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THE RATIONAL USE OF I.V. HYDROCHLORIC ACID IN THE TREATMENT OF METABOLIC ALKALOSIS
Br.J. Anaesth. (1977), 49, 811
THE RATIONAL USE OF I.V. HYDROCHLORIC ACID IN THE TREATMENT OF METABOLIC ALKALOSIS L. I. G. WORTHLEY SUMMARY
With the introduction of potent diuretic agents to medical practice and with modern operative techniques permitting extensive thoracic and abdominal surgery, non-respiratory alkalosis may occur as a severe, even life-threatening, state (Wilson et al., 1972; Lawson, Butler and Ray, 1973). Characteristically, the alkalosis persists only if the patient has an associated unreplaced loss of saline or potassium chloride, and restoration of the effective extracellular fluid volume or correction of the total body potassium chloride defect allows correction of the pH abnormality without additional therapy. However, in the presence of cardiac, renal or hepatic failure, the alkalotic state may become refractory. Furthermore, in these conditions saline, potassium chloride or ammonium chloride infusions may be contraindicated. In a direct attempt to correct the acid-base defect without involving renal or hepatic mechanisms, i.v. hydrochloric acid has been used (Elkington and Danowski, 1955; Frick and Senning, 1964; Rampini and Frick, 1964; Girardet, 1967; Bradham, 1968; Beach and Jones, 1971; Abouna, Veazay and Terry, 1974; Brennan, 1974; Worthley and Pain, 1974; Harken et al., 1975; Shavelle and Parke, 1975; Williams, 1976). This approach has been criticized, however, as haemolysis (Whelton, 1974), tissue necrosis (Shavelle and Parke, 1975) and the necessity for central venous cannulation (Brennan, 1974) make it potentially hazardous. This report describes four patients with severe refractory metabolic alkalosis, which was corrected by i.v. hydrochloric acid without complication. L. I. G. WORTHLEY, M.B., B.S., F.R.A.C.P., F.F.A.R.A.C.S.,
Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000.
PATIENTS AND METHODS
During a 2-year period in which 65 patients with metabolic alkalosis (pH greater than 7.45) were treated, four patients developed a severe alkalosis refractory to a conventional therapeutic regime outlined below, and i.v. hydrochloric acid was considered. Initially, 0.9% saline was administered until the central venous pressure (cv.p.) increased by 5-8 cm H 2 O from its original value (zero reference point at mid-axillary line, patient supine). The infusion was discontinued if values greater than 10 cm H 2 O were obtained, a precaution deemed necessary to minimize the risk of acute pulmonary oedema (Russell, 1974). All patients had an initial cv.p. value less than 8 cm H 2 O. Pulmonary venous wedge pressure measurements were not recorded and although they might have facilitated the early detection of pulmonary oedema, observation of cv.p. following saline infusion, and clinical signs of left heart failure were considered to be a simpler yet acceptable alternative (Baek et al., 1975). Potassium chloride (in amounts ranging from 100 to 200 mmol/day) was infused until the serum concentration of potassium increased to 4.5 mmol/litre. Fluid loss by nasogastric aspiration was replaced with 0.45% saline with potassium 27 mmol/litre. If these methods did not correct the alkalosis within 72 h, the state was deemed to be refractory. The four patients with refractory alkalosis had varying degrees of renal and hepatic failure so that infusions of ammonium chloride, lysine or arginine hydrocnloride or administration of acetazolamide were contraindicated or unlikely to be of therapeutic benefit. Before the infusion of hydrochloric acid was commenced, venous blood was collected for estimations of serum sodium, potassium, chloride (Technicon S.M.A. 6/60 auto-analyser), haptoglobin and
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A method for the assessment and management of factors both causing and maintaining a primary metabolic alkalosis is presented. During a 2-year period 65 patients with metabolic alkalosis were treated with saline and potassium chloride infusions. In four patients the alkalosis was refractory and required additional therapy. An infusion of hydrochloric acid 0.12-0.24 mol/litre through a central venous line corrected the alkalosis without causing haemolysis or tissue necrosis. The maximum rate of infusion suggested is 0.2 mmol H+.kg body w t " 1 . ^ 1 .
812
BRITISH JOURNAL OF ANAESTHESIA TABLE I. Biochemical data in patients 1-4 during the 72-h period of saline and potassium chloride infusions
Patient 1
Patient 2
Patient 3
Patient 4
Day
Day
Day
Day
2
3
1
2
3
1
2
3
1
2
3
I.v. infusion Na+ (mmol/24 h) K+ (mmol/24 h) Cl (mmol/24 h)
646 185 831
308 69 377
231 40 271
624 202 826
346 107 453
346 107 453
600 155 755
323 60 383
192 40 232
400 112 512
262 51 313
169 32 201
Arterial acid-base data PH Paco, (kPa) HCOjT (mmol/litre) Base excess (mmol/litre)
7.55 7.54 7.50 6.7 7.9 6.0 41 44 38 + 14 + 17 + 18
7.55 5.3 34
7.61 7.67 6.0 5.5 50 40 + 11 + 18 + 27
7.47 6.0 32
7.54 6.3 39
7.50 5.3 30
7.51 6.0 35
7.52 6.8 41
+8
7.55 6.7 42 + 16 + 18
Water input (litre)
5.4
4.0
4.5
6.1
4.5
5.5
5.8
4.2
4.5
4.2
3.4
3.2
Water output Gastric (litre) Urine (litre)
2.4 1.8
2.0 2.5
1.5 2
2.1 2.5
2.5 2.2
2.5 3.0
1.8 2.7
2.2 2.5
1.5 2.8
1.2 2.1
1.4 1.8
1.2 1.5
haemoglobin. Arterial blood was collected also for pH and blood-gas analysis; serum and blood-gas estimations were repeated both during and immediately after the hydrochloric acid infusion. Biochemical data are presented in table I. The infusion of hydrochloric acid was through a central venous catheter with its tip placed high in the right atrium. A subclavian approach was used and the catheter position confirmed subsequently by chest x-ray. The four patients described were considered to have normal respiratory function from considerations of history, physical examination and chest x-ray. In the three patients with hypercapnia, reference to an in vivo acid-base diagram (Goldberg et al., 1973) indicated that a primary metabolic alkalosis with respiratory compensation existed. The quantity of hydrochloric acid to be infused was calculated from the chloride deficit, assuming the chloride space to be 20% of total body weight. This calculation was used only as an initial estimate as arterial acid-base studies taken during the infusion, and the use of an in vivo acid-base diagram as a flow chart (Flenley, 1971; Goldberg et al., 1973) allowed a more accurate determination of the amount of acid necessary. The hydrochloric acid was infused over periods of 12-48 h as a 0.12-0.24 mol/litre solution (120240 mmol H+/litre) consisting of 60-120 ml of hydrochloric acid 2.0 mol/litre added to 5% dextrose 1 litre.
