a) SUMMARY
b) CERBERA MANGHAS
c) CERBERA ODOLLAM
d) FOXGLOVE
e) OLEANDER
f) DIGITALIS LANATA
g) OTHER

a) CERBERA MANGHAS: A 50-year-old man intentionally ingested 3 cerebra manghas seeds and within approximately 2 hours he developed a heart rate of 22 beats/minute with complete atrioventricular block. The patient was hemodynamically stable and did not require atropine or temporary pacing. Following supportive care to treat hyperkalemia the patient fully recovered with no sequelae (Tsai et al, 2008).
b) CERBERA MANGHAS: In Sri Lanka, a man died approximately 5 hours after ingestion of cerbera manghas fruit (also known as natchchukkai seeds in this region). Bradycardia (40 beats/minute), hypotension (100/60 mmHg) and drowsiness were observed upon admission. Atropine was administered. However, the patient developed severe bradycardia with third degree AV block followed by ventricular fibrillation, which did not respond to treatment (Eddleston & Haggalla, 2008).

a) OLEANDRIN - A 49-year-old man with diabetes and coronary heart disease drank an infusion from leaves which he thought would treat his diabetes and developed complete heart block, ventricular fibrillation and cardiac arrest. Despite aggressive care, the patient died within a few hours. Postmortem blood analysis revealed the presence of oleandrin at a concentration of 10 ng/mL (Wasfi et al, 2008).
b) DIGITALIS PURPUREA - A 64-year-old man intentionally ingested a whole digitalis purpurea (digitoxin) plant and was initially asymptomatic. On presentation, repeated doses of activated charcoal were given. ECG changes occurred about 5 hours after exposure, but the patient remained hemodynamically stable. Ten vials (the entire hospital supply) of Digibind were given at the onset of ECG changes. Within 30 minutes of developing bradycardia, followed by a sinus pause, the patient went into cardiac arrest, which did not respond to resuscitation (Ramlakhan & Fletcher, 2007). Significant amounts of plant material were found during postmortem exam.

a) Hypotension may result from the bradycardia or dysrhythmias (Eddleston & Haggalla, 2008; Newman et al, 2004; Haynes et al, 1985; Gupta et al, 1997; Tracqui et al, 1998).

a) Mild hypertension (149/85) was reported in a 42-year-old female who had been exposed to smoke from burning oleander prunings. The patient's hypertension resolved upon supportive care (Khasigian et al, 1998).

a) ATRIAL FIBRILLATION with nonspecific ST segment changes and intraventricular conduction delays were seen more than 12 hours postingestion of an oleander tea (Driggers et al, 1989).
b) STROPHANTUS TINCTURE - Chronic ingestion of a homeopathic preparation of strophanthus tincture resulted in third-degree heart block, atrial fibrillation with many PVCs in a 76-year-old female with a history of hypertension and congestive heart failure Within 30 minutes of receiving 5 vials of Digibind(R), ECG showed normal sinus rhythm without further ECG abnormalities (Ogunlana et al, 2000).

