RENAL AND GENITOURINARY PROCEDURES

Transurethral Resection of the Prostate

Pathophysiology of Prostate Hypertrophy

The prostatic gland consists of four closely integrated zones—the anterior, peripheral, central, and preprostatic zones. Each zone consists of secretory, smooth muscle, and fibrotic tissue. All four zones are enclosed in one capsule. The gland is rich in blood supply. Arteries and veins penetrate the prostatic capsule and branch inside the gland. The venous sinuses adjacent to the capsule are particularly large.

As early as the 4th decade of life, nodules begin to develop in the preprostatic zone and form middle, lateral, and posterior lobes. The middle and posterior lobes are most often associated with symptoms of urinary tract obstruction. ^[117]

Surgical Procedures

Transurethral resection of the prostate (TURP) is performed by inserting a resectoscope through the urethra and resecting prostatic tissue with an electrically powered cutting-coagulating metal loop. As much prostatic tissue as possible is resected, but the prostatic capsule is usually preserved. if the capsule is violated, large amounts of irrigation solution are absorbed into the circulation and the periprostatic and retroperitoneal spaces.

Bleeding during TURP is common, but usually controllable; however, when large venous sinuses are opened, hemostasis becomes difficult. If bleeding becomes uncontrollable, the procedure should be terminated as quickly as possible and a Foley catheter passed into the bladder and traction applied to it. The catheter's inflated balloon exerts lateral pressure on the prostatic bed and reduces bleeding. Bleeding requiring transfusion occurs in about 2.5% of TURP procedures.^[118]

Irrigation Solutions

Ideally, an irrigation solution for TURP should be isotonic, electrically inert, nontoxic, transparent, easy to sterilize, and inexpensive. Unfortunately, such a solution does not exist. Distilled water is electrically inert and inexpensive and has excellent optical properties; however, it is extremely hypotonic. When absorbed into the circulation in large amounts, plain water causes hemolysis, shock, and renal failure.

In recent years, a number of nearly isotonic irrigation solutions have become available. Commonly used are solutions of glycine, 1.2% and 1.5%; mannitol, 3% to 5%; glucose, 2.5% to 4%; sorbitol, 3.5%; Cytal (a mixture of sorbitol, 2.7%, and mannitol, 0.54%); and urea, 1% ( Table 54-11 ). These solutions are purposely moderately hypotonic to preserve their transparency.

Although they cause no significant hemolysis, excessive absorption of modern irrigation solutions might lead to other complications, such as pulmonary edema and hyponatremia. In addition, the solutes may have adverse effects. Glycine may cause cardiac and retinal toxic effects, mannitol rapidly expands the blood volume and might

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Replacement of distilled water with nearly isosmotic solutions has eliminated hemolysis and its sequelae as a complication of TURP. Moreover, the incidence of severe CNS problems associated with extreme hyponatremia, such as convulsions and coma, has been reduced. However, the other major problem associated with the absorption of large volumes of irrigating solution, overhydration, still remains.

Anesthetic Techniques

Spinal anesthesia is the most frequently used anesthetic for TURP in the United States and is believed to be the technique of choice by many. A spinal anesthetic provides adequate anesthesia for the patient and good relaxation of the pelvic floor and the perineum for the surgeon. The signs and symptoms of water intoxication and fluid overload can be recognized early because the patient is awake. Accidental bladder perforation is also recognized easily if the spinal level is limited to T10 because the patient would experience abdominal or shoulder pain. Satisfactory regional anesthesia for TURP involves achieving an anesthetic block level that interrupts sensory transmission from the prostate and bladder neck. In addition, the uncomfortable sensation of bladder distention must be considered.^{[119] [120]}

As explained earlier, the visceral pain sensation from the prostate and bladder neck is transmitted by afferent parasympathetic nerve fibers derived mostly from the second and third sacral roots traveling with the pelvic splanchnic nerves. Bladder sensation is supplied by sympathetic nerves of the hypogastric plexus, derived from nerve roots extending inferiorly from T11 to L2. Therefore, regional anesthesia resulting in a sensory level to T10 will be required to eliminate the discomfort caused by bladder distention and other aspects of this procedure; however, slightly lower sensory levels will often suffice for smaller lesions. In one study in which bladder pressure was monitored and kept low, anesthetic levels to T12 or L1 were adequate, but midlumbar blocks to L3 were not.^[121] Sensory levels above T9 should not be sought because the capsular sign (i.e., pain on perforation of the prostatic capsule) will not be present should perforation occur.

