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Roberthahn.seBritish Journal of Anaesthesia 96 (1): 8–20 (2006) Advance Access publication November 29, 2005 Fluid absorption in endoscopic surgery Department of Anaesthesia, Karolinska Institute, South Hospital, SE-118 83, Stockholm, Sweden Fluid absorption is an unpredictable complication of endoscopic surgery. Absorption of smallamounts of fluid (1–2 litre) occurs in 5–10% of patients undergoing transurethral prostaticresection and results in an easily overlooked mild transurethral resection (TUR) syndrome.
Large-scale fluid absorption is rare but leads to symptoms severe enough to require intensivecare. Pathophysiological mechanisms consist of pharmacological effects of the irrigant solutes, thevolume effect of the irrigant water, dilutional hyponatraemia and brain oedema. Other less widelyknown factors include absolute losses of sodium by urinary excretion and morphological changesin the heart muscle, both of which promote a hypokinetic circulation. Studies in animals, volun-teers and patients show that irrigation with glycine solution should be avoided. Preventivemeasures, such as low-pressure irrigation, might reduce the extent of fluid absorption butdoes not eliminate this complication. Monitoring the extent of absorption during surgery allowscontrol of the fluid balance in the individual patient, but such monitoring is not used widely.
However, the anaesthetist must be aware of the symptoms and be able to diagnose this com-plication. Treatment should be based on administration of hypertonic saline rather than ondiuretics. New techniques, such as bipolar resectoscopes and vaporizing instead of resectingtissue, result in a continuous change of the prerequisites for fluid absorption and its consequences.
Br J Anaesth 2006; 96: 8–20 Keywords: complications, hyponatraemia; complications, irrigation; complications, surgery;kidney, diuretics, mannitol; metabolism, sorbitol; pharmacokinetcs, glycine Many endoscopic surgical procedures require the use of have been reported. Severe events are associated with an irrigating fluid to dilate the operating field and to absorption of >3 litre of fluid.
wash away debris and blood. A potential complication of The TUR syndrome can occur with other operations such irrigation is systemic absorption of the fluid to including transcervical resection of the endometrium the extent that overt symptoms are produced. The conse- quences depend on the rate, volume and nature of the fluid cystoscopy,109 127 arthroscopy,69 rectal tumour surgery, vesical ultrasonic lithotripsy and percutaneus nephrolitho-tripsy.19 24 115 Fluid absorption was described, in 1947, as the cause of renal damage after transurethral resection of the prostate (TURP).
Irrigating fluid is most frequently absorbed directly into the The sterile water used for irrigation apparently caused vascular system when a vein has been severed by electro- intravascular haemolysis when absorbed. Within a few surgery. The driving force is the fluid pressure, which needs years, the modern non-electrolyte solutions containing gly- to exceed the venous pressure of 1.5 kPa.66 The period of cine, mannitol or sorbitol were introduced to prevent time that the fluid pressure exceeds 2 kPa (15 mm Hg) haemolysis, without dispersing the electric current used increases significantly with the absorbed volume.41 77 for cutting with the resectoscope. However, other adverse Major fluid absorption rarely stops once initiated and effects due to fluid absorption soon became apparent. They often coincides with a decrease in arterial pressure.48 arose in both the cardiovascular and nervous systems and, in Extravasation occurs after instrumental perforation of the the late 1950s, became known as the ‘transurethral resec- prostatic capsule during TURP, the uterine wall in TCRE,89 tion (TUR) syndrome'. Since then, several hundred life- or the bladder wall during cystoscopy127 and TUR of bladder threatening32 60 96 and even fatal5 12 69 87 100 TUR syndromes tumours.20 38 Several litres of irrigating fluid are rapidly The Board of Management and Trustees of the British Journal of Anaesthesia 2005. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org Fluid absorption during endoscopy deposited in the periprostatic, retroperitoneal or intraperi- An alternative approach is to measure the amount of toneal spaces. The fluid pressure only needs to exceed the absorbed fluid and the number of patients who develop intra-abdominal pressure of 0.5 kPa for extravasation to symptoms. The likelihood of symptoms developing can then be described in terms of ‘risk' for increasing volumes Extravasation is more common during renal stone sur- of absorbed fluid (Figs 2 and 3). Such data allows valid gery,24 115 while direct intravascular absorption is the comparison of the incidence of symptoms with various more common during TURP31 34 45 48 and TCRE.89 irrigating fluids.
