• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
Understanding acid base balance - Curr Pediatrics 2003

Understanding acid base balance - Curr Pediatrics 2003



Understanding acid base balance - Curr Pediatrics 2003

Understanding acid base balance - Curr Pediatrics 2003



Total Views
Views on SlideShare
Embed Views



1 Embed 1

http://www.slideee.com 1



Upload Details

Uploaded via as Adobe PDF

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
Post Comment
Edit your comment

    Understanding acid base balance - Curr Pediatrics 2003 Understanding acid base balance - Curr Pediatrics 2003 Document Transcript

    • Understanding acid--base balance Andrew Durward* and Ian Murdoch* * ConsultantinPaediatric Intensive Care,Paediatric Intensive Care Unit,9thfloor,Guy’sTower Block,Guy’sHospital, StThomasStreet,London,SE19RT,UK Summary Traditionally, the Hendersen--Hasselbalchmodelhasbeenusedto analyse clinical acid--base problems.Simplistically, this approach def|nes pH as a function of car- bon dioxide and bicarbonate concentrations in aqueous solutions.The def|nition of the metabolic component of an acid--base relationship withthis approach is, however,lim- itedasbicarbonatevarieswiththeconcentrationofdissolvedcarbondioxide.Theselim- itations are partly overcome by use of the base excess or anion gap. Stewart’s physiochemical theory of acid--base has been used further to describe acid--base bal- ance in the context of abnormalities in electrolytes or albumin.This review focuses on some of the limitations and practical uses of these approaches in the interpretation of metabolic acid--base disorders. c 2003 Published by Elsevier Ltd. KEYWORDS metabolic acidosis; base excess; anion gap; hyperchloraemia; strong ion gap PRACTICE POINTS * The HCO3 À concentrationis a poor marker for the metabolic component of an acid--base relationship because it is dependent on pCO2 * The standard base excess (SBE) overcomes this limitation by using a reference pCO2 value of 40mmHg * The SBE def|nes the magnitude but not the cause of a metabolic acidosis * The anion gap determines the cause of a metabolic acidosisbutisunderestimatedbyhypoalbuminaemia * Calculation of Stewart’s strong ion gap is an accu- rate method to quantify the presence of an un- measured anion * The chloride to sodium ratio is a simple bedside tool to evaluate acid--base disorders and assist in the diagnosis of hyperchloraemic (raised Cl:Na ra- tio) or raised SIG acidosis (low Cl:Na ratio) RESEARCHDIRECTIONS * Clarify the nature of the strong ion gap in meta- bolic acidosis and the metabolic compensatory responses that follow * This may lead to novel therapeutic strategies for what remains a potentially life-threatening biochemical disorder Disorders of acid--base regulation are one of the com- monest metabolic abnormalities in acutely ill children or adults.1--3 Profound acid--base disturbances at either end of the pH spectrum (acidaemia or alkalaemia) have been associated with increased disease morbidity and adverse outcome.4,5 Under normal circumstances, powerful reg- ulatory mechanisms maintain the hydrogen ion concen- tration between 37 and 42nmol/l (pH 7.37--7.43). In disease, acid--base imbalance may result from either re- spiratory (ventilatory) or metabolic derangements. His- torically, clinical acid--base abnormalities have been interpretedusing thepH notationproposedby Sorensen and the pCO2/bicarbonate model of Henderson and Hasselbalch (H--H).6 Unfortunately, this ‘traditional’ H--H approach has a number of important limitations when applied to the in- vivo analysis of bloodin the clinical context.The purpose of this review is to discuss some of these limitations and how they can be overcome in order to aid diagnosis and treatment of some of the common acid--base abnormal- ities encountered in paediatrics. THE pHNOTATION At the turn of last century, Sorensen proposed the con- ceptof a‘hydrogenion exponent’ which he symbolized as ARTICLE IN PRESS Correspondence to: AD.Tel.: +44(0) 207 9552564; Fax: +44(0) 207 9552563; E-mail: Andrew.Durward@gstt.sthames.nhs.uk Current Paediatrics (2003) 13, 513--519 c 2003 Published by Elsevier Ltd. doi:10.1016/j.cupe.2003.08.009
