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Clinical Investigations

Rapid Saline Infusion Produces Hyperchloremic Acidosis in Patients Undergoing Gynecologic Surgery

Scheingraber, Stefan MD; Rehm, Markus MD; Sehmisch, Christiane; Finsterer, Udilo MD

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Background: Changes in acid‐base balance caused by infusion of a 0.9% saline solution during anesthesia and surgery are poorly characterized. Therefore, the authors evaluated these phenomena in a dose‐response study.
Methods: Two groups of 12 patients each who were undergoing major intraabdominal gynecologic surgery were assigned randomly to receive 0.9% saline or lactated Ringer's solution in a dosage of 30 ml [middle dot] kg‐1 [middle dot] h‐1. The pH, arterial carbon dioxide tension, and serum concentrations of sodium, potassium, chloride, lactate, and total protein were measured in 30‐min intervals. The serum bicarbonate concentration was calculated using the Henderson‐Hasselbalch Equation andalso using the Stewart approach from the strong ion difference and the amount of weak plasma acid. The strong ion difference was calculated as serum sodium + serum potassium ‐ serum chloride ‐ serum lactate. The amount of weak plasma acid was calculated as the serum total protein concentration in g/dl [middle dot] 2.43.
Results: Infusion of 0.9% saline, but not lactated Ringer's solution, caused a metabolic acidosis with hyperchloremia and a concomitant decrease in the strong ion difference. Calculating the serum bicarbonate concentration using the Henderson‐Hasselbalch Equation orthe Stewart approach produced equivalent results.
Conclusions: Infusion of approximately 30 ml [middle dot] kg‐1 [middle dot] h‐1 saline during anesthesia and surgery inevitably leads to metabolic acidosis, which is not observed after administration of lactated Ringer's solution. The acidosis is associated with hyperchloremia.
This article is accompanied by an Editorial View. Please see Prough DS, Bidani A: Hyperchloremic metabolic acidosis is a predictable consequence of intraoperative infusion of 0.9% saline. Anesthesiology 1999; 90:1247–9.
DESPITE the common practice of crystalloid infusion during surgery, few data have been published that describe acid‐base changes associated with infusion of 0.9% saline. The recognition that 0.9% saline contains chloride in a nonphysiologic concentration led to the introduction of lactated Ringer's solution. [1] Only a few experimental data [2–4] and some recent case reports [5–8] exist that support the occurrence of metabolic acidosis in the course of large 0.9% saline infusions. This acidosis is still called "dilutional acidosis." [9] All published studies are based on traditional knowledge of the acid‐base balance. [10] By comparing two groups of patients who received 0.9% saline or lactated Ringer's solution, we assessed the influence of crystalloid infusion on acid‐base changes. We planned to compare the changes in serum bicarbonate concentration (Bic), as calculated by the Henderson‐Hasselbalch Equation withthose calculated using the Stewart equations. Fifteen years ago, Stewart developed a mathematically derived approach to acid‐base chemistry. [11]
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Materials and Methods

