Ebook Marinos the little ICU book (2/E): Part 2

(BQ) Part 1 book Marinos the little ICU book has contents: Acid-Base analysis, organic acidoses, metabolic alkalosis, acute kidney injury, abdominal infections, abdominal infections, abdominal infections, nutritional requirements, parenteral nutrition, antimicrobial therapy,... and other contents.

Chapter 23

Acid-Base Analysis

This chapter describes how to identify acid-base disorders using the pH, PCO2 and bicarbonate (HCO3)concentration in blood Included are: (a) simple rules for the identification of primary, secondary, andmixed acid-base disorders, (b) formulas for determining the expected acid-base changes for each of theprimary acid-base disorders, and (c) a description of the “anion gap” and how it is used

I ACID-BASE BALANCE

According to traditional concepts of acid-base physiology, the hydrogen ion (H+) concentration inextracellular fluid is determined by the balance between the partial pressure of carbon dioxide (PCO2)and the bicarbonate (HCO3) concentration (1):

[H+] = k × (PCO2/HCO3)

(k is a proportionality constant) This means that all acid-base disorders are defined by two variables: PCO2 and HCO3 This is shown in Table 23.1

A Types of Acid-Base Disorders

1 A respiratory acid-base disorder is a change in [H+] that is a direct result of a change in PCO2.According to Equation 23.1, an increase in PCO2 will increase the [H+] and produce a respiratory acidosis, while a decrease in PCO2 will decrease the [H+] and produce a respiratory alkalosis.

2 A metabolic acid-base disorder is a change in [H+] that is a direct result of a change in HCO3

Equation 23.1 predicts that an increase in HCO3 will decrease the [H+] and produce a metabolic alkalosis, while a decrease in HCO3 will increase the [H+] and produce a metabolic acidosis.

3 Acid base disorders can be primary (the principal disturbance) or secondary (an additional

disturbance)

B Compensatory Responses

1 Compensatory responses are designed to limit the change in H+ concentration produced by theprimary acid-base disorder This is accomplished by changing the secondary variable in the samedirection as the primary variable (e.g., a primary increase in PCO2 is accompanied by acompensatory increase in HCO3), as shown in Table 23.1

2 Compensatory responses do not completely correct the change in [H+] produced by the primaryacid-base disorder (2)

3 The specific features of compensatory responses are described next The equations that describethese responses are shown in Table 23.2

in 30–120 minutes, and can take 12 to 24 hours to complete (2) The magnitude of the response isdefined by the equation below (2)

Δ PaCO2 = 1.2 × Δ HCO3Using a normal PaCO2 of 40 mm Hg and a normal HCO3 of 24 mEq/L, the above equation can berewritten as follows:

(23.4)

(23.5)

Expected PaCO2 = 40 – [1.2 × (24 – HCO3)]

a EXAMPLE: For a primary metabolic acidosis with a plasma HCO3 of 14 mEq/L, the ΔHCO3

is 24 – 14 = 10 mEq/L, the ΔPaCO2 is 1.2 × 10 = 12 mm Hg, and the expected PaCO2 is 40 –

12 = 28 mm Hg If the measured PaCO2 is >28 mm Hg, there is a secondary respiratoryacidosis, and if the measured PaCO2 is <28 mm Hg, there is a secondary respiratory alkalosis

2 Response to Metabolic Alkalosis

The compensatory response to metabolic alkalosis is a decrease in minute ventilation and asubsequent increase in PaCO2 This response is not as vigorous as the response to metabolicacidosis (because the baseline activity of peripheral chemoreceptors is low, so they are easier tostimulate than inhibit) The magnitude of the response is defined by the equation below (2)

Δ PaCO2 = 0.7 × Δ HCO3Using a normal PaCO2 of 40 mm Hg and a normal HCO3 of 24 mEq/L, the above equation can berewritten as follows:

Expected PaCO2 = 40 + [0.7 × (HCO3 – 24)]

a EXAMPLE: For a metabolic alkalosis with a plasma HCO3 of 40 mEq/L, the ΔHCO3 is 40 –

24 = 16 mEq/L, the ΔPaCO2 is 0.7 × 16 = 11 mm Hg, and the expected PaCO2 is 40 + 11 = 51

mm Hg

pH = 7.36–7.44PCO2 = 36–44 mm HgHCO3 = 22–26 mEq/L

c EXAMPLE: Consider a case where the arterial pH is 7.23 and the PaCO2 is 23 mm Hg The

pH and PaCO2 are both decreased (indicating a primary metabolic disorder) and the pH is

c EXAMPLE: Consider a case where the arterial pH is 7.38 and the PaCO2 is 55 mm Hg Onlyone variable (the PaCO2) is abnormal, indicating a mixed metabolic and respiratory disorder.The PaCO2 is elevated, indicating a respiratory acidosis, so the opposing metabolic disorder

must be a metabolic alkalosis Therefore, this condition is a mixed respiratory acidosis and metabolic alkalosis Both disorders are equal in strength because the pH is normal.

