Differential Diagnosis and Treatment of Acidosis

H.P. POVOAS, M.H. WElL

Acidosis may be associated with unrelated disease states and differing mecha-
nisms. Metabolic production of organic acids, respiratory retention of carbon
dioxide or renal loss of bicarbonate represent changes in which [H+] of fluids in
both extracellular and intracellular compartments may be increased. Excesses of
acids and deficits of bicarbonate are defined as metabolic acid base defects and
increases or decreases in the CO2 tension of blood (and tissues) are defined as
respiratory acidosis. An important exception is now recognized. During tissue
ischaemia, excesses of tissue CO2 are generated [1]. The resulting hypercarbic
tissue acidosis due to tissue hypoxia is therefore a metabolic defect rather than
respiratory CO2 retention [2-5].
Metabolic acidosis caused by overproduction of organic acids is further clas-
sified as anion gap acidosis. Anion gaps are characteristic of lactic acidosis, dia-
betic ketoacidosis, poisonings due to renal failure or ingestion or infusion of or-
ganic acids. A gain in hydrogen ions associated hyperchloraemia or a relative
loss of bicarbonate in blood, plasma or serum is recognized as hyperchloraemic
metabolic acidosis. Clinical classification of currently recognized causes of both
metabolic and respiratory acidosis is summarized in Table 1.
For understanding the mechanisms and ultimately the treatment of acid-base
abnormalities, a reasonably precise diagnosis of the underlying disease state is
required. Special focus should initially be on cardiopulmonary, renal, or en-
docrine disease. The most common cause of lactic acidosis is impaired tissue
perfusion [6]. Respiratory symptoms including apnoea, tachypnoea, stridor or
cyanosis may pinpoint alveolar hypoventilation and CO2 retention and therefore
respiratory acidosis.
For practical purposes, acid base disorders may be anticipated based on diag-
nosis of the underlying disease. However, confirmation and quantitation invari-
ably requires laboratory measurements and especially blood gases. The increas-
ingly wider use of "stat" or "point of care" laboratory tests in which acid base
and electrolyte measurements are routinely obtained, more often expose acid
base defect before the underlying cause is diagnosed [7]. The laboratory diagno-
sis of acidosis is based on measurements of blood pH, PC02 and HC0 3. Funda-
A. Gullo (ed.), Anaesthesia, Pain, Intensive Care and Emergency Medicine - A.P.I.C.E.
© Springer-Verlag Italia, Milano 1999
430 H.P. Povoas, M.H. Weil

Table 1. Classification of acid-base disorders

Metabolic acidosis
Respiratory acidosis
Anion gap acidosis Hyperchloraemic acidosis
Low flow states Renal disease Acute
shock renal failure atelectasis
septic renal tubular acidosis pneumonia
haemorrhagic (RIA) recovery from anaesthesia
traumatic Gastrointestinal losses pneumothorax
cardiac arrest pancreatic and biliary haemothorax
Hypoxaemia fistulas open chest and open heart
Anaemia Ureterocolic implantation operations
Diabetic ketoacidosis Inborn errors of metabolism thoracic trauma with flail chest
Hepatic failure carbonic anhydrase smoke inhalation
deficiency pulmonary oedema
Uraemia
oxoprolinuria laparoscopic surgery
Neoplasm esp. Leukemia
Drugs Chronic
D-Iactic acidosis cardiac failure
Surgery cycloxygenase inhibitors
~-adrenergic antagonists chronic bronchitis
cardiopulmonary bypass pulmonary failure
aorta cross clamping angiotensin converting-
enzyme inhibitors chronic obstructive lung
aortic dissection disease
heparin
Drugs tobacco smoking
potassium-sparing diuretics
antibiotics bronchiectasis
trimethoprim-sulfa
nalidixid acid, isoniazid
digitalis overdose
phenformin related drugs including
metformin
chemo therapeutic drugs
5-fluorouracil
Anti-HIVagents
zidovudine
stavudine
Anticonvulsants
sulthiame
topiramate
Anaesthesia
propofol
Salicylates
5-ASA, mesalazine
Hypertonic solutions
laxatives/enemas
saline/dextran
Poisoning
cyanides
iron
salicylates
methanol
ethylene glycol
carbamate
organophosphate
carbon monoxide
Differential Diagnosis and Treatment of Acidosis 431

mental to the understanding of abnormalities in these blood gas parameters, is

the Henderson-Hasselbalch equation [8]:

[HCO -]
pH = pK + log 3
[C0 2 ]

It explains the normal physiological buffering mechanism, by which excess-

es of H+, conventionally expressed as decreases in pH, represent either decreas-
es in HC03- or increases in arterial PC02 (PaC02).