    • ‘pH’. pH was def|ned as the log of the reciprocal of the hydrogen ion concentration. Although widely accepted, use of the pH scale has been criticized because it is a dimensionless number for which changes are not readily translated into changes in hydrogen ion concentration ([H+]).For example, a fallin pH from 7.2 to 7.0represents a change in [H+] from 60 to100nmol/l or an increase of 166%.The importance of the pH scale lies in its linear re- lationship when plotted against the log of pCO2. With development of the pH and pCO2 electrode in the early 1960s, the linear relationship between log pCO2 and pH could then be exploited to solve simple clinical acid--base problems (Fig.1). THE pCO2/BICARBONATE MODELOF ACID--BASE The concentration of [H+ ] in an aqueous solution can be described by the chemical hydration reaction of carbon dioxide (CO2) to carbonic acid (Eq.1). Dissolved CO2 þ H2O2½H2CO3Š 2½HCO3Š þ ½Hþ Š ð1Þ The ionization of carbonic acid generates the bicarbo- nate anion. At physiologic pH (7.4), the reaction is mark- edly shifted to the right with the vast majority of CO2 being carried in blood as HCO3 À .The HCO3 À concentra- tion is dependent on pCO2. As only pH and pCO2 could be directly measured, the HCO3 À concentration was derived by solving the H--H equation.This describes pH as a function of pCO2 and bicarbonate concentration using an empiric pKa value for the carbonic acid system of 6.1 (Eq. 2). pH ¼ 6:1ðpKaÞ þ log½HCO3Š=dissolved CO2 ð2Þ The millimolar concentration of dissolved CO2 can be calculated from the partial pressure of CO2 using its so- lubility coeff|cient (0.00301 at 371C): dissolved CO2 (mmol/l)=pCO2  0.0301. QUANTIFYING THE METABOLIC COMPONENTOF ANACID--BASE DISORDER The base excess The H--H equation describes a chemical reaction. It is not a quantitative expression. As pCO2 is directly mea- sured, the H--H model works well for acute respiratory acid--baseproblems.For example a high pCO2 always sig- nif|es alveolar hypoventilation. However, a raised pCO2 also directly increases the bicarbonate concentration which will increase as more carbonic acid ionizes to HCO3 À . Siggaard-Andersen introduced the base excess (BE) as a means to quantify the metabolic component of an acid--base disturbance independent of pCO2.7 The BE is def|ned as the amount of acid or base re- quired to titrate 1l of blood to a pH of 7.40 at 371C (Eq. 3) at a given haemoglobin (Hb) concentration: BE ¼ ð1 À 0:014  HbÞ Â ðHCO3 À 24Þ þ ð9:5 þ ð1:63  HbÞÞ Â ðpH À 7:4Þ ð3Þ The BE of oxygenated blood with an Hb of15g/dl at a pH of 7.4 andpCO2 of 40mmHg (5.33 kPa) is zero.The BE ARTICLE IN PRESS Figure 1 The linear relationship between pH and log of pCO2 for (a) respiratory acidosis and (b) mixed respiratory and metabolic acidosis. (a) Extrapolation oftheline back to a pHof 7.4 demonstrates that allthe acidosisis explained bypCO2 alone. (b) The respira- toryandmetaboliccomponentofthe acidosisis shownrelativetothereference pCO2 of 40 mmHg (blackhorizontalline) andpH 7.4. 514 CURRENT PAEDIATRICS
