Disturbances of the acid-base equilibrium occur in a wide variety of critical illnessess and are among the most commonly encountered disorders in the ICU. In addition to reflecting the seriousness of the underlying disease, these disorders have their own morbidity and mortality.
A blood pH less than normal ( normal range 7.35-7.45 )is called acidemia; the underlying process causing acidemia is called acidosis. Similarly, alkalemia and alkalosis refer to the pH and the underlying process, respectively. While an acidosis and an alkalosis may coexist, there can be only one resulting pH. Therefore, acidemia and alkalemia are mutually exclusive conditions.
The approach to acid-base derangements should emphasize a search for the cause, rather than an immediate attempt to normalize the pH. Many disorders are mild and do not require treatment. Further, treatment may more detrimental than the acid-base disorder itself. More important is a full consideration of the possible underlying pathologic states, which may facilitate a directed intervention that will benefit the patient more than normalization of the pH would.
Acidemia can cause a decrease in cardiac contractility that is directly proportional to the degree of fall in pH. Both metabolic and respiratory acidemia cause a similar degree of myocardial depression, but the effect of the latter occurs mmore promptly, presumably because of the rapid entry of CO2 into the cardiac cell. Altough metabolic acidemia decreases the threshold for ventricular fibrillation in animals, clinically no increase in arrhytmias is seen, and once fibrillation is established acidemia has no effect on the success of defibrillation. Acidemia also causes stimulation of the sympathetic-adrenal axis, and in severe acidemia this effect is countered by a depressed responsiveness of adrenergic receptors to circulating catecholamines.
Acute respiratory acidemia causes marked increases in cerebral blood flow. Acute elevations of Pco2 to more than 60 mmHg causes confusion and headache, and when it exceeds 70 mmHg loss of consciousness and seizures can occur. However, chronic elevations in CO2 are tipically well tolerated, even when it is as high as 150 mmHg. Also, acute hypercapnia causes depression of diaphragmatic contractility and a decrease in endurance time. The effect of metabolic acidemia on the respiratory muscles is less clear, but probably also consists of depression of contractility.
The effects of acidemia on electrolyte levels are quite complex. Acute infusions of HCl causes an increase in serum potassium. However, administration of organic acids, such as lactic acid and ketoacids, does not raise potassium levels., and may even lower it. The hyperkalemia commonly observed in both lactic acidosis and ketoacidosis is due to factors other than the pH change. Acute respiratory acidemia causes no change, or a slight increment, in serum potassium. Both respiratory and metabolic acidemia cause increased extracellular phosphate concentrations. Clinically, lactic acidosis and ketoacidosis are associated with hyperphosphatemia.
Alkalemia appears to increase myocardial contractility, at least to a pH of 7.7. There is little effect on the threshold for ventricular fibrillation. Also hyperventilation can cause adecrease in systemic vascular resistance, although alkalemia can also cause coronary artery spasm with ECG evidence of ischemia ( in fact respiratory alkalosis can be used as a provocative stimulus in the diagnosis of vasospastic angina ).
Acute respiratory alkalemia causes a decrease in cerebral blood flow, a effect that lasts only about 6 hours. It produces confusion, muoclonus, asterixis, loss of consciousness and seizures. Acute hypocapnea causes a slight reduction in the serum levels of sodium, potassium and phosphorus. Alkalemia also causes an increase in hemoglobin’s affinity for oxygen. However, there are also an increase in the concentration of 2,3 DPG in red blood cells and a change in its morphology, which oppose this effect. The clinical effect of alkalemia-induced changes in oxygen delivery are minimal, and only in patients with tissue hypoxia are the small, acute changes potentially relevant.
Metabolic acidosis is characterized by a primary decrease in bicarbonate ( HCO3 ) concentration and a compensatory decrease in the CO2 concentration. It occurs from either loss of HCO3 or addition of H. HCO3 loss generally occurs through the kidneys or the bowel. Acidosis from decreased renal excretion generally is slow to develop. In contrast, acidosis from increased acid production, as in lactic acidosis or ketoacidosis, can exceed maximal renal excretion and cause a rapidly developing, severe acidosis.
The etiologies of metabolic acidosis are divided into those that cause an increase in the anion gap, which is the difference between measured cations and measured anions. It is defined as :
[ Na ] - [ Cl ] - [ HCO3 ]The normal value is 8 - 14 mEq / L . A normal anion gao acidosis occurs when Cl replaces the HCO3 lost in buffering H. An increased anion gap acidosis occurs when the anion replacing the HCO3 is not one that is routinely measured ( albumin, phosphate, sulfates, lactate, … ). Anions always equal cations, but if the anion is not Cl then the anion gap calculated from routine chemistries will increase. An increased anion gap does not always signify a metabolic acidosis. It increases in alkalemia, because of an increase in the net anionic charge on plasma proteins. Dehydration will also increase it because of an increased protein concentration. However, if it is greater than 20 mEq/l, a metabolic acidosis should be pursued.
