Effects of interventions targeting the systemic inflammatory response to cardiac surgery on clinical outcomes in adults

Key messages

- We are unsure of the benefits of anti-inflammatory interventions after cardiac surgery.

- Further research should explore the role of factors such as age and chronic conditions on the response to anti-inflammatory interventions.

What is the relation between inflammatory response and organ damage after cardiac surgery?

Following cardiac surgery, different organs can be damaged, leading to serious complications, and sometimes death. We still do not clearly know how to prevent this. Some authors think that by reducing an excess of inflammatory response (SIRS, systemic inflammatory response syndrome) with which our body reacts to the surgery we might be able to reduce organ damage. This has been tested in several scientific studies, but results are not conclusive. SIRS is observed in over 80% of patients undergoing major surgery, and in a range between 28.3% to 96.2% in the specific case of heart surgery.

What did we want to find out?

We wanted to understand if reducing the inflammatory response after cardiac surgery had a clinical benefit.

What did we do?

We conducted this review to summarise the results from these studies, by searching databases containing reports of ongoing and completed studies from the last 30 years. We included only studies conducted in adult patients.

What did we find?

Results from 328 studies including 40,255 patients are hereby presented. The effect on inflammatory activity (measured via the level of the main signals circulated in our blood) was not clearly changed. Mortality, on the other hand, was reduced in these studies, although this effect could not be confirmed when we repeated our calculations in the studies conducted at the highest quality standard exclusively. Other signs of inflammation and organ damage were not clearly changed.

In conclusion, further studies are needed before we can understand whether, by targeting inflammation, we can prevent organ damage.

What are the limitations of the evidence?

Our work show inconsistencies in the conclusions of these studies and issues in some of the methods adopted that reduce the confidence in the result of our analysis.

How up-to-date is this evidence?

The evidence is updated to October 2022.

Authors' conclusions: 

A systematic review of RCTs of organ protection interventions targeting innate immune system activation did not resolve uncertainty as to the effectiveness of these treatments, or the role of innate immunity in organ injury following cardiac surgery.

Read the full abstract...

Organ injury is a common and severe complication of cardiac surgery that contributes to the majority of deaths. There are no effective treatment or prevention strategies. It has been suggested that innate immune system activation may have a causal role in organ injury. A wide range of organ protection interventions targeting the innate immune response have been evaluated in randomised controlled trials (RCTs) in adult cardiac surgery patients, with inconsistent results in terms of effectiveness.


The aim of the review was to summarise the results of RCTs of organ protection interventions targeting the innate immune response in adult cardiac surgery. The review considered whether the interventions had a treatment effect on inflammation, important clinical outcomes, or both.

Search strategy: 

CENTRAL, MEDLINE, Embase, conference proceedings and two trial registers were searched on October 2022 together with reference checking to identify additional studies.

Selection criteria: 

RCTs comparing organ protection interventions targeting the innate immune response versus placebo or no treatment in adult patients undergoing cardiac surgery where the treatment effect on innate immune activation and on clinical outcomes of interest were reported.

Data collection and analysis: 

Searches, study selection, quality assessment, and data extractions were performed independently by pairs of authors. The primary inflammation outcomes were peak IL-6 and IL-8 concentrations in blood post-surgery. The primary clinical outcome was in-hospital or 30-day mortality. Treatment effects were expressed as risk ratios (RR) and standardised mean difference (SMD) with 95% confidence intervals (CI). Meta-analyses were performed using random effects models, and heterogeneity was assessed using I2.

Main results: 

A total of 40,255 participants from 328 RCTs were included in the synthesis. The effects of treatments on IL-6 (SMD -0.77, 95% CI -0.97 to -0.58, I2 = 92%) and IL-8 (SMD -0.92, 95% CI -1.20 to -0.65, I2 = 91%) were unclear due to heterogeneity. Heterogeneity for inflammation outcomes persisted across multiple sensitivity and moderator analyses. The pooled treatment effect for in-hospital or 30-day mortality was RR 0.78, 95% CI 0.68 to 0.91, I2 = 0%, suggesting a significant clinical benefit. There was little or no treatment effect on mortality when analyses were restricted to studies at low risk of bias. Post hoc analyses failed to demonstrate consistent treatment effects on inflammation and clinical outcomes. Levels of certainty for pooled treatment effects on the primary outcomes were very low.