DAS : ACID-BASE Indian J. Anaesth.DISORDERS 2003; 47 (5) : 373-379

373

ACID-BASE DISORDERS Dr. Bibhukalyani Das Hydrogen bonding is a key force that maintains the structural integrity of biologic molecules. The structure of all proteins, enzymes that are critical determinant of function is extremely sensitive to local H+ concentration. So, H+ concentration must be maintained within tight limits not to disrupt cellular function. Failure to do this will cripple enzyme mediated reactions in the cell, leading to cell death. pH represents a convenient scale of expressing H+ concentration (pH=log[H+]). Limits of pH compatible with life generally are in range of 7.0 to 7.8, which represents a change in H+ concentration of 86 nEq/L. Fortunately, in terms of compatibility with life, the body is 100,000 and 1,000,000 times more sensitive to changes in extracellular H + than to K + and Na + respectively. The most significant contribution to H+ comes from the cellular oxidation of substrates that produce CO2 (mainly TCA cycle). Total daily production of CO2 ranges from 13000 to 15000 mmol, obviously a vast amount. But as CO2 is a soluble gas and quickly diffuses through biological membranes, the body utilizes CO2 as a buffer rather than allowing as a burden. CO2 + H2O Õ H2CO3 Õ H+ + HCO-3

Increase or decrease in PaCO2 represent derangements of (1) Neural – respiratory control (2) Compensatory changes in response to alternation in plasma HCO-3. Under most circumstances, CO2 production and excretion are matched and PaCO2 is maintained at a steady state at 40 mmHg. Primary CO2 regulation is by neural and respiratory factors i.e. elimination rather than production. Hypercapnia is usually due to hypoventilation, CO2 retention and hypocapnea is by hyperventilation and excessive CO2 washout. Primary changes in PaCO2 can cause Acidosis (PaCO2 > 40 mmHg) or Alkalosis (PaCO2 < 40 mmHg). This primary change evokes cellular buffering (fast system) and renal adaption (slow process). Any change in plasma HCO-3 due to metabolic or renal factor results in compensatory changes in ventilation and thereby blunts the change in blood pH. The kidneys regulate plasma HCO-3 by 3 processes: reabsorption of filtered HCO-3, formation of titratable acid and excretion of NH+4 in urine. PROXIMAL TUBULE

CO2 rapidly leaves the oxidizing cell and enters the interstitial fluid. While diffusing comes in contact of carbonic anhydrase (RBC) and the above reversible reaction results in conversion of excess bicarbonate to CO2 which is excreted through lung – “Open System buffer”. Normal Acid-Base homeostasis System arterial pH is maintained between 7.35 and 7.45 by extracellular and intracellular buffering together with respiratory and renal regulatory mechanisms. Control of PaCO2 by CNS and respiratory system and control of plasma HCO-3 by kidneys stabilize the arterial pH. The components are described by Henderson – Hasselbalch equations – pH = 6.1 + log (HCO-3 / PaCO2 X 0.0301) Prof. and HOD of Anaesthesiology Bangur Institute of Neurology, Kolkata. E-mail : [email protected]

Fig. 1 - Bicarbonate reclamation in the proximal renal tubule.

374

INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003

Kidneys filter 4000 mmol of HCo-3 per day and renal tubules secrete equal amount of H+ to absorb this HCO-3. 80-90% if biocarbonate is reabsorbed in the proximal tubule. The magnitude of this process is modulated by the state of ECF volume, Serum K and pCO2. The distal nephron secretes protons (NH+4 and titratable acid) generated by metabolism amounting 40-60 mmol dl-1. Major means of net H+ excretion is renal ammoniagenesis. Net H+ excretion take place in the distal tubule where it is used to titrate NH3 and HPO-24. At a urine pH of 4.5, only 0.00006 mEq of H+ is excreted in 1500 ml of urine without buffer. Fortunately, the urine contains several buffers that permit the excretion of large amounts of H+ without requiring urinary pH to fall lower than 4.5. H+ excretion by these buffers results in what is termed titratable acidity. The major member of this buffer group is HPO-42 which is available for buffering to about 10 meq of H+ / 24 hours (i.e. 1000 fold of without buffer). Other urinary buffers include creatinine, uricacid and Bhydroxybutyice acid. Metabolic acidosis in face of normal excretion. NH+4 production and excretion are impaired in chronic renal failure, hyperkalaemia and renal tubular acidosis.

