Hyperchloremic Metabolic Acidosis Is a Predictable Consequence of Intraoperative Infusion of 0.9% Saline
Prough, Donald S. MD1; Bidani, Akhil MD, PhD2
This Editorial View accompanies the following article: Scheingraber S, Rehm M, Sehmisch C, Finsterer U: Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology 1999; 90:1265–70.
IN this issue of Anesthesiology, Scheingraber et al. [1
] quantify two phenomena that are important to anesthesiologists and other clinicians caring for perioperative patients: (1) intravenous infusion of 0.9% saline in patients undergoing gynecologic surgery results in hyperchloremic metabolic acidosis and (2) intravenous infusion of either 0.9% saline or lactated Ringer's solution results in hypoproteinemia and a decreased anion gap. Although neither of these observations is surprising, no other data define so clearly the expected effects of conventional intravenous therapy in a population of patients undergoing common procedures of intermediate magnitude. Clarification of these effects is important in interpreting perioperative acid‐base changes and in assessing the need for treatment to modify those changes.
A brief review of the key observations of this study is necessary to appreciate its importance. Scheingraber et al. [1
] randomized 24 women to receive either 0.9% saline or lactated Ringer's solution while undergoing elective gynecologic lower abdominal surgery. During surgical procedures averaging slightly more than 2 h in duration, subjects lost a mean volume of approximately 850 ml blood, received a mean volume of either of the two crystalloids of almost 70 ml/kg, and excreted a mean volume of almost 900 ml urine. During the first 2 h of saline infusion, the serum bicarbonate concentration (HCO3‐
), calculated from the Henderson‐Hasselbalch equation) decreased from 23.5 +/‐ 2.2 mM to 18.4 +/‐ 2.0 mM. The anion gap concentration decreased from 16.2 +/‐ 1.2 mM to 11.2 mM, and the mean serum chloride concentration (Cl‐
) increased from 104 to 115. During the same interval, HCO3‐
in the group receiving lactated Ringer's solution remained similar (23.8 +/‐ 2.0 mM and 23.2 +/‐ 1.7 mM), the anion gap decreased from 15.2 +/‐ 1.4 mM to 12.1 mM, and the mean Cl‐
increased from 104 mM to 106 mM.
The occurrence of hyperchloremic acidosis in the saline group, although consistent with the anecdotal experience of clinicians who have infused large volumes of saline intraoperatively, [2–4
] appears to contradict traditional thinking about acid‐base balance, i.e., that saline infusion alone is unlikely to significantly alter HCO3‐
. Perhaps the most striking experimental evidence supporting that concept is that of Rosenbaum et al., [5
] who infused 50, 75, and 100 ml/kg 0.9% saline over 30 min in anephric dogs and demonstrated decreases in HCO3‐
of only 2.4 +/‐ 0.7, 2.5, and 3.0 mM, respectively, 1 h after infusion. They concluded that the relatively slow infusion rate, coupled with "appropriate cellular buffering," explained the small changes and that the "clinical significance of acute extracellular expansion with saline is moot." In contrast, Scheingraber et al. [1
] infused 70 ml/kg of saline over 120 min in patients with normal renal function and reported decreases in HCO3
) that were twice as large. Apart from the obvious difference in species, no reasons for the disparate findings are apparent.
Curiously, the general concept of hyperchloremic acidosis was infrequently discussed in the anesthesiology literature before 1994. Subsequently, clinical reports described this entity as a consequence of administration of unusually large volumes of saline, most often during prolonged procedures, such as major hepatobiliary or pancreatic surgery, [6
] anterior spinal fusion, [3
] and bilateral nephrectomy. [4
] In the latter two case reports, preexisting urinary tract disease was a possible confounding variable. Miller et al. [2,7
] responded to each of these case reports with letters to the editor emphasizing the pathogenetic role of large volumes of saline and extensive surgery. In contrast to previous reports, Scheingraber et al. [1
] provide unequivocal evidence that hyperchloremic acidosis is a predictable accompaniment of saline administration during procedures of even moderate duration.
