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Acid Base Disorders

PCCSU Volume 25, Lesson 19

PCCSU

The American College of Chest Physicians offers this lesson as a review of a previously offered self-study program. The program provides information on pulmonary, critical care, and sleep medicine issues. CME is no longer available for the PCCSU program.

Objectives

  • Update your knowledge and understanding of pulmonary medicine topics.
  • Update your knowledge and understanding of critical care medicine topics.
  • Update your knowledge and understanding of sleep medicine topics.
  • Learn clinically useful practice procedures.

CME Availability

Effective July 1, 2013, PCCSU Volume 25 is available for review purposes only.

Effective December 31, 2012, PCCSU Volume 24 is available for review purposes only.

Effective December 31, 2011, PCCU Volume 23 is available for review purposes only. CME credit for this volume is no longer being offered

Effective December 31, 2010, PCCU Volume 22 is available for review purposes only. CME credit for this volume is no longer being offered.

Accreditation Statement

The American College of Chest Physicians is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CME Statement

Credit no longer available as of July 1, 2013.

Disclosure Statement

The American College of Chest Physicians (CHEST) remains strongly committed to providing the best available evidence-based clinical information to participants of this educational activity and requires an open disclosure of any potential conflict of interest identified by our faculty members. It is not the intent of CHEST to eliminate all situations of potential conflict of interest, but rather to enable those who are working with CHEST to recognize situations that may be subject to question by others. All disclosed conflicts of interest are reviewed by the educational activity course director/chair, the Education Committee, or the Conflict of Interest Review Committee to ensure that such situations are properly evaluated and, if necessary, resolved. The CHEST educational standards pertaining to conflict of interest are intended to maintain the professional autonomy of the clinical experts inherent in promoting a balanced presentation of science. Through our review process, all CHEST CME activities are ensured of independent, objective, scientifically balanced presentations of information. Disclosure of any or no relationships will be made available for all educational activities.

CME Availability

Volume 25 Through June 30, 2013
Volume 24 Through December 31, 2012
Volume 23 Through December 31, 2011
Volume 22 Through December 31, 2010

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PCCSU Volume 25 Editorial Board

Editor-in-Chief
Steven A. Sahn, MD, FCCP

Director, Division of Pulmonary and Critical Care Medicine, Allergy, and Clinical Immunology
Medical University of South Carolina
Charleston, SC

Dr. Sahn has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Deputy Editor
Richard A. Matthay, MD, FCCP

Professor of Medicine
Section of Pulmonary and Critical Care Medicine
Yale University School of Medicine
New Haven, CT

Dr. Matthay has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Alejandro C. Arroliga, MD, FCCP
Professor of Medicine
Texas A&M Health Science Center
College of Medicine
Temple, TX

Dr. Arroliga has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Paul D. Blanc, MD, FCCP
Professor of Medicine
University of California, San Francisco
San Francisco, CA

Dr. Blanc has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

National Institutes of Health, Flight Attendants Medical Research Institute – university grant monies
University of California San Francisco, US Environmental Protection Agency, California Environmental Protection Agency Air Resources Board – consultant fee
Habonim-Dror Foundation Board of Trustees – fiduciary position

Guillermo A. do Pico, MD, FCCP
Professor of Medicine
University of Wisconsin Medical School
Madison, WI

Dr. do Pico has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Ware G. Kuschner, MD, FCCP
Associate Professor of Medicine
Stanford University School of Medicine
Palo Alto, CA

Dr. Kuschner has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Teofilo Lee-Chiong, MD, FCCP
Associate Professor of Medicine
National Jewish Medical Center
Denver, CO

Dr. Lee-Chiong has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

National Institutes of Health – grant monies (from sources other than industry)
Covidien, Respironics, Inc. – grant monies (from industry-related sources)
Elsevier – consultant fee

Margaret Pisani, MD, MPH, FCCP
Assistant Professor of Medicine
Yale University School of Medicine
New Haven, CT

Dr. Pisani has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Stephen I. Rennard, MD, FCCP
Professor of Medicine
University of Nebraska Medical Center
Omaha, NE

Dr. Rennard has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

AstraZeneca, Biomark, Centocor, Novartis – grant monies (from industry-related sources)