    • is strongly influenced by the Hb concentration, which is the main buffer in blood. As such, it was noted that changesin pCO2 on HCO3 À invivo differed from that ob- servedinvitro and that the discrepancycouldbereduced by using a Hb value of 5g/dl in the Siggaard-Anderson equation for BE. This empiric value was presumed to reflect the average concentration of Hb of the fluid space throughwhichbicarbonate distributes (between Hb15g/ dl in blood to Hb 0g/dl in extracellular fluid). This was called the standard base excess (SBE). As the SBE was independent of pCO2, it was used to def|ne the meta- bolic component of an acid--base disturbance.7 Limitations ofthe BE The compensatory relationships between pCO2 and SBE differ depending on the duration and type of acid--base disturbance.For example, the SBE does not change with acute hypercarbia, but may increase in chronic hyper- carbia due to compensatory bicarbonate retention. In order to facilitate the classif|cation of acid--base dis- orders into acute and chronic, Severinghaus published a nomogram as well as a number of approximate rules to calculate the expected pCO2 change per change in SBE (Table1).8 These rules are, however, misleading when acid--base disturbances are of mixed aetiology, particularly regard- ing the co-existence of acute and chronic acid--base disorders.For example, a patientwith a chronic compen- sated respiratory acidosis has a raised pCO2 and raised SBE.If thispatientdeveloped an acutemetabolic acidosis, the SBE would fall, resulting in a normal SBE and a high pCO2.This is not distinguishable from an acute respira- tory acidosis (normal SBE and raised pCO2). The most important limitation of the SBE is that it cannot deter- mine the cause of a metabolic acidosis, only that it may be present. Recently, a discrepancy of up to 3.7mmol/l has been reported when the BE is measuredusing differ- ent modern blood gas analysers.9 The anion gap Unlike the BE, the anion gap (AG) was introduced to further elucidate the cause of a metabolic acid--base disturbance.The AG is calculated using Eq. 4. AG ¼ ½NAþ Š þ ½Kþ Š À ½C1À Š À ½HCOÀ 3 Š ð4Þ The AGis normally due to the negative charge of plas- ma proteins, predominantly albumin (Eq. 5). AG ¼ ½proteinŠ ¼ 8216 mmol=l ð5Þ A wide AG signif|es the presence of an unmeasured negatively charged anion such as the lactate anion in lac- tic acidosis, with the magnitude of the AG being pro- portional to the concentration of the unmeasured an- ion (Eq. 6). AG ¼ ½proteinŠ þ ½lactate- Š ð6Þ Other examples of a raised AG acidosis are ketones (diabetic ketoacidosis), organic acids in organic acidae- mias and salicylate in salicylate poisoning. A normal AG metabolic acidosis signif|es the mechanism of acidosis is due to hyperchloraemia, for example renal tubular acidosis. Limitations ofthe AG Controversy exists as to what the true reference range for the AG should be. Historically, the range inclusive of K+ varies from 8 to16mmol/l.10 More recently, the refer- ence range has shifted downwards (3--11mmol/l) due to theimproved accuracyof chloridemeasurementwhichis higher than originally reported with flame photometry.11 As the AG relies on a f|xed contribution from the ne- gative charge of proteins, it is grossly underestimated in the presence of hypoalbuminaemia. In critically ill chil- dren who frequently have low albumin concentrations, theincidence of a raised AG acidosis wasunderreported in over 50% of cases if the effect of albumin on the AG was not considered.12 Correction of the AG for albumin produces an averageincreasein the AG of 2.7mEq/l. For- tunately, the accuracy of the AG canbe improvedby cor- recting the AG for albumin concentration (Eq. 7).13 Albumin corrected AG ¼ AG þ ð0:25  ½40 À measured albumin g=lŠÞ ð7Þ Although rare, the AG can also be lowered by the abnormal presence of unmeasured cations such as gammaglobulins or lithium. The strong ion