One might argue that this study is misleading because the total fluid infused by Scheingraber et al. [1
] was excessive for surgical procedures of intermediate magnitude. Patients in the saline group received a total of almost 5,000 ml during the first 120 min of their procedures. However, using conventional crystalloid:blood replacement ratios of 3:1 or 5:1 to replace a mean blood loss of 962 +/‐ 332 ml would require comparable volumes. Therefore, these data should apply to routine clinical practice.
Moreover, in nonsurgical circumstances involving fluid resuscitation with saline, the occurrence of hyperchloremic acidosis has long been recognized. Because 0.45% and 0.9% saline conventionally are used for fluid resuscitation of patients with diabetic ketoacidosis, hyperchloremic acidosis routinely develops during treatment of the hypovolemia associated with this disorder. [8
] Of course, in diabetic ketoacidosis, additional factors contributing to ketoacidosis include the consumption of HCO3‐
in buffering of ketoacids and the loss in the urine of ketoacids that otherwise would be converted to HCO3‐
in the liver.
The study by Scheingraber et al. [1
] also elucidates the influence of perioperative protein dilution on the calculated anion gap. In the two groups, serum proteins decreased from 6.2 to 4.3 g/dl in association with the previously noted decreases in the anion gap. The anion gap is a useful, if imperfect, tool for distinguishing metabolic acidoses, such as ketoacidosis, lactic acidosis, and uremic acidosis, that increase the anion gap from hyperchloremic acidosis, in which the anion gap does not increase. [9
] These observations by Scheingraber et al. [1
] show both the usefulness of assessing the anion gap in managing postoperative metabolic acidosis and the influence of hypoalbuminemia on the anion gap. Because approximately 75% of the normal anion gap is composed of the negatively charged albumin molecule, [9
] both the chronic hypoalbuminemia that accompanies critical illness and the acute dilutional hypoalbuminemia that accompanies rapid crystalloid infusion effectively reduce the upper limit of the normal range of the anion gap. Recently, Figge et al., [10
] based on analysis of blood samples from 9 healthy subjects and 152 critically ill patients, demonstrated that a reduction in serum albumin of 1 g/dl reduced the anion gap by 2.5 mEq/l. Although Scheingraber et al. [1
] do not separate total protein measurements into serum albumin and other proteins, their results are generally consistent with a change of similar magnitude during acute dilutional hypoalbuminemia.
What these data fail to address is the influence, if any, of acute hypoalbuminemia on acid‐base balance in this study. An assumption, based in part on the Stewart approach to acid‐base interpretation, [11
] is that hypoalbuminemia produces metabolic alkalosis that can be reversed by infusion of albumin. Although in vitro data show a linear correlation between albumin concentration and HCO3‐
] the effects of a decrease in total protein of only 2 g/dl, of which a little more than half presumably would represent a decrease in serum albumin, would not be expected to cause a clinically important decrease in HCO3‐
The most important question posed by this study is whether these data should prompt any alteration in clinical management. Mathematically, these data suggest that lactated Ringer's solution is preferable to 0.9% saline because it causes less acid‐base disturbance. However, the changes in serum sodium concentration (Na+
) also merit discussion. One theoretical reason to use 0.9% saline rather than lactated Ringer's solution in patients at risk for intracranial hypertension is that an increase in Na+
will tend to reduce brain water, whereas a decrease in Na+
will tend to increase brain water. [13
] At 120 min into the study by Scheingraber et al., [1
was >or= to 3.5 mM greater in the saline group. This equates to a difference in serum osmolality of >or= to 7.0 mOsm/kg and in serum osmotic pressure of >or= to 135 mmHg. Theoretically, a difference of this magnitude should influence brain water and intracranial pressure.
Is hyperchloremic metabolic acidosis hazardous? Most evidence suggests that it is not. However, correct treatment is absolutely dependent on differentiation of hyperchloremic acidosis from lactic acidosis. Aggressive attempts to improve organ perfusion, based on misdiagnosis of lactic acidosis, could prove harmful. These data show the value of using the anion gap to support the diagnosis of acute dilutional hyperchloremic acidosis. However, they also provide the caveat that the anion gap must be interpreted in light of any accompanying acute hypoalbuminemia. In the presence of an acute decrease in serum albumin, the anion gap should be decreased proportionately; if it is not, other causes of metabolic acidosis should be considered.