a) SUMMARY: Decreased QRS-T interval, T wave flattening or inversion, an irregular ventricular rate, and an increased PR interval have been noted (Gupta et al, 1997; Rich et al, 1993; Driggers et al, 1989).
b) DIGITALIS LANATA: Multiple ECG disturbances including complete heart block and ST and T wave changes were reported in two patients following ingestion for three days of an herbal supplement used as a laxative. One patient had an elevated serum digoxin level of 3.09 ng/mL. Subsequent analysis of the herbal supplement, labeled as plantain, showed that the actual ingredient was digitalis lanata (Slifman et al, 1998).
c) NERIUM OLEANDER: A 66-year-old woman experienced profound bradycardia and multiple ECG abnormalities (brief PAT followed by AV block then a junctional escape rhythm with PVCs) following the ingestion of unprocessed Nerium oleander leaves. A second 26-year-old patient developed similar AV block with intermittent asystolic periods along with a junctional escape rhythm and nonspecific ST and T wave abnormalities (Graeme et al, 1998).
d) NERIUM OLEANDER/TRANSDERMAL: A 59-year-old man with a history of psoriasis developed bradycardia (heart rate 26 beats/minute) after using homemade lotion which he made by boiling Nerium oleander blooms and leaves twice with water. The patient applied this lotion twice daily. ECG revealed a new third-degree AV block with a broad QRS complex and left bundle branch block (LBBB); a previous ECG showed a normal sinus rhythm with first-degree AV block and LBBB. A temporary pacemaker was implanted in the ICU. Because of persistent third-degree block, a definitive DDDR pacemaker was implanted 4 days later. He recovered and was discharged 4 days after the implantation. On follow-up exam, 3 months later, his ECG showed normal sinus rhythm with LBBB (Wojtyna & Enseleit, 2004).
e) CERBERA ODOLLAM: Sinus bradycardia, wandering pacemaker, second-degree SA block and nodal rhythm, nausea, retching and vomiting have occurred following the ingestion of half to one odollam kernel (Gaillard et al, 2004).
f) FOXGLOVE: A 53-year-old woman presented with persistent nausea and vomiting. An ECG showed sinus bradycardia (36 beats/minute) with non-specific ST-T wave abnormalities. It was determined, through detailed questioning, that the patient had ingested foxglove that was mistakenly used in a salad. Laboratory analysis showed a serum digitoxin level of 43 ng/mL (therapeutic range 10 to 32 ng/mL), confirming the diagnosis of foxglove poisoning. With supportive care, the patient's bradycardia and gastrointestinal symptoms gradually resolved (Newman et al, 2004).
g) LILY OF THE VALLEY: Significant conduction disturbances (Grade I-II atrioventricular block) have been reported in children following the ingestion of small amounts of Lily-of-the-valley (Haugen et al, 2001).

a) Three children developed tachycardia after ingesting Lily-of-the-valley (Bruneton, 1999).

a) IRRITATION: Inhalation of plant dust composed of tiny leaf particles may be irritating to people while raking dried leaves.

a) STROPHANTUS TINCTURE: Chronic ingestion of a homeopathic preparation of strophanthus tincture resulted in shortness of breath in a 76-year-old woman with a history of hypertension and congestive heart failure (Ogunlana et al, 2000).

a) WEAKNESS: Fatigue, lethargy, malaise, and confusion (particularly in elderly patients) are common (Porter et al, 1999; LoVecchio et al, 1998; Gupta et al, 1997).
b) CASE REPORT: A 31-year-old woman presented to the ED with malaise, lethargy, vomiting, and blurred vision. She had ingested approximately 2.8 g twice daily of Chomper(R), an herbal supplement with plantain as the key ingredient, for 3 days prior to presentation. An ECG revealed normal sinus rhythm with a "digitalis-effect" in the precordial leads. The patient's serum digitalis level was 4.2 ng/mL. Following supportive care, the patient was discharged 2 days later with a normal ECG and a serum digitalis level of 0.7 ng/mL. A subsequent enzyme immunoassay of a Chomper(R) tablet showed that digitalis lanata was the ingredient within the tablet, instead of plantain (LoVecchio et al, 1998).

a) CASE REPORT: A 13-month-old child was lethargic, pale, vomited and cried inconsolably after a possible ingestion of a material that was later identified as an oleander plant. The patient's level of consciousness deteriorated within minutes following presentation to the ED. The patient gradually recovered (Gupta et al, 1997).

a) A 55-year-old woman became comatose and developed complete AV block 9 hours after a squill plant ingestion. Despite aggressive supportive treatment, the patient died approximately 30 hours after ingestion (Tuncok et al, 1995).

a) Headache has been reported.

a) DYSPHONIA: Slurred speech may be noted (La Couteur & Fisher, 2002; Haynes et al, 1985).

a) CASE REPORT: Toxic seizures were noted in a 96-year-old woman who ingested oleander leaves (Osterloh et al, 1982), and in a patient following a squill plant ingestion (Tuncok et al, 1995).

