Poisoning by Plants

Abstract

Background

Questions on poisoning by plants are a common reason for inquiries to poison information centers (PIC). Over the years 2011–2020, plant poisoning was the subject of 15% of all inquiries to the joint poison information center in Erfurt, Germany (Gemeinsames Giftinformationszentrum Erfurt, GGIZ) that concerned poisoning in children (2.3% in adults). In this patient collective, plant poisoning occupied third place after medical drugs (32%) and chemical substances (24%), and was a more common subject of inquiry than mushroom poisoning (1.5%).

Methods

This review is based on pertinent publications retrieved by a selective literature search in PubMed/TOXLINE on plant poisoning and on 12 epidemiologically and toxicologically relevant domestic species of poisonous plants in risk categories 2 and 3 (up to 2021).

Results

Medical personnel should have basic toxicological knowledge of the following highly poisonous plants: wolfsbane (aconitum), belladonna, angel’s trumpet, cowbane (cicuta virosa), autumn crocus, hemlock, jimson weed, henbane, castor bean (ricinus), false hellebore, foxglove (digitalis), and European yew. The intoxication is evaluated on the basis of a structured history (the “w” questions) and the clinical manifestations (e.g., toxidromes). Special analysis is generally not readily available and often expensive and time-consuming. In case of poisoning, a poison information center should be contacted for plant identification, risk assessment, and treatment recommendations. Specimens of plant components and vomit should be obtained, if possible, for further testing. Measures for the elimination of the poisonous substance may be indicated after a risk–benefit analysis. Specific antidotes are available for only a few types of plant poisoning, e.g., physostigmine for tropane alkaloid poisoning or digitalis antibodies for foxglove poisoning. The treatment is usually symptomatic and only rarely evidence-based. Individualized medical surveillance is recommended after the ingestion of large or unknown quantities of poisonous plant components.

Conclusion

The clinician should be able to recognize dangerous domestic species of poisonous plants, take appropriate initial measures, and avoid overdiagnosis and overtreatment. To improve patient care, systematic epidemiological and clinical studies are needed.

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A national monitoring system for poisonings has not been implemented in Germany as yet; for this reason, epidemiological data are often incomplete. Nevertheless, the analysis of individual datasets is helpful, since questions on poisoning by plants are a common reason for inquiries to poison information centers (PIC) (1). In the period 2011–2020, 15% of all inquiries to the joint PIC (Gemeinsames Giftinformationszentrum, GGIZ) in Erfurt, Germany, concerning children related to plants (adults: 2.3%). In this patient collective, plant poisoning came third after medical drugs (32%) and chemical substances (24%), and was a more common subject of inquiry than mushrooms (1.5%) (1). Similar data are available for other European countries such as Switzerland (2020: drugs 34.8%, household products/chemicals 26.3%, plants 10%, mushrooms 1.7%—for all age groups) (2).

A recent study at the GGIZ showed that in particular children aged 1–6 years were exposed to plants with fruit-like structures (for example, berries, capsules, pods, stone fruits) in the period 2010–2019 (of a total of 7607 relevant fruit plant inquiries, 5284 [69.5%] related to young children) (3). According to the German Federal Statistical Office, a total of 263 patients were treated as inpatients in 2019 following exposure to toxic plants (ICD-10: T62.2) or berries (T62.1), of which 95 were children aged 1–4 years (4).

Although life-threatening plant poisonings are relatively rare in Germany (for example, 39 cases in 2010–19 in the GGIZ catchment area, unpublished data), there is a considerable need for information and education on the broad population level.

This review presents a selection of native poisonous plant species (3, 5– 7). It also provides information relating to the diagnosis and treatment of plant poisonings.

Method and data basis

A selective literature search was carried out in PubMed/TOXLINE using the search terms (plants) AND (poisoning OR intoxication), (fruits OR berries OR seeds OR leaves OR roots) AND (poisoning OR intoxication), and regarding 12 poisonous plant species (Figure, Table 1, eTable 1) with English-language and botanical names up to publication year 2021. Selection criteria included epidemiological relevance (frequency of inquiries to the GGIZ, severe poisonings, fatalities) and high risk assessment by the German Federal Institute for Risk Assessment (Bundesinstitut für Risikobewertung, BfR) (5– 7). A total of 12 poisonous plants in risk categories (RC) 2 and 3 were identified (Figure, Table 1, eTable 1).

Figure.

A selection of 12 native poisonous plants with flowers or fruits/seeds in risk categories 2 and 3 in relation to which a high number of inquiries were made or severe poisonings reported to the joint PIC in Erfurt, Germany, in the period 2010–2019. Since the phenotypic characteristics of these plants (for example, color, flower shape) can vary depending on the season and location, the classification and identification of comparative plants from nature on the basis of illustrations or photos alone is to be regarded as unreliable. For reliable determination—especially in the case of poisoning—trained specialists (for example, botanists, toxicologists, the poison control helpline) should be consulted.

Table 1. Synoptic presentation of the toxicology of native poisonous plants in risk category 2 or 3 in relation to which a high number of inquiries were made or severe poisonings were reported to the joint PIC in Erfurt (GGIZ), Germany, in the period 2010–19.