Step 2: Identify Secondary Disorders

If the first step identified a primary disorder (instead of a mixed disorder), the next step is to calculate theexpected acid-base changes using the equations in Table 23.2 The expected changes are then compared tothe actual changes, and discrepancies between the two are used to identify secondary acid-base problems.This process is demonstrated in the following example

1 EXAMPLE: Consider a case with the following arterial blood gas results: pH = 7.32, PaCO2 = 23

mm Hg, HCO3 = 16 mEq/L

a This represents a primary metabolic acidosis because the pH and PCO2 are both decreased

b Equation 23.3 is then used to calculate the expected PaCO2 from the compensatory response.The expected PaCO2 is 40 – [1.2 × (24 – 16)] = 30.4 mm Hg

c The expected and measured PaCO2 are then compared The measured PaCO2 (23 mm Hg) islower than the expected PaCO2 (30.4 mm Hg), indicating a secondary respiratory alkalosis

Na – (CL + HCO3) = UA – UC

1 The difference between unmeasured anions and unmeasured cations (UA – UC) is the anion gap(AG), so Equation 23.12 can be restated as:

AG = Na – (CL + HCO3) (mEq/L)The anion gap is thus a very simple calculation that involves routinely monitored electrolytes

AG, as shown in Table 23.3

1 High Anion Gap Acidosis

Frequent sources of high AG metabolic acidosis include lactic acidosis, ketoacidosis, and stage renal failure (due to loss of H+ secretion in the distal renal tubules) Other notable sources aretoxic ingestions of methanol (which produces formic acid), ethylene glycol (which produces oxalicacid), and salicylates (which produce salicylic acid) (9)

end-2 Normal Anion Gap Acidosis

Common causes of metabolic acidosis with a normal AG include diarrhea (especially secretorydiarrhea), isotonic saline infusion (see Chapter 10, Section I-B-3), and early renal failure (due toloss of HCO3 reabsorption in the proximal tubules) The HCO3 loss in these conditions is replaced

by chloride for electrical neutrality, and the term hyperchloremic metabolic acidosis is also used

for this type of metabolic acidosis (In high AG metabolic acidoses, the acids dissociate andgenerate anions that balance the decrease in HCO3, so there is no associated hyperchloremia.)

The reliability of the anion gap for detecting strong acids has been inconsistent, and there are a number ofreports showing a normal AG in patients with lactic acidosis (10,11) and ketoacidosis (see Reference 21

b The other factor is the ability of hypoalbuminemia to decrease the AG (13), which isdescribed next

2 Influence of Albumin

The unmeasured anions and cations that normally contribute to the anion gap are shown in Table23.4 Note that albumin is the principal unmeasured anion, and the principal determinant of the anion gap.

a Albumin is a weak acid that contributes about 3 mEq/L to the AG for each 1 g/dL of albumin inplasma (at a normal pH) (3)

b Hypoalbuminemia lowers the AG, and this could hinder or prevent an increase in AG inmetabolic acidoses caused by the accumulation of strong acids Considering thathypoalbuminemia is present in as many as 90% of ICU patients (13), the influence of albumin

5 Fencl V, Leith DE Stewart’s quantitative acid-base chemistry: applications in biology and medicine.Respir Physiol 1993; 91:1–16.

6 Narins RG, Emmett M Simple and mixed acid-base disorders: a practical approach Medicine1980; 59:161–187

11 Schwartz-Goldstein B, Malik AR, Sarwar A, Brandtsetter RD Lactic acidosis associated with anormal anion gap Heart Lung 1996; 25:79–80

12 Adams BD, Bonzani TA, Hunter CJ The anion gap does not accurately screen for lactic acidosis inemergency department patients Emerg Med J 2006; 23:179–182

13 Figge J, Jabor A, Kazda A, Fencl V Anion gap and hypoalbuminemia Crit Care Med 1998;26:1807–1810

14 Mallat J, Barrailler S, Lemyze M, et al Use of sodium chloride difference and corrected anion gap

as surrogates of Stewart variables in critically ill patients PLoS ONE 2013; 8:e56635

(Note: Because the pertinent issues in lactic acidosis are often related to the lactate level rather than the

acidosis, the term hyperlactatemia will be used interchangeably with lactic acidosis.) Several conditionscan be responsible for hyperlactatemia, as shown in Table 24.1 The most prevalent of these conditionsare sepsis and the clinical shock syndromes (i.e., hypovolemic, cardiogenic, and septic shock)

1 Clinical Shock Syndromes

Hyperlactatemia is universal in the clinical shock syndromes (since it is required for the diagnosis)and the prognosis in these conditions is related to the severity of the lactate elevation, and the timerequired for the lactate levels to normalize (lactate clearance) These relationships aredemonstrated in Figure 6.2 (Chapter 6)

2 Sepsis

Serum lactate levels have the same diagnostic and prognostic significance in sepsis as they do in inthe shock syndromes The lactic acidosis in sepsis is not the result of inadequate tissue oxygenation(see Chapter 6, Section III-F), which has important implications for the traditional emphasis onpromoting tissue oxygenation in patients with lactic acidosis

3 Thiamine Deficiency

Thiamine deficiency is often overlooked as a cause of elevated blood lactate levels Thiamine is acofactor for pyruvate dehydrogenase (the enzyme that converts pyruvate to acetyl coenzyme A, andlimits conversion to lactate), and thiamine deficiency can result in severe lactic acidosis (2) (See

Chapter 36, Section III-A for more information on thiamine deficiency.)

