Irrigating fluids in endoscopic surgery

British Journal of Urology (1997), 79, 669 680 REVIEW Irrigating fluids in endoscopic surgery R.G. HAHN Department of Anaesthesia, South Hospital, Stockholm, Sweden sterile water made urologists realize, in 1947, that the Introduction absorption of the irrigating fluid into the circulation Endoscopic operations in the genitourinary tract require through severed prostatic veins must be the cause of the the use of an irrigating fluid to gently dilate mucosal haemolysis. As electrolytes do not allow cutting by spaces and to remove blood and cut tissue from the electrocautery, one or several non-electrolyte solutes operating field. There are several dierent irrigating capable of preventing haemolysis were then added to fluids available commercially and it might be dicult to the irrigating fluid. know which one to use. The choice tends to be governed Glycine was the first suggested as suitable; this amino largely by tradition, although the price and properties of acid is an endogenous substance, transparent in an iso- the fluid (e.g. stickiness and transparency) also play a osmotic (2.2%) solution and reasonably cheap [9]. The role. The pharmacological eects of the fluid become other irrigating fluids used today, mannitol and mixtures important whenever it is absorbed by the patient. of sorbitol and mannitol, were introduced somewhat However, adverse reactions to irrigating fluids have not later [10,11]. The only further development in the been documented as they have for drugs. composition of irrigating fluids since the early 1950s is Most irrigating fluids were developed when the documentation the addition of ethanol up to a concentration of 1%, of safety was much less important than it is which allows fluid absorption to be monitored by expired- today. Pharmacologists and regulatory authorities also breath ethanol tests [12]. pay little attention to these solutions because they are Despite their non-haemolytic properties, absorption of conceived as devices (like soap and detergents) rather the new irrigating fluids continued to be associated with than drugs. Nevertheless, numerous reports of sympto- adverse events which were often summarized as transurethral matic and even fatal fluid absorption during TURP and resection reactions (TUR syndrome). The clinimatic transcervical resection of the endometrium (TCRE, an cal descriptions of this syndrome from the mid-1950s operation for alleviating menorrhagia) emphasize the are still the cornerstones of our view of the risks associ- importance of using an irrigating fluid with a favourable ated with the use of irrigating fluids [13 15]. profile of adverse eects [1 6]. For many years, little comparative data were available showing whether one irrigating fluid is more prone to Incidence of fluid absorption adverse eects than others. However, during the past The uptake of small amounts of irrigating fluid occurs decade several studies covering this topic have been during almost every TURP [16] and TCRE [17,18]. The reported. The purpose of this article is to summarize absorbed volume varies greatly and cannot be predicted those reports and also to review the progress that has in the individual patient, although it tends to be larger been made in understanding the adverse eects during in extended and bloody operations (Fig. 1) [19]. The this period of time. uptake of 1 L of fluid, which corresponds to an acute decrease in the serum sodium concentration of 5 8 mmol/l [12], is the volume above which the risk of History absorption-related symptoms is statistically increased [6]. Sterile water was used as the irrigating fluid during the Large series of patients show that the absorption of early years of TURP. However, obscure reactions with >1 L occurs in 5% [20], 8% [19] and 10% [21] of the post-operative haemoglobinuria sometimes occurred and TURPs performed. Even higher values have been noted severe cases even led to death. Enrichment of the blood in some smaller case series, to judge from the reported with salicylate [7] and glucose [8] when added to the changes in serum sodium [22,23]. Absorption during TCRE is usually larger than during Accepted for publication 21 January 1997 TURP [18,24], which is probably due to spontaneous 1997 British Journal of Urology 669

