Osmotic and metabolic sequelae of volumetric overload in relation to the TUR syndrome

In an attempt to understand the pathophysiology of the transurethral resection syndrome this prospective metabolic study was conducted on 100 consecutive patients undergoing transurethral resection of the prostate (TURP). The volume of glycine absorbed, intravenous fluid given and blood loss were calculated, and serum osmolality, sodium and glycine were measured before, during and after operation. The mean volume of glycine absorbed, fluid gain and blood loss were 0.6, 1.57 and 0.356 litres respectively. The mean weight of prostate resected was 30.8 g and resection time was 56.5 min. The mean serum osmolality dropped from 291 to 286 mOsm/l, sodium dropped from 138 to 132 mmol/l and glycine concentration increased from 293 to 3599 mumol/l post-operatively. Ten patients developed signs suggestive of the TURP syndrome. Multiple regression analysis showed that the most consistent statistically significant factors in relation to the syndrome were volumetric gain and hypo-osmolality. The latter proved to be the only significant factor later post-operatively. The increase in serum glycine and drop in serum sodium concentrations were the best serological markers, reaching significance only after excluding volumetric gain and osmolality from the analysis.     

VISUAL EVOKED POTENTIALS AND CHANGES IN SERUM GLYCINE CONCENTRATION DURING TRANSURETHRAL RESECTION OF THE PROSTATE

Visual evoked potentials were recorded in 10 patients undergoingtransurethral prostatectomy under subarachnoid anaesthesia.They were compared with those obtained in a control group (n=5) having other operative procedures also under spinal anaesthesia.Serum concentrations of glycine, ammonia, glucose and sodium,and osmolality, were determined during the perioperative period.The prostatectomy group demonstrated a significant prolongationof visual evoked potential P₂ latency in the postoperative periodwhen compared with preoperative values (P<0.01). No significantchanges in latency occurred in the control group when measuredat similar times. The prostatectomy group demonstrated a significantincrease in serum glycine concentration (P<0.01); changesin serum ammonia and sodium concentrations and osmolality werenot significant. There was no correlation between visual evokedpotential latency and changes in serum glycine concentration.Changes in visual evoked potential during transurethral prostatectomymay be the result of an accumulation of a metabolite of glycine.     

Glycine solution as an irrigating agent during transurethral prostatic resection. Glycine concentrations in blood plasma

In 17 men undergoing transurethral resection of the prostate (TURP), an isosmotic solution of 2.2% glycine was used for irrigation. The plasma glycine concentration was determined before and immediately after TURP and 2, 6, 24 and 48 hours later. The serum concentrations of sodium, albumin and prostatic acid phosphatase protein (PAP) were used as indicators of fluid absorption. Calculation of the absorbed fluid volume was based on the plasma concentration of glycine, and the disappearance rate of glycine from plasma was estimated. The mean disappearance rate (T 1/2) was 85 min, which was midway between previously observed rates for sorbitol and mannitol. The observed plasma glycine increase after TURP correlated well with fall in serum sodium and rise in serum PAP, with the blood loss during and up to 15 min after TURP, and also with the weight of the resected tissue. The plasma glycine level, highest immediately after TURP, normalized 24-48 hours postoperatively. No signs of ammonia intoxication or marked serum urea increase were seen in these patients, although some had very high plasma glycine values after TURP (mean 10.2, maximum 23 mmol/l) as compared with the preoperative levels (mean 0.2 mmol/l). There was some increase of plasma serine (a normal metabolite of glycine) after TURP. The authors conclude that the irrigating fluid should have a minimal concentration of glycine, near to the level of haemolysis onset, to minimize the plasma dilution effects, including hyponatraemia, and the appearance of metabolites when the irrigating fluid is absorbed.     

