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Fluid absorption during endoscopy Fig 5 Cardiac pathology in animals infused with irrigating fluid. Light microscopy is used with haematoxylin–eosin stain, with the permission of ProfessorJovan Rajs, Karolinska Institute. (A) Focal myocarditis in the heart of a mouse after receiving glycine 1.5%. (B) Focal necrosis of myocytes withinflammatory reaction in a rabbit from glycine 1.5%. (c) Vasodilatation and haemorrhage in the subendocardium in a mouse given mannitol 5%.
(D) Extreme interstitial dilatation in the myocardium of a rabbit sacrificed 2 h after being treated with 100 ml kg 1 of glycine 1.5%.
The incidence of urosepsis seems to be increased by i.v.
fluid absorption during TURP54 and by extravasation in Abdominal pain, which may radiate to the shoulder, is a common first sign of extravasation.37 Extracellularelectrolytes diffuse into the pool of deposited irrigating fluid6 90 and the hyponatraemia is most pronounced 2–4 h Brain oedema is a serious problem and cerebral herniation later.37 This movement of electrolytes is followed by hypo- developing a few hours postoperatively5 100 is a major cause volaemia, with bradycardia and arterial hypotension.6 38 115 of death from fluid absorption, in addition to cardiovascular Extravasation may go undetected until the next day, because or respiratory collapse.12 87 96 Signs of cerebral oedema on of the slow development.127 CT scans were found after absorption of as little as 1 litre ofglycine 1.5% during TCRE72 while this did not occur inyounger male volunteers.104 However, lowering of the serum osmolality in response to larger amounts of glycine Certain features of the pathophysiology are unique to each solutions raises the intracerebral pressure in experimental irrigating fluid.
animals105 and in TURP patients.78 Glycine is an inhibitory neurotransmitter in the retina.
The patient may become comatose after glycine absorp- An excess amount slows down the transmission of impulses tion without having cerebral oedema, but with signs of meta- from the retina to the cerebral cortex. Prolongation of visual- bolic encephalopathy with,98 or without,127 a marked evoked potentials and deterioration of vision occur after increase in blood ammonia, arising from the metabolism absorption of as little as a few hundred millilitres of glycine 1.5%.44 79 82 More pronounced absorption, corresponding toglycine concentrations of 7–8 mmol litre 1, abolishes the oscillatory potentials on the electroretinogram.120 There are Moderate amounts of irrigating fluid (up to 2.5 litre) induce clinical reports of transient blindness after absorption of osmotic diuresis, which results in absolute losses of sodium glycine during most types of endoscopic surgery. Intraocular from the body (40 mmol litre 1 urine).51 112 With larger pressure,99 fundoscopy, pupillary reflexes and brain CT scan amounts of irrigating fluid, they ultimately swell, which are normal, while the pupils may be dilated. The blindness promotes anuria.50 119 In extravasation, failure to void cor- resolves within 24 h.
relates with arterial hypotension,37 92 which causes anoxia of Prickling sensations and facial warmth are early signs of the renal tubular cells.
glycine absorption.56 Vasopressin is released as a specific response to glycine in saline compared with other irrigating solutions. Pulmonary doses exceeding 25–30 g32 112 leading to water retention and oedema is a reported consequence.29 restoration of the serum sodium after fluid absorption more Sterile water is often used for cystoscopy as it offers the surgeon a very clear view of the operating field. Warnings Hyperammonaemic encephalopathy may develop as against using sterile water for irrigation during electro- ammonia is an intermediate product in glycine metabolism.