670 R.G. HAHN Operating time 60 min (n = 518) leakage through the fallopian tubes [25]. Large-scale absorption also seems to be more common during TCRE [26]. Risk estimates for symptoms Operating time > 60 min (n = 182) The estimates for the incidence of TUR syndrome range between 0% [27], 1% [28], 2% [29], 7% [1] and 10% [14,30,31]. However, the TUR syndrome is poorly defined and many mild cases have probably been misinterpreted and wrongly attributed to old age, anaesthesia and excessive blood loss. The symptoms arising might also be dierent depending on the choice of irrigating fluid. Therefore, it is more useful to establish separately the incidence of absorption and the risk of symptoms arising for dierent ranges of absorption of a particular irrigating fluid. Such data for glycine 1.5% plus ethanol 1% have recently become available. In a retrospective review, Olsson et al. [6] found a mean of 1.3 symptoms from the circulatory and nervous system in each TURP during which very little or no glycine was absorbed (0 300 ml). This value increased to 2.3 when 1 2 L of fluid was taken up, while a mean of 5.8 symptoms occurred when >3 L was absorbed [6]. The dose-dependent increase in the number of symptoms arising was corroborated in a subsequent prospective study [21]. These studies were the first to show statistically that the risk of having symptoms increases progressively as more glycine solution is absorbed; most symptoms develop 30 60 min after the completion of surgery. Glycine 2.2% Fig. 1. Fluid absorption during TURP depending on whether the operating time exceeds 1 h. The absorption is larger in extended operations (Mann Whitney test P<0.001) but it may still occur during shorter procedures. The case series is presented in detail in [19]. Dark green, 0 150 ml. Light green, 151 500 ml. Light red, 501 1000 ml. Dark red, 1001 2000 ml. Black, >2000 ml. A combination of animal experiments and clinical studies should form the basis of any assessment of the comparative risks associated with the use of an irrigating fluid. A review of such studies suggests, for example, that a 2.2% solution of glycine, which is marketed in some European countries, should not be used in the clinic. Six of seven volunteers who received 1 L of glycine 2.2% by intravenous infusion over 20 min developed symptoms of visual disturbances and nausea, which were severe in one [32]. However, when the same subjects received glycine 1.5% plus ethanol, they reported only mild skin-prickling sensations, and mannitol solutions (5% and 3% plus ethanol) induced no symptoms at all. Clinical studies also show a high likelihood of symptoms developing as soon as >1L of glycine 2.2% is absorbed [33]. In the mouse, infusions given by the intravenous [34] and intraperitoneal [35] routes show that glycine 2.2% is associated with a poorer chance of survival than the same volume of glycine 1.5%. The increase in glycine content from 1.5%

IRRIGATING FLUIDS IN ENDOSCOPIC SURGERY 671 to 2.2% was originally designed to reduce the dangers glycine infusions, a finding recently corroborated in mice associated with fluid absorption. Inasmuch as no such [48] (Fig. 2). Furthermore, degenerative changes have benefit can be found, glycine 2.2% should be abandoned. been described in the liver and kidneys of rats [49], albeit not in rabbits [37]. Also in patients, glycine 1.5% has been associated Glycine 1.1% with subacute eects on the myocardium. Nine of 11 This irrigant was common in the early days of TURP patients undergoing TURP and absorbing 1 L of glycine [9,14,15]. A reduction of the glycine content from 1.5% solution showed depression or inversion of the T-wave to 1.1% is associated with a poorer outcome in mice on the electrocardiogram 24 h after surgery [50]. In an [34]. In the rabbit, cellular oedema was worse with epidemiological study, absorption exceeding 500 ml glycine 1.0% plus ethanol than with other irrigating doubled the long-term risk of acute myocardial infarction fluids [36], particularly in the liver and in the kidney [51]. The latter finding is interesting in view of the [37]. In human subjects, no advantage of glycine 1.0% higher long-term mortality after transurethral versus over glycine 1.5% was found experimentally [38] or open prostatectomy, which has prompted debate among clinically [21]. It may be concluded that lowering the urologists for some years. glycine content from 1.5% to 1.1% oers no benefit but These reports, implying a high acute mortality and reduces the safety limit for haemolysis, which normally subacute myocardial damage from glycine 1.5%, are occurs slightly below 1.0%. Therefore, glycine 1.1% and worrying. There is an urgent need for further studies on 1.0% should not be used. this topic, as the use of this irrigating fluid is very widespread. Sterile water Despite the adverse experiences with sterile water in the 1940s, it is still used for TURP in some clinics in Europe and the USA and quite frequently in developing countries [39]. This irrigating fluid provides excellent vision during endoscopy as the erythrocytes entering the operating field haemolyse immediately. A retrospective review of thousands of patients undergoing TURP shows that the operative mortality was reduced when the nonhaemolysing solutions were introduced [40] and such a protective eect is supported by results from animal experiments [41]. When sterile water is used, hypertonic mannitol must be given intravenously during the resection to prevent symptoms arising [42,43]. Therefore, sterile water should be reserved for diagnostic procedures. Those who