is largely dissipated through combination of the eliminated H+ with the urinary buffers, chiefly NH3 and disodium phosphate. Reabsorption of a HCO-3 molecule results in elimination of a Cl- and a K+ that offsets the sodium simultaneously reabsorbed. Hepatic ureagenesis consumes HCO-3 and NH-4 Glucose

2HCO3-

Blood Glutamine

a-ketoglutarate +2NH 4 +

Lumen of proximal tubule

URINE

Fig.3 : Renal ammoniagencies.

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 7.357.45) 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.

Fig. 2 – Distal tubular mechanism of net H+ excretion.

Renal pH regulation occurs in the distal tubule, where active transport of H+ derived from cytosolic generation of H2CO3 and net reabsorption of HCO-3 occur. This mechanism is distinct from that of the proximal tubule because of the H+ transport does not need Na+/H+ exchange another important feature of this region is the presence of “nonleaky” tight functions, which facilitate maintenance of the large gradients thus established. Finally, the gradient

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. Types of Acid-Base disorders: (A) Simple acid-base disorders: are common clinical disturbances where compensation is incomplete and pH is abnormal. Examples are •

Metabolic acidosis

•

Metabolic alkalosis

•

Respiratory acidosis and

•

Respiratory alkalosis

DAS : ACID-BASE DISORDERS

(B) Mixed acid-base disturbances : are not merely compensatory disturbances but independently coexisting disorders seen in critically ill patients with extreme changes in pH. Primary respiratory disturbances (primary changes in PaCO2) invoke compensatory metabolic response – secondary changes in HCO-3. Similarly primary metabolic disturbances cause compensatory respiratory responses. The degree of respiratory compensation in metabolic disturbances can be predicated by the equation : PaCO2 = (1.5 x HCO-3) + 8 i.e. the PaCo2 is expected to decrease 1.25 mmHg for each mmol per liter decrease in HCO-3. Physiologic Effects of Acidosis and Alkalosis ON CVS: 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 later occurs more promptly, presumably because of the rapid entry of CO2 into the cardiac cell. Although metabolic acidemia decreases the threshold for ventricular 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. 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 a decrease 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). ON CNS: 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 typically 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. Acute respiratory alkalemia causes a decrease in cerebral blood flow, an effect that last only about 6 hours. It produces confusion, myoclonus, asterixis, loss of consciousness and seizures.

375

On Electrolytes: The effects of acidemia on electrolyte levels are quite complex. Acute infusions of HCI 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 academia causes no change, or a slight increment, in serum potassium. Both respiratory and metabolic academia cause increased extracellular phosphate concentrations. Clinically, lactic acidosis and ketoacidosis are associated with hyperphosphatemia. 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. Diagnosis of acid-base disorders • History and Clinical findings Most common causes of acid-base disorders should be kept in mind. Such as : i) Chronic renal failure expected to cause metabolic acidosis ii) Intestinal obstruction and chronic vomiting likely to cause metabolic alkalosis iii) COPD patients or patients with overdose of sedatives usually exhibit respiratory acidosis and iv) Patients with pneumonia, sepsis or cardiac failure frequently have respiratory alkalosis • Investigations a) Arterial blood Gases estimation shows both pH and PaCO2. [HCO-3] is calculated from Henderson-Hasselbalch equation. Calculated value has to be compared with measured [HCO-3] or total CO2 on electrolyte panel. The two values should agree within 2 mmolL-1. Blood for electrolytes and ABG should be drawn simultaneously prior to therapy as increase in [HCO-3] occurs both in metabolic alkalosis and respiratory acidosis conversely decrease in [HCO-3] seen both in metabolic acidosis and respiratory Alkalosis.

