Skip to main content

Advertisement

Log in

Infusions of rocuronium and cisatracurium exert different effects on rat diaphragm function

  • Experimental
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Objective

Aminosteroidal and benzylisoquinoline neuromuscular blocking agents are used in the intensive care unit to facilitate mechanical ventilation. The use of these agents has been associated with development of critical illness myopathy; however, the relative frequency of myopathy development among agents is not known. The aim of our study was to compare the effects of 24 h infusion of rocuronium or cisatracurium on the diaphragm in mechanically ventilated rats.

Design

Randomized, controlled experiment.

Setting

Basic animal science laboratory.

Subjects

Male Wistar rats, 14 weeks old.

Interventions

Rats were divided into four groups to receive either saline, rocuronium (low dose) or cisatracurium (low or high dose).

Measurements and results

After 24 h, in vitro diaphragm tetanic force was decreased after rocuronium (–33% vs. saline), while the force was more preserved after cisatracurium, even in the high-dose group. Cross-sectional areas of the different diaphragm and gastrocnemius fibers were unaltered. Diaphragmatic MURF-1 mRNA was increased after rocuronium (+44% vs. saline), while unchanged in both cisatracurium groups. Calpain activity was increased after rocuronium (+75% vs. saline) and unchanged in the cisatracurium groups. MURF-1 mRNA expression and calpain activity were negatively correlated with diaphragm force.

Conclusions

Cisatracurium infusion during controlled mechanical ventilation exerted less detrimental effects on diaphragm function and proteolytic activity than infusion of rocuronium, even with the higher effective dose. These data suggest that increased calpain activity and increased activation of the ubiquitin proteasome system play a role in the different effects of these agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Murray MJ, Cowen J, DeBlock H, Erstad B, Gray AW Jr, Tescher AN, McGee WT, Prielipp RC, Susla G, Jacobi J, Nasraway SA Jr, Lumb PD (2002) Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med 30:142–156

    Article  CAS  PubMed  Google Scholar 

  2. Arroliga A, Frutos-Vivar F, Hall J, Esteban A, Apezteguia C, Soto L, Anzueto A (2005) Use of sedatives and neuromuscular blockers in a cohort of patients receiving mechanical ventilation. Chest 128:496–506

    Article  PubMed  Google Scholar 

  3. Sessler CN (2005) Sedation, analgesia, and neuromuscular blockade for high-frequency oscillatory ventilation. Crit Care Med 33:S209–S216

    Article  CAS  PubMed  Google Scholar 

  4. Moore EW, Hunter JM (2001) The new neuromuscular blocking agents: do they offer any advantages? Br J Anaesth 87:912–925

    Article  CAS  PubMed  Google Scholar 

  5. De Jonghe B, Bastuji-Garin S, Sharshar T, Outin H, Brochard L (2004) Does ICU-acquired paresis lengthen weaning from mechanical ventilation? Intensive Care Med 30:1117–1121

    Article  PubMed  Google Scholar 

  6. Olivieri L, Plourde G (2005) Prolonged (more than ten hours) neuromuscular blockade after cardiac surgery: report of two cases. Can J Anaesth 52:88–93

    Article  PubMed  Google Scholar 

  7. Davis NA, Rodgers JE, Gonzalez ER, Fowler AA III (1998) Prolonged weakness after cisatracurium infusion: a case report. Crit Care Med 26:1290–1292

    Article  CAS  PubMed  Google Scholar 

  8. Tousignant CP, Bevan DR, Eisen AA, Fenwick JC, Tweedale MG (1995) Acute quadriparesis in an asthmatic treated with atracurium. Can J Anaesth 42:224–227

    Article  CAS  PubMed  Google Scholar 

  9. Leatherman JW, Fluegel WL, David WS, Davies SF, Iber C (1996) Muscle weakness in mechanically ventilated patients with severe asthma. Am J Respir Crit Care Med 153:1686–1690

    Article  CAS  PubMed  Google Scholar 

  10. Gehr LC, Sessler CN (2001) Neuromuscular blockade in the intensive care unit. Semin Respir Crit Care Med 22:175–188

    Article  CAS  PubMed  Google Scholar 

  11. Gayan-Ramirez G, Decramer M (2002) Effects of mechanical ventilation on diaphragm function and biology. Eur Respir J 20:1579–1586

