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HYDROCHLORIC ACID FOR METABOLIC ALKALOSIS
1332
Intracellular infusion of
Phenylalanine Guthrie
test:
NaOH/HCI destruction of
inhibiting
antibiotics. Row 1:
2,4,6,8,10,12, and 20 mg/dl phenylalanine standards: methanol/
fixation. Row 4: same standards as row 1: NaOH/HCI treatment. Row 2: blood samples: methanol/acetone fixation. Row 3: same blood samples as row 2: NaOH/HC1 treatment. Note same dimensions of growth areas between standards (rows 1 and 4) and between samples 1, 4, 6, 7 (rows 2 and 3). Note disappearance of inhibition area m row 3 as compared with row 2
(upper) and extracellular (lower) pH changes after arginine HCl 3 mmol/kg into intact rats. Data shown are arterial plasma pH and the "mean whole body pHi", an estimate of intracellular pH (complementary to in vivo arterial plasma pH),
determined from the distribution of 14C-labelled 5,5-dimethyl-2,4-oxazolidinedione. Data as change of pH or pHi from pre-infusion value with SEM.
acetone
(samples 2, 3, 5).
(at age 40 days) showed a blood phenylalanine of over 20 mg/dl (21-99 mg/dl by Beckman ’Multichrom B’ aminoacid analyser). The first blood sample was then retested after NaOH/HCl treatment, showing a growth area corresponding to 12 mg/dl. Had this high value been known immediately, a second sample would have been examined urgently and dietary treatment would have been started test
much earlier. Clinical
Chemistry Analytical Laboratory, Ospedale Infantile Regina Margherita, 10126 Turin, Italy
GUGLIELMO BRACCO SEVERO PAGLIARDINI
HYDROCHLORIC ACID FOR METABOLIC ALKALOSIS agree with Dr Knutsen (April 30, p 953) that hydrochloric acid HCl should be the agent of choice for correction of severe metabolic alkalosis. The administration of HCI in titrated form is not new. Zintel et all used ammonium chloride intravenously. This agent is contraindicated in patients with poor liver function, who are at risk of ammonia intoxication and coma. Because of this and other disadvantages arginine HCl or lysine HCl are now given for the treatment of metabolic alkalosis, though NH4Cl is still used
SIR,-We
occasionally. Blood-gas analysis, yielding values for arterial pH, PCO, and P02 tells us about the extracellular compartment of the body but not the large intracellular space, the target of therapy. 2,3 The extracellular space contains about 20% of the total body weight and has a normal pH of 7’4. The intracellular space consists of about 80% of the total body weight and its acid-base parameters cannot be measured routinely, the pH of this compartment being lower than arterial pH at 6’8-6’9. Exact knowledge of the regulatory mechanisms between acid-base equilibrium of both body compartments should be the main condition for the treatment of acid-base disturbances. This regulation occurs at least partly by bicarbonate transfer between intracellular and extracellular space. Two forms of titrated HC1 (NH4Cl and arginine HCI) have disadvantageous effects on intracellular acid-base status.44 1 Zintel HA, Rhoads JE, Ravdin IS. The use of intravenous ammonium-chloride in the treatment of alkalosis. Surgery 1943; 14: 728-31 2. Sch6nleben K, Kessler M, Bünte H. Lokale Sauerstoffversorgung des Gewebes bei pulmonalen and peripheren Verteilungsstörungen der Durchblutung. Anästh Intensivmed 1979; 20: 241-48 3. Rothe KF, Heisler N. Intracellular acid-base balance, correction between intra-and extracellular acid-base status during variation of plasma pH. Acta Anaesth Belg 1979, 30: (Suppl) 65-69. 4. Rothe KF, Schimek F, Kühn K: Gefährliche Nebeneffekte der Therapie mit NH4Cl and Arginin-HCL. Anaesthesist 1982; 31: 502-03.