4 Drugs

A variety of drugs can produce hyperlactatemia, as indicated in Table 24.1 Most cases are due to

an impaired oxidative metabolism, but epinephrine and high-dose β2 agonists promotehyperlactatemia by increasing the production of pyruvate (1)

a METFORMIN: Metformin is an oral hypoglycemic agent that produces lactic acidosis duringtherapeutic dosing The mechanism is unclear, and it occurs primarily in patients with renalinsufficiency (3) The lactic acidosis can be severe, with a mortality rate that exceeds 45% ifuntreated (3,4) Plasma metformin levels are not routinely available, and the diagnosis isbased on excluding other causes of lactic acidosis The preferred treatment is hemodialysis(3,4)

5 Propylene Glycol

Propylene glycol is used as a solvent in intravenous preparations of lorazepam, diazepam, esmolol,nitroglycerin, and phenytoin It is metabolized primarily in the liver, and the principal metabolitesare lactate and pyruvate (5)

1 Serum lactate levels are readily available, and screening tests for lactic acidosis, such as the aniongap, are not necessary (and can be unreliable, as described in Chapter 23, Section III-C)

2 Lactate levels can be measured in venous or arterial blood, with equivalent results (1)

3 The upper limit of normal for serum lactate varies from 1.0 to 2.2 mmol/L in individuallaboratories (1), but 2 mmol/L seems to be a common cutoff point However, lactate levels mustrise above 4 mmol/L to show an association with increased mortality (8), so a cutoff of 4 mmol/Lmay be more appropriate for clinically significant hyperlactatemia

C Alkali Therapy

Therapy aimed at correcting the acidosis does not have a major role in the management of patients withlactic acidosis The following is a brief summary of the relevant issues in alkali therapy for lacticacidosis

1 The Bicarbonate Experience

Clinical studies have consistently shown that sodium bicarbonate infusions are withouthemodynamic benefit or survival benefit in lactic acidosis (9-11) Furthermore, bicarbonateinfusions are accompanied by several undesirable effects (see Table 24.2), including an increase inarterial PCO2 and a paradoxical decrease in intracellular pH (attributed to transcellular movement

of the generated CO2) (9,12)

2 Current Recommendations

Given the lack of benefit, and the associated risk, bicarbonate therapy is not recommended as atreatment modality in lactic acidosis (9,13) Furthermore, bicarbonate therapy has been removedfrom the ACLS guidelines on cardiac arrest (14) Nevertheless, there continue to berecommendations for bicarbonate therapy in cases of severe acidosis, when the pH falls below 7.0(15) The current use of bicarbonate is predominantly as a “desperation measure” to restorevasopressor responsiveness in patients who are rapidly deteriorating

3 Replacement Regimen

The popular fluid for bicarbonate replacement is a 7.5% sodium bicarbonate solution, and Table24.2 shows the composition of this fluid Note the hyperosmolality (which mandates infusionthrough a large vein) and the extremely high PCO2 (which explains the increase in arterial PCO2associated with bicarbonate infusions)

a The bicarbonate dose is determined by estimating the HCO3 deficit with the followingequation (15,16)

HCO3 deficit = 0.6 × wt (kg) × (15 – plasma HCO3)where wt is ideal body weight, and 15 mEq/L is the desired plasma HCO3 (For an adult with

an ideal body weight of 70 kg and a plasma HCO3 of 10 mEq/L, the HCO3 deficit is 0.6 × 70

× (15 – 10) = 210 mEq.)

b The HCO3 deficit can be replaced at a rate of 1 mEq/kg per hour (11) The PaCO2 should bemonitored during bicarbonate infusions, and increases in the PaCO2 should be corrected byadjusting the ventilator settings to provide an increased minute ventilation

c If there is no hemodynamic or clinical improvement after a few hours, the bicarbonate infusionshould be discontinued

II DIABETIC KETOACIDOSIS

A Ketoacids

AcAc and β-OHB are strong acids (ketoacids), and plasma concentrations above 3 mmol/L produce ametabolic acidosis (17) β-OHB is the predominant ketoacid (see Figure 24.1), and is about three timesmore abundant than AcAc Acetone is not a ketoacid, but is responsible for the characteristic “fruity”odor of the breath in patients with ketoacidosis

1 The Nitroprusside Reaction

The nitroprusside reaction is a popular, colorimetric method for detecting ketones in blood andurine The test can be performed with tablets (Acetest) or reagent strips (Ketostix, Labstix,Multistix)

a THE PROBLEM: The nitroprusside reaction has one major shortcoming; i.e., it detects only

acetone and AcAc, and does not detect β-OHB (17), the predominant ketoacid in blood This

limitation is illustrated in Figure 24.1 Note that, in alcoholic ketoacidosis, the totalconcentration of ketoacids in blood is 13 mmol/L (about 4 times the concentration thatproduces an acidosis), but the ketoacids will not be detected because the AcAc level is belowthe threshold for detection (3 mmol/L)

