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Home , Alkalosis, Base excess, Renal compensation, Respiratory acidosis, Respiratory compensation

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REVIEW ARTICLE

The ABC’s of Acid-Base Balance

Gordon S. Sacks, PharmD

The University of Wisconsin—Madison, Madison, Wisconsin

A step-wise systematic approach can be used to determine the etiology and proper management of acid-base disorders. The objectives of this article are to: (1) discuss the physiologic processes in- volved in acid-base disturbances, (2) identify primary and secondary acid-base disturbances based upon arterial gas and laboratory measurements, (3) utilize the for diagnostic pur- poses, and (4) outline a stepwise approach for interpretation and treatment of acid-base disorders. Case studies are used to illustrate the application of the discussed systematic approach.

KEYWORDS: acid-base

J Pediatr Pharmacol Ther 2004;9:235-42

Although acid-base disorders are frequently terms of H+, but due to confusing terminology it encountered in hospital and ambulatory care set- was proposed to convert H+ terminology to pH.1 tings, they are often considered the most difficult When taking the negative logarithm of the H+ areas to understand in . Misdiagnosis due to common misconceptions of acid-base ho- ABBREVIATIONS: AG, Anion gap; HCO3, ; CNS, meostasis often delays identification of the pri- Central nervous system; ECF, ; Hgb, ; ICU, Intensive care unit; THAM, Tromethamine mary disorder, causing a disruption in the deliv- ery of appropriate . By understanding the concentration, pH represents a measure of H+ basic principles of acid-base physiology, the inter- activity. Optimal function for tissues and organs pretation of acid-base data, and the mechanisms within the human body depends on maintaining responsible for acid-base perturbations, the clini- blood pH between 7.10 and 7.60. For purposes of cian should be able to recognize all acid-base dis- diagnosis, the generally accepted range of normal- orders and develop a systematic approach for the ity is pH 7.36 to 7.44. Any pH less than 7.36 is called management of such disorders. acidemia and any pH greater than 7.44 is called alkalemia. Acidemia refers to the acid condition of BACKGROUND the blood (pH < 7.36), whereas acidosis is the pro- cess by which a patient develops acidemia. The same In order to identify acid-base abnormalities and is true for alkalemia and .2 develop a treatment plan, it is necessary to first When an acid-base disorder occurs, the body comprehend the mechanisms responsible for attenuates this physiologic change by making ad- acid-base equilibrium. An acid is defined as a sub- justments through a compensatory mechanism. + stance that can donate a hydrogen ion (H ), Compensation refers to a change of the pH to- whereas a base is a substance that can accept an ward normal. When there is a shift in H+, the body + H . The acidity of body fluids can be expressed in may respond by three different mechanisms: chemical buffering, , or Address correspondence to: Gordon S. Sacks, 2 PharmD, The University of Wisconsin, 777 Highland . The most immediate re- + Avenue, Room 1037 Madison, WI 53705-2222, e-mail: sponse to rapid changes in body H is by chemi- gssacks@.wisc.edu cal buffering with intracellular and extracellular © 2004 Pediatric Pharmacy Advocacy Group buffers. Buffers are agents that minimize the abil-