Absorption in excess of 1 litre of glycine solution, which is associated with a statistically increased risk of symp- toms,92 has been reported in 5–20% of the TURPs performed(Fig. 1). Extravasation is the cause in 20% of these Smoking is the only patient factor known to be associated patients.54 55 92 with large-scale fluid absorption during TURP.43 Patients Fluid absorption is slightly more common during TCRE with prostate cancer who undergo TURP have the same than during TURP,15 28 72 the average being 400–700 ml.
incidence of fluid absorption as those with benign tissue.48 Istre71 reported absorption to be in excess of 1.5 litre in Fluid absorption increases with the extent of the resection 9% of patients, but there also appears to be a learning as the exposure is prolonged.48 Visual indications of fluid curve. In larger case series, the incidence of the TUR syn- absorption to the surgeon are usually lacking, although cap- drome may be <1%.73 sular perforation,103 which occurs in at least 10% of the In one study, fluid absorption exceeded 1 litre in 7% of TURPs, or apparent damage to a venous sinus increases patients undergoing percutaneous renal stone surgery.19 the likelihood of its occurrence.
Gehring and co-workers detected fluid absorption in all During TCRE, fluid absorption occurs more often during 31 patients who underwent this operation, and those with resection of fibroids.71 113 Variable amounts of fluid are extravasation required more opioids and had a longer hos- extravasated via the Fallopian tubes88 but previous steril- pital stay.24 Four of them remained in the ICU for more ization does not alter total absorption.15 89 Symptoms of glycine absorption Mild to moderately severe TUR syndrome occurs in between The incidence and severity of symptoms for increasing 1 and 8% of TURPs performed.25 31 34 111 121 Certain smaller amounts of absorbed fluid have been best established for patient series have a higher incidence,4 7 99 while others do glycine solution. In one retrospective analysis,92 patients not report any cases.26 One problem is that few studies use a who absorbed 0–300 ml of glycine solution had an average clear definition of the TUR syndrome. High variability in of more than one symptom. This increased to more than two fluid absorption and patient's responses makes it necessary when 1–2 litre had been absorbed, to more than three when to include up to 400 patients in any meaningful examination 2–3 litre had been absorbed, and to more than five for vol- of the incidence of the syndrome. The use of a checklist to umes >3 litre. The odds ratio for symptoms to develop was grade symptoms is recommended (Table 1).54 55 92 7 for TURPs during which 1–2 litre of glycine had been Table 1 A checklist used to define and score symptoms included in the TUR syndrome. In three studies,54 55 92 the number and severity of symptoms showed astatistically significant increase as more irrigating fluid was absorbed. HR, heart rate; SAP, systolic arterial pressure Duration <5 min Duration >5 min HR decrease 10–20 bpm HR decrease >20 bpm Repeated decrease SAP up 10–20 mm Hg SAP up >30 mm Hg Score (2) for 15 min SAP down 30–50 mm Hg SAP down >50 mm Hg Repeated drops >50 mm Hg Poor urine output Diuretics are needed Diuretics ineffective Duration <10 min Duration >10 min Transient blindness Duration <5 min Duration 5–120 min Intense or >120 min Repeatedly, <60 min Repeatedly, >60 min Duration <5 min Duration 5–60 min Duration >60 min Objectively exhausted Exhausted for >120 min Somnolent <60 min Severe <60 min Severe >60 min Incidence of fluid absorption (n =817) Prickling sensations Arterial hypotension Fluid absorption (ml) Incidence of symptom (%) Operating time (ml) <500 500– 1000– 1500– 2000– >3000 Fluid absorption (ml) Range of fluid absorption (ml) Fig 2 The incidence of prickling sensations, arterial hypotension, feelings of uneasiness and chest pain with increasing amounts of absorption ofglycine 1.5% during TURP. The absorption was measured by ethanol Fig 1 The incidence of fluid absorption during transurethral prostatic resec- 1%. Data are summarized from three studies54 55 92 using the checklist tion as measured by the ethanol method in 817 consecutive patients, sum- shown in Table 1.
marized from two studies.54 55 The uptake exceeded 500 ml in 16% of theoperations performed (A). The amount of absorbed fluid is difficult to pre-dict from the extent of surgery, although it does become more common and complains of headache. The most consistent signs are brady- more pronounced in prolonged (B) and bloody operations (C). The x–y plotsshow data on 375 patients from three studies,54 55 92 all of those who had cardia and arterial hypotension (Fig. 2). ‘Feeling bad' is fluid absorption and a minority of the patients with zero absorption.
slightly more common than perioperative nausea, whichis reported by 5–10% of the patients. Chest pain occursin 5% of the patients who absorb >1 litre, and is more likely absorbed. Further increases mainly comprised neurological if the blood loss is small.98 Hypertension is statistically symptoms. This dose-dependent increase in the number of unrelated to fluid absorption.
symptoms arising has been corroborated in subsequentprospective studies.54 55 A pooled analysis of the incidenceof various symptoms, based on these three studies which were carried out in the same way, shows that the TUR The most common signs and symptoms are nausea and syndrome has a progressive nature.
arterial hypotension followed by vomiting and low urinaryoutput, all of which become more frequent as more irrigatingfluid is absorbed (Fig. 3). Visual disturbances are reported by 10% of the patients who absorb >500 ml of glycine solution.