2 β-hydroxybutyrate Monitoring

Portable “ketone meters” are now available that provide reliable measurements of β-OHB infingerstick (capillary) blood in about 10 seconds (18) The American Diabetes Associationconsiders this the preferred method for monitoring ketoacidosis (19)

b Elevated troponin I levels without an acute coronary event has been reported in 27% ofpatients with DKA (23).

c Hyperamylasemia is common in DKA, but the amylase is extrapancreatic (19).

d Dehydration is almost universal in DKA, but this may not be reflected in the plasma sodiumconcentration because hyperglycemia draws water from intracellular fluid, which causes adilutional decrease in the serum sodium concentration, and this masks free-water loss(dehydration)

e The dilutional effect of hyperglycemia results in decrease in serum sodium of 1.6 to 2.4 mEq/L for every 100 mg/dL increase in the serum glucose concentration (24,25)

b Note in Table 24.3 that the “corrected” serum sodium concentration is used to select theappropriate IV fluid after hemodynamic stability is achieved This correction refers to thepreviously-described dilutional effect of hyperglycemia on the serum sodium concentration,which is 1.6 to 2.4 mEq/L for every 100 mg/dL increase in the serum glucose

c EXAMPLE: Using 2 mEq/L as the correction factor, if the sodium concentration is 140 mEq/Land the plasma glucose is 600 mg/dL, the dilutional effect is 2 × 5 = 10 mEq/L, so thecorrected sodium concentration is 140 + 10 = 150 mEq/L

d Note also in Table 24.3 that 5% dextrose is added to the IV fluids when the serum glucose

2 Insulin

A protocol for insulin therapy in DKA is shown in Table 24.4 The following are some highlights

a Note that insulin should not be started if the patient is hypokalemic (which is uncommon whenDKA first presents)

b Regular insulin is started with an IV bolus dose of 0.15 units/kg (some consider thisunnecessary) followed by a continuous infusion at 0.1 units/kg/hr

c Insulin infusions are continued until the ketoacidosis has resolved (see later for how this isdetermined) and oral nutrient intake is possible Thereafter, subcutaneous insulin is started asdirected in Table 24.4

d Achieving euglycemia is never advised in the ICU setting because of the risk of hypoglycemia,and the goal of glycemic control is a serum glucose of 150–200 mg/dL (26)

3 Potassium

a Potassium depletion is universal in DKA, with an average deficit of 3–5 mEq/kg (20), but the

b The serum potassium can fall precipitously during insulin therapy (transcellular shift), sopotassium replacement should be started as soon as possible, and serum potassium levelsshould be monitored every 1–2 hours until levels stabilize Adding potassium to the IV fluids,

as indicated in Table 24.5, is usually effective in maintaining normokalemia (19)

4 Phosphate

The situation with phosphate is very similar to potassium (i.e., depletion common but serum levelsrarely low at presentation, and serum levels decline during insulin infusions) with one exception;i.e., routine phosphate replacement has no documented benefit in DKA, and is not recommendedunless phosphate levels are <1 mg/dL (19,26)

5 Alkali Therapy

The recommendations for bicarbonate replacement in DKA are the same as those described earlierfor lactic acidosis; i.e., bicarbonate therapy has no documented benefit in DKA, even when theacidosis is severe (pH 6.9–7.1) (27), and it is not recommended until the pH falls below 7.0 (19)

D Acid-Base Monitoring

1 Resolution of DKA has been defined as a plasma glucose <200 mg/dL, plasma HCO3 ≥18 mEq/L,and venous pH >7.3 (19)

2 The HCO3 and pH will be unreliable when isotonic (0.9%) saline is the predominant resuscitationfluid because the high chloride concentration in isotonic saline produces a hyperchloremicmetabolic acidosis (see Chapter 10, Section I-B-3) that will counteract the increase in serum HCO3from the resolving ketoacidosis

3 The anion gap should be a more reliable measure for monitoring the resolution of DKA.

1 The management of AKA is notable for its simplicity; i.e., infusion of dextrose-containing salinesolutions is usually all that is required The glucose infusion slows hepatic ketone production,while the infused volume promotes the renal clearance of ketones

2 Thiamine supplementation is recommended because glucose infusions can deplete marginalthiamine reserves

4 Perrone J, Phillips C, Gaieski D Occult metformin toxicity in three patients with profound lacticacidosis J Emerg Med 2011; 40:271–275.