J Pediatr Pharmacol Ther 2004 Vol. 9 No. 4 • www.ppag.org 235 JPPT Sacks GS ity of acids and bases to alter pH when added to a Table 1. Normal Blood Gas Values system. Major extracellular buffers in the human Arterial Blood Venous Blood body include bicarbonate (HCO ), hemoglobin 3 pH* 7.40 (7.35–7.45) 7.36 (7.33–7.43) (Hgb) and certain , and phosphates. In- PO † 80–100 mm Hg 35–40 mm Hg tracellular buffering involves H+ entering the cell 2 PCO ‡ 35–45 mm Hg 41–51 mm Hg in exchange for potassium and sodium. Respira- 2 HCO § 22–26 mEq/L 24–28 mEq/L tion is a second line of defense that acts to re- 3 O saturation|| 95% 70% - 75% store the ratio of acid to base by altering the 2 > ¶ –2 to +20 to +4 amount of CO2 gas in the body. The amount of CO CO2 gas in the body is typically referred to as P 2, *pH = identifies the presence of acidemia or alkalemia. †PO pressure exerted by oxygen dissolved in the plasma. which represents the pressure exerted by dissolved 2 = ‡PCO = pressure of dissolved CO gas in the blood. CO gas in the blood. Although CO is produced 2 2 2 2 §HCO3 = bicrobanate. in cells, it diffuses into the plasma to combine with ||O2 saturation = percentage of oxygen that hemoglobin is carrying water to form carbonic acid (H CO ). Thus, it is related to the total amount the hemoglobin could carry. 2 3 ¶Base excess = primarily reflects the concentration of bicarbonate CO helpful to consider P 2 as an acidic substance that and is affected only by metabolic processes; positive values reflect is only controlled by the . and negative values reflect metabolic . Changes in the rate and depth of can Table 1 lists the parameters and normal values be used to adjust the pH of body fluids. For ex- commonly reported in an arterial blood gas ample, in the presence of acidemia the body may (ABG). Acid-base disturbances are typically clas- respond by increasing ventilation and thereby sified according to the cause, resulting in an aci- removing excess CO . Ventilation rate can change 2 dosis (pH < 7.35) or an alkalosis (pH > 7.45). The PCO and pH of blood in a matter of minutes, with 2 causes are either respiratory in nature due to maximal compensation being achieved within 12 changes in breathing rate and pattern or meta- to 24 hours. The kidneys are the final buffering bolic as a result of an accumulation of fixed acids system and can affect blood pH by reabsorbing (e.g., ketones) or excessive loss of bicarbonate HCO , by allowing excess H+ to be excreted in the 3 (e.g., pancreatic fluid). The best method to accu- , and by generating new HCO via acid se- 3 rately and consistently identify the etiology for cretion. Bicarbonate is considered a base, and it acid-base disturbances is to employ a systematic, reflects a metabolic process (versus a respiratory stepwise approach. Five simple steps can be used process) that is only affected by the kidneys. The to identify the primary acid-base disorder and the time required for the kidneys to compensate is body’s attempt to compensate.3 This approach is slow, requiring several hours to change the extra- summarized in Table 2. cellular fluid volume compartment and 5-7 days to achieve maximal compensation. 1. Evaluate the pH First evaluate the ABG to determine the pres- Interpretation of Arterial Blood Gases ence of acidemia or alkalemia. A normal pH is any value between 7.35 and 7.45. Any value < 7.35 In order to most precisely evaluate acid-base indicates acidemia, while a value > 7.45 represents status, an arterial (instead of venous) blood gas is alkalemia. A normal pH may reflect a normal usually preferred. Arterial blood represents a mix- blood gas, or, alternatively, the presence of full ture of blood from various parts of the body com- CO compensation in which the P 2 and HCO3 will pared to venous blood obtained from an extrem- be outside the normal ranges. ity which reveals information primarily about that extremity. Arterial blood also identifies the abil- 2. Identify the primary process: respiratory or ity of the lungs to oxygenate the blood. Mixed metabolic venous blood samples can yield information about CO Normal P 2 is any value between 35 and 45 mm tissue oxygenation, but cannot determine the con- CO Hg. It is important not to confuse P 2 (mm Hg) in tribution of the heart versus lungs. Thus, normal the ABG report with CO2 (mEq/L) in the arterial oxygenation confirms normal lung func- report. “CO2” is reported on the serum tion, but low oxygen concentration in mixed electrolyte report in mEq/L and represents total venous blood could indicate that the heart, lungs, CO2, which is a combination of HCO3 and dissolved or both are failing. CO2/H2CO3 in the blood. Since CO2/H2CO3 are 236 J Pediatr Pharmacol Ther 2004 Vol. 9 No. 4 • www.ppag.org The ABC’s of Acid-Base Balance JPPT

