6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
A) Prehospital GI decontamination is not recommended because of the risk of seizures and subsequent aspiration.
6.5.2) PREVENTION OF ABSORPTION
A) ACTIVATED CHARCOAL 1) CHARCOAL ADMINISTRATION 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.
2) CHARCOAL DOSE 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). 1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
b) ADVERSE EFFECTS/CONTRAINDICATIONS 1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
B) GASTRIC LAVAGE 1) SUMMARY: Gastric lavage may be indicated following a large ingestion if the airway is protected. 2) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes). a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
3) PRECAUTIONS: a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
4) LAVAGE FLUID: a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
5) COMPLICATIONS: a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
6) CONTRAINDICATIONS: a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
6.5.3) TREATMENT
A) MONITORING OF PATIENT 1) Frequent vital signs and continuous pulse oximetry. Monitor serum electrolytes, glucose and renal function. Monitor arterial blood gases and liver enzymes in patients with severe toxicity.
B) VENTRICULAR ARRHYTHMIA 1) SODIUM BICARBONATE a) Serum alkalinization with sodium bicarbonate may be useful in treating dysrhythmias. A reasonable starting dose is 1 to 2 mEq/kg as an IV bolus repeated as needed to maintain arterial pH 7.45 to 7.55. Monitor ECG, arterial blood gases and electrolytes.
b) Infusion of sodium bicarbonate (often with dopamine) has been successful in the treatment of atrioventricular and intraventricular conduction disorders (Yeung et al, 2010; Picciotto et al, 1990; Koppel et al, 1990). Infusion of sodium bicarbonate appeared to antagonize the sodium channel blockade induced by an overdose of propafenone. The QRS duration was shortened from 236 msec to 80 msec and blood pressure was decreased within 24 hours during sodium bicarbonate therapy (Perrone et al, 1994). In another case, a 17-year-old ingested 1350 mg of propafenone and was treated with 2 boluses of 1 mEq/kg of sodium bicarbonate followed by a continuous infusion at a rate of 0.5 mEq/kg/hr for a prolonged QRS of 168 ms and a QTc of 543 ms. The QRS shortened to 90 ms and remained normal over the next 8 hr while the infusion continued. Eight hours after the infusion was stopped the QRS remained stable. A toxicology screen was negative (D'Orazio & Curtis, 2010).
c) CASE REPORT: Treatment with IV sodium bicarbonate improved clinical outcomes in a case of sodium-channel blocker toxicity attributed to propafenone. An otherwise healthy 73-year old woman ingested a therapeutic dose of propafenone (450 mg) for acute atrial fibrillation and collapsed about 1 hour later. She presented to the emergency department with sustained ventricular tachycardia, palpable femoral pulses, and no detectable blood pressure. After defibrillation and lidocaine infusion she converted to sinus rhythm with a QRS width of 158 Msec, but her blood pressure remained undetectable. Additional treatment with 3.6 mg of epinephrine and a dopamine infusion of 25 mcg/kg/min also failed to restore circulation. However, after infusion of 100 mEq of IV sodium bicarbonate, her blood pressure rose to 72/40 mmHg and her QRS narrowed to 136 msec. Continued infusion of an additional 100 mEq of sodium bicarbonate elevated the blood pressure to 94/40 mmHg and narrowed the QRS interval to 104 msec. She recovered uneventfully (Brubacher, 2004).
2) SODIUM LACTATE: Molar sodium lactate infusion reversed malignant ventricular tachycardia in a 5-year-old. At the time of the infusion, the propafenone concentration was within the therapeutic range (Scanu et al, 1991). 3) REFRACTORY NATURE a) The class IC agents have been shown to be moderately refractory to conventional antiarrhythmic drug therapy, cardioversion, and ventricular pacing (Koppel et al, 1990; Spivak et al, 1984).
4) VENTRICULAR DYSRHYTHMIAS SUMMARY 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.
5) ANTIDYSRHYTHMICS a) It is not clear what the treatment of choice should be for these IC agents. Based on similar mechanisms of action, class IC agents (ie, flecainide, encainide) should be avoided. b) Because of crossover in electrophysiologic properties, class IA agents are relatively contraindicated, but there is insufficient experience with overdose to be certain. 1) AVOID: Class IA agents: Quinidine, procainamide, disopyramide.