a) Dizziness is common (La Couteur & Fisher, 2002; Porter et al, 1999; Khasigian et al, 1998).
b) CASE REPORT: A 42-year-old woman presented to the ED 2 days after developing severe dizziness that worsened upon movement. Upon admission to the ED, the patient also experienced a brief syncopal episode. The patient admitted to burning oleander prunings and was periodically exposed to the smoke. A digoxin assay performed 48 hours post-exposure measured at 0.3 ng/mL (Khasigian et al, 1998).

a) One child developed asthenia and agitation after ingesting Lily-of-the-valley (Bruneton, 1999).

a) Patients may develop vomiting, dry mouth, abdominal cramping shortly after ingestion which may continue for several hours preceding deterioration in myocardial contractility (Ogunlana et al, 2000; Porter et al, 1999; Lacassie et al, 2000; Bruneton, 1999; Shumaik et al, 1988; Gupta et al, 1997; Tracqui et al, 1998; Tuncok et al, 1995; Graeme et al, 1998).
b) CASE REPORT: A 42-year-old woman presented to the ED with a two-day history of nausea, continued vomiting, dizziness, and a brief syncopal episode. The patient's symptoms developed shortly after exposure to smoke from burning oleander prunings. Forty-eight hours post-exposure to the oleander smoke, a digoxin assay was measured at 0.3 ng/mL. The patient recovered following treatment with intravenous prochlorperazine and hydroxyzine given intramuscularly (Khasigian et al, 1998).
c) CASE REPORT: A 31-year-old woman ingested approximately 2.8 g twice daily for three days of Chomper(R), an herbal supplement with plantain as the key ingredient, and presented to the ED with complaints of emesis, malaise, lethargy, and blurred vision. The patient's serum digitalis level was 4.2 ng/mL. Subsequent analysis of the Chomper(R) tablet revealed that digitalis lanata was inadvertently substituted for plantain as the key ingredient (LoVecchio et al, 1998).
d) Slifman et al (1998) described two patients who presented to the ED with complaints of nausea, vomiting, and cardiac disturbances. One of the patients had an elevated serum digoxin level of 3.09 ng/mL that was unresponsive to digoxin immune Fab therapy. The patient's serum digoxin level subsequently decreased (1.91 ng/mL) with cholestyramine treatment. Prior to administration, both patients had ingested an herbal supplement for a total of three days before discontinuing due to persistent vomiting.
e) CASE REPORT: A 5-year-old child developed vomiting after ingesting 15 berries of Lily-of-the-valley (Bruneton, 1999).
f) CASE REPORT: A 52-year-old man presented to the emergency department with a 2 month history of nausea, anorexia, colicky abdominal pain, vomiting, diarrhea, lethargy, confusion, metallic taste, dry mouth, sore throat, dizziness, distal paresthesias, tremor, and episodes of slurred speech with blurred, yellow-orange vision. Police investigation revealed that the wife attempted to poison him by using water boiled with roots of Nerium oleander for making coffee over an eight-week period (La Couteur & Fisher, 2002).
g) CASE REPORT (FOXGLOVE): A 53-year-old woman presented with persistent nausea and vomiting. Prior to admission, the patient had been vomiting approximately every hour for 18 hours. An ECG showed sinus bradycardia (36 bpm) with non-specific ST-T wave abnormalities. It was determined, through detailed questioning, that the patient had ingested foxglove that was mistakenly used in a salad. Laboratory analysis showed a serum digitoxin level of 43 ng/mL (therapeutic range 10 to 32 ng/mL), confirming the diagnosis of foxglove poisoning. With supportive care, the patient's bradycardia and gastrointestinal symptoms gradually resolved (Newman et al, 2004).
h) CERBERA ODOLLAM: Sinus bradycardia, wandering pacemaker, second-degree SA block and nodal rhythm, nausea, retching and vomiting have occurred following the ingestion of half to one odollam kernel (Gaillard et al, 2004).

