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Paraquat poisoning

Paraquat poisoning
Literature review current through: Jan 2024.
This topic last updated: Jun 21, 2022.

INTRODUCTION — Paraquat ingestion is a leading cause of fatal poisoning in many parts of Asia, Pacific nations, and the Americas [1]. Paraquat is a rapidly-acting, nonselective herbicide that is relatively inexpensive. These characteristics contribute to its widespread use in much of the developing world.

Paraquat is reasonably safe to use in agriculture: dermal or spray exposure generally causes only limited, localized injury [2]. However, accidental or deliberate ingestion has an extremely high case-fatality rate [3]. Largely for this reason, paraquat has been restricted in many parts of the world. In the rural areas of countries where it remains readily available, it is a common method for intentional self-poisoning [1].

Diquat is a related herbicide that is often formulated with paraquat. There are relatively few reports of diquat poisoning, but it appears to involve mechanisms and manifest clinical features similar to those of paraquat [4]. While evidence is limited, the treatment of diquat poisoning is generally the same as that for paraquat poisoning.

The presentation and management of paraquat poisoning will be reviewed here. General approaches to the assessment of the poisoned patient are discussed separately. (See "General approach to drug poisoning in adults" and "Initial management of the critically ill adult with an unknown overdose".)

PHARMACOLOGY AND CELLULAR TOXICOLOGY — Chemically, paraquat and diquat are classified as bipyridyl compounds. After absorption, paraquat is concentrated inside many cells where it undergoes redox cycling, a process involving repetitive enzyme-mediated cycling between paraquat and paraquat radicals. A by-product of this process is a superoxide radical, a highly reactive oxygen species, which can cause direct cellular damage or react further to form other reactive oxygen species and nitrite radicals [5]. Redox cycling consumes NADPH, one of the cell’s key antioxidant defenses. The resultant oxidative stress created by the production of free radicals and the depletion of NADPH directly causes cell damage (via lipid peroxidation, mitochondrial dysfunction, necrosis and apoptosis) and triggers a pronounced secondary inflammatory response.

Over a period of hours to days these processes lead to multi-organ failure. The organs most affected are those with high blood flow, oxygen tension, and energy requirements, in particular the lungs, heart, kidneys, and liver [6]. The brain is uncommonly affected as paraquat does not readily cross the blood-brain barrier, although paraquat has been detected in the CSF [7].

To reduce the toxicity of these herbicides in the event of ingestion, products containing these herbicides are often co-formulated with an emetic, dye, and stenching agent.

KINETICS — Paraquat is a highly polar and corrosive substance. It is generally not absorbed in significant amounts across intact skin or when droplets are inhaled [2]. Paraquat is rapidly but incompletely absorbed from the gut after ingestion (particularly concentrated solutions). It then rapidly distributes into other tissues, with maximum tissue levels reached about six hours after ingestion. Paraquat is actively taken up by the spermidine/putrescine and other cell membrane transporters, resulting in relatively high concentrations in the lung, kidney, liver, and muscle tissues [7].

Paraquat does not undergo significant metabolism. Elimination of paraquat is primarily by the kidneys, with most ingested paraquat appearing in the urine within 24 hours in minor poisonings. However, in severe paraquat poisoning kidney function is greatly reduced leading to much slower elimination [8]. In patients with severe paraquat poisoning who do not die within 24 hours, the apparent terminal elimination half-life can exceed 100 hours [7].

CLINICAL FEATURES OF POISONING

History — Clinicians should emphasize the following aspects of the history if paraquat poisoning is reported or suspected.

The formulation strength and dose ingested should be estimated. Swallowing more than 30 mL (a mouthful or two) of 20 to 24 percent paraquat concentrate is usually lethal, and as little as 10 mL can cause significant illness [9].

Comorbidities and patient age are important factors. A history of kidney disease and age over 50 years have been linked to worse outcomes [9,10].

The time of ingestion is important in the interpretation of paraquat concentrations and other laboratory studies.