376

INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003

b) Serum electrolytes: Metabolic acidosis leads to hyperkalaemia. For each 0.1 decrease in blood pH, the plasa K+ rises by 0.6 mmolL-1. Diabetic ketoacidosis, Lactic acidosis, diarrhoea, renal tubular acidosis (RTA) are often associated with potassium depletion due to urinary K+ wasting.

7.4, HCO-3 to 25 mmolL-1 and PaCO2 to 40 mmHg i.e. ABG is almost normal but AG shows elevation at 30 mmolL-1 indicating a mixed metabolic alkalosis and metabolic acidosis. Responses on Simple Acid-Base Disturbances

Anion Gap: Anion gap represents unmeasured anions in plasma (normal value – 10 to 12 mmolL-1) AG=Na+-(Cl-+ HCO-3). The unmeasured anions include–Anionic proteins, Phosphate, Sulphate and organic anions.

Disorder

Prediction of Compensation

Metabolic acidosis

Paco2 = (1.5 x HCO-3) + 8 Or Paco2 will 1.25 mmHg per mmolL-1 Or Paco2 = [HCO-3] + 15

An increase in AG is due to increase in unmeasured anions and less commonly due to decrease in unmeasured cations (Ca++, Mg++, K+). The AG may increase with an increase in anionic albumin, either due to increased albumin concentration or alkalosis which alters albumin charge.

Metabolic alkalosis

AG is decreased due to – (1) an increase in unmeasured cations, (2) addition of abnormal cations (Lithium or Cationic immunoglobulins), (3) a reduction in major plasma anion i.e. albumin (nephrotic syndrome), (4) Decrease in anionic charge on albumin (acidosis) or (5) Hyper viscosity and severe hyperlipidemia (which lead to an under estimation of Na+ and Cl- concentration). So simple calculation of the Anion gap evaluates the acid-base disorder. Normal values for HCO-3, PaCO2 and pH do not ensure the absence of an acid-base disturbance. For example, an alcoholic who has been vomiting may develop a metabolic alkalosis with a pH of 7.55, PaCO2 of 48 mmHg HCO-3 of 40 mmolL-1, Na+ - 135, Cl- - 80 and K+-2.8. If he develops superimposed alcoholic ketoacidosis with a b-hydroxybutyrate 15 mm, pH falls to Arterial blood [H+] (nmol/L)

in [HCO-3]

Paco2 will - 0.75 mmHg per mmolL-1 - in [HCO-3] Or Paco2 will - 6 mmHg per 10-mmolL-1 - in [HCO-3] Or Paco2 = [HCO-3] + 15

Respiratory alkalosis Acute Chronic

[HCO-3] will [HCO-3] will

Respiratory acidosis Acute Chronic

[HCO-3] will - 1 mmolL-1 per 10-mmHg - in Paco2 [HCO-3] will 4 mmolL-1 per 10-mmHg - in Paco2

2 mmolL-1 per 10-mmHg 4 mmolL-1 per 10-mmHg

in Paco2 in Paco2

Metabolic acidosis Causes : 1) Increased endogenous acid production (eg. Lactate and Ketoacids) 2)

Loss of HCO-3 (Diarrhoea)

3)

Accumulation of endogenous acid (eg. Renal facture) Clinical metabolic acidosis are of 2 types –

(1) High A.G. acidosis, (2) Normal AG or Hyperchloremic acidosis. High Anion Gap metabolic acidosis Causes are – (1) Lactic acidosis, (2) Ketoacidosis (diabetic, alcoholic ,starvation) (3) Ingested toxins (ethylene glycol, methanol,salicylates ) and (4) Renal failure (acute and chronic) Normal Anion-Gap metabolic acidosis (1) Gastrointestinal loss of bicarbonate(Diarrhea , Urinary diversion)

Fig. 4 -Acid-base nomogram.