a) CASE REPORT/NERIUM OLEANDER: Profuse diarrhea and significant hypokalemia (2.7 mEq/L) occurred in a 52-year-old man with schizoaffective disorder who was seen ingesting the leaves of a bush one day prior to admission. Symptoms were severe enough to require placement of a rectal tube. His hospital course was complicated by aspiration pneumonia, but no long term sequelae was reported. The plant was later identified as white oleander (Nerium oleander) which the patient thought was an herb and had no intent to harm himself (Boswell et al, 2013).

a) A young Haitian woman received an oral and rectal concoction of oleander leaf extract and developed malaise and bloody stools (Blum & Rieders, 1987).

a) Contact dermatitis has been reported from skin contact with the leaves (Apted, 1983).

a) Three children developed rash after ingesting Lily-of-the-valley (Bruneton, 1999).

a) Serum potassium has reached levels as high as 13.5 mEq/L at 4-1/2 hours after intravenous injection of digoxin. A peak level of 8.2 mEq/liter at 14 hours after ingestion has been survived.

a) Serum digoxin concentration can be clinically misleading when digoxin Fab fragments are present because the Fab fragments interfere with digitalis immunoassay measurements (Personal Communication, 1989).
b) An evaluation of 28 assay methods showed 7 methods that could accurately measure free digoxin in the presence of Fab fragments. These assays were (Hansell, 1989):
c) Unbound, biologically active digoxin was accurately measured in the presence of Fab in serum obtained from a 19-month-old child by the Stratus(R) fluorometric enzyme immunoassay (Baxter) (Senecal et al, 1991).
d) RENAL FAILURE: One case of a patient in renal failure whose free serum digoxin concentration rose fourfold 5 days after Fab administration has been reported. The authors attributed this rise to possible Fab fragment/digoxin complex dissociation after ruling out other possible causes. They suggest that patients with renal failure who are treated with Fab fragments should have free serum digoxin concentration monitored (Schneider et al, 1991).
e) Hypoglycemia (43 mg/dL) was noted 13 hours after administration of digoxin immune Fab fragments in a one-week-old infant, despite intravenous glucose administration (42 mg/kg/min) (Kaufman et al, 1990).

a) Institute continuous cardiac monitoring and obtain serial ECG's.

1) Cross-reactivity of digoxin antibodies between oleander glycosides and digoxin in the radioimmunoassay has been demonstrated (Haynes et al, 1985; Shumaik et al, 1988). This assay will detect oleander glycosides and may be helpful in diagnosis of oleander ingestion, but serum levels and toxicity do not necessarily correlate (Osterloh et al, 1982).

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Experimental studies on the use of multiple dose activated charcoal to enhance elimination have demonstrated efficacy of this treatment and are summarized below. Routine use of this treatment is NOT recommended (Anon, 1999). Consider administration of a second dose of activated charcoal in patients with large ingestions, significant toxicity, or when anti-digoxin Fab is not available.

                DIGOXIN
             Type of Study
Human Overdoses*   Human volunteers**
 Lake 1984  (1)     Park 1985    (2)
 Boldy 1985         Lalonde 1985
 Vicas 1987
(1) patient in renal failure
(2) enhanced digoxin clearance only in one
renal failure patient
                DIGITOXIN
              Type of Study
Human overdoses*   Human volunteers**
 Pond 1981          Park 1985
*Includes deliberate and iatrogenic overdoses,
orally and intravenous.
**Includes oral and intravenous dosing.