use it alone during TURP expect no absorption to occur, which can never be guaranteed. a Glycine 1.5% Importantly, the most widely used irrigating fluid, glycine 1.5%, seems to be associated with more serious consequences than solutions containing alternative solutes. The acute mortality is higher in mice [44] and rabbits [36] given an intravenous infusion of glycine 1.5%, compared to that with mannitol and sorbitol b solutions. Furthermore, glycine reduces the vitality and survival of isolated cardiomyocytes [45], which is likely Fig. 2. Myocardial lesions 10 days after an intravenous infusion of glycine 1.5% in a mouse. Dilated interstitium with proliferated to increase the long-term risk of heart disease [46,47]. endothelial cells and fibroblasts in the vicinity of an area of In rabbit hearts, myocardial ischaemic damage could be disrupted myofibres. Arrows point at areas of disruption (upper). detected by special staining techniques after infusions of Foci of necrosis with mono- and polymorphonuclear leucocytic glycine, but not after infusions of mannitol or sorbitol reaction (lower). The photographs were provided by Professor [37]. Subendocardial necrosis also occurred after some Jovan Rajs, Karolinska Institute.

672 R.G. HAHN evidence that local vasodilatation was the cause. Prostatic Central haemodynamics tissue substances are released into the circulation during TURP seems to depress myocardial function, particularly fluid absorption [50,65], which might cause hypotension when the operative duration exceeds 1 h [52]. Evans [66]. Endotoxins may also be dispersed, sometimes in et al. found that stroke volume and the cardiac index association with fluid absorption [67]. A metabolic aci- were reduced but that these changes were prevented by dosis might contribute to the reduction of cardiac output, using irrigating fluid at body temperature [53]. In contrast, although the acidosis is usually fully compensated as long Lawson et al. reported that the induction of anaes- as long as a TUR syndrome is not apparent [68]. thesia is an important cause of haemodynamic Singer et al. measured a very low cardiac output in alterations, while little happens during the surgical one patient with the TUR syndrome which suggests that procedure [54]. cardiodepression or hypovolaemia is responsible for the About 0.5% of patients develop acute myocardial hypotension [69]. The onset of hypotension usually infarction during TURP [55]. However, transient myocardial occurs when fluid absorption has just stopped, when ischaemia has been detected during 20% of blood volume is low [64]. Although irrigating fluid TURPs [56] with no dierence between spinal and absorption does increase the blood volume, the hypervogeneral anaesthesia [57]. It is regrettable that fluid laemia is brief and probably changes very easily into absorption was not considered as a possible cause of hypovolaemia. Other clinical [70] and experimental these ischaemic events. [32,41,71] studies support the view that hypovolaemia Intravenous infusion studies in animals yield conflicting is the likely result of fluid absorption. A temporary results regarding the central haemodynamic eect increase in bleeding during absorption probably of glycine [58,59]. In humans, the infusion of 1.2 L of contributes to this phenomenon [64]. glycine reduced cardiac output and transiently increased The results reported above relate to glycine solution, arterial pressure [38]. Although the haemodynamic but arterial hypotension is also a problem after absorp- changes were fairly small, glycine exerted an eect on tion of sorbitol 3% [72] and of mannitol 3% and 5% the circulation not shared by alternative solutions. [72,73] despite the latter expanding blood volume more However, 30 min later, mannitol and sorbitol-mannitol than glycine 1.5% [32,38,74]. This problem is perhaps were also associated with a low stroke volume and high less pronounced with sorbitol-mannitol solutions, with peripheral resistance, possibly due to the cooling of the which blood pressure can be normal despite a fatal volunteers. Another infusion study supports the view outcome [75]. that glycine elevates blood pressure [32], which is also induced by sterile water [41 43]. Dilutional hypocalcaemia has been implicated as a Cerebral eects source of acute cardiovascular disturbances when Most patients who show a transient deterioration of glycine is absorbed [60,61]. The serum sodium and freecalcium mental status after TURP have absorbed irrigating fluid levels decrease to the same degree during intra- [5]. Nausea, vomiting and confusion occur between six venous infusion of irrigating fluid in volunteers [62] and and nine times more often when 1 2 L of glycine in pigs [63]. Calcium is restored more rapidly, probably solution is absorbed than when no absorption is detected due to mobilization of calcium from bone tissue. [6]. Consciousness might be lowered when even more glycine is absorbed [76], which has been associated with hyperammonaemia [16]. Arterial hypotension The amount of glycine appears to make an independent The classical haemodynamic signs of the TUR syndrome contribution to cerebral eects in volunteers [32] when glycine solution is used consist of a transient and to mortality in mice [34]. However, the hyponatraemia arterial hypertension, that may be absent if the bleeding induced by all irrigating fluids eventually gives rise is profuse, followed by more prolonged hypotension to neurological symptoms caused by cerebral oedema. [14,64]. The risk of post-operative hypotension is actually Istre et al. detected cerebral oedema by CT that correlated already increased when moderate amounts of glycine with nausea after the absorption of as little as 1 L of solution are absorbed; there was a fivefold increase glycine 1.5% in females undergoing TCRE [26]. In sheep, in risk when 1 2 L was absorbed compared with the concentration of sodium and glycine changed much 0 300 ml [6]. less in the cerebrospinal fluid than in serum, while the The mechanism for this hypotension is unclear. My alterations of the osmolality were similar [58]. The research group has recently performed a series of in vitro sodium level in the brain is also eectively maintained experiments using macrophage J774.1 to study the eect during the absorption of sorbitol [72]. of glycine on the nitric-oxide system, obtaining no Serum osmolality usually remains normal or falls by

IRRIGATING FLUIDS IN ENDOSCOPIC SURGERY 673 a maximum of about 10 mosmol/kg when fluid is carbon skeleton seems to be metabolized more easily. absorbed. However, the change in osmolality correctly Most of it is degraded to carbon dioxide and water by indicates tissue oedema only when mannitol is absorbed. the glycine-cleavage system [81], although some glycine As glycine and sorbitol enter the cells, these solutes will enters the citric-acid cycle and causes a moderate elevbe accompanied by water through osmosis, even when ation of the blood levels of the non-essential amino acids serum osmolality is normal. When these irrigating fluids [33,82]. Glycine is also metabolised to glycolic acid and are used, tissue oedema will therefore be greater than glyoxylic acid, which can be detected in plasma and indicated by the serum osmolality (Fig. 3). Thus, the cerebrospinal fluid [83], but this metabolic pathway concept isotonic hyponatraemia is not useful when seems to be of minor importance [81]. As glyoxylate is these irrigants are studied. It is particularly irrelevant a precursor of oxalate, there has been concern as to when ethanol is used to indicate fluid absorption, as this whether glycine promotes the formation of oxalate renal agent increases the osmolality without redistributing stones. However, the excretion of oxalate does not corre- water. late with glycine absorption during TURP [84,85] and The metabolic eects of glycine have received much does not increase after experimental infusion of glycine attention as a possible cause of cerebral eects. A corre- [86]. lation between symptoms and the increase in the serum Sorbitol is metabolized to fructose, with a half-life of level of glutamate has been reported [32,33] but, more 35 min, which may present a problem in a patient with importantly, also between symptoms and hyperammonaemia hypersensitivity to fructose [87]. Mannitol is eliminated after infusion of glycine 2.2% [32] and during by renal excretion with a half-life of 120 min and is not TURP [77]. More than 1.5 L of glycine 1.5% seems to associated with metabolic problems. The elimination be required for any marked increase in the blood becomes prolonged in patients with impaired renal ammonia level to occur [32,78,79]. Whatever the function. reason, the ammonia level does not increase even when Restlessness and epileptic seizures are signs of massive much larger amounts of glycine 1.5% plus ethanol 1% absorption. They are probably caused by hyponatraemia are absorbed [80]. as these symptoms have been associated with the use of Hyperammonaemia implies that the body cannot fully both glycine [14] sorbitol 3% [72], sorbitol-mannitol metabolize the nitrogen component of glycine; the [75] and sterile water [42]. Glycine 1.0% plus ethanol 1% Glycine 1.5% plus ethanol 1% Mannitol 3% plus ethanol 1% Sorbitol 2% plus mannitol 1% Fig. 3. Distribution of irrigating fluid water 30 min (upper row) and 90 min (lower row) after a rapid intravenous infusion of 15 ml/kg of irrigating fluids in 10 healthy male volunteers (mean values). Serum osmolality was essentially unchanged, the mean for the fluids varying between 296 and 301 mosmol/kg, but the glycine still had a more pronounced intracellular distribution than the other fluids (ANOVA P<0.01). The case series was presented in [38] and the calculations are explained in [101] and [103]. Dark green, Blood. Light green, Urine. Light red, Interstitial. Dark red, Intracellular.

