7. TREATMENT

7.1 RESPIRATORY ACIDOSIS

Respiratory Acidosis is corrected by increasing alveolar ventilation and/or treating the cause. Acute respiratory acidosis can probably be corrected rapidly (Prys-Roberts et al, 1967) but chronic respiratory acidosis should be corrected slowly. Rapid lowering of a high PaCO2 has been associated with fits and cardiovascular collapse.

If the patient has a compensatory disturbance (high non-respiratory pH and positive base excess) which has raised the pH towards normal, the kidneys have to correct this disturbance which is equivalent to a metabolic alkalosis. This compensatory metabolic alkalosis does not require treatment if the patient is given a mixed diet with adequate Cl (Polak et al, 1961), and provided there are no complicating factors in its genesis or in the cardiovascular or renal systems. If the compensatory non-respiratory alkalosis is preventing the patient from lowering his PaCO2 the alkalosis may need to be treated by modifying the steroid or diuretic therapy. Acetazolamide (Diamox) can be used to correct the metabolic alkalosis. It differs from other diuretics in producing an acidosis by the loss of Na HCO3 in the urine. When this drug causes loss of base in the urine the sodium content of the E.C.F. must fall. Although acetazolamide will produce a lessening of alkalosis by loss of base, rather than the physiological mechanism of acid retention, the coincidental loss of Na may be a benefit if the patient has any cardiac failure.

7.2 RESPIRATORY ALKALOSIS

7.2.1. Treat the cause

e.g. correct hypoxia or shock if they are causing hyperventilation.

7.2.2. Elevate the PaCO2.

This can be corrected by administering CO2, increasing the dead space or lowering the minute ventilation. These measures will rarely be thought to be necessary.

7.3 METABOLIC ACIDOSIS

7.3.1 Treat the cause.

Stop alimentary loss of base; correct hypoxia; reduce renal acid load by diet; drain abscess in diabetic ketosis and give insulin (see 7.3.2.2.3, ketoacidosis) ; treat shock with intra-venous fluids and stop haemorrhage etc (see 7.3.2.2.2.2, shock) .

7.3.2. Correction of Acidosis

7.3.2.1. Administration of NaCl.

If the acidosis is (a) not affecting the cardiac action and (b) renal function is adequate, the acidosis may be corrected by giving sufficient NaCl (Na + Cl) solution for the kidney to (i) correct the acidosis by excreting HCl (H + Cl) or NH4Cl (NH4 + Cl) and (ii) repair any deficit in E.C.F. volume. This approach applies in alimentary causes of metabolic acidosis where the kidneys are usually able to correct the defects if enough saline is given (Hesse et al, 1966). Correction may be more rapid if Hartmann's solution rather than 0.9% NaCl solution is given to correct the pH disturbance as there is less for kidney to do. The lactate ion has to be converted to HCO3 and some H + Cl will have to be excreted but not as much as with NaCl solution.

7.3.2.2. Administration of Base.

Indications for direct correction of acidosis by giving base:

7.3.2.2.1. The cause cannot be corrected. e.g. renal acidosis, where the kidneys fail to excrete inorganic acid (an end product of protein metabolism). If this defect is the sole manifestation of renal impairment (i.e. renal tubulcar acidosis), it is rational to neutralise the acid with NaHCO2 which can be given by mouth. In most instances renal failure is not manifest solely by acidosis. Usually dialysis or transplantation is necessary to correct the multiple effects of renal failure which include acidosis.

7.3.2.2.2. Where the acidosis is depressing the circulation (i.e. to break the viscious circle of myocardial depression which aggravates acidosis). This is the indication in cardiac arrest (Chazan et al, 1968) or in shock.

7.3.2.2.2.1. Cardiac Arrest. In cardiac arrest, acute lactic acidosis, it is said, may prevent the circulation restarting. NaHCO2 is often given in an empirical and probably excessive dose of "1 bottle" (i.e. 500mls 4.2% NaHC03 = 250meq). PaCO2 rises as some HCO3 is converted to H2CO2. Serum [Na] will rise and circulatory overload may be caused by the Na load. After recovery a metabolic alkalosis will occur until the Na + HCO3 are excreted.