theory of acid--base In1983, Stewart proposed a quantitative physiochemical model for acid--base equilibria similar to the Buffer Base concept originally proposed by Singer and Hastings.14 Although this approach was venomously criticized by proponents of the BE, it has recently undergone a resur- gence and helped to clarify the mechanisms of a number of common acid--base problems frequently encountered in critically ill patients, some of which cannot be easily explained using the conventional H--H model.15 ARTICLE IN PRESS Table 1 The expected change in pCO2 (DpCO2) for a change in SBE (DSBE) according to the duration of acid-- base disturbance Respiratorydisorder Expected (pCO2) Metabolicdisorder Expected (pCO2) Acute SBE  0.0 SBE Â1.0 Chronic SBE  0.4 SBE  0.6 SBE, standard base excess. ACID--BASEBALANCE 515
    • The advantage of Stewart’s approach is that factors influencing pH in vivo are identif|ed and quantif|ed sepa- rately and independently. In this model, the hydrogen ion is generated from the dissociation of water (Eq. 8). H2O þ H2O2½Hþ Š þ ½OHÀ Š ð8Þ Due to thelaws of mass action, theproductof [H] and [OH] is always constant (dissociation constant of water). A changein pHresults when theratio of hydrogen to the hydroxyl anion changes. At a pH of 7.4, the ratio of [H+ ]:[OHÀ ] is 30:1. At neutral pH (6.8), the ratio is 1:1. According to Stewart, only three independent variables influence pH through water dissociation (Eq. 9). The three variables are: (a) carbonic acid, (b) strong ion difference (SID), and (c) weak acids. pH ¼ ½CO2 chargeŠ þ ½SIDŠ þ ½weak acid chargeŠ ð9Þ CO2 charge Stewart’s theory recognizes the contribution of both carbonic acid and its ionized ion bicarbonate to pH. It calculates the total charge contribution of carbon diox- ide for any given pH based on the pCO2. The strongion difference A strong ion is one which is completely dissociated at physiologic pH. This includes most of the electrolytes. HCO3 À is not a strong ion. The SID is the difference between the sum of measured strong cations and anions (Eq.10). SID ¼ ½Naþ Š þ ½Kþ Š À ½C1À Š À ½lactateÀ Š ð10Þ Weakacids The charge of the weak acids albumin and phosphate are included in Stewart’s calculations. The negative charge of albumin is due to its negatively charged histidine residues. Stewart’s strong ion gap The advantage of this physicochemical theory is that one can calculate the expected pH if all three variables are known (pCO2, SID and albumin).The difference between measured and calculated pH is due to the presence of an unmeasured f|xed acid (or its anion to be precise). This can be quantif|ed by calculation of a strong ion gap (SIG) (Eq11). SIG ¼ ½SIDŠ À ½CO2 chargeŠ À ½weak acidsŠ ¼ ½SIDŠÀ½HCOÀ 3 Š ÃÀ½albuminÀ ŠÀ½phosphateÀ Š ÃCO2 charge approximated by ½HCOÀ 3 Š ð11Þ The SIGrepresents the quantityofunmeasuredanions in plasma other than lactate (if lactate is measured, it is included as a strongion).The conceptof the SIG andhow it differs from the AG is shown in Fig. 2. Quantitatively, the SIG and AG correlate very tightly, particularly if the AG is corrected for albumin.3,16 Whatis the signif|cance ofa SIG? The SIG is usually zero (i.e. the negative charge of CO2 and weak acids counterbalances the net positive charge of the SID). A metabolic acidosis with a raised SIG may occur in diabetic ketoacidosis where the SIG quantitatively reflects the plasma ketones concentra- tion. In critically ill patients with metabolic acidosis the nature of the SIG remains unknown. In critically ill children, a raised SIG is usually the dominant mechan- ism of metabolic acidosis rather than lactate, although both may frequently co-exist.3--5 An isolated lactic acidosis is rare. Interpretation