Early Treatment with IgM-enriched Intravenous Immunoglobulin Does Not Mitigate Critical Illness Polyneuropathy And/or Myopathy in Patients with Multiple Organ Failure and SIRS/sepsis: a Prospective, Randomized, Placebo-controlled, Double-blinded...

Overview

Journal Crit Care

Specialty Critical Care

Date 2013 Oct 4

PMID 24088271

Citations 11

Authors

Richard Brunner

Walter Rinner

Christine Haberler

Reinhard Kitzberger

Thomas Sycha

Harald Herkner

Joanna Warszawska

Christian Madl

Ulrike Holzinger

Affiliations

Soon will be listed here.

Abstract

Introduction: Critical illness polyneuropathy and/or myopathy (CIPNM) is a severe complication of critical illness. Retrospective data suggest that early application of IgM-enriched intravenous immunoglobulin (IVIG) may prevent or mitigate CIPNM. Therefore, the primary objective was to assess the effect of early IgM-enriched IVIG versus placebo to mitigate CIPNM in a prospective setting.

Methods: In this prospective, randomized, double-blinded and placebo-controlled trial, 38 critically ill patients with multiple organ failure (MOF), systemic inflammatory response syndrome (SIRS)/sepsis, and early clinical signs of CIPNM were included. Patients were randomly assigned to be treated either with IgM-enriched IVIG or placebo over a period of three days. CIPNM was measured by the CIPNM severity sum score based on electrophysiological stimulation of the median, ulnar, and tibial nerves on days 0, 4, 7, 14 and on the histological evaluation of muscle biopsies on days 0 and 14 and ranged from 0 (no CIPNM) to 8 (very severe CIPNM).

Results: A total of 38 critically ill patients were included and randomized to receive either IgM-enriched IVIG (n = 19) or placebo (n = 19). Baseline characteristics were similar between the two groups. CIPNM could not be improved by IVIG treatment, represented by similar CIPNM severity sum scores on day 14 (IVIG vs. placebo: 4.8 ± 2.0 vs. 4.5 ± 1.8; P = 0.70). CIPNM severity sum score significantly increased from baseline to day 14 (3.5 ± 1.6 vs. 4.6 ± 1.9; P = 0.002). After an interim analysis the study was terminated early due to futility in reaching the primary endpoint.

Conclusions: Early treatment with IVIG did not mitigate CIPNM in critically ill patients with MOF and SIRS/sepsis.

Trial Registration: Clinicaltrials.gov: NCT01867645.

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References

Bolton C, Young G, Zochodne D . The neurological complications of sepsis. Ann Neurol. 1993; 33(1):94-100. DOI: 10.1002/ana.410330115. View

Routsi C, Gerovasili V, Vasileiadis I, Karatzanos E, Pitsolis T, Tripodaki E . Electrical muscle stimulation prevents critical illness polyneuromyopathy: a randomized parallel intervention trial. Crit Care. 2010; 14(2):R74. PMC: 2887197. DOI: 10.1186/cc8987. View

De Letter M, van Doorn P, Savelkoul H, Laman J, Schmitz P, Op de Coul A . Critical illness polyneuropathy and myopathy (CIPNM): evidence for local immune activation by cytokine-expression in the muscle tissue. J Neuroimmunol. 2000; 106(1-2):206-13. DOI: 10.1016/s0165-5728(99)00252-0. View

Norrby-Teglund A, Haque K, Hammarstrom L . Intravenous polyclonal IgM-enriched immunoglobulin therapy in sepsis: a review of clinical efficacy in relation to microbiological aetiology and severity of sepsis. J Intern Med. 2006; 260(6):509-16. DOI: 10.1111/j.1365-2796.2006.01726.x. View

Tennila A, Salmi T, Pettila V, Roine R, Varpula T, Takkunen O . Early signs of critical illness polyneuropathy in ICU patients with systemic inflammatory response syndrome or sepsis. Intensive Care Med. 2000; 26(9):1360-3. DOI: 10.1007/s001340000586. View