Table 2. Systematic Approach to Arterial Blood Gas crease in HCO . When the AG is > 14 mEq/L, 3 3 Interpretation this indicates that the presence of a metabolic 1. Evaluate the pH to determine the presence of acidemia or acidosis should be investigated. The AG does have alkalemia. limitations, though, and a normal AG does not 2. Determine whether the primary process is respiratory or metabolic. exclude the possibility of the accumulation of 3. Calculate the “gaps.” unmeasured anions. Yet, when the AG exceeds 4. Check for the degree of compensation. 25 mEq/L, a is always present. 5. Determine whether there is a 1:1 relationship between anions in the blood. 4. Always check for the degree of compensation The human body has compensatory mecha- only a small fraction of the total CO2 in a serum nisms for returning the abnormal pH toward nor- sample, total CO2 is considered equal to HCO3. mal. During compensation, the component NOT CO If alkalemia is present and the P 2 is less than involved in the primary disorder is adjusted in an 35 mm Hg, then the primary disorder is respira- effort to correct the pH. For example, in a pri- CO tory dysfunction. It is helpful to think of P 2 as an mary metabolic alkalemia the compensatory res- acidic substance when interpreting ABGs, thus a piratory response——results in a deficiency or low amount of an acidic substance CO CO high P 2. As a general rule, the increase in P 2 would be consistent with an alkalemic state. A nor- should equal 0.6 times the increase in the HCO mal HCO is any value between 22 and 26 mEq/L. 3 3 concentration. For example, if the HCO3 in- If the HCO3 is > 26 mEq/L, then the primary dis- creased to 37 mEq/L from a normal value of 25 order has a metabolic cause since HCO3 is con- mEq/L, the appropriate compensation for the sidered a basic substance. There may be a situa- CO CO P 2 is 47 [(12 × 0.6) = 7.2 + normal P 2 of 40 = tion in which two primary disorders coexist. If the CO 47 mm Hg]. In this case, if the actual P 2 is > 50 CO P 2 is < 35 mm Hg and the HCO3 is > 26 mEq/L, mm Hg an additional primary respiratory aci- primary respiratory alkalemia and metabolic al- CO demia is occurring. If the P 2 is < 44 mm Hg, a kalemia are occurring simultaneously. A respira- primary respiratory alkalemia is occurring. The tory etiology is the primary process for acidemia body compensates for metabolic acidemia by in- when the PCO exceeds 45 mm Hg. If the HCO is CO 2 3 creasing the loss of P 2 via the lungs. For com- < 22 mEq/L, then the primary disorder has an pensation of metabolic acidemia, the decrease in underlying metabolic cause. A primary metabolic PCO should equal a factor of 1.3 times the de- acidemia may coexist with a primary respiratory 2 crease in HCO3. For instance, if the HCO3 de- acidemia when the HCO3 is < 22 mEq/L and the creases to 17 mEq/L from 25 mEq/L (a decrease PCO is > 45 mm Hg, respectively. CO 2 of 8), the P 2 should decrease to 30 mm Hg from 40 mm Hg [40 – (1.3 × 8) = 30]. Conversely, if the 3. Always calculate the anion gap CO P 2 were > 33 mm Hg an additional primary res- The anion gap (AG) is an additional tool that CO piratory acidemia would be present; if the P 2 can be used to assist in evaluating acid-base dis- were below 27 mm Hg, a primary respiratory al- turbances. This calculated value represents the kalemia would be in coexistence with the primary difference between the serum concentrations of metabolic acidemia. positively charged ions (cations) and negatively charged ions (anions). This calculation is based 5. Check for a 1:1 relationship of acid-base upon the concept of electrical neutrality, which substances states that the number of cations and anions in The rationale for this concept is based upon serum must be equal. Thus, the anion gap is usu- the earlier stated premise that cations and anions ally calculated by subtracting the sum of measured in the serum should be equal. If there is a dis- serum anions, HCO3 and chloride, from mea- crepancy, the application of this concept will as- sured cations, namely serum sodium. Typically, sist in identification of an underlying metabolic unmeasured anions, such as phosphates, sulfates, alkalemia not detected by using the previously organic acids, and proteins exceed unmeasured mentioned rules. For example, in the presence cations (i.e., , potassium, magnesium), thus of an increased anion gap metabolic acidemia, the AG is 10 ± 4 mEq/L. Each 1 mEq/L increase in the bicarbonate concentration should decrease the AG should occur with an equal 1 mEq/L de- by 1 mEq/L for every 1-point increase in the AG.