A comparison of the effect of 1.5% glycine and 5% glucose irrigants on plasma serum physiology and the incidence of transurethral resection syndrome during prostate resection

OBJECTIVE: To examine changes in the pathophysiology and frequency of the transurethral resection (TUR) syndrome with two irrigation fluids, as variable amounts of irrigation fluid are absorbed during TUR of the prostate (TURP), and although polar solutes are required to prevent an effect on diathermy, the solutes may have effects when absorbed. PATIENTS AND METHODS: Between December 2001 and March 2003, 250 patients were included in a prospective randomized trial comparing glycine 1.5% with 5% glucose irrigation fluids. We measured blood loss, fluid absorption, temperature change, biochemistry including a glycine assay, and peri-operative symptoms. Blood samples were taken immediately before and immediately, 5 and 24 h after TURP. Irrigating fluid absorption during TURP was measured with 1% ethanol as a marker and breath ethanol measurements. Operative details were recorded, including the type of anaesthesia (with or with no sedation), resection time and weight of resected tissue. Peri-operative symptoms were documented prospectively. TUR syndrome was defined as a serum sodium level of < or = 125 mmol/L with two or more associated symptoms or signs of TUR syndrome. RESULTS: Five (2%) patients had TUR syndrome; all five were irrigated with glycine, although this difference was not statistically significant (P = 0.06). Of the five men, three had hypotension, four were tired, one was nauseous, two had parasthesia, two had 'uneasiness', one had blurred vision and two were confused; none had chest pain. There was a large variation between the groups in the level of glycine assayed immediately after TURP; a high glycine level was associated with the TUR syndrome (P = 0.01). There was no difference between the groups in levels of sodium, potassium, urea, creatinine, osmolality, calcium, haematocrit, albumin serum levels or peri-operative blood loss (defined as a change from before to after TURP in haemoglobin level, accounting for transfusions). CONCLUSIONS: An increase in serum glycine was associated with TUR syndrome; there were large variations in the amounts of glycine absorbed, reaching levels many times the upper limit of normal. In other studies, glycine was reportedly toxic, and that the levels recorded were many times the upper limit of normal may have both immediate and long-term effects.     

No evidence of fluid absorption during continuous low-pressure transurethral resection of the prostate: assessment by measuring expiratory breath ethanol concentrations.

OBJECTIVE: Measurement of the ethanol concentration in expired breath during transurethral resection of the prostate (TURP). METHODS: TURP is a noninvasive method to estimate the amount of irrigant absorbed. The expiratory breath ethanol concentrations (EBEC) were measured with a standard alcohol breath analyzer in 35 patients in the course of TURP. All interventions were performed with a 27-french continuous flow resectoscope using a solution of 1. 5% glycine + 1% ethanol as irrigating fluid. Serum sodium and osmolality were measured pre- and postoperatively. No patient developed signs of transurethral resection syndrome; no significant changes in serum sodium, osmolality and EBEC were found throughout the operation. CONCLUSION: Absorption of irrigant fluid during TURP with continuous low-pressure irrigation seems to be extremely slight (if not absent) as measured by expired breath ethanol method.     

COMPARISON OF THE EFFECT OF TWO HEIGHTS OF GLYCINE IRRIGATION SOLUTION ON SERUM SODIUM AND OSMOLALITY DURING TRANSURETHRAL RESECTION OF THE PROSTATE

Background: The absorption of sodium-deficient, hypotonic irrigation solution is believed to contribute, in certain cases, to hyponatraemia and hypo-osmolality and, in severe cases, to the so-called transurethral resection of the prostate (TURP) syndrome. Methods : The effect of the height of 1.5% glycine irrigation solution during intermittent-flow TURP on serum sodium and osmolality was studied pen-operatively in 40 patients. The height of the glycine was set at 70 (n= 20) or 150 (n= 20) cm above the operating table. Results: We found no statistically significant difference in the measured serum sodium (P= 0.929) and osmolality (P= 0.260) values between the two groups during the 24 hr study period. Conclusions: The height of the irrigation solution is not important in the development of hyponatraemia and hypo-osmolality, and other factors are probably more important.     

Effect of osmolar changes on plasma arginine vasopressin (PAVP) in dialysis patients.