Subarachnoid anesthesia is generally preferred over continuous epidural anesthesia for the following reasons. It is technically easier to perform in the elderly, and the duration of surgery is not generally very long. Furthermore, the incomplete block of sacral nerve roots that occasionally occurs with the extradural technique is avoided with subarachnoid anesthesia.

Caudal and sacral blockade has also been used effectively for prostate surgery, and bladder distention is avoided with the use of continuous irrigation. Caudal anesthesia has been used effectively in high-risk patients undergoing laser prostatectomy.^[122] Hemodynamic stability is the main advantage with this technique. Local infiltration of the perineum and the prostatic fossa has also been advocated by some for limited TURP procedures, although the operative analgesia afforded by local infiltration is not comparable in quality to spinal anesthesia. General anesthesia may be necessary in patients who require ventilatory or hemodynamic support, have a contraindication to regional anesthesia, or refuse regional anesthesia.

Advantages of Regional Anesthesia over General Anesthesia

Regional anesthesia offers several advantages over general anesthesia for TURP. The incidence of deep vein thrombosis (DVT) is decreased and the amount of operative blood loss is reduced with regional anesthesia as compared with general anesthesia. The reduction in operative blood loss when regional rather than general anesthesia is used has been shown to be the case in other pelvic procedures in addition to TURP, such as cystectomy and major vaginal surgery.^[123] The decrease in systemic blood pressure secondary to the sympathetic blockade produced by the regional technique was determined not to be the only factor in reducing blood loss. In fact, good evidence indicates that both peripheral venous pressure and central venous pressure decrease during regional anesthesia and spontaneous ventilation. It is postulated that this decrease in peripheral venous pressure might result in reduced blood loss during prostatic and other surgery. Additional factors influencing blood loss during TURP are the vascularity and size of the gland and the duration of surgery. An increase in fibrinolysis during prostate resection as a result of the release of urokinase from prostate tissue also factors into the blood loss that occurs. Other factors that affect blood loss during TURP include the size of the gland, the duration of the procedure, the number of sinuses opened during resection, the presence of infection, and prostate inflammation from repeated or recent catheterizations. These factors make it quite difficult to compare studies evaluating blood loss during TURP or arrive at conclusive findings based on meta-analysis.^{[118] [120] [124]}

Patients undergoing prostatectomy are prone to DVT for a number of reasons, including advanced age and the presence of malignancy, cardiac disease, varicose veins, and obesity. In this case, the increased blood flow resulting from the sympathetic blockade of regional anesthesia may play a role in reducing DVT formation. ^{[125] [126]} Recent data also confirm the earlier belief that regional anesthesia decreases the hypercoagulable tendency in the postoperative period and helps maintain normal coagulation and platelet function; these benefits are believed to be due to modulation of the neuroendocrine response to

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TURP is associated with a particular set of complications with anesthetic implications. These problems must be considered, along with the usual considerations such as the general health of the patient, the length of the procedure, and patient and surgeon preferences, when choosing an anesthetic technique.

The use of regional anesthesia for TURP allows the anesthesiologist the advantage of monitoring the patient's mental status intraoperatively. Excessive absorption of irrigating fluid during the procedure produces a number of problems with cardiovascular and neurologic implications. A change in the patient's mental status provides an early indication that excessive absorption of irrigating fluid has occurred.

CNS symptoms, which include irritability, apprehension, confusion, and headache, provide early warning signs of rapidly developing hyponatremia. The use of regional anesthesia, along with light conscious sedation if desired, enables the anesthesiologist to detect these early signs of hyponatremia. Further progression of hyponatremia (sodium <102 mEq/L) and decreased serum osmolality lead to the development of seizures and coma. The CNS effects become apparent at sodium levels below 120 mEq/L. The cardiovascular effects of severe hyponatremia include negative inotropy, hypotension, and dysrhythmias. At sodium levels below 115 mEq/L, ECG changes are made manifest by QRS widening and ST-segment elevation.^[126]

Visual disturbances such as blurred vision and transient blindness have been reported in association with TURP. The biotransformation of absorbed glycine to ammonia has been implicated in these and other CNS abnormalities. Another potential complication during TURP is bladder perforation secondary to overdistention with irrigation fluid or contact of the bladder wall with the surgeon's resectoscope. Conscious patients may experience symptoms related to perforation well before it becomes apparent to the surgeon, thereby alerting the operating team early on. Signs and symptoms of bladder perforation include bradycardia, hypotension, restlessness, diaphoresis, nausea, abdominal pain, dyspnea, shoulder pain, and hiccups. Extraperitoneal perforation may be manifested as pain in the periumbilical, inguinal, or suprapubic area. Intraperitoneal bladder perforation, a less frequent event, may cause symptoms related to diaphragmatic irritation (i.e., pain referred to the upper part of the abdomen, precordial area, shoulder region, or neck).^[126]

Regional anesthesia for TURP therefore offers some advantages over general anesthesia. Although laboratory monitoring of electrolytes is useful intraoperatively, a change in mental status in a conscious patient provides an early indication of electrolyte disturbances. The sympathetic blockade produced by regional anesthesia increases venous capacitance, thereby decreasing the effect of excess fluid absorption. Bladder perforation is recognized earlier in a conscious or lightly sedated patient, as noted previously.

