qeeveiant 7 a2 OL 15-139 & (Review Article) Ten Golden Rules of Fluid Therapy Man S. Oh, MD. State University of New York, Health Science Center at Brooklyn, Brooklyn, NY 11203 Every day in the hospital wards, physicians are required to write orders for intravenous fluid, but when asked to explain their choices, few are completely comfortable with justification for the order. For example, a patient is on NPO after surgery, and a physician wishes to write a postoperative iv fluid order. The immediate questions that need to be answered would be type of fluid and the rate if its administration. Should it be one liter every 6 hours, every 8 hours, or every 12 hours? Should the solution bbe isotonic saline, isotonic saline, or 5% dextrose in water? Should the solution contain other electrolytes such as potassium, calcium, phos~ phate, magnesium, or bicarbonate? How much and on what basis? It is the hope of this author that understanding a few basic principles such as those to be discussed below will help to alleviate concern and confusion about iv fluid orders that are very commonly experienced by ‘most physicians. Rule #1: The body has a powerful defense against water deficit, but very little against water excess, Don't be generous with fluid. Increase in serum sodium concentration by 4 to § mEq/L above the usual normal value is a powerful stimulus for thirst. A conscious patient will demand or drink water until thirst subsides. On the other hand, hyponatremia does not create feeling of aversion to| water. A patient with severe inappropriate ADH secretion may continue to drink water until he lapses into coma, In other words, insufficient water intake will not remain uncorrected in a conscious patient, whereas there’ is no effective defense mechanism exists to prevent hyponatremia and fluid overload. In the hospital, patients tend to get too much water, and rarely too little water. ‘As a consequence, hyponatremia is a common Postoperative complication; hypematremia seldom occurs during the postoperative period. By the same token, fluid overload resulting in pul- monary congestion is a common occurrence in the hospital, whereas volume depletion leading to hypotension rarely occurs in the hospital. During a lecture given to a group of surgeons some years ago, I asked them to raise hands if they had encountered a hyponatremic complication during the postoperative period in the past 3 ‘months, everyone's hand went up. When asked to raise hands for a hypematremic complication during the postoperative period in the same 3 months, no one raised a hand. Clearly, patients are receiving too much fluid in the postoperative period. Key Words: Ten golden rule, Fluid therapy © Corresponding Author: Man S Oh, M.D. Professor of Internal Medicine, State University of New York, Health Science Center at Brooklyn, Box 21, 450 Clarkson Ave. Brooklyn, NY 11203Tre Korean Jeural of Hepatogy : Vol. 7. No, 2 2001 Rule #2: In determining the water intake, one must know the usual water output: urinary and skin loss of water. ‘The normal water loss from the body includes urinary loss and insensible water loss. Insensible water loss through the skin is about 30 mL/100 calories. Urine water loss depends on daily solute output and urine osmolality. During the postoperative period when urine osmolality frequently tends to be high because of inap~ propriate ADH secretion, one can estimate the expected urine output by assuming that the urine osmolality will be about 800 mOsmVL. An average size adult on normal salt intake excretes about 800 mOsm of solutes per day. At the urine ‘osmolality of 800 mOsm/L, the predicted 24 hour urine volume would be 1 liter. An adult of average size on bed rest consumes about 1,700 calories per day, and hence, the daily skin water loss would be 17%30 = 510 mL. Such a person would need 15 liters of water intake to remain in water balance. The pulmonary water loss in the absence of fever and hyperventilation is ignored in this calculation because the water loss from the lung is about equal to metabolic water production. Because the skin water loss depends on caloric expenditure, one must realize that a chronically ill cachectic patient with markedly reduced caloric expenditure will have much less insensible water loss than a normal person. If such a person is also in a coma and has renal feilure, caloric expenditure will be even more severely depressed. Normally, the brain and the Kidney use 25% and 10% each of the basal caloric expenditure. Rule #% Know the quantities of the electrolytes and nutrients that are being given, and know the volume of initial distribution (usually ECF). 