The effect of changes in plasma osmolality and changes in plasma arginine vasopressin (PAVP) were analyzed in 10 stable chronic hemodialysis patients utilizing four protocols. During regular hemodialysis opposing influences on PAVP (decrease in blood pressure and intravascular volume and increase in serum calcium) resulted in no significant change in PAVP (by analysis of variance). In the second protocol low dialysate calcium (2.5 meq/l) isovolemic hemodialysis was used. PAVP and serum osmolality levels declined from 2.0 +/- 0.4 to 1.4 +/- 0.2 microU/ml (p less than 0.05), and 285 +/- 2.5 mOsm/l to 275 +/- 3.2 mOsm/l respectively. Removal of PAVP by hemodialysis did not occur as evidenced by no difference in arterial-venous PAVP levels and no "rebound" of PAVP for three hours after completion of dialysis (second protocol). Isovolemic low calcium high dialysate sodium (145 meq/l) hemodialysis was utilized in the third protocol. Serum osmolality and PAVP did not change. Addition of a very high dialysate sodium (155 meq/l) to isovolemic low calcium hemodialysis resulted in an increase in plasma sodium, osmolality and AVP (139.7 +/- 0.62 to 144 +/- 0.67 meq/l, 294 +/- 2.79 to 304.3 +/- 2.4 mOsm/l and 1.8 +/- 0.3 to 2.7 +/- 0.5 microU/ml (p less than 0.05 for each) respectively. In conclusion, PAVP responds to changes in plasma osmolality in chronic hemodialysis patients.     

Visual disturbances, serum glycine levels and transurethral resection of the prostate

Transient visual disturbances have been noted in patients undergoing transurethral resection of the prostate. It has been suggested recently that these visual aberrations were secondary to high serum concentrations of glycine from the intravasation of irrigant solutions used during the procedure. We prospectively studied visual acuity, serum electrolytes, glucose, ammonia and glycine concentrations in 18 patients undergoing transurethral resection of the prostate. Of our patient population 22% experienced significant decreases in visual acuity. We found that all patients had significantly elevated serum glycine concentrations but that there was no correlation of visual symptomatology with serum electrolyte or glucose concentrations. Our data further suggest that impeded metabolism of glycine may be more important than the absolute serum concentration in symptomatic patients.     

Determinants of rhabdomyolysis in the diabetic state.

To evaluate the determinants of rhabdomyolysis in the diabetic state, we compared biochemical and clinical features of diabetic patients with (group 1, 41 patients) and without (group 2, 36 patients) rhabdomyolysis. There was no difference in values for serum potassium, bicarbonate, phosphate and calcium between the two groups. Nineteen patients in group 2 and 21 patients in group 1 were hypokalemic. The mean serum sodium level was higher (p less than 0.001) in group 1 patients (148.8 +/- 2.1 mEq/l) than in group 2 patients (135.0 +/- 1.1 mEq/l). Only 1 patient was hypernatremic in group 2, whereas 24 patients had hypernatremia in group 1. Linear regression of the creatine phosphokinase values versus serum sodium levels suggested a high correlation (p less than 0.001). The mean blood glucose level was higher (p less than 0.05) in group 1 patients (640.8 +/- 80.3 mg/dl) when compared to group 2 patients (436.0 +/- 56.7 mg/dl). There was a linear association (p less than 0.05) between the levels of blood glucose and creatine phosphokinase values in the patients with rhabdomyolysis. The mean serum osmolality was 350.3 +/- 8.2 mosm/kg in group 1 patients as compared to 304.9 +/- 3.6 mosm/kg in group 2 patients (p less than 0.001). There was also a significant correlation (p less than 0.001) between the serum osmolality levels and the serum creatine phosphokinase values in group 1 patients. We conclude that serum sodium, serum osmolality and blood glucose are major determinants for the occurrence of rhabdomyolysis in the diabetic state.     

Independent plasma levels of sodium and glycine during transurethral resection of the prostate

This study was done to evaluate the potential role of plasma glycine levels as an indicator of the biochemical changes occurring during or shortly after transurethral resection of the prostate (TURP). Seventeen patients undergoing TURP were studied to determine the fate of the absorbed glycine and its effects on other amino acids and their relationship to changes in serum sodium and osmolarity. Twelve patients showed more than 100 per cent increase in plasma glycine levels with values ranging to more than 100-fold elevation. Only two patients showed a change in serum sodium of greater than 10mEqll with corresponding change in osmolarity. In one such patient there was no accompanying change in plasma glycine. Thus, major changes in plasma glycine and serum sodium may occur independently of one another, and may separately account for manifestations of the reactions following TURP.     