Metabolic acidosis
Anion gap acidosis
The anion gap is defined as the difference between the cations and anions meas-
ured in the plasma:

anion gap = (Na+ + K+) - (CI- + HC0 3-)

and a difference exceeding 12 mEq represents an excess of unmeasured anions,

as illustrated in Fig. 1. Increases in the anion gap are due to abnormal proteins,
excesses of organic anions including hydroxybutirate and aceto-acetate during
diabetic ketoacidosis, inorganic phosphates, sulfates and chlorides. Excesses of
acids are buffered by bicarbonate, according to the Henderson-Hasselbalch
equation such that bicarbonate is decreased. When increases in chloride com-
pensate for the decreases in bicarbonate the anion gap may be unaltered. Renal
failure is typically associated with an anion gap because of the accumulation of
unexcreted anions including phosphate and sulfate [9].
Lactic acidosis. Lactate is a common and now readily measured biochemical
marker. In clinical practice, the L-isomer is measured. Concentrations exceeding
1.5 mmolll are abnormal. Two types of I-lactate excess are defined as Type A
and Type B. Type A represents a failure of O2 delivery to meet 02 demand of
the tissues or an incapability of tissue to utilize oxygen. In the normal aerobic
pathway, pyruvate is metabolized to carbon dioxide and water in the Krebs cy-
cle as shown in Fig. 2. When pyruvate is metabolized aerobically by mitochon-
dria, 36 M of ATP are generated for each mole of glucose. In the absence of
oxygen, glucose is metabolized to pyruvate and this pyruvate is "shunted" to
lactate. This "emergency pathway" generates only 2 M of ATP for every mole
of glucose [10] as shown in Fig. 2. When the oxygen deficit is repaid, lactate is
converted back to pyruvate then oxidized through the Krebs cycle to CO2 and
water or converted back to glucose by gluconeogenesis predominantly in the liv-
er. Lactate accumulation and lactic acidosis in this setting represent a failure to
sustain the oxygen requirements of tissue either because of decreased supply or
increased utilization.
432 H.P. Povoas, M.H. Weil

I
I
•
I
Heol - =: 12
~
\
\
,
I \
I \
I \
I \
I
Na' "'. 141 \
I \
IS3
I Cl-'" 12 I
1'\3 I I
- \ I
\ I
\ I
\
, I
I

\ I
\ I
\
Na+, Ca++, H.... I
.A.NION
\ I
MgH"" 12 GAP UHS.cWS
~
--
MHW6183

Fig. 1. Anion gap

CYTOPLASM 1 AT!'
(A~AEROBfC)

GLUCOSE -t----------.....

