C1-Inhibitor substitution as ultima ratio therapy in septic shock: experience with 15 patients

Introduction

Plasma C1-Inhibitor (C1-INH) is the major inhibitor of both the classical pathway of complement system and contact activation. A relative deficiency of C1-INH has been proposed as an important contributor to the development of shock and organ failure [1,2]. Among others, our working group has published two cases of successful C1-INH substitution in septic patients recently [3].

Methods

In a retrospective study we investigated data of 15 patients with septic shock who received C1-INH concentrate as ultima ratio therapy. The mean substitutional dosage of C1-INH concentrate (Berinert HS', Centeon) was 10.300 units. Mean values for C1-INH activity, antigenic C1-INH level, fluid balance, hemodynamic and respiratory parameters were compared 24 h prior to 96 h after C1-INH administration.

Results

After substitutional therapy the antigenic C1-INH level increased significantly (from 159 to 228%) while the functional C1-INH activity did not change statistically. The daily fluid balance decreased from +2695 to -186 ml/24 h (P = 0.05), hemodynamic parameters were not affected. There was a good tendency towards higher arterial-to-inspired oxygen ratios (P = 0.55) after C1-INH administration.

Conclusion

Our data show significantly higher antigenic C1-INH levels after substitutional therapy but no difference in C1-INH functional activity. This may be due to complex formation of C1-INH with its target proteases. Prior to C1-INH administration the patients had positive fluid balances and impaired arterial-to-inspired oxygen ratios. If This is looked upon as an equivalent to capillary leakage these results encourage to perform a randomised controlled study on C1-INH substitution in septic patients.