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When the bicarbonate concentration decrease is Table 3. Equations for Analysis of Acid-Base Disorders3 less than the increase in the AG, an underlying 1. Anion Gap (AG) = Sodium – (Bicarbonate + Chloride) metabolic alkalemia may be present. This “in- 2. Compensation for Metabolic Acidosis in PCO 1.3 x HCO equality” can be explained by the fact that the ↓ 2 = ↓ 3 3. Compensation for Metabolic Alkalosis serum bicarbonate is higher than expected for CO ↑ in P 2 = 0.6 x ↑ HCO3 the AG because the bicarbonate started at a higher 4. Compensation for CO level as a result of the underlying alkalosis. Acute: for every 10 mm Hg increase in P 2, HCO3 in- creases by 1 mEq/L CO Chronic: for every 10 mm Hg increase in P 2, HCO3 in- Case Studies creases by 4 mEq/L 5. Compensation for CO A collection of case studies is used to illustrate Acute: for every 10 mm Hg decrease in P 2, HCO3 de- the application of this five-step approach to inter- creases by 2 mEq/L CO Chronic: for every 10 mm Hg decrease in P 2, HCO3 de- pret ABGs, discuss the etiology of acid-base disor- creases by 4 mEq/L ders, and develop an appropriate treatment plan. 6. Increased AG Metabolic Acidosis A summary of equations used in the case studies each 1-point ↑ in AG should be equaled by a 1 mEq/L ↓ in HCO is provided in Table 3. 3 7. Normal AG Metabolic Acidosis each 1 mEq/L ↑ in chloride should be equaled by a 1 mEq/L ↓ Case 1 A 2-year-old, 13 kg male with a history of Hirschsprung’s disease is postoperative day 2 following cause this disorder. Both loop and thiazide diuret- a small bowel resection. His nasogastric tube is con- ics promote a disproportionate excretion of chlo- nected to low intermittent suction and draining copious ride in relation to bicarbonate. Administration of amounts of green fluid. Urine output has decreased to 0.3 mL/kg/hr despite receiving maintenance intravenous high-dose penicillin antibiotics (e.g., carbenicil- fluids of dextrose 5%/0.2% normal saline. Laboratory lin, ticarcillin) enhances the secretion of potas- values and ABG on room air are as follows: sium and hydrogen ions because they act as Sodium 144 mEq/L, Potassium 3.2 mEq/L, Chloride nonreabsorbable anions. Alkali administration via 94 mEq/L, or organic acids converted O CO ABG: pH 7.52, P 2 90 mm Hg, P 2 48 mm Hg, HCO3 to bicarbonate, such as lactate, acetate, and cit- 39 mEq/L. rate, may also contribute to metabolic alkalemia. Step 1: Elevated pH indicates the presence of Certain situations require acute management alkalemia. of the alkalemic state. Severe alkalemia may have Step 2: The primary process is metabolic since adverse consequences, such as , muscle CO the HCO3 is elevated and P 2 is not weakness, ileus, and predisposition to arrhythmias decreased. as a result of decreased ionized calcium and in- Step 3: Calculate the gaps. tracellular shifts of potassium, magnesium and AG = 144 – (39 + 94) = 11 mEq/L. A phosphorus.4 Treatment modalities for manage- normal AG is 10 ± 4 mEq/L, thus the ment of metabolic alkalosis can be remembered AG is normal. with the mnemonic CARP: Chloride, Aldoster- Step 4: Check for the degree of compensation. one, Renal perfusion, Potassium. In the patient CO The increase in P 2 is 8.4 (0.6 × 14), with adequate renal function, the first step is to thus 40 + 8.4 = 48.4. The calculated maximize the patient’s ability to excrete excess CO increase in P 2 of 48.4 mm Hg is equal bicarbonate by correcting extracellular fluid CO to the measured P 2 of 48 mm Hg, (ECF) volume depletion with 0.9% saline (NaCl). thus the metabolic alkalemia is fully Then minimize production, admin- compensated. ister IV fluids to improve Renal perfusion, and Step 5: Determine the 1:1 relationship. This supplement Potassium chloride. If alkalemia is calculation is not necessary. due to gastric losses, the patient is usually ECF The mechanism for metabolic alkalosis in this volume-depleted, chloride-depleted, and potas- case is a result of a loss of H+ from gastrointestinal sium-depleted. Initiation of histamine2-receptor fluids via the nasogastric tube. Other etiologies (H2) antagonists or proton pump inhibitors may for metabolic alkalosis are summarized in Table be useful in decreasing gastric acid losses. If alka- 4. Of special note is the ability of medications to lemia is diuretic-induced, potassium and ECF vol-

