ANDRES S. MARRERO, ABELARDO M. PRODIGALIDAD, AUREA Z. AMBROSIO
National Kidney and Transplant Institute Division of Urology, QC, Philippines

Keywords: Prostatectomy, Transurethral

Abstract

Objectives. To determine the correlation of resection time, irrigant volume and prostatic weight with the incidence of transurethral prostatectomy (TURP) syndrome through intraoperative monitoring; and to evaluate the role of resection experience in the occurrence of the syndrome.

Methods. 579 out of 602 patients were selected to undergo intraoperative monitoring of resection time, irrigant volume and resected prostatic weight during transurethral prostatectomy. These variables were correlated with the occurrence of TURP syndrome using univariate and multivariate logistic regression. A risk level in each category was identified, and the incidence of TURP syndrome among combinations of these risk levels was differentiated using chi-square statistic. The incidence of the syndrome between resident and consultant-performed resections was compared using chi-square test with Yates’ correction.

Results. Overall, 35 patients (6.0%) were diagnosed with TURP syndrome. The syndrome correlated significantly with prolonged resection time (p < 0.0001), high prostatic weight (p < 0.0001) and high irrigant volume (p < 0.0001). The incidence markedly increased with resection time exceeding 60 minutes (16.9%), prostatic weight greater than 30 grams (22.4%) and irrigant volume more than 30 liters (23.5%). The presence of at least one of these risk categories has a TURP syndrome incidence of 15.9%; at least two risk categories, 25.3%; and all 3 risk categories, 45.4%. The difference between these subgroups was very highly significant (p = 0.0008). The incidence of TURP syndrome among residents was 25 out of 252 (9.9%) compared to 10 out of 327 (3.1%) among consultants (p = 0.0006).

Conclusions. Prolonged resection time, high prostatic weight and high irrigant volume are important risk factors in the development of TURP syndrome particularly when resection time exceeds 60 minutes, prostatic weight is heavier than 30 grams and irrigant volume is greater than 30 liters. The risk is enhanced by the presence of more than one of these risk categories. Additionally, lack of resection experience remains an important factor in its causation.

That TURP Syndrome is a fallacy has long been discarded as a result of better understanding of the pathophysiology of the disease.^1,2 It is now considered as a distinct clinical entity characterized by a constellation of signs and symptoms secondary to neurologic, cardiovascular and electrolyte imbalance resulting from the absorption of irrigating fluid through prostatic veins or breaches in the prostatic capsule during TURP. ³ Mental confusion, bradycardia, hypotension/hypertension, nausea, vomiting and visual disturbances associated with hyponatremia are most commonly observed.⁴ Although majority are mild in nature and are easily managed with close monitoring and diuretics alone, severe cases may lead to a significant morbidity or even to a preventable mortality which is often attributed to other causes such as myocardial infarction.⁵ This is one of the reasons why TURP, as the "gold standard" in the treatment of benign prostatic hyperplasia, has become a subject of reappraisals leading to the acceptance of medical and minimally invasive forms of therapy. ⁶

In spite of optics improvement, the development of continuous flow resectoscopes, and the utilization of "non-hemolytic" solutions such as glycine, sorbitol and mannitol, TURP syndrome remains a cause of concern not only among resectionists but also among anesthesiologists who, in most instances, make the diagnosis and manage the condition. Considering that TURP is one of the most common surgical procedures performed by most urologists worldwide, the reported incidence of 2% as determined in one large multicenter study⁷ can not be regarded as insignificant, especially in the local setting where distilled water is still used as irrigating fluid and where ideal instrumentation is not readily available.

Early diagnosis and prompt institution of therapy is the key in its successful management.⁸ Diagnosis is a product of vigilance during resection and a high index of suspicion which can be gleaned from the factors known to be related to the development of the syndrome: resection time, the irrigating fluid volume and its rate of infusion, prostatic size, peripheral venous pressure, overall clinical status and surgical skill.⁸ It was reported in the 1950’s that approximately 20 ml per minute of fluid was absorbed during resection, although there appeared to be a wide variation among patients.⁴ In the 1989 American Urological Association (AUA) Cooperative Study, the risk of TURP syndrome was reported to be higher with a resection time exceeding 90 minutes and a gland greater than 45 grams. Non-hemolytic fluids were used in 90% of the cases in this study and no correlation with the volume of the solution utilized or absorbed was inferred. At present, several methods to assess the amount of absorbed irrigant have been proposed but none has been universally applied to actual urologic practice.⁹ What is most practical in a setting where there exists no means of determining the amount of absorbed fluid is to directly measure the amount of irrigant infused during the procedure and, together with the prostatic weight and resection time, correlate these measurements with the occurrence of TURP syndrome inorder to identify patients who are at risk for the syndrome for the purpose of early diagnosis and treatment -- thus the main goal of this study. In addition, surgical experience, as exemplified by whether resection is performed by residents in their early cases of TURP or consultants with at least 5 years of urologic practice, is also evaluated.

