Effects of saline or albumin resuscitation on acid base status and serum electrolytes


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Edward M. Omron MD, MPH
Pulmonary, Critical Care Medicine
Morgan Hill, CA 95037

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Effects of saline or albumin resuscitation on acid base status and serum electrolytes

  1. 1. absence of an adequate assessment of pa- tional goals . . . route of feeding . . . [or] en- REFERENCEStients’ nutritional status (at baseline, dur- teral formulas” but questions the wisdoming the phase of critical illness, and during of conducting a prospective study of early 1. Peake SLB, Moran JLM, Ghelani DRM, et al: The effect of obesity on 12-month survival followingrecovery) and of the nutritional support feeding on mortality on the basis of the admission to intensive care: A prospective study.administered to them (during those time (large) sample size required. However, Crit Care Med 2006; 34:2929 –2939periods), is premature. Further evidence Krenitsky (3) (cited in the letter by Dr. 2. Artinian V, Krayem H, DiGiovine B: Effects ofthrough well-conducted randomized trials Singh), reviewing the case for adjusted early enteral feeding on the outcome of criti-is required to tell whether the fat are indeed body weight in determining caloric re- cally ill mechanically ventilated medical pa-fit or not. quirements, laments the lack of large ran- tients. Chest 2006; 129:960 –967 domized trials. The need for “large scale 3. Krenitsky J: Adjusted body weight, pro: Evi- Navneet Singh, MD, Department of randomized evidence of moderate benefits” dence to support the use of adjusted body weight in calculating calorie requirements. Pulmonary Medicine, Post Graduate (4) would seem to be accepted by the crit- Nutr Clin Pract 2005; 20:468 – 473 Institute of Medical Education and Re- ical care community. Our reading of the 4. Peto R, Baigent C: Trials: The next 50 years. search (PGIMER), Chandigarh, India Krenitsky (3) article, and the counter view Large scale randomised evidence of moderate in the same issue by Ireton-Jones (5) benefits. BMJ 1998; 317:1170 –1171REFERENCES (“. . . it seems reasonable to use an equation 5. Ireton-Jones C: Adjusted body weight, con: Why that incorporates actual body weight”), adjust body weight in energy-expenditure calcu-1. Peake SL, Moran JL, Ghelani DR, et al: The which Dr. Singh does not cite, is that the lations? Nutr Clin Pract 2005; 20:474 – 479 effect of obesity on 12-month survival follow- evidential basis for the proposed body- DOI: 10.1097/01.CCM.0000259489.40571.65 ing admission to intensive care: A prospective weight adjustment coefficients, reflected in study. Crit Care Med 2006; 34:2929 –2939 the lack of agreement between these equa-2. Biolo G, Grimble G, Preiser JC, et al: Meta- Effects of saline or albumin tions and measured energy expenditure, bolic basis of nutrition in intensive care unit patients: Ten critical questions. Position paper does indeed vary between what “someone resuscitation on acid-base status of the ESICM Working Group on Nutrition once told me” (5) and a “2b recommenda- and serum electrolytes and Metabolism. Intensive Care Med 2002; tion at best” (3). Furthermore, if we believe, 28:1512–1520 with Dr. Singh and Krenitsky (3), that the To the Editor:3. Elamin EM: Nutritional care of the obese in- (inappropriate) use of actual body weight in tensive care unit patient. Curr Opin Crit Care I read with interest the recent study by calculating nutritional requirements would 2005; 11:300 –303 Bellomo et al. (1), in which the authors at- have resulted in “overestimation” (Dr.4. Artinian V, Krayem H, DiGiovine B: Effects of tempted to measure the sustained physico- Singh) of caloric expenditure in the obese early enteral feeding on the outcome of criti- chemical consequences of both normal saline or in “overfeeding” (Krenitsky), this would cally ill mechanically ventilated medical pa- and albumin resuscitation on acid-base status tients. Chest 2006; 129:960 –967 have had an adverse effect on precisely that during a period of 5 days in the acutely ill. It5. Krenitsky J: Adjusted body weight, pro: Evi- cohort (the obese) in whom a survival ben- is stated in the discussion that “the type of dence to support the use of adjusted body efit was observed. Any lack of recognition fluid . . . had a minor and probably clinically weight in calculating calorie requirements. that the “provision of optimal nutritional unimportant effect” on changes in acid-base Nutr Clin Pract 2005; 20:468 – 473 support . . . is an important component of status and that “the magnitude in