Is 20 The Magic Numb3r?

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The question of albumin, particularly its use (and usefulness) in patients with sepsis has been debated and revisited a lot over the years, with most of the randomized controlled trials published demonstrating improved hemodynamic parameters, but no mortality benefit when using albumin solutions over crystalloids for fluid resuscitation.

The latest Surviving Sepsis Campaign (SSC 2021) guidelines say the following about albumin in in sepsis:

The lack of proven benefit and higher cost of albumin compared to crystalloids contributed to our strong recommendation for the use of crystalloids as first-line fluid for resuscitation in sepsis and septic shock.

Albumin was suggested as “second-line” fluid resuscitation therapy reserved for patients who received large volumes of crystalloids. The authors cite studies demonstrating higher blood pressures, higher static filling pressures and a lower net fluid balance when albumin is used as a resuscitation fluid of choice in sepsis.

The issue with summarily interpreting the results of sepsis trials involving albumin is that the analyses often include a variety of patient populations (both pediatric and adult) and include studies regardless of the type of albumin solution used, with albumin concentration ranging from 4 to 25%, depending on the trial.

This week’s article, published just over 2 weeks ago, looks at the effectiveness and safety of hyperoncotic (⩾ 20% concentration) albumin solutions in patients with sepsis.

The article, titled “The efficacy, safety and effectiveness of hyperoncotic albumin solutions in patients with sepsis: A systematic review and meta-analysis”, by Bannard-Smith et al, analyzed outcomes from pooled data of 2772 patients from 4 randomized controlled trials.

Three of the studies included compared 20% albumin infusions to crystalloids and one compared 20% albumin infusions to 6% starch infusions.  All of the studies included enrolled adult patients with sepsis, with 2 enrolling patients with severe sepsis, 1 enrolling patients with septic shock and 1 enrolling patients with cirrhosis and sepsis-induced hypotension. Regarding risk of bias, 1 study was deemed as having a low risk of bias, 2 studies had some concerns for bias and 1 had a high risk of bias (mostly derived from bias in measuring outcomes).

Regarding outcomes, the authors looked at 28-day mortality, need for renal replacement therapy (RRT), duration of mechanical ventilation (MV) and duration of shock.

There was no significant reduction in 28-day mortality in patients with sepsis – odds ratio (OR) 0.95, 95% confidence interval (CI) 0.8–1.12.

However, when studies and subgroups including only patients with septic shock were analyzed, a significant reduction in mortality was noted (OR 0.82, 95% CI 0.68–0.98). The study heterogeneity was low in both of the aforementioned analyses. The authors graded the certainty of evidence for 28-day mortality in patients with sepsis as low, owing to lack of blinding in the included trials and the fact that the largest point estimates came from the smallest trials. They also noted that a certain amount of publication bias is possible, as demonstrated by an asymmetrical funnel plot. Due to one of the studies using 6% starch infusions as the control arm, which may increase mortality, a sensitivity analysis was also conducted, excluding the study using starch, with the results remaining consistent and robust despite the exclusion.

On the other hand, evidence of 28-day mortality for patients with septic shock was graded as moderate, with the authors noting more consistent and precise point estimates in this patient subgroup.

Regarding renal outcomes, no significant difference was found between groups regarding the need for RRT (OR 0.91, 95% CI 0.45–1.85).

A significant reduction in cumulative fluid balance (CFB) of up to 1.9 liters was found when using hyperoncotic albumin. However, since the follow-up period for measuring the CFB ranged from 1 to 7 days, this finding could not be reliably quantified and its certainty was graded as very low.

Data on duration of mechanical ventilation and time to resolution of shock could also not be reliably quantified nor pooled due to a high degree of inter-study heterogeneity regarding measurements and definitions of shock resolution. However, when analyzed individually, the studies demonstrated no significant difference in the duration of MV between groups, while showing a shorter time to shock resolution and lower vasopressor requirements (measured by either dose or time spent receiving a pressor).

To conclude, there seems to be a signal of mortality benefit of hyperoncotic albumin in patients with septic shock, according to data pooled from the available RCTs. However, before changing anyone’s practice, this finding should be confirmed by a high-quality robust RCT, which should also seek to answer the question of optimal dosing of hyperoncotic albumin in this patient population.

That’s it for this week, stay safe and keep reading.





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