Oral and gastrointestinal symptoms are common. Patients usually have a painful mouth and pain with swallowing. Nausea, vomiting, and abdominal pain occur in most patients.

A generalized “burning skin” sensation that starts over the first day or two following exposure is reported in over 50 percent of patients and is associated with a substantially increased risk of death [11].

Respiratory complaints indicate systemic poisoning and are associated with fatal outcomes.

Other types of exposures to paraquat include inhalation and topical (skin and/or eye) exposures. These types of exposures are less common and generally just involve local irritation and superficial burns. In the authors’ experience, adverse systemic clinical outcomes do not occur in most cases, particularly if the exposure is on intact skin or mucosa, of a brief duration, and involves a low concentration or volume. Such examples highlight the importance of taking a careful history of such exposures.

Physical examination and basic monitoring — The following should be emphasized when examining the patient with reported or suspected paraquat poisoning.

Inspect the mouth and pharynx for necrosis, inflammation, or ulceration; although the onset of these features may be delayed a number of hours (possibly up to 12) and reach maximum severity some days later (picture 1). Dehydration may be present due to vomiting. Oral intake may be poor or absent due to odynophagia.

Monitor the respiratory rate and pulse oximetry (avoid oxygen unless there is clear evidence of hypoxia (SpO2 <90 percent) as oxygen will increase toxicity).

Monitor the heart rate and blood pressure closely – Early death may result from progressive refractory hypotension.

Examine the chest – Patients are often dyspneic and tachypneic and bilateral crackles may be heard, indicating alveolitis. The extent of lung involvement correlates with a fatal outcome [10]. Subcutaneous emphysema indicates mediastinitis and is frequently associated with a fatal outcome [12].

Examine the abdomen – Patients often report abdominal pain and the abdomen may be diffusely tender.

Examine the skin and eyes for evidence of topical contact; topical paraquat may cause corneal ulceration or non-specific dermatitis. However, significant injury from topical exposure is uncommon, and in cases of life-threatening exposure systemic features overshadow any topical manifestations.

LABORATORY EVALUATION AND DIAGNOSTIC IMAGING — Although some laboratory tests appear to be useful for prognostication following paraquat exposure, few have been prospectively validated so their broader application has not been confirmed. Some laboratory tests are useful for identifying preventable causes of death (eg, severe electrolyte abnormalities) in patients with acute paraquat poisoning.

General testing — In patients with significant poisoning, blood tests should be obtained on admission and then repeated every 6 to 12 hours for the first 48 hours. The frequency of testing, in particular beyond 48 hours, depends upon the clinical situation including the presence and severity of vomiting, diarrhea, and kidney injury, and the prognosis. Unsurprisingly, a plethora of other abnormalities have been linked to worse outcomes in retrospective studies. However, none of these have improved the determination of prognosis when compared with long-established benchmarks (serum paraquat corrected for time, serum creatinine, extent of respiratory involvement) in prospective studies.

Often, tests are used to help determine the prognosis. If the prognosis is poor, then patient comfort and other palliative measures take priority and additional blood tests are not advised. (See 'Ongoing management' below.)

Serum electrolytes Electrolytes may be altered due to vomiting, diarrhea, acute kidney injury, and multiorgan dysfunction. These should be corrected according to routine clinical care.

Kidney function – Acute kidney injury suggests significant paraquat poisoning and may occur due to paraquat-induced acute tubular necrosis or volume depletion. Impaired renal function is associated with increased mortality. A number of serum and urine biomarkers of kidney function increase following acute paraquat poisoning. The most useful and widely available are serum creatinine and serum cystatin C.

The rate of increase in serum creatinine concentrations correlates with survival. An increase less than 3 μmol/L per hour (<0.034 mg/dL per hour) over five hours is associated with survival [13], whereas an increase greater than 4.3 μmol/L per hour (>0.049 mg/dL per hour) over six hours is associated with death [14]. Part of the serum creatinine rise is due to increased production driven by muscle oxidative stress. Thus, while it is an excellent predictor of outcome it is not an accurate reflection of GFR in this setting [15].

