Table of Contents
Acid-base disturbances are diagnosed from a patient’s chemistry and blood gas results, but there are multiple approaches to determining the underlying causes and initiating treatment. This issue presents a summary of the chemistry and physiology of acid-base disturbances and uses a workbook-style format of 8 real-life cases to illustrate the approaches to diagnosing and managing these disorders. Algorithms for acidemia and alkalemia reinforce the stepwise approach.
Primary metabolic acidosis/alkalosis or primary respiratory acidosis/alkalosis: how does diagnosis proceed from this initial characterization?
What are the mechanisms of lactate metabolism and lactic acidosis?
What are the mechanisms of ketone metabolism and ketoacidosis?
The 6 primary states of acid-base disturbances: what are the 6 rules for calculating expected changes in [HCO3-] and PaCO2?
How do the historical approaches to characterization of acid-base disturbances differ, and how is each used?
What are the primary features of: the descriptive/Boston approach; anion gap approach; delta gap approach; Copenhagen/base excess approach; and the quantitative/physico-chemical/Stewart approach?
What is the current evidence on arterial blood gas versus venous blood gas sampling?
When should sodium bicarbonate be given, and what are the recommendations on administration of fluid types?
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Abstract
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Case Presentations
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Opening Case Presentation: Deb Whitehurst
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Introduction
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Critical Appraisal of the Literature
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Background Chemistry and Physiology
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Differential Diagnosis
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Lactate Metabolism and Lactic Acidosis
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Ketone Metabolism and Ketoacidosis
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Diabetic Ketoacidosis
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Alcoholic Ketoacidosis
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Historical Approaches to the Characterization of Acid-Base Disturbances
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The Descriptive (Boston) Approach
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The Anion Gap Approach
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The Delta Gap Approach
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The Copenhagen (Base Excess) Approach
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The Quantitative (Physico-Chemical, or Stewart) Approach
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Complex Disturbances and Integration of Approaches to Characterization
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Controversies and Cutting Edge
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Arterial Blood Gas Versus Venous Blood Gas
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Sodium Bicarbonate for Severe Acidosis
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Normal Saline Versus Balanced Crystalloids
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Disposition
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Summary
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Time- and Cost-Effective Strategies
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Risk Management Pitfalls for Acid-Base Disturbances in the Emergency Department
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Case Conclusion, Deb Whitehurst
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Clinical Pathways
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Clinical Pathway for Acidemia in the Emergency Department
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Clinical Pathway for Alkalemia in the Emergency Department
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Tables and Figures
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Table 1. Emergency Department Sample Track Board
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Table 2. Emergency Department Sample Patient Laboratory Test Results
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Table 3. Evidence-Based Clinical Practice Guidelines Pertinent to Acid-Base Disturbances
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Table 4. Differential Diagnosis of Acid-Base Disturbances
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Table 5. Rules for Expected Responses to Primary Disturbances
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Table 6. The Descriptive (Boston) Approach Example: Luther Radcliffe
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Table 7. The Anion Gap Approach Example: Jacob Cook
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Table 8. Variations of Anion Gap Formulae
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Table 9. The Delta Gap Approach Example: Regina Carver
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Table 10. The Copenhagen (Base Excess) Approach: Heather Little
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Table 11. The Descriptive (Boston) Approach and the Copenhagen (Base Excess) Approach Compared: Leonard Brown
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Table 12. The Quantitative/Physico-Chemical (Stewart) Approach: Tanner Dawson
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Table 13. Integration of Approaches for Complex Disturbances: Brian Sullivan
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Figure 1. Pattern Analysis Diagram
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Figure 2. Gamblegram of Ions in Plasma
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References
Abstract
Acid-base disturbances are physiological responses to a wide variety of underlying conditions and critical illnesses. Homeostasis of acid-base physiology is complex and interdependent with the function of the lungs, kidneys, and endogenous buffer systems. Traditionally, these disturbances have been classified in terms of being caused by either a primary respiratory or a metabolic insult and by chronicity and compensation. While existing literature consists largely of physiology reviews, several well-designed studies and clinical practice guidelines provide relevant new perspectives on interpreting and managing acid-base disturbances. This review outlines several approaches to characterizing disturbances, with a case-based format and algorithms to aid in diagnostic testing and interpretation of arterial blood gases.
Case Presentations
This issue of Emergency Medicine Practice utilizes a workbook approach in order to highlight the strengths and weaknesses of respective approaches to acid-base disturbances. Clinical vignettes are provided with accompanying steps for interpretation. To test your skills, try to interpret the cases before reading the “Methods” and “Interpretation” sections.