+7
+ 12 + 16
CASE REPORTS
Case 1
A 71-year-old man had a 4-h history of anuria, arterial hypoxaemia (Pa 02 6.0 kPa*) and shock 24 h after laparotomy and partial resection of a gangrenous loop of large bowel. The arterial pressure was 60/40 mm Hg, heart rate 108 beat/min, c.v.p. 18 cm H 2 O, serum creatinine 0.52 mmol/litre and bilirubin 111 jimol/litre. His initial treatment consisted of an infusion of isoprenaline 2 (ig/min, oxygen-enriched air (FiOl 0.5) and the administration of gentamicin and lincomycin for suspected sepsis. Throughout the next 48 h he improved gradually, with the arterial pressure stabilizing at 120/80 mm Hg, heart rate 100 beat/min, c.v.p. 7 cm H 2 O and PaOi 18.9 kPa (Fi 02 0.5). However, a persistent ileus developed, producing 1-2 litre/day fluid loss through the nasogastric tube. Four days following admission the creatinine clearance was 23 ml/min, bilirubin 58 (xmol/litre and arterial blood-gas analysis revealed a metabolic alkalosis (pH 7.55, PaCOa 6.0 kPa). This was found to be resistant to the saline and potassium chloride infusion regime (table I); furthermore the patient developed respiratory compensation and hypoxaemia (pH 7.50, Pa C02 7.9 kPa, Pa Os 6.1 kPa (Fi 02 0.28). Correction of the metabolic alkalosis was then considered necessary to restore normal ventilation. * 1 kPa = 7.5 mm Hg.
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1
HYDROCHLORIC ACID FOR METABOLIC ALKALOSIS TABLE
813
j a II. Patient 1: Serum electrolyte, arterial blood-gas, haemoglobin and haptoglobin values during 240 mmol H+ (as hydrochloric acid) in 1 litreof 5% dextrose itj water
24->i
infusion of
Time (h)
Haemoglobin (g/dl)
Haptoglobin (mg/dl)t
mmol/ (litre)
(mmol/ litre)
(mmol/ litre)
(kPa)*
(kPa)
PH
(mmol/ litre)
Base excess (mmol/ litre)
0
13.1 13.5 13.0
183 175 182
139 138 141
4.6 4.4 3.9
88 90 97
6.1 7.6 8.0
7.9 6.7 5.9
7.50 7.49 7.45
44 37 30
+ 18 + 12 +5
12 24
Na+
K+
HCOr
ci-
P&CO,
* F i 0 , 0.28. | Normal range 45-170 mg/dl
Time
haptoglobin values duringan 18-h infusion of III. Patient 2: Serum electrolyte, arterial blood-gas, haemoglobin and 360 mmol H+ as hydrochloric acid in 1.5 litreof 5% dextrose inwater
00
Haemoglobin (g/dl)
0 12 18 36
10.7 10.1 10.4 10.8
Haptoglobin (mg/dl) 370 295 282 285
Na+
K+
(mmol/ litre)
(mmol/ litre)
143 141 138 145
4.0 4.5 4.2 4.9
ci-
(mmol/ Pa 0 , (kPa)'" litre) 90 89 97 104
10.5 11.6 10.5 12.7
Paco, (kPa) 6.0 4.8 3.5 5.3
PH
7.67 7.65 7.57 7.47
HCOj (mmol/ litre) 50 37 23 29
Base excess (mmol/ litre)
+ 27 + 17 +2 +5
* Fl 0 , 0.21.
Hydrochloric acid was administered (table II) and corrected the alkalosis within 24 h. The ileus resolved in the next 2 days and the patient was discharged to a general ward for further convalescence.
next 12 h. Corrective surgery for the pyloric obstruction was performed 1 day later, and subsequent arterial blood-gas analyses were within normal limits. The patient was discharged 15 days later.
Case 2 A 58-year-old man with a past history of chronic duodenal ulcer, analgesic nephropathy and chronic renal failure (creatinine clearance 15 ml/min) was admitted following a 12-h period of intractable vomiting. He had vomited intermittently during the previous 3 months, and this was attributed to pyloric obstruction from scarring and spasm induced by the ulcer. An infusion of 0.9% saline 5 litre containing potassium chloride 134 mmol, through a central venous catheter during 24 h, corrected the initial state of dehydration and electrolyte imbalance. During the following 3 days, despite replacement of nasogastric fluid losses and further infusions of saline and potassium chloride (table I), the alkalosis became refractory. The patient became confused and disorientated with further worsening of the alkalosis (pH 7.67). Hydrochloric acid was administered over an 18-h period, correcting the metabolic alkalosis (table III) and restoring partially the confused state. The patient became fully conscious and co-operative within the
Case3 A 69-year-old man developed a severe ileus following resection of an abdominal aortic aneurysm. The resulting profuse drainage from the nasogastric tube caused pre-renal oliguria. Within 24 h, 0.9% saline 4 hire and potassium chloride 200 mmol in 1 hire of 5% dextrose in water were administered, through a central venous catheter, the equivalent of the nasogastric drainage being replaced with 0.45% saline in addition. The serum potassium concentration increased from 3.2 mmol/litre to 4.8 mmol/litre and the central venous pressure increased from 2 to 10 cm H 2 O. The remaining serum biochemical variables returned to normal apart from creatinine (0.35 mmol/litre), bilirubin (70 (xmol/litre) and urea nitrogen (22 mmol/litre). Despite an improvement in the urinary output, the creatinine clearance during the next 4 days remained at 55 ml/min. With the continuing nasogastric fluid loss a severe refractory metabolic alkalosis with partial respiratory compensation developed (table I). On the 8th day after operation, hydrochloric acid was given i.v. to correct hypoventilation and hypoxaemia
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TABLE
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BRITISH JOURNAL OF ANAESTHESIA
TABLE IV. Patient 3: Serum electrolyte, arterial blood-gas and haemoglobin values during a \0-h infusion of 240 mmol of H+ {as hydrochloric acid) in 1.5 litre of 5% dextrose in water
Time (h)
Haemoglobin (g/dl)
Na+ (mmol/ litre)
0 6 10 24
10.2 10.4 10.2
141 140 137
K+ (mmol/ litre)
Cl(mmol/ litre)
4.9 4.8 4.5
89 92 105
Pao (kPa)*
-Paco (kPa)
pH
HCOj (mmol/ litre)
7.9 10.9 10.5 9.9
6.7 5.7 5.3 6.8
7.55 7.51 7.50 7.45
42 33 30 34
Base excess (mmol/ litre)
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* Fi0, 0.28.
TABLE V. Patient 4: Serum electrolyte, arterial blood-gas, haemoglobin and haptoglobin values during two 12-h infusions of 120 mmol H+ {as hydrochloric acid) in 1 litre of 5% dextrose in water. Each infusion was separated by 24 h
ci-
Haptoglobin (mg/dl)
Na+ (mmol/ litre)
K+ (mmol/ litre)
First infusion 0 10.2 12 9.8
239 220
145 144
5.0 5.2
92 97
Second infusion 0 9.6 12 10.0
225 235
144 144
5.4 5.6
100 102
Time (h)
Haemoglobin (g/dl)
(mmol/ litre)
Base excess (mmol/ litre)
^aco, (kPa)
PH
HCOr (mmol/ litre)
8.3 10.1
6.8 6.5
7.52 7.48
41 35
+ 16 + 11
10.4 11.3
7.1 6.1
7.48 7.47
39 32
+ 14 +8
Pa 0 , (kPa)*
• FlOi = 0.28.