changes inDOI: 10.1097/01.CCM.0000259496.86478.53 the management of (critically ill) obese pa- serum albumin alone seems unlikely to ac- tients” (Dr. Singh), for instance, by a delay count for the changes in pH.” I disagree withThe authors reply: in instituting such support, would poten- the authors’ conclusions and would com- The letter by Dr. Singh raises two ques- tially have had the same adverse effect on ment on a possibly unforeseen aspect in studytions that are perhaps tangential, although outcome. With respect to lack of informa- design. Table 3 of the article reveals that onnot intrinsically unimportant, to our recent tion on “either recent weight loss/gain or day 2, most of the administered albumin in-study (1), namely, the appropriate nutri- weight at admission to the hospital” and fusate in the albumin cohort had dissipatedtional support for the critically ill and the the effect this may have had on the “reli- out of the plasma compartment. In a 70-kgcorrect method for estimating body weight ability of weight taken,” such estimates person with 55% total body water, a 750-mLin obese patients. The thrust of the letter is would have been subject to patient or rel- infusion of 4% albumin would be expected tothat the survival advantage we reported (1) ative recall bias and would not have had the increase serum albumin from 2.64 g/dL tois confounded by potential variability in the status of estimated body mass index (aver- 2.89 g/dL. The actual mean increase in albu-provision of patient nutritional support and age of five independent estimates) used in min was 2.66 g/dL in the cohort. The studyby the use of actual body weight in com- our study. was thus reduced to an analysis of two solu-puting body mass index and patient caloric tions with similar physicochemical character-requirements. Our study was not designed istics (normal saline strong ion differenceto test a hypothesis regarding the appropri- Sandra L. Peake, BM BS, BSc(Hons), [SID] 0 mEq/L and the crystalloid compo-ateness, or otherwise, of the particular pro- FJFICM, PhD, John L. Moran, MBBS, nent of 4% albumin SID 6 mEq/L). Con-vision of nutritional support to outcome. FANZCA, FRACP, FJFICM, MD, Dhaval R. cordance of mean metabolic acid-base Dr. Singh cites a recent study reporting Ghelani, MD, FJFICM, Amanda J. Lloyd, changes (pH, base excess, and bicarbonate) inefficacy of early enteral feeding on intensive RN (ICU Cert), Michaela J. Walker, RN, B both cohorts was to be expected. If the resus-care unit and hospital outcome (2). It is Nurs, Grad Dip (ICN), Department of In- citation fluids initially chosen were moreperhaps ironic that the latter retrospective tensive Care Medicine, The Queen Eliza- widely disparate in SID, for example, one-halfstudy, sourced from a multi-institution da- beth Hospital, Woodville, South Australia, normal saline with 75 mEq/L bicarbonatetabase, provides no information on “nutri- Australia (SID 75 mEq/L) compared with normal1220 Crit Care Med 2007 Vol. 35, No. 4
  2. 2. REFERENCES 1. Bellomo R, Hiroshi M, Craig F, et al: The effects of saline or albumin resuscitation on acid-base status and serum electrolytes. Crit Care Med 2006; 34:2891–2897 2. Schlichtig R, Grogono A, Severinghaus J: Hu- man PaCO2 and standard base excess compen- sation for acid-base balance. Crit Care Med 1998; 26:1173–1179 3. Morgan T: Clinical Review: The meaning of acid-base abnormalities in the intensive care unit: Effects of fluid administration. Crit Care 2005; 9:204 –211 4. Omron E: Comparative quantitative acid-base analysis in coronary artery bypass, severe sep- sis, and diabetic ketoacidosis. J Intensive CareFigure 1. Partitioning standard base excess (SBE) into Delta strong ion difference effective (SIDe) and Med 2005; 20:269 –278Delta nonvolatile weak acid buffer (A ) in albumin cohort. 5. Fencl V, Jabor A, Kazda A, et al: Diagnosis of metabolic acid-base disturbances in critically ill patients. Am J Respir Crit Care Med 2000; 162:2246 –2251 DOI: 10.1097/01.CCM.0000259485.75423.42 The author replies: We read with interest the comments by Dr. Omron concerning our recent article on the effects of saline and albumin resus- citation on acid-base status and serum elec- trolytes (1), a sub-study of the SAFE trial (2). We agree that, given the limited differ- ences in strong ion difference between the fluids, what we report would have been the most likely expected outcome of the study. However, given the known effect of albu- min on acid-base physiology, the expectedFigure 2. Partitioning standard base excess (SBE) into Delta strong ion difference effective (SIDe) and increase in serum albumin