Almirall, Aradigm, AstraZeneca, Boehringer Ingelheim, Defined Health, Dey Pharma, Eaton Associates, GlaxoSmithKline, Medacrop, Mpex, Novartis, Nycomed, Otsuka, Pfizer, Pulmatrix, Theravance, United Biosource, Uptake Medical, VantagePoint – consultant fee/advisory committee

AstraZeneca, Network for Continuing Medical Education, Novartis, Pfizer, SOMA – speaker bureau

Ex Officio
Gary R. Epler, MD, FCCP

Clinical Associate Professor of Medicine
Harvard Medical School
Brigham & Women's Hospital
Boston, MA

Dr. Epler has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Lilly Rodriguez
ACCP Staff Liaison

By Deepa Bangalore, MD; and Janice L. Zimmerman, MD, FCCP

Dr. Bangalore is Intensivist and Dr. Zimmerman is Professor of Clinical Medicine and Head, Critical Care Division, Department of Medicine, The Methodist Hospital, Weill Cornell Medical College, Houston, Texas.

Dr. Bangalore and Dr. Zimmerman have disclosed no significant relationships with the companies/organizations whose products or services may be discussed within this chapter.

Objectives

  1. Describe different approaches to acid-base analysis and their limitations.
  2. Review the diagnosis, manifestations, and management of metabolic acidosis.
  3. Discuss less common causes of metabolic acidosis and their management.
  4. Review the diagnosis, manifestations and management of metabolic alkalosis and respiratory acid-base disorders.

Key words: anion gap; base deficit; lactic acidosis; metabolic acidosis; metabolic alkalosis; respiratory acidosis; respiratory alkalosis; strong ion difference; strong ion gap

Abbreviations: AG = anion gap; Atot = Total weak acid concentration; BE = base excess; SBE = standard base excess; SID = strong ion difference; SIDapp = apparent strong ion difference; SIDeff = effective strong ion difference; SIG = strong ion gap

Acid-base disturbances are common in critically ill and chronically ill patients and result from a variety of underlying clinical disorders. Although the contribution of acid-base disturbances to morbidity and mortality is not always clear, the appropriate analysis of the abnormalities can offer insight into underlying etiologies and potentially influence therapeutic interventions.

Acid-Base Analysis

Three methods of analysis have been used to describe the acid-base status of patients: the traditional approach, base excess (BE) approach, and the physicochemical approach. All of these methods describe the respiratory component of acid-base changes based on change in Pco2 but differ in how the metabolic component of acid-base disorders is analyzed (Table 1).


Table 1Comparison of Components of Acid-Base Analysis Methods

Acid-Base Disorder Traditional Base Excess Physicochemical
Respiratory acidosis Pco2 ↑Pco2 ↑Pco2
Respiratory alkalosis ↓Pco2 ↓Pco2 ↓Pco2
Metabolic acidosis ↓HCO3-, anion gap ↓Base excess ↓SID, ↑Atot
Metabolic alkalosis ↑HCO3- ↑Base excess ↑SID

 


The traditional method relies on analysis of changes in bicarbonate concentration and the anion gap to assess the metabolic component. In general, an increased bicarbonate concentration indicates a metabolic alkalosis and a decreased bicarbonate concentration indicates a metabolic acidosis. The relation of pH and bicarbonate concentration is described by the Henderson-Hasselbalch equation: pH = pK + log HCO3-/H2CO3 = 6.1 + log HCO3-/0.03 × Pco2. The Henderson equation shows the interrelation between pH, HCO3- and pco2: H+ = 24 × Pco2/HCO3-. The anion gap (AG) is used to classify metabolic acidoses into high AG or normal AG type.

Siggaard and Anderson developed nomograms and algorithms that form the methodology for analyzing acid-base status based on BE. Base excess quantifies the degree of metabolic acidosis or alkalosis as the amount of acid or base that must be added to a sample of whole blood in vitro to restore the pH of the sample to 7.40 while the Pco2 is held constant at 40 mm Hg. To correct for inaccuracies when applied in vivo, BE has been modified to standardize the effect of hemoglobin and Pco2.The standard base excess (SBE) formula is written as follows:

SBE = 0.9287 × (HCO3- – 24.4 + 14.83 × [pH – 7.4]),

where SBE is given in mEq/L.