We studied 24 women without apparent cardiac, pulmonary, or renal diseases (classified as American Society of Anesthesiologists physical status I or II) who were scheduled for elective lower abdominal gynecologic surgery. Written informed consent was obtained from each patient before surgery, and the protocol was approved by the ethics committee of our institution. During the study, no patient received colloids, plasma products, or blood transfusions. The patients were assigned randomly to receive either 0.9% saline (saline group, n = 12) or lactated Ringer's solution (Ringer's group, n = 12). The saline solution contained 154 mM sodium and 154 mM chloride; the lactated Ringer's solution contained 130 mM sodium, 5.4 mM potassium, 1.8 mM calcium, 112 mM chloride, and 27 mM lactate.
General anesthesia was induced with intravenous thiopental, sufentanil, and cisatracurium. After tracheal intubation, anesthesia was maintained with isoflurane, 0.4–1.5 vol% in an oxygen‐nitrous oxide mixture of 1:1, and additional doses of sufentanil and cisatracurium as appropriate. Radial arterial and central venous catheters were inserted. Mechanical ventilation was performed to maintain the arterial oxygen tension (PaO(2)) at 250–300 mmHg and the arterial carbon dioxide pressure (PaCO(2)) as close as possible to 40 mmHg. Intraoperative monitoring included end‐tidal PaCO(2), cardiac electric activity, central venous pressure, arterial blood pressure, pulse oximetry, and esophageal temperature. During the operative period, the patient's temperature was kept constant using fluid warmers and warming blankets.
During stable anesthetic conditions and at the time of surgical incision, the investigation was started and arterial blood was withdrawn to measure baseline values (time = 0 min). The samples were analyzed for PaO(2), pH, PaCO(2) (using standard electrodes), the concentrations of serum sodium (Na+), potassium (K+), chloride (Cl) (using ion‐selective electrodes), and serum lactate (Lac) (using the enzymatic method, quantification of hydrogen peroxide) all integrated using a Radiometer analyzer (Radiometer ABL 620 GL; Radiometer Company, Copenhagen, Denmark). In addition, the serum total protein concentration was determined using the Biuret method. After the baseline blood samples were collected, the crystalloid infusion (0.9% saline vs. lactated Ringer's solution) was started. We planned an infusion rate of 30 ml [middle dot] kg‐1 [middle dot] h‐1 in both groups using a common infusion device. Every 30 min, new blood samples were taken, urine production and temperature were measured, and blood loss was estimated. When K+ was less than 3.3 mM, 20 mmol potassium chloride solution, 1 M, was infused with the next infusion bottle. This was necessary in eight patients in the 0.9% saline group and in two patients in the Ringer's solution group.
For each sample, the strong ion difference (SID) was calculated as Na+ + K+ ‐ Cl ‐ Lac. The amount of weak plasma acid was calculated as the product of the serum total protein concentration (g/dl) and the empirically derived factor 2.43, according to van Slyke [12] and called "Prot." The Bic (BicHH) and base excess (BE) were taken from the blood gas analyzer, which uses the Henderson‐Hasselbalch Equation andthe formula of Siggaard‐Andersen. [10] In addition, the Bic was calculated as the difference between SID and Prot (BicS) using the Stewart model. The anion gap was calculated as Na+ + K+ ‐ Cl ‐ BicHH.
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Statistical Analysis
Because all measured and calculated data described before were normally distributed (according to the Kolmogorov‐Smirnov test), they are presented as mean values with standard deviations. For demographic data, Student t tests for unpaired data were performed. Two‐way repeated‐measures analysis of variance compared intragroup and intergroup differences at 30, 60, 90, and 120 min of crystalloid infusion with 0 min. Post hoc testing was performed according to the Student‐Newman‐Keuls method for multiple comparisons. P < 0.05 was considered significant.
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Table 1
Table 1
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Figure 1
Figure 1
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(Table 1) presents patient characteristics. There were no significant differences in weight, height, body surface area, and time of infusion. Because of differences in the duration of surgery, individual differences occurred in infusion times. The total amount of fluid infused during this time was similar and amounted to a mean of approximately 6,000 ml in both groups. Because data for all patients are only complete to 120 min of infusion time beyond that point no mean values are presented (Figure 1). As shown in Table 1, at this point, the volume of crystalloid infusion in relation to body weight also was not significantly different in either groups and was in line with our planned infusion volume (noted previously). Furthermore, there were no significant differences between the groups with respect to estimated blood loss and urine production. The hemoglobin concentration decreased from approximately 12 g/dl to 9 g/dl in both groups (intergroup comparisons, P > 0.05; data not shown).
In Figure 1, pH, PaCO(2), BE, Lac, Na+, Cl, SID, and Prot are shown at the various measuring points described before. During infusion of the crystalloid solution, pH decreased significantly from 7.41 to 7.28 in the saline group. No major pH changes were observed in the patients who received Ringer's solution. In both groups, Pa (CO)(2) did not show major deviations from 40 mmHg. Changes in BE were similar to changes in pH. In the saline group, starting from a control value of ‐0.4 mM, BE decreased to ‐6.7 mM at 120 min. There were no major changes in BE in the Ringer's group. In the saline group, starting from a low level of 0.6 mM, Lac decreased to a mean of 0.4 mM. During the infusion of lactated Ringer's solution, Lac increased slightly to approximately 2 mM. Infusion of 0.9% saline solution led to a slow and continuous increase in Na+. There was a slight but significant decrease in Na+ in the Ringer's group, in which the infused solution contained only 130 mM sodium. Cl increased in both groups, but this increase was by far larger with the application of the 0.9% saline solution. During administration of 0.9% saline, Cl increased from 104 mM to a mean of 115 mM. With the application of lactated Ringer's solution, which contained 112 mM chloride, a slight but significant increase in Cl from 104 mM to 106 mM occurred. K (+) (data not shown) was maintained at a level of approximately 4 mM by substituting potassium as needed (see Materials and Methods), and it did not show any intragroup or intergroup differences.
Table 2
Table 2
