High Spinal Anesthesia Enhances Anti-Inflammatory Responses in Patients Undergoing Coronary Artery Bypass Graft Surgery and Aortic Valve Replacement: Randomized Pilot Study

Abstract

Background: Cardiac surgery induces many physiologic changes including major inflammatory and sympathetic nervous system responses. Here, we conducted a single-centre pilot study to generate hypotheses on the potential immune impact of adding high spinal anaesthesia to general anaesthesia during cardiac surgery in adults. We hypothesized that this strategy, previously shown to blunt the sympathetic response and improve pain management, could reduce the undesirable systemic inflammatory responses caused by cardiac surgery.

Methods: This prospective randomized unblinded pilot study was conducted on 14 patients undergoing cardiac surgery for coronary artery bypass grafting and/or aortic valve replacement secondary to severe aortic stenosis. The primary outcome measures examined longitudinally were serum pro-inflammatory (IL-6, IL-1b, CCL2), anti-inflammatory (IL-10, TNF-RII, IL-1Ra), acute phase protein (CRP, PTX3) and cardiovascular risk (sST2) biomarkers.

Results: The kinetics of pro- and anti-inflammatory biomarker was determined following surgery. All pro-inflammatory and acute phase reactant biomarker responses induced by surgical stress were indistinguishable in intensity and duration between control groups and those who also received high spinal anaesthesia. Conversely, IL-10 levels were markedly elevated in both intensity and duration in the group receiving high spinal anesthesia (p = 0.005).

Conclusions: This hypothesis generating pilot study suggests that high spinal anesthesia can alter the net inflammatory response that results from cardiac surgery. In appropriately selected populations, this may add incremental benefit by dampening the net systemic inflammatory response during the week following surgery. Larger population studies, powered to assess immune, physiologic and clinical outcomes in both acute and longer term settings, will be required to better assess potential benefits of incorporating high spinal anesthesia.

Trial registration: ClinicalTrials.gov NCT00348920.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. CONSORT flow diagram of the study

Fig 2. Kinetics of in vivo chemokine, cytokine and acute phase protein responses following CABG.

Serum obtained at baseline and the time points indicated was analysed as described at Materials and Methods to assess response kinetics for each biomarker individually. All levels are compared to baseline/study entry conditions. Median responses and statistical significance (Wilcoxon) of longitudinal comparisons relative to pre-induction baseline are shown.

Fig 3. Magnitude and duration of systemic pro-inflammatory cytokine responses in individuals receiving supplemental HSA.

Median values are shown for groups receiving HSA plus general anesthetic (open bars) or general anesthetic alone (solid bars). P values reflect inter-group comparisions using Mann-Whitney at the time points indicated.

Fig 4. Anti-inflammatory responses of individuals receiving supplemental HSA.

Median values are shown for HSA plus general anesthetic (open bars) vs general anesthetic alone (solid bars). P values reflect inter-group Mann Whitney comparisions at the time points indicated.

Fig 5. Acute phase protein responses in CABG patients receiving HSA/GA vs general anesthetic alone.

Individuals received HSA plus general anesthetic (open) or general anesthetic alone (solid). P values reflect statistical significance (Mann Whitney).