a) Other reported adverse effects following oral cesium chloride therapy include nausea and vomiting, diarrhea, abdominal pain, hypokalemia, syncope, seizures, and paresthesias.

a) Hypotension occurred in two patients who reportedly ingested cesium chloride, 3 g/day for several weeks, as an alternative cancer therapy. The serum cesium level in one of the patients was 2,100 mcg/dL (Lyon & Mayhew, 2003; Saliba et al, 2001).

a) CASE REPORT - A 43-year-old woman was diagnosed with glioblastoma multiforme and underwent a right temporal lobe resection. Preoperatively, the ECG showed a QTc interval of 446 ms and lab analysis showed potassium and magnesium concentrations of 4.2 mEq/L and 2.4 mg/dL, respectively. Approximately 3 weeks later, she presented to the ED after experiencing 2 brief seizures. After presentation, she became unresponsive following another brief seizure. The initial ECG showed monomorphic ventricular tachycardia necessitating cardioversion. On admission, her ECG revealed a prolonged QTc interval of 624 ms and lab results showed a potassium level of 3.1 mEq/L and a magnesium of 1.7 mg/dL . A detailed medication history revealed that she had taken oral cesium chloride, 9 grams/day for 10 days, as an alternative cancer therapy agent. She had completed the 10-day course the day before hospital admission. Despite electrolyte repletion and normalization, the patient's QTc interval did not normalize until 6 weeks post-admission (Dalal et al, 2004).
b) CASE REPORT - A 47-year-old woman presented to the ED with syncope and recurrent episodes of polymorphic ventricular tachycardia requiring direct current cardioversion. An initial ECG showed QTc interval prolongation of 691 ms. Laboratory data indicated hypokalemia (3.2 mg/dL). The patient's medication history revealed that she had been taking oral cesium chloride, 3 g/day over the previous 3 weeks. With supportive care, the patient gradually recovered with a normalization of her electrolytes and QTc interval (Saliba et al, 2001) The patient had also been consuming green tea, which contains licorice root. Licorice root is believed to have a pseudo-aldosterone effect and may have exacerbated her hypokalemia and subsequently contributed to her dysrhythmias.
c) CASE REPORT - A 52-year-old woman, with a history of colon cancer, presented to the ED with hypotensive syncope, thirsty, and disoriented. An initial ECG showed QT interval prolongation (596 ms) with episodes of polymorphic ventricular tachycardia. Laboratory data showed a potassium level of 3.2 mmol/L (reference range, 3.5 to 5.0). A medication history revealed that she had been ingesting cesium salts, 3 grams/day for several weeks, as an alternative cancer therapy agent. The patient was given potassium supplementation and left against medical advice 3 hours after presentation. The next day, she returned with another episode of syncope. An ECG showed a prolonged QT interval (650 ms) and sinus bradycardia (61 bpm) with premature ventricular complexes. Laboratory data revealed a potassium level of 2.8 mmol/L and a serum cesium level of 2,100 mcg/dL (reference range, < 27 mcg/dL). The patient gradually recovered with a normalization of her QT interval following potassium supplementation and cessation of the cesium therapy (Lyon & Mayhew, 2003).

a) QT interval prolongation has been reported in several patients following ingestion of cesium chloride, up to 9 g/day for several days. All of the patients gradually recovered following supportive care and cessation of cesium chloride therapy (Dalal et al, 2004; Lyon & Mayhew, 2003; Pinter et al, 2002; Saliba et al, 2001).
b) CASE REPORT - A 39-year-old woman presented to the hospital after three episodes of syncope, the last of which required cardiopulmonary resuscitation. A review of her medication history revealed that she had been taking a cesium chloride supplement for the last 2 weeks prior to presentation. An ECG showed QT interval prolongation (QTc 616 ms) and laboratory data revealed mild hypokalemia (serum potassium level 3.1 mEq/L) and mild hypomagnesemia (serum magnesium level of 1.4 mg/dL [normal 1.7-2.1 mg/dL]). Cesium concentration in the urine was elevated (750 mg/L). Following cessation of cesium chloride therapy and correction of her electrolyte abnormalities, the patient's QT interval gradually normalized (Vyas et al, 2006).

a) CASE REPORT - A 62-year-old man presented to the hospital with recurrent syncope approximately 2 months after beginning intravenous therapy with cesium chloride, 2000 mg four times daily for 2 weeks and continuing with 1000 mg orally three times daily. An initial ECG showed a prolonged QT interval of approximately 700 ms and episodes of torsades de pointes. Laboratory data showed a serum potassium level of 2.8 mEq/L and a plasma cesium level of 830 mcmol/L (reference range, 0.0045 to 0.0105). Despite electrolyte repletion and normalization, the patient's QT interval remained prolonged with persistent premature ventricular beats. Six months after cessation of cesium chloride therapy, the QT level was normal (Pinter et al, 2002).

