Tissue concentration of paraquat on day 32 after intoxication and failed bridge to transplantation by extracorporeal membrane oxygenation therapy
© Bertram et al.; licensee BioMed Central Ltd. 2013
Received: 10 April 2013
Accepted: 15 August 2013
Published: 6 September 2013
Paraquat is a highly toxic herbicide, which not only leads to acute organ damage, but also to pulmonary fibrosis. There are only anecdotal reports of rescue lung transplantation, as paraquat is stored and only slowly released from different tissues. Bridging the time to complete depletion of paraquat from the body could render this exceptional therapy strategy possible, but not much is known on the time interval after which transplantation can safely be performed.
We report on a case of accidental paraquat poisoning in a 23 years old Caucasian man, who developed respiratory failure due to pulmonary fibrosis. The patient was listed for high urgency lung transplantion, and extracorporeal membrane oxygenation was implemented to bridge the time to transplantation. The patient died 32 days after paraquat ingestion, before a suitable donor organ was found. In postmortem tissue specimen, no paraquat was detectable anymore.
This case report indicates that complete elimination of paraquat after oral ingestion of a lethal dose is achievable. The determined time frame for this complete elimination might be relevant for patients, in which lung transplantation is considered.
KeywordsParaquat Poisoning Extracorporeal membrane oxygenation Lung transplantation
Paraquat (1,1’-dimethyl-4,4’ bipyridinium dichloride) is a highly toxic contact herbicide, which has been banned in Germany since 2007. However, there are still rare cases of paraquat intoxications with leftovers of paraquat purchased prior to the ban, mostly in form of suicide attempts. After oral ingestion, the intestinal absorption of paraquat is poor (1-5%), but still sufficient to elicit a severe and potentially fatal intoxication. Early toxicity includes oral, pharyngeal and gastrointestinal ulcerations and necroses, acute kidney injury and liver failure . Ingestion of two or more mouthful of paraquat usually leads to circulatory failure within two days, whereas patients, who swallow not more than one mouthful, often survive the early phase of paraquat intoxication . Late toxicity is mostly due to the storage of paraquat in alveolar macrophages, where it reacts with the highly abundant oxygen to form radicals and reactive oxygen species. The reactions of paraquat simultaneously deplete the body of antioxidants . The consequences are pulmonary inflammation and fibrosis, which is the main cause of death in patients surviving the early phase of paraquat poisoning. In case of attempted suicide, the psychiatric background does not allow lung transplantation. In accidental paraquat ingestion, however, lung transplantation could be the only therapeutic strategy, if it is performed after complete depletion of paraquat from the body to prevent recurrence of fibrosis in the allograft. The first attempt of lung transplantation in paraquat intoxication in 1968 failed as the single lung transplantation was performed as early as 7 days after intoxication of a 15 years old boy . Due to recurrence of fibrosis in the allograft, these authors speculated already that paraquat stored in the tissue caused fibrosis of the allograft. Hence, complete depletion of paraquat from the body to prevent fibrosis of the allograft due to redistribution of paraquat from the tissue is necessary. After what time this complete depletion would occur is unknown. Yet the first successful lung transplantation reported by Walder et al.  was performed 44 days after intoxication. Here, we report on a case of accidental paraquat intoxication, in which we attempted to bridge the time to transplantation with extracorporeal membrane oxygenation.