The role of ammonia toxicity in the post transurethral prostatectomy syndrome

To investigate the aetiology of altered mental status following transurethral prostatectomy (TURP), serum electrolyte and blood ammonia levels were measured in 33 patients before and immediately after TURP. The irrigating fluid was 3% sorbitol in 12 patients and 1.5% glycine in 21. Serum electrolyte changes were similar in both groups. Elevated blood ammonia levels were observed in eight of the 21 patients receiving glycine irrigation. Three of these eight patients demonstrated clinical signs of encephalopathy. Absorption of glycine during transurethral prostatectomy appears to produce hyerammonaemia in some patients and may contribute to the encephalopathy.     

Mannitol concentrations in blood plasma in connection with transurethral resection of the prostate using mannitol solution as an irrigating fluid

Thirteen patients undergoing transurethral resections of the prostate (TURP) using iso-osmolar 5% mannitol as an irrigating fluid were studied. Mannitol was determined in serum (plasma), as were sodium, prostatic acid phosphatase protein (PAP) and osmolality as probable indicators of absorption of irrigating fluid. The plasma level of mannitol (mean 2.7 g/l = 15 mmol/l) immediately postoperatively, the increase in serum PAP (mean 93 micrograms/l) and the decrease in serum sodium (mean 8.7 mmol/l) all reflect the amount of irrigating fluid absorbed during TURP. The three variables are intercorrelated. The plasma osmolality was unchanged (mean -1 mosmol/kg). A small but constant fraction of mannitol was found in the erythrocytes 2 hours after the operation, amounting to about 3% of the simultaneous plasma concentration. The mean plasma half-life of mannitol was 127 min in the absence of uraemia. In two cases showing a slight increase in serum creatinine the half-lives were prolonged. An estimate of the volume of fluid absorbed was made from the observed plasma mannitol levels. A fluid absorption of up to 3 litres (mean 1.1 l) was found. A strong diuretic effect was observed in some cases when irrigation with mannitol was combined with i.v. furosemide. We conclude that the i.v. diuretic should be withheld until the extent of fluid absorption has been estimated. If the sodium concentration in the serum is largely unchanged immediately postoperatively, diuresis can be induced by an intravenous diuretic.     

Visual evoked potentials and visual acuity after transurethral resection of the prostate

Changes in visual evoked potentials, visual acuity, blood ammonia levels and serum electrolytes (Na+ and K+) after transurethral resection of the prostate using glycine as an irrigating fluid performed under subarachnoid block were studied in 12 patients, in the pre-operative and immediate postoperative periods. Visual evoked potentials (p100 latency), recorded by shift of a checkerboard pattern, increased significantly from a pre-operative value of mean (SEM) 101.18 (1.63) msec in the right eye, and 102.5 (1.47) msec in the left eye to 108.91 (1.8) msec (p less than 0.01) and 108.08 (2.53) msec (p less than 0.01) respectively in the postoperative phase. There were no changes in visual acuity as assessed by a Snellen's chart, blood ammonia levels and serum electrolyte concentrations. The amount of glycine used intra-operatively for irrigation ranged from 3 to 31 litres.     

Sorbitol concentrations in plasma in connection with transurethral resection of the prostate using sorbitol solution as an irrigating fluid

20 patients undergoing transurethral resection of the prostate (TURP) using 5% sorbitol (N = 13) or Cytosol (N = 7) (5% sorbitol and 0.25% acetic acid) as an irrigating fluid were studied. The sorbitol concentration was determined in serum (plasma), as were sodium, prostatic acid phosphatase protein (PAP) and osmolality, as possible indicators of absorption of irrigating fluid. The plasma level of sorbitol immediately postoperatively, the increase in serum PAP and the decrease in serum sodium all reflect the amount of irrigating fluid absorbed during TURP. The three variables are intercorrelated. The plasma osmolality was not significantly changed. The maximum sorbitol concentration immediately postoperatively in any patient was 6.0 g/l (33.5 mmol/l). The mean for the series was 1.2 g/l (6.8 mmol/l). The mean serum PAP increase was 31 micrograms/l. The serum sodium decrease ranged between 0 and 14 mmol/l, mean 5.0 mmol/l. The mean half-life of sorbitol in plasma was short: 35 min, reflecting rapid metabolism. An estimate of the volume of fluid absorbed was made from the plasma sorbitol levels observed. A fluid absorption up to 2.3 l (mean 0.6 l) was found. A marked diuretic effect up to 14.1 ml/min (mean 7.8 ml/min) was observed in some cases when irrigation with sorbitol was combined with intravenous furosemide given postoperatively.     