(PaOa 5.7 kPa, PaCOs, 7.3 kPa, Fi 0 2 0.21) during a 10-h period (table IV). The ileus subsided within a further 3 days and the acid-base state returned to normal. Case A
A 67-year-old man was admitted with a perforated duodenal ulcer and circulatory failure, arterial pressure 70/50 mm Hg, heart rate 145 beat/min, c.v.p. 3 cm H 2 O. Initial resuscitation with 0.9% saline 3 litre and nasogastric suction produced an unexpectedly rapid clinical improvement. This was thought to justify further conservative therapy as an alternative to surgery. However, 3 weeks later a left subphrenic abscess developed and laparotomy was performed for both drainage of the abscess and vagotomy with pyloroplasty. After operation there developed a severe ileus with excessive nasogastric fluid loss and a metabolic alkalosis resistant to saline and potassium chloride infusions (table I). Hydrochloric acid was then infused in two 12-h periods (table V). The alkalosis improved following the infusions and on the 4th day after operation there was a normal acid-base state.
DISCUSSION
Severe metabolic acidosis has been recognized for many years as a dangerous clinical state and its treatment has become standardized. On the other hand, metabolic alkalosis has been recognized as a clinical problem only recently. Although a "blunted confusional state" may be the only manifestation (Plum and Posner, 1972), the associated complications of cardiovascular instability (Mitchell, Wildenthal and Johnson, 1972; Lawson, Butler and Ray, 1973), partial respiratory compensation (Tuller and Medhi, 1971; Heinemann and Goldring, 1974), and potassium wasting (Schwarz et al., 1968; Filley, 1972) may render a severe alkalotic disturbance a dangerous clinical condition. In the four patients presented, hypoventilation with associated hypoxaemia was the most consistent serious abnormality. The initial pH values in three of the patients (1, 3 and 4) were not overtly abnormal. Thus the alkalaemia was mild although the alkalosis was severe, producing compensatory hypoventilation and an associated hypoxaemia. In these patients a full appreciation of the degree of alkalosis required the
HYDROCHLORIC ACID FOR METABOLIC ALKALOSIS use of an in vivo acid-base diagram (Goldberg et al., 1973). Following the definition of the primary alkalotic state, recognition of the components causing it, as distinct from those which maintain it, becomes necessary (table VI). Correcting the disorder producing H + loss or HCOg" gain, will cure the condition. TABLE VI. Factors causing or maintaining alkalosis
Maintenance of alkalosis (1) Diminished effective extracellular fluid volume (2) Potassium deficiency with mineralocorticoid excess (3) Severe potassium deficiency ( > 450 mmol) (4) Renal failure
The normal kidney has a large capacity to excrete HCOjf. Thus maintenance of the alkalotic state, once its source is eliminated, depends upon a functional renal abnormality (Seldin and Rector, 1972). If an associated depletion in effective extracellular fluid volume exists, proximal tubular reabsorption of sodium is augmented. In the presence of a metabolic alkalosis proximal H + excretion (HCOjf reabsorption) is enhanced also, maintaining the e.c.f. volume at the expense of pH homeostasis (Schwartz et al., 1968; Kurtzman, White and Rogers, 1973). Similarly, if the patient is depleted of potassium and a state of hyperaldosteronism exists, with an adequate distal delivery of Na + , distal H + excretion is increased (Seldin and Rector, 1972; Kurtzman, White and Rogers, 1973). To correct the continuing pH defect, conventional therapy with potassium chloride and sodium chloride, and, occasionally, agents which have an inotropic effect on the heart, are usually all that is required, allowing the excess bicarbonate to be excreted with the infused cations. The role of potassium in the maintenance of an alkalotic state has been defined further following the demonstration that correction of a hypokalaemic state
with non-chloride-containing potassium salts fails to correct the existing alkalosis (Bleich, Tannen and Schwartz, 1966). Furthermore, correction of alkalosis can be achieved in mild hypokalaemic states with infusions of saline alone (Kassirer and Schwartz, 1966), although in the presence of severe potassium depletion a saline resistance has been described (Garella, Chazan and Cohen, 1970). However, correction of an existing hypokalaemia enhances the role of saline in correcting the alkalosis (Kurtzman, White and Rogers, 1970). Thus depletion of the chloride ion had been thought central in maintaining the alkalosis (Schwarz et al., 1968). Recently, however, the correction of the acid-base state with saline-free albumin solutions has suggested that diminished extracellular fluid volume activates the renal mechanism responsible for the persistence of the alkalosis (Kurtzman, White and Rogers, 1973; Warms et al., 1974). The albumin infusion permitted sodium and potassium bicarbonate to be excreted, thus correcting the acid-base disorder (Warms et al., 1974). Although correction of a metabolic alkalosis without potassium or sodium chloride is possible therapeutically it is not desirable if deficiencies in these ions exist. In the presence of renal failure the standard regimes may be insufficient (table VII) and alternative therapy with ammonium chloride, lysine or arginine TABLE VII. Treatment of metabolic alkalosis Indirect (1) Inhibition of renal mechanisms maintaining alkalosis Proximal: Increased functional ECF—NaCl infusion Albumin infusion Inotropic agents in cardiac failure Carbonic anhydrase—inhibition acetazolamide Distal: KC1 Aldosterone inhibition (spironolactone) (2) Following metabolism by liver to urea and HC1 Arginine or lysine hydrochloride NH4C1 Direct I.v. hydrochloric acid
hydrochloride, with conversion to urea and hydrochloric acid in the liver is often effective. However, in the presence of liver failure these agents may be of
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Causes of alkalosis (1) Loss of acid Renal Primary or secondary hyperaldosterone states with K + depletion Gastrointestinal tract Nasogastric suction, vomiting Congenital alkalosis with diarrhoea (2) Gain of alkali NaHCO 3 : oral or parenteral Metabolic conversion of infused acid anions Lactate Citrate Acetate Following hypercapnia
815
816
BRITISH JOURNAL OF ANAESTHESIA
It is proposed that, if i.v. hydrochloric acid is to be infused, the rate of infusion of H + should be no greater than 0.2 mmol. kg" 1 . h" 1 (300-250 mmol/ day), the infusion must be through a central venous catheter, and the acid-base state should be monitored every 6-12 h with arterial blood-gas analysis. In our experience, following correction of saline and potassium chloride deficits, i.v. infusion of hydrochloric acid is a safe and desirable therapy for severe metabolic alkalosis. ACKNOWLEDGEMENTS
I wish to thank Dr R. Pain for his constructive criticism of this report and Miss E. Hilton for typing the manuscript. REFERENCES
Abouna, G. M., Veazay, P. R., and Terry, D. B. (1974). Intravenous infusion of hydrochloric acid for treatment of severe metabolic alkalosis. Surgery, 75, 194. Baek, S. M., Makabali, G. G., Brown, C. W. B., Kusek, J. M., and Shoemaker, W. E. (1975). Plasma expansion in surgical patients with high central venous pressure (CVP): the relationship of blood volume to haematocrit, CVPj pulmonary wedge pressure, and cardiorespiratory changes. Surgery, 78, 304. Beach, F. X. M., and Jones, E. S. (1971). Metabolic alkalosis treated with intravenous hydrochloric acid. Postgrad. Med.J., 47, 516.