The sensory level produced by regional anesthetic techniques should be at approximately T9-10 to prevent the discomfort of bladder distention. Lower sensory levels may be adequate; however, sensory levels above T9 are undesirable because pain caused by perforation of the prostatic capsule (capsular sign) will not be apparent to the patient if this complication occurs. Another benefit of regional anesthesia for TURP is a decreased requirement for analgesics in the immediate postoperative period when compared with general anesthesia.^[127]

Morbidity and Mortality after Transurethral Resection of the Prostate

Although spinal anesthesia offers certain distinct advantages over general anesthesia for TURP surgery, mortality and many markers of patient outcome have been similar for both groups. What constitutes the safest anesthetic for prostatectomies was debated as early as 1924, with proponents of regional anesthesia gaining ground quickly thereafter.^[128] Currently, the 30-day mortality rate associated with TURP is reported to be between 0.2% and 0.8%.^[120] Mortality rates are reported to be similar in patients receiving regional anesthesia or general anesthesia.^[129] It should be noted, however, that with mortality rates as low as 0.2%, a much larger number of patients need to be studied than previously examined in any of the studies to draw a meaningful and statistically significant conclusion.^[119] The postoperative morbidity rate in one study was 18%.^[120] Increased morbidity was found in patients with resections exceeding 90 minutes, gland size greater than 45 g, acute urinary retention, and age older than 80 years. ^[120] Ashton and coworkers^[130] studied 250 men undergoing TURP and observed one postoperative myocardial infarction (0.4%) resulting in one death. The incidence of postoperative complications, namely, myocardial infarction, pulmonary embolism, cerebrovascular accidents, transient ischemia attacks, renal failure, hepatic insufficiency, and the need for prolonged ventilation, is similar when comparing patients receiving regional anesthesia with those receiving general anesthesia.^{[118] [120]}

Postoperative cognitive function after TURP conducted under general versus regional anesthesia has been studied by many investigators. Most studies have failed to demonstrate any significant difference in cognitive function in patients receiving regional anesthesia and those receiving general anesthesia.^[131] Postoperative behavioral changes in TURP patients are believed to be related to fluid absorption and increased cerebral fluid; cerebral oximetry studies have confirmed this relationship.^[132] Preoperative mental impairment in the elderly also influences postoperative mental function, which makes another case against the use of heavy sedation in these patients.

Complications of Transurethral Resection of the Prostate

Absorption of Irrigating Solution

Because the prostate gland contains large venous sinuses, it is inevitable that irrigating solution will be absorbed. Simple principles govern the amount of absorption: (1) the height of the container of irrigating solution above

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Circulatory Overload, Hyponatremia, and Hypo-osmolality

For many years, distilled water was used for bladder irrigation during TURP because it interfered least with visibility; however, absorption of large quantities of water led to dilutional hyponatremia, which resulted in hemolysis of red blood cells and CNS symptoms ranging from confusion to convulsions and coma. Consequently, distilled water was abandoned in favor of isosmotic or nearly isosmotic solutions for TURP. Solutions such as normal saline and Ringer's lactate would be well tolerated when absorbed intravascularly, but these electrolyte solutions are highly ionized and facilitate the dispersion of high-frequency current from the resectoscope. Thus, solutions of nonelectrolytes, such as glucose, urea, glycine, mannitol, sorbitol, or Cytal, have replaced distilled water. Of all the irrigating solutions available today (see Table 54-11 ), glycine and Cytal are the two most commonly used.^[133]

