UMEM Educational Pearls - By Jessica Downing

The role of sodium bicarbonate in the treatment of severe acidemia has been controversial, with some studies suggesting no benefit, and others indicating that it may help reduce need for renal replacement therapy (RRT) and even improve mortality. The BICARICU-2 Trial was an open-label multicenter RCT conducted in France that evaluated the impact of a bicarb infusion among patients with metabolic acidosis and moderate to severe AKI. 

There was no difference in 90 day mortality, but patients in the bicarb group were less likely to be started on RRT (38% vs 47% in the control group) using pre-defined criteria for RRT initiation, and had a 50% lower rate of bloodstream infections. Patients in the bicarb group who were started on RRT met criteria for RRT later than those in the control group (median 31h vs 15.5h).

Study Details:

Patient Population: 

• SOFA score >4 OR arterial lactate > 2mmol/L within 48h of ICU admission
• Metabolic acidosis, defined by pH < 7.2, HCO3- < 20mEq/L, and PaCO2  < 45mmHg
• Moderate to severe AKI, defined as Cr >2.0 x baseline or UOP < 0.5 mL/kg/h for >12h. 
• Patients with severe baseline CKD, ketoacidosis, intoxication with exogenous acids (metformin, salicylate, methanol, ethylene glycol), or ongoing bicarb losses via GI or urinary tracts were excluded.
• The presumed etiology of acidemia was septic shock in over half of included patients, and over 75% were on vasopressors.

Intervention: 

• 4.2% bicarb infusion administered in 125-250 aliquots with a target pH >7.3, though not to exceed 1L/500mEq within 24h. 
• The intervention continued for a maximum of 28d or until ICU DC. 
• Patients in the intervention group received a median of 750mL in the first 48h.

RRT Triggers:

• Immediate: K > 6.5mEq/L with EKG changes or cardiogenic pulmonary edema with no UOP and hypoxia
• 24h after enrollment: UOP <0.3 Ml/kg/h over 24h, pH <7.2 despite resuscitation, K > 6.5 MEq/L.

Show References

Norepinephrine (NE) is widely accepted as the first-line vasopressor for the management of septic shock, supported by the Surviving Sepsis Guidelines (1). The use of vasopressin as a second-line agent is also supported by the Surviving Sepsis Campaign, although the appropriate “triggers” for its addition remain vague. The SSG recommend adding vasopressin when NE infusion rates reach 0.25-0.6 mcg/kg/min, citing a catecholamine-sparing effect and potentially improved mortality (1, 2, 3).

What’s New?

The OVISS study (“Optimal vasopressin initiation in septic shock. The OVISS reinforcement learning study”) used machine learning to derive and internally validate a set of rules guiding the addition of vasopressin to NE for patients with septic shock using multiple databases of patient encounters across multiple institutions (4). 

The machine learning model suggested initiation of vasopressin in more patients (87% vs 31%), earlier,  and in less sick patients than was seen to be common practice:

• Timing: 4h after diagnosis of shock (vs. 5h)
• NE dose: 0.2 mcg/kg/min (vs. 0.37mcg/kg/min)
• Serum lactate: 2.5 mmol/L (vs. 3.6 mmol/L)
• SOFA score: 7 (vs. 9)

Practice consistent with the above triggers was associated with decreased odds of in-hospital mortality (AOR 0.81, 95% CI 0.73-0.91).

Limitations

This was not a prospective study or RCT and was only internally validated. Using databases may limit the number of clinical variables available for analysis, and clinical judgment (how the patient looks) is not reflected.

Bottom Line

Consider adding vasopressin for patients with vasodilatory shock with low MAP despite NE >0.2mcg/kg/min and adequate fluid resuscitation, though more evidence is needed for a strong recommendation. As dual-pressor therapy may be riskier via peripheral IV and vasopressin does not have a direct antidote for extravasation, consider central line placement when adding vasopressin (5,6)

Show References