Poisonous plant	Relevant constituents	Common symptoms of poisoning	Treatment options	References
Wolfsbane Aconitum spp. RC3	Aconitine, mesaconitine, hypaconitine, lycaconitine	(Peri-)oral paresthesia, numbness and pain (anesthesia dolorosa), dysgeusia, dry mouth, nausea, vomiting, dizziness, hypotension, cardiac arrhythmia, bradycardia, seizures,respiratory depression	PD; consider antiarrhythmic drugs (e.g., amiodarone,magnesium sulfate, lidocaine, flecainide) or atropine for bradycardia; consider pacemaker therapy, sedatives	(5, 6, 8– 10)
Belladonna Atropa belladonna RC3	L-Hyoscyamine, atropine (DL-hyoscyamine),scopolamine, atropamine	Anticholinergic syndrome: flushing, dry,warm skin, mydriasis, dry mouth, tachycardia, agitation, confusion, hallucination, inhibition of micturition, hyperthermia, nausea, vomiting	PD, physical cooling (no antipyretic agents!), consider benzodiazepines; antidotein marked anticholinergic or central symptoms (e.g., delirium): physostigmine	(5, 6, 8– 10)
Angel’s trumpet Brugmansia spp. RC3	Scopolamine (L-hyoscine), L-hyoscyamine, atropine (DL-hyoscyamine)	Anticholinergic syndrome (see belladonna), especially seizures, hallucinations, drowsiness, coma	See belladonna; continuous monitoring, especially if there is risk of harm to self or others	(5, 6, 8– 10)
Cowbane Cicuta virosa RC3	Cicutoxin, fool’s parsley, cicutol	Burning pain in the mouth, severe recurrent vomiting, muscle cramps, rhabdomyolysis, kidney failure, coma, hyperthermia, apnea	PD, benzodiazepines, muscle relaxants, hemodialysis (in kidney failure)	(5, 6, 8– 10)
Autumn crocusColchicum autumnale RC3	Colchicine	Furry feeling in mouth/throat, persistent nausea, watery-mucous, sometimes bloody gastroenteritis; electrolyte disorders,exsiccosis, confusion/delirium, bleeding, cardiogenic shock, multiorgan failure	PD (especially activated charcoal), consider cholestyramine (3 x 4 g/day) to interruptenterohepatic circulation; intensive care, hemodialysis (in kidney failure)	(5, 6, 8– 10, e19)
Poison hemlockConium maculatum RC3	Coniine, γ-coniceine	Irritation/burning in oral mucosa, numbness, sore throat, recurrent vomiting, diarrhea,dizziness, „heavy legs“, angina pectoris, seizures, rhabdomyolysis, kidney failure, apnea	PD, benzodiazepines,hemodialysis (in kidney failure)	(5, 6, 8– 10, e9)
Jimson weedDatura stramonium RC3	L-Hyoscyamine, atropine (DL-hyoscyamine),scopolamine	Anticholinergic syndrome (see belladonna), CK elevation	See belladonna and angel’s trumpet	(5, 6, 8– 10)
HenbaneHyoscyamus niger RC3	Scopolamine, L-hyoscyamine, atropine (DL-hyoscyamine)	Anticholinergic syndrome (see belladonna); predominantly central sedating symptoms (sleepiness) due to high scopolamine content	See belladonna and angel’s trumpet	(5, 6, 8– 10)
Castor bean Ricinus communis RC3	Ricin, ricinine	Nausea, hemorrhagic gastroenteritis;exsiccosis, hypotension, tachycardia, hypoglycemia, liver and spleen necrosis, kidney failure, multiorgan failure	PD, close monitoring of liver, kidney, and coagulationvalues	(5, 6, 8– 10, e25)
False hellebore Veratrum spp. RC3	Protoveratrines, jervine, germerine	Similar to wolfsbane: burning in the mucous membranes, (recurrent) vomiting, exsiccosis, bradycardia, hypotension, hypothermia	PD; consider antiarrhythmic drugs (magnesium sulfate,lidocaine, flecainide) or atropine in bradycardia	(5, 6, 8– 10)
FoxgloveDigitalis spp. RC2	Digoxin, digitoxin, gitoxin, lanatoside C	Nausea, (recurrent) vomiting, abdominal pain, AV block, tachycardia, pallor, headache, dizziness, fatigue, color visiondeficiencies (xanthopsia, “yellow vision”), hallucinations	PD (especially activated charcoal), consider cholestyramine (3 x 4 g/day) to interrupt the enterohepatic circulation; electrolyte monitoring (in particular potassium, calcium), antidote: digitalis antibodies, ICU monitoring	(5, 6, 8– 10, 30– 33)
European yewTaxus baccata RC2	Taxine A, B, C; taxols,taxanes, baccatines, cyanogenic glycosides	Choking, nausea, (recurrent) vomiting,abdominal pain, diarrhea, erythema, tachycardia/bradycardia, hypotension, cardiac arrhythmias, seizures, coma, cardiogenic shock, respiratory paralysis	PD (even hours after ingestion of needles); consider antiarrhythmic drugs (lidocaine), consider digitalis antibodies; consider calcium gluconate i.v., ultima ratio: i.v. lipid emulsion	(5, 6, 8– 10)

The risk categorization (RC 2, 3) is in line with the re-evaluation of poisonous plants by the “Toxicity of Plants” Committee at the German Federal Institute for Risk Assessment (7). According to this, fruit plants are classified as RC 2 or 3 if moderate or severe symptoms according to the Poisoning Severity Score (PSS) have been reported in the past following accidental ingestion of small quantities, or if toxic constituents are detectable in the plant in such high concentrations that moderate to severe poisoning, at least in small children, appears possible. CK, creatine kinase; PD, primary detoxification (activated characoal, gastric lavage, endoscopic extraction); ICU, intensive care unit; i.v., intravenous; detailed information is provided in eTable 1.

eTable 1. Detailed presentation of the toxicology of native poisonous plants in risk category 2 or 3 in relation to which a high number of inquiries were made or severe poisonings occurred in the period 2010–19 at the joint PIC in Erfurt, Germany.