PYRUVATE

I
MlT(X'IlOl>.l)RIA
(AEROBIC) ."
'\ N~n (

) KADH ~

Fig. 2. Cellular metabolism

Differential Diagnosis and Treatment of Acidosis 433

Circulatory shock states remain the most common causes of pathological

Type A lactic acidosis and excesses of lactic acid are highly correlated with the
severity of the perfusion deficit [11]. When lactic acidosis occurs in settings un-
related to either excessive oxygen requirements or impaired tissue perfusion, it
is defined as Type B lactic acidosis. Type B lactic acidosis is observed uncom-
monly and in a diversity of clinical disease states. It usually represents metabol-
ic defect in cellular energy metabolism including 1) uncoupling of oxidative
phosphorylation, 2) inhibition of mitochondrial respiration and 3) reduced avail-
ability of substrates for oxidative metabolism. These abnormalities occur in set-
tings of malignancy, vitamin deficiency, adverse reactions to drugs and toxins,
and in rare instances of infection without evidence of circulatory failure. In hu-
man patients with septic shock, Gore [12] demonstrated increased pyruvate oxi-
dation refuting the concept of a sepsis-related impairment in pyruvate dehydro-
genase activity. HIV-infected patients may manifest lactic acidosis following in-
travenous infusion of trimethoprimlsulfamethoxazole (TMP/SMX) for treatment
of Pneumocystis carinii pneumonia [13]. Acidosis is reversed after the drug in-
fusion is stopped. Investigators have implicated anaesthetic agents including
propofol as a cause of Type B lactic acidosis in patients with refractory status
epilepticus [14]. However, it is very likely that lactic acidosis in such patients
represents oxygen deficits associated with extremes of metabolic oxygen re-
quirements during convulsive seizures. Rare cases of lactic acidosis follow ad-
ministration of formin oral hypoglycaemic agents including metformin and
phenformin, especially when there is coexisting renal failure [15-17]. Chronic
use of nucleoside analogs for treatment of HIV-infections including zidovudine,
stavudine, didanosine and fialuridine have also been implicated as potential
causes of Type B lactic acidosis. The mechanism is likely to be impaired mito-
chondrial function associated with DNA inhibition [18].
A distinctly different entity in addition to Type A or B lactic acidosis is D-
lactic acidosis. D-Iactic acid is produced by microorganisms. The D-lactate pro-
ducing microorganisms include species of lactobacillus, bifidobacterium and eu-
bacterium. D-Iactate concentrations are increased to 3 mmollL or more. The
clinical presentation is predominantly neurological with confusion, ataxia and
memory disturbances. Metabolic acidosis is characterized by normal L-Iactate
levels [19]. The abnormalities occur primarily in patients with intestinal dis-
eases in which there is carbohydrate malabsorption, blind loop syndrome after
intestinal surgery [20, 21] and in settings of pancreatitis. Though L-Iactate is
now measured with disarming ease with a lactate electrode [22] or as part of au-
tomated chemistry analysis, this does not apply to D-Iactate which requires spe-
cialized laboratory assays. The management in each instance is that of the un-
derlying cause.
Diabetic ketoacidosis (DKA). DKA is the most common and the most acute
life-threatening complication of diabetes. It is responsible for approximately
110,000 emergency hospital admissions annually in the United States [23]. A
majority of cases represent Type I insulin dependent diabetes mellitus, but a mi-
nority arc associated with Type II adult onset diabetes.
434 H.P. Povoas, M.H. Weil

The initial metabolic defect is either an absolute or relative deficiency of in-

sulin. Excesses of counterregulatory hormones, especially corticosteroids and
catecholamines may be responsible. The metabolic breakdown of fatty acids
produces keto and hydroxy acids. Hyperglycaemia induces osmolal diuresis
with consequent volume depletion. Accordingly patients present with both aci-
daemia and dehydration with hypovolaemia. There is an increased anion gap but
relative hyperchloraemia may minimize the anion gap. Symptoms include
polyuria, polydipsia, nausea, vomiting, abdominal pain and tachypnoea with
"fishmouth" breathing. A typical fruity odor of the patient's breath was identi-
fied by earlier clinicians. Management includes volume repletion, administra-
tion of insulin and concurrent repletion of plasma potassium during reversal of
hyperglycaemia. During volume repletion, even small amounts of insulin typi-
cally reverse keto acid production. Volume repletion restores arterial perfusion
pressure and cardiac output promoting renal excretion of ketones and excesses
of chloride. There is no indication for routine administration of buffer agents, ei-
ther sodium bicarbonate or sodium lactate because there is no evidence of im-
proved outcomes [24, 25].
Poisoning. Poison and drug intoxication remain important causes of anion
gap acidosis in emergency medical settings. Frequent causes are the ingestion of
excesses of salicylates or methanol/ethylene glycol. The ingestion of large doses
of salicylates produces hyperpyrexia and increased total body oxygen consump-
tion. Salicylates uncouple oxidative phosphorylation in mitochondria. Gastric
lavage, activated charcoal and haemodialysis, especially in the presence of renal
failure, are current therapeutic options.
Ingestion of as little as 30 ml of methanol or 100 ml of ethylene glycol may
be fatal. The toxic effect is not the alcohol itself but the metabolites generated
by the action of alcohol dehydrogenase. Methanol generates formic acid and
ethylene glycol generates glycolic and oxalic acid. Both produce a profound an-
ion gap acidosis. Visual disturbances usually follow ingestion of methanol and
stupor or coma after ethylene glycol. Administration of ethanol provides an ap-
propriate antidote. Alcohol dehydrogenase has lOa-fold greater affinity for
ethanol than methanol or ethylene glycol. Haemodialysis is also an effective op-
tion [26, 27].
Other anion gap acidosis. Enemas. Acidosis may follow phosphate intoxica-
tion after use of laxatives or enemas, especially in patients with impaired gut
motility, often a complication of diabetes mellitus [28].
Hypertonic solutions. The infusion of excesses of sodium chloride and espe-
cially hypertonic solutions such as saline-dextran solutions may produce acido-
sis, because of the excesses of acidic chloride ions [29].