Since January 1993, patients who would undergo transurethral prostatectomy in our institution were subjected to regular intraoperative monitoring of resection time, irrigating fluid volume, resected prostatic weight and the signs and symptoms of TURP syndrome. A data base was prepared at the start of the study and measurements of variables were recorded by the monitoring resident during each procedure. Excluded in the study were patients with: preoperative anemia requiring blood transfusion, serum sodium of less than 130 mg/dl, renal insufficiency as determined by elevated serum creatinine, questionable electrocardiograph and chest radiograph findings, previous cerebrovascular accident, and concommitant performance of other transurethral procedures such as cystolitholapaxy, urethrotomy, lithotripsy or retrograde pyelography. Subarachnoid block was used in 90% of the patients. More than 95% had a preoperative clinical status of American Society of Anesthesiology (ASA) Classification II to III. The median age of the study population was 68 years (range, 40 to 97 years). TURP syndrome was diagnosed in the presence of the following signs and symptoms: sudden onset of bradycardia, hypotension/hypertension, restlessness, with or without nausea or vomiting, somnolence, seizures or ECG changes like widened QRS complex or elevated ST segment. In addition , a serum sodium level of less than 130 mEq/Li, or the presence of a hemolysed but properly collected blood specimen was documented. All patients were managed with diuresis, cardiovascular support, constant monitoring and sodium replacement when necessary.

The procedure was performed either by a senior urology resident or consultant at a ratio of 1: 1.3. All utilized a continuous flow Storz resectoscope and distilled water as irrigating solution contained in a uniform receptacle placed at a uniform height of about 50 cm from the level of the prostate. The resection time, irrigating fluid volume and resected prostatic weight were measured and these were correlated with the onset of the signs and symptoms of the TURP syndrome. Tests of significance of the association were expressed as relative risks and their 95% confidence intervals. To detect the group differences that depend on certain relationships among these variables, multivariate analysis was done. A cut-off point or risk level in each category was also identified and the difference between the presence of one or more of these risk categories was analysed using chi-square statistic. The difference in the incidence of TURP syndrome between resident and consultant-performed resections was analysed using chi-square test with Yates’ correction. All tests of hypotheses were two-tailed and p values of 0.05 or lower were considered statistically significant. A CDC/WHO software was utilized in the statistical analysis.

TURP Syndrome was present in 35 out of 579 patients, representing an incidence rate of 6.0%. 11 cases were severe, requiring intensive care unit admission, 5 of whom subsequently expired within a 36-hour period from end of resection . The relationship between resection time, prostatic weight, irrigant volume and TURP syndrome is summarized in Tables I, II and III respectively. The means obtained were: resection time, 48.7 +/-22.7 minutes; prostatic weight, 17 +/-11.7 grams and irrigant volume, 20.5 +/-9.3 liters. The incidence of TURP syndrome appeared higher as the values of these variables increased. However, on closer inspection of these tables, there exists a marked rise in the incidence of the syndrome at a resection time longer than 60 mins, prostatic weight greater than 30 gms and irrigant volume more than 30 lis. This trend was evident even when these were considered as continuous variables. Thus, each variable was converted into ranges as shown in these tables inorder to fit a linearity in the logit and qualify for a logistic regression. The resultant univariate and multivariate analyses demonstrated that TURP syndrome correlated significantly with high values of resection time, prostatic weight and irrigant volume and that all are independent predictors of the occurrence of the syndrome (Table IV).

The incidence of TURP syndrome at each observed risk category was: more than 60 minutes resection time, 24 of 142 (16.9%), prostatic weight heavier than 30 grams, 17 of 76 (22.4%) and irrigant volume greater than 30 liters, 20 of 85 (23.5%). Figure 1 demonstrates the incidences’ marked difference when compared to those falling below the identified risk categories. The incidence of TURP syndrome when at least one, at least two or all three risk categories were present is illustrated in Figure 2. Table V shows that the difference between these subgroups was very highly statistically significant, i.e., the overall risk is indeed higher in the presence of at least two risk categories and highest in the presence of all risk categories. A total of 176 of 579 (30.4%) of the patient population thus fell into a group at risk for TURP syndrome. In contrast, only 7 of the 403 (1.7%) patients who fell below all the risk categories had TUR syndrome. The higher incidence of TUR syndrome in resident-performed resections compared to those performed by consultants (Figure 3) was also very highly significant (Table VI).