Donald S. Prough, M.D.
Rebecca Terry White Distinguished Chair; Department of Anesthesiology; firstname.lastname@example.org
Akhil Bidani, M.D., Ph.D.
Professor and Chief; Section on Pulmonary Medicine and Critical Care; Department of Medicine; The University of Texas Medical Branch; Galveston, Texas 77555–0591
1. Scheingraber S, Rehm M, Sehmisch C, Finsterer U: Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology 1999; 90:1265-70
2. Miller LR, Waters JH: Mechanism of hyperchloremic nonanion gap acidosis. Anesthesiology 1997; 87:1009-10
3. Azzam FJ, Steinhardt GF, Tracy TF Jr, Gabriel KR: Transient perioperative metabolic acidosis in a patient with ileal bladder augmentation. Anesthesiology 1995; 83:198-200
4. Mathes DD, Morell RC, Rohr MS: Dilutional acidosis: Is it a real clinical entity? Anesthesiology 1997; 86:501-3
5. Ronsenbaum BJ, Makoff DL, Maxwell MH: Acid-base and electrolyte changes induced by acute isotonic saline in the nephrectomized dog. J Lab Clin Med 1969; 74:427-35
6. McFarlane C, Lee A: A comparison of Plasmalyte 148 and 0.9% saline for intra-operative fluid replacement. Anaesthesia 1994; 49:779-81
7. Miller LR, Waters JH, Provost C: Mechanism of hyperchloremic metabolic acidosis. Anesthesiology 1996; 84:482-3
8. Adrogue HJ, Wilson H, Boyd AE III, Suki WN, Eknoyan G: Plasma acid-base patterns in diabetic ketoacidosis. N Engl J Med 1982; 307:1603-10
9. Oh MS, Carroll HJ: The anion gap. N Engl J Med 1977; 297:814-7
10. Figge J, Jabor A, Kazda A, Fencl V: Anion gap and hypoalbuminemia. Crit Care Med 1998; 26:1807-10
11. Fencl V, Rossing TH: Acid-base disorders in critical care medicine. Annu Rev Med 1989; 40:17-29
12. Rossing TH, Maffeo N, Fencl V: Acid-base effects of altering plasma protein concentration in human blood in vitro. J Appl Physiol 1986; 61:2260-5
13. Zornow MH, Todd MM, Moore SS: The acute cerebral effects of changes in plasma osmolality and oncotic pressure. Anesthesiology 1987; 67:936-41
This article has been cited 46 time(s).
Anesthesia and AnalgesiaEarly postoperative respiratory acidosis after large intravascular volume infusion of lactated Ringer's solution during major spine surgeryAnesthesia and Analgesia
AnaesthesistThe Stewart model. "Modern" approach to the interpretation of the acid-base metabolismAnaesthesist
Anesthesia and AnalgesiaNew light on intravascular volume replacement regimens: What did we learn from the past three years?Anesthesia and Analgesia
Anesthesia and Analgesia
The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients
Anesthesia and Analgesia, 93(4):
Sepsis, Kidney and Multiple Organ Dysfunction
Intravenous fluids and acid-base balance
Sepsis, Kidney and Multiple Organ Dysfunction, 144():
Severe metabolic acidosis resulting from a dislocated gastric band
Obesity Surgery, 14(4):
Journal of Trauma-Injury Infection and Critical Care
Burn resuscitation with two doses of 4 mL/kg hypertonic saline dextran provides sustained fluid sparing: A 48-hour prospective study in conscious sheep
Journal of Trauma-Injury Infection and Critical Care, 49(2):
Anasthesiologie & Intensivmedizin
Recommendations for per-operative infusion therapy for newborn,infant and babies - By scientific work group children anaesthesia of German society for Anaesthesiology and intensive care (DGAI)
Anasthesiologie & Intensivmedizin, 48():
Renal FailureEffects of normal saline vs. lactated ringer's during renal transplantationRenal Failure
Intensive Care MedicineCrystalloid strong ion difference determines metabolic acid-base change during acute normovolaemic haemodilutionIntensive Care Medicine
Critical CareClinical review: The meaning of acid-base abnormalities in the intensive care unit - effects of fluid administrationCritical Care
Intensive Care MedicineA critique of Stewart's approach: the chemical mechanism of dilutional acidosisIntensive Care Medicine
