Disorders in Critically Ill Patients

(1)

Professor of Medicine, Department of Medicine, Chief, Division of Nephrology and Hypertension, Rutgers New Jersey Medical School, Newark, NJ, USA

Keywords

Metabolic acidosisMetabolic alkalosisRespiratory acidosisChronic respiratory acidosisRespiratory alkalosisMixed acidbase disorders

Acid–base disorders are extremely common in patients admitted to the critical care units because of multiorgan dysfunction. Sepsis, septic shock, toxin ingestion, diabetic ketoacidosis, removal of vomitus by nasogastric suction, massive transfusion with citrated blood, and renal as well as respiratory failure are some of the important causes for acid–base disorders. Hyperchloremic metabolic acidosis is frequently seen due to fluid resuscitation with normal saline or fluids that contain high Cl⁻. Among acid–base disorders, some reports suggested metabolic acidosis as the predominant disorder in critically ill patients. For example, an observational cohort study reported that 64% had acute metabolic acidosis. Other studies showed metabolic alkalosis to be the most common acid–base disorder in critically ill patients. Therefore, it is difficult to predict which acid–base disorder predominates in critically ill patients. It should be noted that any acid–base disorder is associated with high morbidity and mortality in critically ill patients. Lindner et al. [1] described an acid–base disorder called hypernatremic alkalosis in critically ill patients. Their study included 51patients who developed hypernatremia (serum Na⁺ level > 149 mEq/L) after admission to intensive care units (ICUs). Based on an increase in base excess, hypernatremia was accompanied by an increase in serum HCO₃ ⁻ level and pH. The authors suggest that hypernatremic alkalosis should be part of the differential diagnosis of metabolic acid–base disorders. In this chapter, we will discuss the pathophysiology and management of only four primary acid–base disorders (metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis) in critically ill patients.

Metabolic Acidosis

As mentioned above, metabolic acidosis is the most frequently observed acid–base disorder in critically ill patients. Metabolic acidosis develops because of three reasons: (1) renal failure; (2) addition of either endogenous or exogenous anions (H⁺); and (3) loss of HCO₃ ⁻ from the kidney or gastrointestinal tract. As usual, metabolic acidosis is classified into high anion gap (AG) or normal AG groups. Table 16.1 shows the most common causes of metabolic acidosis in critically ill patients.

Table 16.1

Most common causes of high and normal AG metabolic acidosis in intensive care units

Cause	Unmeasured anions causing high or normal AG
High AG acidosis
Renal failure Acute kidney injury, uremic acidosis	Sulfate, phosphate, urate
Addition of H ⁺
Lactic acid	L-Lactate
Ketoacidosis	Acetoacetate, β-hydroxybutyrate
Methanol	Formate
Ethylene glycol	Gycolate, oxalate
Propylene glycol	L-Lactate
Aspirin	Salicylate, L-lactate, ketoacids
Acetaminophen (Tylenol)	Pyroglutamate (5-oxoproline)
Normal AG acidosis
Hyperchloremic metabolic acidosis	Cl⁻ due to normal saline infusion
Acute diarrhea	HCO₃ ⁻ due to gastrointestinal loss
Enteric fistulae	HCO₃ ⁻ due to gastrointestinal loss
Recovery phase of diabetic ketoacidosis	Loss of ketoacid anions and infusion of Cl⁻-rich solutions
Cationic amino acids (arginine, lysine, histidine) in parenteral nutrition	H⁺ as a metabolic product of these amino acids

Selected Conditions of Metabolic Acidosis

L-Lactic acidosis

The most extensively studied anion causing high AG metabolic acidosis in critical care units (ICUs) is lactic acid. Indeed, lactic acidosis is the predominant cause of metabolic acidosis in ICUs. As discussed in Chap. 5, type A lactic acidosis is due to hypoxia, but sepsis is probably the most important cause of this acid–base disorder. Measurements of lactate in ICUs are routinely performed, as lactate levels have a prognostic significance. Both absolute levels of lactate and its clearance have been used in various clinical settings as markers of length of stay, severity of shock, morbidity, and mortality. It was shown that patients with septic shock whose initial lactate levels in the Emergency Department were >2 mmol/L had a higher in-hospital mortality rate than those whose levels were 2 or <2 mmol/L. Also, it was shown that lactate levels are associated with proportional increases in mortality rate. One study reported about 70% mortality in critically ill patients with blood lactate levels between 3 and 4 mmol/L.