surgery are based on both animal experiments119 and clinical Blood ammonia concentrations >100 mmol litre 1 (normal experience;80 but, more recently, several authors have rec- range 10–35) are associated with neurological symptoms, ommended the fluid for limited resections.30 68 81 Although and values up to 800 mmol litre 1 have been reported.63 there is no agreement about how much sterile water is Ammonia is released from the liver and kidneys and needed to cause renal failure, damage requiring chronic removed in the head and limbs. The blood concentration haemodialysis still occurs with accidental and unexpected correlates with the glycine dose and symptoms such as con- absorption of sterile water.20 Serum potassium might also fusion.56 Interindividual variability is great, however, and patients may show neurological symptoms after absorbing Sterile water could be expected to promote cerebral large amounts of glycine 1.5% while still having a normal oedema more vigorously than other electrolyte-free irrigat- blood ammonia concentration. Only 15–20% of volunteers show an increase in blood ammonia when challenged by aglycine overload.53 There is a vague correlation betweenhyperammonaemia and visual disturbances,44 82 while these Comparing outcomes factors are independent from cerebral oedema. Other meta- The clinician has an interest in knowing which irrigation bolic products of glycine have also been associated with fluid is associated with the least danger if fluid absorption neurological symptoms. Among them are glycolic acid occurs. This issue was studied by Hahn's group during the and glyoxilic acid, which accumulate in the cerebrospinal 1990s. A consistent finding in these studies was the poor fluid,97 98 and glutamate (glutamic acid), the elevation of performance of glycine 1.5%.
which shows a time-course similar to the symptoms.33Some of the metabolic symptoms of glycine absorptioncan be recognized in hyperglycinaemia, which is a rare dis- order of amino acid metabolism characterized by episodes of Zhang and colleagues128 studied rat cardiac myocytes and ketosis and metabolic acidosis that may proceed to coma.
found that 99% of cells were viable after being mixed with Oxalate is an end-product of glycine metabolism, but sorbitol 2% or mannitol 1%, while only 83% of them were studies in volunteers and TURP patients refute the assertion viable after glycine 1.5%.
that glycine markedly increases oxalate excretion.
In live mice, i.v. infusion of irrigating fluids was associ- Allergic reactions to mannitol are very rare. Mannitol ated with survival in 20% (glycine 1.5%), 32% (sorbitol 2% concentrations >5% are often used for purposes other with mannitol 1%) and 60% (mannitol 5%).91 Survival after than irrigation and entail the risk of acute renal failure in glycine administration was dependent on both the glycine dehydrated patients.64 dose and the accompanying fluid volume after both i.v.129 Metabolic complications of sorbitol are due to a primary and intraperitoneal95 administration. Isotonic glycine 2.2% metabolite, fructose. Rapid administration of fructose, com- was associated with the poorest outcome. Glycine 1.5%, pared with absorption of 5 litre of sorbitol 5% for more than 100 ml kg 1 for more than 60 min, was fatal in two out 30 min, causes lactic acidosis.9 Fructose might also induce of seven rabbits, while no animal died after mannitol 3% or coma in patients with liver disease.125 Infusion of sorbitol sorbitol–mannitol.50 Glycine solution induced the greatest has lead to death of patients with intolerance to fructose, increase in cardiac weight and tissue damage in the heart, because of lack of the aldolase B enzyme.106 Finally, hypo- kidneys, liver and brain. Maatman and colleagues76 reported glycaemia develops in young patients with fructose-1,6- microscopic damage to the liver and kidney of rats given diphosphatase deficiency who are given sorbitol.
glycine 1.5% by i.v. and retroperitoneal infusion, while the Normal saline is used for irrigation with the bipolar resec- histology was normal after Ringer's solution and water. The toscope. Although cerebral oedema is unlikely, infusion of water content of the mouse hearts increased markedly after 25 ml kg 1 of isotonic electrolyte solution for more than infusion of glycine 1.5%, but not after normal saline or 15 min in women caused sensations of swelling in the hands glycine 1.5% in normal saline.93 and face, slight dyspnoea, abdominal sensations and anal- In pigs, mannitol 5% increased the blood volume more gesia around the lips.46 Twice the volume infused for more than glycine 1.5%, and maintained the haemodynamic pro- than 1 h was followed by mental changes and discomfort from file better during infusion.105 The intracranial pressure dou- swelling.123 Moreover, normal saline causes hyperchlo- bled during infusion of glycine 1.5%, but was unchanged in raemic acidosis due to its excessive content of chloride.122 response to mannitol 5%. The peripheral vascular resistance Because of the greater plasma volume expansion,112 acute was increased during infusion of glycine 1.5% in sheep112 volume overload is more likely during absorption of normal and pigs.105 For both fluids, cardiac output and aortic blood Fluid absorption during endoscopy flow decreased by as much as 50% after the infusion was Absorption (ml) = –223+6440 breath ethanol (mg ml−1)/ completed.105 A similar cardiodepression has been observed irrigant ethanol conc (%)+17×time (min) in dogs given glycine 1.5%.