Hermans G, Wilmer A, Meersseman W, Milants I, Wouters P, Bobbaers H . Impact of intensive insulin therapy on neuromuscular complications and ventilator dependency in the medical intensive care unit. Am J Respir Crit Care Med. 2006; 175(5):480-9. DOI: 10.1164/rccm.200605-665OC. View

Koch S, Spuler S, Deja M, Bierbrauer J, Dimroth A, Behse F . Critical illness myopathy is frequent: accompanying neuropathy protracts ICU discharge. J Neurol Neurosurg Psychiatry. 2010; 82(3):287-93. DOI: 10.1136/jnnp.2009.192997. View

W Sander H, Golden M, Danon M . Quadriplegic areflexic ICU illness: selective thick filament loss and normal nerve histology. Muscle Nerve. 2002; 26(4):499-505. DOI: 10.1002/mus.10233. View

van Doorn P, Kuitwaard K, Walgaard C, van Koningsveld R, Ruts L, Jacobs B . IVIG treatment and prognosis in Guillain-Barré syndrome. J Clin Immunol. 2010; 30 Suppl 1:S74-8. PMC: 2883091. DOI: 10.1007/s10875-010-9407-4. View

10.

Guarneri B, Bertolini G, Latronico N . Long-term outcome in patients with critical illness myopathy or neuropathy: the Italian multicentre CRIMYNE study. J Neurol Neurosurg Psychiatry. 2008; 79(7):838-41. DOI: 10.1136/jnnp.2007.142430. View

11.

Latronico N, Bolton C . Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis. Lancet Neurol. 2011; 10(10):931-41. DOI: 10.1016/S1474-4422(11)70178-8. View

12.

Rich M, Bird S, Raps E, McCluskey L, Teener J . Direct muscle stimulation in acute quadriplegic myopathy. Muscle Nerve. 1997; 20(6):665-73. DOI: 10.1002/(sici)1097-4598(199706)20:6<665::aid-mus2>3.0.co;2-6. View

13.

Berlot G, Dimastromatteo G . Use of IgM and IgA-enriched immunoglobulins in the treatment of severe sepsis and septic shock. Clinical experience. Minerva Anestesiol. 2004; 70(10):739-43. View

14.

Bednarik J, Vondracek P, Dusek L, Moravcova E, Cundrle I . Risk factors for critical illness polyneuromyopathy. J Neurol. 2005; 252(3):343-51. DOI: 10.1007/s00415-005-0654-x. View

15.

Sapir T, Shoenfeld Y . Facing the enigma of immunomodulatory effects of intravenous immunoglobulin. Clin Rev Allergy Immunol. 2006; 29(3):185-99. DOI: 10.1385/CRIAI:29:3:185. View

16.

Latronico N, Tomelleri G, Filosto M . Critical illness myopathy. Curr Opin Rheumatol. 2012; 24(6):616-22. DOI: 10.1097/BOR.0b013e3283588d2f. View

17.

Fenzi F, Latronico N, Refatti N, Rizzuto N . Enhanced expression of E-selectin on the vascular endothelium of peripheral nerve in critically ill patients with neuromuscular disorders. Acta Neuropathol. 2003; 106(1):75-82. DOI: 10.1007/s00401-003-0704-3. View

18.

Gruther W, Benesch T, Zorn C, Paternostro-Sluga T, Quittan M, Fialka-Moser V . Muscle wasting in intensive care patients: ultrasound observation of the M. quadriceps femoris muscle layer. J Rehabil Med. 2008; 40(3):185-9. DOI: 10.2340/16501977-0139. View

19.

Tugrul S, Ozcan P, Akinci O, Seyhun Y, Cagatay A, Cakar N . The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis [ISRCTN28863830]. Crit Care. 2002; 6(4):357-62. PMC: 125317. DOI: 10.1186/cc1523. View

20.

Hund E . Neurological complications of sepsis: critical illness polyneuropathy and myopathy. J Neurol. 2002; 248(11):929-34. DOI: 10.1007/s004150170043. View