136 ‘The quantities of mono-valent ions such as Na, K, Cl, and HCOs are usually expressed in mg. On the other hand, multivalent ions are usually quantified as grams or percent(9%6), based on the entire formula weight of the compound. For example, 10 mL of a 10% solution of calcium gluconate contains 1 g (1000 mg) of calcium gluconate-dihydrate. In other words, the 10 gram per 100 mL of the solution includes not only the weight of calcium but also the weight of gluconate as well as 2 molecules of, which is part of a calcium-gluconate-dihydrate crystal. ‘The content of elemental Ca in this solution is only 90 mg. 10 mL of a 1096 solution of calcium chloride, however, contains 270 mg of elemental calcium; the calcium chloride crystal also exists as a dihydrate. Thus, the same 10 mL in 10% solution of the latter calcium salt contains 3 times as much calcium as the former. One gram of MgSOx contains only 96 mg (8 meq or 4 mmol) of Mg, as the compound exists as ‘MgSO.7HO. A physician writing an order for an electrolyte additive has the obligation to find out the actual content of the critical element. ‘The physician's desk reference (PDR) usually has the required information. Rule #4: Know the aim of fluid therapy. When an intravenous fluid is given, the purpose is either to expand the vascular volume or to change the concentration of a particular electrolyte. The physician writing the order must have a clear aim, For example, when saline (sodium containing solution) is given, the purpose is either the expansion of vascular volume or an inerease or decrease in serum Na concentration. If a patient with congestive heart failure with massive edema has severe and ‘symptomatic hyponatremia, the physician mightbe forced to administer a saline solution. In this setting, clearly the purpose is to increase serum sodium concentration with minimal expansion of vascular volume. The solution of choice must be hypertonic saline. In a patient with severe volume depletion and moderate hyponatremia, expansion of vascular volume is the immediate goal, and the ideal solution would be isotonic saline. One may be tempted to use a hypertonic saline in such a setting, thinking that it will correct both hypovolemia and hyponatre However, rapid administration of a large amount of hypertonic saline needed to correct the volume depletion might correct hyponatremia too fast, with central pontine myelinolysis as a consequence. Rule #5: Don't be an indian giver. An indian giver is a person who gives a gift and then takes it back, If the purpose is to give Na, one should not remove it at the same time unless there are specific reasons for increasing urinary Na. When a patient in congestive heart failure treated with a diuretic develops pre-renal azotemia with a marked increase in BUN and creatinine, a physician might order intravenous saline, but with continuation of diuretic therapy because of fear of pulmonary congestion. This would be an example of sodium being given and being removed at the same time. Exceptions can be made to the rule of not giving saline and diuretics simultaneously in the case of treatment of hyperkalemia, hypercalcemia, and hyponatremia, Sometimes a physician will restrict oral water intake in order to increase serum Na, and will give normal saline intravenously at the same time: another example of a conflicting order. Use of isotonic saline instead of hypertonic saline in this situation represents administration of additional water. 