a) WHOLE BOWEL IRRIGATION/INDICATIONS: Whole bowel irrigation with a polyethylene glycol balanced electrolyte solution appears to be a safe means of gastrointestinal decontamination. It is particularly useful when sustained release or enteric coated formulations, substances not adsorbed by activated charcoal, or substances known to form concretions or bezoars are involved in the overdose.
b) CONTRAINDICATIONS: This procedure should not be used in patients who are currently or are at risk for rapidly becoming obtunded, comatose, or seizing until the airway is secured by endotracheal intubation. Whole bowel irrigation should not be used in patients with bowel obstruction, bowel perforation, megacolon, ileus, uncontrolled vomiting, significant gastrointestinal bleeding, hemodynamic instability or inability to protect the airway (Tenenbein et al, 1987).
c) ADMINISTRATION: Polyethylene glycol balanced electrolyte solution (e.g. Colyte(R), Golytely(R)) is taken orally or by nasogastric tube. The patient should be seated and/or the head of the bed elevated to at least a 45 degree angle (Tenenbein et al, 1987). Optimum dose not established. ADULT: 2 liters initially followed by 1.5 to 2 liters per hour. CHILDREN 6 to 12 years: 1000 milliliters/hour. CHILDREN 9 months to 6 years: 500 milliliters/hour. Continue until rectal effluent is clear and there is no radiographic evidence of toxin in the gastrointestinal tract.
d) ADVERSE EFFECTS: Include nausea, vomiting, abdominal cramping, and bloating. Fluid and electrolyte status should be monitored, although severe fluid and electrolyte abnormalities have not been reported, minor electrolyte abnormalities may develop. Prolonged periods of irrigation may produce a mild metabolic acidosis. Patients with compromised airway protection are at risk for aspiration.

a) There is a cross-reactivity of OLEANDER cardiac glycosides with various digoxin or digitoxin immunoassays(Osterloh et al, 1982; Shumaik et al, 1988; Dasgupta & Datta, 1998) and this assay may be helpful in the diagnosis of oleander ingestion.