The SBE changes with any change in weak acid concentrations. A change in base excess describes a change in the metabolic component of acid-base status, with positive BE indicating metabolic alkalosis and negative BE indicating metabolic acidosis.

The physicochemical approach, sometimes referred to as Stewart’s approach, identifies three independent variables that determine acid-base status: Pco2, strong ion difference (SID), and total nonvolatile weak acids (Atot).1,2 These variables also determine changes in dependent variables, such as pH, HCO3-, CO32-, OH- and H+. The SID is the difference between the sum of all strong cation concentrations and the sum of all strong anion concentrations. All concentrations must be expressed in mEq/L. The formula for calculating SID (in mEq/L) is as follows:

SID = [Na+ + K+ + Ca2 + Mg2+] – [Cl- + Lactate].

This calculation is also referred to as the apparent SID (SIDapp), taking into account that there are other unmeasured ions in the plasma. Under normal circumstances, the cationic concentration exceeds the anionic concentration so that plasma SIDapp is approximately +40 to 42 mEq/L. In pathologic conditions, strong anions, such as lactate, formate, sulfates, ketoacids, and fatty acids, may be present in higher concentrations. Plasma proteins, such as albumin (which carries a negative charge at physiologic pH), and inorganic phosphates are the main components of Atot, but also contribute to SID. According to the physicochemical approach, metabolic acid-base changes result only from changes in SID and/or Atot. SID changes with deficits or excess of water in plasma (associated with changes in Na+ concentrations) and changes in the concentrations of strong anions (such as Cl-). Changes in Atot are primarily attributable to changes in the concentration of phosphates and albumin.

Effective SID (SIDeff) is an estimate of the anions that balance the excess cations in order to maintain electroneutrality. SIDeff is derived from Pco2 (from which HCO3- and CO32- can be estimated) and the concentration of weak acids (albumin and phosphate), with the following formula, in which albumin is measured in g/L and PO4 in mmol/L:

   SIDeff = (12.2 × Pco2/10-pH) + 10 × [Albumin × (0.123 × pH – 0.631)] + [PO4 × (0.309 × pH – 0.469)].

A simplified formula for bedside use has been suggested to approximate SIDeff,1 again with albumin in g/L and PO4 in mmol/L:

SIDeff = HCO3- + 0.28 × Albumin + 1.8 × PO4.

Strong ion gap (SIG) is the difference between the apparent and effective SID (SIG = SIDapp – SIDeff).3 It is a measure of the balance of anions and cations, similar to the AG. SIG is positive in situations where unmeasured anions are in excess (acidosis) and negative when unmeasured cations are in excess (alkalosis). “Strong ion gap” is a misnomer as both strong and weak ions may produce a gap. In healthy people, the SIG has a mean value of approximately 0 mEq/L.

Attempts to identify which method of acid-base analysis is most correct or most clinically useful have resulted in numerous debates and studies.4-6 Support for each of these methods can be found in the literature. Studies have also found that the traditional approach using the AG corrected for albumin concentration was equivalent to the physicochemical approach for diagnosis of acid-base disorders in ICU patients. In a retrospective study, the SIG was found to correlate with the anion gap corrected for all known anions, such as albumin and phosphates.3 Several studies have also found high correlations between the SID, BE, and AG. Although the physicochemical approach is comprehensive in identifying acid-base imbalances, it is cumbersome to use at the bedside. It does allow identification of the components contributing to metabolic disorders (strong ions, weak acids, or changes in albumin). However, it is not clear whether identification of subtle acid-base abnormalities by the physiochemical method is of clinical significance. The traditional approach, in which AG corrected for albumin concentration is used, is easy to apply at the bedside but fails to account for the influence of other nonbicarbonate buffers and electrolytes on acid-base status. The traditional approach allows diagnosis of the acid-base disorder but does not always identify the mechanism. The BE approach has the advantage of readily available results from arterial blood gas analysis. However, it cannot be used to identify coexisting metabolic acidoses and alkaloses, nor does it aid in identifying the etiology of an acid-base abnormality.

The clinician must be aware of the limitations and advantages of each acid-base approach. The clinician should integrate the analysis of the acid-base status with the patient’s clinical history and additional testing results when determining the most appropriate interventions. Analysis of acid-base status in a critically ill patient at a single point in time provides only a snapshot of a complex and rapidly changing environment.

