Clinical Investigations

The Clinical Picture of Severe Systemic Capillary-Leak Syndrome Episodes Requiring ICU Admission

Pineton de Chambrun, Marc MD, MSc^1,2; Luyt, Charles-Edouard MD, PhD²; Beloncle, François MD, MSc³; Gousseff, Marie MD⁴; Mauhin, Wladimir MD, MSc¹; Argaud, Laurent MD, PhD⁵; Ledochowski, Stanislas MD^6,7; Moreau, Anne-Sophie MD⁸; Sonneville, Romain MD, PhD⁹; Verdière, Bruno MD¹⁰; Merceron, Sybille MD¹¹; Zappella, Nathalie MD¹¹; Landais, Mickael MD¹²; Contou, Damien MD¹³; Demoule, Alexandre MD, PhD¹⁴; Paulus, Sylvie MD¹⁵; Souweine, Bertrand MD, PhD¹⁶; Lecomte, Bernard MD¹⁷; Vieillard-Baron, Antoine MD, PhD¹⁸; Terzi, Nicolas MD, PhD¹⁹; Azoulay, Elie MD, PhD²⁰; Friolet, Raymond MD²¹; Puidupin, Marc MD²²; Devaquet, Jérôme MD²³; Mazou, Jean-Marc MD²⁴; Fedun, Yannick MD²⁵; Mira, Jean-Paul MD, PhD²⁶; Raphalen, Jean-Herlé MD²⁷; Combes, Alain MD, PhD²; Amoura, Zahir MD, MSc¹

Author Information

¹Service de Médecine Interne 2, Centre Hospitalier Universitaire (CHU) La Pitié–Salpêtrière, Université Paris 6, APHP, Paris, France.

²Service de Réanimation Médicale, CHU La Pitié–Salpêtrière, Université Paris 6, APHP, Paris, France.

³Service de Réanimation Médicale, CHU d’Angers, Angers, France.

⁴Service de Médecine Interne, CH Bretagne Atlantique, Vannes, France.

⁵Service de Réanimation Médicale, CHU Edouard-Herriot, Lyon, France.

⁶Service de Réanimation, CHU Lyon-Sud, Pierre-Bénite, France.

⁷Service de Réanimation Polyvalente, CH Pierre Oudot, Bourgoin Jallieu, France.

⁸Service de Réanimation Médicale, CHRU Lille, Lille, France.

⁹Service de Réanimation Médicale, CHU Bichat, APHP, Paris, France.

¹⁰Service de Réanimation Polyvalente, Hôpital Delafontaine, Saint-Denis, France.

¹¹Service de Réanimation Polyvalente, CH André-Mignot, Le Chesnay, France.

¹²Service de Réanimation Médicale, CHU Hôtel-Dieu, Nantes, France.

¹³Service de Réanimation Médicale, CHU Henri-Mondor, APHP, Créteil, France.

¹⁴Service de Pneumologie et de Réanimation Médicale, CHU La Pitié–Salpêtrière, APHP, Paris, France.

¹⁵Service de Réanimation Chirurgicale, CHU Lyon-Est, Hôpital Louis-Pradel, Bron, France.

¹⁶Service de Réanimation Médicale, Hôpital Gabriel-Montpied, CHU Clermont-Ferrand, Clermont-Ferrand, France.

¹⁷Service de Réanimation Polyvalente, CH Notre-Dame de la Miséricorde, Ajaccio, France.

¹⁸Service de Réanimation Médicale, CHU Ambroise-Paré, APHP, Boulogne-Billancourt, France.

¹⁹Service de Réanimation Médicale, CHU Grenoble, Grenoble, France.

²⁰Service de Réanimation Médicale, CHU Saint-Louis, APHP, Paris, France.

²¹Service de Réanimation, Hôpital du Valais-Institut Central, Sion, Switzerland.

²²Service de Réanimation, Hôpital d’Instruction des Armées Desgenettes, Lyon, France.

²³Service de Réanimation Polyvalente, CH Foch, Suresnes, France.

²⁴Service de Réanimation, CH Dax, Dax, France.

²⁵Service de Réanimation Polyvalente, CH Bretagne Atlantique, Vannes, France.

²⁶Service de Réanimation Médicale, CHU Cochin, APHP, Paris, France.

²⁷Service de Réanimation Adulte, CHU Necker–Enfants Malades, APHP, Paris, France.

Members of the EurêClark Study Group are listed in Appendix 1 (Supplemental Digital Content 1, https://links.lww.com/CCM/C646).

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Dr. Luyt received funding from Bayer Healthcare and Merck Sharp and Dohme (MSD). Dr. Demoule’s institution received funding from Philips, and he received funding from Medtronic, MSD, Maquet, Covidien, Philips, Drager, Resmed, Fisher & Paykel. Dr. Azoulay’s institution received funding from MSD, Pfizer, Gilead, Fisher & Paykel, Alexion, and Basilea; he received funding from Gilead Sciences (board meeting) and funding for lectures from Astellas, Gilead, and Alexion; and he received support for article research from Assistance Publique - Hôpitaux de Paris France. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: [email protected]

Critical Care Medicine 45(7):p 1216-1223, July 2017. | DOI: 10.1097/CCM.0000000000002496

Abstract

Objective:

Systemic capillary-leak syndrome is a very rare cause of recurrent hypovolemic shock. Few data are available on its clinical manifestations, laboratory findings, and outcomes of those patients requiring ICU admission. This study was undertaken to describe the clinical pictures and ICU management of severe systemic capillary-leak syndrome episodes.

Design, Setting, Patients:

This multicenter retrospective analysis concerned patients entered in the European Clarkson’s disease (EurêClark) Registry and admitted to ICUs between May 1992 and February 2016.

Measurements and Main Results:

Fifty-nine attacks occurring in 37 patients (male-to-female sex ratio, 1.05; mean ± sd age, 51 ± 11.4 yr) were included. Among 34 patients (91.9%) with monoclonal immunoglobulin G gammopathy, 20 (58.8%) had kappa light chains. ICU-admission hemoglobin and proteinemia were respectively median (interquartile range) 20.2 g/dL (17.9–22 g/dL) and 50 g/L (36.5–58.5 g/L). IV immunoglobulins were infused (IV immunoglobulin) during 15 episodes (25.4%). A compartment syndrome developed during 12 episodes (20.3%). Eleven (18.6%) in-ICU deaths occurred. Bivariable analyses (the 37 patients’ last episodes) retained Sequential Organ-Failure Assessment score greater than 10 (odds ratio, 12.9 [95% CI, 1.2–140]; p = 0.04) and cumulated fluid-therapy volume greater than 10.7 L (odds ratio, 16.8 [1.6–180]; p = 0.02) as independent predictors of hospital mortality.

Conclusions:

We described the largest cohort of severe systemic capillary-leak syndrome flares requiring ICU admission. High-volume fluid therapy was independently associated with poorer outcomes. IV immunoglobulin use was not associated with improved survival; hence, their use should be considered prudently and needs further evaluation in future studies.