238 J Pediatr Pharmacol Ther 2004 Vol. 9 No. 4 • www.ppag.org The ABC’s of Acid-Base Balance JPPT

Table 4. Causes of Metabolic Alkalosis The decrease in bicarbonate is 20 (25 – CO Extracellular Fluid or Chloride Depletion 5 = 20), so the P 2 should decrease to loss of gastrointestinal fluid (i.e., vomiting, nasogastric CO 14 mm Hg (∆P 2 = 1.3 × 20 = 26; 40 – suction) 26 = 14). The compensation for the Post hypercapnea Medications metabolic acidemia is not complete be- CO diuretic therapy (loop and thiazides) cause the P 2 of 19 mm Hg is slightly extended penicillins (carbenicillin, ticarcillin) high for normal compensation. Thus, Mineralocorticoid excess the PCO is consistent with a mild su- 2 perimposed respiratory acidosis. A sec- ond disorder, respiratory acidosis, is ume is often depleted. Converting to potassium- present. sparing diuretics may help prevent recurrences. Step 5: 1:1 Relationship – The bicarbonate de- If the ECF volume is severely contracted, tempo- crease of 20 (25 – 5 = 20), is close rarily stopping or reducing the dose of diuretics enough to the AG of 18 (30 – 12 = 18) until the disorder has resolved may be required. to exclude an underlying metabolic al- Alkalemia due to high-dose corticosteroid admin- kalosis. istration may necessitate changing to a corticos- The mechanism for metabolic acidosis in this case teroid with lower mineralocorticoid activity such is in association with the patient’s sep- as dexamethasone or methylprednisolone. Aceta- tic shock. Calculation of the AG is useful because it zolamide may be used to promote bicarbonate reveals information about the probable cause and diuresis if adequate renal perfusion is present. the most appropriate therapy for the acidosis. Clini- Rarely, intravenous HCl has been used to treat cal causes of a metabolic acidosis with an increased severe metabolic alkalemia, but it must be extem- anion gap are summarized in Table 5. Metabolic poraneously prepared by a pharmacist since it is acidosis with a normal anion gap (hyperchloremic not commercially available. Concentrated HCl is acidosis) is usually caused by either gastrointestinal mixed with intravenous fluids to make 0.1 N HCl bicarbonate loss, altered renal function, or the use in 5% dextrose and must be administered via a of certain medications. central vein. If a patient is receiving parenteral Management of patients with metabolic acido- nutrition, chloride salts (e.g., NaCl, KCl) of elec- sis depends on the origin of the disorder. If the trolyte solutions may be used and H2-antagonists acidosis is due to gastrointestinal losses, correc- can be added to the formulation. tion involves treating the underlying cause. In Case 2, the appropriate therapy would be man- Case 2 agement of the septic shock. Severe acidemia can A 9-year-old female with a history of Crohn’s dis- precipitate adverse consequences such as reduced ease is admitted to the hospital with a perforated bowel cardiac output, decreased strength of respiratory and peritonitis. After undergoing for a colec- muscles, , progressive obtundation tomy and peritoneal irrigation, she is transferred to the 4 intensive care unit (ICU). Postoperatively, she becomes and coma. Alkalinizing agents are available for septic with a temperature of 103°F. ABG and labora- the treatment of metabolic acidosis. Sodium bi- tory values upon arrival to the ICU are as follows: pH carbonate is the cornerstone of alkali therapy. CO Because of risks associated with bicarbonate 7.12, P 2 19 mm Hg, HCO3 5 mEq/L, Sodium 140 mEq/L, Potassium 4.8 mEq/L, Chloride therapy, specific dosing guidelines must be fol- 105 mEq/L. lowed. As a general rule, sodium bicarbonate is Step 1: Acidemia is present since the pH is < not used as a treatment modality unless a patient 7.35. is experiencing life-threatening adverse conse- Step 2: The primary process is metabolic since quences (i.e., cardiovascular depression) or dis- the bicarbonate is decreased and the plays a pH < 7.20 with circulatory instability. So- CO P 2 is not increased. dium bicarbonate is not recommended during Step 3: Anion gap is dramatically elevated: 140 cardiac arrest. The predominant source of acid