The patient sometimes reports transient prickling and burn- Arterial hypertension becomes less common when more ing sensations in the face and neck, becomes restless and irrigating fluid is being absorbed. Depressed consciousness Fluid absorption during endoscopy The incidence of acute myocardial infarction during TURP is between 1 and 3%.70 Evidence of cardiac isch- aemia, using Holter ECG, was found in 25% of TURP patients, mostly in those with known cardiovascular disease.124 A marginal increase in cardiac enzymesoccurred in 7% of all TURP patients,70 but the incidence was higher in patients with glycine absorption.49 Severe TUR syndrome is rare but well described in the literature. A review of 24 severe cases (glycine 1.5%) Arterial hypotension showed that neurological symptoms occurred in 92%, car- diovascular symptoms in 54%, visual disturbances in 42%,digestive tract signs in 25% and renal failure in 21%. The mortality was 25%.100 Pharmacokinetics and pharmacodynamics Glycine is a non-essential amino acid which was introduced in 1948 as an irrigating fluid solute (usually 1.5%) with low cost and lack of allergic reactions. The plasma concentration in humans is 0.3 mmol litre 1, which is raised 25-fold on Incidence of symptom (%) administration of 1 litre of this fluid. The distribution half- life is only 6 min,51 while the terminal half-life is between 40 min and several hours.33 51 56 The half-life is dose- Poor urine output dependent36 which is probably due to intracellular accumu- lation of glycine.86 Penetration into the central nervous system is restricted,126 but may be clinically important.112 Elimination of glycine occurs primarily in the liver, yield- ing ammonia. Only 5–10% of an excess dose is excreted unchanged in the urine, promoting an osmotic diuresis.56 The plasma concentration and urinary excretion of other <500 500– 1000– 1500– 2000– >3000 non-essential amino acids are also increased.32 33 Visual disturbances correlate with a plasma glycine con- Range of fluid absorption (ml) centration of 5–8 mmol litre 1 44 82 while higher concentra-tions produce transient blindness.120 Nausea and vomiting Fig 3 The incidence of nausea, arterial hypotension, vomiting and poor develop when the plasma glycine concentration exceeds urinary output with increasing amounts of absorption of glycine 1.5% after 10 mmol litre 1.25 33 Concentrations measured in fatal TURP. The absorption was measured by ethanol 1%. Data are summarizedfrom three studies using the checklist shown in Table 1.
TUR syndromes have been 21 and 80 mmol litre 1.5 96 Mannitol is an isomer of glucose used as a 3 or 5% solu- develops in 5% of the patients after absorption of >1 litre tion. After a short distribution phase, mannitol spreads of fluid. Diarrhoea occurs in 20% of those who absorb throughout the extracellular fluid space. The elimination >3 litre.
half-life is 100 min51 but can be twice85 and even four Abdominal pain is reported by 10–20% of patients who times1 longer in TURP patients with a moderately elevated absorb >1 litre of fluid. This symptom is strongly related to serum creatinine concentration.
extravasation, which is also associated with a higher inci- Mannitol is not metabolized and is excreted unchanged in dence of arterial hypotension and poor urinary output.37 the urine,1 promoting an osmotic diuresis. This effect makes The clinician should be aware of a mild TUR syndrome, it inappropriate to combine irrigation with mannitol 5% and which is easily overlooked. This presents with nausea and postoperative diuretic therapy.75 85 However, mannitol is not often a sudden reduction in arterial pressure 30–45 min after diuretic in a 0.5–1% concentration as an irrigating fluid the operation.54 55 92 Serum sodium is lowered 5–10 mmol mixed with 2–3% sorbitol.84 87 A maximum concentration of 2 g litre 1 was measured in The ‘mini-mental' status test shows that glycine absorp- 10 volunteers who received 1.2 litre of mannitol 3%.51 tion has a strong association with transient confusion after Plasma concentrations >4 g litre 1 were associated with TURP.83 Apparent confusion may occur in response to bradycardia and hypotension after TURP75 while other absorption of 1–2 litre,114 but is more consistent with larger authors found few or no symptoms after absorption of man- absorption volumes4 25 and might proceed to depressed nitol 5%,1 a fact probably attributable to the isotonic nature consciousness33 102 115 and coma.60 100 116 of mannitol 5%.