Metabolic Acidosis

Metabolic acidosis is a common acid-base disorder in critically ill patients that may contribute to acute ventilatory and circulatory deterioration. Comorbid conditions and therapeutic interventions (eg, fluid resuscitation, diuretics, mechanical ventilation) may both lead to mixed acid-base disorders in these patients. Although metabolic acidosis is suggested by a low bicarbonate level, diagnosis requires a careful analysis of additional factors, such as albumin concentration, unmeasured anions, and coexisting acid-base disorders.

The traditional method of analysis focuses on the AG to suggest etiologies of metabolic acidoses (see Tables 2 and 3). The AG is usually calculated as [Na+ – (Cl- + HCO3-)], although calculation including potassium—[(Na+ + K+) – (Cl- + HCO3-)]—is also used. The normal AG is usually 8 to 12 ± 4 to 6 mEq/L, but the normal range varies with the laboratory and whether potassium is included in the calculation. The majority of unmeasured anions contributing to the AG in normal individuals are albumin and phosphate. Decreases in either of these components will decrease the AG and could mask an increase in organic acids, such as lactate. Correcting the AG for changes in albumin concentration increases the utility of the traditional method in detecting metabolic acidoses.7,8 For every decrease of 1 g/dL in albumin, a decrease of 2.5 to 3 mEq in AG occurs. The corrected AG can be calculated as follows, with albumin given in g/dL:

Corrected AG = Observed AG + 2.5 × (Normal Albumin – Measured Albumin).


Table 2Causes of Normal Anion Gap (Hyperchloremic) Metabolic Acidosis

GI Loss of HCO3-
Diarrhea
Ileostomy
Ureterosigmoidostomy
Renal Loss of HCO3-
Proximal renal tubular acidosis
     Isolated
     Fanconi syndrome
     Familial
     Cystinosis
     Tyrosinemia
     Multiple myeloma
     Wilson disease
     Ifosfamide
     Osteopetrosis
Carbonic anhydrase inhibitors
Ileal bladder
Reduced Renal H+ Secretion
Distal renal tubular acidosis (classic type I)
     Familial
     Hypercalcemic/hypercalciuric states
     Sjögren syndrome
     Autoimmune disease
     Amphotericin
     Renal transplant
Type 4 renal tubular acidosis
     Hyporeninemic hypoaldosteronism
     Tubulointerstitial disease
     Nonsteroidal antiinflammatory drugs
Defective mineralocorticoid synthesis/secretion
     Addison disease
     Acquired adrenal enzymatic defects (chronic heparin therapy)
     Congenital adrenal enzymatic defects
Inadequate renal response to mineralocorticoid
     Sickle cell disease
     Systemic lupus
     Potassium-sparing diuretic
     Pseudohypoaldosteronism (type 1 and 2)
Early uremia
HCl/HCl Precursor Ingestion/Infusion
HCl
NH4Cl
Arginine Cl
Other
Recovery from sustained hypocapnia
Treatment of diabetic ketoacidosis
Toluene inhalation with good renal function

 


Table 3Causes of an Increased Anion Gap and Strong Ion Gap

Renal failure
Ketoacidoses
     Diabetic ketoacidosis
     Alcoholic ketoacidosis
     Starvation
     Metabolic errors
Lactic acidoses
     l-lactic acidosis
     d-lactic acidosis
Toxins
     Acetaminophen
     Cyanide
     Ethylene glycol
     Iron
     Isoniazid
     Metformin
     Methanol
     Paraldehyde
     Propofol
     Propylene glycol
     Salicylates
     Toluene
     Valproic acid
Dehydration
Sodium salts
     Sodium lactate*
     Sodium citrate
     Sodium acetate
     Sodium penicillin ( >50 mU/d)
Decreased unmeasured cations
     Hypomagnesemia*
     Hypocalcemia*
     Alkalemia

*Already accounted for in SIG.