Poisonous plant	Relevant constituents	Sites of action	Frequent symptoms of poisoning	Fatal dose	Treatment options	Special aspects	References
Wolfsbane Aconitum spp. RC 3	Aconitine, mesaconitine, hypaconitine, lycaconitine	Voltage-gated sodium channels (enhanced depolarization)	(Peri-)oral paresthesia, numbness and pain (anesthesia dolorosa), dysgeusia, dry mouth, nausea, vomiting, dizziness, hypotension, cardiac arrhythmia, bradycardia, seizures,respiratory depression	A few grams of plant material (adults: 1–2 mg aconitine per kg BW); 2–5 g of root	PD; consider antiarrhythmic drugs (e.g., amiodarone, magnesium sulfate, lidocaine, flecainide) or atropine for bradycardia; consider pacemakertherapy, sedatives	All plant parts poisonous; transcutaneous absorption of poison possible (caution: protective gloves when handling stools, vomit!); risk ofconfusion with: lovage, parsley, horseradish root	(5, 6, 8– 10)
Belladonna Atropa belladonna RC 3	L-Hyoscyamine, atropine (DL-hyoscyamine), scopolamine, atropamine	Muscarinic acetylcholine receptors (competitiveantagonism)	Anticholinergic syndrome: flushing, dry, warm skin, mydriasis, dry mouth,tachycardia, agitation, confusion, hallucination, inhibition of micturition, hyperthermia, nausea, vomiting	Children: approx. 2–5 berries; adults: approx. 10–20 berries	PD, physical cooling(no antipyretic agents!), consider benzodiazepines; antidote in marked anticholinergic or central symptoms (e.g., delirium): physostigmine	All plant parts poisonous (particularly the sweet berries); transcutaneous absorption of poison possible; sometimesmisused as a drug	(5, 6, 8– 10)
Angel’s trumpet Brugmansia spp. RC 3	Scopolamine (L-hyoscine), L-hyoscyamine, atropine (DL-hyoscyamine)	Muscarinic (alsonicotinergic in high doses) acetylcholine receptors (competitive antagonism)	Anticholinergic syndrome (see belladonna),especially seizures, hallucinations, drowsiness, coma	A few blossoms and leaves	See belladonna; continuous monitoring, especially if there is a risk of harmto self or others	All plant parts toxic; transcutaneous absorption of poison possible; often as cultivated garden pot plants; sometimes misused as a drug; hallucinations lasting several days	(5, 6, 8– 10)
Cowbane Cicuta virosa RC 3	Cicutoxin, fool’s parsley, cicutol	GABA-gated chloride channels (GABAAreceptors) (antagonism)	Burning pain in the mouth, severe recurrent vomiting, muscle cramps, rhabdomyolysis, kidney failure, coma, hyperthermia, apnea	A few grams of plantmaterial	PD, benzodiazepines, muscle relaxants,hemodialysis (in kidney failure)	Found in: marshybiotopes; all fresh plant parts are toxic (especially roots), carrot-like odor; risk of confusion with: celery, ground elder	(5, 6, 8– 10)
Autumn crocus Colchicum autumnale RC 3	Colchicine	Mitosis(inhibition of spindle formation)	Furry feeling in mouth/throat, persistent nausea, watery-mucous, sometimes bloody gastroenteritis; electrolyte disorders, exsiccosis, confusion/delirium, hemorrhage, cardiogenic shock, multiorgan failure	Children: approx. 5–10 seeds Adults: 30–85 g of leaves (approx. 20 mg colchicine)	PD (in particular activated charcoal), consider cholestyramine (3 x 4 g/day) to interrupt enterohepatic circulation; intensive care, hemodialysis (in kidney failure)	All plant parts toxic(especially seeds); relatively long symptom latency (2–6 h), risk of confusion with: wild garlic leaves (but with garlic-like odor), young lily of the valley leaves	(5, 6, 8– 10, e19)
Poison hemlock Conium maculatum RC 3	Coniine, γ-coniceine	Nicotinergic acetylcholine receptors (competitiveantagonism)	Irritation/burning in the oral mucosa, numbness, sore throat, recurrent vomiting, diarrhea, dizziness, “heavy legs,” chest pain, seizures, rhabdomyolysis, kidney failure, apnea	Approx. 5–8 g plantmaterial	PD, benzodiazepines,hemodialysis (in kidney failure)	All plant parts toxic;transcutaneous absorption of poison possible; unpleasant odor (“mouse urine”)	(5, 6, 8– 10, e9)
Jimson weed Datura stramonium RC 3	L-Hyoscyamine, atropine (DL-hyoscyamine), scopolamine	Muscarinic (and alsonicotinergic in high doses) acetylcholine receptors (competitive antagonism)	Anticholinergic syndrome (see belladonna), CK elevation	A few grams of plantmaterial	See belladonna and angel’s trumpet	All plant parts toxic(especially seeds); transcutaneous absorption of poison possible; the fruits may be mistaken for chestnuts, burdock, the seeds with “spices”, “urge to undress,” likely due to hyperthermia	(5, 6, 8– 10)
Henbane Hyoscyamus niger RC 3	Scopolamine, L-hyoscyamine, atropine (DL-hyoscyamine)	Muscarinic (and alsonicotinergic in high doses) acetylcholine receptors (competitive antagonism)	Anticholinergic syndrome (see belladonna);predominantly centrally sedating symptoms (sleepiness) due to high scopolamine content	Children: approx. 15 seeds	See belladonna and angel’s trumpet	All plant parts toxic(especially seeds); sometimes misused as a drug; risk of confusion with: fruits > Cape gooseberry; poppy seed capsules; roots: > black salsify, parsnip	(5, 6, 8– 10)
Castor bean Ricinus communis RC 3	Ricin, ricinine	Ribosomes (inactivation of protein biosynthesis)	Nausea, hemorrhagic gastroenteritis; exsiccosis, hypotension, tachycardia, hypoglycemia, liver and spleen necrosis, kidney failure, multiorgan failure	Children: approx. 5–6 seeds (in isolated cases, 1 seed), depending on degree of crushing/chewing Adults: approx. 10–20 seeds, depending on degree of crushing/chewing	PD, close monitoringof liver, kidney, and coagulation values	Long latency period (> 24 h) possible; popularornamental and garden plant; attractive seeds with hazelnut-like taste; used as jewelry; toxicity increases with degree of crushing and depends on the route of exposure; ricin content depends heavily on location; the seeds may be mistaken for various beans, nuts	(5, 6, 8– 10, e25)
False hellebore Veratrum spp. RC 3	Protoveratrines, jervine, germerine	Voltage-gated sodium channels (increaseddepolarization)	Similar to wolfsbane: burning in the mucous membranes, (recurrent) vomiting, exsiccosis,bradycardia, hypotension, hypothermia	A few grams of plantmaterial; 1–2 g of root	PD; consider antiarrhythmic drugs (magnesium sulfate, lidocaine,flecainide) or atropine in bradycardia	All plant parts toxic,transcutaneous absorption of poison possible (caution: protective gloves when handling stool, vomit!); risk of confusion with: yellow gentian; root resembles valerian	(5, 6, 8– 10)
Foxglove Digitalis spp. RC 2	Digoxin, digitoxin, gitoxin, lanatoside C	Sodium/potassiumATPase of cardiom yocytes (inhibition)	Nausea, (recurrent)vomiting, abdominal pain, AV block, tachycardia, pallor, headache, dizziness, fatigue, color vision deficiencies (xanthopsia, “yellow vision”), hallucination	A few leaves	PD (in particular activated charcoal), consider cholestyramine (3 x 4 g/day) to interrupt the enterohepatic circulation; electrolyte monitoring (inparticular potassium, calcium), antidote: digitalis antibodies, ICU monitoring	All plant parts toxic(especially leaves); ornamental and garden plants; commercial immunoassays available for cardiac glycoside diagnosis; risk of confusion with: mullein, borage, comfrey, ribwort leaves	(5, 6, 8– 10, 30– 33)
European yew Taxus baccata RC 2	Taxine A, B, C; taxols, taxanes, baccatines,cyanogenic glycosides	Mitosis(inhibition of spindle formation), respiratory chain (cytochrome-c oxidase inhibition)	Choking, nausea, (recurrent) vomiting, abdominal pain, diarrhea, erythema, tachycardia/bradycardia, hypotension, cardiacarrhythmias, seizures, coma, cardiogenic shock, respiratory paralysis	Adults: 50–100 g of needles (“a few tablespoons” or “a handful” of needles)	PD (even hours after ingestion of needles); consider antiarrhythmic drugs (lidocaine), consider digitalis antibodies; consider calcium gluconate i.v., ultima ratio: i.v. lipid emulsion	All plant parts toxic (especially needles), except the red, sweet-tasting aril; common in gardens and parks; frequently used as method of suicide (e.g., tea prepared from needles), toxicity depends on degree of crushing or chewing of seeds, needles	(5, 6, 8– 10)