ofacid--base abnormalities with Stewart’s theory Classif|cation of acid--base disorders using Stewart’s the- ory is shown in Table 2. The major difference between this theory and the traditional H--H approach is that pH may change due to primary changes in electrolytes (via a changein SID) or albumin concentration For example, an increase in chloride relative to sodium will narrow the SID and directly result in metabolic acidosis.Conversely, hypochloraemia or hypoabuminaemia have an alkaliniz- ing effect on plasma. Stewart’s theory allows a quantita- tive evaluation of the primary and compensatory mechanisms of acid--base disorders to be identif|ed. Un- like the BE or AG, it can be used to analyse acid--base problems in the presence of electrolyte abnormalities or hypoalbuminaemia. It is, however, mathematically cumbersome to perform at the bedside. ARTICLE IN PRESS Figure 2 A gamblegram showing the difference between the anion gap and strong ion gap.The unmeasured quantity of f|xed acid is labelled as XÀ and the charge contribution of albumin as AlbÀ .The effective strongion difference (SIDe) is the sum ofthe HCO3 and weak acids (albumin). Strong ion gap (SIG=SID -- SIDe). 516 CURRENT PAEDIATRICS
    • The Cl:Na ratio (normal range 0.75--0.79) The Cl:Na ratio serves as a simple substitute to quantify the role of hyperchloraemia in acid--base disturbances.3 According to Stewart’s theory, a high Cl:Na ratio (40.79) has an acidifying effect and a low Cl:Na ratio (o0.75) has an alkalinizing effect on plasma. In patients with metabolic acidosis, a raised Cl:Na ratio (40.79) points to hyperchloraemia as the cause of acidosis, its magnitude being proportional to the ratio.On the other hand, a low Cl:Na ratio (o0.75) in the face of a metabolic acidosis points to a raised SIG.This is because the ion of the raised SIG is negatively charged.To maintain electro- neutrality, other plasma anions such as chloride and albu- min must fall as a compensatory response if the cations (Na and K) remain constant. In clinical practice, both the Cl:Na ratio and albumin charge appear low in the presence of tissue acids.3 The association of a normal Cl:Na ratio (between 0.75 and 0.79) and metabolic acidosis indicates a mixed meta- bolic acidosis (i.e. mild hyperchloraemia associated with a raised SIG).The lower theratio, the greater the contri- bution of the SIG. This is a commonly observed in shocked patients resuscitated with normal saline. In this manner, use of the Cl:Na ratio in metabolic acidosis may obviate the need to use the complex calculations of Stewart for calculation of the SIG. This ratio is, however, limited by the accuracy of both Cl and Na measurement. In metabolic alkalosis, the Cl:Na ratio is usually low. This is most likely due to a primary fall in chloride rather than an increase in bicarbonate. For example, the di- uretic lasix induces a greater renal chloride loss than sodium (renal Cl loss=urine Na+K loss), thus lowering the Cl:Na ratio and causing a metabolic alkalosis through an increase in SID. UNDERSTANDING CLINICAL ACID-- BASE PROBLEMS: METABOLIC ACIDOSIS The following examples illustrate how a combined ap- proach using a combination of the above methods helps to identify themechanism of metabolic acidosis.Case1, 2 and 3 have a metabolic acidaemia of the similar magnitude (normal pCO2, low HCO3 À and negative SBE) Table 3. Case1:Hyperchloraemic metabolic acidosis The mechanism of metabolic acidosis cannot be deter- mined from the SBE alone.The AG is normal, therefore it is a hyperchloraemic metabolic acidosis. This is con- f|rmed by the raised Cl:Na (0.83) and absence of any unmeasured anions (SIG=0). An example of a hyper- chloraemic acidosis is