Anaesth Crit Care Pain Med 37 (2018) 495–497
Editorial
Treatment of acute acidaemia in the seriously ill patient:
Should base be given?
A R T I C L E I N F O
Keywords:
Sodium bicarbonate
Severe acidaemia
Metabolic acidosis
Respiratory acidosis
NHE1
Acute severe acidaemia, defined as a plasma pH of 7.20 [1]
or 7.15 [2] that is present for minutes to a few days, is associated
with decreased hemodynamic function, increased cardiac arrhythmogenicity, increased tissue inflammation, and increased mortality [3]. The critical factors producing the cellular dysfunction with
acute acidaemia is a decrement in intracellular pH (pHi) and
interstitial pH (pHe) rather than systemic plasma pH alone.
Therefore, improving the pH of all three compartments should be a
major goal of therapy [4].
The most effective strategy for treatment of acute acidaemia is
elimination of the underlying cause such as administration of
crystalloid to improve blood pressure and hemodynamic function
or treatment of infection in patients with sepsis. However, if this is
not possible, or the clinician desires to speed the recovery of acidbase balance, administration of base, primarily in the form of
sodium bicarbonate, is often recommended [5].
There remains great controversy about the value of the
administration of sodium bicarbonate in acute severe acidaemia
[5]. In order for the clinician to make an informed decision about
the use of bicarbonate in the treatment of acute severe acidaemia,
he/she must understand the rationale for its use, its perceived
benefits and limitations, and any alternative therapy available.
1. Causes of severe acidaemia
Assuming an appropriate respiratory response, severe acidaemia will be observed when serum [HCO3-] falls below 10 mEq/L.
However, many patients with severe acidaemia do not have
metabolic acidosis alone, but rather have mixed metabolic and
respiratory acidosis [6]. Since the generation and retention of
carbon dioxide after bicarbonate administration is a major concern
(see below), any impairment in the elimination of carbon dioxide
will affect the clinician’s prescription for base administration.
Thus, documenting whether metabolic acidosis with appropriate
respiratory compensation or a mixed metabolic and respiratory
disturbance is present is a critical step in determining whether and
how much sodium bicarbonate should be administered.
The major metabolic causes of severe acidaemia are lactic
acidosis and ketoacidosis; whereas, other high anion gap acidosis
such as toxic alcohol poisoning or Tylenol poisoning are uncommon [7]. The non-anion gap metabolic acidosis associated with
aggressive administration of chloride-containing solution is
frequent, but is generally mild to moderate in degree [8]. Therefore,
the overwhelming majority of the information about the use
of bicarbonate in the treatment of severe acidaemia has been
obtained from studies of lactic acidosis and ketoacidosis. Thus, I
will restrict my comments only to the use of bicarbonate in the
treatment of these acid-base disorders.
2. Impact of base administration on mortality and
haemodynamics
In both prospective and retrospective studies in children and
adults, bicarbonate did not reduce morbidity or mortality of
diabetic ketoacidosis [9]. Similarly, in several of the studies of lactic
acidosis in adults published in English, bicarbonate did not reduce
mortality [1,6,10]. On the other hand, in a single study published in
the Chinese literature, administration of sufficient bicarbonate to
raise blood pH to 7.25 as associated with less mortality when the
goal of therapy was blood pH of 7.15 [11].
In the recent large multi study of Jaber et al. [1], although
sodium bicarbonate did not reduce the composite of mortality at
day 30 and at least one organ failure at day 7 (primary outcome), it
did reduce the primary outcome when given to a subset of patients
with acute kidney injury network scores of 2–3 who were being
dialysed (70% vs. 82%). The reason for the benefit of bicarbonate in
the treatment of metabolic acidosis associated with severe AKI is
unclear. In patients who were dialysed, it might be explained
by the ability of dialysis to aid in the control of volume, serum
osmolality, and ionized calcium during treatment, factors that
might affect the response to sodium bicarbonate therapy. In
patients who were not dialysed the reasons behind the benefits of
bicarbonate are less clear. Be that as it may, this intriguing finding
merits further investigation, and if confirmed would support the
use of sodium bicarbonate under these circumstances.
Not only did bicarbonate administration not reduce mortality in
most of the reported studies, it did not improve hemodynamic
function in patients with diverse causes of lactic acidosis more
than an equivalent quantity of sodium chloride assessed both at
https://doi.org/10.1016/j.accpm.2018.11.005
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Editorial / Anaesth Crit Care Pain Med 37 (2018) 495–497
30 minutes [12] or 60 minutes postinfusion [13]. Similar studies of
diabetic ketoacidosis have not been performed, although a single
observational study revealed that spontaneous correction of
diabetic ketoacidosis in patients was not associated with any
improvement in cardiac contractility [14].
effects of sodium bicarbonate. Indeed, the improvement in cardiac
contractility when a selective NHE1 inhibitor is given along with
bicarbonate is not different than when the NHE1 inhibitor is given
alone [22].
