This study evaluated whether sodium bicarbonate infusion improved outcomes in critically ill patients with severe metabolic acidemia. The study randomized 389 ICU patients to receive either sodium bicarbonate infusion aimed at achieving an arterial pH of ≥7.30, or no bicarbonate (control group). The primary outcome of all-cause mortality at day 28 and presence of organ failure at day 7 was not improved with bicarbonate in the overall population. However, in the subgroup of patients with acute kidney injury, the primary outcome occurred less frequently with bicarbonate. Additionally, more days alive without renal replacement therapy were seen with bicarbonate both overall and in acute kidney injury patients.

1. Sodium bicarbonate therapy for patients
with severe metabolic acidaemia in the
intensive care unit (BICAR-ICU)
Dr.Riteshkumar Banode
SSH Hospital Nagpur

2. Background
• Acute acidaemia is frequently observed during critical illness, reported
incidence varying from14% to 42%.
• Persistent acidaemia carries with poor prognosis, with a mortality rate as
high as 57% when the pH stays below 7⋅20.
• Sodium bicarbonate infusion for the treatment of severe metabolic
acidaemia is a possible treatment option but remains controversial.
Surveys and observational studies have, however, reported that more
than half of the critical care physicians or nephrologists would consider
sodium bicarbonate infusion for a patient with severe metabolic
acidaemia whatever its cause.

3. 2017 Surviving Sepsis Campaign stated that “the effect of sodium
bicarbonate administration on hemodynamics and vasopressor
requirements at lower pH(than 7.15) as well as the effect on clinical
outcomes at any pH level, is unknown” and that “no studies have examined
the effect of bicarbonate administration on outcomes”.
• The absence of high-level evidence leaves ICU clinicians uncertain whether
sodium bicarbonate infusion is beneficial, ineffective, or indeed harmful to
patients with severe acidemia.
• So this study was carried out to evaluate whether sodium bicarbonate
infusion would improve these outcomes in critically ill patients.

4. Study Design
• Multicenter, open-label, randomized, controlled, phase 3 trial
• N=389 ICU patients with severe acidemia
– Bicarbonate (n=195)
– Control (n=194)
• Setting: 26 ICUs in France
• Enrollment: 2015-2017
• Analysis: Intention-to-treat
• Primary outcome: All-cause mortality at day 28 and the presence of ≥1
organ failure at day 7

5. Study Population
Inclusion Criteria
• Adult patients age ≥18 years
• Admission to ICU with severe acidemia, defined as pH ≤7.20, PaCO2 ≤ 45
mm Hg, and sodium bicarbonate concentration ≤ 20 mmol/L
• Sequential Organ Failure Assessment (SOFA) score of 4 or more, or arterial
lactate concentration of 2 mmol/L or more

6. Exclusion Criteria
• Respiratory acidosis
• Proven digestive or urinary tract loss of sodium bicarbonate
(volume loss ≥ 1500 mL/day)
• Stage IV chronic kidney disease
• Ketoacidosis
• Sodium bicarbonate infusion within 24 hours before screening

11. Interventions
• Randomized to a group in an open label fashion:
– Control - No bicarbonate
– Bicarbonate 4.2% sodium bicarbonate intravenously
with aim of goal arterial pH of ≥7.30 during 28-day ICU
admission or ICU discharge;
– recommended infusion at 125-250 mL in 30 min, with
max 1L in 24 hours after inclusion

13. Management common to both groups
• Indications for renal-replacement therapy (RRT) were standardised
• RRT was strongly recommended in the event of hyperkalaemia (>6⋅5
mmol/L) with electrocardiogram signs or cardiogenic pulmonary oedema
with no urine output, or both
• At 24 h after inclusion, RRT was recommended when two of three criteria
were present:
– urine output less than 0⋅3 mL/kg per h for at least 24 h
– arterial pH less than 7⋅20 despite resuscitation
– hyperkalaemia (>6⋅5 mmol/L)
• Each study site chose the method of RRT according to the local guidelines

14. Outcomes
Comparisons are control vs. bicarbonate.
• Primary Outcomes
• Composite all-cause mortality at day 28 and the presence of ≥1 organ
failure at day 7.
Note that the following outcomes were not defined as primary outcomes
• All-cause mortality at day 28
• ≥1 organ failing at day 7
Pre-specified subgroup analysis patients with AKIN scores of 2-3 (n=182)
• composite of death from any cause by day 28 and the presence of at
least one organ failure at day 7
• All-cause mortality at day 28
• ≥1 organ failing at day 7

15. Secondary Outcomes
• Renal replacement during ICU stay
• Time from enrollment to initiation of renal replacement therapy (hours)
• Renal replacement therapy-free days during ICU stay in survivors
• Renal replacement therapy-free days during ICU stay

16. Primary outcome

17. Figure 2: Time to death in the overall population (A) and patients with
prespecified acute kidney injury (B)

18. Secondary outcomes

19. Secondary outcomes

20. Secondary outcomes

21. Secondary outcomes

22. 28-day mortality risk difference in the overall population and in the three
prespecified strata (C)

23. Adverse Events
• ≥1 lab with serum Na >145 mmol/L 29% vs. 49% (absolute difference 19.9,
95% CI 10.4 to 29.4; P<0.001)
• ≥1 lab with serum Ca <0.9 mmol/L 15% vs. 24% (absolute difference 9.7,
95% CI 1.8 to 17.5; P=0.017)
• ≥1 lab with blood pH >7.45 9% vs. 16% (absolute difference 7.1, 95% CI 0.6
to 13.6; P=0.032)

24. Weaknesses
• Composite primary outcome.
• 24% of the control group received bicarbonate
• Physicians were not blinded.
• The protocol suggested a range of 4⋅2% sodium bicarbonate volume
(125–250 mL per infusion) in the bicarbonate group rather than
using a formula to calculate the base deficit and provide a tailored
sodium bicarbonate infusion; therefore, we cannot extrapolate
whether different ways of administration would have resulted in
different outcomes
• No data was collected for mechanical ventilation settings which
may have influenced the patients acid-base status

25. Conclusion
• In this trial, reported that in the overall population sodium bicarbonate
infusion was not associated with an improvement in the primary outcome
(ie, composite criteria of organ failure at day 7 and any cause of death at
day 28).
• In patients with acute kidney injury (with Acute Kidney Injury Network
scores of 2 or 3 at enrolment), the primary outcome occurred less
frequently in the bicarbonate group than in the control group.
• Additionally, the number of days alive and free from renal-replacement
therapy was higher in the bicarbonate group than in the control group
both in the overall study population and in the a-priori defined stratum of
patients with acute kidney injury.

27. • THANKS