The risk categorization (RC 2, 3) is in line with the re-evaluation of poisonous plants by the “Toxicity of Plants” Committee at the German Federal Institute for Risk Assessment (7). According to this, fruit plants are classified as RC 2 or 3 if moderate or severesymptoms according to the Poisoning Severity Score (PSS) have been reported in the past following accidental ingestion of small quantities, or if toxic constituents are detectable in the plant in such high concentrations that moderate to severe poisoning, at least in small children, appears possible

CK, creatine kinase; GABA, γ-aminobutyric acid; GABAA receptors, GABA type A receptors; ICU, intensive care unit; i.v., intravenous; BW, body weight; PD, primary detoxification (activated charcoal, gastric lavage, endoscopic extraction)

In addition, a selective search was conducted in PubMed for publications on specific toxidromes and treatment measures, as well as in TOXLINE on plant constituents up to publication year 2021. The literature selection focused on oral forms of poisoning. In those cases where there is a lack of evidence or no basis in the literature, the measures recommended here should be seen as an expert opinion based on the experience of the authors or on established clinical practice.

Initial measures and determining the severity of poisoning

Experience has shown that the level of risk is usually unclear (for example, a questionably symptomatic child that has ingested an unknown number of unknown berries). For this reason, the situation should be assessed in a structured manner by means of (third-party) history (“w” questions):

• What (which plant parts from which species of plant) and how much was ingested when, how, and why?

• Which other individuals are affected and how?

• What are the leading symptoms (table 2), syndromes (toxidromes), preexisting diseases, and medications?

Table 2. Clinically and toxicologically relevant organ findings and cardinal symptoms in plant poisonings according to (18).

Mouth/throat	Substance residues, vomit, salivation, mucosalstatus
Lung ventilation	Breath odor, respiratory rate, lung auscultation,oxygen saturation (SaO 2 /SpO 2)
Circulation	Pulse rate, blood pressure, capillary recirculation,blood gas analysis, ECG
Neurological status	Vigilance (GCS), agitation, hallucinations, pupil size,pupillary response, impaired vision, impaired hearing, motor function, muscle tone, reflexes, seizures
Other	Body temperature, skin changes, abdominal palpation and auscultation, urogenital examination (e.g., fecal or urinary incontinence), indications of suicide (e.g., suicide note), situation in which the individual is found/circumstances surrounding poisoning, other affected individuals

In the case of unconscious patients or children, plant remnants in the oral cavity or in vomit may indicate that poisonous plant exposure has occurred.

Even in the case of asymptomatic individuals and ingestion of small amounts of plants, it is advisable to first inquire at the control center of the local PIC for a risk assessment. Likewise, the PIC provides patients and lay persons with appropriate advice in the event of poisoning, for example regarding initial measures or clarifying whether a medical consultation is needed.

In order to make a risk assessment, the risk must be estimated on the basis of all available information (“estimated risk”). The prediction of the risk or course of poisoning depends on numerous factors. The amount of relevant constituents can vary strongly depending on the part of the plant. Some plants contain the highest concentrations of toxic agents in their fruits (e.g., belladonna) or seeds (e.g., castor bean [ricinus], autumn crocus), in their leaves or needles (e.g., yew), or even in their roots (e.g., false hellebore). The severity of poisoning also depends on the amount ingested and the degree of crushing or chewing. Crushed plant parts release more toxic agents due to the increased surface area, or ingredients are better absorbed from them. The toxic effect may also depend on the following factors (8– 14):

• Age (children and the elderly are often particularly vulnerable)

• Comorbidities (for example, kidney or liver failure)

• Enzyme make-up (toxicogenetics, for example, cytochrome status of the liver)

• Route of exposure (for example, oral, inhalation, dermal, ocular)

• Duration of exposure (chronic versus acute).

Overall, due to multiple variables, there is a high degree of uncertainty in prognostic statements regarding human intoxications.