5 Wilson KC, Reardon C, Theodore AC, Farber HW Propylene glycol toxicity: a severe iatrogenicillness in ICU patients receiving IV benzodiazepines Chest 2005; 128:1674–1681

6 Arroglia A, Shehab N, McCarthy K, Gonzales JP Relationship of continuous infusion lorazepam toserum propylene glycol concentration in critically ill adults Crit Care Med 2004; 32:1709–1714

7 Orringer CE, Eusace JC, Wunsch CD, Gardner LB Natural history of lactic acidosis after grand-malseizures A model for the study of anion-gap acidoses not associated with hyperkalemia N Engl JMed 1977; 297:796–781

8 Okorie ON, Dellinger P Lactate: biomarker and potential therapeutic target Crit Care Clin 2011;27:299–326

9 Forsythe SM, Schmidt GA Sodium bicarbonate for the treatment of lactic acidosis Chest 2000;117:260–267

10 Cooper DJ, Walley KR, Wiggs RR, et al Bicarbonate does not improve hemodynamics in criticallyill patients who have lactic acidosis: a prospective, controlled clinical study Ann Intern Med 1990;112:492–498

11 Mathieu D, Neviere R, Billard V, et al Effects of bicarbonate therapy on hemodynamics and tissueoxygenation in patients with lactic acidosis: A prospective, controlled clinical study Crit Care Med1991; 19:1352–1356

12 Kimmoun A, Novy E, Auchet T, et al Hemodynamic consequences of severe lactic acidosis in shockstates: from bench to bedside Crit Care 2015; 19:175

13 Dellinger RP, Levy MM, Rhodes A, et al Surviving Sepsis Campaign: International guidelines formanagement of severe sepsis and septic shock, 2012 Intensive Care Med 2013; 39:165–228

14 Link MS, Berkow LC, Kudenchuk PJ, et al Part 7: Adult advanced cardiovascular life support:

2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation andEmergency Cardiovascular Care Circulation 2015; 132(Suppl 2):S444–S464

15 Sabatini S, Kurtzman NA Bicarbonate therapy in severe metabolic acidosis J Am Soc Nephrol2009; 20:692–695

16 Rose BD, Post TW Clinical physiology of acid-base and electrolyte disorders 5th ed New York:McGraw-Hill, 2001:630–632

17 Cartwright MM, Hajja W, Al-Khatib S, et al Toxigenic and metabolic causes of ketosis andketoacidotic syndromes Crit Care Clin 2012; 601–631

18 Plüdderman A, Hemeghan C, Price C, et al Point-of-care blood test for ketones in patients withdiabetes: primary care diagnostic technology update Br J Clin Pract 2011; 61:530–531

19 American Diabetes Association Hyperglycemic crisis in diabetes Diabetes Care 2004;27(Suppl):S94–S102

20 Charfen MA, Fernandez-Frackelton M Diabetic ketoacidosis Emerg Med Clin N Am 2005;23:609–628

21 Gamblin GT, Ashburn RW, Kemp DG, Beuttel SC Diabetic ketoacidosis presenting with a normalanion gap Am J Med 1986; 80:758–760

22 Slovis CM, Mork VG, Slovis RJ, Brain RP Diabetic ketoacidosis and infection: leukocyte count anddifferential as early predictors of serious infection Am J Emerg Med 1987; 5:1–5.

23 AlMallah M, Zuberi O, Arida M, Kim HE Positive troponin in diabetic ketoacidosis withoutevident acute coronary syndrome predicts adverse cardiac events Clin Cardiol 2008; 31:67–71

24 Rose BD, Post TW Hyperosmolal states: hyperglycemia In: Clinical physiology of acid-base andelectrolyte disorders 5th ed New York, NY: McGraw-Hill, 2001; 794–821

25 Moran SM, Jamison RL The variable hyponatremic response to hyperglycemia West J Med 1985;142:49–53

26 Westerberg DP Diabetic ketoacidosis: evaluation and treatment Am Fam Physician 2013; 87:337–346

27 Morris LR, Murphy MB, Kitabchi AE Bicarbonate therapy in severe diabetic ketoacidosis AnnIntern Med 1986; 105:836–840

28 McGuire LC, Cruickshank AM, Munro PT Alcoholic ketoacidosis Emerg Med J 2006; 23:417–420

Metabolic Alkalosis

Metabolic acidosis gets all the headlines, but metabolic alkalosis is the most common acid-base disorder

in hospitalized patients (1-3) The prevalence of metabolic alkalosis can be attributed to three factors: (a)common etiologies (e.g., diuretic therapy), (b) a tendency for the alkalosis to be sustained (thanks tochloride), and (c) failure to identify and correct the factors that maintain the alkalosis

I ORIGINS

Metabolic alkalosis is defined as an increase in the bicarbonate (HCO3) concentration in extracellularfluid (plasma) that is not an adaptive response to hypercapnia The normal range for the plasma HCO3 is22–26 mEq/L

a Chloride depletion promotes the renal retention of HCO3 by increasing HCO3 reabsorption,and inhibiting HCO3 secretion, in the distal renal tubules Both effects are mediated by a

decrease in the luminal chloride concentration The renal actions of chloride depletion are considered the principal cause of sustained cases of metabolic alkalosis (3,4)

b Hypokalemia has the same effects as chloride depletion (though the mechanisms differ)

B Etiologies

The common conditions that precipitate and/or maintain a metabolic alkalosis are shown in Table 25.1,along with the mechanisms involved in each condition.