– (105 + 5) = 30 [normal AG = 10 ± 4]. in the tissues is accumulated CO2 due to inad- Step 4: Compensation for metabolic acidosis equate circulation, thus administration of sodium is calculated using the following for- bicarbonate will exacerbate tissue acidosis. The CO mula: ∆P 2 = 1.3 × decrease in HCO3. role of alkali therapy in lactic acidosis is contro-

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Table 5. Causes of Metabolic Acidosis brain barrier and cell membranes more readily Increased Anion Gap – Think of the mnemonic: A MUDPIE than bicarbonate. “Overshoot alkalosis” may re- sult from aggressive exogenous bicarbonate load- ing. Bicarbonate is consumed as a buffer for ke- Uremic renal failure tone bodies or and regenerated when Diabetic and other forms of ketoacidosis these organic acids are later metabolized, thus the Paraldehyde patient may develop excess ECF bicarbonate once Ischemic or idiopathic lactic acidosis Ethylene glycol the underlying cause of the acidosis is corrected. Overcompensation may occur because bicarbon- Normal Anion Gap ate equilibrates slowly across the blood brain bar- Gastrointestinal losses of HCO 3 rier. A systemic alkalemia may result because the Diarrhea brainstem areas that control ventilation continue Enteric fistula Pancreatic fistula to sense severe acidosis even after the systemic Ureteral diversions pH has been increased with exogenous bicarbon- Uretero-sigmoidostomy ate. Because of the tremendous load of sodium Ileal bladder associated with undiluted sodium bicarbonate Ileal ureter (1000 mEq sodium per liter), severe pulmonary Proximal edema and hypernatremia may develop. Caution Distal must be exercised when using this therapy in pa- Buffer deficiency (phosphate, ammonia) tients with congestive heart failure and renal fail- Medications Carbonic anhydrase inhibitors (i.e., acetazolamide) ure. Coadministration of loop diuretics may pre- Amphotericin B vent this complication. If the patient is receiving parenteral nutrition, acetate salts of electrolyte versial. Since most cases of lactic acidosis are due solutions (i.e., sodium acetate, potassium acetate) to inadequate tissue perfusion, the potential for may be used in the formulation. However, these poor of bicarbonate-generated CO2 ex- are often regarded as unreliable sources because ists in some tissues when bicarbonate therapy is their alkalinizing properties are dependent on used. Effective treatment goals with bicarbonate their conversion to bicarbonate which may be therapy include reversing the detrimental con- influenced by liver disease or circulatory failure. sequences of severe acidemia by returning the Dichloroacetate and Carbicarb are two investiga- pH to approximately 7.20 and the plasma bicar- tional agents used to treat metabolic acidosis, but bonate to 10 mEq/L. To estimate the amount of these are not routinely available in most practice sodium bicarbonate to achieve this goal, multi- settings. Tromethamine (THAM) is commercially ply the apparent volume of distribution of bicar- available in the United States, but no therapeutic bonate (0.5 L/kg) × body weight (kg) × (desired advantage to sodium bicarbonate has been dem- 4 [HCO3] – current [HCO3]). For a 30 kg patient onstrated. THAM corrects metabolic acidosis by with a plasma HCO3 of 5, the calculated dose of combining with hydrogen ions from carbonic acid sodium bicarbonate is 75 mEq infused as an in- to form bicarbonate and a cationic buffer. Its use travenous infusion over 1-2 hours [(0.5)(30)(5) is limited by the potential for severe inflamma- = 75]. To avoid risks associated with bicarbonate tion, vascular spasms, and tissue necrosis if infil- therapy, it has been recommended to add two tration occurs. 50-mL injections of 8.4% sodium bicarbonate to The oral route may be used for alkali replace- one liter of 0.2% normal saline.4 An 8.4% solu- ment. Sodium bicarbonate tablets are often used tion contains 1 mEq of sodium and 1 mEq of bi- for maintenance therapy in patients with chronic carbonate, so this manipulation would render this bicarbonate losses (i.e., renal tubular acidosis). solution nearly isotonic (~140 mEq sodium per Many patients dislike the taste of the tablets, so bak- liter). ing soda (60 mEq bicarbonate/tsp) may be used as Excessive administration of sodium bicarbon- an alternative. Shohl’s solution (sodium citrate/cit- ate has been associated with several problems. ric acid) is a liquid dosage form preferred by some CO Increased P 2 generation and a worsening of aci- patients. Citrate preparations, however, may in- dosis in the central nervous system may occur as crease gastrointestinal absorption of aluminum and a result of CO2 that freely diffuses across the blood this may be a problem in renal failure patients.