If non-toxic or low-toxic plants/plant parts (risk categories [RC] 0, 1) or clearly non-relevant quantities have been ingested, further measures are usually not required (15). In the case of potentially relevant plant poisoning (high risk assessment), the first priority is to monitor and support vital functions (the ABCDE approach) (15– 17). Medical lay persons should undertake initial measures at the scene according to instructions given by the emergency department or in consultation with the PIC (box). These include preventing exposure to toxic agents (for example, manually removing plant residues from the oral cavity) and administering fluids in the form of water, tea, or juice to individuals that are awake.

BOX. Initial measures in oral plant poisonings. Measures modified from (e26).

• First-aid measures for lay persons in plant poisonings

  • Keep calm

  • Do not induce vomiting (do not administer saltwater)

  • Stop further ingestion of plant parts (for example, remove plant parts from the mouth)

  • If the person is awake: encourage them to drink water, juice, or tea (no milk)

  • If the person is unconscious: basic life support (if applicable, follow instructions given by the rescue coordination center)

  • Consult the local poison information center or a physician

  • Follow expert advice (for example, present to hospital)

  • If possible, take samples of the whole plant or several plant parts for special analysis (fruits, stems, leaves, root); alternatively, photo-document as many plant parts as possible (for example, with a smartphone)

• Medical first-aid measures at the scene of plant poisoning

  • Support vital functions (the ABCDE approach)

  • Take (third-party) history

  • If the level of risk is unclear and in order to determine the plant species (risk assessment), consult the poison information center

  • Where appropriate, primary detoxification by administering activated charcoal (0.5–1 g/kg body weight [BW] or 10- to 40-fold excess to toxic agent or a maximum dose of 50 g in the case of a single administration)

  • If available: administer antidotes in consultation with the poison information center

  • If possible, take samples of the whole plant or several plant parts (fruits, stems, leaves, root); alternatively, photo-document as many plant parts as possible

  • Take samples of blood, urine, and vomit for analysis/forensics

  • Transport (potentially) at-risk patients to hospital/emergency department under medical supervision

• Initial in-hospital measures for plant poisonings

  • Support vital functions (the ABCDE approach)

  • Obtain further information, take a more in-depth and comprehensive history

  • Consult the poison information center regarding methods of primary and secondary detoxification and/or antidote administration

  • Monitoring and symptom-oriented treatment

To estimate the initial severity of poisoning and the clinical course, it is helpful to ascertain, for example, the modified Poisoning Severity Score (PSS) (etable 2) (16, 18).

eTable 2. Modified Poisoning Severity Score (PSS) according to Persson et al. for the grading of poisoning severity (modified from [18]).

Organ system	No symptoms	Minor symptoms	Moderate symptoms	Severe symptoms	Death
	No symptoms or signs related to plant poisoning	Mild, transient, and spontaneously resolving symptoms related to plant poisoning	Pronounced or prolonged symptoms related to plant poisoning	Severe or life-threatening symptoms related to plant poisoning	Death related to plant poisoning
	0	1	2	3	4
Gastrointestinal tract	No symptoms	● Abdominal pain, vomiting, diarrhea ● Mucosal irritation (1st degree burns), mouth ulcerations ● Endoscopy: mucosal erythema, swelling	● Vomiting, abdominal pain, diarrhea, lasting longer than 2 h ● 2nd or 3rd degree burns in small areas of mucosa ● Mild dysphagia ● Endoscopy: ulceration	● Massive hematemesis, perforation ● 2nd or 3rd degree burns in large areas of mucosa ● Severe dysphagia ● Endoscopy: deep ulceration, circumferential lesions, perforation	Death
Respiratory tract		● Irritation, coughing, breathlessness, mild dyspnea, mild bronchospasm ● Abnormal chest X-ray without symptoms	● Prolonged coughing, bronchospasm, dyspnea, stridor ● Reduced oxygen saturation ● Abnormal chest X-ray with mild/moderate symptoms	● Manifest respiratory insufficiency (e.g., severe bronchospasm, airway obstruction, glottal edema, pulmonary edema, acute respiratory distress syndrome (ARDS), pneumonitis, pneumothorax) ● Abnormal chest X-ray with severe symptoms
Nervous system		● Drowsiness, dizziness, tinnitus, restlessness ● Ataxia, mild extrapyramidal motor movement disorders ● Mild cholinergic or anticholingeric symptoms ● Paresthesia ● Mild visual or auditory disturbances	● Unconsciousness with appropriate response to pain stimuli ● Slowed breathing ● Confusion, agitation, hallucinations, delirium ● Brief seizures (focal or generalized) ● Pronounced extrapyramidal motor motor movement disorders ● Pronounced cholinergic or anticholingeric symptoms ● Localized, non-life-threatening paralysis ● Pronounced visual or auditory disturbances	● Unconsciousness with or without inappropriate response to pain stimuli ● Impaired respiratory drive ● Pronounced agitation ● Prolonged seizures or status epilepticus, opisthotonus ● Generalized or life-threatening paralysis ● Blindness or deafness
Cardiovascular system		● Isolated extrasystoles ● Mild or transient hypo-/ hypertension	● Moderate sinus bradycardia (adults: 40–50/min, children: 60–80/min, neonates: 80–90/min) ● Moderate sinus tachycardia (adults: 140–180/min, children: 160–190/min, neonates: 160–200/min) ● Frequent extrasystoles, atrial fibrillation/flutter ● 1st–2nd Degree AV block ● Widened QRS complex or prolonged QT time/repolarization disturbances ● Myocardial ischemia ● Pronounced hypo-/hypertension	● Severe sinus bradycardia (adults: < 40/min, children: < 60/min, neonates: < 80/min) ● Pronounced sinus tachycardia (adults: > 180/min, children: > 190/min, neonates: > 200/min) ● Life-threatening cardiac arrhythmias ● 3rd Degree AV block ● Asystole ● Myocardial infarction ● Circulatory shock ● Hypertensive crisis
Kidneys		● Minimal proteinuria/hematuria	● Massive proteinuria/hematuria ● Renal dysfunction (e.g., oliguria, polyuria, serum creatinine of ˜200–500 µmol/L)	● Kidney failure (e.g., anuria, serum creatinine of > 500 µmol/L)
Liver		● Minimal rise in transaminases (ASAT, ALAT ˜2–5 x normal)	● Pronounced rise in transaminases (ASAT, ALAT ˜5–50 x normal) ● No other abnormal biochemical markers (e.g., ammonia, clotting factors) ● No clinical evidence of liver dysfunction	● Extreme rise in transaminases (> 50 x normal) ● Other pathological biochemical markers (e.g., ammonia, clotting factors) ● Clinical evidence of liver failure
Muscular system		● Mild pain, tenderness ● CK ˜250–1 500 IU/L	● Moderate pain, rigidity, cramping, fasciculation ● Rhabdomyolysis ● CK ˜1 500–10 000 IU/L	● Intense pain, extreme rigidity, generalized cramping and fasciculation ● Rhabdomyolysis with complications ● CK >10,000 IU/L ● Compartment syndrome
Metabolism		● Mild acid-base disturbances (HCO3− ˜15–20 or 30–40 mmol/L, pH ˜7.25–7.32 or 7.50–7.59) ● Mild electrolyte and fluid disturbances (K + 3.0–3.4 or 5.2–5.9 mmol/L) ● Mild hypoglycemia (˜50–70 mg/dL or 2.8–3.9 mmol/L in adults) ● Hyperthermia of short duration	● More pronounced acid-base disturbances (HCO3− ˜10–14 or >40 mmol/L; pH ˜7.15–7.24 or 7.60–7.69) ● More pronounced electrolyte and fluid disturbances (K + 2.5–2.9 or 6.0–6.9 mmol/L) ● More pronounced hypoglycemia (˜30–50 mg/dL or 1.7–2.8 mmol/L in adults) ● Hyperthermia of longer duration	● Severe acid-base disturbances (HCO3− < 10 mmol/l; ph < 7.15 or > 7.7) ● Severe electrolyte and fluid disturbances (K + < 2.5 or > 7.0 mmol/L) ● Severe hypoglycemia (< 30 mg/dl or < 1.7 mmol/l in adults) ● Dangerous hypo- or hyperthermia
Blood system		● Mild hemolysis ● Mild methemoglobinemia (MetHb ˜10–30%)	● Moderate hemolysis ● Pronounced methemoglobinemia (MetHb ˜ 30–50%) ● Coagulation disorders without bleeding ● Moderate anemia, leukopenia, thrombocytopenia	● Massive hemolysis ● Severe methemoglobinemia (MetHb > 50%) ● Coagulation disorders with bleeding ● Severe anemia, leukopenia, thrombocytopenia