renal tubular acidosis.Use of large quantities of chloride-rich saline may also cause a base def|cit secondary to hyperchloraemia. Clinicians may erroneously interpret the base def|cit as a marker of decreased tissue perfusion, and further perpetuate the ARTICLE IN PRESS Table 2 The acidifying or alkalinizing effect of Stewart’s independent variables Acidifyingeffect Alkalinizingeffect CO2 m k SID k m Albumin m k Phosphate m k SID, strongion difference. Table 3 Blood gas, electrolyte and albumin concentrations for four hypothetical patients illustrating differenttypes of meta- bolic acidosis.For simplicity, the pCO2 hasbeen set at 40 mmHg to removethe contribution of a respiratorycomponent. Case number Case1 Case 2 Case 3 Case 4 pH 7.25 7.25 7.25 7.4 pCO2 (kPa) 40 40 40 40 HCO3 À 17.4 17.5 17.5 26 SBE À8.2 À8.2 À8.2 0.8 Na 140 140 126 140 Cl 116 101 98 116 Albumin (g/l) 40 40 30 10 Lactate (mmol/l) 2 2 2 2 Anion gap (mEq/l) 10.6 25.5 14.5 2 SIG (mEq/l) 0 15 7.5 2 Cl:Na ratio 0.83 0.72 0.78 0.83 Assume a Kof 4 mmol/l.SIG, strongion gap;SBE, standardbase excess. Normalrange for SIGis 073 mEq/l. Normalrange for Cl:Na ratiois 0.75--0.79. ACID--BASEBALANCE 517
    • acidosis if more saline is administered.17 Use of more physiologic resuscitation fluids such as Hartman’s solution does not induce hyperchloraemia.18 Case 2: Metabolic acidosis due to increased tissue acids (raised SIG) The SBE and degree of acidosis is similar to Case1. It is a raised AG acidosis because the AG is raised (25mEq/l). The exact quantity of tissue acids can be quantif|ed by the SIG (15mEq/l, normal SIG=073mEq/l). The Cl:Na ratio is low (o0.75) due to the compensatory fall in chloride relative to sodium.This type of metabolic acido- sis is common in critically ill patients.The nature of the SIGmaybe ketonesin diabetic ketoacidosis or, for exam- ple, a specif|c amino acid if due to an inborn error of metabolism. In septic shock, the nature of the SIG remains unknown, butpresumablyreflects accumulation of metabolic acids produced following tissue hypoxia or decreased perfusion.15 Case 3: Mixed hyperchloraemic and tissue metabolic acidosis Once again, the SBE alone cannot identify the cause of acidosis. However, as the AG appears to be within nor- mallimits (o16mEq/l) a hyperchloraemic acidosis should be considered. However, the absolute Cl (98mmol/l) is also notraised.On closer inspection the patient is hypo- natraemic. The Cl:Na ratio is on the upper limit of normal (0.78).Itis nothigh enough for the hyperchlorae- mia to cause this degree of acidosis alone, therefore another acidifying influence must be present -- the SIG which is marginally elevated (7.5mEq/l).This is an exam- ple of a mixed metabolic acidosis due to a slightly raised SIG and mild hyperchloraemia (relative to sodium). The AG is falsely low because of hypoalbuminaemia (30g/l). Correction of the AG reveals that the true AG is in fact slightly raised at 17mEq/l [i.e 14.5+0.25Â (40--30)]. Hy- poalbuminaemia according to Stewart’s theory has an al- kalinizing effect on plasma. In this case, the low albumin and hyponatraemia masked the true cause of metabolic acidosis. Case 4:Hyperchloraemic metabolic acidosis masked by hypoalbuminaemia ThepH, pCO2 and SBE, AG arenormal and the anion gap is not raised.There does not appear to be an acid--base abnormality.The Cl:Na ratio is, however, raised at 0.84. As thepHisnormal the acidifyingeffectof hyperchlorae- mia must be opposed by an alkalinizing process of equal magnitude.On closer inspection there is marked hypoal- buminaemia (10g/l). According to Stewart, thereduction in the weak acid albumin has a similar but opposite quantitative effect on the dissociation of water compared with the