypotension and circulatory collapse.
MEDICATION
First Line
• Furosemide:
– Indicated to treat PE and hypervolemia when diuresis does not occur spontaneously
– Furosemide: 20–100 mg IV
– Water diuresis outpaces sodium diuresis, correcting both hypervolemia and hyponatremia.
– Routine use to counteract fluid absorption is not supported by the literature.
Second Line
• Hypertonic saline:
– Indicated for serum Na+ <120 mEq/L or multiple symptoms
– Na+ deficit is calculated: (preop Na+ - postop Na+) for total body water (TBW)
– TBW in males = 0.6 for weight in kg
– Determine amount of 3% hypertonic saline (513 mEq/L) needed to correct deficit
– Increasing serum Na by 0.5–1 mEq/L/h is considered a safe rate to avoid central pontine myelinolysis.
• In case of cerebral edema, more rapid correction is indicated, as the risk of brainstem herniation exceeds that of osmotic demyelination.
ALERT
Correcting sodium too quickly in hyponatremia can lead to central pontine myelinolysis and permanent neurologic injury. Recommended correction for life-threatening hyponatremia is no more than 1 mmoL/L/h in the ICU setting (4)[B].
SURGERY/OTHER PROCEDURES
Very rarely, decompression of a large retroperitoneal or pelvic irrigant collection is indicated in order to prevent further absorption of hypo-osmolar fluid.
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
N/A
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• When recognized and treated early, prognosis is favorable.
• Mortality 0.2–0.8%
• If therapy is delayed and hyponatremia is severe, risk of significant morbidity and mortality.
COMPLICATIONS
• Cardiopulmonary collapse
• Central pontine myelinolysis
• Cerebral edema and brainstem herniation
• Seizures
• Transient blindness
FOLLOW-UP
Patient Monitoring
• Hemodynamic monitoring and close attention to serum electrolytes, especially sodium, is essential during and after procedure.
• Serial neurologic exams/mental status exams should be performed until symptoms improve.
Patient Resources
Urology Care Foundation. http://www.urologyhealth.org/urology/index.cfm?article=144
REFERENCES
1. Mebust WK, et al. Transurethral prostatectomy: Immediate and postoperative complications. Cooperative study of 13 participating institutions evaluating 3,885 patients. J Urol. 1989;141:243–247.
2. Hahn RG. Fluid and electrolyte dynamics during development of the TURP syndrome. Br J Urol. 1990;66:79–84.
3. Hahn RG, Sandfeldt L, Nyman CR. Double-blind randomized study of symptoms associated with absorption of glycine 1.5% or mannitol 3% during transurethral resection of the prostate. J Urol.1998;160:397–401.
4. Weissman JD, Weissman BM. Pontine myelinolysis and delayed encephalopathy following the rapid correction of acute hyponatremia. Arch Neurol. 1989;46:926–927.
ADDITIONAL READING
• Borboroglu PG, Kane CJ, Ward JF, et al. Immediate and postoperative complications of transurethral prostatectomy in the 1990s. J Urol. 1999;162:1307–1310.
• Hong JY, Yang SC, Ahn S, et al. Preoperative comorbidities and relationship of comorbidities With postoperative complications in patients undergoing transurethral prostate resection. J Urol. 2011;185:1374–1378.
• Mamoulakis C, Skolarikos A, Schulze M, et al. Results from an international multicenter double-blind randomized controlled trial on the perioperative efficacy and safety of bipolar vs monopolar transurethral resection of the prostate. BJU Int. 2012;109:240–248.
See Also (Topic, Algorithm, Media)
• Bladder Outlet Obstruction (BOO)
• Hyponatremia, Urologic Considerations
• Prostate, Benign Hyperplasia/Hypertrophy (BPH)
CODES
ICD9
• 276.1 Hyposmolality and/or hyponatremia
• 276.69 Other fluid overload
• 997.5 Urinary complications, not elsewhere classified
ICD10
• E87.1 Hypo-osmolality and hyponatremia
• E87.70 Fluid overload, unspecified
• N99.89 Oth postprocedural complications and disorders of GU sys
CLINICAL/SURGICAL PEARLS
• Diagnosis of the TUR syndrome requires high clinical suspicion.
• Prompt diagnosis, evaluation, and management are essential to prevent adverse events.
• If a significant extraperitoneal perforation occurs during the TUR, consider abandoning procedure after achieving hemostasis to prevent excessive fluid absorption.
• Limit resection time to <60–90 min.
• Consider open prostatectomy, or other appropriate options (eg, laser assisted techniques), for adenoma >100 g.
• Use of bipolar resectoscopes to perform TURP permits use of saline irrigation reducing risk of TUR syndrome.