Relatively smaller increases are noted with serum cystatin C concentrations [16], but an increase greater than 0.009 mg/L per hour over six hours predicts death [14].

Acute kidney injury generally resolves over a couple of weeks in patients who survive that long [17].

Blood gas Alkalemia may occur due to excessive vomiting, but it is usually only present early in the course of acute poisoning. Acidemia is commonly observed due to a combination of respiratory acidosis (from paraquat-induced alveolitis or aspiration pneumonitis) and metabolic acidosis (from diarrhea, acute kidney injury, mitochondrial toxicity, or hypotension).

A venous blood gas (VBG) is a useful screening test and may be used for serial monitoring but is unreliable in hypotensive patients. Critically ill patients managed in a critical care setting usually receive an arterial line and their acid-base status is followed by arterial blood gases unless palliative measures are introduced. (See "Venous blood gases and other alternatives to arterial blood gases".)

Compensatory hyperventilation by the patient in response to hypoxia or acidemia may correct the blood pH in mild acidosis but is usually insufficient in cases of severe poisoning. Persistent hypoxia is associated with an invariably fatal outcome [18].

Arterial lactate Lactic acidosis occurs in cases of severe paraquat poisoning due to multiorgan dysfunction, hypotension, and hypoxic acute respiratory distress syndrome. The severity of lactic acidosis following volume resuscitation reflects the severity of poisoning. Two retrospective studies, noted that a lactate concentration above 4.4 mmol/L (40 mg/dL) [19] or 3.35 (30 mg/dL) mmol/L [20], respectively, was associated with a fatal outcome (sensitivity 82 and 74 percent, respectively; specificity 88 and 91 percent, respectively). Thus, the lactate concentration can be used to help determine prognosis. Serial measurements are typically needed, as one-time measurements may be unrepresentative.

Diagnostic imaging of chest Chest radiographs are useful for assessing patients with clinical features suggestive of acute lung injury, including hypoxia, hyperventilation, and crackles on auscultation. Infiltrates may be a direct effect of paraquat (usually bilateral) or aspiration (more commonly focal, particularly involving the right lung). Radiographic changes may also include diffuse alveolar infiltrates or pneumomediastinum (the latter is associated with increased mortality) in the early phase (one to two weeks post exposure) (image 1), findings consistent with acute respiratory distress syndrome (ARDS), and reticulo-interstitial infiltrates several weeks or later post-poisoning from progressive fibrosis (image 2). A repeat chest radiograph should be obtained to document progression or regression in the signs of lung injury, particularly if there is doubt regarding the cause and other treatment is to be pursued. Lung ultrasound can also be used to monitor changes in acute lung injury from paraquat poisoning [21]. (See "Acute respiratory distress syndrome: Clinical features, diagnosis, and complications in adults", section on 'Clinical features'.)

Toxicology screen ‒ Paraquat poisoning does not usually lead to alterations in a patient’s level of consciousness. Therefore, in patients with altered mental status in whom history may be limited, we perform routine toxicologic testing. This includes obtaining an electrocardiogram to screen for exposure to cardiotoxic agents and testing for acetaminophen (APAP) exposure. However, in the authors’ experience, ingestion of other poisons is rare in patients with paraquat poisoning.

Specific testing for paraquat exposure

Urine paraquat Qualitative confirmation of paraquat in the urine is inexpensive and easily performed in a laboratory. The main role of this test is to confirm or exclude exposure to paraquat [22-24]. The presence of paraquat is confirmed by a color change noted after the addition of a dithionite solution (picture 2). The test should be performed on a fresh urine sample around six hours after ingestion. However, the test is likely to be positive after a few hours and remains positive for several days after large ingestions. Ready-made paraquat detection kits are available free of charge from Syngenta and can be obtained using the contact information in the following reference [25].