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Case 3 Table 6. Causes of Respiratory Alkalosis A 5-year-old, 25 kg boy sustained severe head inju- Psychogenic ries, a grade IV splenic laceration, a tibia-fibula fracture, Anxiety and a pulmonary contusion after being hit by a car while riding his bicycle. He is stabilized and transferred to the Severe asthma intensive care unit with the following laboratory values Pneumonia and ABG on admission: Sodium 135 mEq/L, Potassium Pulmonary embolus Congestive heart failure/pulmonary edema 3.1 mEq/L, Chloride 103 mEq/L, pH 7.51, PCO 25 mm 2 Infection Hg, HCO 22 mEq/L. 3 Gram-negative Step 1: Alkalemia is present since the pH > Fever 7.45. Increased intracranial pressure Step 2: The primary process is respiratory be- Head trauma /hemorrhage CO cause the P 2 is < 40 mm Hg and the Tumor HCO3 is not increased. Salicylate toxicity Step 3: AG is normal [135 – (103 + 22) = 10]. Liver disease Step 4: Compensation for respiratory alkalemia Excessive is calculated by the following formula: the HCO decreases by 2 mEq/L for breathing after several days of persistent diarrhea. She 3 is treated with intravenous steroids, aerosolized every 10 mm Hg decrease in PCO (for 2 bronchodilators, and oxygen, but her breathing con- acute respiratory alkalosis). Since the tinues to worsen. Laboratory values and ABG are as CO decrease in P 2 is 15 (40 – 25 = 15 mm follows: Sodium 137 mEq/L, Potassium 2.1 mEq/L, Hg), the calculated decrease is 3. In this CO Chloride 111 mEq/L, pH 6.94, P 2 60 mm Hg, HCO3 case, the calculated decrease is identi- 15 mEq/L. cal to the actual decrease (25 – 22 = 3), Step 1: Acidemia is present (pH < 7.35). so only acute respiratory alkalemia is Step 2: The primary process is both respiratory present with normal compensation. If CO (P 2 > 40 mm Hg) and metabolic the situation is chronic (> 3 days), the (HCO3 is decreased). degree of compensation varies: for ev- Step 3: AG is normal [137 – (111 + 15) = 11]. CO ery P 2 decrease of 10 mm Hg, the Step 4: Compensation – There is no need to

HCO3 decreases by 4 mEq/L. If the perform this calculation since the co- calculation of the degree of metabolic existence of two academic abnormali- compensation is not close to the actual ties confirms the absence of compen-