reduced SID associated with hyper- chloraemia. Although this type of acid--base abnormality is unusual, it illustrates the value of Stewart’s physio- chemical acid--base theory over the conventional ap- proach. CONCLUSION The interpretation of clinical acid--base disorders can be facilitated by understanding the limitations of the con- ventional pCO2/bicarbonate approach in conjunction with the physiochemical theory of Stewart. In Stewart’s model, plasma electrolytes and weak acids such as albumin play a major physiologic role in either generating or compensating for changes in hydrogen ion con- centration. Although it is beyond the scope of this review, a better understanding of acid--base physiology may lead to improvements in the diagnosis and treat- ment of some of the acid--base disorders encountered in paediatrics. REFERENCES 1. Cusack RJ, Rhodes A, Lochhead P et al. The strong ion gap does not have prognostic value in critically ill patients in a mixed medical/surgical adult ICU. Intens Care Med 2002; 28: 864--869. 2. Balasubramanyan N, Havens PL, Hoffman GM. Unmeasured anions identified by the Fencl-Stewart method predict mortality better than base excess, anion gap, and lactate in patients in the pediatric intensive care unit. Crit Care Med 1999; 27: 1577--1581. 3. Durward A, Skellett S, Mayer A, Taylor D, Tibby SM, Murdoch IA. The value of the chloride: sodium ratio in differentiating the aetiology of metabolic acidosis. Intens Care Med 2001; 27: 828-- 835. 4. Anderson LE, Henrich WL. Alkalemia-associated morbidity and mortality in medical and surgical patients. South Med J 1987; 80: 729--733. 5. Hatherill M, Waggie Z, Purves L, Reynolds L, Argent A. Mortality and the nature of metabolic acidosis in children with shock. Intens Care Med 2003; 29: 286--291. 6. Severinghaus JW, Astrup PB. History of blood gas analysis. II. pH and acid--base balance measurements. J Clin Monit 1985; 1: 259--277. 7. Severinghaus JW. Acid--base balance controversy. Case for standard-base excess as the measure of nonrespiratory acid--base imbalance. J Clin Monit 1991; 7: 276--277. 8. Schlichtig R, Grogono AW, Severinghaus JW. Human PaCO2 and standard base excess compensation for acid--base imbalance. Crit Care Med 1998; 26: 1173--1179. 9. Mentel A, Bach F, Schuler J et al. Assessing errors in the determination of base excess. Anesth Analg 2002; 94: 1141--1148. 10. Oh MS, Carroll HJ. The anion gap. N Engl J Med 1977; 297: 814--817. 11. Lolekha PH, Vanavanan S, Lolekha S. Update on value of the anion gap in clinical diagnosis and laboratory evaluation. Clin Chim Acta 2001; 307: 33--36. ARTICLE IN PRESS 518 CURRENT PAEDIATRICS
    • 12. Durward A, Mayer A, Skellett S et al. Hypoalbuminaemia in critically ill children: incidence, prognosis, and influence on the anion gap. Arch Dis Child 2003; 88: 419--422. 13. Figge J, Jabor A, Kazda A, Fencl V. Anion gap and hypoalbuminemia. Crit Care Med 1998; 26: 1807--1810. 14. Stewart PA. Modern quantitative acid--base chemistry. Can J Physiol Pharmacol 1983; 61: 1444--1461. 15. Kellum JA, Kramer DJ, Pinsky MR. Strong ion gap: a methodology for exploring unexplained anions. J Crit Care 1995; 10: 51--55. 16. Hatherill M, Waggie Z, Purves L, Reynolds L, Argent A. Correction of the anion gap for albumin in order to detect occult tissue anions in shock. Arch Dis Child 2002; 87: 526--529. 17. Skellett S, Mayer A, Durward A, Tibby SM, Murdoch IA. Chasing the base deficit: hyperchloraemic acidosis following 0.9% saline fluid resuscitation. Arch Dis Child 2000; 83: 514--516. 18. Kellum JA. Metabolic acidosis in the critically ill: lessons from physical chemistry [see comments]. Kidney Int 1998; 66 (Suppl.): 81--86. ARTICLE IN PRESS ACID--BASEBALANCE 519