a) CASE REPORT/OLEANDER: Fab fragments may have provided benefit in an adult who had asymptomatic sinus bradycardia secondary to a large ingestion of oleander leaves (Nerium oleander). The heart rate prior to administration of 5 vials of Digibind(R) was 30 to 45, after treatment the rate was 56 (Shumaik et al, 1988). More studies are needed to determine if FAB fragments are clinically useful in the treatment of oleander poisoning.
b) They have also been effective in treating a patient with lanatoside C intoxication (Hess et al, 1979), and oleander poisoning (Shumaik et al, 1988), and have been shown to interact with a number of other plant extracts containing cardiac glycosides (Cheung et al, 1991).
c) Specific antibodies have been successfully used in the management of severe acute digoxin and digitoxin poisoning in children (Zucker et al, 1982; Murphy et al, 1982; Rossi et al, 1984; Woolf et al, 1990), in premature infants with renal failure (Presti et al, 1985; Menget et al, 1989), and adults (Smith et al, 1976; Leikin et al, 1985; Schaumann et al, 1986; Smolarz et al, 1985; Spiegel & Marchlinski, 1985).
d) Martin-Dupont et al (2000) reported that the efficacy of the Fab therapy is questionable because of the risk of cross-reactivity with a variety of plant cardiac glycosides and with compounds unrelated to digoxin and digitoxin(Lacassie et al, 2000).
e) In a 36-year-old woman poisoned with an herbal preparation marketed for "internal cleansing" possibly contaminated with Digitalis lanata, an empiric 10 vials of digoxin-specific Fab were found to be beneficial in resolving the clinical symptoms (Barrueto et al, 2003).
f) CERBERA ODOLLAM: A 51-year-old woman developed severe bradycardia (heart rate: 30 beats/minute), hypotension (BP 90/60 mmHg) and an abnormal ECG (including atrial flutter with variable atrioventricular block, slow ventricular response, shortened QT interval and peaked T-waves) after intentionally ingesting an unknown amount of seeds from a Cerbera odollam ("Pong-pong") tree that was purchased via the Internet. Hyperkalemia (7.5 mmol/L) and an elevated creatinine (2.6 mg/dL) were found on laboratory exam. A digoxin level was undetectable (less than 0.3 ng/mL) and a toxicology screen was noncontributory. Supportive therapy included atropine, calcium gluconate, sodium bicarbonate, glucose and insulin therapy. She also received 10 vials of digoxin immune Fab resulting in normal sinus rhythm with further improvement of other ECG findings. She received an additional 10 vials of digoxin immune Fab with complete resolution of ECG abnormalities within 24 hours. The patient recovered completely (Kassop et al, 2014).
g) FOXGLOVE: A 46-year-old Asian female developed nausea, vomiting, lethargy, dizziness, and weakness after ingesting 4 large foxglove leaves 4 hours previously. Her ECG revealed sinus and junctional bradycardia (transiently dipped into the 30s) with intermittent second degree AV block. Her digoxin and potassium levels were 0.8 ng/mL (normal levels 1.9 or less) and 4.5 mEq/L, respectively. She was treated with 2 vials of Digibind(R) approximately 24 hours postingestion. Since her bradycardia and AV block persisted and her digoxin level did not change, she was treated with 2 additional vials of Digibind(R) approximately 48 hours postingestion, without notable effect. She was discharged 2 days later with transient AV block. The authors believed that in the case of foxglove ingestion, the measured digitalis level does not necessarily reflect all of the cardiac alkaloids that are present in serum (Porter et al, 1999).
h) A 22-year-old man presented to the emergency department after an intentional overdose of a homemade foxglove extract. Clinical symptoms with symptomatic bradyarrhythmia and ECG changes were consistent with cardiac glycoside poisoning. Treatment with digoxin-specific Fab fragments resulted in transient clinical and ECG improvement. The use of Fab did not result in a shortened clinical course in this episode of foxglove poisoning, as one would expect in the setting of commercial glycoside product poisoning (Rich et al, 1993)
i) STROPHANTUS TINCTURE: A 76-year-old woman with a history of hypertension and congestive heart failure, who had been on a homeopathic preparation of strophanthus tincture (15 drops daily) for many years in Hungary, developed vomiting dyspnea and bradycardia (40 bpm) after ingesting the recently refilled preparation from a pharmacy. Her ECG revealed third-degree heart block, atrial fibrillation with many PVCs; digoxin level was 0.4 ng/mL. She was placed on an external pacemaker and was given 5 vials (200 mg) of intravenous Digibind. Within 30 minutes, ECG showed normal sinus rhythm without further ECG abnormalities. The authors suggested that Digibind may be useful in the treatment of Strophanthus poisoning despite low digoxin levels (Ogunlana et al, 2000).
j) A dramatic and rapid reversal of advanced cardiac rhythm disturbances (accelerated AV junctional rhythm, AV junctional tachycardia, various severe ventricular dysrhythmias) and hyperkalemia was reported in 21 of 26 patients with advanced life threatening digitalis intoxication following the administration of Fab fragments of digoxin specific antibodies (Smith et al, 1982).
k) In a multicenter study of 63 patients with digoxin or digitoxin toxicity, a positive, dramatic response from Fab fragments occurred in 53. Seven patients were excluded for various reasons. Diagnosis was uncertain in the 3 treatment failures. Response was usually within 30 minutes of administration (Wenger et al, 1985).
l) ANIMALS: Digoxin specific antibodies have been shown to reverse toxicity and prevent mortality in animals given a lethal dose of digoxin (Schmidt & Butler, 1971; Hess et al, 1979; Hess et al, 1980; Ochs & Smith, 1977; Lechat et al, 1984); and oleander (Clark et al, 1991).

a) Treatment with Fab fragments should be considered in those severely intoxicated patients who fail to respond to immediately available conventional therapy as outlined below or in patients who meet the criteria listed below.
b) Manifestations of severe toxicity might include severe ventricular dysrhythmias (ventricular tachycardia, ventricular fibrillation), progressive bradydysrhythmias (severe sinus bradycardia), or second or third degree heart block not responsive to atropine (Prod Info DigiFab(R) intravenous injection lyophilized powder for solution, 2012).
c) Digoxin Fab fragments are indicated if the potassium concentration exceeds the upper limit of the normal range (5.5 mEq/L in adults or 6 mEq/L in children) in association with severe digitalis intoxication (Prod Info DigiFab(R) intravenous injection lyophilized powder for solution, 2012).
d) Patients taking digoxin therapeutically may become toxic with ingestions of smaller amounts.
e) In symptomatic cases of poisoning by an unknown pharmacologically active cardiac glycoside, one study recommends the administration of an empiric 10 vials of digoxin-specific Fab (Barrueto et al, 2003).