Opening Case Presentation: Deb Whitehurst
It is Friday night and you have just received sign-out from your partner, who was finishing the swing shift, leaving you to function as the single provider in a critical access ED. Immediately after he leaves, local EMS radios in to give report about a patient en route:
“This is rescue 59 coming to your facility with a 56-year-old white woman with fever, chills, and lethargy. She is a patient being treated at University Hospital for ovarian cancer and last had chemotherapy 1 week ago. Her family says she has had fever up to 103°F since last night and recently had a CT scan showing a mass impinging on her ureter. Initial vital signs are: heart rate, 148 beats/min; blood pressure, 88/52 mm Hg; respiratory rate, 30 breaths/min; temperature 39° C; and oxygen saturation, 95% on 2L NC. We have not been able to obtain IV access, and we will be at your back door in 4 minutes.”
As you begin to prepare a resuscitation room, you appreciate that this febrile patient may be in septic shock, which is an inherently acidemic state. You wonder how best to determine whether an acidosis is purely due to sepsis or is confounded by additional acid-base disturbances. You also wonder what kind of IV fluids are best for resuscitation and whether there is a role for bicarbonate…
After your initial evaluation, the charge nurse informs you that there have been several new patient arrivals, and you review the track board, along with the results of their laboratory tests. (See Tables 1 and 2.)
Introduction
Acid-base disturbances are observed frequently in patients with complex or critical illness and may be associated with a wide range of underlying conditions. Recognition of how homeostasis is maintained and the ability to identify and characterize disturbances is fundamental to the practice of emergency medicine. Acidemia is defined as the state in which the extracellular pH is abnormally low, typically < 7.35. Alkalemia is the state in which the pH is abnormally high, typically > 7.45. By contrast, the terms acidosis and alkalosis refer to the underlying physiological processes that result in an abnormal pH. A patient can exist in a state of acidemia or alkalemia, never in both. Nonetheless, several independent disturbances may coexist such that a patient experiences concomitant acidosis and alkalosis, known as mixed disturbances, the cumulative sum of which determines overall pH.
This issue of Emergency Medicine Practice provides a review of the basic science and physiological principles from which clinical paradigms are based, complimentary approaches to the characterization and diagnosis of acid-base disturbances, a series of real-life case presentations that highlight the approaches, principles for initial evaluation and management, and consideration for special populations and circumstances.
Critical Appraisal of the Literature
A literature search was undertaken utilizing multiple available databases. A MEDLINE search with the MeSH heading of acid base imbalance restricted to humans from 1965 through 2018 yielded over 26,000 results. Additional databases and search strategies were queried, including Google Scholar and the Cochrane Database of Systematic Reviews. Reference lists from the identified articles/abstracts as well as major textbooks in internal medicine, critical care, and nephrology were screened for additional citations. Clinical practice guidelines and position statements from major relevant professional organizations were also reviewed. (See Table 3.)
Boolean operators and MeSH headings were applied to structure the literature search and included: acid base imbalance, acidosis, alkalosis, acidemia, alkalemia, ketoacidosis, anion gap, with or without additional terms including poisoning, toxicology, emergency department, arterial blood gas, COPD, metformin, lactates, sepsis, crystalloid, colloid, sodium bicarbonate, practice guidelines, and emergency medical services. Both authors screened these results independently for articles considered to be landmark publications, highly impactful, or from the highest-quality journals. Fifty-one citations were subsequently included in this review.
Risk Management Pitfalls for Acid-Base Disturbances in the Emergency Department
1. “The patient was hypoxic, so I applied supplemental oxygen by nonrebreathing mask until the SpO2 was 100%.”
Oxygen-induced hypercapnia and hyperoxia are proven consequences of excessive supplemental oxygen therapy in patients with COPD. Mechanisms are complex and not due simply to decreased hypoxic respiratory drive, but a titrated oxygen strategy targeting maximum SpO2 of 88% to 92% should be employed.5
3. “The septic patient was severely acidotic, so I gave her sodium bicarbonate boluses.”
Existing evidence does not support the routine administration of sodium bicarbonate for most causes of acidosis. In some cases, this may be harmful and should be considered only if there is immediately life-threatening acidemia (eg, pH < 6.9), bicarbonate-losing conditions, or at the direction of a specialist.
6. “I had to intubate the COPD patient – his pCO2 was 70!”