2) Class IB agents: Lidocaine, phenytoin, mexiletine, tocainide. These agents may be the best alternative based on electrophysiologic properties, but could also exacerbate toxicity; experience in overdose is limited.
c) NOTE: PHENYTOIN shares some of the same cardiovascular effects as propafenone and may have contributed to toxicity in a child (McHugh & Perina, 1987); it should NOT be used. 6) LIDOCAINE a) LIDOCAINE/INDICATIONS 1) Ventricular tachycardia or ventricular fibrillation (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010; Vanden Hoek et al, 2010).
b) LIDOCAINE/DOSE 1) 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. a) Once circulation has been restored begin a maintenance infusion of 1 to 4 milligrams per minute. If dysrhythmias recur during infusion repeat 0.5 milligram/kilogram bolus and increase the infusion rate incrementally (maximal infusion rate is 4 milligrams/minute) (Neumar et al, 2010).
2) 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). c) LIDOCAINE/MAJOR ADVERSE REACTIONS 1) 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).
d) LIDOCAINE/MONITORING PARAMETERS 1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).
7) AMIODARONE a) AMIODARONE/INDICATIONS 1) Effective for the control of hemodynamically stable monomorphic ventricular tachycardia. Also recommended for pulseless ventricular tachycardia or ventricular fibrillation in cardiac arrest unresponsive to CPR, defibrillation and vasopressor therapy (Link et al, 2015; Neumar et al, 2010). It should be used with caution when the ingestion involves agents known to cause QTc prolongation, such as fluoroquinolones, macrolide antibiotics or azoles, and when ECG reveals QT prolongation suspected to be secondary to overdose (Prod Info Cordarone(R) oral tablets, 2015).
b) AMIODARONE/ADULT DOSE 1) For ventricular fibrillation or pulseless VT unresponsive to CPR, defibrillation, and a vasopressor therapy give an initial dose of 300 mg IV followed by 1 dose of 150 mg IV. For stable ventricular tachycardias: Infuse 150 milligrams over 10 minutes, and repeat if necessary. Follow by a 1 milligram/minute infusion for 6 hours, then a 0.5 milligram/minute. Maximum total dose over 24 hours is 2.2 grams (Neumar et al, 2010).
c) AMIODARONE/PEDIATRIC DOSE 1) Infuse 5 milligrams/kilogram as a bolus for pulseless ventricular tachycardia or ventricular fibrillation; may repeat twice up to 15 mg/kg. Infuse 5 milligrams/kilogram over 20 to 60 minutes for perfusing tachycardias. Maximum single dose is 300 mg. Routine use with other drugs that prolong the QT interval is NOT recommended (Kleinman et al, 2010).
d) ADVERSE EFFECTS 1) Hypotension and bradycardia are the most common adverse effects (Neumar et al, 2010).
8) CASE REPORTS a) Flecainide overdose, another IC agent, was treated successfully with: 1) Ventricular tachycardia refractory to parenteral antiarrhythmic agents and pacing responded to rapid intravenous infusion of amiodarone (Sagie et al, 1988).
2) Blood pressure and adequate heart rate were maintained with a pacemaker and catecholamine in a 42-year-old man who ingested an unknown large amount of flecainide (Gotz et al, 1991).
9) PACEMAKER a) Pacemaker failure was noted in one patient as the dose of propafenone was increased (Coumel et al, 1984).
b) Other authors have also observed arrhythmias refractory to pacing at high doses, which became controllable as the dose decreased (Anon, 1984).
C) FAT EMULSION 1) SUMMARY: Lipid resuscitation therapy (LRT) therapy should be considered in cases of severe propafenone toxicity with hemodynamic instability. 2) Intravenous lipid emulsion (ILE) has been effective in reversing severe cardiovascular toxicity from local anesthetic overdose in animal studies and human case reports. Several animal studies and human case reports have also evaluated the use of ILE for patients following exposure to other drugs. Although the results of these studies are mixed, there is increasing evidence that it can rapidly reverse cardiovascular toxicity and improve mental function for a wide variety of lipid soluble drugs. It may be reasonable to consider ILE in patients with severe symptoms who are failing standard resuscitative measures (Lavonas et al, 2015). 3) The American College of Medical Toxicology has issued the following guidelines for lipid resuscitation therapy (LRT) in the management of overdose in cases involving a highly lipid soluble xenobiotic where the patient is hemodynamically unstable, unresponsive to standard resuscitation measures (ie, fluid replacement, inotropes and pressors). The decision to use LRT is based on the judgement of the treating physician. When possible, it is recommended these therapies be administered with the consultation of a medical toxicologist (American College of Medical Toxicology, 2016; American College of Medical Toxicology, 2011): a) Initial intravenous bolus of 1.5 mL/kg 20% lipid emulsion (eg, Intralipid) over 2 to 3 minutes. Asystolic patients or patients with pulseless electrical activity may have a repeat dose, if there is no response to the initial bolus.