The unexpected finding was the continuous rise of mtracellular 0 - 082 pH units by the end of the experiment (p<0. .01),
pH up to
Intravenous injection of 3 mmol/kg body
mass NH4Cl or arginine Sprague-Dawley rats resulted in a fall in arterial (extracellular) plasma pH accompanied by an increase of intracellular pH of more than 0 -08 (see figure). An increase in intracellular pH in metabolic alkalosis is not what is wanted. The
HCI in intact
result of a decrease in extracellular and an increase in intracellular pH, resulting from NH4CI and arginine-HCl application is a reduction in the difference between the two pH values, which is usually C’4-0-6, depending upon the pH range. The distribution and effects of ionised drugs are pH dependent. Varying pH differences between intracellular and extracellular compartments by infusing titrated HCl may result in unpredictable pharmacological effects especially in intensive care patients where several drugs may be used at the same time. reduced intracellular bicarbonate Neither agent concentration-ie, NH4Cl and arginine HC 1 have no intracellular buffer effect. When HCI was infused, there was a considerable reduction of both the extracellular pH and the intracellular pH of skeletal muscle, heart muscle, liver, spleen, and brain tissue.’ Because of these findings we have, for more than two years, been using 0.22 mol/1 HCI to correct metabolic alkalosis in intensive care patients. This solution is usually given via a central venous catheter. It has an osmolarity of 400 mosmol/I and may be given via peripheral veins if necessary, though we prefer the central venous route. The only problem has been the large amount of water needed to correct severe metabolic alkalosis, especially in patients who have undergone open heart surgery. In these circumstances a 0 -33 mol/1 solution may lead to a satisfactory reduction of the water load; 1’ 0 0 mol/1 HCI, as described by Kwun et al,6 seems to us likely to cause problems. Nothing is known about the effects of commercially available aminoacid solutions on intracellular acid-base status. Our experience with NH4CI and arginine HCl suggests difficulties with the use of aminoacid solutions during the treatment of metabolic alkalosis. Furthermore, the use of fat emulsions in intensive care patients may also be risky.7,8 In vivo measurements of the influences of aminoacid solutions on intracellular acid-base status net
are now
under
investigation in our laboratory.
Department of Anaesthesia, University of Tübingen, D 7400 Tübingen, West Germany
KARL FRIEDRICH ROTHE
5. Rothe KF. Tierexperimentelle Untersuchungen zum Einflub von Veränderungen des extrazellulären pH Wertes auf den intrazellulären pH Wert von Geweben Habilitationsschrift zur Erlangung der venia legendi, Tübingen, 1979. 6. Kwun KB, Boucherit T, Wong J, Bryan-Brown ChW. Treatment of metabolic alkalosis with intravenous infusion of concentrated hydrochloric-acid. Crit Care Med 1982; 10: 230. 7. Hulman G, Pearson HJ, Fraser I, Bell PRF: Agglutination of Intralipid by sera of acutely ill patients. Lancet 1982; ii: 1426-28. 8. Hulman G, Pearson HJ, Fraser I, Bell PRF. Agglutination of Intralipid by serum Lancet 1983; i: 985-86.
Intracellular infusion of
Phenylalanine Guthrie
test:
NaOH/HCI destruction of
inhibiting
antibiotics. Row 1:
2,4,6,8,10,12, and 20 mg/dl phenylalanine standards: methanol/
fixation. Row 4: same standards as row 1: NaOH/HCI treatment. Row 2: blood samples: methanol/acetone fixation. Row 3: same blood samples as row 2: NaOH/HC1 treatment. Note same dimensions of growth areas between standards (rows 1 and 4) and between samples 1, 4, 6, 7 (rows 2 and 3). Note disappearance of inhibition area m row 3 as compared with row 2
(upper) and extracellular (lower) pH changes after arginine HCl 3 mmol/kg into intact rats. Data shown are arterial plasma pH and the "mean whole body pHi", an estimate of intracellular pH (complementary to in vivo arterial plasma pH),
determined from the distribution of 14C-labelled 5,5-dimethyl-2,4-oxazolidinedione. Data as change of pH or pHi from pre-infusion value with SEM.
acetone
(samples 2, 3, 5).
