Etiology

TUR syndrome is a constellation of signs and symptoms caused by the

intravascular absorption of hypotonic fluids during endoscopic surgery. It
is most commonly reported following transurethral resection of the
prostate (TURP), but it may complicate any endoscopic procedure in which
hypotonic irrigation is used,
18
including cystoscopy, bladder tumor
resection, percutaneous nephrolithotripsy, and transcervical endometrial
resection. Intravascular absorption of irrigant occurs primarily through
direct infusion into open venous channels; however, reabsorption of
extravasated fluid following inadvertent perforation of the prostatic capsule
or bladder wall also may occur. This distinction is important because TUR
syndrome secondary to direct intravascular absorption presents acutely,
whereas TUR syndrome associated with extravasation may be delayed up to
24 hours.
19

Early reports of TUR syndrome noted reddish discoloration of the serum,
progressive oliguria, azotemia, pulmonary edema, and even death following
the absorption of large amounts of sterile water during TURP. Non-
electrolyte solutions with osmolalities similar to serum (275-290 mOsm/kg
H
2
O) were introduced when it was recognized that the rapid absorption of
water could cause intravascular hemolysis and subsequent renal failure.
These solutions included glycine, mannitol, and sorbitol. Although the risk
of hemolysis with such solutions is negligible, TUR syndrome remains a
concern, albeit less common, because all modern irrigants are hypo-
osmolar relative to serum (1.5% glycine = 200 mOsm/kg). The incidence of
TUR syndrome among patients undergoing TURP with glycine is 1% to
10%.
18
Mortality ranges from 0.2% to 0.8%.
19

Mechanism
The mechanism of TUR syndrome is not universally agreed upon. Leading
theories include the following
18,20
:
1. 1.
Intravascular fluid absorption
2. 2.
Hyponatremia
3. 3.
Hyperammonemia
4. 4.
Hyperglycinemia
Although many consider hyponatremia to be the primary cause of TUR
syndrome, multiple factors are likely responsible. This may help to explain
the heterogeneous presentation of this syndrome.
It is estimated that 20 mL of irrigation fluid is absorbed per minute of
resection during TURP.
50
Rapid or prolonged intravascular absorption
causes a transient hypervolemia as demonstrated by an initial rise in
central venous pressure (CVP), which plateaus within 15
minutes.
18,22
Hypertension and reflex bradycardia are common early;
however, as the syndrome progresses, a hypokinetic hemodynamic phase
characterized by hypotension and bradycardia often develops. This
hemodynamic shift reflects a decline in both cardiac output and
intravascular volume, which begin once irrigation is
discontinued.
18,23,24
Factors responsible include natriuresis, osmotic diuresis,
intracellular uptake of water, hyponatremia, hypocalcemia, and
hypothermia among others.
Hyponatremia results from (1) expansion of the extracellular compartment
by the infusion of hypotonic fluid (i.e., dilutional hyponatremia), and (2)
increase in the urinary excretion of sodium (i.e., natriuresis). The relative
contribution of dilution and natriuresis toward hyponatremia depends on
the amount of irrigation absorbed and the timing of serum sodium
analysis.
25
Early in the course of absorption, sodium dilution predominates
because the majority of fluid remains extracellular. As the osmotic gradient
widens, water is progressively drawn into the intracellular space such that
hyponatremia reaches nadir when hypotonic irrigation is stopped. Less
than 50% of the absorbed fluid remains extracellular 30 minutes after
infusion has ended.
Serum sodium is commonly used to quantify extracellular fluid (ECF)
volume expansion; however, this suggests that it is only at the completion
of surgery that such an estimate is accurate. The degree of hyponatremia is
an inaccurate measure of extracellular hydration at all other points in the
postoperative period. Cases of irrigant extravasation represent an exception
to this rule because hyponatremia in this setting is most pronounced 2 to 4
hours after surgery due to delayed reabsorption. The systemic absorption of
glycine stimulates renal sodium excretion.
18
Natriuresis accounts for 20% of
the hyponatremia at the conclusion of glycine infusion and 30% to 60%
when measured 30 minutes later. Taken together, the extracellular volume
contraction, intracellular volume expansion, and natriuresis that occur
following the absorption of hypotonic fluids call into question the use of
fluid restriction and loop diuretics as treatment for TUR syndrome.
Severe acute hyponatremia (<120 mEq/L), particularly in the context of
hypervolemia, is a risk factor for cerebral edema and possible mortality.
Early symptoms of cerebral edema include nausea, vomiting, and
confusion. Seizures, obtundation, and coma may develop if the
hyponatremia is not corrected promptly. Hypertension and bradycardia
(i.e., Cushing reflex) also may arise as a consequence of heightened
intracranial pressure. Radiologic studies demonstrate that cerebral edema
may occur following the absorption of as little as 1 L of hypotonic
irrigation.
26
By comparison, irrigation with normal saline causes a greater
expansion of the intravascular space, but cerebral edema is uncommon.
18

The most common irrigant used during TURP today is 1.5% glycine.
Independent of volume and electrolyte imbalance, glycine and its
metabolites retain properties that directly contribute to TUR syndrome in a
dose-dependent manner.
27,28
Glycine is metabolized by the liver into
ammonia and glyoxylic acid. A small proportion (10%) is excreted
unchanged by the kidneys and promotes an osmotic diuresis and
natriuresis.
18
Within the retina and central nervous system, glycine functions
as an inhibitory neurotransmitter. Visual disturbance is reported in 10% of
patients absorbing more than 500 mL of 1.5% glycine solution.
18,27,28
With
continued absorption, this may progress to transient blindness, which
generally resolves within 24 hours and requires no specific
treatment.
29
Depending on the volume of glycine absorbed, a spectrum of
mental status changes may be noted. The spectrum includes confusion,
depressed consciousness, and coma. Glycine also impairs cardiac
conduction and contractility through the generation of subendocardial
hypoxic lesions.
30

Ammonia represents an intermediate product in the hepatic metabolism of
glycine. Normally, ammonia is further metabolized by the liver into urea,
which is then excreted by the kidneys. In cases of renal or hepatic
insufficiency, however, the metabolism of ammonia is impaired and
hyperammonemic encephalopathy may occur. Serum ammonia levels tend
to correlate with the incidence and severity of neurologic
symptoms.
31
Hyperammonemic encephalopathy secondary to glycine
absorption is self-limited and will gradually correct once the infusion is
stopped. Only supportive measures need be provided.
Risk Factors
Potential risk factors for the development of TUR syndrome are listed
in Box 5-1.
18
Although the extent of resection correlates with the volume of
irrigation absorbed and the incidence of TUR syndrome, in turn, the
relationship between TUR syndrome and irrigation pressure is not as
precise. Two large studies have failed to demonstrate any correlation
between bag height and fluid absorption during TURP.
32,33
Smoking has been
shown to be an independent predictor of large-scale fluid absorption (>1 L)
in patients undergoing TURP. This is thought to reflect an increase in
prostatic microvessel density among smokers.
34