    Article  CAS  PubMed  Google Scholar 

  12. Jaber S, Sebbane M, Koechlin C, Hayot M, Capdevila X, Eledjam JJ, Prefaut C, Ramonatxo M, Matecki S (2005) Effects of short vs. prolonged mechanical ventilation on antioxidant systems in piglet diaphragm. Intensive Care Med 31:1427–1433

    Article  PubMed  Google Scholar 

  13. Testelmans D, Maes K, Wouters P, Gosselin N, Deruisseau K, Powers S, Sciot R, Decramer M, Gayan-Ramirez G (2006) Rocuronium exacerbates mechanical ventilation-induced diaphragm dysfunction in rats. Crit Care Med 34:3018–3023

    Article  CAS  PubMed  Google Scholar 

  14. Laghi F, Tobin MJ (2003) Disorders of the respiratory muscles. Am J Respir Crit Care Med 168:10–48

    Article  PubMed  Google Scholar 

  15. Testelmans D, Maes K, Wouters P, Decramer M, Gayan-Ramirez G (2006) Different effects of two families of neuromuscular blocking agents on rat diaphragm function during controlled mechanical ventilation. Proc Am Thoracic Soc [Abstract] 3:A137

    Google Scholar 

  16. Gayan-Ramirez G, De Paepe K, Cadot P, Decramer M (2003) Detrimental effects of short-term mechanical ventilation on diaphragm function and IGF-I mRNA in rats. Intensive Care Med 29:825–833

    Article  PubMed  Google Scholar 

  17. Dekhuijzen PN, Gayan-Ramirez G, de Bock V, Dom R, Decramer M (1993) Triamcinolone and prednisolone affect contractile properties and histopathology of rat diaphragm differently. J Clin Invest 92:1534–1542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Takamure M, Murata KY, Tamada Y, Azuma M, Ueno S (2005) Calpain-dependent alpha-fodrin cleavage at the sarcolemma in muscle diseases.Muscle Nerve 32:303–309

    Article  CAS  PubMed  Google Scholar 

  19. Kent MP, Veiseth E, Therkildsen M, Koohmaraie M (2005) An assessment of extraction and assay techniques for quantification of calpain and calpastatin from small tissue samples. J Anim Sci 83:2182–2188

    Article  CAS  PubMed  Google Scholar 

  20. Czogalla A, Sikorski AF (2005) Spectrin and calpain: a `target' and a `sniper' in the pathology of neuronal cells. Cell Mol Life Sci 62:1913–1924

    Article  CAS  PubMed  Google Scholar 

  21. Booij LH (2001) Is succinylcholine appropriate or obsolete in the intensive care unit? Crit Care 5:245–246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Whetstone Foster JG, Clark AP (2006) Functional recovery after neuromuscular blockade in mechanically ventilated critically ill patients. Heart Lung 35:178–189

    Article  PubMed  Google Scholar 

  23. Prielipp RC, Coursin DB, Wood KE, Murray MJ (1995) Complications associated with sedative and neuromuscular blocking drugs in critically ill patients. Crit Care Clin 11:983–1003

    CAS  PubMed  Google Scholar 

  24. De Jonghe B, Sharshar T, Lefaucheur JP, Authier FJ, Durand-Zaleski I, Boussarsar M, Cerf C, Renaud E, Mesrati F, Carlet J, Raphael JC, Outin H Bastuji-Garin S (2002) Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA 288:2859–2867

    Article  PubMed  Google Scholar 

  25. Filatov GN, Rich MM (2004) Hyperpolarized shifts in the voltage dependence of fast inactivation of Nav1.4 and Nav1.5 in a rat model of critical illness myopathy. J Physiol 559:813–820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Murray MJ, Brull SJ, Bolton CF (2006) Brief review: Nondepolarizing neuromuscular blocking drugs and critical illness myopathy. Can J Anaesth 53:1148–1156

    Article  PubMed  Google Scholar 

  27. Gutmann L, Blumenthal D, Gutmann L, Schochet SS (1996) Acute type II myofiber atrophy in critical illness. Neurology 46:819–821

    Article  CAS  PubMed  Google Scholar 

  28. Gayan-Ramirez G, Testelmans D, Maes K, Racz GZ, Cadot P, Zador E, Wuytack F, Decramer M (2005) Intermittent spontaneous breathing protects the rat diaphragm from mechanical ventilation effects. Crit Care Med 33:2804–2809

    Article  PubMed  Google Scholar 

  29. DeRuisseau KC, Shanely RA, Akunuri N, Hamilton MT, Van Gammeren D, Zergeroglu AM, McKenzie M, Powers SK (2005) Diaphragm unloading via controlled mechanical ventilation alters the gene expression profile. Am J Respir Crit Care Med 172:1267–1275