Replacement of distilled water with nearly isosmotic solutions has eliminated hemolysis and its sequelae as a complication of TURP. Furthermore, the incidence of severe CNS problems associated with extreme hyponatremia, such as convulsions and coma, has been reduced^[134] ; however, the other major problem associated with the absorption of large volumes of irrigating solution, overhydration, still remains. Under usual conditions, only 20% to 30% of a load of crystalloid solution remains in the intravascular space; the remainder enters the interstitial space. When intravascular pressure is increased, movement of fluid into the interstitial space and the development of pulmonary edema are favored. Whether symptoms of circulatory overload will develop in a given patient depends on the patient's cardiovascular status, the amount and rapidity of absorption of irrigating fluid, and the extent of surgical blood loss.^[134] It is obvious that the situation is dynamic and that patients must be monitored carefully. In this regard, spinal or epidural anesthesia, supplemented with only light intravenous sedation, has the advantage of allowing the patient's subjective judgment to contribute to assessment of his or her condition during surgery. In addition, the cardiovascular depression associated with the administration of potent inhaled anesthetics is avoided. Another advantage of regional anesthesia is that the sympathetic block that it produces increases venous capacitance and tends to mitigate intraoperative fluid overload. As a note of caution, when the block dissipates, venous capacity acutely decreases and circulatory overload can occur.

Concomitant with the circulatory overload caused by significant absorption of irrigating fluid are usually hyponatremia and hypo-osmolality. TURP syndrome has been typically described as being caused by hyponatremia and subsequent water intoxication. It is now recognized that the classic CNS signs of TURP are not caused by the hyponatremia per se but are due to the accompanying acute serum hypo-osmolality that allows movement of water into cells and causes cerebral edema. ^{[133] [134]}

The use of nonelectrolyte isosmotic irrigating solutions has reduced the incidence of severe CNS complications because extreme extracellular fluid hypo-osmolality does not occur and the subsequent development of cerebral edema is avoided.^{[133] [134]} That CNS symptoms occur at all is probably due to the fact that the incidence and extent of hyponatremia are unchanged. The concentration of extracellular sodium must be in the physiologic range for depolarization of excitable cells and production of the action potential. When extracellular sodium levels fall below 100 mEq/L, consciousness is lost and convulsions may ensue.^[134] Signs and symptoms of cardiovascular dysfunction secondary to hyponatremia may also occur, such as arrhythmias, hypotension, and pulmonary edema^[135] ; however, it is often impossible to separate the latter events from those attributable to fluid overload.

Glycine Toxicity

Since the early 1980s, attention has turned to the absorption of glycine (HO₂ -CCH₂ -NH₂ ), a nonessential amino acid, as a possible cause of some CNS symptoms associated with TURP. For example, in one publication, five cases of transient blindness were attributed to glycine toxicity.^[136] Glycine has a distribution similar to that of aminobutyric acid, the latter being an inhibitory transmitter in the brain; it has been suggested that glycine is also a major inhibitory transmitter acting in the spinal cord and brainstem.^[136] Normal plasma glycine levels are 13 to 17 mg/L, whereas levels as high as 1029 mg/L were measured during one episode of blindness. Twelve hours later, the glycine level in this case had fallen to 143 mg/L, by which time vision had returned; however, an overall correlation between plasma glycine levels and CNS toxicity has not been established, so the relationship, though interesting, must still be considered speculative. Glycine has also been implicated in the myocardial depression and hemodynamic changes associated with TURP syndrome.^[137]

Ammonia Toxicity

Absorption of glycine may result in CNS toxicity as a result of oxidative biotransformation of glycine to ammonia.^{[138] [139]} In a report of delayed awakening after TURP in three patients,^[138] an association with elevated blood ammonia concentrations was noted. Blood ammonia levels as high as 500 M were noted in this and another case report.^[139] Deterioration of CNS function is said to occur when ammonia levels exceed 150 M. In a prospective study examining glycine metabolism, blood ammonia levels were increased postoperatively in 12 of 26 patients in whom 1.5% glycine was used as the irrigating solution for TURP.^[138] Blood glycine levels were also measured. Interestingly, glycine and ammonia levels did not correlate; in fact, the opposite relationship was prevalent. Furthermore, high ammonia levels were not necessarily associated with CNS symptoms of toxicity.

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Perforation

Another relatively common complication of TURP is perforation of the bladder.^[140] Perforations usually occur during difficult resections and are most often made by the cutting loop or knife electrode. Some, however, are made by the tip of the resectoscope, whereas others may result from overdistention of the bladder with irrigation fluid. Most perforations are extraperitoneal, and in a conscious patient they result in pain in the periumbilical, inguinal, or suprapubic regions; additionally, the urologist may note the irregular return of irrigating fluid. Less often, the perforation is through the wall of the bladder and is intraperitoneal, or a large extraperitoneal perforation may extend into the peritoneum. In such cases, pain may be generalized in the upper part of the abdomen or be referred from the diaphragm to the precordial region or the shoulder. Other signs and symptoms, such as pallor, sweating, abdominal rigidity, nausea, vomiting, and hypotension, have been reported; their number and severity depend on the location and size of the perforation and the type of irrigating fluid. In an early series of 2015 cases in which the incidence of complications of TURP was examined, perforation occurred in 25 patients (1.2%).^[141] Four deaths and five additional major complications occurred in the 12 patients in whom suprapubic cystostomy was delayed more than 2 hours after perforation. Distilled water was the bladder irrigant in most of these cases, so it is not clear whether these morbidity and mortality data are still relevant.