There is controversy surrounding the use of base in cardiac arrest (Stackpool 1986, Narins and Cohen 1987), as in the emergency situation it is impractical to obtain biochemical evidence before treatment (Leading Article, Lancet, 1976). Non-respiratory acidosis does not occur in all cases of cardiac arrest (Stewart, 1964, Chazan et al, 1968). Inadequate ventilation causing a high PCO2 is as frequent a cause of low pH in cardiac arrest as is metabolic acidosis. There is no reason for thinking that the low pH due to CO2 has much cardiovascular depressant effect (Schultz et al, 1960; Prys-Roberts et al, 1967; Gerst et al, 1964).

If the circulation is restored rapidly after resuscitation is commenced (i.e. pulse and/or consciousness) than any NaHCO2 infusion which may have been started should be stopped until the situation is assessed biochemically (Rackwitz et al, 1976).

Mattar et al, 1974, investigated 12 patients in whom NaHCO3 was administered during cardiac arrest resuscitation. Full measurements were not available in all cases. The doses of NaHCO3 were between 45 and 270meq. The mean changes were:

		before NaHCO3	after NaHCO3
Osmolality ( mOsmol/litre)		302	377
pH		7.34	7.54
HCO2 (mEq/litre)		21	50
Na (mEq/litre)		138	170

It has also been shown (Fillmore et al, 1970) that even if it is possible to effectively adjust pH abnormalities during resuscitation by use of alkali, restarting heart action still may not occur. Presumably this lack of restarting was be due to overwhelming myocardial damage or inadequate circulation provided by the cardiac massage. This was suggested by the rising lactic acid level which was probably an effect rather than the cause of continuing inadequate heart action.

It is still common practice to administer NaHCO3 during cardiac arrest. In some institutions NaHCO3 infusion is left set up on each cardiac arrest trolley to save time in starting its administration.

The dose required to correct a low non-respiratory pH is arbitrary in the individual patient. I would advise that a base-line specimen of blood should be taken before the NaHCO3 administration, if this is possible. Venous blood from a central vein if one (e.g. the internal jugular) is being used to administer drugs is satisfactory, but arterial might be better. Follow up blood measurements would then be done as resuscitation continues and is completed, to examine pH, osmolality, Na, K , PCO2, PO2 and lactate levels.

In summary I would conclude that correction of non-respiratory pH during cardiac resuscitation is not as important as once was thought, and that monitoring of biochemical changes before and after such correction should be routine.

7.3.2.2.2.2. Shock. In shock accompanied by acidosis it is rational to administer base together with other haemodynamic management, i.e. raising the C.V.P., giving inotropic agents, oxygen, etc. (Manger et al; 1962, Ledingham, 1962; MacKenzie, 1965). When base is given in shock it is not rational to give it over some hours after having decided on a dose. The acidosis should be corrected as quickly as possible in two or three steps controlled by non-respiratory pH, base excess or standard bicarbonate measurements, e.g. first dose (7.4 - non-respiratory pH) x body weight (kg) x 7meq or - (0.1 x base excess x body weight) meq. Subsequent doses are estimated after the effect of the first dose has been observed. Dosage of NaHCO2 (or any other intravenously administered electrolytes) cannot be determined by formulae. Response to initial dosage will suggest magnitude of subsequent doses. Factors which would have to be taken into account if dosage was to be predicted would have to include cause of acidosis, the circulatory state and the magnitude of the acidosis. The degree of acidosis alters the requirements of NaHCO2 by a function which is not a direct proportion (Garella et al, 1973).

7.3.2.2.3. Diabetic Keto-Acidosis. The use of HCO3 in diabetic keto-acidosis is also controversial. Acidosis has been claimed to be a cause of insulin resistance in diabetic acidosis (Walker et al, 1963). This study was not controlled. Regimes including HC03 have been advocated without conclusive evidence of benefit (Solar et al, 1973; Solar et al, 1974). Administering NaHC03 in diabetic keto-acidosis may exaggerate changes in serum K particularly if this is changing rapidly following high doses of insulin.

It now obvious that many of the problems of managing diabetic acidosis (i.e. ketotic and non-ketotic) were iatrogenic, i.e. due to large intermittent I.V. and I.M. dosage of insulin, rapid and erratic alterations in blood pH, K and glucose levels. Diabetic acidosis can be corrected over a period of about 6 hours with low dose I.V. infusions of insulin. There is steady biochemical and clinical improvement without swings in blood glucose or K levels. Only small doses of K are necessary and in most instances HCO3 is not given, although when it has been, it has apparently not produced adverse effects (Alberti et al, 1973; Page et al, 1974; Kidson et al, 1974; Semple et al, 1974; King et al, 1974 and Shaw et al, 1974). If NaHC03 is to be used in diabetic acidosis its use should probably be limited to patients with severe acidosis (pH<7) and the initial dose should probably be not greater than 100meq in a 70kg patient.