Corrections for changes in phosphate concentration have less impact on the AG. Every decrease of 1 mg/dL in phosphate leads to a decrease of 0.5 mEq in AG. Pathologic paraproteinemias also decrease the AG because immunoglobulins (IgG) are largely cationic. Conversely, an elevated AG does not always reflect an underlying acidosis. In patients with significant alkalemia (usually pH >7.5), albumin is more negatively charged, which increases unmeasured anions in the absence of an acidosis. The respiratory compensation for metabolic acidosis (an increase in minute ventilation) can be estimated by either of the following formulas, both with Pco2 expressed in mm Hg: Pco2 = 1.5 × HCO3- + 8 ± 2 or Pco2 = 1.2 × ΔHCO3-.

The delta gap (Δgap) is a concept used to identify additional acid-base disorders when a metabolic acidosis is present. It is based on the assumption that every increase of 1 mEq/L in the AG will result in a similar decrease in the HCO3- concentration. The calculation is expressed as follows: Δgap = (deviation of the AG from normal) – (deviation of HCO3- concentration from normal). Although the expected normal value is zero, small deviations may not be significant and must always be interpreted along with clinical information. A positive Δgap suggests the concomitant presence of a metabolic alkalosis and a negative value suggests the presence of a hyperchloremic normal AG acidosis.

The physicochemical approach suggests a different approach to classifying metabolic acidoses (Table 4): free water excess, increase in strong anions (hyperchloremia), and increase in weak acids. When a change in extracellular fluid volume is accompanied by an alteration in the proportional water content of the plasma, there is a reduction in SID that leads to acidosis. Hyperchloremia leads to a reduction in the SID and a consequent decrease in pH. The physicochemical approach to acid-base analysis suggests that the acidosis seen in fluid-resuscitated patients is a result of the chloride concentration changes rather than dilution of the bicarbonate concentration. Following normal saline infusion, the plasma Cl- concentration increases to a greater extent than Na+ concentration. Aggressive fluid infusion can also result in dilution of total weak acids (Atot), and this could give rise to a concomitant metabolic alkalosis.


Table 4Primary Metabolic Acid-Base Disturbances Described by the Physicochemical Approach

  Acidosis Alkalosis
Water deficit/excess ↓Na+,↓SID (dilution acidosis) ↑Na+, ↑SID (concentration alkalosis)
Change in strong anions ↑Cl-, ↓SID ↓Cl-, ↑SID
↑Unmeasured acid, ↓SID
Change in weak acids ↑Albumin, ↑phosphate, ↑Atot, ↓SID ↓Albumin, ↓phosphate, ↓Atot, ↑SID

 


Crystalloids with a SID of zero, such as saline solution, cause an acidosis by lowering extracellular SID enough to overwhelm the metabolic alkalosis of Atot dilution.

When infusions containing organic anions such as l-lactate are administered, l-lactate can be regarded as a weak ion that does not contribute to fluid SID, provided it is readily metabolized. The presence of weak acids contributing to Atot must be considered with administration of colloids. Albumin and gelatin preparations contain weak acids, whereas starch preparations do not. The SID and presence of weak acids in fluid options may affect the choice of fluid replacement therapy for specific acid-base effects.

Specific Acidoses
Lactic Acidosis: Two types of lactic acidosis exist: type A and type B. Type A lactic acidosis is usually present in critically ill patients and results from overproduction of l-lactate through anaerobic glucose metabolism as a result of inadequate tissue oxygen delivery.9 l-lactate often accounts for the unmeasured anion detected by an increased anion gap. Type B lactic acidosis is associated with adequate oxygen delivery and is being recognized more frequently. Type B lactic acidosis results from altered cell metabolism (usually mitochondrial function), increased aerobic metabolism or glucose production with enhanced pyruvate production, or inhibition of cytochrome oxidase. β-Agonists, including epinephrine and dobutamine, stimulate glycolysis with production of excess pyruvic acid that may not be cleared owing to inhibition of pyruvate dehydrogenase. Excess pyruvic acid is converted to lactate. Several drugs can also result in elevated lactate levels without evidence of hypoperfusion (Table 5). In addition, type B lactic acidosis can be associated with certain malignancies, such as lymphomas and leukemias. It is important to recognize the presence and etiology of type B lactic acidoses in order to distinguish them from the more clinically ominous type A lactic acidosis. In some cases, specific medications may need to be discontinued because the lactate level suggests toxicity.