Transient Bacteremia and Septicemia

The prostate harbors many bacteria, which can be a source of intraoperative and postoperative bacteremia through the prostatic venous sinuses. This risk is further increased by the presence of an indwelling urinary catheter. Bacteremia is usually asymptomatic and easily treated with commonly used antibiotic combinations that are effective against gram-positive and gram-negative bacteria. In 6% to 7% of patients, however, septicemia may occur.^[120] Common manifestations include chills, fever, and tachycardia. In severe cases, bradycardia, hypotension, and cardiovascular collapse may occur, with mortality rates between 25% and 75%. Aggressive treatment with antibiotics and cardiovascular support is warranted.

Hypothermia

Irrigating fluids stored at room temperature are frequently used during TURP. Heat loss as a result of irrigation and significant absorption of this fluid may lead to a decrease in the patient's body temperature and cause shivering. ^[142] The use of warmed irrigating solutions has been shown to be efficacious in reducing heat loss and the resultant shivering.^[143] Although one may believe that warming of fluids might cause increased bleeding because of vasodilation, such is not the case, as shown by the study of Heathcote and Dyer. ^[144] The use of systemic and intrathecal opioids decreases postoperative shivering from cold.^[145]

Bleeding and Coagulopathy

A hypertrophied prostate is highly vascular, and operative bleeding is usually significant.^[146] The blood is washed into the draining bucket and mixed with ample quantities of irrigant fluid. Hence, estimation of blood loss is quite inaccurate and extremely difficult. Efforts have been made to quantify blood loss based on resection time (2 to 5 mL/min of resection time) and size of the prostate in grams (20 to 50 mL/g); however, these guidelines are rough estimates at best, and the patient's vital signs and serial hematocrit values should be monitored to better assess the blood loss and need for transfusion. Because adrenergic receptors are abundant in prostate tissue, the use of adrenergic agonists would cause vasoconstriction of prostatic blood vessels and a decrease in blood loss. In a 1993 study, blood loss during TURP was reduced by 50% with preoperative use of methoxamine.^[147]

Abnormal bleeding after TURP occurs in less than 1% of cases; it is believed by some to be due to systemic fibrinolysis caused by plasmin. The prostate releases plasminogen activator, which converts plasminogen to plasmin. Others believe that the fibrinolysis is secondary to disseminated intravascular coagulation triggered by the systemic absorption of resected prostate tissue, which is rich in thromboplastin.^[118] If primary fibrinolysis is suspected, aminocaproic acid may be effective when given intravenously in a dose of 4 to 5 g during the first hour, followed by 1 g/hr.^[118]

TURP Syndrome ( Table 54-12 )

TURP syndrome is a term applied to a constellation of symptoms and signs caused primarily by excessive absorption of irrigating fluid. Neurologic manifestations, such as restlessness, agitation, confusion, altered sensorium, seizure, and coma, result from water intoxication and dilutional hyponatremia, which collectively produce cerebral edema. The neurotoxic effects of glycine and ammonia may further compound the clinical situation. The cardiovascular effects reflect volume overload and hyponatremia. Hypertension and bradycardia are frequently seen because of acute hypervolemia. If serum sodium levels rapidly decrease to less than 120 mEq/L, negative inotropic effects are manifested as hypotension and ECG changes of widened QRS complexes and ventricular ectopy.^{[118] [134]} Pulmonary edema, congestive heart failure, and cardiorespiratory arrest have been reported in these patients.

Treatment of TURP syndrome consists of fluid restriction and a loop diuretic such as furosemide. Hypertonic saline (3% sodium chloride) is rarely, if ever necessary and should be considered only in patients with severe hyponatremia. CNS complications of hypertonic saline include cerebral edema and pontine myelinolysis. ^{[119] [134]} Cardiovascular support should be provided as necessary.

Anesthetic considerations for TURP should include positioning. TURP is usually performed in the lithotomy position with a slight Trendelenburg tilt. Such positioning would result in changes in pulmonary blood volume, a decrease in pulmonary compliance, a cephalad shift of the diaphragm, and a decrease in lung volume parameters such as residual volume, functional residual volume, tidal volume, and vital capacity. Cardiac preload may increase.

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