a) ADMINISTRATION: Administer intravenously over 30 minutes, infused through a 0.22 micron membrane filter. If cardiac arrest is imminent, a bolus injection can be given. Reconstitute each vial in 4 milliliters of sterile water for injection to provide a solution containing approximately 10 mg/mL of digoxin immune Fab (Prod Info DigiFab(R) intravenous injection lyophilized powder for solution, 2012).
b) Intraosseous Fab fragments were ineffective in reversing digitalis toxicity in an animal model. This route of administration is not recommended.
c) Interpretation of serum digoxin concentrations after plant ingestions is difficult and they should not be used to guide therapy. The ideal dose for these patients in unknown, an initial dose of 2 vials is reasonable, titrate further doses to clinical condition. Administer 10 to 20 vials for critically ill patients or patients in cardiac arrest (Prod Info DigiFab(R) intravenous injection lyophilized powder for solution, 2012).
d) Fab fragments will not cross-react with the structurally related drugs spironolactone, testosterone, or cortisone (Zalcberg et al, 1983).

a) HYPOKALEMIA
b) SERUM CONCENTRATIONS
c) APNEA: A neonate developed transient apnea during the Fab infusion (Antman et al, 1990).
d) HYPOGLYCEMIA: Developed in a one-week-old infant 13 hours after administration of 40 milligrams of digoxin immune Fab fragments for treatment of an estimated overdose of 600 micrograms given over 7 days for treatment of paroxysmal supraventricular tachycardia, despite intravenous glucose administration (Kaufman et al, 1990).
e) SKIN TESTING: May be appropriate for high risk patients (known allergy to sheep proteins or previous treatment with Digoxin Immune Fab (ovine)), but is not recommended in most cases.
f) CONGESTIVE HEART FAILURE: May be precipitated in patients who require digitalis to maintain cardiac output who are then given Fab fragments (Antman et al, 1990).
g) DISEASE STATE
h) RECRUDESCENT TOXICITY: Patients receiving less than the estimated adequate dose of Fab were more likely to experience recrudescent toxicity (Hickey et al, 1991).
i) The incidence of recrudescent toxicity was 3 percent in a study of 77 adults.
j) The onset of recrudescent toxicity was frequently within 3 days of the initial treatment of Fab. One case of recrudescent toxicity occurred as late as 11 days.

a) Dialysis is probably first-line therapy to restore potassium to normal levels in an anephric patient. Digoxin and the digoxin immune Fab complex are believed to be poorly dialyzable due to molecular weights in excess of 500 as well as due to extensive tissue binding of digoxin and the large volume of distribution of digoxin (Clifton et al, 1989).
b) In an anephric patient, one might predict failure to clear the Fab/digoxin complex. The reticuloendothelial system has been suggested as a mechanism to eliminate the complex (Prod Info Digibind, 94). The elimination half-life will probably be delayed in these patients.
c) The question of whether this delay in elimination would lead to release of newly unbound digoxin into the blood should also be a consideration in the use of digoxin Fab fragment therapy in functionally anephric patients (Prod Info DIGIBIND(R) IV injection, 2003).

a) Digoxin binding to digoxin Fab fragment was observed to be virtually irreversible in a 2-year-old for 19 days postingestion (Hewett et al, 1989).
b) Rebound of free digoxin levels has been frequently reported following Fab fragment administration (Sinclair et al, 1989; Hursting et al, 1987; Hewett et al, 1989). Peak rebound levels usually occur within 24 hours, but may be delayed. If the measurement of free digoxin is not available, the decision to administer additional Fab fragments should be made on clinical grounds.

a) Atropine is useful in the management of bradycardia, and varying degrees of heart block due to the digitalis-induced effects of enhanced vagal tone on SA node rhythmicity and on conduction through the AV node (Smith & Willerson, 1971; Duke, 1972).