Only symptoms for selected organ systems, as well as some important laboratory chemical function parameters that are particularly relevant for oral plant poisoning, are graded here. The organ system most severely affected defines the grade of severity (none = 0, minor= 1, moderate= 2, severe= 3, fatal = 4 symptoms/laboratory parameter abnormalities). The PSS can be used to grade both the initial severity and the course of poisoning.

CK, creatine kinase; K+, potassium; MetHb, methemoglobin; PSS, poisoning severity score

Plant identification

For a reliable risk assessment in plant poisonings, it is important to determine the species of the plant. Species identification and toxicological evaluation often present difficulties. Therefore—even if identification and risk assessment appear to be reliable—additional expert advice should be sought. Local experts such as horticulturists, botanists, toxicologists, pharmacists, and PIC staff may be able to assist in species identification. For example, the “Vergiftungsunfälle bei Kindern” (poisoning accidents in children) app released by the German Federal Institute for Risk Assessment (Bundesinstitut für Risikobewertung, BfR) (19) provides information on plant poisoning, including photos to aid identification. Commercial apps can also help in the identification of species. Identification results—often presented as probability data with a ranking—should always be critically scrutinized and compared with other sources of information.

It is always advisable to preserve fruits and other plant parts (stems, leaves, but preferably the whole plant), as well as vomit, for the purposes of species identification at a later time. If this is not possible (for example, in the case of trees), the plant and parts of the plant that have been consumed should be photographed.

In the case of syndromic poisoning (toxidrome), the clinical picture may be able to narrow down the group of toxic agents (20, 21). In plant poisonings, the anticholinergic syndrome that occurs in the setting of tropane alkaloid intoxication (for example, atropine, scopolamine) is particularly relevant. Typical symptoms include (22, 23): tachycardia, hyperthermia, tachypnea, mydriasis, warm/dry skin, dry mucous membranes, urinary retention, tremor, intestinal atony, as well as agitation and hallucinations. Usually, only partial symptoms become manifest (22, 23).

Primary detoxification

Primary detoxification comprises measures to prevent absorption of the poison (16, 24, 25). Once the indication has been established from a critical perspective, the following measures should preferentially be used in routine clinical toxicological practice (16, 25, 26):

• administration of activated charcoal;

• where appropriate, gastric lavage or endoscopic removal.

However, the evidence is overall weak. The recommendations are based primarily on individual case reports, expert opinions, and position papers, as well as on clinical experimental studies with small numbers of voluntary subjects. Randomized controlled studies on the treatment of specific plant poisonings are not available to date.

Administration of activated charcoal

Activated charcoal, due to its large surface area and high adsorption capacity, is able to bind plant substances and reduce absorption of the poison. Its administration is liberally recommended even in cases of moderate poisoning (PSS > 1) or in cases of poisoning by unknown plants in which there is a possibility of severe poisoning but no increased risk of aspiration (25). Emergency medical services generally carry the drug, which has been declared by the WHO as “indispensable” (compare with the “Bremer Liste”). It should be administered as soon as possible, at best within 30–60 min of ingestion, together with plenty of fluids (water, tea, fruit juice) (25, 27). The selected dose should exceed the toxic agent 10–40 fold or be equivalent to 0.5–1 g/kg body weight in children or 50 g orally in adults (where appropriate, via gastric tube) (25). More detailed recommendations on establishing the indication as well as on evidence-based dosages for plant poisoning, not to mention data on clinical outcome, are not available. Experimental inhibition of absorption using 50 g of activated charcoal in adults is 40–47% after 30–60 min and 17–21% after 120–180 min (27).