Hyperchloraemic metabolic acidosis

This type of acidosis occurs in settings of renal failure, especially renal tubular
defects with renal losses of bicarbonate, extrarenal losses of bicarbonate, miner-
alocorticoid deficiency or resistance to the effects of mineralocorticoids.
Differential Diagnosis and Treatment of Acidosis 435

Renal failure. With a decline in renal function, the kidney's capability to

maintain the acid base balance is compromised. Because of decreased ammoni-
agenesis, less ammonium is secreted from the medullary interstitium into the
medullary collecting ducts, reducing ammonium diffusion and active hydrogen
ion secretion, which explains metabolic acidosis often with hyperchloraemia.
Renal tubular acidosis (RTA). Both proximal and distal renal tubules normal-
ly secrete hydrogen ion [H+] and reabsorb bicarbonate from the luminal fluid.
Renal tubular defects account for failure to excrete the normal acid loads result-
ing in hyperchloraemic acidosis. The renal tubular defects are classified accord-
ing to the site of involvement. Functional impairment of the distal nephron is
classified as a type I defect and of the proximal nephron as a type II defect.
Mixed pattern is designated a type III defect. Aldosterone deficiency represents
a so-called type IV renal tubular defect [30].
Type I. Distal renal tubular acidosis (DRTA) represents either a defect in se-
cretion of H+ or loss of transport capability of H+ against a concentration gradi-
ent between extracellular fluid and urine in the terminal segments of the
nephron. This precludes reduction of the urinary pH to less than 5.5 units. In
lieu of H+ secretion there is excessive K+ excretion and therefore hypokalaemia.
The abnormality is a genetic autos somal dominant defect.
Type II. Proximal renal tubular acidosis is characterized by defects in H+ se-
cretions in the proximal tubule. This accounts for decreased bicarbonate reab-
sorption, losses of bicarbonate in the urine and decreased serum bicarbonate.
Ultimately, there is hypokalaemic and hyperchloraemic acidosis. This disorder
is presently managed with replacement therapy.
Type III. These defects were recognized in infants in whom bicarbonate loss-
es and incapacity to lower urine pH coexist with severe acidaemia.
Type IV. This tubular disorder is related to either a lack of aldosterone or
failure of aldosterone to stimulate H+ secretion in the cation exchange segment
of the distal tubule. Replacement therapy with mineralocorticoids and small
doses of bicarbonate is usually effective.
Bicarbonate loss. The most frequent causes of bicarbonate losses that ac-
count for metabolic acidosis include diarrhoea, vomiting and pancreatic fistula.
All may produce profound hyperchloraemic acidosis [31].

Respiratory acidosis
Respiratory acidosis is diagnosed when PC02 concentrations exceed normal
ranges when measured on arterial blood. In clinical practice, primary increases
in arterial PC02 (PaC0 2) usually are due to impaired alveolar ventilation. Either
or both extra and intra-pulmonary disorders may be implicated. Extra-pul-
monary causes due to neuromuscular disorders with decreased respiratory drive,
abnormalities of respiratory muscle function, skeletal causes or intrathoracic ab-
436 H.P. Povoas, M.H. Weil

