885CHAPTER 72 Acid Base Disorders Base Excess and Standard Base Excess BE is defined as the amount of strong acid (or strong base) in molecules per liter that must be added in vitro to a whole blood s[.]
CHAPTER 72 Acid-Base Disorders Base Excess and Standard Base Excess BE is defined as the amount of strong acid (or strong base) in molecules per liter that must be added in vitro to a whole blood sample to return the pH of the sample to 7.4 while the Pco2 is kept constant at 40 mm Hg.15,18,25,32,34,35 For example, in a “normal” blood sample (pH is 7.4 and Pco2 of 40 mm Hg), the BE is mmol/L Positive values signify an excess of metabolic bases, negative values an excess of metabolic acids.34,35 In order to make this tool clinically applicable, a nomogram was developed to allow BE calculation by automated blood gas analyzers.34–37 Of the available tools, BE is least influenced by changes in Paco2 This means that BE does not change in acute respiratory acidosis or alkalosis In metabolic acidosis, BE decreases and becomes negative (2BE or base deficit), whereas it becomes positive in metabolic alkalosis (simply called BE or 1BE) However, despite its benefits, there are several limitations of the use of BE.37–39 For clinical accuracy and reproducibility, several assumptions were incorporated into a nomogram, including correction factors, adjusted formulas,15,35,37,40 and an estimate of hemoglobin concentration The chosen hemoglobin concentration was 50 g/L (5 g/dL) as an estimation of the concentration of hemoglobin as it is diluted throughout the body.36,37 BE calculated this way is called standard base excess (SBE), a parameter reported by modern gas analyzers and used in the classical approach to acid-base balance (see eBox 72.1) Additionally, SBE does not provide information about the origin or mechanisms of the metabolic acid-base derangement.21 Most notably, SBE represents the net effect of all metabolic acid-base abnormalities In certain situations, coexisting metabolic acidosis and alkaloses may cancel each other; the resultant “normal” SBE will mistakenly suggest that no acid-base derangement exists Nearly 15% to 18% of critically ill adults with acid-base disorders have normal SBE.15,18,41 Bicarbonate-Based Approach Criticism of the SBE led to the development of alternative tools for assessment of acid-base disturbances, focusing primarily on the role of bicarbonate in determining the appropriateness of the metabolic response.13,15,33,37–39 As [H1] is tightly controlled, when an acid-base derangement develops, several physiologic responses become active over time so that pH changes can be minimized.37,38 Schwartz and Relman concluded that several patterns could be detected and that this approach allowed an improved understanding in how changes in pH and Pco2 modify the concentration of bicarbonate in an acute or chronic respiratory disorder38 (eTable 72.1) These patterns are sometimes referred to as Winter’s rules or Worthley’s rules depending on the location of clinical practice.38,42 With this approach, primary metabolic disorders can be predicted based on changes in Pco2 in the context of a normal respiratory compensation.38 These are useful to describe physiologic compensation, for uncovering mixed acid-base disorders, and to differentiate acute from chronic respiratory imbalances (See eTable 72.1 and eBox 72.2).15,38 Anion Gap and Corrected Anion Gap The anion gap (AG) was first proposed by Emmet and Narins to understand primarily metabolic acidoses.41 It is founded conceptually on the principle of electroneutrality: in an aqueous solution such as plasma, there can be no net electrical charge.5,23 This means that in order to maintain neutrality, positive-charged cations must equal negative-charged anions18,24 (see eBox 72.1): 885 Na K Ca 2 Mg 2 H Cl HCO3 proteins PO4 2 SO4 2 OH CO32 lactate XA (Eq 72.7) where [XA2] equals the unmeasured acid anions (UMAs) Depending on the clinical setting, [K1] is often omitted and its effect neglected.41 Therefore, the AG is commonly defined as follows6,24: ( ) ( AG Na K Cl HCO3 ( AG Na Cl HCO3 ) ) (Eq 72.8A) (Eq 72.8B) The sum of the difference in charge results in a gap of between 12 and 16 mmol/L or mEq/L Typically, normal values are 16 mEq/L or mmol/L if [K1] is included or 12 mEq/L without it, with variations of 62 to mEq/L.41 However, this historical reference value is now both lower and narrower