Bleich, H., Tannen, R. L., and Schwartz, W. B. (1966). Induction of metabolic alkalosis by correction of potassium deficiency. J. Clin. Invest., 45, 573. Bradham, G. B. (1968). The intravenous use of hydrochloric acid in the treatment of severe alkalosis. Am. Surg., 34, 551. Brennan, M. F. (1974). Treatment of metabolic alkalosis. Lancet, 1, 990. Dacrou, W., Harding, P. E., Kimber, R. J., and Kutkaite, D. (1972). Traumatic haemolysis after heart valve replacement: a comparison of haematological investigations. Aust. N.Z.J. Med.,2, 118. Elkington, J. R., and Danowski, T. S. (1955). The Body Fluids, p. 536. Baltimore: Williams and Wilkins. Felig, P., and Marliss, E. (1972). The glycemic responses to arginine in man. Diabetes, 21, 308. Filley, G. F. (1972). Acid-base and Blood-gas Regulation, p. 117. Philadelphia: Lea-Febiger. Flenley, D. C. (1971). Another non-logarithmic acid-base diagram. Lancet, 1, 961. Frick, P. G., and Senning, A. (1964). The treatment of severe metabolic alkalosis with intravenous N/10 or N/5 hydrochloric acid. Ger. Med. Mon., 9, 242. Garella, S., Chazan, J. A., and Cohen, J. J. (1970). Salineresistant metabolic alkalosis or chloride-wasting nephropathy. Ann. Intern. Med., 73, 31. Girardet, P. (1967). Intravenous injection of hydrochloric acid in a case of serious metabolic hypochloraemic alkalosis. Rev. Med. Suisse Rom., 87, 278. Goldberg, M., Green, S. B., Moss, M. L., Marbach, C. B. and Garfinkel, D. (1973). Computer-based instruction and diagnosis of acid-base disorders. J.A.M.A., 233, 269. Harken, A. H., Gabei, R. A., Fencl, V., and Moore, F. D. (1975). Hydrochloric acid in the correction of metabolic alkalosis. Arch. Surg., 110, 819. Heinemann, H. O., and Goldring, R. M. (1974). Bicarbonate and the regulation of ventilation. Am.J. Med., 57, 361. Hertz, P., and Richardson, J. A. (1972). Arginine induced hyperkalemia in renal failure patients. Arch. Intern. Med., 130, 778. Kassirer, J. P., and Schwartz, W. B. (1966). Correction of metabolic alkalosis in man without repair of potassium deficiency: a re-evaluation of the role of potassium. Am.J. Med., 40, 10. Kurtzman, N. A., White, M. G., and Rogers, P. W. (1970). The effect of potassium on renal bicarbonate reabsorption. Clin. Res., 18, 507. (1973). Pathophysiology of metabolic alkalosis. Arch. Intern. Med., 131, 702. Lawson, N. W., Butler, G. H., and Ray, C. T. (1973). Alkalosis and cardiac arrhythmias. Anesth. Analg. (Cleve.), 52, 951. Mitchell, J. H., Wildenthal, K., and Johnson, R. L., jr (1972). The effects of acid-base disturbances on cardiovascular and pulmonary function. Kidney Internal., 1, 375. Plum, F., and Posner, J. B. (1972). Diagnosis of Stupor and Coma, p. 204. Philadelphia: Davis. Rampini, S., and Frick, P. G. (1964). Intravenous hydrochloric acid in the treatment of hypochloraemic alkalosis. Helv. Paediatr. Acta, 19, 391. Russell, W. J. (1974). Central Venous Pressure, p. 61. London: Butterworth.
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limited therapeutic benefit and may be hazardous, arginine hydrochloride having the independent disadvantages also of producing hyperkalaemia (Hertz and Richardson, 1972) and hyperglycaemia (Felig and Martiss, 1972). Administration of hydrochloric acid, on the other hand, corrects metabolic alkalosis without using renal or hepatic mechanisms. The previously recorded complications of haemolysis (Whelton, 1975) and tissue necrosis (Shavelle and Parke, 1975) were not observed in the four cases presented. In each of the patients no significant decrease in haemoglobin concentrations occurred and in patients 1,2 and 4 the haptoglobin concentrations, although increased by stress, did not decrease following the acid infusion, indicating the absence of even minor degrees of haemolysis (Dacrou et al., 1972). This was attributed to the (central venous) route of administration. In the second patient rapid administration of hydrochloric acid produced inappropriate hyperventilation and hypocapnia, suggesting an intracellular-extracellular H+ disequilibrium. In a case described previously in which hydrochloric acid was administered at a rate in excess of 400 mmol/24 h, an inappropriate hypocapnia occurred also (Abouna, Veazay and Terry, 1974).
HYDROCHLORIC ACID FOR METABOLIC ALKALOSIS
USAGE RATIONNEL DE L'ACIDE CHLORHYDRIQUE ADMINISTRE PAR VOIE INTRAVEINEUSE DANS LE TRAITEMENT DE L'ALCALOSE METABOLIQUE RESUME
L'auteur presente dans ce document une mithode permettant d'evaluer et de controler les facteurs qui provoquent et entretiennent l'alcalose mdtabolique primaire. Pendant une periode de 2 ans, il a traite 65 malades souffrant d'alcalose m^tabolique a l'aide d'infusions de serum salin et de chlorure de potassium. Sur quatre malades, l'alcalose a 6te refractaire et a necessite un traitement compltaientaire. L'infusion d'acide chlorhydrique a raison de 0,12-0,24 mol/ litre administree a l'aide d'un tube veineux central a remidie a l'alcalose sans causer d'htaiolyse ou de necrose des tissus. Le taux d'infusion maximal sugg£re dans cet article est de 0,2 mmol H+/kg de poids de corps par heure.
DIE RATIONALE ANWENDUNG VON INTRAVENOS VERABREICHTER SALZSAURE BEI DER BEHANDLUNG METABOLISCHER ALKALOSE ZUSAMMENFASSUNG
Vorgelegt wird eine Methode zur Bewertung und Behandlung der Faktoren, durch die eine primare metabolische Alkalose verursacht wird. Innerhalb einer Periode von 2 Jahren wurden 65 Patienten mit metabolischer Alkalose durch Infusionen mit Salz und Kaliumchlorid behandelt. Bei vier Patienten war die Alkalose refraktar und erforderte eine zusatzliche Therapie. Eine Infusion von 0,120,24 mol/liter Salzsaure durch eine Zentralvenenleitung behob die Alkalose, ohne Hamolyse oder Gewebsnekrose hervorzurufen. Als maximale Infusionsrate werden 0,2 mmol H + kg Korpergewichf'.h" 1 empfohlen. EL EMPLEO RACIONAL DEL ACIDO CLORHIDRICO I.V. EN EL TRATAMIENTO DE ALCALOSIS METABOLICA SUMARIO
Se presenta un metodo para la evaluaci6n y tratamiento de factores que causan y mantienen una alcalosis metabolica primaria. Durante un periodo de dos afios se trat6 a 65 pacientes con infusiones salina y de cloruro potasico. En cuatro pacientes la alcalosis fue refractaria y preciso tratamiento adicional. Una infusion de acido clorhidrico 0,12-0,24 mol/litro, mediante administration venosa central, corrigio la alcalosis sin causar hemolisis o necrosis histica. El indice maximo de infusion sugerido es de 0,2 mmol H+/kg peso corporal/hora.