A qualitative study in 233 patients presenting within 12 hours of poisoning noted that compared to a control solution (paraquat 2 mg/L), a negative urinary dithionite test corresponded to 100 percent survival. In contrast, the mortality was 40 percent when the urinary dithionite test was positive [24].

A number of methods for conducting the urine dithionite test have been described. We suggest the following method using freshly prepared solutions. Add 100 mg of sodium dithionite to 10 mL of 2 M sodium hydroxide, then add 200 µL of this solution to 2 mL of urine [24]. A similar method involves adding 1 g of sodium bicarbonate and 1 g of sodium dithionite (or 2 mL of 1 percent sodium dithionite in 1 molar sodium hydroxide) to 10 mL of urine [23]. Observe for a color change: blue suggests paraquat and green suggests diquat [26]. This test is semi-quantitative, whereby the darker the color the higher the concentration. Thus, it is likely that patients whose urine turns darker blue will fare worse.

Serum paraquat concentration – The serum paraquat concentration relative to the time of poisoning predicts the likelihood of death following acute poisoning. Several validated nomograms have been developed that correlate the serum paraquat concentration with mortality risk. The accuracy of these nomograms is similar, with a sensitivity and specificity of about 90 percent, although they are better at predicting death than survival [3].

The Proudfoot nomogram, best cut-off for the Severity in Paraquat Poisoning (SIPP), and the 50-50 survival prediction line are shown in the attached figure (figure 1). The SIPP score is calculated by multiplying the paraquat concentration (mg/L) by the time since poisoning (hours). A SIPP score less than 10 (the best cut-off) indicates survival is likely; the higher the score the more rapidly death may be expected [27].

Challenges to the clinical use of serum paraquat concentrations and related nomograms include an imprecise or unknown time since exposure, and the need to have access to a paraquat assay in a relevant time frame. Laboratories performing quantitative paraquat assays are uncommon and the test is infrequently performed. The delay to obtain a result may be days or even weeks (often long after the patient has died).

Qualitative serum paraquat testing – An alternative qualitative approach is to conduct the dithionite test in the plasma of patients with a positive urinary dithionite test. Here, the dithionite solution is prepared as described above, but it is added to 2 mL of plasma, instead of urine. Compared with the control solution, an equivocal color change was associated with 50 percent mortality, while a definitive color change was associated with 100 percent mortality [24]. Potentially, the dithionite test may be used to approximate the serum paraquat concentration by comparing the extent of the color change to a color chart [28], but further validation is required.

In patients with dermal, ocular, or inhalational exposure, there is generally no need for any laboratory investigations, but a urinary dithionite test can be done at 6 hours to reassure the patient. If there is any doubt about systemic absorption from a dermal exposure (eg, a large exposure on broken skin), further testing can be performed at 12 hours post-exposure to account for delayed absorption.

DIAGNOSIS — The diagnosis of paraquat poisoning is usually determined by a history of ingestion, or other exposure, along with strong supporting evidence from the physical examination, notably the presence of oropharyngeal burns in the case of oral exposure (picture 1), and the subsequent development of acute kidney injury, metabolic acidosis, or acute respiratory distress syndrome. The diagnosis can be confirmed with urine or blood tests, such as the urine dithionite test. (See 'Laboratory evaluation and diagnostic imaging' above.)

DIFFERENTIAL DIAGNOSIS — The diagnosis of paraquat poisoning is usually clear from the history. Difficulties are most likely to arise in the setting of an ingestion of an unknown agrochemical when paraquat/diquat are possibilities. The combination of severe oropharyngeal burns and systemic toxicity makes paraquat extremely likely. No other pesticides cause such severe mucosal burns (although minor ulceration is common with many herbicides) [29,30]. Conversely, most corrosive substances do not cause acute systemic toxicity (eg, acute kidney injury). The typical syndrome associated with acute paraquat poisoning has been mistaken initially for HIV-related infections (oral candidiasis and Pneumocystis jirovecii pneumonia) [31]. The diagnosis of paraquat poisoning can generally be rapidly confirmed with the urine dithionite test. (See 'Laboratory evaluation and diagnostic imaging' above.)