Protracted, repetitive, or delayed administration of activated charcoal can possibly still be effective in poisoning by plants containing constituents that are subject to pronounced enterohepatic and/or enteroenteric circulation (for example, colchicine, digitalis glycosides). The mechanisms at work here include, on the one hand, the primary removal of active substances even from distal sections of the gastrointestinal tract and, on the other, secondary detoxification via what is referred to as gastrointestinal dialysis. The latter describes an effect in the enteroenteric circulation whereby the intestinal wall serves as a semipermeable membrane, and substances diffuse from the blood into the activated charcoal in the intestine (25, 28). The indication for activated charcoal administration should likewise be established liberally in cases of poisoning by highly toxic (for example, castor bean [ricinus], wolfsbane), difficult-to-digest (for example, yew needles), or anticholinergic poisonous plants (for example, belladonna, angel’s trumpet) (25, 28). Informative clinical studies are lacking. The cumulative dose should not exceed 300 g in adults (25).

Activated charcoal is administered for mild intoxications (PSS 0–1) only in exceptional cases: when it is readily available and can prevent the onset of symptoms of poisoning (25).

Contraindications include clouding of consciousness (and unprotected airways), recurrent vomiting, noncompliance, bleeding (for example, in ricin intoxication), and gastrointestinal tract injury. Plant-based alcohols, glycols, and oxalic acid are not adsorbed due to their physical properties (25). A combination of laxatives is not recommended (25, 27– 29). As a general rule, activated charcoal (for example, from pharmacies) can also be administered by lay persons after consultation with a physician (25).

According to older reports, the polystyrene derivative cholestyramine is also able to inhibit absorption of lipophilic poison/toxic agents (for example, digitalis glycosides) by interrupting enterohepatic circulation (30– 33). In the early phase of poisoning, however, activated charcoal should be preferred due to its high capacity to rapidly absorb poison (25).

Gastric lavage and endoscopic removal

According to a clinical toxicology position paper, there is insufficient evidence as yet to justify the routine use of gastric lavage (34). In selected individual cases (for example, life-threatening situations), the measure can by all means be effective (34).

Endoscopic removal of plant residues is the preferred option, since the effectiveness of elimination can be better assessed and guided due to direct visualization. Comparative studies on gastric lavage in plant poisonings are lacking.

Both measures can be recommended even some time after ingestion (> 60 min), for example after ingestion of difficult-to-digest plant parts such as yew needles—much like pharmacobezoar formation in tablet intoxication. Also, both methods can be performed in unconscious patients while preventing aspiration.

Obsolete measures

Due to the significant side effects (for example, cardiotoxicity), poor evidence, and practicability of ipecac syrup, gastric lavage and endoscopic removal should always be preferred. This holds true even though, according to an older experimental study from 1993 with 19 participants, iatrogenic emesis induced by ipecac syrup was significantly superior to gastric lavage in terms of retrieval rate of 30 technetium capsules (54.1 ± 21.3% standard deviation [SD] capsules vomited versus 30.3 ± 17.4% SD capsules recovered by gastric lavage, p = 0.0021) (35). Vomiting induced using apomorphine or mechanical stimulation is also obsolete due to its low practicability (availability, controllability), patchy evidence, and potential side effects (for example, respiratory depression with apomorphine) (36– 39).

The gastric clearance rate is incomplete when such measures are taken (59% after 30 min, 44% after 60 min; study with 20 voluntary subjects) (40). The administration of saltwater, for example, by lay persons in the context of first aid, is also contraindicated, since this may lead to patients requiring treatment for hypernatremia (e1, e2).

Further measures

Diagnostic work-up

Laboratory diagnostics are performed in a problem-oriented manner and include, at a minimum, obtaining a blood count as well as measuring blood glucose, serum electrolytes, blood gases, retention values (creatinine, urea), muscle parameters (creatine kinase, myoglobin), liver count (aspartate aminotransferase [ASAT], alanine aminotransferase [ALAT], gamma-glutamyl transferase [GGT]), blood coagulation, and, where appropriate, a pregnancy test.

Although the diagnosis of plant poisoning usually has to be made on the basis of history, symptoms/toxidromes, and the poisoning scenario (e.g., plant species/part, amount ingested) due to the relative unavailability of laboratory analysis, blood, urine, and vomit samples should be taken early on as a matter of course and for forensic purposes. Molecular biological analysis for the identification of poisonous plants is gaining in importance (e3). Special investigations are generally time- and cost-intensive and should not delay treatment measures.

Commercially available diagnostic digoxin immunoassays are often cross-reactive in plant poisonings with plant-derived cardiac glycosides. Due to a lack of validation, they are not suitable for treatment monitoring following the administration of a digitalis antidote, but they may be able to provide qualitative information where required (e4– e6).

Secondary detoxification

In individual cases, secondary detoxification procedures can be used to attempt the removal of toxic agents that have already been absorbed (24, e7). In addition to the abovementioned administration of activated charcoal (gastrointestinal dialysis), these include hemodialysis if the toxic agents are dialyzable and the poisoning scenario is life-threatening (Table 1, eTable 1) (e8). These procedures also serve to eliminate myoglobin in the context of toxic rhabdomyolysis (for example, in poisoning with hemlock) or to eliminate lactate in the case of subsequent lactic acidosis in intensive care patients (e9– e11).

Owing to significant advances in dialysis technology involving the use of biocompatible high-flux membranes, hemoperfusion with activated charcoal or exchange resins has been used less and less in recent years and is reserved for specialized centers.

Individual case reports on the benefits of forced diuresis (for example, using loop diuretics) or urine alkalinization (for example, using sodium bicarbonate) are available for only a handful of plant poisons (e12, e13). These methods should not be routinely used (e12).

