Repeated pulse of methylprednisolone and cyclophosphamide with
continuous dexamethasone therapy for patients with severe
paraquat poisoning
Ja-Liang Lin, MD; Dan-Tzu Lin-Tan, RN; Kuan-Hsing Chen, MD; Wen-Hung Huang, MD
Objective: Paraquat is widely used in the world, and all treatments
for paraquat poisoning have been unsuccessful. Many
patients have died of paraquat poisoning in developing countries.
A novel anti-inflammation method was developed to treat severe
paraquat-poisoned patients with >50% to <90% predictive mortality:
initial pulse therapy with methylprednisolone (1 g/day for 3
days) and cyclophosphamide (15 mg/kg/day for 2 days), followed
by dexamethasone 20 mg/day until PaO2 was >11.5 kPa (80 mm
Hg) and repeated pulse therapy with methylprednisolone (1 g/day
for 3 days) and cyclophosphamide (15 mg/kg/day for 1 day),
which was repeated if PaO2 was <8.64 kPa (60 mm Hg).
Design: Randomized controlled trial.
Setting: Academic medical center in Taiwan.
Patients: Twenty-three paraquat-poisoned patients with
>50% and <90% predictive mortality assessed by plasma paraquat
levels were prospectively and randomly assigned to the
control and study groups at a proportion of 1:2.
Interventions: The control group received conventional therapy
and the study group received the novel repeated pulse treatment
with long-term steroid therapy.
Measurements and Main Results: We measured patient mortality
during the study period. There was not a different distribution
of basal variables between the two study groups. The mortality
rate (85.7%, six of seven) of the control group was higher
than that of the study group (31.3%, five of 16; p .0272).
Conclusions: The novel anti-inflammatory therapy reduces the
mortality rate for patients with severe paraquat poisoning. (Crit
Care Med 2006; 34:368–373)
At that time, given the constraints I felt that this is an acceptable study and started treating paraquat poisoning patients with the immunosuppressive treatment used in the RCT.
Few months later a letter written to the editor highlighted that the study is not adequately powered to detect such a difference in the out come.(Gunawardena G et
al. Randomized control trial of immunosuppression in
paraquat poisoning. Crit Care Med. 2007;35(1):330-1.)
I also noted there is some overlap between the CONSORT checklist for researchers doing RCTs(attached) and RAAMbo check list.However sample size is mentioned in CONSORT list only.
I am wondering why such an important component of an RCT that can invalidate a trial results even when rest of "RAAMbo"validity criteria are fulfilled is not taken into consideration during the critical appraisal process of a RCT.
Greatly value your input as it will enrich my learning experience at the EBM course.
Ruwan Parakramawansha
Trainee in Clinical Pharmacology, Therapeutics and Toxicology
University Hospital Llandough