Gastric secretions are rich in H+ (50–100 mEq/L), CL- (120–160 mEq/L), and, to a lesser extent,

K+ (10–15 mEq/L) (5) As a result, loss of gastric secretions (e.g., from nasogastric suction)creates multiple risks for metabolic alkalosis (i.e., loss of H+, CL-, K+, and volume loss)

3 Diuretics

Thiazide diuretics and “loop” diuretics like furosemide promote metabolic alkalosis via urinarylosses of H+, CL-, K+, and volume (1-3) Urinary chloride losses (chloruresis) match the sodium

losses (natriuresis), and must be replaced to correct the alkalosis

4 Hypokalemia

Hypokalemia can precipitate a metabolic alkalosis (via transcellular shift of H+) and also helps tomaintain the alkalosis (by decreasing the renal excretion of HCO3) (1-3)

is often sustained because of coexisting chloride depletion (3)

7 Massive Transfusion

Each unit of packed red blood cells (PRBCs) contains about 17 mEq of citrate (used as ananticoagulant), which generates HCO3 when metabolized Transfusion of more than 8 units ofPRBCs can produce a metabolic alkalosis (3)

8 Others

Other causes of metabolic alkalosis include mineralocorticoid excess (primaryhyperaldosteronism), hypercalcemia and milk-alkali syndrome (chronic ingestion of calciumcarbonate-containing antacids that promote hypercalcemia), and laxative abuse

Δ PaCO2 = 0.7 × Δ HCO3

2 Using a normal PaCO2 of 40 mm Hg, and a normal plasma HCO3 of 24 mEq/L, the expected PaCO2can be calculated as follows:

Expected PaCO2 = 40 + [0.7 × (plasma HCO3 – 24)]

3 EXAMPLE: For a patient with a metabolic alkalosis and a plasma HCO3 of 40 mEq/L, the βHCO3

is 40 – 24 = 16 mEq/L, the ΔPaCO2 is 0.7 × 16 = 11.2 mm Hg, and the expected PaCO2 is 40 +

11.2 = 51.2 mm Hg This example demonstrates that a considerable rise in plasma HCO 3 (to 40 mEq/L) is needed to produce significant hypercapnia (i.e., PaCO2 >50 mm Hg)

III EVALUATION

The likely source(s) of metabolic alkalosis is usually apparent In the rare case of uncertainty, the urinarychloride concentration can be informative, as described next

A Urinary Chloride

The urinary chloride concentration can be used to classify metabolic alkalosis as chloride-responsive or chloride-resistant; the conditions associated with each category are listed in Table 25.2

(25.4)

1 Chloride-Responsive Alkalosis

A chloride-responsive metabolic alkalosis is characterized by a low urinary chloride concentration(<15 mEq/L), indicating chloride depletion

CL- deficit (mEq) = 0.2 × wt (kg) × (100 – plasma CL-)(wt is lean body weight in kg, and 100 is the desired plasma chloride in mEq/L) Thecorresponding volume of isotonic saline (0.9% NaCL) is determined as follows:

Volume (L) = CL- deficit / 154(154 is the chloride concentration in mEq/L in isotonic saline) This method is summarized in Table25.3 If the patient is hemodynamically stable, the infusion rate of saline should be 125–150 mL/hrabove the hourly fluid losses

2 EXAMPLE A 70 kg adult with protracted vomiting has a metabolic alkalosis with a plasmachloride of 80 mEq/L The chloride deficit in this case is 0.2 × 70 × (100 – 80) = 280 mEq Thevolume of isotonic saline needed to correct this deficit is 280/154 = 1.8 liters

c The recommended dose is 5–10 mg/kg (PO or IV), and the peak effect occurs about 15 hourslater (10).

C Hydrochloric Acid

Intravenous infusions of hydrochloric acid (HCL) are reserved for the rarest cases of metabolic alkalosisthat are: (a) severe (pH >7.6), (b) uncorrected by other means, and (c) appear to be harmful

1 The dose of HCL is determined by estimating the hydrogen ion (H+) deficit with the followingequation (2,9):

H+ deficit (mEq) = 0.5 × wt (kg) × (plasma HCO3 – 30)(25.5)

(wt is the lean body weight in kg, and 30 is the desired plasma HCO3)

2 The preferred HCL solution for intravenous use is 0.1N HCL, which contains 100 mEq H+ per liter.The volume of 0.1N HCL (in liters) needed to replace the H+ deficit is calculated as follows:

Volume (L) = H+ Deficit / 100This method is summarized in Table 25.4

3 HCL solutions are extremely corrosive, and extravasation can result in life-threatening tissuenecrosis (11) Infusion through a large, central vein is advised, and the infusion rate should not exceed 0.2 mEq/kg/hr (9)

4 EXAMPLE A 70 kg adult has a refractory metabolic alkalosis with a plasma HCO3 of 50 mEq/Land an arterial pH of 7.61 The H+ deficit is 0.5 × 70 × (50 – 30) = 700 mEq The correspondingvolume of 0.1N HCL is 700/100 = 7 liters, and the maximum infusion rate is (0.2 × 70)/100 = 0.14L/hour (140 mL/hr)

5 The entire H+ deficit does not have to be replaced, and the HCL infusion can be stopped when theplasma pH falls below 7.6

REFERENCES

1 Laski ME, Sabitini S Metabolic alkalosis, bedside and bench Semin Nephrol 2006; 26:404–421

2 Khanna A, Kurtzman NA Metabolic alkalosis Respir Care 2001; 46:354–365

3 Rose BD, Post TW Metabolic alkalosis In: Clinical Physiology of Acid-Base and ElectrolyteDisorders 5th ed New York: McGraw-Hill, 2001:551–577.