(at age 40 days) showed a blood phenylalanine of over 20 mg/dl (21-99 mg/dl by Beckman ’Multichrom B’ aminoacid analyser). The first blood sample was then retested after NaOH/HCl treatment, showing a growth area corresponding to 12 mg/dl. Had this high value been known immediately, a second sample would have been examined urgently and dietary treatment would have been started test
much earlier. Clinical
Chemistry Analytical Laboratory, Ospedale Infantile Regina Margherita, 10126 Turin, Italy
GUGLIELMO BRACCO SEVERO PAGLIARDINI
HYDROCHLORIC ACID FOR METABOLIC ALKALOSIS agree with Dr Knutsen (April 30, p 953) that hydrochloric acid HCl should be the agent of choice for correction of severe metabolic alkalosis. The administration of HCI in titrated form is not new. Zintel et all used ammonium chloride intravenously. This agent is contraindicated in patients with poor liver function, who are at risk of ammonia intoxication and coma. Because of this and other disadvantages arginine HCl or lysine HCl are now given for the treatment of metabolic alkalosis, though NH4Cl is still used
SIR,-We
occasionally. Blood-gas analysis, yielding values for arterial pH, PCO, and P02 tells us about the extracellular compartment of the body but not the large intracellular space, the target of therapy. 2,3 The extracellular space contains about 20% of the total body weight and has a normal pH of 7’4. The intracellular space consists of about 80% of the total body weight and its acid-base parameters cannot be measured routinely, the pH of this compartment being lower than arterial pH at 6’8-6’9. Exact knowledge of the regulatory mechanisms between acid-base equilibrium of both body compartments should be the main condition for the treatment of acid-base disturbances. This regulation occurs at least partly by bicarbonate transfer between intracellular and extracellular space. Two forms of titrated HC1 (NH4Cl and arginine HCI) have disadvantageous effects on intracellular acid-base status.44 1 Zintel HA, Rhoads JE, Ravdin IS. The use of intravenous ammonium-chloride in the treatment of alkalosis. Surgery 1943; 14: 728-31 2. Sch6nleben K, Kessler M, Bünte H. Lokale Sauerstoffversorgung des Gewebes bei pulmonalen and peripheren Verteilungsstörungen der Durchblutung. Anästh Intensivmed 1979; 20: 241-48 3. Rothe KF, Heisler N. Intracellular acid-base balance, correction between intra-and extracellular acid-base status during variation of plasma pH. Acta Anaesth Belg 1979, 30: (Suppl) 65-69. 4. Rothe KF, Schimek F, Kühn K: Gefährliche Nebeneffekte der Therapie mit NH4Cl and Arginin-HCL. Anaesthesist 1982; 31: 502-03.
The unexpected finding was the continuous rise of mtracellular 0 - 082 pH units by the end of the experiment (p<0. .01),
pH up to
Intravenous injection of 3 mmol/kg body
mass NH4Cl or arginine Sprague-Dawley rats resulted in a fall in arterial (extracellular) plasma pH accompanied by an increase of intracellular pH of more than 0 -08 (see figure). An increase in intracellular pH in metabolic alkalosis is not what is wanted. The
HCI in intact
result of a decrease in extracellular and an increase in intracellular pH, resulting from NH4CI and arginine-HCl application is a reduction in the difference between the two pH values, which is usually C’4-0-6, depending upon the pH range. The distribution and effects of ionised drugs are pH dependent. Varying pH differences between intracellular and extracellular compartments by infusing titrated HCl may result in unpredictable pharmacological effects especially in intensive care patients where several drugs may be used at the same time. reduced intracellular bicarbonate Neither agent concentration-ie, NH4Cl and arginine HC 1 have no intracellular buffer effect. When HCI was infused, there was a considerable reduction of both the extracellular pH and the intracellular pH of skeletal muscle, heart muscle, liver, spleen, and brain tissue.’ Because of these findings we have, for more than two years, been using 0.22 mol/1 HCI to correct metabolic alkalosis in intensive care patients. This solution is usually given via a central venous catheter. It has an osmolarity of 400 mosmol/I and may be given via peripheral veins if necessary, though we prefer the central venous route. The only problem has been the large amount of water needed to correct severe metabolic alkalosis, especially in patients who have undergone open heart surgery. In these circumstances a 0 -33 mol/1 solution may lead to a satisfactory reduction of the water load; 1’ 0 0 mol/1 HCI, as described by Kwun et al,6 seems to us likely to cause problems. Nothing is known about the effects of commercially available aminoacid solutions on intracellular acid-base status. Our experience with NH4CI and arginine HCl suggests difficulties with the use of aminoacid solutions during the treatment of metabolic alkalosis. Furthermore, the use of fat emulsions in intensive care patients may also be risky.7,8 In vivo measurements of the influences of aminoacid solutions on intracellular acid-base status net
are now
under
investigation in our laboratory.
Department of Anaesthesia, University of Tübingen, D 7400 Tübingen, West Germany
KARL FRIEDRICH ROTHE
5. Rothe KF. Tierexperimentelle Untersuchungen zum Einflub von Veränderungen des extrazellulären pH Wertes auf den intrazellulären pH Wert von Geweben Habilitationsschrift zur Erlangung der venia legendi, Tübingen, 1979. 6. Kwun KB, Boucherit T, Wong J, Bryan-Brown ChW. Treatment of metabolic alkalosis with intravenous infusion of concentrated hydrochloric-acid. Crit Care Med 1982; 10: 230. 7. Hulman G, Pearson HJ, Fraser I, Bell PRF: Agglutination of Intralipid by sera of acutely ill patients. Lancet 1982; ii: 1426-28. 8. Hulman G, Pearson HJ, Fraser I, Bell PRF. Agglutination of Intralipid by serum Lancet 1983; i: 985-86.