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The SID decreased initially in both groups. With a continuous 0.9% saline infusion, the decrease was significantly larger, approximately 9 mM, compared with the decrease that occurred with lactated Ringer's solution. Because of dilution with crystalloids and surgical bleeding, the serum total protein concentration decreased in both groups from a mean of approximately 6.2 g/dl to 4.3 g/dl. In Figure 1, the mean serum total protein concentration is presented as Prot calculated with the factor 2.43, as described before. In Table 2, mean values for BicHH, BicS, anion gap, and the difference of anion gap and Prot are shown. The mean values for BicHH and BicS were virtually identical in both groups. It should be noted that BicHH represents the gold standard calculation using the Henderson‐Hasselbalch equation, whereas BicS was obtained using only Na+, K+, Cl, Lac, and Prot. In the saline group, BicHH and BicS decreased from approximately 23 mM to 18 mM. No major changes in BicHH and BicS occurred in the Ringer's solution group. The anion gap showed similar changes in both groups, with a decrease from approximately 16 mM to 12 mM during the period of crystalloid infusion. The difference of anion gap and Prot was slightly positive in both observation groups at all measuring points, with nearly identical values in both groups and a slight increase from approximately 1 mM to 2 mM during the observation period.
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The main finding of this study was a rather impressive acidosis (7.41 to 7.28) after a relatively brief interval (2 h) of 0.9% saline infusion, but not after lactated Ringer's solution infusion at rates of approximately 35 ml [middle dot] kg‐1 [middle dot] h‐1 during anesthesia and surgery. This acidosis with the 0.9% saline infusion clearly had a metabolic origin, because PaCO(2) was kept constant and there was no lactic acidosis, because Lac even decreased slightly. Although described before, [2–4] there seems to be great uncertainty about the effects of large 0.9% saline infusions on acid‐base balance, as shown by a few recent case reports [5–8] and several letters to the editor. [13–17] Our finding of metabolic acidosis associated with 0.9% saline, but not with lactated Ringer's solution, can be interpreted in two ways, and they seem to be contradictory. [18] The conventional Henderson‐Hasselbalch or Siggaard‐Andersen approach [10] tells us that metabolic acidosis occurred in the saline group as shown by constant PaCO(2) and decreasing BicHH and BE, whereas in the Ringer's group no significant change occurred in the acid‐base balance. Undoubtedly, hyperchloremia would be identified as the main cause of this metabolic acidosis.
The Stewart approach, which is discussed in detail elsewhere, [19] defines PaCO(2), SID, and the sum of all anionic charges of weak plasma acids (called Atot by Stewart and calculated in the way we calculated Prot) as independent pH‐regulating variables, whereas pH and the Bic are dependent variables. [11] The Stewart approach has been applied less commonly in the last decade. Only a few studies in exercise medicine, [20,21] experimental medicine, [22] and critical care medicine [23–26] have used this model. In discussing this model, two methodologic aspects are important: our method of measuring lactate, and the estimation of the anionic component of weak plasma acids in conjunction with the problem of undefined cations and anions.
First, the lactate electrode incorporated in the blood gas and electrolyte analyzer used in this study measures L (+) lactate, which is the form that naturally occurs in blood. The lactated Ringer's solution used in this study (27 mM lactate) is racemic, with L (+) lactate being the dominant fraction. Analyzing this product provided lactate values of approximately 21 mM for pure solution, approximately 12 mM for a 1:1 dilution with normal saline, and 2.5 mM for a 1:10 dilution with saline. Therefore, the values for Lac shown in Figure 1 and used to calculate SID might be correct indeed.
Second, estimating the net anionic charges of weak plasma acids by multiplying the serum total protein concentration (g/dl) by 2.43, according to van Slyke, [12] is a simplification. Figge et al. [27,28] have shown that only plasma albumin, but not the globulins, bear negative charges. The authors developed a rather complicated mathematical model to calculate the weak acid component from plasma albumin and plasma phosphate concentrations. However, Kowalchuk and Scheuermann [21] used both ways to estimate the weak acid component in heavily exercising humans and did not find relevant differences between measured and calculated values of pH and the Bic using the van Slyke factor versus the Figge model. Another indication that our values for Prot might be a reasonable estimate of the weak acid component of our patients comes from the finding that, in this study, the anion gap closely reflected changes in serum total protein concentration and therefore Prot (Table 2). The fact that throughout the study period there was only a slightly positive mean difference between the anion gap and Prot of 1 or 2 mM in both groups also implies that there should have been a nearly equal amount of unidentified cations and anions in our patients.
Figure 2
Figure 2
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(Figure 2) illustrates changes in BicHH and BicS, and therefore in pH, in the context of SID and Prot, according to the Stewart model. Variables in Figure 2 were calculated using mean values of the two groups after 120 min of crystalloid infusion time compared with the corresponding baseline values. With the 0.9% saline infusion, changes in Bic were accompanied by a profound decrease in SID by approximately 9 mM and were probably attenuated by a simultaneous decrease in Prot. In the Ringer's group, SID and Prot decreased nearly to the same amount, and the Bic was virtually unchanged with the crystalloid infusion. Whether the Henderson‐Hasselbalch approach or the Stewart model is more valuable in interpreting and understanding acid‐base changes resulting from crystalloid infusion can be debated.
Hyperchloremic acidosis caused by large 0.9% saline infusions seems to be benign, unless it is confused with hypoperfusion. The pH values greater than 7.20 do not seem to have major pathophysiologic implications in the clinical setting we describe. Nevertheless, we believe that hyperchloremic acidosis caused by a 0.9% saline infusion should be treated to provide a BE close to zero at the end of surgery (or, alternatively, lactated Ringer's solution should be used). In our experience in the early postoperative period, metabolic acidosis caused by hyperchloremia and respiratory acidosis caused by opiate analgesics may become additive and result in pH values much less than 7.20. A systematic analysis of this topic might provide valuable information.
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American Journal of Physiology-Regulatory Integrative and Comparative Physiology
Hypertonic saline reduces neutrophil-epithelial interactions in vitro and gut tissue damage in a mouse model of colitis
Tillinger, W; McCole, DF; Keely, SJ; Bertelsen, LS; Wolf, PL; Junger, WG; Barrett, KE
American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 295(6): R1839-R1845.
Anesthesia and Analgesia
Excessive use of hetastarch: An iatrogenic cause of bleeding and hypocalcemia? In response
Gan, TJ; Bennett-Guerrero, E; Mythen, MG
Anesthesia and Analgesia, 90(6): 1456.