4 Luke RG, Galla JH It is chloride depletion alkalosis, not contraction alkalosis J Am Soc Nephrol2012; 23:204–207

5 Gennari FJ, Weise WJ Acid-base disturbances in gastrointestinal disease Clin J Am Soc Nephrol2008; 3:1861–1868

6 Javaheri S, Kazemi H Metabolic alkalosis and hypoventilation in humans Am Rev Respir Dis1987; 136:1011–1016

10 Marik PE, Kussman BD, Lipman J, Kraus P Acetazolamide in the treatment of metabolic alkalosis incritically ill patients Heart Lung 1991; 20:455–458

11 Buchanan IB, Campbell BT, Peck MD, Cairns BA Chest wall necrosis and death secondary tohydrochloric acid infusion for metabolic alkalosis South Med J 2005; 98:822

Acute Kidney Injury

As many as 70% of ICU patients have some degree of acute renal dysfunction, and about 5% require renalreplacement therapy (1) The acute renal dysfunction that occurs in critically ill patients is called acute kidney injury, and this chapter describes the diagnostic and therapeutic considerations related to this

1 Prerenal Disorders

Prerenal disorders are extrarenal, and promote AKI by decreasing renal blood flow (e.g.,hypovolemia) Correcting these disorders may, or may not, improve renal function, depending onthe severity and duration of the flow impairment in the kidneys

b AIN involves inflammatory injury in the renal parenchyma, and is described later in thechapter

3 Postrenal Obstruction

Postrenal obstruction is responsible for 10% of cases of AKI (4) The obstruction can involve themost distal portion of the renal collecting ducts (papillary necrosis), the ureters (from aretroperitoneal mass), or the urethra (strictures or prostatic enlargement) Obstructing renal calculi

2 Fractional Excretion of Sodium

The fractional excretion of sodium (FENa) is the fraction of filtered sodium that is excreted in theurine, and is equivalent to the fractional sodium (Na) clearance divided by the fractional creatinine(Cr) clearance, as expressed by the following equation:

3 Fractional Excretion of Urea

The fractional excretion of urea (FEU) is conceptually similar to the FENa, but it is not influenced

by diuretics (10), which is a major advantage over the FENa The FEU is equivalent to thefractional urea clearance divided by the fractional creatinine clearance, as expressed by thefollowing equation:

II INITIAL MANAGEMENT

The following are recommendations for the initial encounter with a patient who develops AKI, especiallywhen associated with oliguria

A What to Do

1 As just mentioned, it is often difficult to rule out a pre-renal component in oliguric AKI, anduncertainty should prompt a fluid challenge (See Chapter 7, Section III-A, for recommendations onfluid challenges.)

2 If volume infusion is not indicated, or does not correct the problem, then proceed as follows:

a Reduce fluid intake as much as possible

b Discontinue potentially nephrotoxic drugs Com-mon offenders are listed in Table 26.3

c Adjust the dose of drugs that are excreted in the urine

1 Do not give furosemide to correct oliguria (3) Intra-venous furosemide does not improve renalfunction in AKI, and does not convert oliguric to non-oliguric renal failure (1,3,12) Furosemidecan increase urine output during the recovery phase of AKI (13), and can be used at that time ifvolume overload is a problem

2 Do not use low-dose dopamine to increase renal blood flow in AKI (3,14,15) Low-dose dopaminedoes not improve renal function in patients with AKI (14,15), and it can have deleterious effects(e.g., decreased splanchnic blood flow, inhibition of T-cell lymphocyte function) (15)

III SPECIFIC CONDITIONS

A Contrast-Induced Nephropathy

Iodinated contrast agents can damage the kidneys in several ways, including direct renal tubular toxicity,renal vasoconstriction, and the generation of toxic oxygen metabolites (16) The incidence of contrast-induced nephropathy (CIN) is 8–9% (17) CIN appears within 72 hours after the contrast study, and mostcases resolve within two weeks without renal replacement therapy (24)

1 Predisposing Conditions

The risk of CIN is increased by diabetes, dehydration, renal dysfunction (serum creatinine >1.3mg/dL in males, and >1.0 mg/dL in females), and the use of nephrotoxic drugs (3)

2 Prevention

a INTRAVENOUS HYDRATION: The most effective preventive measure in high-risk patients

is intravenous hydration (if permitted) with isotonic saline at 100–150 mL/hr started 3 to