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Schwartz, W. B., Van Ypersele, De Strihou, C , and Kassirer, J. P. (1968). Role of anions in metabolic alkalosis and potassium deficiency. AT. Engl. J. Med., 279, 630. Seldin, D. W., and Rector, F. C. (1972). The generation and maintenance of metabolic alkalosis. Kidney Internat., 1, 306. Shavelle, H. S., and Parke, R. (1975). Postoperative metabolic alkalosis and acute renal failure: a rationale for the use of hydrochloric acid. Surgery, 78, 439. Tuller, M. A., and Mehdi, F. (1971). Compensatory hypoventilation and hypercapnoea in primary metabolic alkalosis. Am.J. Med., 50, 281. Warms, P. C , Michelis, M. F., Singh, H., Fusco: R. D., Eichenholz, A., and Davis, B. B. (1.974). Effect of hyperoncotic solutions on electrolyte excretion in metabolic alkalosis. Metabolism, 23, 417. Whelton, A. (1974). Treatment of metabolic alkalosis. Lancet, 1, 1055. Williams, S. E. (1976). Hydrogen ion infusion for treating severe metabolic alkalosis. Br. Med.J., 2, 1189. Wilson, R. F., Gibson, D., Percinel, A. K., Ali, M. A., Baker, G., Le Blanc, L. P., and Lucas, C. (1972). Severe alkalosis in critically ill surgical patients. Arch. Surg., 105, 197. Worthley, L., and Pain, R. W., (1974) Treatment of metabolic alkalosis. Lancet, 1, 1055.
817
THE RATIONAL USE OF I.V. HYDROCHLORIC ACID IN THE TREATMENT OF METABOLIC ALKALOSIS L. I. G. WORTHLEY SUMMARY
With the introduction of potent diuretic agents to medical practice and with modern operative techniques permitting extensive thoracic and abdominal surgery, non-respiratory alkalosis may occur as a severe, even life-threatening, state (Wilson et al., 1972; Lawson, Butler and Ray, 1973). Characteristically, the alkalosis persists only if the patient has an associated unreplaced loss of saline or potassium chloride, and restoration of the effective extracellular fluid volume or correction of the total body potassium chloride defect allows correction of the pH abnormality without additional therapy. However, in the presence of cardiac, renal or hepatic failure, the alkalotic state may become refractory. Furthermore, in these conditions saline, potassium chloride or ammonium chloride infusions may be contraindicated. In a direct attempt to correct the acid-base defect without involving renal or hepatic mechanisms, i.v. hydrochloric acid has been used (Elkington and Danowski, 1955; Frick and Senning, 1964; Rampini and Frick, 1964; Girardet, 1967; Bradham, 1968; Beach and Jones, 1971; Abouna, Veazay and Terry, 1974; Brennan, 1974; Worthley and Pain, 1974; Harken et al., 1975; Shavelle and Parke, 1975; Williams, 1976). This approach has been criticized, however, as haemolysis (Whelton, 1974), tissue necrosis (Shavelle and Parke, 1975) and the necessity for central venous cannulation (Brennan, 1974) make it potentially hazardous. This report describes four patients with severe refractory metabolic alkalosis, which was corrected by i.v. hydrochloric acid without complication. L. I. G. WORTHLEY, M.B., B.S., F.R.A.C.P., F.F.A.R.A.C.S.,
Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000.
PATIENTS AND METHODS
During a 2-year period in which 65 patients with metabolic alkalosis (pH greater than 7.45) were treated, four patients developed a severe alkalosis refractory to a conventional therapeutic regime outlined below, and i.v. hydrochloric acid was considered. Initially, 0.9% saline was administered until the central venous pressure (cv.p.) increased by 5-8 cm H 2 O from its original value (zero reference point at mid-axillary line, patient supine). The infusion was discontinued if values greater than 10 cm H 2 O were obtained, a precaution deemed necessary to minimize the risk of acute pulmonary oedema (Russell, 1974). All patients had an initial cv.p. value less than 8 cm H 2 O. Pulmonary venous wedge pressure measurements were not recorded and although they might have facilitated the early detection of pulmonary oedema, observation of cv.p. following saline infusion, and clinical signs of left heart failure were considered to be a simpler yet acceptable alternative (Baek et al., 1975). Potassium chloride (in amounts ranging from 100 to 200 mmol/day) was infused until the serum concentration of potassium increased to 4.5 mmol/litre. Fluid loss by nasogastric aspiration was replaced with 0.45% saline with potassium 27 mmol/litre. If these methods did not correct the alkalosis within 72 h, the state was deemed to be refractory. The four patients with refractory alkalosis had varying degrees of renal and hepatic failure so that infusions of ammonium chloride, lysine or arginine hydrocnloride or administration of acetazolamide were contraindicated or unlikely to be of therapeutic benefit. Before the infusion of hydrochloric acid was commenced, venous blood was collected for estimations of serum sodium, potassium, chloride (Technicon S.M.A. 6/60 auto-analyser), haptoglobin and
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A method for the assessment and management of factors both causing and maintaining a primary metabolic alkalosis is presented. During a 2-year period 65 patients with metabolic alkalosis were treated with saline and potassium chloride infusions. In four patients the alkalosis was refractory and required additional therapy. An infusion of hydrochloric acid 0.12-0.24 mol/litre through a central venous line corrected the alkalosis without causing haemolysis or tissue necrosis. The maximum rate of infusion suggested is 0.2 mmol H+.kg body w t " 1 . ^ 1 .
812
BRITISH JOURNAL OF ANAESTHESIA TABLE I. Biochemical data in patients 1-4 during the 72-h period of saline and potassium chloride infusions
Patient 1
Patient 2
Patient 3
Patient 4
Day
Day
Day
Day
2
3
1
2
3
1
2
3
1
2
3
I.v. infusion Na+ (mmol/24 h) K+ (mmol/24 h) Cl (mmol/24 h)
646 185 831
308 69 377
231 40 271
624 202 826
346 107 453
346 107 453
600 155 755
323 60 383
192 40 232
400 112 512
262 51 313
169 32 201
Arterial acid-base data PH Paco, (kPa) HCOjT (mmol/litre) Base excess (mmol/litre)
7.55 7.54 7.50 6.7 7.9 6.0 41 44 38 + 14 + 17 + 18
7.55 5.3 34
7.61 7.67 6.0 5.5 50 40 + 11 + 18 + 27
7.47 6.0 32
7.54 6.3 39
7.50 5.3 30
7.51 6.0 35
7.52 6.8 41
+8
7.55 6.7 42 + 16 + 18
Water input (litre)
5.4
4.0
4.5
6.1
4.5
5.5
5.8
4.2
4.5
4.2
3.4
3.2
Water output Gastric (litre) Urine (litre)
2.4 1.8
2.0 2.5
1.5 2
2.1 2.5
2.5 2.2
2.5 3.0
1.8 2.7
2.2 2.5
1.5 2.8
1.2 2.1
1.4 1.8
1.2 1.5
haemoglobin. Arterial blood was collected also for pH and blood-gas analysis; serum and blood-gas estimations were repeated both during and immediately after the hydrochloric acid infusion. Biochemical data are presented in table I. The infusion of hydrochloric acid was through a central venous catheter with its tip placed high in the right atrium. A subclavian approach was used and the catheter position confirmed subsequently by chest x-ray. The four patients described were considered to have normal respiratory function from considerations of history, physical examination and chest x-ray. In the three patients with hypercapnia, reference to an in vivo acid-base diagram (Goldberg et al., 1973) indicated that a primary metabolic alkalosis with respiratory compensation existed. The quantity of hydrochloric acid to be infused was calculated from the chloride deficit, assuming the chloride space to be 20% of total body weight. This calculation was used only as an initial estimate as arterial acid-base studies taken during the infusion, and the use of an in vivo acid-base diagram as a flow chart (Flenley, 1971; Goldberg et al., 1973) allowed a more accurate determination of the amount of acid necessary. The hydrochloric acid was infused over periods of 12-48 h as a 0.12-0.24 mol/litre solution (120240 mmol H+/litre) consisting of 60-120 ml of hydrochloric acid 2.0 mol/litre added to 5% dextrose 1 litre.