normalities may preclude normal ventilation. Thoracic trauma with flail chest,
thoracotomy, sedation, narcosis, anaesthesia and neuromuscular blockade are
frequent precipitating events for global alveolar hypoventilation in the absence
of primary pulmonary causes. Nevertheless the most common cause is de-
creased alveolar ventilation due to primary lung disease including chronic ob-
structive lung diseases, pulmonary oedema, infiltrative lung diseases including
pneumonia, and atelectasis. Finally the primary cause may be partial or com-
plete asphyxia due to airway obstruction and rarely due to breathing gas mix-
tures which have high CO 2 contents.
Failure of carbon dioxide excretion first appears during exercise when large
amounts of carbon dioxide are produced and in amounts that fail to be excreted
by the lungs. PC02 is typically measured in the arterial blood but may also be
measured on capillary and venous blood. Because of the high permeability of
carbon dioxide gas, increases in arterial PC02 are accompanied by tissues hy-
percarbia. The carbon dioxide in blood and tissues is converted, in part, to
H2C03 such as to generate excesses of H+ with decreases in pH. Accordingly,
the severity of acidosis is also related to the bicarbonate concentration.
Two mechanisms for compensation are identified. The first is that of renal re-
tention of HC03- such as to counterbalance the effects of CO2 by increasing bi-
carbonate. The implications of such emerge from the Henderson-Hasselba1ch
equation as shown above. The second is excretion of excesses of hydrogen ions
which of themselves result in reabsorption of bicarbonate. The treatment of un-
complicated respiratory acidosis is that of restoring more normal alveolar venti-
lation by external interventions and especially mechanical ventilation after a
patent airway is secured. The ultimate treatment is that of the underlying cause.

Buffer agents
Buffer preparations that have come into clinical use include sodium bicarbonate,
sodium lactate and a preparation of Carbicarb®, which is not yet approved for
the use in the USA but is used in Europe. Carbicarb® is an equimolar combina-
tion of sodium carbonate and sodium bicarbonate. Bicarbonate generates carbon
dioxide, Carbicarb® does not. Tromethamine (THAM) is an organic buffer that
reduces carbon dioxide tension in tissues and is of special advantage because it
does not increase osmolality.

Tromethamine (THAM)
THAM (tris-hydroxymethyl aminomethane) is a biologically inert amino alco-
hol of low toxicity, which buffers carbon dioxide and acids in vitro and in vivo.
THAM supplements the buffering capacity of the blood bicarbonate system, ac-
cepting a proton, generating bicarbonate and decreasing the partial pressure of
carbon dioxide in arterial blood (PaC0 2). Unlike bicarbonate, which requires an
Differential Diagnosis and Treatment of Acidosis 437

open system for carbon dioxide elimination for its buffering effect, THAM is ef-
fective in a closed or semiclosed system, and maintains its buffering power in
settings of hypothermia. It therefore has theoretical advantages for treatment of
acidaemia associated with carbon dioxide retention. However, THAM may also
depress respiration and produce hypoglycaemia. Nevertheless it is an appropri-
ate option for acute treatment of salicylate or barbiturate overdose because in-
creases in serum pH favor increased excretion of these drugs. THAM is also an
ingredient of cardioplegic solutions and for preservation of liver prior to trans-
plantation. It is also employed for chemolysis of renal calculi [32].

Sodium bicarbonate
Sodium bicarbonate (NaHC03) is the most widely employed buffer agent. The
indications for routine reversal of metabolic acidosis by the intravenous infusion
of sodium bicarbonate is a controversial issue. There is a potential disequilibri-
um of bicarbonate shifts across cell membranes after sodium bicarbonate ad-
ministration, resulting in "paradoxical" intracellular acidosis [33]. It is also a
major cause of hyperosmolar states with resulting cerebral injury, especially in
settings of CPR.