and pulmonary oedema may develop on the operatingtable,14 21 32 particularly during operations associated witha small blood loss.35 Hypervolaemia is followed by a longer and more prob- lematic hypokinetic haemodynamic phase, which is charac-terized by low cardiac output, hypovolaemia and low arterial pressure.8 14 105 110 Factors promoting the haemodynamic Plasma dilution 0.1 changeover include natriuresis, osmotic diuresis and, with glycine and sorbitol, intracellular uptake of water. Hypona-traemia, hypocalcaemia,13 14 low serum osmolality,100 acute lowering of the body temperature23 and release of prostatic substances118 or endotoxins111 may also contribute. There-fore, bradycardia and a marked decrease in systolic arterial Fig 4 Computer simulation of the plasma dilution resulting from experi- pressure down to 50–70 mm Hg at the end of, or just after, mental infusion of 1.5 litre of three irrigating fluids for more than 20 min in10 volunteers. There are only small differences between the fluids despite the operation is often the first sign suggesting TUR syn- the differences in half-life of the solutes. Calculation is based on data from drome.4 14 110 Pulmonary oedema might also develop late, indicating that serum sodium is <100 mmol litre 1 11 102 incoexistence with severe hypo-osmolality.18 Sorbitol is metabolized to fructose and glucose in the liver and has a distribution half-life of 6 min and a terminal half-life of 33 min.51 As for glycine, 5–10% of an infused Disturbances of cardiac function due to excess water might load is excreted unchanged by the kidneys. Plasma sorbitol be an important cause of cardiovascular collapse. Depres- concentrations corresponding to 2 litre of absorbed fluid sion of the conductivity system, bradycardia, and depression have been reported after TURP without associated untoward of the ST segment and T wave is common also in humans effects. However, in five patients with TUR syndrome (of with massive fluid absorption.4 49 87 96 102 whom two died), the total serum concentration of irrigant Animal studies have shown damage to the myocardial solutes was between 5.4 and 12.0 g litre 1 when irrigation histoskeleton in association with irrigating fluids and that was performed with a mixture containing sorbitol 2.7% and glycine in particular causes hypoxic lesions in the subendo- mannitol 0.54%.87 The major portion of this solute concen- cardium50 52 57 105 (Fig. 5) and an acute increase in the tration can be attributed to sorbitol.
weight of the heart.93 105 The ECG shows a bradycardiawith prolongation of the PQ time, widening of the QRS Water in irrigation fluids complex and reduction of the QRS amplitude, all ofwhich correlate with the outcome.93 The fluid volume in which the solutes are dissolved adds tothe symptoms of fluid absorption. The volume expansion ofthe intravascular space and dilution of the plasma has been quantified in volunteers. Mannitol 3% expands the plasma Dilution of plasma proteins rarely exceeds 25%, but might more than glycine 1.5%104 while sorbitol–mannitol takes an intermediate position (Fig. 4).
(<120 mmol litre 1) may cause muscle weakness, muscular The lower osmolality of irrigating fluid compared with twitches, epileptic seizures and shock.25 99 This key finding plasma means that irrigant water enters the cells very is often accompanied by reduction of serum osmolality of quickly after absorption takes place. Glycine and sorbitol 10–25 mosmol kg 1, as most irrigating fluids are hypo- enter the cells and, by virtue of osmosis, bring water intra- osmolar (200 mosmol kg 1). Ghanem and Ward25 reported cellularly. Cellular oedema develops with a delay related a strong correlation between low serum osmolality and to the half-life of the solute and, together with urinary excre- symptoms and Desmond18 between osmolality and pul- tion and surgical haemorrhage, reduces the extracellular monary oedema. Serum potassium often increases tran- overhydration.104 105 siently by 15–25% in response to fluid absorption,particularly after absorption of glycine.56 82 The hyper-kalaemia is probably related to intracellular uptake of the General pathophysiology irrigant solute.
Absorption of a volume large enough to cause TUR syn- drome is accompanied by metabolic acidosis with pH levels Fluid absorption causes a transient hypervolaemia with an ranging from 7.10 to 7.25.63 127 Hypoxia has also been increase in central pressures, which plateaus within reported,28 but it is less consistent and is more common 15 min.32 35 Shortness of breath, uneasiness, chest pain
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.
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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Valoración económica de la oportunidades y riesgos ¿Hay que poner precio a la biodiversidad para conservarla? Con la colaboración de: Conclusiones del Seminario sobre la valoración económica de la biodiversidad, oportunidades y riesgos. Madrid, 30 septiembre - 1 octubre de 2011
Chin. Phys. B Vol. 24, No. 1 (2015) 014704 TOPICAL REVIEW — Magnetism, magnetic materials, and interdisciplinary research Surface modification of magnetic nanoparticles in Chu Xin(储 鑫), Yu Jing(余 靓), and Hou Yang-Long(侯仰龙 Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing 100871, China (Received 4 November 2014; published online 9 December 2014)