The mortality rate secondary to TUR syndrome was 5 of 35 (14.3%). Three of these were performed by residents. Capsular perforation was present in 39 cases (6.7%), 12 of which were reported by residents within the first 30 minutes of resection. 8 of 39 (20.5%) capsular perforations developed the syndrome.

Despite the recently observed decrease in the frequency of transurethral prostatectomy owing mainly to the criticisms raised against the safety of the procedure, it remains the gold standard of treatment for BPH. Thus, common complications such as transurethral resection syndrome continue to be widely reported.¹⁰ The introduction of glycine, sorbitol and mannitol in developed countries has substantially diminished its incidence, but this is not so in institutions where distilled water is still being utilized. Our 6.0% incidence rate attests to this fact.

There appears to be a disparity between urologists’ and anesthesiologists’ opinion in terms of the diagnostic criteria for TURP Syndrome. Olsson and associates evaluated the signs and symptoms of the syndrome in 273 patients and reviewed cases over the previous 50 years, and they have included, among others, chest pains, pricking sensation, chills, diarrhea, and abdominal pain as part of the symptom complex.¹¹ Most urologists would ascribe these to advanced stage, blood loss, preoperative co-morbidities, or to medications. It is not surprising therefore to find incidence ranging from 2% to 10% in different prospective studies.¹¹ Yet, the most clinically important consequence of some urologists’ claim that they have not encountered a case of TURP syndrome in their many years of resection is misdiagnosis, which may lead to therapeutic delay or even improper treatment. If this "unpopular" symptoms were to be included in this study, the actual incidence would reach 12% -- an unacceptably high rate in the mare urologica.

A persistent problem in the confirmation of the diagnosis is the presence of hemolysis in majority of our blood samples, such that the actual level of serum sodium could not be accurately measured. However, although hyponatremia is traditionally equated to the causality of the syndrome, establishing natremia level is not mandatory in the diagnosis particularly when signs and symptoms are overt and when other possible causes are not evident.¹² On the other hand, hemolysis is a clue that certain degree of dilutional hyponatremia or hypoosmolality has occurred. This fact emphasizes not only the dilemma in diagnosis but more importantly, the danger in using distilled water as irrigating solution. Gatchalian and associates formally initiated the use of isoosmotic mannitol in the local scene in 1987¹³ but this has not been subsequently practiced and neither did it find favor among other urologists mainly due to added expense and the absence of a readily available preparation specifically intended for transurethral resection. Intravascular hemolysis is probably the only morbidity minimized through the use of non-hemolytic solutions. The overall picture of TURP syndrome has not changed, and in fact, other electrolyte abnormalities such as hyperglycinemia or hyperammonemia have been reported with the use of these solutions.¹¹

Our results show an increasing incidence of TURP syndrome at longer resection time and higher irrigating fluid volume. However, the relationship does not appear to be linear. Instead, there is a marked increase in the incidence at the identified risk levels of 60 mins and 30 lis respectively. As observed, however, even a low amount of irrigant (less than 12 li.) and less than 30 mins. of resection time could cause severe syndrome as seen in 2 of our patients. Capsular perforation was present in both cases and this would probably explain the early and severe symptoms. These patients, operated on by senior residents in their first three months of TURP, eventually expired within 16 hours despite aggressive therapy. This is a proof of the hazards of capsular perforation and may indicate that absorption occurs more rapidly in open sinuses - an event that is less tolerated than when absorption occurs over a certain period of time. In addition, it implies the need for constant communication between the surgeon and the anesthesiologist particularly when procedural deviations occur during resection. Doll and associates, in their combined American and European multicenter study on the complications of transurethral prostatectomy, reported a 10% incidence of capsular perforation.⁵ This rate was admittedly an underestimation since most of the surgeons who reported perforation were exceptional specialists. It is observed in our study that capsular perforation is more common among residents. Whether this incidence is real or consultants merely tend to underreport capsular perforation could not be determined in this study.