674 R.G. HAHN [38]. When 1 L of glycine 1.5% is infused, the amount Visual disturbances of glycine in the primary urine far exceeds the capacity Blurring of vision was first reported to be a complication for reabsorption, which also results in osmotic diuresis of glycine absorption in 1956 [14]. The condition might [58,82]. About 10% of a glycine load [82] and sorbitol proceed to transient blindness and is sometimes the only load [96] is eliminated in this way (Fig. 4). Osmotic sign of fluid absorption [88] while it can also be part of diuresis is indisputable with mannitol, as the urine is a severe TUR syndrome [89]. Funduscopic findings the main route of elimination [73,96]. [88,90] and intra-ocular pressure [22] remain normal, Two hours after an infusion of 1 L of irrigating fluid, while the pupillary reflexes may be present or absent. nearly all the fluid volume has been excreted regardless Wong et al. have studied this phenomenon by measur- of whether glycine, sorbitol or mannitol has been infused ing visually evoked potentials in the dog [59] and during [32,38,78] (Fig. 3). The situation is not the same when TURP [91]. They found a prolongation of the time larger amounts are administered. In the rabbit, the required for impulses to travel through the visual pathways excretion of glycine solution then becomes much less when glycine levels were 5 10 mmol/l, which than for sorbitol and mannitol [36]. In the sheep, 46% corresponds to the administration of 1 2 L of glycine of the water load was excreted 3.5 h after a glycine load, 1.5% in an adult male [82]. Later studies of TURP while the corresponding value after infusions of isotonic [92,93] and in the laboratory [79] show that disturbances saline was 70% [58]. These dierences are due to a of the visual pathways may occur when much greater intracellular accumulation of glycine solution less glycine is absorbed. After 10 volunteers received five [95], which results in a dose-dependent half-life [97], incremental doses of 200 ml of glycine 2.2%, visual and also because glycine stimulates secretion of ADH disturbances with changes in visually evoked potentials from the neurohypophysis. This hormone aggravates the occurred in five, sometimes after as little as one dose hyponatraemia and maintains the fluid overload. [79]; the EEG was unchanged. Elevated plasma levels of ADH occur when the glycine Marked visual disturbances have not been associated dose exceeds 20 g in sheep [58] and in patients undergoing with irrigating fluids other than glycine nor with water TURP [89,98,99]. intoxication. Therefore, a toxic eect of glycine on the retina, where it acts as an inhibitory neurotransmitter, is the likely cause. Glycine levels in the vitreous fluid Sodium losses increase in parallel with those of the cerebrospinal fluid The hyponatraemia associated with the TUR syndrome during glycine overload, and amounts to 3 5% of those is often interpreted as the result of dilution alone. found in plasma [94]. As with skeletal muscle [95], the Therefore, authors have suggested that spontaneous glycine concentration in the vitreous fluid remains [41,75] or stimulated [29,100] diuresis should be the unchanged for several hours. chief therapy. Recent studies have altered this view; there is a loss of sodium during the osmotic diuresis associated with irrigating fluids. Large amounts of Water excretion glycine also stimulate the release of atrial natriuretic The excretion of urine is rapidly increased by all irrigat- peptide in excess of that expected by the volume load, ing fluids, albeit more promptly when mannitol is given which further promotes natriuresis [101]. Urinary excretion (mmol) 300 250 200 150 100 50 0 Glycine 1.0% + ethanol 1% Glycine 1.5% + ethanol 1% Infusion Mannitol 3% + ethanol 1% Sorbitol 2% + mannitol 1% Sodium Potassium Calcium Urea Creatinine Amino acids Mannitol Sorbitol Osmotic gap Fig. 4. Composition of urine 90 min after an intravenous infusion of 15 ml/kg of irrigating fluids in 10 healthy male volunteers (mean values). The osmotic gap represents negatively charged ions, which were not measured. The case series is presented in [38].