Carbicarb®
Carbicarb® (Na2C03 0.33 molar NaHC0 3 0.33 molar), is a carbon dioxide-con-
suming buffer which was developed to minimize excess CO2 generation [34].
Comparisons between sodium bicarbonate and Carbicarb®, confirm that Car-
bicarb® buffers excesses of [H+] without increasing arterial PC02 [35]. Howev-
er, like sodium bicarbonate Carbicarb® failed to reverse intracellular acidosis in-
cluding myocardial acidosis, nor improve outcomes during cardiac resuscita-
tion. [36, 37]. Although buffer agents may not improve the success of initial re-
suscitation when administered during CPR, there is experimental data which in-
dicate that it may ameliorate postresuscitation myocardial dysfunction and
thereby improve postresuscitation survival [38].
Carbicarb® has been used for the treatment of hypoxic lactic acidosis. When
compared with sodium bicarbonate or sodium chloride, Carbicarb® had a more
beneficial haemodynamic effect with respect to increasing cardiac output and
arterial perfusion pressure. It also increased cardiac contractility [39]. However,
there is currently no persuasive data to favor its clinical use. Neither diabetic ke-
toacidosis or the acidosis of hypovolaemic shock were improved after adminis-
tration of Carbicarb® [40].
438 H.P. Povoas, M.H. Weil

References
1. Johnson BA, Weil MH 1991) Redefining ischemia due to circulatory failure as dual defects of
oxygen deficits and of carbon dioxide excesses. Crit Care Med 19: 1432-1438
2. von Planta M, Weil MH, Gazmuri, RJ et al (1989) Myocardial acidosis associated with CO2
production during cardiac arrest and resuscitation. Circulation 80:684-692
3. Desai VS, Weil MH, Tang W et al (1993) Gastric intramural PC0 2 during peritonitis and
shock. Chest 104:1254-1258
4. Sato Y, Weil MH, Tang Wet al (1997) Esophageal PC02 as a monitor of perfusion failure dur-
ing hemorrhagic shock. J Appl Physiol 82:558-562
5. Nakagawa Y, Weil MH, Tang W et al (1998) Sublingual capnometry for diagnosis and quanti-
tation of circulatory shock. Am J Respir Crit Care Med 157: 1838-1843
6. Astiz ME, Rackow EC, Kaufman B et al (1988) Relationship of oxygen delivery and mixed
venous oxygenation to lactic acidosis in patients with sepsis and acute myocardial infarction.
Crit Care Med 16:655-658
7. Weil MH, Michaels S, Puri VK et al (1981) The stat laboratory: facilitating blood gas and
biochemical measurements for the critically ill and injured. Am J Clin Pathol 76:34-42
8. Henderson LJ (1908) The theory of neutrality regulation in the animal organism. Am J Physi-
0121:427-448
9. Ishihara K, Szerlip HM (1998) Anion gap acidosis. Semin NephroI18:83-97
10. Weil MH, von Planta M, Gazmuri RJ et al (1988) Incomplete global myocardial ischemia
during cardiac arrest and resuscitation. Crit Care Med 16(10):997-1001
11. Weil MH, Afifi AA (1970) Experimental and clinical studies on lactate and pyruvate as indi-
cators of the severity of acute circulatory failure (shock). Circulation 41:989-1001
12. Gore DC, Jahoor F, Hibbert JM et al (1996) Lactic acidosis during sepsis is related to in-
creased pyruvate production, not deficits in tissue oxygen availability. Ann Surg 224:97-102
13. Porras MC, Lecumberri IN, Castrillon JL (1998) Trimethoprimlsulfamethoxazole and meta-
bolic acidosis in HIV-infected patients. Ann Pharmacother 32: 185-189
14. Hanna JP, Ramundo ML (1998) Rhabdomyolysis and hypoxia associated with prolonged
propofol infusion in children. Neurology 50:301-303
15. Latif MA, Weil MH (1979) Circulatory defects during phenformin lactic acidosis. Intensive
Care Med 5:135-139
16. Bell PM, Hadden DR (1997) Metformin. Endocrinol Metab Clin North Am 26:523-537
17. Lalau JD, Lacroix C, Compagnon P et al (1995) Role of metformin accumulation in met-
formin-associated lactic acidosis. Diabetes Care 18:779-784
18. Sundar K, Suarez M, Banogon PE et al (1997) Zidovudine-induced fatal lactic acidosis and
hepatic failure in patients with acquired immunodeficiency syndrome: report of two patients
and review of the literature. Crit Care Med 25:1425-1430
19. Uribarri J, Oh MS, Carroll HJ (1998) D-lactic acidosis. A review of clinical presentation, bio-
chemical features, and pathophysiologic mechanisms. Medicine (Baltimore) 77:73-82
20. Kadakia SC (1995) D-lactic acidosis in a patient withjejunoileal bypass. J Clin Gastroenterol
20:154-156
21. Bongaerts GP, Tolboom JJ, Naber AH et al (1997) Role of bacteria in the pathogenesis of
short bowel syndrome-associated D-lactic acidemia. Microb Pathog 22:285-293
22. Marbach EP, Weil MH (1967) Rapid enzymatic measurement of blood lactate and pyruvate.
Use and significance of metaphosphoric acid as a common precipitant. Clin Chern 13:
314-325
23. Brandenburg MA, Dire DJ (1998) Comparison of arterial and venous blood gas values in the
initial emergency department evaluation of patients with diabetic ketoacidosis. Ann Emerg
Med 31 :459-465
24. Okuda Y, Adrogue HJ, Field JB et al (1996) Counterproductive effects of sodium bicarbonate
in diabetic ketoacidosis. J Clin Endocrinol Metab 81:314-320
25. Green SM, Rothrock SG, Ho JD et al (1998) Failure of adjunctive bicarbonate to improve
outcome in severe pediatric diabetic ketoacidosis. Ann Emerg Med 31 :41-48
Differential Diagnosis and Treatment of Acidosis 439