MANAGEMENT

Overview — The management of paraquat or diquat exposure is determined on an individual basis depending upon the amount ingested and the time elapsed since the exposure. Although recommended treatments are similar, there is much greater experience with paraquat than diquat poisoning. Overall, none of the current treatments have proven effective for patients with severe poisoning and prognosis is uniformly poor in all centers, including those who treat aggressively with multimodal therapies.

Symptoms and signs of paraquat poisoning usually manifest within 12 hours so patients should be monitored for at least this duration. However, a negative urinary dithionite test beyond six hours post-ingestion suggests that exposure was minimal and the patient can be medically cleared if asymptomatic. (See 'Specific testing for paraquat exposure' above.)

When appropriate, gastrointestinal decontamination is recommended to limit systemic exposure. Hemoperfusion or hemodialysis followed by continuous hemodiafiltration or repeated hemoperfusion may be beneficial if commenced within four hours of poisoning. (See 'Gastrointestinal decontamination' below and 'Indications for extracorporeal therapies' below.)

Many antidotes with logical mechanisms of action have been proposed, in particular antiinflammatory and antioxidant therapies. However, only limited animal and human data support the efficacy of such treatments. This relates, in part, to the limitations of most studies conducted to date (uncontrolled, small, inadequate blinding), and thus more research is required to clarify their effect. (See 'Specific treatments and antidotal therapy' below.)

Given the high mortality from acute paraquat poisoning, some centers administer all potential treatments to patients with acute paraquat poisoning in the hope of a beneficial effect. A better approach may be to emphasize palliative care of the patient outside of a critical care environment (eg, titrated parenteral morphine or fentanyl for pain and dyspnea and oxygen for dyspnea with desaturation) when death seems highly likely based upon the history (amount of exposure), prognostic tests, or clinical signs of deterioration. Adequate analgesia should be provided in all cases. We use titrated fentanyl or morphine. (See 'Medical management versus palliative care' below.)

Initial resuscitation — Resuscitation of the patient with acute paraquat poisoning follows standard guidelines except that oxygen therapy should not be administered unless there is confirmed hypoxia, as oxygen may exacerbate the oxygen-mediated cellular damage induced by redox cycling. Fluid losses are usually treated with 2 or 3 L of isotonic crystalloid, unless the presentation to hospital was extremely delayed (eg, more than 24 hours), in which case larger volumes may be needed. Continuous pulse oximetry is required to monitor for deteriorating gas exchange. Signs of severe systemic illness (eg, severe hypoxia, hypotension, or acidosis) indicate a poor prognosis. The institution of more advanced treatments, including tracheal intubation, mechanical ventilation, and hemodynamic support with vasopressors, is generally futile in this setting, but clinical decisions should also be based upon the history (amount of exposure), prognostic tests, and clinical signs of deterioration. If active treatment is to be pursued, then standard guidelines for such advanced treatments are acceptable.

Gastrointestinal decontamination — Activated charcoal (1 g/kg in water; maximum dose 50 g) or Fuller’s Earth (2 g/kg in water; maximum dose 150 g in water) should be given as soon as possible per oral or via a nasogastric tube. It is anticipated that effects are maximized if gastrointestinal decontamination is given within approximately two hours of ingestion, but a benefit from giving charcoal after this (up to 12 hours of ingestion) in lesser degrees of poisoning cannot be excluded. Treatment should not be delayed for confirmatory testing. (See 'Laboratory evaluation and diagnostic imaging' above.)

Clinical trials demonstrating the effectiveness of gastrointestinal decontamination are lacking, but both activated charcoal and Fuller’s Earth adsorb paraquat in vitro and thus may be beneficial in minor exposures (eg, small accidental ingestion) [2]. Neither treatment is toxic. Fuller’s Earth is no longer widely available.