concentrationDelta nonvolatile weak acid buffer (A ) in normal saline cohort. with its intravenous administration, the tendency of saline to rapidly move outside the intravascular compartment faster thansaline (SID 0 mEq/L), a larger and sus- ently normal SBE. The loss of plasma weak albumin, the possibility existed that a dif-tained physicochemical consequence would acid buffer content is equivalent to a gain in ferential effect would be seen. We consid-have been detected over the study period. base or a hypoalbuminemic alkalosis (5). ered that if such an effect existed, critical Crystalloid infusion modifies standard Beyond day 2 in both cohorts, the resolu- care clinicians should be aware of it, be-base excess (SBE) (2) and ultimately pH by tion of strong anion excess had begun, with cause it would help them understand thesimultaneously altering plasma strong ion concurrent unmasking of the hypoalbu- acid-base consequences of fluid expansiondifference effective (SIDe) and nonvolatile minemic alkalosis, thus accounting for the with a given solution in greater detail. Theweak acid buffer content (A ), of which development of a metabolic alkalosis after separate and differential effect of albuminserum albumin is the major determinant day 2. The effects of hypoalbuminemia resuscitation on serum chloride seen in(3, 4). SBE relates to SIDe and A by the completely account for the evolution of a patients treated with larger amounts of flu-relationship: SBE Delta SIDe Delta A metabolic alkalosis during the clinical re- ids, for example, had not been previously(4). The prefix Delta refers to the deviation of covery phase. Without partitioning the SBE reported. We believe, however, that weSIDe and A from normal values (SIDe 39 into physicochemical components, this al- might have been misunderstood in our de-mEq/L and A , where albumin 4.3 g/dL, kalinizing effect would not be realized. scription of the effects of albumin on acid-inorganic phosphate 3.6 mg/dL). Figures 1 The author has not disclosed any per- base physiology. When we say that “theand 2 plot SBE, Delta SIDe, and Delta A in sonal or financial conflicts of interest magnitude in changes in serum albuminboth 4% albumin and normal saline cohorts with regard to this publication. alone seems unlikely to account for thefrom baseline to day 5. At baseline in both changes in pH,” we refer to the relativecohorts, the initial metabolic acidosis from Edward M. Omron, MD, MPH, FCCP, differences in serum albumin changes fromstrong anion excess, the negative Delta Pulmonary and Critical Care Special- baseline with saline vs. albumin in relationSIDe, was balanced by the alkalinizing ef- ists, Novi, MI; and the Department of to the relative change in pH and base excessfect of a nonvolatile weak acid buffer deficit, Medicine, Uniform Services University from baseline in each group. An increase inpositive Delta A , resulting in an appar- of Health Sciences, Bethesda, MD serum albumin concentration of 10 g/L canCrit Care Med 2007 Vol. 35, No. 4 1221
  3. 3. be calculated to account for an additional provements have set off intensivists to- Table 1. Descending trend in hypoglycemia with2.5 mEq/L of base excess change toward ward early, tight insulin hyperglycemia each new protocol revisionacidification (3). The relative difference for control (2– 4). Such an approach will un- Protocol Patients Incidence ofthe change in mean serum albumin con- doubtedly expose patients to the risk of Revision on Hypoglycemic Hypoglycemiccentration from baseline was 1.1 g/L be- hypoglycemia, a complication difficult to Version Protocol Events Eventstween the two groups. This difference recognize in noncommunicative, sedated,would account for an albumin-associated mechanically ventilated patients, who Original 5 22 4.40acidifying effect of approximately 0.3 constitute approximately half of a medi- Draft 1 12 25 2.08mEq/L. The difference for the change in cal intensive care unit population (5). Draft 2 17 21 1.23 Draft 3 13 13 1.00base excess, however, was 1.1 mEq/L. Thus, Of note, this report presents decreasing Draft 4 23 5 0.21we continue to argue that changes in albu- hypoglycemia rates (7.6—0.3%) with inten-min concentration alone cannot account sive insulin treatment. The problem here isfor the changes in base excess values seen in the denominators used for calculations.in our patients. Importantly, however, our Multiple (hourly) glucose measurements in We agree that accurate complication re-statement does not refer to the absolute a given patient are not independent events; porting is imperative when implementingchanges in albumin over time with