Gynecologic Oncology
Effect of hemodilution on tissue perfusion and blood coagulation during radical hysterectomy
Santoso, JT; Hannigan, EV; Levine, L; Solanki, DR; Mathru, M
Gynecologic Oncology, 82(2): 252-256.

Nature Reviews Nephrology
Fluid balance and acute kidney injury
Prowle, JR; Echeverri, JE; Ligabo, EV; Ronco, C; Bellomo, R
Nature Reviews Nephrology, 6(2): 107-115.
American Journal of Respiratory and Critical Care Medicine
An Official ATS/ERS/ESICM/SCCM/SRLF Statement: Prevention and Management of Acute Renal Failure in the ICU Patient An International Consensus Conference in Intensive Care Medicine
Brochard, L; Abroug, F; Brenner, M; Broccard, AF; Danner, RL; Ferrer, M; Laghi, F; Magder, S; Papazian, L; Pelosi, P; Polderman, KH
American Journal of Respiratory and Critical Care Medicine, 181(): 1128-1155.
Renal Failure
Effects of normal saline vs. lactated ringer's during renal transplantation
Khajavi, MR; Etezadi, F; Moharari, RS; Imani, F; Meysamie, AP; Khashayar, P; Najafi, A
Renal Failure, 30(5): 535-539.
Intensive Care Medicine
Mortality and the nature of metabolic acidosis in children with shock
Hatherill, M; Waggie, Z; Purves, L; Reynolds, L; Argent, A
Intensive Care Medicine, 29(2): 286-291.
Current Problems in Surgery
Trauma evaluation and resuscitation
Rabinovici, R; Frankel, HL; Kaplan, LJ
Current Problems in Surgery, 40(): 596-681.

Critical Care
Bench-to-bedside review: A brief history of clinical acid-base
Story, DA
Critical Care, 8(4): 253-258.
Critical Care
Severe hyperlactatemia with normal base excess: a quantitative analysis using conventional and Stewart approaches
Tuhay, G; Pein, MC; Masevicius, FD; Kutscherauer, DO; Dubin, A
Critical Care, 12(3): -.
Pediatric Clinics of North America
Postresuscitation care
Kleinman, ME; Srinivasan, V
Pediatric Clinics of North America, 55(4): 943-+.
British Journal of Anaesthesia
Seven misconceptions regarding volume therapy strategies-and their correction
Boldt, J
British Journal of Anaesthesia, 103(2): 147-151.
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Unappreciated aspects of fluid and electrolyte physiology and implications to patient recovery
Wilkes, P; Akbari, A
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 57(7): 636-640.
Annales Francaises D Anesthesie Et De Reanimation
Is it more necessary to prescribe hydroxyethylstarch?
Mimoz, O; Capdevila, X
Annales Francaises D Anesthesie Et De Reanimation, 28(6): 515-516.
Hypernatremic alkalosis. Possible counterpart of hyperchloremic acidosis in intensive care patients?
Hofmann-Kiefer, KF; Chappell, D; Jacob, M; Schulke, A; Conzen, P; Rehm, M
Anaesthesist, 58(): 1210-1215.
Anions and the anaesthetist
Maloney, DG; Appadurai, IR; Vaughan, RS
Anaesthesia, 57(2): 140-154.

Anesthesia and Analgesia
Early postoperative respiratory acidosis after large intravascular volume infusion of lactated Ringer's solution during major spine surgery
Takil, A; Eti, Z; Irmak, P; Gogus, FY
Anesthesia and Analgesia, 95(2): 294-298.
Intensive Care Medicine
Subcutaneous gas tensions closely track ileal mucosal gas tensions in a model of endotoxaemia without anaerobism
Venkatesh, B; Morgan, T; Hall, J; Endre, Z; Willgoss, D
Intensive Care Medicine, 31(3): 447-453.
Critical Care
Clinical review: The meaning of acid-base abnormalities in the intensive care unit - effects of fluid administration
Morgan, TJ
Critical Care, 9(2): 204-211.
Pediatric Nephrology
Preventing neurological complications from dysnatremias in children
Moritz, M; Ayus, JC
Pediatric Nephrology, 20(): 1687-1700.
Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie
Requirements and expectations for optimal volume replacement
Zander, R; Adams, HA; Boldt, J; Hiesmayr, MJ; Meier-Hellmann, A; Spahn, DR; Standl, T
Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie, 40(): 701-719.
Clinical Science
Hartmann's solution and Ringer's lactate: targeting the fourth space
Wilkes, NJ
Clinical Science, 104(1): 25-26.

British Journal of Anaesthesia
Strong ions, weak acids and base excess: a simplified Fencl-Stewart approach to clinical acid-base disorders
Story, DA; Morimatsu, H; Bellomo, R
British Journal of Anaesthesia, 92(1): 54-60.
Critical Care
Clinical review: Acid-base abnormalities in the intensive care unit
Kaplan, LJ; Frangos, S
Critical Care, 9(2): 198-203.
Anesthesia and Analgesia
The role of the anesthesiologist in fast-track surgery: From multimodal analgesia to perioperative medical care
White, PF; Kehlet, H; Neal, JM; Schricker, T; Carr, DB; Carli, F
Anesthesia and Analgesia, 104(6): 1380-1396.
Avoiding latrogenic hyperchloremic acidosis - Call for a new crystalloid fluid
Dorje, P; Adhikary, G; Tempe, DK
Anesthesiology, 92(2): 625-626.

Schweizerische Medizinische Wochenschrift
Volume therapy in hypotensive trauma patients
Pargger, H; Studer, W; Ruttimann, U
Schweizerische Medizinische Wochenschrift, 130(): 1509-1515.

Acta Anaesthesiologica Scandinavica
Small-volume resuscitation: from experimental evidence to clinical routine. Advantages and disadvantages of hypertonic solutions
Kreimeier, U; Messmer, K
Acta Anaesthesiologica Scandinavica, 46(6): 625-638.

Jama-Journal of the American Medical Association
Prevention of radiocontrast nephropathy - Back to basics
Chertow, GM
Jama-Journal of the American Medical Association, 291(): 2376-2377.