+7
+ 12 + 16
CASE REPORTS
Case 1
A 71-year-old man had a 4-h history of anuria, arterial hypoxaemia (Pa 02 6.0 kPa*) and shock 24 h after laparotomy and partial resection of a gangrenous loop of large bowel. The arterial pressure was 60/40 mm Hg, heart rate 108 beat/min, c.v.p. 18 cm H 2 O, serum creatinine 0.52 mmol/litre and bilirubin 111 jimol/litre. His initial treatment consisted of an infusion of isoprenaline 2 (ig/min, oxygen-enriched air (FiOl 0.5) and the administration of gentamicin and lincomycin for suspected sepsis. Throughout the next 48 h he improved gradually, with the arterial pressure stabilizing at 120/80 mm Hg, heart rate 100 beat/min, c.v.p. 7 cm H 2 O and PaOi 18.9 kPa (Fi 02 0.5). However, a persistent ileus developed, producing 1-2 litre/day fluid loss through the nasogastric tube. Four days following admission the creatinine clearance was 23 ml/min, bilirubin 58 (xmol/litre and arterial blood-gas analysis revealed a metabolic alkalosis (pH 7.55, PaCOa 6.0 kPa). This was found to be resistant to the saline and potassium chloride infusion regime (table I); furthermore the patient developed respiratory compensation and hypoxaemia (pH 7.50, Pa C02 7.9 kPa, Pa Os 6.1 kPa (Fi 02 0.28). Correction of the metabolic alkalosis was then considered necessary to restore normal ventilation. * 1 kPa = 7.5 mm Hg.
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1
HYDROCHLORIC ACID FOR METABOLIC ALKALOSIS TABLE
813
j a II. Patient 1: Serum electrolyte, arterial blood-gas, haemoglobin and haptoglobin values during 240 mmol H+ (as hydrochloric acid) in 1 litreof 5% dextrose itj water
24->i
infusion of
Time (h)
Haemoglobin (g/dl)
Haptoglobin (mg/dl)t
mmol/ (litre)
(mmol/ litre)
(mmol/ litre)
(kPa)*
(kPa)
PH
(mmol/ litre)
Base excess (mmol/ litre)
0
13.1 13.5 13.0
183 175 182
139 138 141
4.6 4.4 3.9
88 90 97
6.1 7.6 8.0
7.9 6.7 5.9
7.50 7.49 7.45
44 37 30
+ 18 + 12 +5
12 24
Na+
K+
HCOr
ci-
P&CO,
* F i 0 , 0.28. | Normal range 45-170 mg/dl
Time
haptoglobin values duringan 18-h infusion of III. Patient 2: Serum electrolyte, arterial blood-gas, haemoglobin and 360 mmol H+ as hydrochloric acid in 1.5 litreof 5% dextrose inwater
00
Haemoglobin (g/dl)
0 12 18 36
10.7 10.1 10.4 10.8
Haptoglobin (mg/dl) 370 295 282 285
Na+
K+
(mmol/ litre)
(mmol/ litre)
143 141 138 145
4.0 4.5 4.2 4.9
ci-
(mmol/ Pa 0 , (kPa)'" litre) 90 89 97 104
10.5 11.6 10.5 12.7
Paco, (kPa) 6.0 4.8 3.5 5.3
PH
7.67 7.65 7.57 7.47
HCOj (mmol/ litre) 50 37 23 29
Base excess (mmol/ litre)
+ 27 + 17 +2 +5
* Fl 0 , 0.21.
Hydrochloric acid was administered (table II) and corrected the alkalosis within 24 h. The ileus resolved in the next 2 days and the patient was discharged to a general ward for further convalescence.
next 12 h. Corrective surgery for the pyloric obstruction was performed 1 day later, and subsequent arterial blood-gas analyses were within normal limits. The patient was discharged 15 days later.
Case 2 A 58-year-old man with a past history of chronic duodenal ulcer, analgesic nephropathy and chronic renal failure (creatinine clearance 15 ml/min) was admitted following a 12-h period of intractable vomiting. He had vomited intermittently during the previous 3 months, and this was attributed to pyloric obstruction from scarring and spasm induced by the ulcer. An infusion of 0.9% saline 5 litre containing potassium chloride 134 mmol, through a central venous catheter during 24 h, corrected the initial state of dehydration and electrolyte imbalance. During the following 3 days, despite replacement of nasogastric fluid losses and further infusions of saline and potassium chloride (table I), the alkalosis became refractory. The patient became confused and disorientated with further worsening of the alkalosis (pH 7.67). Hydrochloric acid was administered over an 18-h period, correcting the metabolic alkalosis (table III) and restoring partially the confused state. The patient became fully conscious and co-operative within the
Case3 A 69-year-old man developed a severe ileus following resection of an abdominal aortic aneurysm. The resulting profuse drainage from the nasogastric tube caused pre-renal oliguria. Within 24 h, 0.9% saline 4 hire and potassium chloride 200 mmol in 1 hire of 5% dextrose in water were administered, through a central venous catheter, the equivalent of the nasogastric drainage being replaced with 0.45% saline in addition. The serum potassium concentration increased from 3.2 mmol/litre to 4.8 mmol/litre and the central venous pressure increased from 2 to 10 cm H 2 O. The remaining serum biochemical variables returned to normal apart from creatinine (0.35 mmol/litre), bilirubin (70 (xmol/litre) and urea nitrogen (22 mmol/litre). Despite an improvement in the urinary output, the creatinine clearance during the next 4 days remained at 55 ml/min. With the continuing nasogastric fluid loss a severe refractory metabolic alkalosis with partial respiratory compensation developed (table I). On the 8th day after operation, hydrochloric acid was given i.v. to correct hypoventilation and hypoxaemia
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TABLE
814
BRITISH JOURNAL OF ANAESTHESIA
TABLE IV. Patient 3: Serum electrolyte, arterial blood-gas and haemoglobin values during a \0-h infusion of 240 mmol of H+ {as hydrochloric acid) in 1.5 litre of 5% dextrose in water
Time (h)
Haemoglobin (g/dl)
Na+ (mmol/ litre)
0 6 10 24
10.2 10.4 10.2
141 140 137
K+ (mmol/ litre)
Cl(mmol/ litre)
4.9 4.8 4.5
89 92 105
Pao (kPa)*
-Paco (kPa)
pH
HCOj (mmol/ litre)
7.9 10.9 10.5 9.9
6.7 5.7 5.3 6.8
7.55 7.51 7.50 7.45
42 33 30 34
Base excess (mmol/ litre)
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* Fi0, 0.28.
TABLE V. Patient 4: Serum electrolyte, arterial blood-gas, haemoglobin and haptoglobin values during two 12-h infusions of 120 mmol H+ {as hydrochloric acid) in 1 litre of 5% dextrose in water. Each infusion was separated by 24 h
ci-
Haptoglobin (mg/dl)
Na+ (mmol/ litre)
K+ (mmol/ litre)
First infusion 0 10.2 12 9.8
239 220
145 144
5.0 5.2
92 97
Second infusion 0 9.6 12 10.0
225 235
144 144
5.4 5.6
100 102
Time (h)
Haemoglobin (g/dl)
(mmol/ litre)
Base excess (mmol/ litre)
^aco, (kPa)
PH
HCOr (mmol/ litre)
8.3 10.1
6.8 6.5
7.52 7.48
41 35
+ 16 + 11
10.4 11.3
7.1 6.1
7.48 7.47
39 32
+ 14 +8
Pa 0 , (kPa)*
• FlOi = 0.28.
