Intensive Care Med

https://doi.org/10.1007/s00134-019-05835-3

WHAT’S NEW IN INTENSIVE CARE

The Janus faces of bicarbonate therapy

© 2019 Springer-Verlag GmbH Germany, part of Springer Nature

State of the art on organ function. Although often performed [7, 9], this
Metabolic acidosis is characterized by a primary reduc- treatment has not to date been supported by the few pro-
tion in plasma bicarbonate concentration below spective studies available [10, 11].
20  mmol/L in the Henderson–Hasselbalch method and
with either an imbalance between strong plasma cations Controversies
concentration compared to the strong anions concentra- The risk–benefit balance of sodium bicarbonate infusion
tion (decreasing thus the strong ion difference) and/or an to increase the plasma pH level has been challenged by
excess in non-volatile weak acids in the Stewart–Fencl the absence of high-quality prospective studies and the
method [1, 2]. Acidemia is the term used if the plasma possible side effects of its infusion.
pH is equal to or below 7.38, acidemia being described Sodium bicarbonate is indeed associated with a sig-
as severe when the pH is equal to or below 7.20 [3, 4]. nificant risk of hypokalemia, hypernatremia, volume
Metabolic acidemia can be associated with organ failure, overload, ionized hypocalcemia and metabolic alkalo-
in particular respiratory failure (increased ventilatory sis [1, 12]. Uncertain adverse effects such as paradoxical
demand) and cardiovascular failure (arterial vasodila- intracellular acidosis secondary to the passive diffusion
tion, decreases in cardiac inotropism and cardiac output, of carbon dioxide across the cellular membrane has also
ventricular arrhythmia) [1, 5, 6]. Metabolic acidemia is been reported in some in  vitro experiments using dif-
observed in 14–42% of the critically ill patients [7] and, ferent types of cells and buffer conditions [13], but has
when acidemia is severe (pH < 7.20) and persists, is asso- never been reported in humans [14]. The retention of
ciated with 50–60% mortality in the Intensive Care Unit carbon dioxide following rapid sodium bicarbonate infu-
(ICU) [7, 8]. The best treatment option to treat metabolic sion might also occur especially in spontaneous breath-
acidosis is the causal treatment which can be very differ- ing patients with type II hypercapnic respiratory failure.
ent according to the disease. Facing metabolic acidemia, a Acidosis is associated with a decreased hemoglobin
short list of strong indications (gastrointestinal or urinary affinity for oxygen (Bohr effect) and the rapid infusion of
loss of bases, ethylene glycol, methanol and salicylate sodium bicarbonate might be associated with an increase
poisoning) and non-indications (diabetic ketoacidosis, in hemoglobin affinity for oxygen lowering the oxygen
tumor lysis syndrome) have been recommended [1, 3]. In availability to the cells [15].
other situations, such as lactic acidosis, in order to save This side effect, illustrated by a mean drop in the cen-
time in view of the elimination of the underlying cause, tral vein oxygen saturation of 4 mmHg in one physiologi-
one may suggest to administer intravenous sodium bicar- cal study, appears to be transient [10].
bonate to counter balance the negative effects of acidemia Whether it is the bicarbonate or the sodium load that
is associated with the plasma pH increase is another con-
troversy. In the Henderson-Hasselbalch method, since
*Correspondence: s‑jaber@chu‑montpellier.fr
3
Intensive Care Unit, Anesthesiology and Intensive Care, Anesthesia pH = plasma pKa + log10 ­[HCO3−]/0.03 × ­[PaCO2] is the
and Critical Care Department B, Saint Eloi Teaching Hospital, Centre central equation, it is the load in H ­ CO3− which is asso-
Hospitalier Universitaire Montpellier, University Montpellier, 1, 80 Avenue ciated with the increase in the plasma pH. The Stewart–
Augustin Fliche, 34295 Montpellier Cedex 5, France
Full author information is available at the end of the article Fencl method claims that the independent parameter
that regulates the pH is the difference between measured
cations and anions (named strong ion difference) rather sepsis and moderate to severe acute kidney injury). The
than plasma bicarbonate concentration [2]. According to primary endpoint was a composite score of mortality by
the Stewart–Fencl method, sodium bicarbonate infusion day 28 and the presence of an organ failure (assessed by
would then increase the plasma pH level because of the the SOFA score) at day 7. The Kaplan–Meier method
massive sodium intake without chloride. estimate of the probability of survival at day 28 between
the control group and bicarbonate group in the over-
Recent advances in knowledge all population was not significant (46% [95% CI 40–54]
We recently performed the first large multiple center vs 55% [49–63]; p = 0.09). However, after multivariate
randomised clinical trial in which 400 severe acidemic analysis, sodium bicarbonate infusion was associated
(pH ≤ 7.20) critically ill patients were randomised to with fewer deaths (crude HR 0.783, 95% CI 0.0589–1.040;
either intervention (4.2% intravenous sodium bicarbo- p = 0.091; and adjusted HR 0.727, 95% CI 0.540–0.979;
nate) to target a pH equal or greater than 7.30 or con- p = 0.0356). The number of days alive free from renal
trol (no intravenous sodium bicarbonate) [12]. Three replacement therapy was significantly lower in the con-
strata were preplanned (age with a cutoff of 65 years, trol group than in the bicarbonate group (8 (0–28) vs 19

Fig. 1  Among the 400 critically ill patients with severe metabolic acidemia enrolled in the BICAR-ICU trial, 182 were enrolled in the moderate
to severe acute kidney injury stratum and randomised to the 4.2% sodium bicarbonate group or to the no sodium bicarbonate (control) group
[12]. The primary composite outcome as well as the day mortality was lower in the bicarbonate group than in the control group. After taking into
consideration the absolute risk reduction of death, six patients (95 % confidence interval 3 to 50) was the estimate number of patients needed to be
treated to save one life by day 28
(1–28), p = 0.015). In the prespecified stratum of patients Received: 4 September 2019 Accepted: 17 October 2019
with moderate or severe acute kidney injury, the Kaplan–
Meier method estimate of survival by day 28 between the
control group and bicarbonate group was significant (63%
[95% CI 52–72] vs 46% [35–55]; p = 0·0283). Accord- References
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Conflicts of interest
Pr. Jaber reports receiving consulting fees from Drager, Fisher & Paykel and
Fresenius.

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