6. Conclusions and future directions
3. Adverse effects of bicarbonate administration
Adverse effects of bicarbonate administration include volume
overload, metabolic alkalosis, and cerebral oedema in children
with DKA [7]. However, the most important adverse effects
reported include: a pH-dependent decrease in the level of ionized
calcium [12]; and intracellular acidification of various tissues due
to accumulation of carbon dioxide [15]. The inevitability of the
latter complication has been questioned, as in some studies
infusion of bicarbonate to an acidemic animal or human failed to
reduce pHi or even raised it [16]. Unfortunately, the explanation
for the discrepant effects were not clear. However, it is postulated
that acidification of tissues is more common when large quantities
of bicarbonate are administered at a rapid rate. To monitor the
presence and the magnitude of this complication, assessment of
acid-base parameters in central venous blood is useful [17].
Patients with lactic acidosis can have hypocalcaemia prior to
bicarbonate therapy and the hypocalcaemia can be exacerbated
with bicarbonate treatment, particularly if alkalemia develops
[12]. In this regard, twenty-five percent of patients receiving
bicarbonate for the treatment of acute acidaemia in the study of
Jaber et al. [1] developed hypocalcaemia.
The potential success of the prevention of hypocalcaemia and
tissue accumulation of carbon dioxide following bicarbonate
infusion to allow the positive effects of bicarbonate therapy to
be expressed was shown by studies of rats with acute lactic
acidosis in which both alterations were prevented: this resulted in
improved cardiac contractility and vascular responsiveness to
catecholamines [18].
In summary, bicarbonate administration to non-dialysis
patients with lactic acidosis or diabetic ketoacidosis does not
reduce mortality or improve cardiovascular function. As noted, this
might be attributed to tissue accumulation of carbon dioxide and
hypocalcaemia during treatment. Therefore, their minimization or
prevention might allow more of the positive effects of bicarbonate
administration to be expressed.
4. Additional bases for treatment of acute acidaemia
Other bases that were designed to avoid tissue accumulation of
carbon dioxide with their administration have been studied. THAM
(tris-buffer) raised plasma [HCO3-] and pH in patients with lactic
acidosis and was not associated with carbon dioxide retention
in patients with combined metabolic and respiratory acidosis
[19]. Also, carbicarb1 a 1:1 mixture of sodium bicarbonate and
disodium carbonate improved acid-base parameters and cardiac
function in animal studies, but not in studies of humans [20]. Both
agents are presently not being manufactured.
5. Other mechanisms of cellular injury as targets for treatment
Activation of the myocardial sodium hydrogen exchanger NHE1
with lactic acidosis causes, accumulation of detrimental quantities
of sodium and calcium, cellular injury, impaired haemodynamics,
and increased mortality in animal models, which can be prevented
by treatment with selective NHE1 inhibitors [21]. Administration
of sodium bicarbonate can exacerbate this process by reducing the
proton gradient against which the sodium-hydrogen exchanger
must pump: a potential additional reason to explain the injurious
Bicarbonate administration to patients with lactic acidosis and
ketoacidosis does not improve haemodynamics or reduce mortality in the majority of clinical and experimental studies. As noted,
this failure could be due to hypocalcaemia and accumulation
of carbon dioxide with bicarbonate administration and studies in
humans to determine whether their prevention is beneficial is
warranted.
Also, the recognition of the potential role of activation of the
myocardial NHE1 and its enhancement by bicarbonate administration in depressing haemodynamics suggests administration
of NHE1 inhibitors might further enhance beneficial effects of
bicarbonate or other bases.
The acidaemia in seriously ill patients is of major concern to the
clinician. Developing effective methods of treatment is of critical
importance. Although as presently prescribed, bicarbonate might
not be beneficial, examination of putative measures to improve its
effectiveness or the use of other bases is clearly indicated.
Disclosure of interest
The author declares that he has no competing interest.
Acknowledgements
Dr Kraut has a pending patent for treatment of acute metabolic
acidosis.
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Jeffrey A. Kraut MD *
Medical and Research Services VHAGLA Healthcare System,
UCLA Membrane Biology Laboratory, and Division of Nephrology
VHAGLA Healthcare System and David Geffen School of Medicine,
Los Angeles, CA, USA
*Correspondence. Division of Nephrology, VHAGLA Healthcare
System, 11301 Wilshire Boulevard, Los Angeles CA 90073, USA
E-mail address: jkraut@ucla.edu