Transurethral resection syndrome. A prospective study.

Significant hyponatraemia has been reported following transurethral prostatectomy (TURP) in 11-41% of cases. The majority of previous studies have been performed retrospectively. A prospective study was undertaken of 100 patients undergoing TURP. In all, a 24-Charr sheath with non-irrigating, resectoscope and 1.5% glycine as irrigant was used. Volume of irrigant used, weight of prostate and length of procedure were recorded. Serum electrolytes were measured at anaesthetic induction and immediately on transfer to the recovery room. In none of the 100 patients was there a statistically significant fall in serum sodium following resection. No clinical changes of transurethral resection (TUR) syndrome occurred. This study confirms that TUR syndrome and a significant fall in serum sodium can be virtually prevented in TURP and the use of an irrigating resectoscope or a trocar in the average case is not necessary.     

Isotonic hyponatremia and cerebrospinal fluid sodium during and after transurethral resection of the prostate

We examined the effects on the central nervous system of hyponatremia during transurethral resection of the prostate (TURP). Initially, a prospective study was done on 165 consecutively treated patients undergoing TURP, to evaluate symptoms related to the serum osmolality. There were ten patients with hyponatremia below 120 mEq·L⁻¹, and in whom the serum sodium decreased to 111.9±6.4 mEq·L⁻¹ (mean±SD) postoperatively, the measured serum osmolality remained near normal. The calculated osmolality decreased to 237.4±11.9 mOsm·kg⁻¹ and the estimated osmolar gap was 33.5±10.4 mOsm·kg⁻¹ due to absorption of the irrigating sorbitol. Neurological symptoms were mild and complications such as seizures or loss of consciousness nerver occurred. There were five other patients with hyponatremia (serum sodium 118.0±6.7 mEq·L⁻¹) from whom lumbar cerebrospinal fluid (CSF) was collected before and after TURP through a single puncture. CSF sodium did not decrease throughout 1.5 h after TURP, and there was a CSF-to-serum sodium gradient. Our study shows that in cases of acute dilution hyponatremia during and after TURP, symptoms are mild because the serum osmolality remains near normal and CSF sodium does not decrease despite severe postoperative hyponatremia.     

Severe hyponatremia without severe hypoosmolality following transurethral resection of the prostate (TURP) in end-stage renal disease

A 55-year-old man on chronic hemodialysis underwent a transurethral resection of the prostate (TURP), during which 3% sorbitol solution was used for urethral irrigation. Following the procedure, he developed symptomatic hyponatremia (serum sodium, 106 mEq/L), but had only mild hypoosmolality (serum osmolality, 269 mosm/kg). The "osmolal gap" was 47 mosm/kg, probably from sorbitol absorbed systemically during the TURP. Hemodialysis raised the serum sodium to 118 mEq/L, and the serum osmolality to 284 mosm/kg, while lowering the osmolal gap to 26 mosm/kg. The presence of severe hyponatremia with only modest hypoosmolality may occur in patients with renal failure following the systemic absorption of hypotonic fluids containing solutes such as sorbitol and mannitol. Hemodialysis offers the advantages of correcting the hyponatremia while removing the unmeasured solute, thus preventing rapid increases in the serum osmolality.     

Is using ethanol–glycine irrigating fluid monitoring and ‘good surgical practice’ enough to prevent harmful absorption during transurethral resection of the prostate?