due to the use of ionselective electrode testing, which results in higher chloride values than previous techniques Several studies have reported “normal” AG values (K1 not included) as 6.6 mEq/L (range, 2.6–10.6 mEq/L).43 Because it may be influenced by laboratory measurement techniques, it is necessary to understand each institution’s expected normal AG.3,44 It is affected by any change in concentrations of either unmeasured anions or cations not included in Eq 72.8A and 72.8B.45 Increases in AG are due to the accumulation of unmeasured anions, such as lactate or ketones, which cause a drop in chloride or bicarbonate levels to maintain electroneutrality This condition is termed anion-gap acidosis or simply gap acidosis While this approach is good for detecting unmeasured anions as the cause of metabolic acidosis (such as lactic acidosis, ketoacids), it has some limitations.45 Proteins and phosphate levels are often low in the critical care setting, leading to a decrease in AG This is particularly true in pediatric patients, in whom hypoalbuminemia may be common.45 In those with low albumin, the AG can be corrected (AGCORR) as follows43,46: ( AGCORR AGOBSERVED 2.5 [ normal albumin g/dL ] ) [ o bserved albumin g/dL ] (Eq 72.9) The albumin-corrected AG (AGCORR) can uncover an acidosis in the setting of hypoalbuminemia, which adds sensitivity for detecting unmeasured anions, including lactate, although the specificity for hyperlactatemia is poor.47,48 AG is a powerful tool for the clinician in the categorization of metabolic acidosis, as not all forms of metabolic acidosis result in an elevated AG (eTable 72.2).45 Employing the AGCORR allows one to distinguish normal AG (hyperchloremic) acidosis from gap acidosis (increased AG; eBox 72.3).43,46 Despite this, it is important to note that AG interpretation is more challenging in mixed acid-base disorders, which are often present in patients with critical illness The ratio of the change in AG to the change in HCO3– (also referred to as the DAG/DHCO3– ratio) may assist in differentiating a mixed metabolic acidosis from AG metabolic acidosis In the former situation, the ratio is less than In patients with AG metabolic acidosis (such as that due to lactic acidosis, glycol ingestion), the ratio is often between and 1.6, since for every mEq/L increase in anion there is a corresponding decrease in serum HCO32 (see eBox 72.1).49 885.e1 eTABLE Acid-Base Approach: Acid-Base Patterns and Expected Compensatory Responses 72.1 Primary Disorder Expected Changes [HCO32] (mEq/L or mmol/L) Metabolic acidosisb Primary decrease ,22 Expected Changes Pco2 (mm Hg)a Expected Changes SBE (mmol/L) Bicarbonate Approach 1.1 Pco2 (1.5 HCO32) (8 2) or Pco2 g 1.2 1.5 mm Hg for each mEq/L [HCO32] g Base deficit ,23 SBE Approach Pco2 40 SBE or Pco2 g mm Hg for each mEq/L SBE g Metabolic alkalosisc Primary increase 26 Bicarbonate Approach Pco2 (0.7 HCO32) (21 2) or Pco2 h 0.7 mm Hg for each mEq/L HCO32] h Base excess 13 SBE Approach Pco2 40 (0.6 SBE) or Paco2 h 0.6 mm Hg for each mEq/L [HCO32] h Acute respiratory acidosis [(Pco2 40)/10] 24 or [HCO32] h 0.1 mEq/L for each mm Hg Pco2h Primary Pco2 increase 45 DpH 0.008 (Pco2 40) Chronic respiratory acidosis [(Pco2 40)/3] 24 or [HCO32] h 0.3 mEq/L for each mm Hg Pco2h Primary Pco2 increase 45 DpH 0.003 (Pco2 40) 0.4 (Pco2 40) or SBE h 0.4 mEq/L for each mm Hg Pco2 h Acute respiratory alkalosis [(40 Pco2)/5] 24 or [HCO32] g 0.2 mEq/L for each mm Hg Pco2 g Primary Pco2 decrease ,35 DpH 0.008 (40 Pco2) Chronic respiratory alkalosis [(40 Pco2)/10] 24 or [HCO32] g 0.4 mEq/L for each mm Hg g Pco2 Primary Pco2 decrease ,35 DpH 0.017 (40 Pco2) 0.4 (Pco2 40) or g 0.4 mEq/L for each mm Hg g a Always adjust Pco2 values to the height above sea level Empirical rules for expected values and compensation are minimally affected In metabolic acidosis, hyperventilation Pco2 decreases in a highly predictable fashion if respiratory and CNS function are normal c In metabolic alkalosis, compensatory respiratory hypoventilation is highly variable even if respiratory and CNS function are normal Acute minutes to hours; chronic several days or longer CNS, Central nervous system; Pco2, partial pressure of carbon dioxide; SBE, standard base excess b 885.e2 • eBox 72.2 Approach to Acid-Base Derangements: Additional Clues • eBOX 72.3 Causes of Metabolic Acidosis in Critically Ill Patients Metabolic acid-base derangement