Increased lactate levels are related to overproduction or decreased clearance by the liver and kidneys. Studies have shown that decreased clearance is associated with higher length of ICU stay and mortality. In a cohort of trauma patients, initial lactate level and its clearance at 6 hours were associated with decreased mortality. In patients with sepsis or septic shock, at least 10% clearance of lactate within 6 hours of presentation has been shown to have a lower mortality rate than those patients with decreased clearance of lactate. Thus, both higher levels and decreased clearance of lactate are associated with higher mortality rate.

Blood lactate levels <5 mmol/L may not have any effect on pH in an individual with serum HCO₃ ⁻ level of 24 mEq/L. However, low blood lactate levels in a patient with low HCO₃ ⁻ level may have a significant effect on pH. Let us consider the following ABG in a normal subject and critically ill patient.

ABG in normal subject with normal lactate level (1 mmol/L)

pH = 7.40
pCO₂ = 40 mmHg
[HCO₃ ⁻] = 24 mEq/L
pO₂ = 96 mmHg

ABG in a normal subject with 3 mmol/L increase in lactate level is given below (assuming 1 HCO₃ ⁻ ion buffers 1 lactate anion (H⁺); the resulting HCO₃ ⁻ level is 21 mEq/L).

pH = 7.37
pCO₂ = 38 mmHg
[HCO₃ ⁻] = 21 mEq/L
pO₂ = 96 mmHg

Note that this pH of 7.37 will have no significant physiologic change in the body. However, an increase in lactate level of 3 mmol/L will have a profound change in pH and physiologic change in the body.

Initial ABG due to ketoacidosis in a patient with normal lactate level (1 mmol/L).

pH = 7.32
pCO₂ = 30 mmHg
[HCO₃ ⁻] = 15 mEq/L
pO₂ = 92 mmHg

ABG in the presence of 3 mmol/L increase in blood lactate level.

pH = 7.20
pCO₂ = 30
HCO₃ ⁻ = 12 (assuming 1 HCO₃ ⁻ ion buffers 1 lactate anion (H⁺); 15–3 12 mEq/L)
pO₂ = 89 mmHg

Thus, a small increase in blood lactate can have a profound effect on pH in a critically ill patient.

Treatment of lactic acidosis is discussed in Chap. 5, which includes fluid resuscitation, antibiotic use in sepsis, elimination of the cause and judicious use of alkalinizing agents, if required, vasopressors, optimization of O₂ delivery, and renal replacement therapy. Use of NaHCO₃ is controversial.

Ketoacidosis

Diabetic ketoacidosis rather than starvation or alcohol ketoacidosis is a frequent cause of ICU admission. The pathophysiology and management of diabetic ketoacidosis are discussed in Chap. 6.

Toxin-induced metabolic acidosis

Ingestion of methanol, ethylene glycol, and aspirin with electrolyte and acid–base abnormalities requires management in an ICU setting. At times, patients with acetaminophen overdose may present with high AG metabolic acidosis, and these patients may require urine measurements of pyroglutamate (5-oxoproline). The pathophysiology and management of each of these toxin-associated acid–base disorders are discussed in Chap. 7.

Propylene glycol

It is a common vehicle for many drugs used in ICUs. It is metabolized to lactic acid by alcohol dehydrogenase. Discontinuation of propylene glycol-containing drugs resolves the high AG metabolic acidosis.

Hyperchloremic metabolic acidosis (HCMA)

Of all the causes of HCMA (renal tubular acidosis, renal failure), infusion of large quantities of normal saline during volume resuscitation is the most important cause of this acid–base disorder in ICU patients.