(PaOa 5.7 kPa, PaCOs, 7.3 kPa, Fi 0 2 0.21) during a 10-h period (table IV). The ileus subsided within a further 3 days and the acid-base state returned to normal. Case A
A 67-year-old man was admitted with a perforated duodenal ulcer and circulatory failure, arterial pressure 70/50 mm Hg, heart rate 145 beat/min, c.v.p. 3 cm H 2 O. Initial resuscitation with 0.9% saline 3 litre and nasogastric suction produced an unexpectedly rapid clinical improvement. This was thought to justify further conservative therapy as an alternative to surgery. However, 3 weeks later a left subphrenic abscess developed and laparotomy was performed for both drainage of the abscess and vagotomy with pyloroplasty. After operation there developed a severe ileus with excessive nasogastric fluid loss and a metabolic alkalosis resistant to saline and potassium chloride infusions (table I). Hydrochloric acid was then infused in two 12-h periods (table V). The alkalosis improved following the infusions and on the 4th day after operation there was a normal acid-base state.
DISCUSSION
Severe metabolic acidosis has been recognized for many years as a dangerous clinical state and its treatment has become standardized. On the other hand, metabolic alkalosis has been recognized as a clinical problem only recently. Although a "blunted confusional state" may be the only manifestation (Plum and Posner, 1972), the associated complications of cardiovascular instability (Mitchell, Wildenthal and Johnson, 1972; Lawson, Butler and Ray, 1973), partial respiratory compensation (Tuller and Medhi, 1971; Heinemann and Goldring, 1974), and potassium wasting (Schwarz et al., 1968; Filley, 1972) may render a severe alkalotic disturbance a dangerous clinical condition. In the four patients presented, hypoventilation with associated hypoxaemia was the most consistent serious abnormality. The initial pH values in three of the patients (1, 3 and 4) were not overtly abnormal. Thus the alkalaemia was mild although the alkalosis was severe, producing compensatory hypoventilation and an associated hypoxaemia. In these patients a full appreciation of the degree of alkalosis required the
HYDROCHLORIC ACID FOR METABOLIC ALKALOSIS use of an in vivo acid-base diagram (Goldberg et al., 1973). Following the definition of the primary alkalotic state, recognition of the components causing it, as distinct from those which maintain it, becomes necessary (table VI). Correcting the disorder producing H + loss or HCOg" gain, will cure the condition. TABLE VI. Factors causing or maintaining alkalosis
Maintenance of alkalosis (1) Diminished effective extracellular fluid volume (2) Potassium deficiency with mineralocorticoid excess (3) Severe potassium deficiency ( > 450 mmol) (4) Renal failure
The normal kidney has a large capacity to excrete HCOjf. Thus maintenance of the alkalotic state, once its source is eliminated, depends upon a functional renal abnormality (Seldin and Rector, 1972). If an associated depletion in effective extracellular fluid volume exists, proximal tubular reabsorption of sodium is augmented. In the presence of a metabolic alkalosis proximal H + excretion (HCOjf reabsorption) is enhanced also, maintaining the e.c.f. volume at the expense of pH homeostasis (Schwartz et al., 1968; Kurtzman, White and Rogers, 1973). Similarly, if the patient is depleted of potassium and a state of hyperaldosteronism exists, with an adequate distal delivery of Na + , distal H + excretion is increased (Seldin and Rector, 1972; Kurtzman, White and Rogers, 1973). To correct the continuing pH defect, conventional therapy with potassium chloride and sodium chloride, and, occasionally, agents which have an inotropic effect on the heart, are usually all that is required, allowing the excess bicarbonate to be excreted with the infused cations. The role of potassium in the maintenance of an alkalotic state has been defined further following the demonstration that correction of a hypokalaemic state
with non-chloride-containing potassium salts fails to correct the existing alkalosis (Bleich, Tannen and Schwartz, 1966). Furthermore, correction of alkalosis can be achieved in mild hypokalaemic states with infusions of saline alone (Kassirer and Schwartz, 1966), although in the presence of severe potassium depletion a saline resistance has been described (Garella, Chazan and Cohen, 1970). However, correction of an existing hypokalaemia enhances the role of saline in correcting the alkalosis (Kurtzman, White and Rogers, 1970). Thus depletion of the chloride ion had been thought central in maintaining the alkalosis (Schwarz et al., 1968). Recently, however, the correction of the acid-base state with saline-free albumin solutions has suggested that diminished extracellular fluid volume activates the renal mechanism responsible for the persistence of the alkalosis (Kurtzman, White and Rogers, 1973; Warms et al., 1974). The albumin infusion permitted sodium and potassium bicarbonate to be excreted, thus correcting the acid-base disorder (Warms et al., 1974). Although correction of a metabolic alkalosis without potassium or sodium chloride is possible therapeutically it is not desirable if deficiencies in these ions exist. In the presence of renal failure the standard regimes may be insufficient (table VII) and alternative therapy with ammonium chloride, lysine or arginine TABLE VII. Treatment of metabolic alkalosis Indirect (1) Inhibition of renal mechanisms maintaining alkalosis Proximal: Increased functional ECF—NaCl infusion Albumin infusion Inotropic agents in cardiac failure Carbonic anhydrase—inhibition acetazolamide Distal: KC1 Aldosterone inhibition (spironolactone) (2) Following metabolism by liver to urea and HC1 Arginine or lysine hydrochloride NH4C1 Direct I.v. hydrochloric acid
hydrochloride, with conversion to urea and hydrochloric acid in the liver is often effective. However, in the presence of liver failure these agents may be of
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Causes of alkalosis (1) Loss of acid Renal Primary or secondary hyperaldosterone states with K + depletion Gastrointestinal tract Nasogastric suction, vomiting Congenital alkalosis with diarrhoea (2) Gain of alkali NaHCO 3 : oral or parenteral Metabolic conversion of infused acid anions Lactate Citrate Acetate Following hypercapnia
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BRITISH JOURNAL OF ANAESTHESIA
It is proposed that, if i.v. hydrochloric acid is to be infused, the rate of infusion of H + should be no greater than 0.2 mmol. kg" 1 . h" 1 (300-250 mmol/ day), the infusion must be through a central venous catheter, and the acid-base state should be monitored every 6-12 h with arterial blood-gas analysis. In our experience, following correction of saline and potassium chloride deficits, i.v. infusion of hydrochloric acid is a safe and desirable therapy for severe metabolic alkalosis. ACKNOWLEDGEMENTS
I wish to thank Dr R. Pain for his constructive criticism of this report and Miss E. Hilton for typing the manuscript. REFERENCES
Abouna, G. M., Veazay, P. R., and Terry, D. B. (1974). Intravenous infusion of hydrochloric acid for treatment of severe metabolic alkalosis. Surgery, 75, 194. Baek, S. M., Makabali, G. G., Brown, C. W. B., Kusek, J. M., and Shoemaker, W. E. (1975). Plasma expansion in surgical patients with high central venous pressure (CVP): the relationship of blood volume to haematocrit, CVPj pulmonary wedge pressure, and cardiorespiratory changes. Surgery, 78, 304. Beach, F. X. M., and Jones, E. S. (1971). Metabolic alkalosis treated with intravenous hydrochloric acid. Postgrad. Med.J., 47, 516.