Normal anion gap acidosis occures from loss of HCO3 through the kidneys or the gut, or from the addition of an acid with Cl as the accompaining anion. The most common cause in the ICU is diarrhea; in its absence, a renal tubular acidosis is likely. The other causes are usually obvious from the history and medication list. The etiologies of normal anion gap metabolic acidosis are listed in table 1. The etioligies of increased anion gap acidosis are given in table 2. The most important cause is lactic acidosis, which is discussed separetly below.
Gastrointestinal Loss of Bicarbonate Diarrhea Urinary diversion Small bowel, pancreatic, or bile drainage ( fistulas, surgical drains ) Cholestiramine Renal Loss of Bicarbonate ( or Bicarbonate equivalent ) Renal tubular acidosis Recovery phase of Ketoacidosis Renal Insufficiency Acidifying Substances HCl, NH4Cl, Arginine HCl, Lysine HCl, Sulfur |
Lactic acidosis is the most common and most important acidosis encountered in the ICU. The acidemia has physiologic significance and, perhaps most important, serve as a marker for a diverse group of serious underlying conditions. Its definition is somewhat arbitrary, but its’s commonly defined as an arterial lactate level greater than 5 mmol/l, with an arterial pH less than 7.35 . Increased lactate levels correlate well with increasing mortality in patients with cardiogenic shock. In other types of shock the correlation is not as good, and there is considerable overlap between survivors and non-survivors, which is due, in part, to the influence on lactate levels of such factors as nutritional status and liver disease. However, the trend in lactate levels in a given patient can be helpful in gauging the effect of therapy and assessing prognosis.
Ketoacidosis - diabetic, alcoholic, starvation Lactic acidosis Uremia Toxins - Ethylene glycol, methanol, salicylate, paraldehyde |
The etiologies of lactic acidosis are listed in table 3. Most occur secondarily to a handful of processes as shock ( the most common ), hypoxia, seizures, regional ischemia ( mesenteric or in an extremity ), and toxin exposure accounts for the majority of remainig cases. The treatment of lactic acidosis is primarily the treatment of the disease causing the metabolic derangment. Therapies aimed at ameliorating the acidosis itself are attempts to prevent further deterioration until the primary process can be controlled.
Increased Oxygen Consumption
Strenuous exercise
Grand mal seizures
Neuroleptic malignant syndrome
Severe asthma
Pheochromocytoma
Decreased Oxygen Delivery
Decreased Cardiac Output
Hypovolemia
Cardiogenic shock
Decreased Arterial Oxygen Content
Profound anemia
Severe hypoxemia
Regional Ischemia
Microcirculatory Disturbances
Sepsis
Alterations in Cellular Metabolism
Diabetes
Thiamine deficiency
Severe alkalemia
Hypoglicemia
Malignancy
Toxins and Drugs
Congenital
Decreased Lactate Clearance
Fulminant hepatic failure
d-Lactate
|
HCO3 has long been the standard therapy, but its use is suffering a dramatic change in the recent years. There is often a near stiochiometric relationship between HCO3 administered and lactate production. Its administration causes an increase in CO2 production, because of its metabolism to H2O and CO2. Ventilation must be increased if a rise in Pa CO2 is to be avoided. In patients in controlled mechanical ventilation, an increase in the minute ventilation can be used to lower the Pa CO2 and raise the pH without the administration of HCO3. Also, incresed CO2 translates into decreased intracellular pH ( pHi ), since CO2 equilibrates across cell membranes more rapidly than HCO3.
Carbicarb is a buffer that has been developed as an alkalinizing agent and to cause a smaller increase in Pa CO2 than HCO3. It effectively increases arterial pH, equal to that produced by HCO3, but with a lower sodium load and lower osmolality. Its use is undergoing clinical trials. Dichloroacetate increases the activity of the pyruvate-dehydrogenase complex, thereby enhancing the conversion of pyruvate into acetil-CoA and its entry into the Krebs cycle. The results to date are promising, but its still waiting results of randomized trials.
Both hemodialysis and peritoneal dialysis have been used to treat lactic acidosis. It uses either HCO3 or Acetate as a buffer and does not correct the acidemia by removing hydrogen ions; its utility lies in its ability to prevent volume overload during the administration of large amounts of HCO3, so having the same potential adverde effects as intravenous HCO3. It has the advantage of removing lactate, which may have negative effects on the myocardium and cellular metabolism.
So, the decision of whether to use HCO3 is a difficult one. Some authors, because the lack of data supporting its use, do not recommend its use in lactic acidosis regardless of the pH. Others use it when the pH approaches 7.0 . If it is used, it should be administered slowly and preferably in an isotonic mixture.