    Article  PubMed  PubMed Central  Google Scholar 

  30. Shanely RA, Zergeroglu MA, Lennon SL, Sugiura T, Yimlamai T, Enns D, Belcastro A, Powers SK (2002) Mechanical ventilation-induced diaphragmatic atrophy is associated with oxidative injury and increased proteolytic activity. Am J Respir Crit Care Med 166:1369–1374

    Article  PubMed  Google Scholar 

  31. DeRuisseau KC, Kavazis AN, Deering MA, Falk DJ, Van Gammeren D, Yimlamai T, Ordway GA, Powers SK (2005) Mechanical ventilation induces alterations of the ubiquitin–proteasome pathway in the diaphragm. J Appl Physiol 98:1314–1321

    Article  CAS  PubMed  Google Scholar 

  32. Jackman RW, Kandarian SC (2004) The molecular basis of skeletal muscle atrophy. Am J Physiol Cell Physiol 287:C834–C843

    Article  CAS  PubMed  Google Scholar 

  33. Di Giovanni S, Molon A, Broccolini A, Melcon G, Mirabella M, Hoffman EP, Servidei S (2004) Constitutive activation of MAPK cascade in acute quadriplegic myopathy. Ann Neurol 55:195–206

    Article  PubMed  Google Scholar 

  34. Latronico N, Peli E, Botteri M (2005) Critical illness myopathy and neuropathy. Curr Opin Crit Care 11:126–132

    Article  PubMed  Google Scholar 

  35. Attaix D, Ventadour S, Codran A, Bechet D, Taillandier D, Combaret L (2005) The ubiquitin–proteasome system and skeletal muscle wasting. Essays Biochem 41:173–186

    Article  CAS  PubMed  Google Scholar 

  36. Kandarian SC, Jackman RW (2006) Intracellular signaling during skeletal muscle atrophy. Muscle Nerve 33:155–165

    Article  CAS  PubMed  Google Scholar 

  37. Cai D, Frantz JD, Tawa NE Jr, Melendez PA, Oh BC, Lidov HG, Hasselgren PO, Frontera WR, Lee J, Glass DJ, Shoelson SE (2004) IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell 119:285–298

    Article  CAS  PubMed  Google Scholar 

  38. Fareed MU, Evenson AR, Wei W, Menconi M, Poylin V, Petkova V, Pignol B, Hasselgren PO (2006) Treatment of rats with calpain inhibitors prevents sepsis-induced muscle proteolysis independent of atrogin-1/MAFbx and MuRF1 expression. Am J Physiol Regul Integr Comp Physiol 290:R1589–R1597

    Article  CAS  PubMed  Google Scholar 

  39. McDonald MC, Mota-Filipe H, Paul A, Cuzzocrea S, Abdelrahman M, Harwood S, Plevin R, Chatterjee PK, Yaqoob MM, Thiemermann C (2001) Calpain inhibitor I reduces the activation of nuclear factor-kappaB and organ injury/dysfunction in hemorrhagic shock. FASEB J 15:171–186

    Article  CAS  PubMed  Google Scholar 

  40. Goll DE, Thompson VF, Li H, Wei W, Cong J (2003) The calpain system. Physiol Rev 83:731–801

    Article  CAS  PubMed  Google Scholar 

  41. Machida K, Ishibashi R, Hara T, Ohtsuka A, Hayashi K (2003) Effects of corticosterone on Ca2+ uptake and myofibrillar disassembly in primary muscle cell culture. Biosci Biotechnol Biochem 67:244–249

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors sincerely thank Mrs. Petra Weckx for cutting muscle samples and staining the histological sections. We also thank Prof. E. Verbeken for the evaluation of the H&E-stained sections. This study was supported by FWO-Vlaanderen #G.0389.03, KUL Research Foundation OT/02/44 and AstraZeneca Pharmaceuticals. Dries Testelmans is an aspirant of the “Fonds voor Wetenschappelijk Onderzoek – Vlaanderen”

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ghislaine Gayan-Ramirez.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Testelmans, D., Maes, K., Wouters, P. et al. Infusions of rocuronium and cisatracurium exert different effects on rat diaphragm function. Intensive Care Med 33, 872–879 (2007). https://doi.org/10.1007/s00134-007-0584-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-007-0584-4

Keywords

Navigation