Table 5Drugs and Conditions Associated With Type B Lactic Acidosis

Dobutamine
Epinephrine
Etomidate
Linezolid
Lorazepam
Metformin
Nucleoside reverse transcriptase inhibitors
Pentobarbital
Propofol
Tetracyclines
Thiamine deficiency
Valproic acid

 


d-lactic Acidosis: d-lactic acidosis can result from overgrowth of d-lactate-producing bacteria, such as Lactobacillus species, Streptococcus bovis, Bifidobacterium species, and Eubacterium species in patients with anatomic (ileojejunal bypass) or functional short bowel syndrome (malabsorption).10 d-lactate is not measured by laboratory assays but does contribute to the AG as an unmeasured anion. Symptoms can be precipitated after ingestion of carbohydrates with absorption of d-lactate from the affected intestinal segment, but can also occur after consumption of dairy products or lactobacillus tablets. Symptoms of d-lactic acidosis include transient neurologic findings, such as headache, weakness, delirium, visual disturbances, dysarthria, ataxia, cranial nerve palsies, and changes in affect.

Pyroglutamic Acidosis: Pyroglutamic acid is recognized as another etiology of anion gap metabolic acidosis, especially in association with acetaminophen use.11,12 Pyroglutamic acid (5-oxoproline) can be overproduced when glutathione is depleted (associated with acetaminophen use, sepsis, liver dysfunction, and malnutrition) through effects on the γ-glutamyl cycle, resulting in increased production of γ-glutamylcysteine, which is converted to pyroglutamic acid. Additionally, inhibition of 5-oxoprolinase (associated with penicillins and vigabatrin) can lead to pyroglutamic acidosis. The dose of acetaminophen associated with pyroglutamic acidosis has been variable but acidosis resolves with discontinuation of acetaminophen. Repletion of glutathione stores with N-acetylcysteine has been suggested despite the lack of evidence.

Hospital-Acquired Acidoses: Some drugs used in critically ill patients can lead to anion gap metabolic acidoses that are important to recognize. Propylene glycol is a solvent found in IV formulations of lorazepam, diazepam, etomidate, phenytoin, nitroglycerin, esmolol, phenobarbital, pentobarbital, and other drugs. The greatest risk for causing acidosis occurs with the use of high-dose lorazepam for more than 3 days.13 However, toxicity has also been reported with short-term high-dose use. Lorazepam contains 830 mg/mL of propylene glycol and accumulation occurs with doses >0.1 mg/kg/h or in the presence of hepatic or renal dysfunction. Signs and symptoms correlate with an increased osmolar gap. The clinical manifestations of propylene glycol toxicity can mimic sepsis and other inflammatory disorders. These manifestations include CNS depression or agitation, renal dysfunction, seizures, arrhythmias, and hemolysis. Management includes discontinuation of lorazepam and substitution of another sedating drug.

Propofol infusion syndrome is typically seen in pediatric patients but is being reported more frequently in the adult population.14 Acidosis results from lactate production. The exact etiology is unknown but may be related to mitochondrial utilization of free fatty acids or a genetic predisposition. Reported risk factors include dose, duration of use, age, sepsis, head injury, steroid use and catecholamine infusion. Experience is variable but the syndrome is usually associated with doses >4 µg/kg/h and durations longer than 48 h. Manifestations can include arrhythmias, heart failure, rhabdomyolysis, hyperkalemia, acute renal failure, bradycardia, and hyperlipemia. An increased need for inotropic support in a patient receiving propofol with no other clear etiology can be a clue to propofol infusion syndrome.

Clinical Manifestations and Management of Metabolic Acidosis
The predominant clinical manifestations of metabolic acidosis may be difficult to distinguish from manifestations of the underlying disorder. Metabolic acidosis results in increased cerebral blood flow but mental status is often decreased. Pulmonary effects include an increase in minute ventilation, respiratory failure, pulmonary edema, and increased pulmonary vascular resistance. Cardiovascular effects may include arrhythmias and a decrease in myocardial function or response to catecholamines. Acute acidemia enhances oxygen unloading from hemoglobin by shifting the oxyhemoglobin dissociation curve to the right. However, if acidosis persists, it causes the red blood cell concentration of 2,3-diphosphoglycerate to fall and restores the oxyhemoglobin dissociation curve to baseline. Other metabolic effects of metabolic acidosis include hyperkalemia, hypercalcemia, insulin resistance, and increased protein catabolism. Chronic metabolic acidosis can lead to development of osteoporosis, osteomalacia, renal osteodystrophy, renal hypertrophy, nephrocalcinosis, and nephrolithiasis.

