Skip to main content

Advertisement

Log in

Improved survival in severe paraquat poisoning with repeated pulse therapy of cyclophosphamide and steroids

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

Abstract

Purpose

To clarify the efficacy of repeated methylprednisolone (MP) and cyclophosphamide (CP) pulse therapy and daily dexamethasone (DEX) therapy in patients with severe paraquat (PQ) poisoning.

Methods

A total of 111 patients with severe PQ poisoning and dark-blue color in urine tests within 24 h of intoxication were included prospectively. The control group consisted of 52 patients who were admitted between 1998 and 2001 and who received high doses of CP (2 mg/kg per day) and DEX (5 mg every 6 h) for 14 days. The study group consisted of 59 patients who were admitted from 2002 to 2007 and who received initial MP (1 g) for 3 days and CP (15 mg/kg per day) for 2 days, followed by DEX (5 mg every 6 h) until a PaO2 of >80 mmHg had been achieved, or treated with repeated 1 g MP for 3 days and 1 g CP for 1 day if the PaO2 was <60 mmHg.

Results

There were no differences between the two groups with regard to baseline data and plasma PQ levels. The study group patients had a lower mortality rate (39/59, 66%) than the control group patients (48/52, 92%; P = 0.003, log-rank test). Multivariate Cox regression analysis revealed that the repeated pulse therapy was correlated with decreased hazard ratios (HR) for all-cause mortality (HR = 0.50, 95% CI 0.31–0.80; P = 0.004) and death from lung fibrosis-related hypoxemia (HR = 0.10, 95% CI 0.04–0.25; P < 0.001) in severely PQ-intoxicated patients.

Conclusion

Repeated pulses of CP and MP, rather than high doses of CP and DEX, may result in a lower mortality rate in patients with severe PQ poisoning.

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

Similar content being viewed by others

References

  1. Vale JA, Meredith TJ, Buckly BM (1987) Paraquat poisoning: clinical features and immediate general management. Hum Toxicol 6:41–47

    Article  PubMed  CAS  Google Scholar 

  2. Lin JL, Liu L, Leu ML (1986) Recovery of respiratory function in survivors with paraquat intoxication. Arch Environ Health 50:432–439

    Article  Google Scholar 

  3. Wilks MF, Fernando R, Ariyananda PL, Eddleston M, Berry DJ, Tomenson JA, Buckley NA, Jayamanne S, Gunnell D, Dawson A (2008) Improvement in survival after paraquat ingestion following introduction of a new formulation in Sri Lanka. PLoS Med 5:e49

    Article  PubMed  Google Scholar 

  4. Addo E, Poon-King T (1986) Leukocyte suppression in treatment of 72 patients with paraquat poisoning. Lancet i:1117–1120

    Article  Google Scholar 

  5. Perriens JH, Benimadho S, Lie Kiauw I, Wisse J, Chee H (1992) High dose cyclophosphamide and dexamethasone in paraquat poisoning: a prospective study. Hum Exp Toxicol 11:129–134

    Article  PubMed  CAS  Google Scholar 

  6. Lin JL, Wei MC, Leu YC (1996) Pulse therapy with cyclophosphamide and methylprednisolone in patients with moderate to severe paraquat poisoning: a preliminary report. Thorax 51:661–663

    Article  PubMed  CAS  Google Scholar 

  7. Lin JL, Leu ML, Liu YC, Chen GH (1999) A prospective clinical trial of pulse therapy with glucocorticoid and cyclophosphamide in moderate to severe paraquat poisoned patients. Am J Respir Crit Care Med 159:357–360

    PubMed  CAS  Google Scholar 

  8. Chen GH, Lin JL, Huang YK (2002) Combined methylprednisolone and dexamethasone therapy for paraquat poisoning. Crit Care Med 30:2584–2587

    Article  PubMed  Google Scholar 

  9. Lin NC, Lin JL, Lin-Tan DT, Yu CC (2003) Combined initial cyclophosphamide with repeated methylprednisolone pulse therapy for severe paraquat poisoning from dermal exposure. J Toxicol Clin Toxicol 41:877–881

    Article  PubMed  CAS  Google Scholar 

  10. Lin JL, Lin-Tan DT, Chen KH, Huang WH (2006) Repeated pulse of methylprednisolone and cyclophosphamide with continuous dexamethasone therapy for patients with severe paraquat poisoning. Crit Care Med 34:368–373