Neuroimaging Clinics of North America
Pediatric neuroanesthesia
Soriano, SG; Eldredge, EA; Rockoff, MA
Neuroimaging Clinics of North America, 17(2): 259-+.
Perioperative management of Jehovah's Witness patients - Special consideration of religiously motivated refusal of allogeneic blood transfusion
Habler, O; Voss, B
Anaesthesist, 59(4): 297-+.
Anesthesia and Analgesia
In vitro effects of different medium molecular hydroxyethyl starch solutions and lactated Ringer's solution on coagulation using SONOCLOT
Konrad, CJ; Markl, TJ; Schuepfer, GK; Schmeck, J; Gerber, HR
Anesthesia and Analgesia, 90(2): 274-279.

Anesthesia and Analgesia
Are lactated Ringer's solution and normal saline solution equal with regard to coagulation?
Boldt, J; Haisch, G; Suttner, S; Kumle, B; Schellhase, F
Anesthesia and Analgesia, 94(2): 378-384.

Wiener Klinische Wochenschrift
Stewart's acid-base approach
Funk, GC
Wiener Klinische Wochenschrift, 119(): 390-403.
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)
Suempelmann, R; Holinberger, H; Schmidt, J; Strauss, JM
Anasthesiologie & Intensivmedizin, 48(): S73-S77.

Anesthesia and Analgesia
Glucose as a Marker of Fluid Absorption in Bipolar Transurethral Surgery
Piros, D; Fagerstrom, T; Collins, JW; Hahn, RG
Anesthesia and Analgesia, 109(6): 1850-1855.
Journal of Comparative Physiology B-Biochemical Systemic and Environmental Physiology
mRNA expression analysis of the physiological responses to ammonia infusion in rainbow trout
Nawata, CM; Wood, CM
Journal of Comparative Physiology B-Biochemical Systemic and Environmental Physiology, 179(7): 799-810.
Annales Francaises D Anesthesie Et De Reanimation
Hyperchloraemic metabolic acidosis during plasma volume replacement
Ichai, C; Levraut, J; Giunti, C
Annales Francaises D Anesthesie Et De Reanimation, 21(3): 179-181.
UNSP S0750765802005713/EDI
Annales Francaises D Anesthesie Et De Reanimation
Hyperchloraemic metabolic acidosis during plasma volume replacement
Blanloeil, Y; Roze, B; Rigal, JC; Baron, JF
Annales Francaises D Anesthesie Et De Reanimation, 21(3): 211-220.
UNSP S0750765802005725/SSU
Transplantation Proceedings
Intravenous fluid therapy in renal transplant recipients: Results of a US survey
O'Malley, CMN; Frumento, RJ; Bennett-Guerrero, E
Transplantation Proceedings, 34(8): 3142-3145.
PII S0041-1345(02)03593-5
International Journal of Artificial Organs
New ideas in science and medicine and the renal control of acid-base balance
Bellomo, R; Ronco, C
International Journal of Artificial Organs, 28(): 957-960.

British Journal of Anaesthesia
Four and a fifth and all that
Cunliffe, M; Potter, F
British Journal of Anaesthesia, 97(3): 274-277.
Critical Care
Strong ion difference in urine: new perspectives in acid-base assessment
Gattinoni, L; Carlesso, E; Cadringher, P; Caironi, P
Critical Care, 10(2): -.
ARTN 137
Hyperchloremic acidosis increases circulating inflammatory molecules in experimental sepsis
Kellum, JA; Song, MC; Almasri, E
Chest, 130(4): 962-967.
Acta Anaesthesiologica Scandinavica
Monitoring of peri-operative fluid administration by individualized goal-directed therapy
Bundgaard-Nielsen, M; Holte, K; Secher, NH; Kehlet, H
Acta Anaesthesiologica Scandinavica, 51(3): 331-340.
Journal of Intensive Care Medicine
Endpoints of resuscitation for the victim of trauma
Ward, KR; Ivatury, RR; Barbee, RW
Journal of Intensive Care Medicine, 16(2): 55-75.

Anesthesia and Analgesia
Lactate versus chloride: Which is better?
O'Connor, MF; Roizen, MF
Anesthesia and Analgesia, 93(4): 809-810.

Journal of Cardiothoracic and Vascular Anesthesia
A prospective, randomized comparison of thromboelastographic coagulation profile in patients receiving lactated Ringer's solution, 6% hetastarch in a balanced-saline vehicle, or 6% hetastarch in saline during major surgery
Martin, G; Bennett-Guerrero, E; Wakeling, H; Mythen, MG; El-Moalem, H; Robertson, K; Kucmeroski, D; Gan, TJ
Journal of Cardiothoracic and Vascular Anesthesia, 16(4): 441-446.
Childs Nervous System
Anesthesia for epilepsy surgery in children
Soriano, SG; Bozza, P
Childs Nervous System, 22(8): 834-843.
Volume therapy with colloid solutions preserves intestinal microvascular perfusion in endotoxaemia
Schaper, J; Ahmed, R; Schafer, T; Elster, A; Enigk, F; Habazettl, H; Mousa, S; Schafer, M; Welte, M
Resuscitation, 76(1): 120-128.
Critical Care
Albumin and artificial colloids in fluid management: where does the clinical evidence of their utility stand?
Groeneveld, ABJ
Critical Care, 4(): S16-S20.