In studies based on infusing 1 litre of irrigating fluid for more than 20–30 min, glycine 1.5% elicits more symptomsthan mannitol 3% and 5%,56 104 while glycine 2.2%is worst.56 Glycine, but not mannitol 3% or sorbitol– mannitol solutions, reduces cardiac output by increasingperipheral resistance.84 The diastolic and mean arterial pres-sures become slightly increased.56 84 104 Ethanol, which can be added to the fluid to allow moni- toring of fluid absorption, has no effect on the fluid balance in prostatectomy patients given glycine 1.5%. Ethanol read- Fluid absorption indicated by ethanol (ml) ily enters the cells and only slightly increases the resistance to haemolysis.55 The breath ethanol concentration is prac-tically identical regardless of whether the ethanol is added Measured fluid absorption (ml) to glycine 1.0%, glycine 1.5% or mannitol 3%.56 84 104 Fig 6 Early graph, from 1989, showing the fluid absorption as indicated bycareful measurements of the volumetric fluid balance corrected for bloodloss at the end of any 10 min period of TURP vs the fluid absorption as obtained by a regression equation based on the expired breath ethanolconcentration, the ethanol concentration in the irrigating fluid and the period In a two-centre evaluation, glycine 1.0% had the same inci- of time during which ethanol has been detected. Most of the data are from dence of symptoms as glycine 1.5%,55 but mannitol 3% had refs 31 and 34.
a significantly lower incidence of symptoms, such as nausea,than glycine 1.5%.54 Cardiovascular events did not differbetween the fluids. Inman and colleagues70 found no differ- Gravimetry implies that the patient is operated on on a ence, based on 205 patients, in symptoms and cardiac bed-scale and that an increase in body weight implies fluid enzymes between glycine 1.5% and sorbitol–mannitol.
absorption. The method must take blood loss and all i.v.
infusions into account, and recordings should be madewhen the bladder is empty. Coppinger and colleagues16 108 Measuring fluid absorption have shown that the gravimetric method is quite accurate, Fluid absorption can be quantified by measuring serum when incorporating modern transducers and potential errors sodium in all cases where the solution lacks electrolytes.
are considered.
The method is best applied repeatedly during surgery, but is Central venous pressure increases transiently on intravas- rarely used clinically because of practical problems and cular administration of irrigating fluid, but the method is invasiveness. As a rule, serum sodium is only measured relatively insensitive because 500 ml must be absorbed at the end of surgery. The hyponatraemia then correlates within 10 min to increase the pressure by 2 mm Hg.45 with the amount of absorbed fluid, although smaller absorp- The result is also affected by blood loss and other fluid tion events may be blurred by variability and the sodium therapy111 but it may be recommended for poor-risk content of other infusions. Serum sodium is also a poor guide to the degree of extracellular overhydration during the post- Measurement with isotopes was long considered to be operative phase.42 the most reliable method to quantify fluid absorption,77 Volumetric fluid balance is based on the calculation of the but modern safety precautions make them difficult to apply.