Decontamination is not useful with delayed presentations due to the rapid absorption and high toxicity of paraquat. Gastric lavage and forced emesis are contraindicated due to paraquat-induced caustic injury. However, in cases that present early, a nasogastric tube should be inserted and the stomach contents aspirated prior to administration of charcoal.

Topical and inhalation exposure — Exposed skin should be washed thoroughly with soap and water as soon as possible for up to 15 minutes (see "Topical chemical burns: Initial evaluation and management", section on 'Water irrigation'). Staff are at negligible risk of secondary contamination (being poisoned while treating the patient) when universal precautions are used.

Ocular exposures should be decontaminated using standard methods for corrosive exposures. We recommend rinsing the eye using an appropriate technique for 30 minutes with isotonic saline and then managed as per standard guidelines for ocular exposures. (See "Topical chemical burns: Initial evaluation and management", section on 'Patient with eye exposure'.)

Inhalation exposures involve removal of the patient from the source. This should already have been accomplished by the time the patient has presented to a healthcare facility.

Monitoring — Pulse oximetry should be monitored continuously for signs of deteriorating gas exchange. Cardiac toxicity is uncommon and cardiac monitoring is generally unnecessary.

Specific treatments and antidotal therapy

Indications for extracorporeal therapies — We suggest treatment with hemoperfusion for four hours if it can be initiated within four hours of ingestion [32,33]. Unfortunately, this is not possible in most cases of paraquat ingestion. Ideally, paraquat exposure should be confirmed but signs of severe poisoning should not be present prior to commencing therapy, as more time is required for these to appear and prognosis is poor in this context. (See "Hemoperfusion", section on 'Indications'.)

Animal studies and several clinical studies in humans using different approaches, including a single treatment with hemoperfusion, multiple treatments, or hemoperfusion followed by continuous hemodiafiltration, many published in non-English language journals, have reported benefit from early extracorporeal therapy [34-38].

Other extracorporeal therapies, such as intermittent hemodialysis or hemofiltration, should be nearly as effective in enhancing elimination at comparable blood flow rates because paraquat has low protein binding. Concomitant hemodialysis and hemoperfusion may even be superior [39]. Thus, in patients who present soon after ingestion, it is reasonable to use these therapies if hemoperfusion is not available. A meta-analysis of 290 patients enrolled in three randomized controlled trials concluded that compared with hemoperfusion alone, hemoperfusion followed by continuous venovenous hemofiltration prolonged the time to death but did not significantly decrease mortality [40]. Hemodialysis or hemofiltration may also be used in patients with acute kidney injury as renal replacement therapy according to standard criteria. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose".)

A rebound in the plasma paraquat concentration may follow hemoperfusion but this effect can be minimized by following with a continuous extracorporeal technique.

Antiinflammatory and immunosuppressive therapy — Our practice is to give dexamethasone 8 mg intravenously (IV) every 8 hours for the first 72 hours to patients with acute paraquat poisoning. If there is evidence of severe poisoning, we continue this therapy for up to five weeks.

The initial enthusiasm for antiinflammatory plus immunosuppressive therapy, primarily using a combination of cyclophosphamide and glucocorticoid, has not been validated by rigorous studies and we do not recommend treatment with this combination [41]. The largest randomized controlled trial completed to date (298 patients) reported no benefit [42]. The results of earlier uncontrolled or small randomized trials suggested benefit, but methodological problems limit their applicability [43]. A large retrospective study noted modest benefits from immunosuppression regimens that included dexamethasone (but not other therapies), especially when combined with hemoperfusion [37].

Existing data from randomized controlled trials do not demonstrate a benefit from a traditional Chinese medicine called Xuebijing, which is thought to have antiinflammatory effects [44].

Antioxidant therapy — Several antioxidants have been studied in the treatment of acute paraquat poisoning, but further research in humans is needed. Pending additional study, our practice is to administer acetylcysteine continuously while patients are experiencing acute toxicity (ie, are hospitalized). (See "Acetaminophen (paracetamol) poisoning: Management in adults and children", section on 'Acetylcysteine administration and monitoring'.)