Normal saline contains high Cl⁻ (154 mEq/L). Recent studies have shown that infusion of solutions containing high Cl⁻ to critically ill patients has caused not only hyperchloremic metabolic acidosis but also acute kidney injury. Balanced electrolyte solutions with low Cl⁻ concentration, on the other hand, caused less adverse effects compared to normal saline.

Recovery phase of diabetic ketoacidosis

Hyperchloremic metabolic acidosis does develop in some patients in the recovery phase of DKA because the regeneration of HCO₃ ⁻ from ketones is decreased due to loss of excess ketones in the urine prior to hospitalization. Also, administration of fluids that contain high chloride may contribute to this type of transient acidosis.

Renal failure

Acute kidney injury (AKI) is rather common in ICU patients, and high AG metabolic acidosis develops in most of these patients. AKI superimposed on CKD (chronic kidney disease) is also common. In both AKI and CKD, decreased excretion of H⁺ is due to impaired net acid excretion. Details of acid–base disorders in kidney disease are discussed in Chap. 8.

Parenteral nutrition

Acid–base disorders of parenteral nutrition are discussed in Chap. 17.

Clinical Manifestations

Metabolic acidosis affects the functions of almost all organ systems. Some of the important clinical manifestations are summarized in Table 16.2.

Table 16.2

Clinical manifestations of metabolic acidosis

Cardiovascular

Decreased contractility at pH <7.1

Decreased cardiac responsiveness to catecholamines

Decreased fibrillation threshold

Arterial vasodilation and hypotension

Respiratory

Increased minute ventilation

Dyspnea

Decreased diaphragmatic contractility

Neurologic

Altered mental status

Increased cerebral blood flow

Decreased cerebral metabolism

Others

Decreased anaerobic metabolism

Increased protein catabolism

Increased metabolic rate

Impaired phagocytosis

Decreased ATP production

Impaired skeletal growth

Management

Identification of the cause or offending agent and starting the appropriate therapy are the initial steps in the management of a patient with metabolic acidosis. The management of various causes of metabolic acidosis was discussed in previous chapters, and only the summary is presented in Table 16.3.

Table 16.3

Management of metabolic acidosis in critically ill patients

Cause	Treatment
High AG acidosis
Acute kidney injury, uremic acidosis	Renal replacement therapies (RRT) (hemodialysis, CVVHD, CVVHDF)
Lactic acid	Circulatory support with fluids and vasopressors, alkalizing agents (NaHCO₃ or THAM, if indicated), thiamine, riboflavin, CVVHD or CVVHDF. Insulin and glucose
Ketoacidosis	Volume replacement, insulin
Methanol	Supportive care (hydration with normal saline), NaHCO₃, if indicated, i.v. folinic acid followed by folate, fomepizole, ethanol, if fomepizole not available, RRT if indicated
Ethylene glycol	Same as above except for folinic acid and folate. Thiamine and pyridoxine
Propylene glycol (PA)	Discontinue PA
Aspirin	Circulatory support with hydration, oral activated charcoal, NaHCO₃ to alkalinize urine, hemodialysis, if indicated
Acetaminophen (Tylenol)	NaHCO₃, hemodialysis
Normal AG acidosis
Hyperchloremic metabolic acidosis due to NaCl administration	Use balanced solutions
Acute diarrhea	NaHCO₃

CVVHD continuous venovenous hemodialysis, CVVHDF continuous venovenous hemodiafiltration

Metabolic Alkalosis

Not only metabolic acidosis but also metabolic alkalosis is rather common in ICUs. Metabolic alkalosis develops when H⁺ is removed or HCO₃ ⁻ is added to the body. Once metabolic alkalosis develops, it should be maintained. There are several causes that generate and maintain metabolic alkalosis, which are discussed in Chap. 11. The most common causes of metabolic alkalosis are shown in Table 16.4. Additional causes of metabolic alkalosis in non-ICU settings are presented in Chap. 11.

Table 16.4

Most common causes of metabolic alkalosis in intensive care units

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