Intensive Care Medicine
Dilutional acidosis or uncovered cellular metabolism?
Davenport, A
Intensive Care Medicine, 35(): 2009-2011.
Intensive Care Medicine
Dilutional acidosis: where do the protons come from?
Gattinoni, L; Carlesso, E; Maiocchi, G; Polli, F; Cadringher, P
Intensive Care Medicine, 35(): 2033-2043.
Pediatric Anesthesia
Changes in acid-base, electrolyte and hemoglobin concentrations during infusion of hydroxyethyl starch 130/0.42/6: 1 in normal saline or in balanced electrolyte solution in children
Sumpelmann, R; Witt, L; Brutt, M; Osterkorn, D; Koppert, W; Osthaus, WA
Pediatric Anesthesia, 20(1): 100-104.
Avoiding latrogenic hyperchloremic acidosis - Call for a new crystalloid fluid - Reply
Prough, DS; Bidani, A
Anesthesiology, 92(2): 626-627.

American Journal of Respiratory and Critical Care Medicine
Diagnosis of metabolic acid-base disturbances in critically ill patients
Fencl, V; Jabor, A; Kazda, A; Figge, J
American Journal of Respiratory and Critical Care Medicine, 162(6): 2246-2251.

Acta Clinica Belgica
General aspects of physiology and pathophysiology of metabolic acidosis in the critically ill
Van Biesen, W; Lameire, N
Acta Clinica Belgica, 55(3): 133-140.

Anesthesia and Analgesia
A randomized, double-blind comparison of lactated ringer's solution and 0.9% NaCl during renal transplantation
O'Malley, CMN; Frumento, RJ; Hardy, MA; Benvenisty, AI; Brentjens, TE; Mercer, JS; Bennett-Guerrero, E
Anesthesia and Analgesia, 100(5): 1518-1524.
Annales Francaises D Anesthesie Et De Reanimation
Controlled hypernatremia
Petit, L; Masson, F; Cottenceau, V; Sztark, F
Annales Francaises D Anesthesie Et De Reanimation, 25(8): 828-837.
American Journal of Physiology-Renal Physiology
Dietary sodium chloride intake independently predicts the degree of hyperchloremic metabolic acidosis in healthy humans consuming a net acid-producing diet
Frassetto, LA; Morris, RC; Sebastian, A
American Journal of Physiology-Renal Physiology, 293(2): F521-F525.
Acta Clinica Belgica
Fluid resuscitation: Colloids vs crystalloids
Vincent, JL
Acta Clinica Belgica, 62(): 408-411.

Anesthesia and Analgesia
The effect of different crystalloid solutions on acid-base balance and early kidney function after kidney transplantation
Hadimioglu, N; Saadawy, I; Saglam, T; Ertug, Z; Dinckan, A
Anesthesia and Analgesia, 107(1): 264-269.
Kidney International
Assessing acid-base disorders
Adrogue, HJ; Gennari, FJ; Galla, JH; Madias, NE
Kidney International, 76(): 1239-1247.
American Journal of Physiology-Regulatory Integrative and Comparative Physiology
Lactic and hydrochloric acids induce different patterns of inflammatory response in LPS-stimulated RAW 264.7 cells
Kellum, JA; Song, MC; Li, JY
American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 286(4): R686-R692.
Critical Care
Clinical review: The meaning of acid-base abnormalities in the intensive care unit - epidemiology
Gunnerson, KJ
Critical Care, 9(5): 508-516.
Academic Emergency Medicine
Effect of normal saline infusion on the diagnostic utility of base deficit in identifying major injury in trauma patients
Sinert, R; Zehtabchi, S; Bloem, C; Lucchesi, M
Academic Emergency Medicine, 13(): 1269-1274.
British Journal of Anaesthesia
The balanced concept of fluid resuscitation
Boldt, J
British Journal of Anaesthesia, 99(3): 312-315.

Metabolic acidosis in the critically ill: Part 2. Causes and treatment
Morris, CG; Low, J
Anaesthesia, 63(4): 396-411.
Intensive Care Medicine
The value of the chloride: sodium ratio in differentiating the aetiology of metabolic acidosis
Durward, A; Skellett, S; Mayer, A; Taylor, D; Tibby, SM; Murdoch, IA
Intensive Care Medicine, 27(5): 828-835.

Pediatric Anesthesia
Unexpected hypernatremia during pulmonary resection in a 7-year-old child with hydatid disease
Johr, M; Berger, TM; Winiker, H
Pediatric Anesthesia, 16(6): 697-698.
Journal of Emergency Medicine
Management of sepsis during the early "golden hours"
Raghavan, M; Marik, PE
Journal of Emergency Medicine, 31(2): 185-199.
Hyperchloraemia causes metabolic acidosis by reducing strong ion difference
Dorje, P; Bree, SE; Adhikary, G; Mclaren, DI
Anaesthesia, 55(1): 94.

Interpreting the base deficit
Thomas, R; Power, KJ
Anaesthesia, 55(7): 696-697.

Archives of Disease in Childhood
Chasing the base deficit: hyperchloraemic acidosis following 0.9% saline fluid resuscitation
Skellett, S; Mayer, A; Durward, A; Tibby, SM; Murdoch, IA
Archives of Disease in Childhood, 83(6): 514-516.

Intensive Care Medicine
The strong ion gap does not have prognostic value in critically ill patients in a mixed medical/surgical adult ICU
Cusack, RJ; Rhodes, A; Lochhead, P; Jordan, B; Perry, S; Ball, JAS; Grounds, RM; Bennett, ED
Intensive Care Medicine, 28(7): 864-869.
Anaesthesia and Intensive Care
Acid-base and bio-energetics during balanced versus unbalanced normovolaemic haemodilution
Morgan, TJ; Venkatesh, B; Beindorf, A; Andrew, I; Hall, J
Anaesthesia and Intensive Care, 35(2): 173-179.