A range of antioxidants, including acetylcysteine (usually administered at a similar or higher dose than that used for acetaminophen/paracetamol poisoning), sodium salicylate, deferoxamine, vitamin C (ascorbic acid), and vitamin E (alpha-tocopherol), have modest effects in animal studies and are sometimes used on the basis that they have possible benefit and low toxicity [45].

Ongoing management — Avoid oxygen therapy unless there is marked hypoxia (at which point a fatal outcome is inevitable) [18]. Electrolyte abnormalities should be corrected according to usual practice. Regular monitoring of blood lactate concentrations and renal function gives insight into the patient’s prognosis. Acute hepatic injury and pancreatitis may occur but have not been shown to influence prognosis.

The likely outcome is generally apparent within a day or two of the ingestion. At this stage, patients are either critically ill with severe poisoning, display mild to moderate poisoning but adequately compensate without intervention (in which case death is still possible but will occur days or weeks later), or are asymptomatic.

Renal failure generally resolves over a number of weeks, but maintenance renal replacement therapy may be required during that time [17]. In contrast, lung injury generally becomes progressively more severe for several weeks (image 2). Lung transplantation has been performed but generally failed due to persistent, albeit low, serum paraquat concentrations, which injure the pulmonary allograft [46].

Diquat poisoning may still be associated with severe multiorgan failure and rapid death, similar to paraquat. However, patients surviving this exposure are more likely to recover and not experience delayed or progressive respiratory failure [47].

Medical management versus palliative care — Swallowing more than 30 mL of 20 to 24 percent (w/v) paraquat formulation is typically lethal [9]. Once manifestations of systemic toxicity appear, aggressive and invasive therapies in an intensive care unit are unlikely to improve outcomes or assist the patient and relatives to accept the outcome. Instead, we believe patients manifesting clinical and biochemical evidence of severe poisoning should be provided supportive (but not intensive) care. Notable manifestations of severe poisoning include tachypnea and hypoxia on room air, refractory hypotension despite adequate fluid resuscitation, and clinical or radiographic evidence of mediastinitis (including pneumothorax). Other signs associated with high mortality include severe acidosis, hypoxemia, and a rapid decline in renal function (see 'Laboratory evaluation and diagnostic imaging' above). Nomograms to help determine prognosis are available. (See 'Specific testing for paraquat exposure' above.)

Methods for providing quality palliative care are reviewed separately. (See "Withholding and withdrawing ventilatory support in adults in the intensive care unit" and "Approach to symptom assessment in palliative care" and "Overview of managing common non-pain symptoms in palliative care".)

PEDIATRIC CONSIDERATIONS — Exposures in children less than 10 years of age are usually accidental, as opposed to adults whose exposure is often intentional [48,49]. Therefore, in children there is often great uncertainty about the dose ingested. If the child spits out the herbicide preparation without swallowing, there may be oropharyngeal but no systemic features. Otherwise, the manifestations and treatment are similar to those of adults.

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment".)

SUMMARY AND RECOMMENDATIONS

Introduction – Paraquat is a rapidly-acting, nonselective herbicide that is highly toxic when ingested and a leading cause of fatal poisoning in many parts of Asia, Pacific nations, and the Americas. Topical and inhalational exposure is far less toxic. Diquat is a related herbicide that is often formulated with paraquat. Diquat poisoning appears to involve mechanisms and manifest clinical features similar to those of paraquat. (See 'Introduction' above.)

Swallowing more than 30 mL (a mouthful or two) of 20 to 24 percent paraquat concentrate is usually lethal, and as little as 10 mL can cause significant illness. Therefore, it is important to know the concentration and dose of paraquat.

Clinical features of poisoning – Patients who have ingested paraquat often complain of mouth pain, pain with swallowing, nausea, vomiting, and abdominal pain. A “burning skin” sensation is common. Respiratory complaints indicate systemic poisoning and are associated with fatal outcomes. (See 'Clinical features of poisoning' above.)