exists if any of the following occurs: • pH is abnormal • pH and Pco2 have changed in the same direction (both increased or both decreased) • Respiratory compensation is intact if Paco2 resembles last two digits of pH (e.g., pH 7.23 and Paco2 #23 mm Hg) Respiratory acid-base derangement is overlapped if any of the following occurs: • pH is abnormal but Pco2 is reported within normal limits • Pco2 reported is higher than expected Pco2 (respiratory acidosis overlapped) • Pco2 reported is lower than expected Pco2 (respiratory alkalosis overlapped) Respiratory acid-base derangement exists if any of the following occurs: • Paco2 is abnormal • Pco2 and pH have changed in opposite directions (i.e., raised Pco2 and decreased pH or vice versa) Calculation of the pH can be estimated as (see eTable 72.1): • 0.008 change in Pco2, there is no compensation; then the derangement is acute • 0.003 but ,0.008 change in Pco2, there is a partial compensation • 0.003 change in Pco2, there is full compensation; then the derangement is chronic • 0.008 change in Pco2, there is an overlapping metabolic derangement Mixed derangement (acidosis and alkalosis) if any of the following occurs: • Paco2 is abnormal and pH has not changed as expected or is within normal values • pH is abnormal and Paco2 has not changed as expected or is within normal values Anion Gap Acidoses: Accumulation of Unmeasured Anions Modified from Marino PL Acid-base interpretations In: Marino PL, ed The Little ICU Book of Facts and Figures Philadelphia: Lippincott Williams & Wilkins; 2009:349-362 Excessive 0.9% saline or hypertonic saline resuscitation HCl, NH4Cl, arginine-HCl administration Total parenteral nutritiona Endogenous Source of Acids Type A hyperlactatemia (decreased tissue O2 delivery) • Hypoperfusion • Mitochondrial disorders • Inborn errors of carbohydrate metabolism Type B hyperlactatemia (not associated with tissue hypoxia) • Adrenalin infusion • Reactive hyperglycemia • Liver failure • Drug-induced mitochondrial inhibition (e.g., linezolid) • Miscellaneous Ketoacidosis (diabetic, alcoholic, starvation, inborn errors of metabolism) Acute kidney injury: accumulation of phosphates, sulfates, and organic ions Unidentified anions in sepsis other than lactate Inborn errors of metabolism (organic academia, fatty oxidation defects) Tumor lysis Massive rhabdomyolysis Late metabolic acidosis of prematurity Exogenous Source of Acids Ingested toxins and drugs • Methanol, formic acid, keto acids • Glycols—Ethylene glycol, glycolic acid, oxalic acid, paraldehyde • Ethanol • Salicylate, salicylic acid, acetic acid • Illegal drugs Total parenteral nutritiona Nonanion Gap Acidoses Exogenous Chloride Load Loss of Cations From the Lower Gastrointestinal Tract (Postpyloric Gastrointestinal Fluid Losses) Infectious secretory diarrhea and dehydration Short bowel syndrome Drainage from ostomies, tubes, fistulas (small bowel, pancreatic, or biliary drainage) Sulfamylon, cholestyramine Urinary reconstruction using bowel segments Kidney-Related Causes Chronic kidney disease (impaired ammonium [NH41] generation) Renal tubular acidoses Hypoaldosteronism Recovery phase of diabetic ketoacidosis Urinary tract obstruction Drug-mediated loss of cations and tubulopathies • Acetazolamide • Amphotericin B • K1-sparing diuretics a Total parenteral nutrition may cause both anion gap and non–anion gap acidosis In the first case, an excessive amount of exogenous acid is the cause, mainly if liver or renal functions are impaired In the latter case, an unbalanced, excessive chloride content in the formulation provokes the derangement, which is easily produced in the setting of renal failure 885.e3 eTABLE Approach to Acid-Base Derangements in Critical Care 72.2 Step Inquiry Assessment Action Clinical suspicion of acid-base derangement Check peripheral venous blood sample for CO2 and pH Obtain ABG if peripheral CO2 or pH are abnormal or if clinical picture justifies it pH? pH ,7.35 n acidosis with acidemia pH 7.45 n alkalosis with alkalemia If pH 7.35–7.45, unbalance is not yet ruled out Check Pco2 and base excess Primary respiratory disorder? Pco2 and pH have moved in opposite directions There is a respiratory abnormality Use traditional approaches (bicarbonate approach or base excess; see eTable 72.1 and eBox 72.1) Primary metabolic disorder? Pco2 and pH have moved in the same direction There is a metabolic problem with