Continuous Blood Filtration Shows Potential for Treating Paraquat-induced PF
The technique may have implications for the treatment of patients with paraquat-induced pulmonary fibrosis (PF), a Chinese study suggests.
Paraquat is primarily effective in weed and grass control and commonly used as an herbicide in some Asian countries. However, the chemical is toxic to humans at low doses.
According to scientists, acute paraquat poisoning is a serious public health problem, primarily because it is associated with a 60-70% mortality rate and has no specific antidote.
If ingested, paraquat is transported through the bloodstream into the lungs, where it triggers a significant inflammatory response that leads to lung injury and PF. The chemical also can trigger multiple organ failure, though many studies have found that pulmonary complications are the leading cause of death following paraquat poisoning.
Because paraquat travels through the blood, researchers at the Harrison International Peace Hospital affiliated with Hebei Medical University, in China, sought to develop a treatment method for paraquat poisoning involving the blood.
The team was interested in hemoperfusion, a technique in which the blood is passed through an external filter in order to remove a toxin.
Specifically, the impact of routine versus continuous hemoperfusion on the survival rate of patients with acute paraquat poisoning and on the treatment of PF was the focus of this study, which compared the two methods.
A total of 82 patients — 44 women, 38 men, with an average age of 36.79 — with mild or moderate paraquat poisoning were treated with hemoperfusion at the Harrison hospital between January 2017 and December 2018. All of the patients were poisoned with paraquat through the mouth and treatment was started within 4.5 hours of the poisoning. Severe cases were excluded based on a paraquat blood concentration greater than 30 mg/L.
Of the 82 patients, just under half (40 people) received routine hemoperfusion, in which the blood-filtering therapy was initially performed for two hours, and then repeated three more times every eight hours. The remaining patients (42 people) received a continuous hemoperfusion, in which the treatment was initially performed for four hours, and then continued until paraquat was not detectable in the blood.
A JF-800A Hemoperfusion Machine by Jianfan Biotechnology was used for the procedure, with resin as the absorbing material.
The levels of paraquat in the blood were analyzed before, during, and after the treatment at specific time points.
In the routine hemoperfusion group, the average paraquat concentration was 17.58 mg/L before treatment and 9.54 mg/L eight hours after the treatment. At 24 hours after treatment, the concentration was 4.86 mg/L.
Meanwhile, among those in the continuous hemoperfusion group, the concentration was 15.71 mg/L before treatment, 6.35 mg/L four hours after treatment, and 4.02 mg/L six hours after. No paraquat was detected eight hours after treatment, indicating that the continuous method was more effective at removing paraquat from the bloodstream.
The patients were followed for 28 days after admission. In the routine group, the survival rate was 35% (14 out of 40) as compared with 55% (23 out of 42) in the continuous group. Those rates suggest that continuous hemoperfusion was better at improving the survival rate of these patients, and lowering mortality.
The team then looked at a number of biomarkers to evaluate the efficacy of the treatment, finding evidence that paraquat poisoning caused PF due to spikes in three specific proteins: procollagen 3 N-terminal peptide (PIIINP), collagen type IV (CIV), and TGF-Beta 1.
The researchers found that the buildup of these proteins occurred over a seven-day period following treatment, but that the build-up was slower in patients receiving the continuous treatment compared with the routine therapy method.
Another metric, the Sequential Organ Failure Assessment (SOFA) score, showed that the continuous hemoperfusion group were at a reduced risk of multiple organ failure compared with the routine group.
Further, the use of high-resolution computerized tomography (HRCT) imaging of the lungs found reduced inflammation and signs of damage in patients on the continuous treatment regimen.
Finally, the researchers analyzed two other factors — malondialdehyde (MDA) and superoxide dismutase (SOD) activity — both considered biomarkers for oxidative stress, a pathway associated with lung damage.
In the continuous hemoperfusion group, MDA was increased and SOD was decreased at three days following treatment. But at seven days MDA was decreased and SOD was increased, suggesting that the treatment was slowing down oxidative stress and possibly preventing the sudden onset of fibrosis.
Based on the results, the researchers concluded that the hemoperfusion technique administered early and in a continuous manner in cases of acute paraquat poisoning has the potential to improve survival rates and to reduce the onset of PF.
“Our study clarified that compared with HP [hemoperfusion], CHP [continuous hemoperfusion] treatment exhibited a better therapeutic effect on mild and moderate APP [acute paraquat poisoning] patients, providing data support for the clinical promotion of CHP in the treatment of APP,” the researchers wrote.