GB2234897A

GB2234897A - Irrigating fluid for transurethral resections

Info

Publication number: GB2234897A
Application number: GB9017018A
Authority: GB
Inventors: Ashok Shumsher Jung Bahad Rana
Original assignee: Individual
Current assignee: Individual
Priority date: 1989-08-02
Filing date: 1990-08-02
Publication date: 1991-02-20
Also published as: GB9017018D0; GB8917660D0

Abstract

An irrigating fluid particularly suitable for use to transurethral resections comprises an aqueous solution of glycine and L-arginine.

Description

Title: Prophylaxis of Transurethral Resection Reactions DESCRIPTION This invention is concerned with prevention and/or treatment of transurethral resection (TUR) reaction or TUR prostate syndrome when glycine solution is used as irrigating fluid.

Irrigating fluid absorption in patients during transurethral resection of prostate is a recognised complication.

When pure water was used for irrigation during transurethral resection, absorption of such water led to hypotonicity and intravascular haemolysis in some patients (Creevy, Journal of Urology 1947).

Nesbit and Glickman (Journal of Urology 1948) recommeded glycine solution to prevent such intravascular haemolysis. Since then, 1.5% w/v glycine solution remains to be the most commonly used irrigating fluid for transurethral resection in most western countries. A three litre bag would contain about EOOm/M of glycine.

Even with the introduction of 1.5% glycine solution, although preventing serious intravascular haemolysis, absorption during transurethral resection could still produce symptoms called TUR-reaction or TURP-Syndrome (Harrison et al Journal of Urology 1956). Characteristic symptons of TUR-reaction include bradycardia, tachypnoea, restlessness, apprehension, muscular twitching, delayed awakening from general anaesthesia, transient blindness, confusion, convulsion, collapse, coma and death in the worst cases (Wakin, K G et al Journal of Urology 1971, Harrison et al 1956 (above) and Appelt G L et al Journal of Urology 1979).

Traditionally the solvent fraction of irrigating fluid has been blamed for this reaction. Absorption of the irrigating fluid could produce hyponatraemia and nypervolaemia which have been blamed for TUR-reaction.

As a precaution against such reaction many suggestions came in the literature.

Fillman et al JAMA 1959 suggested limiting the resection to one hour.

Harrison et al (above) made various recommendations. These included limiting the resection time, using low irrigation pressure, not attempting repeated fulguration of venous bleeding, and lastly by leaving a rim of prostatic tissue and not reaching to the capsule until the very end of resection.

Hurlbert et al Anaesthesiology 1979 reported a case of water intoxication following absorption of 1.5% glycine after only 15 minutes of TURP (with absorption of about 6 litres of fluid).

As the attempts to prevent TUR-reaction continued, attentions were also directed towards the system of using irrigating fluid.

Madsen and Naber Journal of Urology 1973(9) stressed the point of hanging the irrigating fluid bag not higher than 60cms above the operating table in order not to raise the pressure in the prostatic fossa and thereby prevent the absorption of irrigating fluid.

Iglesias J J et al Journal of Urology 1975 showed that the volume of irrigating fluid absorption during TURP will be lower if continuous irrigation and suction and resectoscope is used. This system maintained the intravesical pressure below Scms of water, which is lower than the pressure in the pelvic veins.

Stephenson T P et al BJU 1980 did not find any significant difference between the intermittent and continuous suction methods for irrigating fluid absorption or for operating time of TURP.

Rao et al BJU 1983 showed the modification of irrigant supply system. The height of the fluid column was maintained at 15cms above the symphysis pubis and the final bladder pressure was kept around 15cms of water - much lower than existing system. This also kept the flow rate constant.

Recently more attention has been drawn toward the solute fraction of the irrigating fluid.

The effect of absorbed glycine from irrigating fluid was studied by Fitzpatrick et al BJU 1981. They showed high levels of oxalates and glycolates (the metabolic products of glycine) in the urine in patients who also had hyponatraemia.

Zucker and Bull Can. Anaesth. Soc. Journal 1984 showed that the majority of patients (12/17) after TURP with 1.5% glycine used as irrigating fluid, showed more than 100D increase in plasma glycine levels. Only a small number of patients (4/17) had serum sodium dropped by 5-lOmEq/1. They pointed out how inappropriate it was to regard hyponatraemia only as the measure of severity of irrigating fluid absorption.