Anaesthesia, Pain, Intensive Care and Emergency: A.P.I.C.E
Incidents provoked specifically by certain drugs used in anaesthesia
Klimek, M; Ottens, TH; Grune, F
Anaesthesia, Pain, Intensive Care and Emergency: A.P.I.C.E, (): 325-331.

Critical Care
Causes of metabolic acidosis in canine hemorrhagic shock: role of unmeasured ions
Bruegger, D; Kemming, GI; Jacob, M; Meisner, FG; Wojtczyk, CJ; Packert, KB; Keipert, PE; Faithfull, NS; Habler, OP; Becker, BF; Rehm, M
Critical Care, 11(6): -.
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
Morgan, TJ; Power, G; Venkatesh, B; Jones, MA
Anaesthesia and Intensive Care, 36(6): 822-829.

Critical Care
Determinants of blood pH in health and disease
Kellum, JA
Critical Care, 4(1): 6-14.

Anasthesiologie & Intensivmedizin
Perioperative optimisation of oxygen delivery in high-risk patients
Wiebalck, A; Mollhoff, T; Hachenberg, T; Bach, F; Berendes, E; Muller, M; Emmerich, M; Rommelsheim, K; Tonner, PH; Scholz, J; Bottiger, BW; Meier-Hellmann, A
Anasthesiologie & Intensivmedizin, 43(6): 327-339.

Journal of Intensive Care Medicine
Concepts of the strong ion difference applied to large volume resuscitation
Powner, DJ; Kellum, JA; Darby, JM
Journal of Intensive Care Medicine, 16(4): 169-176.

British Journal of Anaesthesia
Pathophysiology and clinical implications of perioperative fluid excess
Holte, K; Sharrock, NE; Kehlet, H
British Journal of Anaesthesia, 89(4): 622-632.

Kidney International
Stewart and beyond: New models of acid-base balance
Corey, HE
Kidney International, 64(3): 777-787.

Obesity Surgery
Severe metabolic acidosis resulting from a dislocated gastric band
Bruegger, D; Rehm, M; Da Silva, L; Christ, F; Finsterer, U
Obesity Surgery, 14(4): 555-558.

International Journal of Artificial Organs
Prevention of acute renal failure - fluid repletion and colloids
Jakob, SM
International Journal of Artificial Organs, 27(): 1043-1048.

Anesthesia and Analgesia
Hyperchloremic acidosis in the critically ill: One of the strong-ion acidoses?
Story, DA; Morimatsu, H; Bellomo, R
Anesthesia and Analgesia, 103(1): 144-148.
Journal of Applied Physiology
Prediction of dilutional acidosis based on the revised classical dilution concept for bicarbonate
Lang, W; Zander, R
Journal of Applied Physiology, 98(1): 62-71.
Veterinary Clinics of North America-Equine Practice
Resuscitation and emergency management for neonatal foals
Corley, KTT; Axon, JE
Veterinary Clinics of North America-Equine Practice, 21(2): 431-+.
Critical Care
Quantitative physico-chemical analysis of the acidosis of cardiac arrest
Bailey, H
Critical Care, 9(4): 347-348.
Perioperative fluid management - Response
Rehm, M
Anaesthesist, 55(): 1114-1116.

Clinical Nutrition
The history of 0.9% saline
Awad, S; Allison, SP; Lobo, DN
Clinical Nutrition, 27(2): 179-188.
Paediatric Anaesthesia
Intraoperative fluid and glucose management in children
Leelanukrom, R; Cunliffe, M
Paediatric Anaesthesia, 10(4): 353-359.

Anesthesia and Analgesia
Hyperchloremic acidosis: The classic example of strong ion acidosis
Constable, PD
Anesthesia and Analgesia, 96(4): 919-922.
Critical Care
Acid-base status of critically ill patients with acute renal failure: analysis based on Stewart-Figge methodology
Rocktaeschel, J; Morimatsu, H; Uchino, S; Goldsmith, D; Poustie, S; Story, D; Gutteridge, G; Bellomo, R
Critical Care, 7(4): R60-R66.
Effects of hyperchloremic acidosis on arterial pressure and circulating inflammatory molecules in experimental sepsis
Kellum, JA; Song, MC; Venkataraman, R
Chest, 125(1): 243-248.

Metabolic acidosis developing during cardiopulmonary bypass is related to a decrease in strong ion difference
Alston, RP; Cormack, L; Collinson, C
Perfusion-Uk, 19(3): 145-152.
Changes of serum chloride and metabolic acid-base state in critical illness
Funk, GC; Doberer, D; Heinze, G; Madl, C; Holzinger, U; Schneeweiss, B
Anaesthesia, 59(): 1111-1115.

Anaesthesia and Intensive Care
Monitoring of acid-base and regulating variables during abdominal lavage
Scheingraber, S; Boehme, J; Scharbert, G; Dralle, H
Anaesthesia and Intensive Care, 32(5): 637-643.

Journal of Cardiothoracic and Vascular Anesthesia
Calcium supplementation of saline-based colloids does not produce equivalent coagulation profiles to similarly balanced salt preparations
Roche, AM; James, MFM; Bennett-Guerrero, E; Mythen, MG
Journal of Cardiothoracic and Vascular Anesthesia, 20(6): 807-811.
Article supports findings of previous comparison
Drummond, GB
Anesthesiology, 92(2): 624-625.

Anesthesia and Analgesia
Are there acid base changes during transurethral resection of the prostate (TURP)?
Scheingraber, S; Heitmann, L; Weber, W; Finsterer, U
Anesthesia and Analgesia, 90(4): 946-950.