Metabolic alkalosis is characterized by a primary increase in HCO3 concentration and a compensatory increase in Pa CO2. As the normal kidney can excrete HCO3 loads of up to 10 mEq/Kg/day, for metabolic alkslosis to persist there must be both a process that elevates its serum levels and a stimulus for renal reabsoption. The former is usually acid loss from the stomach or from the kidney, and the last due to hypovolemia with a Cl deficit ( renal tubules with a strong sodium avidity ), hipokalemia or an increase in mineralocorticoid activity. When Cl deficit is present, HCO3 is reabsorbed with sodium and metabolic alkalosis will persist until the Cl deficit is replaced. Hypokalemia increases tubular HCO3 reabsorption and mineralocorticoid excess increases HCO3 by way increased secretion of H ions in the cortical collecting tubule.
The major causes in the ICU are vomiting, nasogastric suction, diuretics, corticosteroids, overventilation of patients with chronically increased HCO3 levels, and acetate used in total parenteral nutrition. If the etiology is not clear, a trial of volume and Cl replacement, as well as correction of kypokalemia, can be attempted. If it fails, a search for increased mineralocorticoids may be warranted.
Most cases are predictable and preventable by replacing diuretic-induced potassium losses, minimizing nasogastric suction, use of H2 blockers, and avoidance Pa CO2 in patients with chronic obstructive pulmonary disease. Once it is established, removal of precipitating factors and correction of electrolyte deficits generally suffice to restore acid-base balance. Rarely, acetazolamide, continuous arteriovenous hemodialysis and hydrochloric acid are used when rapid correction ( pH > 7.6 ) is needed. In mineralocorticoid excess, removal of the source is the best therapy, combination of sodium restriction, potassium replacement, and spironolactone or amiloride being alternatives.
Respiratory acidosis is characterized by a primary increase in Pa CO2 and a compensatory increase in HCO3. Respiratory acidosis represents ventilatory failure. Decreased alveolar ventilation arises from a decrease in minite ventilation or from an increase in dead space without a compensatory rise in minute ventilation. A rise in CO2 production will produce hypercapnea unless ventilation does not increase appropriately. The etilogies can be classified according to which part of the respiratory system is affected. Thus hypercapnea can result from abnormalities in the neural control of ventilation, in the chest wall and respiratory muscles, or in the lungs and upper airways. Pulmonary diseases are the most common in the ICU. Drugs that depress respiratory drive should always be sought in a patient presenting with ventilatory failure, particularly if no pulmonary disease is present.
Treatment includes reversing causal disorders, increasing minute ventilation, decreasing dead space, and decreasing CO2 production. This often requires intubation and mechanical ventilation.
Respiratory alcalosis is characterized by a primary reduction in the arterial PCO2, followed by a secondary two-phase reduction in HCO3, a small acute decrease due to tissue buffers and a larger chronic decrement due to a decrease in renal titratae acid excretion and an increase in renal HCO3 excretion. It occurs when alveolar ventilation is increased relative to CO2 production.
Hyperventilation is a nonspecific response to a variety of stimuli. The challenge is to distinguish those that are manifestations of serious diseases. Virtually any pulmonary disorder can cause stimulation of pulmonary parenchymal receptors and hyperventilation. Hypoxia, toxins and inadequate mechanical ventilation can stimulate the respiratory center.
Treatment is that of the underlying cause. In cases where a severe alkalemia is present, generally with superimposed metabolic alkalosis, sedation may be necessary. In sepsis, where a significant portion of cardiac output can go to respiratory muscles, intubation and muscle relaxation are often required to control hyperventilation and redirect blood flow.
Finally, everytime we are dealing with an acid base disorder, we have to check for appropriate compensations of the primary disturbance, as to be able to distinguish simple from combined acid-base disorders, which are very frequent in ICU patients. The following formulas summarize this knowledge :
Metabolic Acidosis :
Metabolic Alkalosis :
PCO2= ( 0.7 x HCO3 ) + 21
Respiratory Acidosis :
Acute - HCO3 = [ ( PCO2 - 40 ) / 10 ] + 24
Chronic - HCO3 = [ ( PCO2 - 40 ) / 3 ] + 24
Respiratory Alkalosis :
Acute - HCO3 = [ ( 40 - PCO2 / 5 ) ] + 24
Chronic - HCO3 = [ ( 40 - PCO2 ) / 2 ] + 24
1) “ Acid Base Disorders “ - in Principles of Critical Care Medicine, Mc Graw Hill 1992.
2) “ Critical Care Medicine “ - in Cecil Textbook of Medicine, Saunders 1996.
3) “ Intensive Care “ - in Oxford Texbook of Medicine, Oxfor Medical Publications 1996
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