Bleich, H., Tannen, R. L., and Schwartz, W. B. (1966). Induction of metabolic alkalosis by correction of potassium deficiency. J. Clin. Invest., 45, 573. Bradham, G. B. (1968). The intravenous use of hydrochloric acid in the treatment of severe alkalosis. Am. Surg., 34, 551. Brennan, M. F. (1974). Treatment of metabolic alkalosis. Lancet, 1, 990. Dacrou, W., Harding, P. E., Kimber, R. J., and Kutkaite, D. (1972). Traumatic haemolysis after heart valve replacement: a comparison of haematological investigations. Aust. N.Z.J. Med.,2, 118. Elkington, J. R., and Danowski, T. S. (1955). The Body Fluids, p. 536. Baltimore: Williams and Wilkins. Felig, P., and Marliss, E. (1972). The glycemic responses to arginine in man. Diabetes, 21, 308. Filley, G. F. (1972). Acid-base and Blood-gas Regulation, p. 117. Philadelphia: Lea-Febiger. Flenley, D. C. (1971). Another non-logarithmic acid-base diagram. Lancet, 1, 961. Frick, P. G., and Senning, A. (1964). The treatment of severe metabolic alkalosis with intravenous N/10 or N/5 hydrochloric acid. Ger. Med. Mon., 9, 242. Garella, S., Chazan, J. A., and Cohen, J. J. (1970). Salineresistant metabolic alkalosis or chloride-wasting nephropathy. Ann. Intern. Med., 73, 31. Girardet, P. (1967). Intravenous injection of hydrochloric acid in a case of serious metabolic hypochloraemic alkalosis. Rev. Med. Suisse Rom., 87, 278. Goldberg, M., Green, S. B., Moss, M. L., Marbach, C. B. and Garfinkel, D. (1973). Computer-based instruction and diagnosis of acid-base disorders. J.A.M.A., 233, 269. Harken, A. H., Gabei, R. A., Fencl, V., and Moore, F. D. (1975). Hydrochloric acid in the correction of metabolic alkalosis. Arch. Surg., 110, 819. Heinemann, H. O., and Goldring, R. M. (1974). Bicarbonate and the regulation of ventilation. Am.J. Med., 57, 361. Hertz, P., and Richardson, J. A. (1972). Arginine induced hyperkalemia in renal failure patients. Arch. Intern. Med., 130, 778. Kassirer, J. P., and Schwartz, W. B. (1966). Correction of metabolic alkalosis in man without repair of potassium deficiency: a re-evaluation of the role of potassium. Am.J. Med., 40, 10. Kurtzman, N. A., White, M. G., and Rogers, P. W. (1970). The effect of potassium on renal bicarbonate reabsorption. Clin. Res., 18, 507. (1973). Pathophysiology of metabolic alkalosis. Arch. Intern. Med., 131, 702. Lawson, N. W., Butler, G. H., and Ray, C. T. (1973). Alkalosis and cardiac arrhythmias. Anesth. Analg. (Cleve.), 52, 951. Mitchell, J. H., Wildenthal, K., and Johnson, R. L., jr (1972). The effects of acid-base disturbances on cardiovascular and pulmonary function. Kidney Internal., 1, 375. Plum, F., and Posner, J. B. (1972). Diagnosis of Stupor and Coma, p. 204. Philadelphia: Davis. Rampini, S., and Frick, P. G. (1964). Intravenous hydrochloric acid in the treatment of hypochloraemic alkalosis. Helv. Paediatr. Acta, 19, 391. Russell, W. J. (1974). Central Venous Pressure, p. 61. London: Butterworth.
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limited therapeutic benefit and may be hazardous, arginine hydrochloride having the independent disadvantages also of producing hyperkalaemia (Hertz and Richardson, 1972) and hyperglycaemia (Felig and Martiss, 1972). Administration of hydrochloric acid, on the other hand, corrects metabolic alkalosis without using renal or hepatic mechanisms. The previously recorded complications of haemolysis (Whelton, 1975) and tissue necrosis (Shavelle and Parke, 1975) were not observed in the four cases presented. In each of the patients no significant decrease in haemoglobin concentrations occurred and in patients 1,2 and 4 the haptoglobin concentrations, although increased by stress, did not decrease following the acid infusion, indicating the absence of even minor degrees of haemolysis (Dacrou et al., 1972). This was attributed to the (central venous) route of administration. In the second patient rapid administration of hydrochloric acid produced inappropriate hyperventilation and hypocapnia, suggesting an intracellular-extracellular H+ disequilibrium. In a case described previously in which hydrochloric acid was administered at a rate in excess of 400 mmol/24 h, an inappropriate hypocapnia occurred also (Abouna, Veazay and Terry, 1974).
HYDROCHLORIC ACID FOR METABOLIC ALKALOSIS
USAGE RATIONNEL DE L'ACIDE CHLORHYDRIQUE ADMINISTRE PAR VOIE INTRAVEINEUSE DANS LE TRAITEMENT DE L'ALCALOSE METABOLIQUE RESUME
L'auteur presente dans ce document une mithode permettant d'evaluer et de controler les facteurs qui provoquent et entretiennent l'alcalose mdtabolique primaire. Pendant une periode de 2 ans, il a traite 65 malades souffrant d'alcalose m^tabolique a l'aide d'infusions de serum salin et de chlorure de potassium. Sur quatre malades, l'alcalose a 6te refractaire et a necessite un traitement compltaientaire. L'infusion d'acide chlorhydrique a raison de 0,12-0,24 mol/ litre administree a l'aide d'un tube veineux central a remidie a l'alcalose sans causer d'htaiolyse ou de necrose des tissus. Le taux d'infusion maximal sugg£re dans cet article est de 0,2 mmol H+/kg de poids de corps par heure.
DIE RATIONALE ANWENDUNG VON INTRAVENOS VERABREICHTER SALZSAURE BEI DER BEHANDLUNG METABOLISCHER ALKALOSE ZUSAMMENFASSUNG
Vorgelegt wird eine Methode zur Bewertung und Behandlung der Faktoren, durch die eine primare metabolische Alkalose verursacht wird. Innerhalb einer Periode von 2 Jahren wurden 65 Patienten mit metabolischer Alkalose durch Infusionen mit Salz und Kaliumchlorid behandelt. Bei vier Patienten war die Alkalose refraktar und erforderte eine zusatzliche Therapie. Eine Infusion von 0,120,24 mol/liter Salzsaure durch eine Zentralvenenleitung behob die Alkalose, ohne Hamolyse oder Gewebsnekrose hervorzurufen. Als maximale Infusionsrate werden 0,2 mmol H + kg Korpergewichf'.h" 1 empfohlen. EL EMPLEO RACIONAL DEL ACIDO CLORHIDRICO I.V. EN EL TRATAMIENTO DE ALCALOSIS METABOLICA SUMARIO
Se presenta un metodo para la evaluaci6n y tratamiento de factores que causan y mantienen una alcalosis metabolica primaria. Durante un periodo de dos afios se trat6 a 65 pacientes con infusiones salina y de cloruro potasico. En cuatro pacientes la alcalosis fue refractaria y preciso tratamiento adicional. Una infusion de acido clorhidrico 0,12-0,24 mol/litro, mediante administration venosa central, corrigio la alcalosis sin causar hemolisis o necrosis histica. El indice maximo de infusion sugerido es de 0,2 mmol H+/kg peso corporal/hora.
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