BICAR-ICU

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Jaber S, et al. "Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial". The Lancet. 2018. 392(10141):31-40.
PubMedFull text

Clinical Question

In acutely ill patients in the intensive care unit with severe acidemia, does treatment with sodium bicarbonate decrease the composite of death from any cause by day 28 and presence of at least one organ failure by day 7?

Bottom Line

In this study, ICU patients with severe acidemia treated with sodium bicarbonate did not have improvement in the composite outcome of death from any cause by day 28 and the presence of at least one organ failure at day 7.

Major Points

Guidelines

Design

  • Multicenter, open-label, randomized, controlled, phase 3 trial
  • N=389
    • Bicarbonate (n=195)
    • Control (n=194)
  • Setting: 26 intensive care units in France
  • Enrollment: May 5, 2015 to May 7, 2017
  • Analysis: Intention-to-treat
  • Primary outcome: composite of death from any cause by day 28 and the presence of at least one organ failure at day 7

Population

Inclusion Criteria

  • Adult patients age >/=18 years
  • 48 hours within 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

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

Baseline Characteristics

Comparisons are control group vs bicarbonate group

  • Median age: 65 vs 66 years
  • Female sex: 37% vs 41%
  • BMI: 27 vs 26
  • Simplified Acute Physiology Score II: 60 vs 59
  • Sepsis: 115 vs 123
  • AKIN 2-3: 46% vs 47%
  • Condition associated with acidemia at enrollment
    • Cardiac arrest: 9% vs 9%
    • Septic shock: 51% vs 55%
    • Hemorrhagic shock 40% vs 45%
    • Others 38% vs 25%
  • Laboratory results
    • Arterial pH: 7.15 vs 7.15
    • Serum bicarbonate: 13 vs 13
    • PaCO2: 37 vs 38
    • Serum lactate 5.3 vs 6.3
    • Serum creatinine: 1.76 vs 1.67
  • Physiologic support:
    • Invasive mechanical ventilation: 82% vs 84%
    • Vasopressor support: 80% vs 79%

Interventions

  • Randomized to receive no bicarbonate (control group) or sodium bicarbonate infusion (bicarbonate group)
    • Stratification by study site, age with cutoff of 65 years, presence of suspected sepsis, and presence of AKIN score of 2 or 3
  • Bicarbonate group received 4.2% sodium bicarbonate intravenously with aim of goal arterial pH of >/= 7.30 during 28-day ICU admission or ICU discharge
    • Protocol recommended infusion at 125-250 mL in 30 min, with max 1L in 24 hours after inclusion

Outcomes

Comparisons are control group vs bicarbonate group.

Primary Outcomes

Composite of Death from any cause by day 28 or the presence of at least one organ failure at day 7
71% vs 66% (absolute difference estimate -5.5, 95% CI -15.2 to 4.2; p=0.24)
In patients with AKIN scores of 2-3 (n=182), composite of death from any cause by day 28 or the presence of at least one organ failure at day 7
82% vs 70% (absolute difference estimate -12.3, 95% CI -26.0 to -0.1; p=0.0462)

Secondary Outcomes

Renal replacement during ICU stay
52% vs 35% (absolute difference estimate -16.7, 95% CI -26.4 to -7.0; p=0.0009)
Time from enrollment to initiation of renal replacement therapy (hours)
7 vs 19 (absolute difference estimate 8.8, 95% CI 3.9 to 15.6; p<0.0001)
Renal replacement therapy-free days during ICU stay in survivors
28 vs 28 (absolute difference estimate 0, 95% CI 0 to 0; p=0.47)
Renal replacement therapy-free days during ICU stay
8 vs 19 (absolute difference estimate 0, 95% CI 0 to 1.0; p=0.015)

Subgroup Analysis

The authors included an a-priori analysis of patients with AKIN scores of 2 or 3, with results described above.

Adverse Events

Criticisms

  • Unable to blind treating physicians and nursing since arterial blood gases are affected by bicarbonate administration
  • 24% of control group received sodium bicarbonate, potentially underestimating treatment effect.

Funding

Further Reading