Systemic absorption of glycine solution and the TUR syndrome : clinical, pathophysiological and pharmacological aspects

Sammanfattning: Transurethral resection of the prostate (TURP) requires the use of an irrigating fluid to remove blood and debris to visualise the operating area. Despite modern technique, unpredictable amoumts of irrigating fluid, which usually consists of glycme 1.5% in sterile water, enters the circulation during nearly every routine TURP. This may give rise to clinical symptoms involving the cardiovascular and central nervous system usually referred to as the transurethral resection syndrome (TUR syndrome). The purpose of this thesis is to study clinical and physiological chamges in body functions following systemic irrigating fluid absorption. The results of a retrospective evaluation of symptoms of the TUR syndrome in 273 patients showed that even a moderate-sized absorption (as small as 1000 ml) was associated with a significantly increased risk of symptoms involving the circulatory (primarily arterial hypotension) and the central nervous systems (nausea and vomiting). The incidence and severity of the symptoms increased with larger volumes and started usually 30-60 mm after surgery. In a prospective study of 100 patients, glycine absorption was the only operative factor associated with transient mental dysfunction as evaluated by a mmi-mental status test. In a long-term follow-up of 846 TURP patients, glycine absorption of >500 ml and a blood loss of <275 ml during the operation were independently associated with anincreased risk of acute myocardial infarction. Studies with experimental administration of electrolyte-free irrigating fluids were also conducted. In sheep, anintravenous volume load had no harmful effects on kidney function. However, a high renal excretion of solutes andelectrolytes promoted hypo-osmolality which was not alleviated until hypertonic saline treatment was given. Thistreatment also redistributed water from the cells to the interstitial compartment. In humans, intravenous infusions of 15 ml/kg of glycine-ethanol solution over 20 min reduced cardiac output and promoted mild hypertension. These effects were not seen after infusions of alternative irrigating fluids. A pharmacokinetic evaluation showed that glycinebecomes distributed in a fluid space much larger than the estimated extracellular fluid volume. By means of a new mathematical model, the size of the fluid space expanded by the glycine solution was found to be smaller than the extracellular fluid volume, 6-9 litres. In conclusion, absorption of irrigating fluid containing glycine has transient effects on the centralhaemodynamics and on mental status, but it is also associated with an increased long-term risk of acute myocardialinfarction.