Treatment of metabolic acidosis requires identification of the underlying etiology. Treatment of normal AG metabolic acidoses (hyperchloremic) involves replacing volume with a low-chloride, bicarbonate-containing fluid. Other interventions may include insulin for diabetic ketoacidosis, antidote for poisonings, renal replacement therapy for acute kidney injury, and restoration of oxygen delivery in hypoperfusion states. Administration of bicarbonate does not improve outcome in metabolic acidosis. Some studies suggest that bicarbonate may improve myocardial responsiveness when the pH is <7.1 and the patient has severe hemodynamic instability. However, myocardial performance is often normal in metabolic acidosis.

Metabolic Alkalosis

Metabolic alkalosis is diagnosed by findings of increased pH with an increased bicarbonate concentration using the traditional method. In the physicochemical approach, the bicarbonate change is seen as the effect rather than the cause. An increase in the SID resulting from a decrease in Cl- or water deficit with increase in Na+ can result in a metabolic alkalosis (Table 4). Hypoalbuminemia is another cause of metabolic alkalosis detected by physicochemical analysis that may be missed by other approaches. Hypophosphatemia alone does not cause enough change in Atot to result in metabolic alkalosis because the normal value of phosphate is only about 1 mmol/L.

Etiologies of metabolic alkalosis can be characterized as chloride depleted (hypovolemic) or chloride expanded (hypervolemic; Table 6). Urine chloride <20 mEq/L can be used to distinguish chloride-depleted causes of metabolic alkalosis. Hypokalemia is common to all causes of metabolic alkalosis.


Table 6Etiologies of Metabolic Alkalosis

Hypovolemic, chloride depleted
     GI loss of H+
          Vomiting
          Gastric suction
          Cl− rich diarrhea
          Villous adenoma
     Renal loss of H+
     Diuretics
     Posthypercapnia
Hypervolemic, chloride expanded
     Renal loss of H+
          Primary hyperaldosteronism
          Primary hypercortisolism
          Adrenocorticotropic hormone excess
Pharmacologic hydrocortisone/mineralocorticoid excess
Renal artery stenosis with right ventricular hypertension
Renin-secreting tumor
Hypokalemia
Bicarbonate overdose
     Pharmacologic overdose of NaHCO3
     Milk-alkali syndrome
     Massive blood transfusion

Reprinted with permission from Zimmerman.15


Clinical Manifestations and Management of Metabolic Alkalosis
Clinical manifestations of metabolic alkalosis include tachycardia, arteriolar constriction including the coronary arteries, supraventricular and ventricular arrhythmias, hypoventilation, decreased cerebral blood flow, altered mental status, and seizures. Metabolic effects include stimulation of anaerobic glycolysis, hypokalemia, hypomagnesemia, hypophosphatemia, and decreased ionized calcium concentrations. Oxygen release at the tissue level may be impaired in metabolic alkalosis because a leftward shift in the oxyhemoglobin dissociation curve decreases hemoglobin’s oxygen affinity.

Treatment involves identifying the cause and correcting it, if possible. Volume replacement with chloride-containing fluid is indicated for etiologies associated with chloride depletion. It is important to correct metabolic alkalosis before ventilator weaning in an intubated patient as this acid-base disorder causes compensatory hypoventilation. Potassium deficiencies should be corrected. It is rarely necessary to administer hydrochloric acid to correct severe metabolic alkalosis. Deliberate hypoventilation with sedation in intubated patients may be an option for severe conditions. Although acetazolamide will increase excretion of bicarbonate, efficacy is limited and administration can result in metabolic acidosis and exacerbate potassium losses.

Respiratory Disorders

Increases and decreases of Paco2 indicate respiratory acidosis and respiratory alkalosis, respectively. The clinical manifestations of respiratory disorders depend on the absolute change and the rate of change in Paco2, the underlying etiology (Tables 7 and 8), and the presence of hypoxemia. Evaluation of the respiratory component of acid-base abnormalities is the same for all three methods of acid-base analysis. Formulas for changes in Paco2 arising from acute and chronic respiratory disorders allow prediction of pH and bicarbonate concentration. These formulas are less helpful when chronic and acute respiratory conditions are present simultaneously.