IRRIGATING FLUIDS IN ENDOSCOPIC SURGERY 675 The urinary excretion of sodium represents an absolute induced by all irrigating fluids is associated with loss of loss as the irrigant contains no electrolytes. The loss extracellular ions, such as sodium, while the solutes increases linearly with the volume of fluid absorbed, and used in the irrigants (except mannitol) diuse intracellularly amounts to 100 mmol when 4 L of fluid has been taken and are also metabolized. Therefore, a situation up (Fig. 5). This fluid absorption results in an acute develops with a persistent slightly reduced serum osmolality decrease of 30 mmol/l in the serum sodium level [12], and a gradually increasing cellular oedema (Fig. 6). but the subsequent losses of sodium are sucient to Calculations of the fluid distribution in volunteers indicate reduce it by 10 mmol/l. Hence, the natriuresis makes that glycine hydrates the cells more than other spontaneous restoration of the serum sodium level irrigants (Fig. 3). Similar results have been found by more dicult. light microscopy of vital organs in animals overhydrated Operations in which there is blood loss along with with irrigating fluids [37]. There is no evidence of selfcorrection fluid absorption will also incur the entrapment of sodium of the hypo-osmolality and cellular oedema ions. Electrolytes from the interstitial fluid enter the during the first hours after overhydration corresponding blood when irrigating fluid is being absorbed, while to 3 L in an adult male [58,101,103]. water travels in the opposite direction [64]. Therefore, some of the electrolytes lost from bleeding vessels and by the excretion of urine are derived from the interstitial Retroperitoneal absorption fluid. The magnitude of this entrapment increases with Irrigating fluid may be deposited in a pool in the retroperitoneal blood loss, but it usually does not exceed 10 15 mmol space if there is an instrumental perforation of the during an operation [102]. prostatic capsule. These events occur in 1% of the patients undergoing TURP [2,29] and may be fatal [15,75, 104,105]. The fluid probably exerts pressure on the caval Progressive cellular oedema vein and diuses, in part, through the peritoneal membrane The role of the kidney and the dierences in distribution [2,106]; metabolic acidosis may be severe [105]. between lost and added solutes are important in under- The pathophysiological events involved in extravasation standing why irrigating fluids cause cellular and brain were first studied in animals by Mahoney et al. oedema even when serum osmolality is marginally [107] while later studies were conducted in humans changed. It is dicult for the kidneys to maintain a high level of water excretion without losing large amounts of osmotically active solutes [58,103]. The osmotic diuresis Fluid absorption 100 80 r = 0.94 P < 0.005 glycine Sodium excretion (mmol) 60 40 Na Na Na 20 Na 0 0 1 2 3 4 Fig. 6. Schematic drawing illustrating how glycine solution causes cellular oedema despite adequate urine flow. The glycine in the Infused glycine solution (L) absorbed fluid distributes outside and inside the cells while the Fig. 5. The urinary excretion of sodium during and after intra- induced osmotic diuresis carries along sodium that is present venous infusion of glycine solution in sheep and humans. Each outside the cells only. Losses of intracellular ions are relatively point denotes the mean value from one study with a correction for small. Glycine is primarily metabolized to water and to carbon a baseline excretion of 0.06 mmol/min. From [102], with dioxide, which is removed by breathing. All these factors promote permission. intracellular distribution of the irrigant water. Urine

676 R.G. HAHN [108,109]. They show that electrolytes from the extra- although TUR syndromes are still not completely cellular fluid enter the pool of fluid. A reduction of the prevented [121]. plasma volume ensues as the solutes travelling in the other direction, e.g. glycine or sorbitol, are metabolized or accumulate intracellularly. Mild to moderate hyponatraemia Temperature and hypo-osmolality develop with a delay, Feeling cold is a frequent complaint from patients under- the lowest value usually being recorded 2 4 h after the going TURP. A drop in body temperature alters the operation [2,108]. Uptake of the irrigant water by the haemodynamic situation [53] and may result in shivering