137 ‘Man S. Oh Ten Galion ules of Fd Theany Rule #6 Know that hypertonic saline contains less water than isotonic saline. Most physicians are afraid to administer hypertonic saline to a patient with congestive heart failure; the rationale is that it contains more sodium than isotonic saline, and therefore is more likely to cause pulmonary congestion and volume overload than would isotonic saline. However, the other side of the coin is that hypertonic saline contains less water than does isotonic saline. When hypertonic saline is administered to a patient with volume overload, the likely purpose is to increase serum sodium concentration, and hence giving sodium, not water, is the main goal. For the same amount of sodium given, hypertonic saline contains less water than isotonic saline, and hence safer. It is water, not salt, that causes pulmonary congestion. Rule #7: Be familiar with different iv solutions and iv additives. In order to write an intelligent iv fluid order, the physician must be knowledgeable about the types of iv solutions and iv additives that are available. For example, saline solutions are available at 0.45%, 0.9%, 3%, 5%, and 35%, Remember that percent in this case refers to grams per 100 mL. Thus, a 0.9% solution of NaCl contains 0.9 g of NaCl in 100 mL or 9 g in one liter. Likewise, dextrose is available as 2.596, 59%, 10%, and 50%. solutions, 5% dextrose solution contains 5 g of dextrose in 100 mL and hence 50 g in a liter. If 100 g of glucose is to be given in a day, 2 liters of 596 dextrose solution would be needed. If the need for the fluid restriction limits intake to only 1 liter of fluid a day, 1 liter of 1096 solution of dextrose will provide the same 100.g of glucose.The Korean Jura of Hepat : Vol. 7. No 2.2001 Rule #& Know that the kidney does not manu- facture water or electrolytes, The only exception is bicarbonate. “The spleen retains more water and sodium than the kideny.” ‘The obvious truth that the kidney does not ‘manufacture any electrolyte or water other than bicarbonate is commonly forgotten. Physicians often make statements based on such mis- conceptions. For example, if diarrhea causes loss of potassium in the stool that exceeds the potassium intake, renal conservation of potassium ‘would not prevent relentless potassium depletion. ‘The most the kidney can do in such a setting would be not to excrete any potassium at all, which is impossible as long as there is urine ‘output. In that sense, the spleen, which loses no potassium, is doing a better job in preventing potassium depletion. Likewise, in the absence of sodium or water intake, the expression, renal sodium or renal water retention, is meaningless. Rule #8: For short-term fluid therapy, divalent ions (Ca, Mg, and P) do not need replacement. Daily K intake: 40-60 mEa, and daily NaCl intake: 75-150 mmol (what is contained in 1/2 - 1 liter of normal saline). Daily glucose requirement: 100 g. In the absence of food intake, about 100 g of glucose should be given in order to supply the brain’s daily energy requirement. When carbo- hydrate is not given, glucose requirement is met by gluconeogenesis through protein breakdown. ‘The production of 100 g of glucose requires catabolism of about 160 g of proteins. Rule #10 Think about COP-Wedge gradient. Intravenous solutions can be classified into two main types: crystalloids and colloids. 138 Crystalloids are solutions of readily-diffusible electrolytes, and colloids solutions of large molecular weight substances whose diffusion across the capillary membrane is restricted. Administration of crystalloids increases pulmonary capillary wedge pressure, and at the same time decreases colloid osmotic pressure (COP). Both factors operate to increase fluid movement into the pulmonary interstitium. On the other hand administration of colloids, while it increases both pulmonary arterial wedge pressure, also increases the COP, which tends to limit Quid movement out of the capillary. The difference between the colloid osmotic pressure and the wedge pressure (COP-wedge gradient) determines the rate of accumulation of pulmonary edema fluid: an increased gradient prevents pulmonary edema ‘and decreased gradient predisposes to pulmonary edema. ‘The main determinant of COP is the plasma protein concentration, particularly plasma albumin concentration. The colloid osmotic pressure, as the name implies, is the osmotic pressure contributed by solutes that are relatively impermeable to the capillary membrane, and therefore proportionate to the osmolality contributed by the impermeable solutes. When a patient needs to be treated with ‘a volume expanding solution but there is concen that the patient is in danger of pulmonary congestion, use of a colloid solution should be considered. Common colloids used are albumin, plasmanate, and fresh