The low PaCO2 which is present in the initial phases of diabetic acidosis may persist after the blood pH has returned to normal. This is probably not due to delay in return of the CSF pH to normal (King et al, 1974).

7.3.2.2.4 Neonatal resuscitation. NaHCO2 is used in neonatal resuscitation (Clark et al, 1968). The use is analogous to its use in cardiac arrest. The need or efficacy of the treatment as a routine has not been established. When used, pH electrolyte studies should be done, at least retrospectively. Hypernatraemia and intracranial haemorrhage have been associated with administration of NaHCO2 in the neonatal period (Simmon et al, 1974; Volpe, 1974).

7.3.2.2.5 Neonatal Respiratory Distress Syndrome (RDS). NaHCO2 has been used to correct the "chronic" acidosis of this syndrome (Usher,1963). The acidosis is presumably due to hypoxia and correction of this (Daily et al,1971; Smith and Daily,1971) if possible, would be more rational (Dell and Winters,1972). In other cases CO2 retention may be the cause of low pH. In these cases increased ventilation would be the rational treatment. (Ostrea et al,1976). When it has been given in the patients with RDS to correct acidosis, NaHCO2 gives an acute rise in PaCO2. Tham causes an acute fall in PaCO2. These changes in PaCO2 last for some minutes (Baum et al,1975).

7.3.2.3 Complications of NaHCO2 Therapy

• Metabolic alkalosis which may then cause respiratory depression.
• Hypernatraemia and hyperosmolality (Mattar et al,1974; Bishop et al,1976).
• Changes in other electrolytes especially lowering of serum [K].
• Fluid retention in patients who have disorders which will lead to fluid retention if excess Na is given.
• Acute rise in PaCO2 due to neutralization of HCO3 (Singer et al, 1956; Ostrea and Odell, 1972; Baum et al, 1975).
• Intracranial haemorrhage (Simmons et al, 1974; Volpe, 1974; Papil et al, 1978).

7.3.2.4 Tham

Tham (Nahas, 1961) is an organic base (often referred to as a buffer) used to correct acidosis. It has no obvious advantages over sodium bicarbonate. Its claimed advantages include ability to correct intracellular acidosis. A separate syndrome of intracellular acidosis is not clinically recognised. Its main value might be in situations in which Na load may be undesirable, e.g. cardiogenic shock. Although, as Tham is an osmotically active agent it may have similar effects on extracellular fluid volume as Na. It might be of use if one wished to correct the low pH of respiratory acidosis directly (Manfredi et al, 1960), as some have claimed (Mithoefer et al,1965 and 1968) that bronchospasm is relieved by direct correction of low pH. Its main disadvantages are inconvenience of preparation (it is supplied in a powder) and that it causes respiratory depression. Respiratory depression would presumably be caused by any substance which raised blood pH including Na0H or NaHCO2. Such depression could be managed by intermittent positive pressure ventilation so is not in itself an absolute reason for not using Tham.

7.4 METABOLIC ALKALOSIS

7.4.1 Remove the cause (e.g. relieve pyloric obstruction or modify diuretic regime).

7.4.2.1 Administration of NaCl. Ingestion or injection of sufficient sodium chloride solution for the kidney to correct the alkalosis by excretion of Na + HCO3 .

7.4.2.2 Administration of Acid. Direct correction of alkalosis with ammonium chloride or hydrochloridc acid solution, infusion or ingestion (Bradham, 1968, Leading Article (a) 1974, Sanderson, 1974; Pain et al, 1974; Abouna, 1974; Harken et al, 1975 and Worthley, 1977). This is indicated only if the alkalosis is very severe or renal or cardiac function are poor. Usually there is an associated reduction of extracellular volume so some Na has to be given in the form of NaCl. Compensation for non-respiratory alkalosis is CO2 retention achieved by hypoventilation. The hypoventilation may result in hypoxaemia which may necessitate oxygen therapy.