12 hours before the procedure and continued for 6–24 hours after the procedure (18) Foremergency procedures, at least 300–500 mL isotonic saline should be infused just prior to theprocedure

b N-ACETYLCYSTEINE: N-acetylcysteine (NAC) is a glutathione surrogate with antioxidantactions that has had mixed results as a protective agent for CIN (1) However, the pooledresults of 16 studies using high-dose NAC show a 50% risk-reduction for CIN (18) The high- dose NAC regimen is 1,200 mg orally twice daily for 48 hours, beginning the night before the contrast procedure For emergency procedures, the first 1,200 mg dose should be given

5 AIN usually resolves after the offending agent is discontinued, but recovery can take months

C Myoglobinuric Renal Injury

AKI develops in one-third of patients with diffuse muscle injury (rhabdomyolysis) (21,22) The culprit ismyoglobin, which is released by the injured muscle, and can damage the renal tubular epithelial cells

1 Diagnosis

The widespread myocyte injury in rhabdomyolysis produces marked elevations in the creatinekinase (CK) levels in blood (CK levels of 20,000–30,000 U/L are not uncommon) However, the

diagnosis of AKI can be difficult in this setting because the injured myocytes release creatine,which elevates the serum creatinine, and oliguria can be the result of hypovolemia, which occurswith rhabdomyolysis (23) The distinguishing feature in this setting is the presence or absence ofmyoglobin in the urine.

2 Myoglobin in Urine

bound iron, which is used to detect occult blood in urine If the test is positive, the urine iscentrifuged (to separate erythrocytes) and the supernatant is passed through a micropore filter (toremove hemoglobin) A positive test after these measures is evidence of myoglobin in urine Apositive dipstick test with no red blood cells in the urine sediment also provides supportiveevidence of myoglobinuria

Myoglobin can be detected in urine with the orthotoluidine dipstick reaction (Hemastix) for heme-a The presence of myoglobin in urine does not ensure the diagnosis, but the absence of myoglobin in urine excludes the diagnosis of myoglobinuric renal injury (22)

3 Management

Aggressive volume resuscitation to promote renal blood flow is the most effective measure for

preventing or limiting myoglobinuric renal injury Alkalinizing the urine can also limit the renalinjury, but is difficult to accomplish About 30% of patients with myoglobinuric renal injury requiredialysis (22)

D Abdominal Compartment Syndrome

An increase in intraabdominal pressure (IAP) can adversely affect renal function by decreasing both renalperfusion pressure and the net filtration pressure across the glomerulus (24) As a result, oliguria is one ofthe first signs of intraabdominal hypertension (IAH) (24) When IAH is associated with organ

dysfunction, the condition in called abdominal compartment syndrome (ACS).

1 Predisposing Conditions

ACS is traditionally associated with abdominal trauma, but several conditions can raise the IAPand predispose to ACS, including gastric distension, bowel obstruction, ileus, ascites, bowel walledema, hepatomegaly, positive-pressure breathing, upright body position, and obesity (25) Several

of these factors can co-exist in critically ill patients, which explains why IAH is discovered in as many as 60% of patients in medical and surgical ICUs (26)

a LARGE VOLUME RESUSCITATION: Large-volume resuscitation can raise IAP bypromoting edema in the abdominal organs (particularly the bowel) One report of ICU patientswith a positive fluid balance >5 liters over 24 hours found that 85% of the patients had ICH,and 25% had ACS (27)

2 Measuring Intraabdominal Pressure

IAP is measured as the pressure in a decompressed urinary bladder (intravesicular method), using

specialized bladder drainage catheters (Bard Medical, Covington, GA) Patients must be in thesupine position, with no abdominal muscle contractions, and the pressure transducer should bezeroed in the mid-axillary line The IAP is then measured (in mm Hg) at the end of expiration (24)

A Indications

1 The usual indications for RRT include:

a Volume overload

b Life-threatening hyperkalemia or metabolic acidosis

c Manifestations of uremia (e.g., encephalopathy)

d Removal of toxins (e.g., ethylene glycol)

2 Otherwise, the optimal timing for RRT in acute renal failure is unclear (29)

Hemodialysis removes solutes by diffusion, which is driven by the concentration gradient of the solutes

across a semipermeable membrane To maintain this concentration gradient, the blood and dialysis fluidare driven in opposite directions across the dialysis membrane (see Figure 26.1) This is known as

countercurrent exchange.

1 Method

To perform acute hemodialysis, a large-bore double-lumen catheter is inserted percutaneously intothe internal jugular or femoral veins, and advanced into the superior or inferior vena cava (See

Appendix 3 for the size and flow characteristics of hemodialysis catheters.) Venous blood iswithdrawn through one lumen of the catheter by a pump in the dialysis machine, which propels theblood at a rate of 200–300 mL/min as it passes the dialysis membrane and returns through the otherlumen of the catheter (29)

2 Method

The popular method at present is continuous venovenous hemofiltration (CVVH), which has a

circuit design similar to hemodialysis (i.e., a large-bore, double-lumen cath-eter is used tocannulate one of the vena cavae, and a pump is used to circulate blood through the hemofiltration