frozen plasma, dextran, and hydroxyethyl starch. ‘The usual unit of osmotic pressure is mmHg, whereas the usual unit of osmolality is mOsmvL, and the latter can be converted to mmHg through the Van't Hoff equation: Osmotic pressure (mmHg) = osmolality (mOsnVL) x 193The osmolal concentration of non-permeable solutes in the plasma attributable to plasma proteins is about 0.84 mOsm/L (0.6 mOsm/L of albumin and 024 mOsnV/L of globulin). The colloid osmotic pressure calculated with this equation would be 162 mmHg. However, the actual colloid osmotic pressure determined with ‘an oncometer is 23-25 mmilg. The discrepancy is explained by the Gibbs~Donnan equilibrium, ‘The Gibbs-Donnan equilibrium indicates that the product of diffusible cations and anions of the plasma must be equal to the product of diffusible anions and cations of the interstitial fluid. Because of the net charge imbalance of plasma proteins, the total number of diffusible anions 139 en S. On Ten Golden Pes of Pid Therapy ‘and cations of the plasma is greater than the sum of diffusible cations and anions of the interstitial fluid when diffusible ions are in diffusion equilibrium according to the Gibbs- Donnan equilbrium. Hence, the colloid osmotic pressure contributed by plasma proteins is partly due to the presence of plasma proteins per se but partly due to a difference in concentration of diffusible ions. As a consequence, a decrease in plasma protein concentration reduces colloid ‘osmotic pressure disproportionately. For example, when total plasma protein concentration is reduced bby 508 COP is reduced by more than 50%.cdeevsyaix| a7 al 2 8 mr 1-16 BY BS] ES} Ase AS AE MAAR URS SAY uray, ops] epsal* MBL - WEP - AMS - 1S - MSS - e+ - OS - AAS - Baal (Abstract Renal Function Indices Predicting the Prognosis of Patients with Liver Cirrhosis Jeong Ihn Seo, M.D., Soon Koo Baik, M.D., Jae Woo Kim, M.D., Dae Wook Rhim, M.D., Yong Soon Park, M.D., Hyun Soo Kim, M.D., Dong Ki Lee, M.D., Sang Ok Kwon, M.D., and Sei Jin Chang, Ph.D.* Department of Internal Medicine, Preventive Medicine’, Yonsei University, Wonju College of Medicine, Korea Background/Aims: Renal dysfunction commonly develops in patients with established liver disease. ‘The assessment of renal function is of clinical importance in patients with cirrhosis and ascites. Renal function indices such as glomerular filtration rate and the plasma renin activity (PRA) could be better predictors of survival than the parameters usually used to estimate liver function including Child-Pugh score, This study was designed to find whether renal function indices are useful in determining the prognosis concerned with the survival of patients with liver cirrhosis. Methods: A total of 110 patients was selected and followed for 89 weeks. As indices reflecting renal function, creatinine clearance rate, PRA, aldosterone concentration, and the pulsatility index (PI) and resistive index (RI) by Doppler ultrasonography were measured. The prognostic values of these indices were determined by comparison and analysis according to survival or death of the patients. For the statistics, univariate and multivariate analysis was done. Results: Child-Pugh score (10), creatinine clearance rate (<80 mL/min), plasma alodosterone concentration (> 15 ng/dL), PRA (28 ng/mL/hr), renal PI (21.15) and RI (20.7) were prognostic indicators in univariate analysis (p<0.05). Multivariate analysis disclosed two independent survival predictors of creatinine clearance rate (<80 mL/min) (OR:5.37, 95% CI: 209-1382) and plasma aldosterone concentration (215 ng/dL) (OR: 365, 95% Cl: 1.09-12.18). Conclusion: Various renal function indices are closely related to the survival of patients with liver cirrhosis. Creatinine clearance rate and plasma aldosterone concentration are especially important prognostic factors in predicting the survival of patients with liver cirrhosis. (Korean J Hepatol 200137:140-146) Key Words: Liver cirrhosis, Prognosis, Renal function, Doppler ultrasonography © GF Mores 441 19%: HAL AF ore 5a OR: Se) AMIY 5A Ig) © Abbreviations: Pl, pulsuiity index: PRA, plasma renin activity: Rl, resistive index. O AMAA MET, BUS OH MG WE AFA AH AFAR Aabrls OF) 220-701 Phone! O38) 741-C822: PAX: 083) 765-782: E-mail skbaik(@wonju,yonse.ac kr ‘ood MI Abr ebolotA) etal whestale. 140