difference between the amount of irrigating fluid used and Isotopes are a sensitive tool for detecting low-grade the volume recovered. Positive values are regarded as absorption. The accuracy is hampered by many factors, Ethanol is based on the same principle as isotopes that a including variations in bag-to-bag content, spillage, blood tracer is added to the irrigating fluid and that the body con- loss and urinary excretion. Haemodilution during surgery centration measured is an index of fluid absorption. Mea- should be considered in the blood loss figure to accurately surements of the ethanol concentration in the exhaled breath account for the plasma loss. All these factors make volu- can be made during surgery with relatively little effort. The metric balance an unreliable tool,94 and it must be refined to first clinical trial used glycine 1.5% with ethanol 2%,31 but be accurate.31 34 45 Volumetric fluid balance is more useful later studies concluded that 1% was suitable for clinical during TCRE as the confounding influence of blood loss is use.34 The sensitivity is 75 ml per 10 min of surgery, much smaller than during TURP (Fig. 6).58 and any further elevation of the breath ethanol concentration implies that more fluid is being absorbed (Fig. 6). Ethanol Low-pressure irrigation monitoring method can be applied during both spinal and Performing TURP with a low fluid pressure, below the general anaesthesia and in patients with poor lung function.
critical pressure for intravascular absorption, would limit The method has been well evaluated worldwide. Two the risk. This can be achieved by applying a suprapubic reviews are available.39 40 evacuation instrument (Reuter's trocar)101 or a special Absorption of fluid directly into the bloodstream is channel in a resectoscope (the Iglesias technique).
accompanied by a prompt decrease in serum sodium, eleva- Several authors have found irrigation using the suprapu- tion of the central venous pressure and an increase in the bic trocar to be efficient,65 while others have not. There is serum or breath concentration of any marker present in the even more widespread scepticism about the effectiveness fluid. These elevations correlate with the volume of of the Iglesias method. Heidler59 reported development of absorbed irrigant fluid as obtained by gravimetric weighing severe hyponatraemia in 3 out of 30 patients undergoing and very careful measurements of volumetric balance.
TURP using an Iglesias resectoscope. In contrast, only Extravasation is detected immediately only by gravi- 1 patient out of 60 developed severe hyponatraemia when metric weighing and volumetric fluid balance, while serum the pressure was maintained below 2 kPa using the supra- sodium and breath ethanol become apparent 15–20 min pubic trocar. In another study, the trocar maintained a low later.37 The maximum concentrations are approximately pressure (<1.5 kPa) only in half of the operations.41 Five one-third of those indicated by intravascular absorption, mild TUR syndromes occurred in 500 patients using this and a further increase after the operation is characteristic.39 evacuation device.121 The variable effectiveness is probablybecause of outflow obstruction by blood clots, which raisesthe fluid pressure. Low-pressure irrigation is probably more efficient if combined with monitoring of the intravesical Several methods have been proposed to reduce the risk of fluid absorption and its associated dangers. None of them iscapable of eliminating the complication.
Bipolar resectoscope A bipolar technique allows the use of normal saline for irrigation, which will influence the signs of TUR syndrome.
Fluid absorption varies between surgeons and depends on The incidence of mental changes and abdominal pain will be their skill in avoiding prostatic capsule perforations and the similar to that with sorbitol–mannitol irrigation,46 122 123 and opening up of venous sinuses. However, studies do not sup- vascular overload resulting in pulmonary oedema could be port that experienced surgeons have less fluid absorption expected as a more common problem.29 during their operations61 74 but those who obtain immediatefeedback via ethanol monitoring learn how to operate with less fluid absorption.74 Alternative techniques to TURP have been developed, one Spinal anaesthesia does not reduce absorption48 but of them being vaporization of the prostate. Fluid absorption allows early detection of gross changes in mental status.
and blood loss are less pronounced during this operation, but This approach offers limited possibilities to interact with fluid absorption of up to 3 litre may still occur.
the absorption process as symptoms require the build-upof a considerable absorption volume.