a) Cesium chloride was intravenously administered in dogs, either as a bolus dose (n=6) or as a loading dose followed by a sustained infusion (n=30). Ventricular dysrhythmias occurred in 28 of the 30 dogs who received the sustained infusion protocol. Dysrhythmias included monoform ventricular tachycardia alone (n=14), polyform ventricular tachycardia alone (n=10), and isolated premature ventricular complexes without ventricular tachycardia (n=2). Four of the dogs developed both polyform and monoform ventricular tachycardia. Ventricular tachycardia deteriorated to ventricular fibrillation in 23 of the 28 dogs. Cessation of the cesium infusion in 7 of the dogs resulted in the complete resolution of the dysrhythmias.

a) Circumoral paresthesia was reported following an acute ingestion of 40 grams of cesium chloride and is believed to be due to potassium depletion (Sartori, 1984).
b) CASE REPORT - A 41-year-old man self-initiated a 5-week course of cesium chloride, 6 grams/day orally in two divided doses. During the course of therapy, the patient experienced minor tingling of the hands and feet and around the mouth and cheeks (Neulieb, 1984).
c) CASE REPORT - A 52-year-old woman experienced circumoral paresthesia after beginning therapy with oral cesium salts, 3 grams/day for several weeks (Lyon & Mayhew, 2003).

a) CASE REPORT - A 62-year-old man experienced his first episode of syncope during intravenous cesium chloride therapy, 2000 mg four times daily for two weeks, as an alternative treatment for prostate cancer. He continued to experience recurrent syncope after switching to oral cesium chloride therapy, 1000 mg three times daily. An ECG showed QT interval prolongation and episodes of torsades de pointes. Discontinuation of cesium chloride therapy resolved the patient's syncope and ECG abnormalities (Pinter et al, 2002).
b) CASE REPORT - Syncope secondary to hypotension was reported in a 52-year-old woman who began taking cesium salts, 3 grams/day orally for several weeks, as an alternative cancer therapy agent (Lyon & Mayhew, 2003).
c) CASE REPORT - A 39-year-old woman presented to the hospital after three episodes of syncope, the last of which required cardiopulmonary resuscitation. A review of her medication history revealed that she had been taking a cesium chloride supplement for the last 2 weeks prior to presentation. An ECG showed QT interval prolongation (QTc 616 ms) and laboratory data revealed mild hypokalemia (serum potassium level 3.1 mEq/L) and mild hypomagnesemia (serum magnesium level of 1.4 mg/dL [normal 1.7-2.1 mg/dL]). Cesium concentration in the urine was elevated (750 mg/L). Following cessation of cesium chloride therapy and correction of her electrolyte abnormalities, the patient's QT interval gradually normalized (Vyas et al, 2006).

a) Seizures occurred in a 43-year-old woman approximately 1 day after completing a 10-day course of cesium chloride therapy, 9 grams/day, as an alternative cancer therapy agent (Dalal et al, 2004).

a) Nausea was reported following an acute ingestion of 40 grams of cesium chloride, and is believed to be due to potassium depletion (Sartori, 1984).
b) Nausea, vomiting, watery diarrhea, and abdominal discomfort occurred in a 43-year-old woman during a self-initiated 10-day course of cesium chloride therapy, 9 grams/day, as an alternative cancer therapy agent. The patient's symptoms resolved following supportive care and cessation of cesium chloride therapy (Dalal et al, 2004).
c) CASE REPORT - A 47-year-old woman experienced frequent watery diarrhea while taking 3 grams/day orally of cesium chloride as an alternative agent for the prevention of breast cancer. The diarrhea resolved following discontinuation of cesium chloride (Saliba et al, 2001).
d) CASE REPORT - A 41-year-old man self-initiated a 5-week course of cesium chloride, 6 grams/day orally in two divided doses. During the first 3 weeks of cesium chloride administration, his morning and evening meals were diet-restricted to a high fiber, high potassium diet. After discontinuation of the high fiber meals, the patient developed nausea followed by diarrhea. Restarting the high fiber meals resolved the patient's symptoms (Neulieb, 1984).
e) CASE REPORT - A 52-year-old woman experienced several episodes of diarrhea while ingesting 3 g/day of cesium salts for several weeks (Lyon & Mayhew, 2003).