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
Wilkes, NJ; Woolf, R; Mutch, M; Mallett, SV; Peachey, T; Stephens, R; Mythen, MG
Anesthesia and Analgesia, 93(4): 811-816.

Anesthesia and Analgesia
Normal saline versus lactated Ringer's solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: An outcome study
Waters, JH; Gottlieb, A; Schoenwald, P; Popovich, MJ; Sprung, J; Nelson, DR
Anesthesia and Analgesia, 93(4): 817-822.

Clinical Science
(Ab)normal saline and physiological Hartmann's solution: a randomized double-blind crossover study
Reid, F; Lobo, DN; Williams, RN; Rowlands, BJ; Allison, SP
Clinical Science, 104(1): 17-24.

Critical Care
Pro/con clinical debate: Do colloids have advantages over crystalloids in paediatric sepsis?
Khandelwal, P; Bohn, D; Carcillo, JA; Thomas, NJ
Critical Care, 6(4): 286-288.

International Journal of Artificial Organs
Impact of continuous veno-venous hemofiltration on acid-base balance
Rocktaschel, J; Morimatsu, H; Uchino, S; Ronco, C; Bellomo, R
International Journal of Artificial Organs, 26(1): 19-25.

Critical Care
Science review: Quantitative acid-base physiology using the Stewart model
Wooten, EW
Critical Care, 8(6): 448-452.
Scandinavian Journal of Clinical & Laboratory Investigation
Acid base and electrolyte changes after hypertonic saline (7.5%) infusion: A randomized controlled clinical trial
Kolsen-Petersen, JA; Nielsen, JOD; Tonnesen, E
Scandinavian Journal of Clinical & Laboratory Investigation, 65(1): 13-22.
Intensive Care Medicine
Changes in acid-base balance following bolus infusion of 20% albumin solution in humans
Bruegger, D; Jacob, M; Scheingraber, S; Conzen, P; Becker, BF; Finsterer, U; Rehm, M
Intensive Care Medicine, 31(8): 1123-1127.
International Journal of Artificial Organs
Plasma acid-base changes in chronic renal failure: A Stewart analysis
Story, DA; Tosolini, A; Bellomo, R; Leblanc, M; Bragantini, L; Ronco, C
International Journal of Artificial Organs, 28(): 961-965.

Transplantation Proceedings
Comparison of the Effects of Normal Saline Versus Plasmalyte on Acid-Base Balance During Living Donor Kidney Transplantation Using the Stewart and Base Excess Methods
Kim, SY; Huh, KH; Lee, JR; Kim, SH; Jeong, SH; Choi, YS
Transplantation Proceedings, 45(6): 2191-2196.
What Is the Clinical Relevance of Dilutional Acidosis?
Rehm, M; Finsterer, U
Anesthesiology, 95(3): 811.

Critical Care Medicine
Hyperchloremia is the dominant cause of metabolic acidosis in the postresuscitation phase of pediatric meningococcal sepsis*
O’Dell, E; Tibby, SM; Durward, A; Murdoch, IA
Critical Care Medicine, 35(10): 2390-2394.
PDF (364) | CrossRef
Hyperchloremic Metabolic Acidosis Is a Predictable Consequence of Intraoperative Infusion of 0.9% Saline
Prough, DS; Bidani, A
Anesthesiology, 90(5): 1247-1249.

PDF (2444)
Comparison of Point-of-Care Versus Central Laboratory Measurement of Electrolyte Concentrations on Calculations of the Anion Gap and the Strong Ion Difference
Morimatsu, H; Rocktäschel, J; Bellomo, R; Uchino, S; Goldsmith, D; Gutteridge, G
Anesthesiology, 98(5): 1077-1084.

PDF (324)
Kinetics of Isotonic and Hypertonic Plasma Volume Expanders
Drobin, D; Hahn, RG
Anesthesiology, 96(6): 1371-1380.

PDF (231)
Incidence of Propofol Infusion Syndrome during Noninvasive Radiofrequency Ablation for Atrial Flutter or Fibrillation
Cravens, GT; Packer, DL; Johnson, ME
Anesthesiology, 106(6): 1134-1138.
PDF (264) | CrossRef
Two Reports of Propofol Anesthesia Associated with Metabolic Acidosis in Adults
Funston, JS; Prough, DS
Anesthesiology, 101(1): 6-8.

PDF (270)
Metabolic Acidosis Associated with Propofol in the Absence of Other Causative Factors
Burow, BK; Johnson, ME; Packer, DL
Anesthesiology, 101(1): 239-241.

PDF (443)
Isotonic Fluid Absorption during Hysteroscopy Resulting in Severe Hyperchloremic Acidosis
Schäfer, M; Von Ungern-Sternberg, BS; Wight, E; Schneider, MC
Anesthesiology, 103(1): 203-204.

PDF (82)
Hydroxyethyl Starches: Different Products – Different Effects
Westphal, M; James, MF; Kozek-Langenecker, S; Stocker, R; Guidet, B; Van Aken, H
Anesthesiology, 111(1): 187-202.
PDF (735) | CrossRef
Acidosis Associated with Perioperative Saline Administration: Dilution or Delusion?
Prough, DS; White, RT
Anesthesiology, 93(5): 1167-1169.

Role of Pump Prime in the Etiology and Pathogenesis of Cardiopulmonary Bypass–associated Acidosis
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Back to Top | Article Outline
Acid‐base balance; crystalloid infusion; hyperchloremia; metabolic acidosis; Stewart approach

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