(2)

Small bowel, pancreatic, or bile drainage (fistulas, surgical drains)

(3)

Renal loss of bicarbonate (or bicarbonate equivalent) Renal tubular acidosis, Recovery phase of Ketoacidosis , Renal Insufficiency

DAS : ACID-BASE DISORDERS

(4)

Acidifying Substances HCl, NH4Cl, Arginine HCl, Lysine HCl, Sulfur.

Lactic acidosis is the most common and most important acidosis encountered in the ICU. The acidaemia 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 it is commonly defined as an arterial lactate level greater than 5 mmolL-1, 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 judging the effect of therapy and assessing prognosis. Etiologies of lactic acidosis 1. Increase Oxygen Consumption: Strenuous exercise, Grand mal seizures, Neuroleptic malignant syndrome, Severe asthma, Pheochromocytoma 2.

Decreased Oxygen Delivery: Decreased Cardiac Output , Hypovolemia , Cardiogenic shock

3.

Decreased Arterial Oxygen Content: Profound anemia , Severe hypoxemia

4.

Regional Ischemia: Microcirculatory Disturbances , Sepsis

5.

Alterations in Cellular Metabolism: Diabetes, Thiamine deficiency, Severe alkalemia, Hypoglycemia, Malignancy

6.

Toxins and Drugs

7.

Congenital

8.

Decreased Lactate Clearance Fulminant hepatic failure

Treatment of metabolic acidosis : Underlying condition must be treated. Lactic acidosis mostly 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 remaining causes. So in lactic acidosis circulatory insufficiency must be corrected, tissue perfusion restored. Vasoconstrictors

377

must be avoided. The treatment of lactic acidosis is primarily the treatment of the disease causing the metabolic derangement. Therapies aimed at ameliorating the acidosis itself are attempts to prevent further deterioration until the primary process can be controlled. 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 HCO 3 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 PaCO2 is to be avoided. In patients on controlled mechanical ventilation, an increase in the minute ventilation can be used to lower the PaCO2 and raise the pH without the administration of HCO3. Also, increased 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 PaCO2 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 pyruvatedehydrogenase complex, thereby enhancing the conversion of pyruvate into acetyl-CoA and its entry into the Krebs cycle. The results to date are promising, but results of randomized trials are still waiting. 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 adverse 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. Due to lack of supporting data, some authors, 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. Diabetic Ketoacidosis (plasma glucose >300 mgdl-1) must be treated with Insulin. Insulin also prevents production of ketones. In Alcoholic ketoacidosis ECF deficits should be replaced by 5% dextrose in 0.9% Nacl. In drug induced metabolic acidosis due to salicylates, vigorous gastric lavage

378

with isotonic saline followed by administration of activated charcoal should be done. In case of ingestion of ethylene glycol , prompt institution of a saline osmotic diuresis, followed by thiamine and pyridoxine supplement, fomepizole or ethanol and haemodialysis has to be done. Fomepizole 7 mgkg-1 loading dose has the advantage of a predictable decline in ethylene glycol level without any adverse effects. Both uraemic acidosis and hyperchloremic acidosis require oral alkali replacement to maintain HCO-3 between 20 and 24 mmolL-1. This can be accomplished with alkali of 1.0 to 1.5 mmolkg-1 per day. Alkali replacement prevents muscle catabolism and harmful effect of H+ on bone. Sodium citrate (Shohl’s solution) or NaHCO3 tablets are equally effective. Associated hyperkalemia should be treated with frusemide (60-80 mgday-1). Metabolic alkalosis Metabolic alkalosis is characterized by a primary increase in HCO-3 concentration and a compensatory increase in PaCO2. As the normal kidney can excrete HCO-3 loads of up to 10 meqkg-1day-1, for metabolic alkalosis 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), hypokalemia or an increase in mineralocorticoid activity. When Cldeficit is present, HCO-3 is reabsorbed with sodium and metabolic alkalosis will persist until the Cl- deficit is replaced. Hypokalemia increases tubular HCO-3 reabsorption and mineralocorticoid excess increases HCO-3 by 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 HCO-3 levels, and acetate used in total parenteral nutrition. If the etiology is not clear, a trial of volume and Cl- replacement, correction of hypokalemia, 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 PaCO2 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 hemodialysis and hydrochloric acid are used

INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003

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 Acid-Base Disorders I. Alkalosis A. Central nervous system stimulatio

I I . Acidosis A. Central

1. Pain

1. Drugs (anesthetics, morphine, sedatives)

2. Anxiety, psychosis

2. Stroke

3. Fever

3. Infection

4. Cerebrovascular accident

B. Airway

5. Meningitis, encephalitis

1. Obstruction

6. Tumor

2. Asthma

7. Trauma B. Hypoxemia or Tissue hypoxia

C. Parenchyma 1. Emphysema

1. High attitude, Paco2

2. Pneumoconiosis

2. Pneumonia, pulmonary edema

3. Bronchitis

3. Aspiration

4. Adult respiratory distress syndrome

4. Severe anemia

5. Barotrauma

C. Drugs or hormones

D. Neuromuscular

1. Pregnancy, progesterone

1. Poliomyelitis

2. Salicylates

2. Kyphoscoliosis

3. Nikethamide

3. Myasthenia

D. Stimulation of chest receptors 1. Hemothorax

4. Muscular dystrophies E. Miscellaneous

2. Flail chest

1. Obesity

3. Cardiac failure

2. Hypoventilation

4. Pulmonary embolism

3. Permissive hypercapnia.

E. Miscellaneous 1. Septicemia 2. Hepatic failure 3. Mechanical hyperventilation 4. Heat exposure 5. Recovery from metabolic acidosis

Respiratory acidosis Respiratory acidosis is characterized by a primary increase in PaCO2 and a compensatory increase in HCO-3. Respiratory acidosis represents ventilatory failure. Decreased alveolar ventilation arises from a decrease in minute ventilation or from an increase in dead space without

DAS : ACID-BASE DISORDERS

a compensatory rise in minute ventilation. A rise in CO2 production will produce hypercapnea unless ventilation does not increase appropriately. The etiologies 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 alkalosis Respiratory alkalosis is characterized by a primary reduction in the arterial PCO2, followed by a secondary two-phase reduction in HCO-3, a small acute decrease due to tissue buffers and a larger chronic decrement due to a decrease in renal titratable acid excretion and an increase in renal HCO-3 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. Mixed acid-base disorders Mixed acid-base disorders are defined as independently coexisting disorders, not merely compensatory responses are often seen in patients in critical care units and can lead to dangerous extremes of pH. A patient with diabetic ketoacidosis (metabolic acidosis) may develop an independent respiratory problem leading to respiratory acidosis or alkalosis. Patients with underlying pulmonary disease may not respond to metabolic acidosis with appropriate ventilatory response because of insufficient respiratory reserve. Such imposition of respiratory acidosis

379

on metabolic acidosis can lead to severe acidemia and a poor outcome. When metabolic acidosis and metabolic alkalosis coexist in the same patient the pH may be normal or near normal. When the pH is normal, an elevated anion gap denotes the presence of a metabolic acidosis. A diabetic patient with ketoacidosis may have renal dysfunction resulting in simultaneous metabolic acidosis. Patients who have ingested an overdose of drug combinations such as sedatives and salicylates may have mixed disturbances as a result of the acid-base response to the individual drugs (metabolic acidosis mixed with respiratory acidosis or respiratory alkalosis, respectively). Even more complex are triple acid-base disturbances. For example, patients with metabolic acidosis due to alcoholic ketoacidosis may develop metabolic alkalosis due to vomiting and superimposed respiratory alkalosis due to the hyperventilation of hepatic dysfunction or alcohol withdrawal. To be comprehensive, when dealing with an acid base disorder, one should 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 : PCO2 = ( 1.5 x HCO3 ) + 8 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 For further reading : 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 Textbook of Medicine, Oxford Medical Publications 1996.

4)

“Harrison’s Principles of Internal Medicine” –15th Edition, Volume I.

5)

“Biochemistry and Disease” – Bridging Basic Science and Clinical Practice: Robert M. Cohn, Kark S. Roth 1996.