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Vasostatin-I, a chromogranin A-derived peptide, in non-selected critically ill patients: distribution, kinetics, and prognostic significance

Intensive Care Medicine volume 38, pages 1514–1522 (2012)Cite this article

Abstract

Purpose

Chromogranin A (CGA) is released in the plasma during life-threatening illnesses. Its N-terminal 1–76 peptide, vasostatin-I (VS-I), has never been assessed in critically ill patients. Our aim was to examine whether the admission VS-I concentration has prognostic significance without having to specify a primary diagnosis.

Methods

VS-I concentrations were assessed with a new ELISA in 481 consecutive patients and 13 healthy controls. CGA and standard biological tests (including lactate) were performed; the simplified acute physiological score II (SAPS II) was calculated. Mortality was assessed at day 28. In a subgroup of 13 patients with shock, serial VS-I doses were given over 60 h.

Results

Critically ill patients had higher admission VS-I concentrations than controls [4.06 (2.78; 7.61) vs. 2.85 (2.47; 3.22) ng/ml, p < 0.001]. The plasma VS-I concentration was significantly lower in survivors than in non-survivors [3.70 (2.67; 6.12) vs. 5.75 (3.65; 11.20) ng/ml] and in the absence of shock [3.58 (2.59; 5.05) vs. 5.93 (3.30; 11.06) ng/ml, p < 0.001]. The survival rate was better in patients with VS-I concentrations under the median value of 3.97 ng/ml (p < 0.001). Admission VS-I and lactate values were independent predictors of mortality (p < 0.01). Moreover, taking them together, combined with age, provided a better indication for predicting mortality than taking each alone (p < 0.01).

Conclusions

Significant amounts of VS-I are detected on admission in critically ill patients. A plasma VS-I concentration above 3.97 ng/ml is associated with poor outcome, and in routine practice simultaneous measurements of the three independent factors VS-I, lactate and age can affect the assessment of severity.

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Acknowledgments

The authors thank the University of Strasbourg, the hospital Hautepierre, the Inserm and the ANR for financial support. Cisbio Bioassays Research and Development (Bagnols/Cèze, France) provided the Elisa kit required for VS1–76 doses free of charge. This study was also supported by a grant from the French National Research Agency (ANR-08-BIOT-006, for Cisbio bioassays, Bagnols/Cèze, France), INSERM research unit U977 (Strasbourg, France) and the University Hospital of Strasbourg (Strasbourg, France) as partners. The sponsors took full administrative responsibility, but had no role in the design of the study; recruitment of patients; management, analysis or interpretation of the data; or the preparation, review or approval of the article. F. Schneider acknowledges the logistical help of the Centre d’Investigation Clinique, Hôpitaux Universitaires de Strasbourg, France.

Conflicts of interest

All the authors state that they have no conflicts of interest to declare.

Author information

Affiliations

  1. Service de Réanimation Médicale, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg and INSERM U977, Université de Strasbourg, Strasbourg, France

    Francis Schneider & Thierry Lavigne

  2. Laboratoire des Biomatériaux et Ingéniérie Tissulaire, INSERM U977, Université de Strasbourg, Strasbourg, France

    Charlotte Bach, Thomas Lavaux & Marie-Hélène Metz-Boutigue

  3. Cisbio Bioassays, Codolet, France

    Hélène Chung & Patrick Garnero

  4. Service de Réanimation Médicale, Hôpital Central, Faculté de Médecine, Université de Nancy, Nancy, France

    Pierre-Edouard Bollaert

  5. Service de Réanimation Médicale et des Maladies Infectieuses, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France

    Michel Wolff

  6. Department of Biological and Technological Research, San Raffaele H. Scientific Institute, Milan, Italy

    Luca Crippa & Angelo Corti

  7. Service de Réanimation Chirurgicale, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    Anne Launoy

  8. Service de Réanimation Médicale, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France

    Xavier Delabranche

  9. Laboratoire de Biostatistique et Informatique Médicale, Faculté de Médecine de Strasbourg Université de Strasbourg, Strasbourg, France

    Nicolas Meyer

  10. INSERM U977 Biomatériaux et ingéniérie tissulaire, Institut Leriche 2ème étage, Hôpital Civil, Porte de l’Hôpital, BP 426, 67091, Strasbourg, France

    Marie-Hélène Metz-Boutigue

Authors
  1. Francis Schneider
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  2. Charlotte Bach
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  7. Michel Wolff
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  8. Angelo Corti
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  12. Nicolas Meyer
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  14. Marie-Hélène Metz-Boutigue
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Corresponding author

Correspondence to Marie-Hélène Metz-Boutigue.

Additional information

Charlotte Bach and Hélène Chung contributed equally.

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Appendices

Appendix 1

Main causes of referral of patients.

  • In the no SIRS no infection group: neurological causes (ischemic or hemorrhagic stroke and status epilepticus 28 %); acute respiratory failure 27 % (including alveolar hypoventilation in COPD and acute cardiogenic pulmonary edema); self-poisoning with or without alcohol 25 %; metabolic causes 9.5 % (including acute renal failure); miscellaneous 9.5 %.

  • In the SIRS group: acute respiratory failure 28 %; emergency abdominal surgery 19 %; out-of-hospital cardiac arrest 17 %; self-poisoning with aspiration 11 %; metabolic causes 10 %; miscellaneous 15 % (including mild liver failure and/or pancreatitis).

  • In the severe SIRS group: out-of-hospital cardiac arrest 22 %; emergency surgery 20 %; acute respiratory failure 17 % (including mostly ARDS of non-infectious cause); neurological causes 11 %; miscellaneous 30 % (including severe acute liver failure and pancreatitis).

Appendix 2

Kaplan-Meier survival curve (28 days) according to the median admission VS-I value.

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Schneider, F., Bach, C., Chung, H. et al. Vasostatin-I, a chromogranin A-derived peptide, in non-selected critically ill patients: distribution, kinetics, and prognostic significance. Intensive Care Med 38, 1514–1522 (2012). https://doi.org/10.1007/s00134-012-2611-3

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Keywords

  • Chromogranin A
  • Critically ill
  • Outcome
  • Lactate
  • SAPS II
  • Vasostatin