Archives of Disease in Childhood
Hyperchloraemic acidosis in patients given rapid isotonic saline infusions
Archives of Disease in Childhood, 92(6):
AnaesthesiaMetabolic acidosis in the critically ill: Part 2. Causes and treatmentAnaesthesia
Emergency Medicine JournalComparison of lactated Ringer's solution and 0.9% saline in the treatment of rhabdomyolysis induced by doxylamine intoxicationEmergency Medicine Journal
Avoiding latrogenic hyperchloremic acidosis - Call for a new crystalloid fluid - Reply
Anesthesia and Analgesia
Perioperative fluid management
Anesthesia and Analgesia, 94(3):
(Ab)normal saline and physiological Hartmann's solution: a randomized double-blind crossover study
Clinical Science, 104(1):
Journal of Applied PhysiologyPrediction of dilutional acidosis based on the revised classical dilution concept for bicarbonateJournal of Applied Physiology
Clinical NutritionThe history of 0.9% salineClinical Nutrition
Anesthesia and Analgesia
Are lactated Ringer's solution and normal saline solution equal with regard to coagulation?
Anesthesia and Analgesia, 94(2):
Fluid resuscitation for the trauma patient
Feasibility of a porcine adult intensive care model
Comparative Medicine, 54(1):
Critical CareCauses and effects of hyperchloremic acidosis - ReponseCritical Care
Article supports findings of previous comparison
Annales Francaises D Anesthesie Et De ReanimationHyperchloraemic metabolic acidosis during plasma volume replacementAnnales Francaises D Anesthesie Et De Reanimation
American Journal of Physiology-Heart and Circulatory Physiology
Pyruvate improves cerebral metabolism during hemorrhagic shock
American Journal of Physiology-Heart and Circulatory Physiology, 281(2):
Anesthesia and Analgesia
Perioperative fluid management
Anesthesia and Analgesia, ():
Anaesthesia and Intensive Care
Acid-base and bio-energetics during balanced versus unbalanced normovolaemic haemodilution
Anaesthesia and Intensive Care, 35(2):
Anaesthesia and Intensive Care
Acid-base effects of a bicarbonate-balanced priming fluid during cardiopulmonary bypass: comparison with Plasma-Lyte 148. A randomised single-blinded study
Anaesthesia and Intensive Care, 36(6):
Critical CareQuantitative physico-chemical analysis of the acidosis of cardiac arrestCritical Care
Perioperative fluid management - Response
Wiener Klinische WochenschriftWhy are infusion solutions so (badly) combined? A historical perspectiveWiener Klinische Wochenschrift
Schweizerische Medizinische Wochenschrift
Volume therapy in hypotensive trauma patients
Schweizerische Medizinische Wochenschrift, 130():
Anions and the anaesthetist
Critical CareBench-to-bedside review: Treating acid-base abnormalities in the intensive care unit - the role of renal replacement therapyCritical Care
Anasthesiologie & Intensivmedizin
Perioperative fluid and volume therapy in children
Anasthesiologie & Intensivmedizin, 51():
Anesthesia and AnalgesiaHyperchloremic acidosis in the critically ill: One of the strong-ion acidoses?Anesthesia and Analgesia
Critical Care MedicineThe effects of saline or albumin resuscitation on acid-base status and serum electrolytes*Critical Care Medicine
Critical Care MedicineIll effects of sodium chlorideCritical Care Medicine
Current Opinion in AnesthesiologySaline versus balanced hydroxyethyl starch: does it matter?Current Opinion in Anesthesiology
Anion gap; bicarbonate; lactated Ringer's solution; serum albumin
© 1999 American Society of Anesthesiologists, Inc.
Publication of an advertisement in Anesthesiology Online does not constitute endorsement by the American Society of Anesthesiologists, Inc. or Lippincott Williams & Wilkins, Inc. of the product or service being advertised.
Highlight selected keywords in the article text.