blood occurs fairly slowly. [122,123], which markedly increases oxygen conblood The number of symptoms for dierent ranges of sumption. The ability to compensate for heat loss by absorption is the same as for absorption directly into the increasing heat production is impaired in elderly men. vascular system, but the tendency to cause abdominal The time required to regain normal temperature after pain, bradycardia and arterial hypotension is greater [6]. the operation increases with the age of the patient [122]. There is also a high risk of failure to diurese spon- Bladder irrigation is an important source of heat loss; taneously, which is associated with the hypotension the use of irrigating fluids at room temperature results [6,15,107]. Severe TUR syndromes have been reported in a decrease in body temperature of 1 2 C [123 125]. following extravasation with both glycine [2], sorbitol This decrease is smaller with an irrigant heated to 37 C [110] and sorbitol-mannitol [75]. ( prewarmed ) than with a fluid used at ambient temperature, This special form of the TUR syndrome can also occur but it still averages 1 C during TURP [123,124], if the bladder is perforated. Then, irrigating fluid accumu- regardless of whether general or spinal anaesthesia is lates directly in the peritoneal cavity during TURP [110] used [122,124]. A continuously warmed irrigating or during transurethral resection of bladder tumours medium is needed to limit the drop in body temperature [111]. to below 1 C [125,126]. The decrease in temperature is greater during TURP than during transurethral resection of bladder tumours Prevention of fluid absorption when the irrigating fluid is prewarmed [126]. This The incidence and volume of fluid absorption can be dierence may be explained by fluid absorption, which reduced, but no method is capable of eliminating it operates as a specific cooling mechanism [127]. This completely. Stopping the resection after 1 h of surgery is contributes to the chilling and shivering which some- helpful, as the risk of fluid absorption is somewhat higher times occur even when prewarmed fluid has been in prolonged operations (Table 1). The degree of fluid absorbed [6]. absorption is also a matter of surgical skill; consultants usually cause less absorption than residents [20], although this is not supported by all studies [112]. Treatment Several methods are aimed at reducing the pressure The treatment of mild adverse eects of irrigating fluids in the operating field, from which fluid absorption occurs consist of supportive measures only. Nasal oxygen and at a pressure of about 2 kpa [113,114]. The height of an anti-emetic if nausea occurs are usually sucient. the irrigating fluid bag above the operating table did not Absorption of >2 L of fluid should be monitored for correlate with fluid absorption in 550 patients under- 4 6 h in the post-operative follow-up because sudden going TURP [115]. Ekengren et al. found that the cardiovascular disturbances may pose a problem [6]. maximum but not the mean pressure or the period of Patients who have absorbed >3 L should be treated excessive pressure (>2 kpa), increased when the fluid overnight in the intensive care unit. There is a threat to bags were placed higher [114]. Furthermore, the life and a knowledge of adequate management is therefore capacity of the bladder was a statistically more important essential. factor than the bag height in determining the intraves- Visual disturbances need no treatment as they resolve ical pressure. spontaneously within 8 h. Hypertension may develop at Continuous-flow methods have been claimed to the end of surgery but needs no treatment. It should decrease fluid absorption [116,117], although some subside quickly and be reversed to hypotension, which is authors have found no such reduction [113,118] and more troublesome. This shock-like hypotension should be TUR syndrome still occurred [28]. Perhaps the key to treated without delay with judicious infusion of a colloid success is to check that a low pressure is actually combined with adrenergic drugs. Metabolic acidosis obtained, as outflow obstruction occurs readily. should be compensated by the intravenous infusion of a Monitoring the intravesical pressure allows a more buer. Depressed consciousness is managed with maintenance consistent reduction of fluid absorption [119,120] of a free airway and positive-pressure ventilation.