They stressed the point of measuring glycine in blood as more appropriate of irrigating fluid absorption because 15mls of glycine irrigating fluid absorption would approximately double the plasma glycine concentration i.e. 100S increase, whilst diluting the serum sodium by only 0.1D.

Hoekstra et al Journal of Urology 1983 ascribed three cases of TURP-syndrome characterised by stupor and coma. All three patients had transurethral resection of prostate with glycine as irrigating fluid. Their blood ammonia levels were elevated by more than 10 times the normal level. They all improved when their blood ammonia level came down to normal. In their prospective study, 46% patients developed hyperammonaemia following TURP using 1.5% glycine.

Shepard et al BJU 1987 studied the patients who underwent TURP using 1.5% glycine solution. 38% of them showed hyperammonaemia, 14% of these had developed clinical signs of encephalopathy. They concluded: "There is no specific treatment for hyperammonaemia other than the support of cardiovascular and respiratory function. It can easily be prevented by avoiding the use of 1.5g glycine as a urological irrigant".

Thus, prevention of or at least reducing hyperammonaemia is believed to be one way of eliminating or reducing the effect of TUR-reaction or TURP syndrome.

It is known from various sources such as Piero Gullino - Archieves of Biochemistry and Biophysics 1956, J. Fahey - J. Clin Investigation 1957 and Nathens et al - J. Lab and Clinical Medicine 1958 that L-arginine has a protective effect against hyperammonaemia in various hosts but no connection between that and preventing TUR reaction or TURPsyndrome has ever been made.

A first ojbect of this invention is to reduce or eliminate TUR-reactions following TURP.

A second object of this invention is to provide a novel irrigating fluid, especially for use in TURP.

A third object of this invention is to provide a method of treating TUR-reactions.

According to the invention it is proposed that Larginine be administered to a patient before, during or after TURP.

In particular, the invention proposes an irrigating fluid, especially for TURP, comprising an aqueous solution of glycine and L-arginine.

L-arginine is preferably included in the irrigating fluid in an amount of upto about 15t preferably upto about 10%, especially from about 5 - 10% of the glycine. The glycine will preferably continue to be used as a 1 to 2, especially 1.5%, w/v solution.

Thus, in specific examples of an irrigating fluid of the invention a 3 litre bag of aqueous irrigating fluid will contain 600m M of glycine and either 60m M or 30m M or L-arginine.

Alternatively, L-arginine may be adminstered separately from surgical procedure, such as by parenteral administration say as a component of protein nutrition supplied intravenously. Such protein nutrition will usually comprise a selection of amino acids and L-arginine may be present in any suitable amount. Amounts upto 10% or even higher, preferably from 5 to 10% by weight of amino acids may be suitable.

It is envisaged that the administration of Larginine to a patient of TURP will prevent or reduce hyperammonaemia and so prevent or reduce effects of TURreaction.

This invention will now be further described with reference to the following examples: Example 1 An irrigating fluid suitable for use in transurethral reactions was made as a 3 litre bag containing in aqueous solution 600m M of glycine and 60m M of L-arginine.

Example 2 An irrigating fluid suitable for use in transurethral reactions was made as a 3 litre bad containing in aqueous solution 600m M of glycine and 30m M of L-arginine.

Claims

1. An irrigating fluid, especially for TURP, comprising an aqueous solution of glycine and Larginine.

2. An irrigating fluid as claimed in claim 1, wherein glycine is present is an amount of from 1 to 2% w/v solution.

3. An irrigating fluid as claimed in claim 2, wherein glycine is present in an amount of 1.5% w/v solution.

4. An irrigating fluid as claimed in claim 1, 2 or 3, wherein L-arginine is present in an amount of upto 15% by weight of the glycine.

5. An irrigating fluid as claimed in claim 4, wherein L-arginine is present in an amount of upto about 10% by weight of the glycine.

6. An irrigating fluid as claimed in claim 4, wherein L-arginine is present in an amount of from 5 to 10% by weight of the glycine.

7. An irrigating fluid as claimed in claim 1 and substantially as hereinbefore described with reference to either of the examples.