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Matters arising
Methotrexate and postoperative complications
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  1. A Wluka1,
  2. R Buchbinder2,
  3. S Hall3,
  4. G Littlejohn4
  1. 1Department of Epidemiology and Preventive Medicine, Monash University, Australia
  2. 2Department of Epidemiology, Cabrini Hospital, Malvern, Australia and Monash University, Australia
  3. 3Cabrini Medical Centre, Malvern, Australia
  4. 4Monash Medical Centre, Clayton, Australia
  1. Correspondence to:
    Dr A Wluka, Department of Epidemiology and Preventive Medicine, Monash University, Central and Eastern Clinical School, Alfred Hospital, Prahran, Victoria 3181, Australia
  1. D M Grennan5,
  2. J Gray5
  1. 5Department of Rheumatology, Wrightington Hospital NHS Trust, Hall Lane, Appley bridge, Wigan WN6 9EW, UK

    http://dx.doi.org/10.1136/ard.61.1.86

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      Grennan et al report the safety of continued methotrexate in the perioperative period.1 Previous investigators have despaired of answering this question definitively owing to the difficulty in recruiting subjects.2 It is reassuring to see that methotrexate use throughout the postoperative period does not interfere with wound healing or increase the incidence of early complications.

      Despite this important finding, we believe that the results of this study should be regarded with some reservation: continuation of methotrexate throughout the perioperative period should be accompanied by significant caution. The elderly and those with renal impairment are at increased risk of methotrexate related pancytopenia.3–5 Indeed, in a community based, observational study of methotrexate use in 460 patients we found the perioperative period to be especially hazardous for patients with renal impairment and sepsis.6 Two subjects developed pancytopenia under these conditions, one of whom died.

      Although all consecutive patients were included in the study by Grennan et al, it is unclear whether Wrightington Hospital is a tertiary referral centre. Renal impairment is an important comorbidity, although no comment is made about the prevalence of this in the study group. It is important to note that this is a study of methotrexate use in elective surgery.

      We suggest caution should be taken in patients with renal impairment (best assessed by creatinine clearance) and in the elderly with comorbid cardiovascular disease when approaching surgery. Sudden volume loss, bleeding, or dehydration will impair methotrexate excretion and increase the risk of bone marrow toxicity in this group. It may be prudent in those assessed as at high risk of this complication to stop methotrexate one week before the operation and restart treatment one or two weeks after the operation, depending on postoperative progress. This time period without methotrexate treatment will not alter disease control in the vast majority of patients, although after four weeks without treatment, most will have a flare of the disease.7

      References

      1. ↵
        Grennan DM, Gray J, Loudon J, Fear S. Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopedic surgery. Ann Rheum Dis2001;60:214–17.
        OpenUrlAbstract/FREE Full Text
      2. ↵
        Alarcon GS, Moreland LW, Jaffe K, Phillips RM, Bocanegra T, Russell IJ. The use of methotrexate perioperatively in patients with rheumatoid arthritis undergoing major joint replacement surgery: will we ever have consensus about its use? J Clin Rheumatol1996;2:6–8.
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      3. ↵
        Howland WL. Methotrexate-associated bone marrow suppression following surgery. Arthritis Rheum1988;31:1586–7.
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      4. Buchbinder R, Hall S, Harkness A, Littlejohn G, Ryan PF. Severe bone marrow failure due to low dose methotrexate. J Rheumatol1988;15:1586–8.
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      5. ↵
        Gutierrez-Ureña S, Molina JF, García CO, Cuéllar ML, Espinoza LR. Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis. Arthritis Rheum1996;39:272–6.
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      6. ↵
        Wluka AE, Buchbinder R, Mylvaganam A, Hall S, Harkness A, Lewis D, et al. Long term community based methotrexate use in rheumatoid arthritis: 12 year follow up of 460 patients. J Rheumatol2000;27:1864–71.
        OpenUrlPubMedWeb of Science
      7. ↵
        Kremer JM, Rynes JM, Bartholomew LE. Severe flare of rheumatoid arthritis after discontinuation of long-term methotrexate therapy. Am J Med1987;82:781–6.
        OpenUrlCrossRefPubMedWeb of Science

      Authors' reply

      Dr Wluka draws attention to the potential hazard of methotrexate prescribing in subjects with chronic renal failure and sepsis, and we would not disagree with this point. The risk of surgery is increased by any coincidental medical disease including renal failure and sepsis as well as chronic vascular disease. We noted this in our study.

      The role of the doctor/rheumatologist is to ensure that any such chronic medical problems are under optimal control before elective orthopaedic surgery. Methotrexate treatment should not be withdrawn from patients with rheumatoid arthritis if the disease is well controlled before elective surgery. The comments of Dr Wluka do not invalidate this conclusion.