Other Potential Treatments
Enhanced elimination of paraquat
Peritoneal dialysis or haemodialysis may be required in patients with acute renal failure, but they are ineffective in enhancing the elimination of paraquat from the body.
Haemoperfusion has been postulated as a treatment for a number of years but its efficacy remains controversial. While charcoal columns are very efficient at removing paraquat from the blood, paraquat is rapidly distributed to other tissues and redistributes back to the blood relatively slowly. i.e. toxic levels in tissues occur early in the course of the poisoning.
When considering the use of haemoperfusion in paraquat poisoning, note that:
1. Patients who have ingested borderline lethal quantities of paraquat, or have survival probabilities between 20 and 70 percent,
and present within a few hours (probably < 6-10 hours) post ingestion may benefit from haemoperfusion (since the paraquat may not have distributed to the tissues / lungs in toxic quantities and even small differences in the paraquat level may affect survival probability).
2. Patients who have taken many times the lethal dose of paraquat, or have very poor prognosis on survival probability curves, are not helped by haemoperfusion (Hampson and Pond, 1988).
3. The use of 'continuous' haemoperfusion is probably not life-saving but may prolong survival. This may allow the use of other treatment modalities to be considered (e.g. lung transplantation, see below) (Suzuki et al., 1993).
Prevention and treatment of pulmonary fibrosis
Patients with moderate intoxication who do not die from early, multiorgan failure often develop progressive pulmonary fibrosis. This leads to respiratory failure and death within a few weeks. Several treatment modalities have attempted to prevent this.
Cyclophosphamide and steroid therapy
Several studies have looked at the use of cyclophosphamide and steroid therapy. Addo and Poon-King (1986) claimed a 72% survival rate in 72 patients treated with cyclophosphamide (5 mg/kg/day to a maximum total of 4 g) and dexamethasone (8 mg eight-hourly over two weeks). However, the plasma paraquat data of 25 patients showed that 7 survivors had no measurable paraquat levels, and of the other 18 only the six patients with the lowest plasma concentration survived. Lin et al., (1999) reported results of a prospective, randomised study of pulse therapy with cyclophosphamide (1g/day over 2 days) and methylprednisolone (1g/day over 3 days) in 142 patients. Seventy-one patients died from fulminant poisoning within one week, and cyclophosphamide did not make any difference. In the group of moderately to severely poisoned patients, only 4/22 patients treated with cyclophosphamide died, compared to 16/28 in the control group. Plasma paraquat concentrations were not available, but the authors stated that there was no difference in severity of poisoning between the two groups based on the urine dithionite test. However, the beneficial effects of the cyclophosphamide-dexamethasone regime have been disputed and in a prospective study Perriens et al., (1992) did not find any difference in mortality between 14 patients who had received standard treatment and the 33 patients who had received high-dose cyclophosphamide and dexamethasone. A final answer regarding the usefulness of this therapy can therefore not been given at this stage.
Radiotherapy
Radiotherapy has been suggested to decrease the number of fibroblasts (very radiosensitive) in the lung, and hence decrease fibrosis. However, there is no conclusive evidence that it improves survival.
Lung transplantation
Although lung transplantation has been tried in several cases, success has been reported in only one (Walder et al., 1997). This was performed 5 weeks after the initial presentation (the patient was supported with mechanical ventilation during this time until a donor was found). Supportive treatment also consisted of haemodialysis until no paraquat was detected in the plasma or dialysate.
Other agentsA wide range of therapeutic substances have been studied experimentally. Some have been used in humans, but most of the published work is based on single or a small number of cases (for a detailed review see Lock and Wilks, 2001). Agents which have been used clinically include:
- antioxidants (vitamins C and E) and superoxide dismutase to reduce free radical toxicity
- N-acetyl cysteine to increase intracellular glutathione
- desferrioxamine to chelate iron which acts as catalyst in the production of hydroxyl radicals
- propranolol to block paraquat uptake into the lung
- inhaled nitric oxide to improve pulmonary gas exchange