Table 7Etiologies of Respiratory Acidosis

Airway obstruction
     Foreign body
     Tongue displacement
     Laryngospasm
     Obstructed endotracheal tube
     Severe bronchospasm
     Obstructive sleep apnea
Respiratory center depression
     General anesthesia
     Sedative or narcotic drugs
     Cerebral injury, ischemia
Increased CO2 production
     Malignant hyperthermia
     Shivering
     Hypermetabolism
     High-carbohydrate diet
Neuromuscular disorders
     Drugs or toxins
     Electrolyte disorders
     Spinal cord injury
     Guillain-Barré syndrome
     Myasthenia gravis
     Polymyositis
Lung conditions
     Restrictive disease
     Obstructive disease
     Hemothorax or pneumothorax
     Flail chest
     Acute lung injury
     Obesity-hypoventilation syndrome
Inappropriate ventilator settings

Reprinted with permission from Zimmerman.15

 


Table 8Etiologies of Respiratory Alkalosis

Hypoxemic drive
     Pulmonary disease with arterial-alveolar gradient
     Cardiac disease with right-to-left shunt
     Cardiac disease with pulmonary edema
     High altitude
Acute and chronic pulmonary disease
     Emphysema
     Pulmonary embolism
     Pulmonary edema
Mechanical overventilation
Stimulation of respiratory center
     Neurologic disorders
     Pain
     Psychogenic
     Liver failure with encephalopathy
     Sepsis/infection
     Salicylates
     Progesterone
     Pregnancy
     Fever

Reprinted with permission from Zimmerman.15


In acute respiratory acidosis, the following formulas apply:

Decrease in pH = 0.08 × (Paco2 – 40)/10, and
Increase in [HCO3-] = ΔPaco2/10 ± 3.

The formulas for chronic respiratory acidosis are as follows:

Decrease in pH = 0.03 × (Paco2 – 40)/10, and
Increase in [HCO3-] = 3.5 × ΔPaco2/10.

For acute respiratory alkalosis, use the following formulas:

Increase in pH = 0.08 × (40 – Paco2)/10, and
Decrease in [HCO3-] = 2 × ΔPaco2/10.

For chronic respiratory alkalosis, these are the formulas:

Increase in pH = 0.03 × (40 – Paco2)/10, and
Decrease in [HCO3-] = (5 to 7) × ΔPaco2/10.

Clinical Manifestations and Management of Respiratory Acidosis
Respiratory acidosis can result in somnolence, confusion, combativeness, delusions, stupor, and coma. Cerebral vasodilation can also increase cerebral blood flow and intracranial pressures. Cardiovascular manifestations include tachycardia, hypertension, depressed myocardial contractility, peripheral vasodilation, and arrhythmias. Severe hypercapnia causes renovascular constriction and hypoperfusion via the renin-angiotensin axis. Hypercapnia also stimulates antidiuretic hormone secretion, resulting in increased salt and water retention. There is a complex interplay of Paco2 and pH on the oxyhemoglobin dissociation curve as CO2 shifts it to the right (Bohr effect) and acidemia shifts the curve to the left. This effect is further complicated by increased 2,3-diphosphoglycerate concentrations in chronic respiratory acidosis.

The treatment of respiratory acidosis is to provide ventilation, which may necessitate intubation and mechanical ventilation in some patients. Bicarbonate administration offers no benefit and generates additional CO2 for elimination.

Clinical Manifestations and Management of Respiratory Alkalosis
Acute respiratory alkalosis (hyperventilation) can cause circumoral numbness, paresthesias, muscle cramps, carpopedal spasms, and seizures. Low Paco2 causes cerebral vasoconstriction with the potential for hypoperfusion, an increase in plasma catecholamines, tachycardia, and arrhythmias (especially with pH >7.6). Metabolic changes include hypokalemia, hypophosphatemia, and ionized hypocalcemia.

Management of significant respiratory alkalosis involves treating the underlying condition (ie, supplying oxygen, analgesic administration, adjusting ventilator settings). In some circumstances, sedation may be needed to control severe respiratory alkalosis.


References

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