Laboratory values after referral (3rd day after paraquat ingestion); pathological values are bold
17.7 / nl
4.4 – 11.3 / nl
4.65 / fl
4.50 – 5.90 / fl
13.5 – 17.5 g/dl
80 – 100 fl
26 – 34 pg
31 – 37 g/dl
0.9 – 1.25
26 – 35 sec
3.6 – 5.4 mmol/l
138 – 148 mmol/l
97 – 108 mmol/l
2.15 – 2.60 mmol/l
0.83 – 1.67 mmol/l
< 8 mg/l
59 – 104 μmol/l
3.3 – 6.7 mmol/l
< 171 U/l
< 35 U/l
< 45 U/l
< 7 U/l
40 – 129 U/l
< 55 U/l
5.32 – 12.91 U/l
< 248 U/l
< 17 μmol/l
Paraquat levels in different tissues / materials
Tissue / material
< 0.01 mg/l*
< 0.2 μg/g*
< 0.2 μg/g*
Autopsy tissue specimens
< 0.2 μg/g
< 0.2 μg/g
< 0.2 μg/g
< 0.2 μg/g
< 0.2 μg/g
< 0.2 μg/g
< 0.2 μg/g
< 0.2 μg/g
< 0.2 μg/g
< 0.2 μg/g
< 0.2 μg/g
Treatment options in paraquat poisoning are limited. This holds especially true for the use of extracorporeal treatment methods, which are currently evaluated in a standardized approach . Since the main problems arise from irreversible lung damage, the major goal is to reduce intestinal absorption and enhance elimination of paraquat before it can be stored in the tissue. Administration of activated charcoal and gastric lavages are regularly performed. However, intestinal absorption of paraquat is a rapid process and high paraquat plasma levels are reached within minutes to 4 hours after paraquat ingestion . When our patient came to the hospital approximately 6 h after paraquat ingestion, serum levels might already have reached their maximum, so charcoal administration and gastric lavage probably had no effect.
Although paraquat is eliminated by the kidneys, forced diuresis has no proven benefit on mortality. The early initiation of charcoal hemoperfusion within the first hours after paraquat poisoning seems to have a beneficial prognostic effect on survival , but the majority of patients with paraquat poisoning do not benefit from extracorporeal methods including hemoperfusion, hemodialysis or hemofiltration [13, 14]. The reason for that might be that the ingested paraquat reaches the lungs before renal replacement therapy can be implemented. Paraquat is stored in different tissues, expecially the lung, but also in brain, liver, kidney, bile and muscle in varying amounts [15–17], from where it is only released slowly. Finally, immunosuppressive therapy regimens and antioxidants  have been used to prevent the development of fibrosis, including high-dose steroids, cyclophosphamid , and sirolimus , with varying success. But even with this aggressive therapy, pulmonary fibrosis develops in most patients including ours, so that lung transplantation seems to be the last option in absence of contraindications. However, lung transplantation can only be successful, if the body is completely depleted of paraquat. Otherwise, fibrosis would potentially recur in the allograft. The first attempt of single lung transplantation in a case of paraquat poisoning was reported as early as 1968. The transplantation was performed seven days after accidental paraquat ingestion, when there was still paraquat detectable in the patient’s blood (0.4 mg/l) and the explanted left lung (8.50 μg/g). Two weeks after the transplantation, the patient died from respiratory failure. Postmortem histopathology revealed the same paraquat-induced fibrotic changes in both the native right and the transplanted left lung, indicating a recurrence of fibrosis caused by paraquat released from its body stores. At this time, no paraquat could be detected in both the native and the transplanted lung postmortem, but other tissues were not examined . Walder et al.  reported the first successful single lung transplantations performed 44 days after paraquat ingestion. The patients showed no signs of recurrent pulmonary fibrosis in the allograft and survived at least one year. However, serum was free from detectable paraquat levels as early as 4 d after paraquat ingestion, when serum levels still reached 0.15 mg/l in our patient despite daily hemodialysis.
Our patient was listed for high-urgency lung transplantation, because all of the described treatment strategies failed. We used extracorporeal support to bridge the time to transplantation, but the patient developed septic multiorgan failure and finally died before a suitable donor organ was available. In postmortem tissue specimen no paraquat could be detected, suggesting that lung transplantation would potentially have been successful. Furthermore, the donation of otherwise undamaged organs would have been possible without endangering the recipient, as has been demonstrated for corneas in single cases .
In a variety of tissue samples obtained postmortem, we can show that complete elimination paraquat after oral ingestion of a lethal dose is achievable. The determined time frame for this complete elimination might be relevant for patients, in which lung transplantation is considered.
Written informed consent was obtained from the patient’s legal representative for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Series Editor of this journal.
Veno-venous extracorporeal membrane oxygenation
Veno-arterial extracorporeal membrane oxygenation.
The publication of the study is supported by the DFG-project “Open Access Publication”.
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