either they are autocorrelated. The proper report- an intensive insulin protocol; however,group. Persistent hypoalbuminemia, as Dr. ing of hypoglycemia should express: pa- the number of glucose checks per day wasOmron correctly points out in his letter, tients with hypoglycemia events ( 80 mg/ not different over time in the differentdid significantly contribute to the meta- dL)/patients exposed to treatment, as in iterations of the protocol. Therefore,bolic alkalosis seen after day 3 in both Table 4 of the article (5/23 21%), and not events per sample equate to fewer eventsgroups, once the strong ion difference ef- as events/samples. per patient. Expressing the data as pa-fect abated. Finally, we agree with Dr. Om- Appropriate complication reporting is of tients with hypoglycemic events/numberron that analysis of complex acid-base extreme importance as community non- of patients exposed to treatment yieldschanges in critically ill patients can only be teaching hospitals’ event rates with inten- the same descending trend in hypoglyce-logically conducted using Stewart’s meth- sive insulin treatment may be in excess of mia with each new protocol revision (Ta-odology (4). those observed in a tightly monitored study ble 1). trial in a university hospital. As expressed in the letter by Dr. Freire Rinaldo Bellomo, MD, FRACP, FJFICM, and colleagues, we accept that there are Intensive Care, Austin Hospital, Heidel- Amado X. Freire, MD, MPH, Jaime F. additional challenges in community hos- berg, Australia Avecillas, MD, José C. Yataco, MD, pitals. One purpose of sharing our data Nancy E. Freire, MD, Division of Pul- was to reinforce the importance of pilotingREFERENCES monary, Critical Care, and Sleep Med- intensive insulin protocols in small, closely icine, University of Tennessee Health observed populations before wide dissemi-1. Bellomo R, Morimatsu H, French C, et al: The Science Center COM at Memphis, nation. Furthermore, we believe that before effects of saline or albumin resuscitation on Memphis, TN all hospitals adopt such a guideline, addi- acd-base status and serum electrolytes. Crit Care Med 2006; 34:2891–2897 tional primary data on patient benefit in REFERENCES medical intensive care units and on non-2. The SAFE Study Investigators: A comparison of albumin and saline for fluid resuscitation in 1. Clayton SB, Mazur JE, Condren S, et al: Eval- sepsis diagnoses are needed. the intensive care unit. N Engl J Med 2004; uation of an intensive insulin protocol for Because of the requests for the Medi- 350:2247–2256 septic patients in a medical intensive care cal University of South Carolina (MUSC)3. Liskaser FJ, Bellomo R, Hayhoe M, et al: Role unit. Crit Care Med 2006; 34:2974 –2978 protocol, it is provided with this response of pump primein the etiology and pathogene- 2. van den Berghe G, Wouters P, Weekers F, et online at http://www.ccmjournal.org. sis of cardiopulmonary bypass-associated aci- al: Intensive insulin therapy in the critically ill This protocol is provided as a starting dosis. Anesthesiology 2000; 93:1170 –1173 patients. N Engl J Med 2001; 345:1359 –1367 point for further adaptations, and the4. Stewart PA: Modern quantitative acid-base 3. Krinsley JS: Effect of an intensive glucose management protocol on the mortality of crit- Medical University of South Carolina ac- chemistry. Can J Physiol Pharmacol 1983; 61:1444 –1461 ically ill adult patients. Mayo Clin Proc 2004; cepts no liability for its use. 79:992–1000DOI: 10.1097/01.CCM.0000261218.55180.97 4. van den Berghe G, Wilmer A, Hermans G, et Stephanie B. Clayton, PharmD, BCPS, al: Intensive insulin therapy in the medical Baptist Hospital, Nashville, TN;Hypoglycemia risk: A cause for ICU. N Engl J Med 2006; 354:449 – 461 Charlie Strange, MD, Medical Univer- 5. Freire AX, Bridges L, Umpierrez GE, et al: Ad- sity of South Carolina, Charleston, SCconcern in the intensive care unit mission hyperglycemia and other risk factors ashyperglycemia control debate predictors of hospital mortality in a medical ICU population. Chest 2005; 128:3109 –3116 REFERENCETo the Editor: DOI: 10.1097/01.CCM.0000259490.04729.9E 1. Clayton SB, Mazur JE, Condren S, et al: Eval- Clayton and colleagues (1) describe a uation of an intensive insulin protocol foruseful protocol of insulin infusion to con- The authors reply: septic patients in a medical intensive caretrol hyperglycemia in a medical intensive We thank Dr. Freire and colleagues for unit. Crit Care Med 2006; 34:2974 –2978care unit. Recent reports of outcome im- their comments regarding our study (1). DOI: 10.1097/01.CCM.0000259547.35467.B61222 Crit Care Med 2007 Vol. 35, No. 4