Vasoconstrictor with vasopressin injected at the operating Reduction of surgical time site is claimed to reduce fluid absorption during TCRE27 and It is a common belief that dangerous fluid absorption during might possibly have the same effect during TURP.107 Dur- TURP is prevented by keeping the operating time below ing TCRE, pretreatment with hormones to reduce endome- 1 h.18 However, massive absorption has been described trial thickness affects the risk of fluid absorption in many, after as little as 15 min of surgery (Fig. 1).34 48 87 but not in all, studies.113 Lowering the fluid bag Placing the irrigating fluid bag at 60 cm above the operating table was advocated early on as a method of controlling fluid Visual disturbances resolve spontaneously within 24 h and absorption.77 However, two studies comprising nearly 600 need no treatment.32 79 Mild adverse events are treated by patients could not demonstrate any correlation between bag supportive measures, including antiemetics. Hypertension is height and fluid absorption during TURP.47 117 The reason is likely to be transient. The cardiovascular collapse can be probably that the urologist tends to operate at a certain fluid reversed if treatment is instituted promptly. Bradycardia and pressure, which might be much lower than the maximum hypotension should be treated with atropine, adrenergic possible pressure indicated by the bag height.22 drugs and i.v. calcium.110 Although fluid restriction was Fluid absorption during endoscopy recommended previously,8 plasma volume expansion is and it should be noted that most symptoms appear indicated as hypovolaemia and low cardiac output develops 30–45 min after surgery is completed. At that time, the as soon as irrigation is discontinued.32 35 105 110 119 hyponatraemia is explained by natriuresis and not by Specific treatment includes hypertonic saline, which is dilution. However, symptoms related to fluid absorption indicated when several symptoms develop or the serum develop in 3–5% of patients. Neurological symptoms sodium concentration is <120 mmol litre 1. Both experi- are prominent whem glycine 1.5% is used. Some mental10 21 and clinical3 25 60 102 studies support the use of patients develop a severe TUR syndrome which involves this treatment, although serum sodium concentrations a hypokinetic circulation and damage to the heart. Their down to 100 mmol litre 1 may be fatal.87 Patients who treatment should be based more on hypertonic saline than do not receive hypertonic saline, or with a delay of several on furosemide.
hours, more frequently suffer residual neurological damage To control fluid absorption, the surgical training should be guided by immediate feedback about fluid absorption. The Warnings about pontine myelinolysis resulting from rapid surgeon should be notified about ongoing fluid absorption correction of hyponatraemia originally pertained to chronic whenever it exceeds 1 litre. This allows steps to be taken to hyponatraemia, but recent studies question rapid correction prevent excessive absorption. Treatment can be instituted also in acute hyponatraemia. Raising the serum sodium con- early and the optimal concentration of postoperative care be centration by 1 mmol litre 1 h 1 may be taken as a safe rate.2 chosen. The most viable methods to monitor fluid absorption Hypertonic saline combats cerebral oedema, but it also are ethanol monitoring and gravimetric weighing. Little is expands the plasma volume, reduces cellular swelling and yet known about the risks associated with alternative resec- increases urinary excretion without increasing the total sol- tion techniques, such as the bipolar resectoscope.
ute excretion. In the past, there was a fear of hypertonicsaline inducing pulmonary oedema,8 87 but this has notbeen seen in clinical experience.
Supplementary data The primary indication of i.v. furosemide is to combat acute pulmonary oedema and to induce diuresis when this The complete list of 320 references is available as supple- does not occur spontaneously. In other situations, the best mentary data to the online version of this article, at www.bja.
practice is probably to withhold this until the patient is haemodynamically stable and hypertonic saline is infused.
No studies support its routine use in the treatment of fluid absorption. In fact, furosemide after TURP aggravates thehyponatraemia and hypovolaemia.17 Early treatment with 1 Allge´n LG, Norle´n H, Kolmert T, Berg K. Absorption and elim- ination of mannitol solution when used as an isotonic irrigating furosemide is based on the belief that hyponatraemia is agent in connection with transurethral resection of the prostate.
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