respiratory compensation or SBE ,–3? There is a metabolic acidosis or Clinical suspicion of acidosis in spite of inconclusive pH, Pco2, SBE (and HCO32)? Anions? Check lactate and albumin Calculate AGCORRLACT Use surrogates of SID and SIG: For SIG, use AGCORRLACT AGCORRLACT mEq/L SIG acidosis (normochloremic or gap acidosis) Lactate mmol/L or 50% of SBE? Predominant lactic metabolic acidosis Lactate ,2 mmol/L; normal Cl2? Check ATOT and full calculation of SIDAPP, SIDEFF, and SIG SIG 50% of SBE? Yes: Predominant SIG metabolic acidosis (normochloremic acidosis, Gap acidosis) No: Predominant SID metabolic acidosis (hyperchloremic acidosis, non-Gap acidosis) If no single anion group accounts for 50% of SBE, there is probably a mixed disorder Compensations? Use bicarbonate or base excess observational patterns (see eTable 72.1 and eBox 72.2) Remember: Under ventilatory support or with neural or respiratory problems, respiratory compensation can be modified or not completed Hypoalbuminemia is common in PICU Extreme low levels (,2 g/dL) may modify AG and, potentially, pH Diuretics may modify metabolic response to acidosis through Na1 and Cl2 losses in urine; uGap can be useful to assess renal response Final analysis? Define the A-B derangement: Simple vs mixed? Compensated vs noncompensated? Construct differential diagnosis of the possible underlying causes Treatment? Focus on the underlying disorder Compensate every electrolyte unbalance Consider bicarbonate and mechanical ventilation in severe cases (pH ,7.1) Follow PALS guidelines Reassessment according to progress Each line should be read from left to right (Inquiry n Assessment n Action) before proceeding to the next step, starting again from the left side, in the same order See text for calculation of AGCORRLACT, SIDAPP, SIDEFF, SIG, uGap; for bicarbonate and SBE, see eTable 72.1 and eBox 72.2 ABG, Arterial blood gas; AGCORRLACT, anion gap corrected for albumin and lactate; ATOT, total nonbicarbonate plasma anions (weak acids); CVC, central venous catheter; HCO32, bicarbonate; Na1 and Cl2, Na1 and Cl2 blood levels; PALS, pediatric advanced life support; Pco2, carbon dioxide partial pressure; SBE, standard base excess; SIDAPP, strong ion difference (apparent); SIDEFF, strong ion difference (effective); SIG, strong ion gap; tCO2, total CO2; uGap, urinary anion gap 886 S E C T I O N V I I Pediatric Critical Care: Renal In addition to correcting the anion gap for hypoalbuminemia (AGCORR) further corrections may be suggested depending on the clinical situation.45 For example, when using AGCORR, hyperchloremic acidosis may go undetected if due to dilutional alkalosis.48 Theoretically, a “corrected” chloride would be needed However, the concept of “corrected chloride” is criticized by some, as no other part of the AG equation is “corrected” for water excess or deficit and as correction of the chloride assumes a fixed sodiumchloride relationship.50–52 However, in order to avoid the influence of lactate on AGCORR that could mask the detection of other unmeasured anions, it has been suggested that AG should be corrected not only for albumin but also for lactate by subtracting the serum lactate concentration (in mmol/L) from the already albumin-corrected AG (Eq 72.8A and 72.8B): mmol AGCORRLACT Albumin corrected AG lactate L (Eq 72.10) Serum Osmolar Gap Serum osmolality is determined by the concentrations (in mmol/L) of solutes in the plasma In health, sodium salts (mainly chloride and bicarbonate), glucose, and urea are the primary circulating solutes.5 If no other unmeasured solutes are present in serum at millimolar concentrations greater than mmol/L, then these three concentrations can be used to predict the measured osmolality53: Calculated Sosm mg mg gluc o se, BUN, mmol dL dL 2x serum Na, L 18 2.8 (Eq 72.11) The measured osmolality and the calculated osmolality should be similar (within mosmol/kg) If there is an elevation in the serum osmolal gap, this is suggestive of glycol ingestion such as ethylene glycol, diethylene glycol, propylene glycol, or alcohols such as methanol, ethanol, and isopropyl alcohol.53 Strong Ion Difference Strong ion difference (SID) is defined as the charge difference between the sum of all strong cations and all strong anions When SID is calculated from direct measurement of serum-strong ions, it is termed apparent SID (SIDAPP)3,48,54 with the understanding that more unmeasured