Minimizing the amount of absorbed irrigating fluid during resection has been the subject of several studies.^14-23 The use of a bladder pressure device to warn the surgeon against high intravesical pressure elevation of more than 1.5 kPa was found to be effective regardless of age, prostatic mass, resection time and speed or hemorrhage.¹⁴ Continuous monitoring of body weight during resection was reported by Lyon and Narayan.¹⁵ A scale that fits into the operating table determined than no syndrome occurs if weight gain of 2 kg is not exceeded. It is also observed that a 20% reoperation and a 10% late rebleeding rates reflect incomplete resection, as the operator protects against invasion of fluid into the venous plexuses and prostatic capsule. Monitoring serum sodium changes has also been employed by means of a gadget attached to a peripheral line.¹⁶ However, this cumbersome ion-selective monitor is not readily available even in highly specialized centers. Other techniques include estimating the amount of "lost" irrigating solution, estimating concentrations of radioisotopes incorporated with the irrigant, and regular interval monitoring.¹⁷ Perhaps the most popular technique, introduced and practiced in some Scandinavian countries is measuring the amount of absorbed ethanol added to the irrigant at the start of resection with the aid of an alcometer attached to the respirator.^18-20 Introduced by Hulten in 1986, it was found to be more accurate and effective than any of the aforementioned methods. Collaborating with the Hulten technique, Hahn and associates pointed out that the uptake of fluid usually begins midway during the resection and continues throughout the procedure, regardless of whoever performs the resection.¹⁸ Based on this method, it appears that the onset of absorption is usually associated with a sudden onset of hypotension. This technique, however, also lacks specificity since measurements obtained rely on a crude formula to correct for the effects of metabolism, diffusion and excretion making quantification of the total amount of ethanol absorbed questionable. Moreover, "false alarms" are common and the volumetric fluid balance does not accurately reflect absorption.¹¹

The search for the ideal and clinically applicable technique of fluid assessment is relevant not only in terms of prevention, diagnosis and treatment, but also in the overall standard of care of patients undergoing transurethral surgery. It is timely in view of the concerns that have been raised against endoscopic prostatectomy. Its application to other procedures such as percutaneous nephrolithotomy, ureteroscopy, or transcervical endometrial resection remains to be explored.²⁴

Although the incidence of TURP syndrome increased at higher prostatic weights in this study, the relationship is also non-linear since there is a marked increase once prostatic weight reaches 30 gms. This obtained lower risk level compared to the AUA cooperative study (45 gms) may merely be a reflection of the kind of irrigant used and the presence of capsular perforation early during resection thereby forcing termination of the procedure. Size, however, is not the sole determinant. Highly vascular prostates tend not only to cause more severe hemorrhage during resection, which is often the greater cause of concern, but also to enhance absorption inherently due to the larger vessels through which the irrigant traverses.¹⁸ In cases where symptoms are persistent despite correction of anemia secondary to hemorrhage, TURP syndrome should therefore be highly entertained.

The higher rate and severity of TURP syndrome among patients operated on by residents during their early months of resection and its decline during the latter part of the year, merely reiterates the obvious: adequate technical skill is a necessity when performing TURP.

The standard treatment of TURP syndrome includes constant monitoring, diuretics, hypertonic saline and, occasionally, Sodium bicarbonate. Criticisms on this mode of therapy, particularly on saline infusion and rapid correction of hyponatremia have been raised due to the occurrence of grave, albeit rare, neurologic sequelae, mainly central pontine myelinosis.⁶ For severe cases, early use of invasive hemodynamic monitoring, intravenous Calcium, inotropes, plasma volume expanders, hyperventilation to possibly reduce the degree of cerebral edema have been proposed.⁶ Hemodialysis is also suggested particularly when biochemical derangements are severe and are not readily responsive to diuresis.²⁵ Thus, it is also important to formulate a consensus on the present-day management of TURP syndrome.

TURP syndrome remains a significant complication of TURP. Patients are particularly at risk in the development of the syndrome when exposed to a resection time longer than 60 minutes, resected prostatic weight heavier than 30 grams and irrigant volume greater than 30 liters. The risk is enhanced when more than one of these risk levels are present or when TURP is performed by inexperienced resectionists or residents in their early stage of training. Monitoring resection time, resected prostatic weight and irrigant volume intraoperatively with particular attention to these identified risk levels, may therefore be beneficial not only in the early diagnosis of TURP syndrome but more importantly, in early institution of treatment and prevention of progression into more severe form which may prove unresponsive to standard therapy.

Figure 2. Incidence of TURP syndrome In Combination of Various Risk Categories*

Figure 3. Comparison of TUR syndrome Between Resident and Consultant-Performed TURP

References

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Division of Urology, National Kidney and Transplant Institute, East Avenue, Quezon City, Philippines 1100

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