a) ATROPINE/DOSE

a) Phenytoin is useful in the management of digitalis induced ventricular dysrhythmias (PVCs, ventricular tachycardia and bigeminy) and improves conduction through the AV node (Damato et al, 1970; Helfant et al, 1967).
b) Low dose phenytoin (ADULT: 25 milligrams/dose intravenously at 1 to 2 hour intervals; CHILD: 0.5 to 1 milligram/kilogram/dose intravenously at 1 to 2 hour intervals) appears to improve AV conduction (Rumack et al, 1974).
c) Larger doses are needed for the management of ventricular dysrhythmias: LOADING DOSE FOR ADULTS AND CHILDREN: Administer 15 mg/kg up to 1 gram IV not to exceed a rate of 0.5 mg/kg/min. MAINTENANCE DOSE: ADULT: Administer 2 mg/kg IV every 12 hours as needed; CHILD: Administer 2 mg/kg every 8 hours as needed.
d) MONITOR SERUM PHENYTOIN LEVELS just prior to initiating and during maintenance therapy to assure therapeutic levels of 10 to 20 mcg/mL (39.64 to 79.28 nanomoles/liter). Monitor ECG carefully.

a) Lidocaine is useful in the management of ventricular tachydysrhythmias, PVCs, and bigeminy. Lidocaine does not improve conduction through the AV node.
b) LIDOCAINE/DOSE
c) LIDOCAINE/MAJOR ADVERSE REACTIONS
d) LIDOCAINE/MONITORING PARAMETERS

a) Magnesium has been reported to reverse digoxin induced dysrhythmias (French et al, 1984; Neff et al, 1972; Reisdorff et al, 1986; Kinlay & Buckley, 1995). It should be used extremely cautiously if at all in the presence of renal failure.
b) DOSE: ADULT: 20 mL of 20% solution over 20 minutes by slow infusion. Infusion should be stopped if patient vomits, becomes hypotensive, develops worsening heart block, or loses deep tendon reflexes. Magnesium levels in serum should be followed.

a) Ventricular fibrillation refractory to cardioversion and lidocaine was successfully treated with amiodarone 300 milligrams intravenously in a 26-year-old man who ingested 25 milligrams of digoxin (Maheswaran et al, 1983).
b) Amiodarone was also successful in treating a 61-year-old man with digoxin toxicity resistant to lidocaine and phenytoin (Nicholls et al, 1985).

a) The therapeutic reference range for digoxin is 0.9 to 2.0 ng/mL (Slifman et al, 1998).
b) The therapeutic reference range for digitoxin is 10 to 32 ng/mL (Newman et al, 2004).

a) A 23-year-old woman presented to the ED with persistent nausea and vomiting, lethargy, and irregular heartbeats. The patient had admitted to ingesting an herbal supplement, used as a laxative, for a total of 3 days but had discontinued its use due to persistent vomiting. The patient's serum digoxin level was 3.66 ng/mL. The herbal supplement was subsequently identified as containing digitalis lanata instead of the labeled ingredient of plantain (Slifman et al, 1998).
b) The serum digoxin levels, in a 31-year-old woman and her husband, were 4.2 ng/mL and 5.2 ng/mL, respectively, after ingestion of an herbal laxative mistakenly containing digitalis lantana instead of plantain (LoVecchio et al, 1998).
c) A 53-year-old woman presented with persistent nausea and vomiting. An ECG showed sinus bradycardia (36 bpm) with nonspecific ST-T wave abnormalities. It was determined, through detailed questioning, that the patient had ingested foxglove that was mistakenly used in a salad. Laboratory analysis showed a serum digitoxin level of 43 ng/mL (therapeutic range: 10 to 32 ng/mL), confirming the diagnosis of foxglove poisoning. With supportive care, the patient's bradycardia and gastrointestinal symptoms gradually resolved (Newman et al, 2004).

a) A 49-year-old man with a history of diabetes ingested an infusion that contained oleander to aid with his diabetes. The patient died within a few hours of ingestion. Antemortem blood samples demonstrated the presence of oleandrin at a concentration of approximately 10 ng/mL (in a previously published nonfatal oleander poisoning a serum concentration of oleandrin was 1.6 ng/mL) (Wasfi et al, 2008).