26. McMartin KE, Ambre JJ, Tephly TR (1980) Methanol poisoning in human subjects. Role for
formic acid accumulation in the metabolic acidosis. Am J Med 68:414-418
27. Gabow PA, Clay K, Sullivan JB et al (1986) Organic acids in ethylene glycol intoxication.
Ann Intern Med 105:16-20
28. Kirschbaum B (1998) The acidosis of exogenous phosphate intoxication. Arch Intern Med
158:405-408
29. Moon PF, Kramer GC (1995) Hypertonic saline-dextran resuscitation from hemorrhagic
shock induces transient mixed acidosis. Crit Care Med 23(2):323-331
30. BatHe D, Flores G (1996) Underlying defects in distal renal tubular acidosis: new understand-
ings. Am J Kidney Dis 27:896-915
31. DuBose TD Jr (1997) Hyperkalemic hyperchloremic metabolic acidosis: pathophysiologic in-
sights. Kidney Int 51:591-602
32. Nahas GG, Sutin KM, Fermon C et al (1998) Guidelines for the treatment of acidaemia with
THAM. Drugs 55:191-224
33. Goldsmith DJ, Forni LG, Hilton PJ (1997) Bicarbonate therapy and intracellular acidosis.
Clin Sci (Colch) 93:593-598
34. Filley GF, Kindig NB (1984) Carbicarb, an alkalinizing ion-generating agent of possible clin-
ical usefulness. Trans Am Clin Climatol Assoc 96: 141-153
35. Sun JH, Filley GF, Hord K et al (1987) Carbicarb: an effective substitute for NaHC0 3 for the
treatment of acidosis. Surgery 102:835-839
36. Kette F, Weil MH, von Planta M et al (1990) Buffer agents do not reverse intramyocardial aci-
dosis during cardiac resuscitation. Circulation 81: 1660-1666
37. Gazmuri RJ, von Planta M, Weil MH et al (1990) Cardiac effects of carbon dioxide-consum-
ing and carbon dioxide-generating buffers during cardiopulmonary resuscitation. J Am ColI
Cardiol 15(2):482-490
38. Sun S, Weil MH, Tang W et al (1996) Effects of buffer agents on postresuscitation myocardial
dysfunction. Crit Care Med 24:2035-2041
39. Rhee KH, Toro LO, McDonald GG et al (1993) Carbicarb, sodium bicarbonate, and sodium
chloride in hypoxic lactic acidosis. Effect on arterial blood gases, lactate concentrations, he-
modynamic variables, and myocardial intracellular pH. Chest 104:913-918
40. Beech JS, Williams SC, lIes RA et al (1995) Haemodynamic and metabolic effects in diabetic
ketoacidosis in rats of treatment with sodium bicarbonate or a mixture of sodium bicarbonate
and sodium carbonate. Diabetologia 38:889-898