IRRIGATING FLUIDS IN ENDOSCOPIC SURGERY 677 Intravenous calcium may be used to treat acute 5 Nilsson A, Hahn RG. Mental status after transurethral cardiac disturbances during surgery [60 62,69]. The resection of the prostate. Eur Urol 1994; 26: 1 5 administration of hypertonic saline is indicated when 6 Olsson J, Nilsson A, Hahn RG. Symptoms of the many adverse eects develop or the serum sodium transurethral resection syndrome using glycine as the irrigant. J Urol 1995; 154: 123 8 concentration drops below 120 mmol/l. It consists of 7 Landsteiner EK, Finch CA. Hemoglobinemia the intravenous infusion of 3 5% saline solution, usually accompanying transurethral resection of the prostate. N in a volume of 300 500 ml over 4 h. Both experimental Engl J Med 1947; 237: 310 2 [100,128] and clinical [31,76,129] studies support the 8 Creevy CD. Hemolytic reactions during transurethral usefulness of this treatment. There is no evidence that prostatic resection. J Urol 1947: 58: 125 31 hypertonic saline can result in pontine myelinolysis 9 Nesbit RM, Glickman SI. The use of glycine solution as when given to treat acute hyponatraemia in humans an irrigating medium during transurethral resection. where supplementation is started promptly and the J Urol 1948; 59: 1212 6 serum sodium concentration is increased by 2 mmol/l 10 Goodwin WE, Carson JF, Scott WW. Hemoglobinemia and per hour [129]. lower nephron nephrosis following transurethral prostatic Two-thirds of the hypertonic saline restores serum surgery. The use of a new nonhemolytic irrigating solution 3% mannitol as preventive. J Urol 1951; sodium and osmolality, while one third redistributes 65: 1075 92 water from the cells to the extracellular space [103], 11 Schulte TL, Hammer HJ, Reynolds LR. Clinical use of where it becomes available to diuretic treatment with Cytal in urology. J Urol 1954; 71: 656 9 frusemide. The latter drug is widely used in the treatment 12 Hahn RG. Ethanol monitoring of irrigating fluid absorption of fluid absorption, but such use is questionable in the (review). Eur J Anaesth 1996; 13: 102 15 absence of hypertonic saline as frusemide acts by increas- 13 Bulkley GJ, O Conor VJ, Sokol JK. Overhydration during ing sodium excretion. The eect may even be poor in transurethral prostatic resection. JAMA 1954; 156: the hyponatraemic patient. Mannitol 15% is a better 1042 44 choice, as this solution operates independently from the 14 Harrison RH, Boren JS, Robison JR. Dilutional hyponatra- serum sodium level and also increases the extracellular emic shock: another concept of the transurethral prostatic osmolality [42,43,128,130]. In the absence of pulmonresection reaction. J Urol 1956; 75: 95 110 15 Conger KB, Karafin L. A study of irrigating medium ary oedema, diuretic therapy should not be instituted extravasation during transurethral surgery. J Urol 1957; until the cardiovascular situation is stable; it is usually 78: 633 43 sucient to start this 30 60 min after the operation. 16 Hoekstra PT, Kahnoski R, McCamish MA, Bergen W, Extravasation should be treated with the same meas- Heetderks DR. Transurethral prostatic resection synures applied when the irrigating fluid passes directly into drome a new perspective: encephalopathy with the circulation. Morbidity and mortality can also be associated hyperammonaemia. J Urol 1983; 130: 704 7 reduced by surgical drainage of the retroperitoneal fluid 17 Chui PT, Short T, Leung AKL, Tan PE, Oh TE. Systemic [104], but this treatment seems to be necessary only absorption of glycine irrigation solution during endoafter massive absorption [2]. Such drainage removes metrial ablation by transcervical endometrial resection. extracellular electrolytes that have moved into the fluid Med J Austr 1992: 157: 667 9 pool. The magnitude of these losses is dependent on 18 Olsson J, Hahn RG. 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