Important examination findings associated with paraquat poisoning include pulmonary abnormalities (dyspnea, tachypnea, hypoxia, crackles), tachycardia, hypotension, oral lesions (picture 1), and abdominal tenderness. Symptoms and signs of paraquat poisoning usually manifest within 12 hours so patients should generally be monitored for at least this duration. (See 'Physical examination and basic monitoring' above.)

Laboratory testing – In patients with significant poisoning, blood tests should be obtained on admission and then repeated every 6 to 12 hours for the first 48 hours. Recommended tests are complete blood count (CBC), serum chemistries, blood gas, and arterial lactate. Often, tests are used to help determine the prognosis and serial tests are unnecessary if the prognosis is poor. (See 'General testing' above.)

Diagnosis – The diagnosis of paraquat poisoning is suspected from a history of ingestion, or other exposure, along with strong supporting evidence from the physical examination, notably the presence of oropharyngeal burns in the case of oral exposure, and the subsequent development of acute kidney injury, metabolic acidosis, or acute respiratory distress syndrome. The diagnosis is confirmed with urine or blood tests. (See 'Diagnosis' above.)

Adding dithionite solution to a urine sample is a qualitative test used to confirm or exclude exposure to paraquat. A negative urinary dithionite test on a fresh urine sample six hours after ingestion suggests that exposure was minimal and the patient can be medically cleared if asymptomatic. (See 'Specific testing for paraquat exposure' above.)

A serum paraquat concentration, although not routinely available, predicts the likelihood of death following acute poisoning when plotted relative to the time of ingestion on predictive nomograms (figure 1).

Overview of management – The management of paraquat exposure is determined on an individual basis depending upon the amount ingested and the time elapsed since the exposure. Overall, none of the current treatments have proven effective for patients with signs of severe poisoning and prognosis is uniformly poor in all centers, including those who treat aggressively with multimodal therapies. (See 'Overview' above.)

Resuscitation of the patient with acute paraquat poisoning follows standard guidelines except that oxygen therapy should not be administered unless there is confirmed hypoxia, as it may exacerbate the oxygen-mediated cellular damage.

Fluid losses are usually treated with 2 or 3 L of isotonic crystalloid; larger volumes may be needed if there is greater than a 24-hour delay in presentation.

Continuous pulse oximetry is required to monitor for deteriorating gas exchange. Signs of severe systemic illness (eg, severe hypoxia, hypotension, or acidosis) indicate a poor prognosis. (See 'Monitoring' above and 'Ongoing management' above.)

Gastrointestinal decontamination – In patients who present within approximately two hours of ingestion, we suggest that activated charcoal (1 g/kg in water; maximum dose 50 g) or Fuller's earth (2 g/kg in water; maximum dose 150 g in water) be given as soon as possible per oral or via a nasogastric tube (Grade 2C). (See 'Gastrointestinal decontamination' above.)

Extracorporeal therapy – In all patients with confirmed paraquat exposure who can have extracorporeal therapy initiated within four hours of ingestion, we suggest treatment with hemoperfusion or hemodialysis (Grade 2C). Hemoperfusion or hemodialysis are continued for four hours. (See 'Antiinflammatory and immunosuppressive therapy' above.)

Antiinflammatory and antioxidant therapies – For patients manifesting systemic toxicity but without signs of inevitable death, we suggest treatment with high-dose glucocorticoids and acetylcysteine (Grade 2C). We typically use dexamethasone 8 mg intravenously (IV) every eight hours, for several weeks, and acetylcysteine 300 mg/kg per day while hospitalized. These antidotes are of low toxicity and might provide some small benefit. (See 'Antiinflammatory and immunosuppressive therapy' above and 'Antioxidant therapy' above.)

Palliative care – Given the high mortality and the absence of effective treatment, the authors believe it may be best to emphasize palliative care of the patient outside of a critical care environment when death seems highly likely based upon the history (amount of exposure), prognostic tests, or clinical signs of deterioration. (See 'Medical management versus palliative care' above.)

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