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) Obtain an ECG, institute continuous cardiac monitoring and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders (particularly hypokalemia, hypocalcemia, and hypomagnesemia). Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.

a) Ventricular tachycardia or ventricular fibrillation (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010; Vanden Hoek et al, 2010).

a) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010). Only bolus therapy is recommended during cardiac arrest.
b) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).

a) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010).

a) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).

a) Withdraw the causative agent. Hemodynamically unstable patients with Torsades de pointes (TdP) require electrical cardioversion. Emergent treatment with magnesium (first-line agent) or atrial overdrive pacing is indicated. Detect and correct underlying electrolyte abnormalities (ie, hypomagnesemia, hypokalemia, hypocalcemia). Correct hypoxia, if present (Drew et al, 2010; Neumar et al, 2010; Keren et al, 1981; Smith & Gallagher, 1980).
b) Polymorphic VT associated with acquired long QT syndrome may be treated with IV magnesium. Overdrive pacing or isoproterenol may be successful in terminating TdP, particularly when accompanied by bradycardia or if TdP appears to be precipitated by pauses in rhythm (Neumar et al, 2010). In patients with polymorphic VT with a normal QT interval, magnesium is unlikely to be effective (Link et al, 2015).

a) Magnesium is recommended (first-line agent) for the prevention and treatment of drug-induced torsades de pointes (TdP) even if the serum magnesium concentration is normal. QTc intervals greater than 500 milliseconds after a potential drug overdose may correlate with the development of TdP (Charlton et al, 2010; Drew et al, 2010). ADULT DOSE: No clearly established guidelines exist; an optimal dosing regimen has not been established. Administer 1 to 2 grams diluted in 10 milliliters D5W IV/IO over 15 minutes (Neumar et al, 2010). Followed if needed by a second 2 gram bolus and an infusion of 0.5 to 1 gram (4 to 8 mEq) per hour in patients not responding to the initial bolus or with recurrence of dysrhythmias (American Heart Association, 2005; Perticone et al, 1997). Rate of infusion may be increased if dysrhythmias recur. For persistent refractory dysrhythmias, a continuous infusion of up to 3 to 10 milligrams/minute in adults may be given (Charlton et al, 2010).
b) PEDIATRIC DOSE: 25 to 50 milligrams/kilogram diluted to 10 milligrams/milliliter for intravenous infusion over 5 to 15 minutes up to 2 g (Charlton et al, 2010).
c) PRECAUTIONS: Use with caution in patients with renal insufficiency.
d) MAJOR ADVERSE EFFECTS: High doses may cause hypotension, respiratory depression, and CNS toxicity (Neumar et al, 2010). Toxicity may be observed at magnesium levels of 3.5 to 4.0 mEq/L or greater (Charlton et al, 2010).
e) MONITORING PARAMETERS: Monitor heart rate and rhythm, blood pressure, respiratory rate, motor strength, deep tendon reflexes, serum magnesium, phosphorus, and calcium concentrations (Prod Info magnesium sulfate heptahydrate IV, IM injection, solution, 2009).

a) Institute electrical overdrive pacing at a rate of 130 to 150 beats per minute, and decrease as tolerated. Rates of 100 to 120 beats per minute may terminate torsades (American Heart Association, 2005). Pacing can be used to suppress self-limited runs of TdP that may progress to unstable or refractory TdP, or for override refractory, persistent TdP before the potential development of ventricular fibrillation (Charlton et al, 2010). In a case series overdrive pacing was successful in terminating TdP associated with bradycardia and drug-induced QT prolongation (Neumar et al, 2010).

a) Potassium supplementation, even if serum potassium is normal, has been recommended by many experts (Charlton et al, 2010; American Heart Association, 2005). Supplementation to supratherapeutic potassium concentrations of 4.5 to 5 mmol/L has been suggested, although there is little evidence to determine the optimal range in dysrhythmia (Drew et al, 2010; Charlton et al, 2010).

a) Isoproterenol has been successful in aborting torsades de pointes that was resistant to magnesium therapy in a patient in whom transvenous overdrive pacing was not an option (Charlton et al, 2010) and has been successfully used to treat torsades de pointes associated with bradycardia and drug induced QT prolongation (Keren et al, 1981; Neumar et al, 2010). Isoproterenol may have a limited role in pharmacologic overdrive pacing in select patients with drug-induced torsades de pointes and acquired long QT syndrome (Charlton et al, 2010; Neumar et al, 2010). Isoproterenol should be avoided in patients with polymorphic VT associated with familial long QT syndrome (Neumar et al, 2010).
b) DOSE: ADULT: 2 to 10 micrograms/minute via a continuous monitored intravenous infusion; titrate to heart rate and rhythm response (Neumar et al, 2010).
c) PRECAUTIONS: Correct hypovolemia before using; contraindicated in patients with acute cardiac ischemia (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
d) MAJOR ADVERSE EFFECTS: Tachycardia, cardiac dysrhythmias, palpitations, hypotension or hypertension, nervousness, headache, dizziness, and dyspnea (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
e) MONITORING PARAMETERS: Monitor heart rate and rhythm, blood pressure, respirations and central venous pressure to guide volume replacement (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).

a) Mexiletine, verapamil, propranolol, and labetalol have also been used to treat TdP, but results have been inconsistent (Khan & Gowda, 2004).

a) Avoid class Ia antidysrhythmics (eg, quinidine, disopyramide, procainamide, aprindine), class Ic (eg, flecainide, encainide, propafenone) and most class III antidysrhythmics (eg, N-acetylprocainamide, sotalol) since they may further prolong the QT interval and have been associated with TdP.

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):