OBJECTIVE: To evaluate the utility of using a tracer of 1% ethanol in 1.5% glycine for the early detection of irrigation fluid absorption during transurethral resection of the prostate (TURP). PATIENTS AND METHODS: In all, 126 men undergoing TURP were irrigated with a solution of 1% ethanol and 1.5% glycine; their expired air was tested for ethanol every 20 min, and again at the end of the procedure. Maximum absorption by the breath-ethanol reading was compared with the serum concentration of absorbed glycine (analysed by anion-exchange chromatography). RESULTS: Complete data on 120 men were assessed; 75% of the men absorbed irrigation fluid, with glycine levels above the normal range. The sodium levels tended to decrease with increasing glycine levels (Spearman's rank correlation coefficient, - 0.57; 120 men) and five men (4%) developed clinical features of the TUR syndrome. There was a weak correlation between breath-ethanol levels and serum glycine levels (Spearman's rank correlation coefficient, 0.54). The experience of the surgeon, the weight of the resected chips, and the operative duration were not significantly predictive of irrigation fluid absorption. CONCLUSIONS: A rising breath-ethanol level indicates irrigation fluid absorption. However, irrigating fluid absorption is unpredictable, supporting the case for alternative, potentially safer irrigants.     

Plasma haemoglobin concentrations and other influx variables in blood in connection with transurethral resection of the prostate using distilled water as an irrigating fluid

Eight patients undergoing transurethral resection of the prostate (TURP) using sterile distilled water as an irrigating fluid were studied. The concentrations of plasma haemoglobin, serum sodium, serum prostatic acid phosphatase protein (PAP) and plasma osmolality were determined as possible indicators of absorption of irrigating fluid. In 3 patients there was a marked increase in plasma haemoglobin immediately postoperatively with a maximum of 3.3 g haemoglobin/l plasma. In the remaining 5 patients the plasma haemoglobin level did not exceed 0.7 g/l immediately postoperatively. In all cases there was a fairly rapid return of the elevated plasma haemoglobin level to preoperative values. There was also a postoperative increase in the serum PAP level which was not correlated with the simultaneous increase in plasma haemoglobin concentration. There was no significant change in the sodium, potassium or albumin concentration in serum nor in plasma osmolality postoperatively. There was some decrease in the postoperative serum creatinine and uric acid levels. The preoperative serum creatinine concentration was within reference limits in 7 patients and borderline high in 1 patient. The haemoglobin binding plasma protein haptoglobin showed a slight non-significant increase immediately postoperatively and a significant decrease in concentration 2 hours postoperatively. The mean plasma haemoglobin concentration immediately postoperatively did not exceed the mean preoperative haemoglobin binding capacity of serum. The mean preoperative haemoglobin binding capacity was 1.2 g/l and the mean plasma haemoglobin level was 1.2 g/l immediately postoperatively. Two hours later the mean plasma haemoglobin level was 0.8 g/l. The mean serum haptoglobin concentration was 2.4 g/l preoperatively, 2.6 g/l immediately postoperatively and 2.0 g/l 2 hours later.(ABSTRACT TRUNCATED AT 250 WORDS)     

Observations regarding the use of the aquaretic agent conivaptan for treatment of hyponatremia

The treatment of hyponatremia, especially euvolemic and hypervolemic hyponatremia, has changed with the development of drugs which function as vasopressin receptor antagonists. These agents increase solute-free water excretion by the kidney resulting in an aquaresis. Conivaptan, a vasopressin receptor antagonist, has recently been approved by the FDA in the United States for use in the therapy of both euvolemic and hypervolemic hyponatremia. This report summarizes one center's experience with ten patients treated with this new drug. The patients had euvolemic hyponatremia with serum sodium levels less than 128 mEq/l. The same protocol was used in all patients with the conivaptan being given as a 20-mg intravenous loading dose followed by a 20-mg continuous 24-h infusion. Review of the data revealed that six of the ten patients had an excellent response to the therapy, with serum sodium increasing by a mean of 8.5 +/- 0.8 mEq/l (increases ranged from 7 to 12 mEq/l over 24 h). No significant changes in serum potassium levels or mean arterial pressures were noted. Two of the ten patients experienced a decrease in urine osmolality without a significant increase in serum sodium. Two other patients had only slight decreases in urine osmolality, and no significant increase in serum sodium levels. The data reveal that conivaptan is useful in the management of significant hyponatremia. There were no significant untoward effects, with the exception of one patient whose blood pressure decreased during the conivaptan infusion and who responded to cessation of the infusion and saline replacement therapy. This new class of drugs holds great promise for the treatment of dilutional hyponatremic disorders.