value for the HCO3 (± 2 mEq/L), an sation. additional primary metabolic disorder Step 5: 1:1 Relationship – In a normal AG is present. metabolic acidosis, any decrease in Step 5: 1:1 Relationship – Since the AG is nor- HCO3 should be equal to the increase mal, the bicarbonate decrease of 3 (25 – in chloride. The change in HCO3 was 22 = 3) is the same as the chloride in- 10 mEq/L (25 – 15 = 10) and the chlo- crease of 3 (103 – 100 = 5). Thus, no ride level increased by 11 mEq/L (111 underlying metabolic alkalosis exists. – 100 = 11), so the relationship of HCO3 The mechanism for respiratory alkalosis in this to chloride was approximately 1:1. CO case is decreased P 2 from ventilation in excess Thus, no underlying metabolic alkalo- of CO2 production due to head trauma. Other sis is present. clinical causes for respiratory alkalosis are sum- In situations of mixed acid-base disorders (i.e., marized in Table 6. Management of respiratory metabolic and respiratory acidosis), it is often alkalosis primarily involves treating the underly- helpful to determine the primary process in or- ing cause. In mechanically ventilated patients, it der to determine the most appropriate manage- may be necessary to suppress patient-triggered ment. Measurement of urinary can be breaths with opiates or sedative agents. employed to differentiate the cause of the nor- mal AG metabolic acidosis.3 The responds Case 4 to gastrointestinal HCO3 loss with a compensa- A 6-year-old female with steroid-dependent asthma tory loss of ammonium in the urine, thereby acidi- presents to the Emergency Department with labored fying the urine. Ammonium is the predominant J Pediatr Pharmacol Ther 2004 Vol. 9 No. 4 • www.ppag.org 241 JPPT Sacks GS

Table 7. Causes of Respiratory Acidosis tion would further decline due to an intracellu- Impaired Central Nervous System (CNS) lar shift causing additional muscle weakness and CNS disease (e.g., injury, neoplasm, infection) potentially a fatal respiratory collapse. The mecha- Drug/poison (e.g., opiates, alcohols, anesthetics) nism for the respiratory acidosis in this case is the Metabolic (e.g., anoxia) Mechanical patient’s hypoventilation from severe airway ob- Airway obstruction (e.g., severe asthma, foreign body, struction and fatigue. Other causes for respira- tumor) tory acidosis are listed in Table 7. The patient is Pneumothoraces treated with mechanical ventilation for the respi- Neuromuscular Spinal cord injury ratory acidosis and aggressive intravenous potas- 5 Paralyzing agents sium chloride replacement for her . When potassium exceeds 3.3 mEq/L, the patient Guillain-Barré, ALS, MS can slowly be treated with sodium bicarbonate if Loss of area Severe pneumonia the pH remains less than 7.20. Dosing guidelines Severe pulmonary edema for sodium bicarbonate are the same as previously Emphysema outlined. Massive pulmonary embolus In summary, acid-base disorders are common in both hospitalized and ambulatory patients. These unmeasured cation and its excretion is usually disorders may exist as single or mixed entities as accompanied by chloride. A urine delta gap can illustrated in the case studies. A systematic approach be calculated by subtracting urinary chloride from to acid-base disturbances can assist the clinician in urinary sodium and potassium (i.e., urine delta identifying all the abnormalities present so that gap = [urinary sodium + urinary potassium] – appropriate treatment can be initiated and its re- urinary chloride). Under normal circumstances, sponse can be accurately monitored. 20 – 40 mEq/L of ammonium is excreted each day in the urine, and the urine delta gap has a REFERENCES negative value of –20 to 0 mEq/L. The normal response to an acid load is an increase in renal 1. Narins RG, Emmett M. Simple and mixed production of ammonia, with an increase in urine acid-base disorders: a practical approach. ammonium excretion. In metabolic acidosis, am- Medicine 1980;59:161-87. monium excretion should increase dramatically 2. Preuss HG. Fundamentals of clinical acid-base if acidification is intact, resulting in a large nega- evaluation. Clin Lab Med 1993;13:103-16. tive urine delta gap (–20 to –50 mEq/L). If a de- 3. Rutecki GW, Whittier FC. Applying five rules fect in renal acidification is present (i.e., renal in everyday acid-base cases. Consultant tubular acidosis), ammonium excretion is im- 1997;37:3067-75. paired and the urine delta gap is a positive value. 4. Adrogue HJ, Madias NE. Management of life- Knowledge of this patient’s urinary electrolytes threatening acid-base disorders: first of two confirmed that the likely cause of the normal an- parts. N Engl J Med 1998;338:26-34. ion gap metabolic acidosis was the diarrhea. How- 5. Adrogue HJ, Madias NE. Management of life- ever, should this patient’s treatment begin with threatening acid-base disorders: second of two administration of sodium bicarbonate to correct parts. N Engl J Med 1998;338:107-11. the metabolic process, the potassium concentra-

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