Many patients with obstructive airway disease chronically retain carbon dioxide that is accompanied by a compensatory renal response of increased bicarbonate production and resorption, over time, to raise the pH back closer to normal. The decision to initiate mechanical ventilation should be based on mental status, historical ABG comparisons, and consideration for compensated or uncompensated processes.
Tables and Figures
References
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.
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Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-1343. (Clinical practice guideline)
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American College of Medical Toxicology. Guidance document: management priorities in salicylate toxicity. J Med Toxicol. 2015;11(1):149-152. (Clinical practice guideline)
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Rossaint R, Bouillon B, Cerny V, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Crit Care. 2016;20:100. (Clinical practice guideline)
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Soar J, Nolan JP, Bottiger BW, et al. European Resuscitation Council guidelines for resuscitation 2015: section 3. Adult advanced life support. Resuscitation. 2015;95:100-147. (Clinical practice guideline)
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O’Driscoll BR, Howard LS, Earis J, et al. British Thoracic Society guideline for oxygen use in adults in healthcare and emergency settings. BMJ Open Respir Res. 2017;4(1):e000170. (Clinical practice guideline)
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Hamm LL, Nakhoul N, Hering-Smith KS. Acid-base homeostasis. Clin J Am Soc Nephrol. 2015;10(12):2232-2242. (Renal physiology review)
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Lee S-W, Hong Y-S, Park D-W, et al. Lactic acidosis not hyperlactatemia as a predictor of inhospital mortality in septic emergency patients. Emerg Med J. 2008;25(10):659-665. (Prospective observational; 126 patients)
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Adeva-Andany M, López-Ojén M, Funcasta-Calderón R, et al. Comprehensive review on lactate metabolism in human health. Mitochondrion. 2014;17:76-100. (Review)
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DeFronzo R, Fleming GA, Chen K, et al. Metformin-associated lactic acidosis: current perspectives on causes and risk. Metabolism. 2016;65(2):20-29. (Review)
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Wutrich Y, Barraud D, Conrad M, et al. Early increase in arterial lactate concentration under epinephrine infusion is associated with a better prognosis during shock. Shock. 2010;34(1):4-9. (Retrospective cohort; 100 patients)
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Scheiner B, Lindner G, Reiberger T, et al. Acid-base disorders in liver disease. J Hepatol. 2017;67(5):1062-1073. (Review)
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Mulhausen R, Eichenholz A, Blumentals A. Acid-base disturbances in patients with cirrhosis of the liver. Medicine (Baltimore). 1967;46(2):185-189.
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Bellomo R. Bench-to-bedside review: lactate and the kidney. Crit Care. 2002;6(4):322-326. (Review)
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Peters AL, Buschur EO, Buse JB, et al. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015:dc150843. (Case series; 9 patients)
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Robinson AM, Williamson DH. Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiol Rev. 1980;60(1):143-187. (Review)
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Kamel KS, Halperin ML. Acid-base problems in diabetic ketoacidosis. N Engl J Med. 2015;372(6):546-554. (Review)
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McGuire LC, Cruickshank AM, Munro PT. Alcoholic ketoacidosis. Emerg Med J. 2006;23(6):417-420. (Review)
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Umpierrez GE, DiGirolamo M, Tuvlin JA, et al. Differences in metabolic and hormonal milieu in diabetic- and alcohol-induced ketoacidosis. J Crit Care. 2000;15(2):52-59. (Prospective observational; 20 patients)
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Berend K. Diagnostic use of base excess in acid-base disorders. N Engl J Med. 2018;378(15):1419-1428. (Review)
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Bunker JP. The great trans-Atlantic acid-base debate. Anesthesiology. 1965;26:591-594. (Editorial)
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Schwartz WB, Relman AS. A critique of the parameters used in the evaluation of acid-base disorders. Whole-blood buffer base and standard bicarbonate compared with blood pH and plasma bicarbonate concentration. N Engl J Med. 1963;268:1382-1388. (Landmark review)
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Brackett NC Jr, Wingo CF, Muren O, et al. Acid-base response to chronic hypercapnia in man. N Engl J Med. 1969;280(3):124-130. (Prospective observational; 20 patients)
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Miller M, Eriksson L, Fleisher L, et al. Perioperative Acid-Base Balance. In: Miller's Anesthesia, 8th Ed. Philadelphia, PA: Elsevier Saunders. 2015; pages 1811-1829. (Textbook chapter)
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Stinebaugh BJ, Austin WH. Acid-base balance. Common sense approach. Arch Intern Med. 1967;119(2):182-188. (Clinical report and case review)
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