In the case of lipophilic cardiotoxic agents (for example, taxine B) with high distribution volumes, high-dose intravenous lipid emulsion (lipid resuscitation) can be considered in the form of an individual attempt at treatment in life-threatening poisoning (e13– e17). It is assumed that the toxicity of some poisons can be reduced by, for example, redistribution in the lipid phase, thereby reducing uptake at the site of action (e7, e18). At the same time, a redistribution of toxic agents to lipid-containing tissues occurs, accompanied by metabolic degradation (inactivation), prolonged excretion, or storage. Nonspecific organ-protective effects of lipids, for example on the myocardium, are also under debate (e18).

In (continuous) 12-lead ECG monitoring, arrhythmias, bundle branch blocks, widened QRS complexes, and prolonged QT interval can be determined at the scene in cases of poisoning by cardiotoxic plants (for example, wolfsbane, foxglove, European yew, autumn crocus). ECG monitoring for at least 24 h is indicated if cardiotoxic poisonous plants have been ingested (e13, e19).

Antidotes

Antidotes are available for only a handful of plant poisonings: physostigmine salicylate (physostigmine) is able to antagonize the anticholinergic effect of tropane alkaloids (found, for example, in angel’s trumpet, jimson weed, belladonna) and is indicated in particular for central symptoms such as delirium (e20, e21). According to case reports, digitalis antibodies (anti-digoxin Fab-fragments) can be effective in poisonings by plant-derived cardiac glycosides (cardenolides/cardenolide glycosides) from foxglove (digoxin, digitoxin, digitoxigenin) and oleander (oleandrin) (e5, e6). However, in contrast to medicinal digitalis poisoning, there is less evidence for the clinical efficacy of digitalis antibodies in plant-derived cardenolide poisoning (e5). For convallatoxin (from lily of the valley), which is also one of the cardiac glycosides, no antagonistic effect could be detected for digitalis antibodies in the laboratory—although digoxin-specific immunoassays cross-react in diagnostic tests (e4). The postulated effect of digitalis antidote in poisoning by European yew (due to immunological cross-reactivity with taxine B) is currently unclear (e13, e22, e23). Where appropriate, the administration of this antidote can be considered on a case-by-case basis in life-threatening yew poisoning.

Monitoring and further treatment

Due to delayed poison absorption or possible symptom latency, patients should be monitored medically (ideally [pre-]hospitalization) following ingestion of relevant or unknown amounts of toxic plant constituents. The duration and (instrument-based) extent of mandatory monitoring depend on, among other things, the type of plant, the amount ingested, preexisting diseases, and age, and should be determined on a case-by-case basis. For patients that have ingested non-toxic or low-toxic plants (for example, RC 0, RC 1) or clearly harmless amounts, alone the administration of fluids in the form of water, tea, or juices is adequate.

In all other cases, the treatment of plant poisonings is predominantly symptomatic: maintaining fluid and electrolyte balance, analgesic therapy, spasmolysis, and, in severe cases, intensive care measures ranging from, for example, controlled ventilation for respiratory depression (for example, in yew or hemlock poisoning) to extracorporeal membrane oxygenation (ECMO) (e24).

As a matter of principle in cases of unexplained disorders of consciousness, one should consider other causes such as (herbal) drug, medication, and alcohol intoxication, as well as hypoglycemia. Suicidal plant poisonings (for example, using European yew) in the period 2016–20 at the joint PIC comprised 10–55% mixed intoxications in which other toxins were ingested alongside the plant poison (unpublished data). Suicidal patients require appropriate monitoring and early psychiatric referral.

Summary

In order to improve patient care, systematic epidemiological studies, for example, using a national monitoring system with regular reporting, as well as clinical studies on the treatment of plant poisonings, are required.

Questions on the article in issue 18/2022:

Poisoning by Plants

The submission deadline is 5 May 2023. Only one answer is possible per question.Please select the answer that is most appropriate.

Question 1

What percentage of child-related inquiries to the Joint Poisons Information Center in Erfurt (GGIZ), Germany, in the period 2011–2020 were related to possible poisonings by plants?

1. 0.5%

2. 5%

3. 15%

4. 25%

5. 55%

Question 2

What is the cumulative dose of activated charcoal that should not be exceeded when administered to adults?

1. 50 g

2. 100 g

3. 150 g

4. 250 g

5. 300 g

Question 3

Which of the following methods should be preferentially used for primary detoxification?

1. Administration of saltwater

2. Endoscopic removal of plant residues

3. Administration of ipecac syrup

4. Administration of apomorphine

5. Mechanically induced vomiting

Question 4

Xanthopsia is a typical symptom of poisoning by which plant?

1. Jimson weed

2. Angel’s trumpet

3. European yew

4. Foxglove

5. Hellebore

Question 5

How does the polystyrene derivative cholestyramine cause inhibition of the absorption of toxins?

1. By interrupting the enterohepatic circulation

2. By affecting renal function

3. By inducing vomiting

4. By accelerating gastric passage

5. By accelerating diuresis

Question 6

Which of the following are typical symptoms of poisoning with poison hemlock or cowbane?

1. AV block and visual disturbances

2. Hypothermia and impaired micturition

3. Rhabdomyolysis and kidney failure

4. Fatigue and visual disturbances

5. Hallucinations and impaired micturition

Question 7

Non-toxic or low-toxic plants or plant parts are assigned to which risk category?

1. RC 1 and RC 2

2. RC 0 and RC 1

3. RC 0 and RC 4

4. RC 3 and RC 4

5. RC 4 and RC 5

Question 8

Which antidote can be used in the case of poisoning by belladonna, jimson weed, and angel’s trumpet?

1. Digitalis antibodies

2. Protamine

3. Naloxone

4. Physostigmine salicylate

5. Neostigmine

Question 9

Which toxicologically relevant constituents are present in European yew, among others?

1. Digoxin, digitoxin

2. Ricin, ricinine

3. Scopolamine, atropine

4. Colchicine, atropine

5. Taxine A, B, C

Question 10

In which cardiac glycoside poisoning are digitalis antibodies less likely to be used?

1. Digitoxin

2. Convallatoxin

3. Digoxin

4. Digitoxigenin

5. Oleandrin