    Article  PubMed  CAS  Google Scholar 

  11. Scherrmann JM, Houze P, Bismuth C, Bourdon R (1987) Prognostic value of plasma and urine paraquat concentrations. Hum Toxicol 6:91–93

    Article  PubMed  CAS  Google Scholar 

  12. Braithwaite RA (1987) Emergency analysis of paraquat in biological fluids. Hum Toxicol 6:91–93

    Article  Google Scholar 

  13. Sawada Y, Yamamoto I, Hirokane T, Nagai Y, Satoh Y, Ueyama M (1988) Severity index of paraquat poisoning. Lancet 1:1333

    Article  PubMed  CAS  Google Scholar 

  14. Proudfoot AT, Stewart MS, Levitt T, Widdop B (1979) Paraquat poisoning: significance of plasma-paraquat concentrations. Lancet 2:330–332

    Article  PubMed  CAS  Google Scholar 

  15. Cartin-Ceba R, Haugen EN, Iscimen R, Trillo-Alvarez C, Juncos L, Gajic O (2009) Evaluation of "Loss" and "End stage renal disease" after acute kidney injury defined by the Risk, Injury, Failure, Loss and ESRD classification in critically ill patients. Intensive Care Med 35:2087–2095

    Article  PubMed  Google Scholar 

  16. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, The ADQI workgroup (2004) Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8:R204–R212

    Article  PubMed  Google Scholar 

  17. Koo JR, Kim JC, Yoon JW, Kim GH, Jeon RW, Kim HJ, Chae DW, Noh JW (2002) Failure of continuous venovenous hemofiltration to prevent death in paraquat poisoning. Am J Kidney Dis 39:55–59

    Article  PubMed  Google Scholar 

  18. Gil HW, Kang MS, Lee EY, Hong SY (2008) Association between plasma paraquat level and outcome of paraquat poisoning in 375 paraquat poisoning patients. Clin Toxicol 46:515–518

    Article  CAS  Google Scholar 

  19. Bismuth C, Hall AH, Baud FJ, Borron S (1996) Pulmonary dysfunction in survivors of paraquat poisoning. Vet Hum Toxicol 38:220–222

    PubMed  CAS  Google Scholar 

  20. Fox DA, McCune WJ (1994) Immunosuppressive drug therapy of systemic lupus erythematosus. Rheum Dis Clin 20:265–299

    CAS  Google Scholar 

  21. Youshida T, Tanaka M, Sotomatsu A, Okamoto K (1999) Effect of methylprednisolone pulse therapy on superoxide production of neutrophils. Neurol Res 21:509–512

    Google Scholar 

  22. Peter JV, John P, Graham PL, Moran JL, George IA, Bersten A (2008) Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis. BMJ 336:1006–1009

    Article  PubMed  Google Scholar 

  23. Meduri GU, Marik PE, Chrousos GP, Pastores SM, Arlt W, Beishuizen A, Bokhari F, Zaloga G, Annane D (2008) Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature. Intensive Care Med 34:61–69

    Article  PubMed  CAS  Google Scholar 

  24. Dinis-Oliveira RJ, Remião F, Duarte JA, Ferreira R, Sánchez Navarro A, Bastos ML, Carvalho F (2006) P-glycoprotein induction: an antidotal pathway for paraquat-induced lung toxicity. Free Radical Biol Med 41:1213–1224

    Article  CAS  Google Scholar 

  25. Dinis-Oliveira RJ, Duarte JA, Remião F, Sánchez-Navarro A, Bastos ML, Carvalho F (2006) Single high dose dexamethasone treatment decreases the pathological score and increases the survival rate of paraquat-intoxicated rats. Toxicology 227:73–85

    Article  PubMed  CAS  Google Scholar 

  26. Editorial (1986) Cyclophosphamide for paraquat poisoning? Lancet ii:375–376

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ja-Liang Lin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lin, JL., Lin-Tan, DT., Chen, KH. et al. Improved survival in severe paraquat poisoning with repeated pulse therapy of cyclophosphamide and steroids. Intensive Care Med 37, 1006–1013 (2011). https://doi.org/10.1007/s00134-010-2127-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-010-2127-7

Keywords

Navigation