ions might also be present (see eBox 72.1): ( ) ( ) SID APP Na K Ca 2 Mg 2 C l (Eq 72.12A) The “normal” range of SIDAPP ranges from 38 to 42 mEq/L.15,18,21,55 Unless elevated, lactate is ignored, as its contribution to total SID is negligible However, given that in the critical care setting there is an increased risk that lactate or other strong anions are increased, lactate should be included in those cases: SID APP ( ) ( ) Na K Ca 2 Mg 2 C l lactate (Eq 72.12B) In critical illnesses, SIDAPP may be substantially reduced, even when there is no evidence of a metabolic acid-base derangement.42,56,57 In “stable” critical care patients, SIDAPP values have been reported to be between 33.0 and 41.5 mEq/L.42 The lower the baseline of the SIDAPP, the greater the susceptibility to acid load during critical illness.55–57Additional strong anions may become significant in various clinical states (hyperlactatemia, ketoacids, medications or toxin ingestions, organic acidemias, or other inborn errors of metabolism) They may eventually influence the value of SIDAPP.55–58 It is important to note that direct measure of anions is not available at bedside (with the exception of lactate); therefore, it may not be convenient to use SIDAPP for assessing strong ions status, particularly among the most critically ill patients Urinary Anion Gap A urinary anion gap (uGap) was described some time ago to compare the loss of measured strong cations (sodium and potassium) with the loss of chloride.59 This urinary gap has also been designated by some authors as the urine strong ion difference (uSID) or the urinary net charge gap.21,24,60 Similar to the serum SID, the uSID estimates the unmeasured urinary ions, which reflects the ability of the kidney to counteract nonrenal acid-base disorders (see eBox 72.1) The capacity of the kidney to excrete ammonium chloride in acidosis allows the elimination of anions with conservation of sodium for volume uGap uSID uNa uK uCl (Eq 72.13) When a strong ion enters the plasma, normally functioning kidneys will increase the excretion of chloride as ammonium chloride while trying to maintain [Na1] and [K1] within the normal ranges.61 A positive uSID indicates excretion of an unmeasured anion.60 This loss of anions decreases the plasma strong ion difference Without those nonbicarbonate anions, metabolic acidosis and resultant retention of chloride (the positive-charge gap) will result in a decreased plasma SID, suggesting a renal cause of acidosis (such as renal tubular acidosis) If metabolic alkalosis is present, a positive urinary gap suggests renal loss of strong cations (sodium and potassium) In order to acidify the extracellular space, there will be a conservation of chloride because of a decrease in the plasma SID and in the bicarbonate concentration.5,60 In the presence of volume and potassium depletion, metabolic alkalosis is maintained, not corrected, by the kidneys.62 A negative value for the uSID indicates the presence of the unmeasured cation, ammonium (excretion of ammonium chloride) The loss of ammonium chloride in the urine of a patient with metabolic acidosis is a normal renal response to nonrenal causes of metabolic acidosis This is due to urinary chloride losses leading to increased plasma SID and the subsequent formation of more bicarbonate.13,29,63 Summary Many available tools, equations, and corrections are available to assist in the interpretation of acid-base disorder These tools allow the clinician to detect complex, mixed acid-base derangements in the critical care setting Tools of the traditional approach are the first-line choice for assessing respiratory acid-base disturbances and for the initial appraisal of metabolic problems (see eTables 72.1 and 72.2) For more complex situations, SID APP, uGap, and AG CORRLACT may provide useful information ... is abnormal and pH has not changed as expected or is within normal values • pH is abnormal and Paco2 has not changed as expected or is within normal values Anion Gap Acidoses: Accumulation of... osmolality and the calculated osmolality should be similar (within mosmol/kg) If there is an elevation in the serum osmolal gap, this is suggestive of glycol ingestion such as ethylene glycol,... chloride while trying to maintain [Na1] and [K1] within the normal ranges.61 A positive uSID indicates excretion of an unmeasured anion.60 This loss of anions decreases the plasma strong ion