b) Follow with an intravenous infusion of 0.25 mL/kg/min of 20% lipid emulsion (eg, Intralipid). Evaluate the patient's response after 3 minutes at this infusion rate. The infusion rate may be decreased to 0.025 mL/kg/min (ie, 1/10 the initial rate) in patients with a significant response. This recommendation has been proposed because of possible adverse effects from very high cumulative rates of lipid infusion. Monitor blood pressure, heart rate, and other hemodynamic parameters every 15 minutes during the infusion.
c) If there is an initial response to the bolus followed by the re-emergence of hemodynamic instability during the lowest-dose infusion, the infusion rate may be increased back to 0.25 mL/kg/min or, in severe cases, the bolus could be repeated. A maximum dose of 10 mL/kg has been recommended by some sources.
d) Where possible, LRT should be terminated after 1 hour or less, if the patient's clinical status permits. In cases where the patient's stability is dependent on continued lipid infusion, longer treatment may be appropriate.
4) CASE REPORT: In one case of propafenone toxicity, LRT successfully decreased QRS interval and the amount of vasopressors required after standard therapy failed. The case involved a 21-year-old woman who intentionally ingested 150 mg of propafenone and deteriorated into severe hemodynamic instability. CPR was initiated shortly after the ambulance arrived and again in transit to the hospital. She was intubated and ventilated. Sinus bradycardia with first grade AV block and a QRS interval of 320 msec without cardiac output were documented. Output was restored after 30 minutes of CPR and she was transported to the emergency department; however, CPR was again required for asystole that converted to wide-complex tachycardia. Standard supportive therapy was administered with high dose vasopressors and sodium bicarbonate but the QRS interval persisted at 300 msec. Decontamination with laxatives and active charcoal were also administered. Hemodynamic shock persisted and LRT was initiated with a bolus of 100 mL 20% lipid emulsion, followed by a continuous infusion at 100 mL/hr for a total dose of 1000 mL. Vasopressor requirements dropped by 40% and the QRS interval narrowed to 200 msec within 1 hour of LRT. However, due to irreversible neurologic damage and prolonged shock, the patient died on day 3 of admission (ten Tusscher et al, 2011). D) BRADYCARDIA 1) ATROPINE/DOSE a) ADULT BRADYCARDIA: BOLUS: Give 0.5 milligram IV, repeat every 3 to 5 minutes, if bradycardia persists. Maximum: 3 milligrams (0.04 milligram/kilogram) intravenously is a fully vagolytic dose in most adults. Doses less than 0.5 milligram may cause paradoxical bradycardia in adults (Neumar et al, 2010). b) PEDIATRIC DOSE: As premedication for emergency intubation in specific situations (eg, giving succinylchoine to facilitate intubation), give 0.02 milligram/kilogram intravenously or intraosseously (0.04 to 0.06 mg/kg via endotracheal tube followed by several positive pressure breaths) repeat once, if needed (de Caen et al, 2015; Kleinman et al, 2010). MAXIMUM SINGLE DOSE: Children: 0.5 milligram; adolescent: 1 mg. 1) There is no minimum dose (de Caen et al, 2015).
2) MAXIMUM TOTAL DOSE: Children: 1 milligram; adolescents: 2 milligrams (Kleinman et al, 2010).
2) ISOPROTERENOL INDICATIONS a) Used for temporary control of hemodynamically significant bradycardia in a patient with a pulse; generally other modalities (atropine, dopamine, epinephrine, dobutamine, pacing) should be used first because of the tendency to develop ischemia and dysrhythmias with isoproterenol (Neumar et al, 2010).
b) ADULT DOSE: Infuse 2 micrograms per minute, gradually titrating to 10 micrograms per minute as needed to desired response (Neumar et al, 2010).
c) CAUTION: Decrease infusion rate or discontinue infusion if ventricular dysrhythmias develop(Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
d) PEDIATRIC DOSE: Not well studied. Initial infusion of 0.1 mcg/kg/min titrated as needed, usual range is 0.1 mcg/kg/min to 1 mcg/kg/min (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
E) HYPOTENSIVE EPISODE 1) SUMMARY 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.
2) DOPAMINE 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).
3) NOREPINEPHRINE 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 1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
4) EPINEPHRINE a) ADULT 1) BOLUS DOSE: 1 mg intravenously/intraosseously every 3 to 5 minutes to treat cardiac arrest (Link et al, 2015).
2) INFUSION: Prepare by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate) (Lieberman et al, 2010). Used primarily for severe hypotension (systolic blood pressure 70 mm Hg), or anaphylaxis associated with hemodynamic or respiratory compromise, may also be used for symptomatic bradycardia if atropine and transcutaneous pacing are unsuccessful or not immediately available (Peberdy et al, 2010).
b) PEDIATRIC 1) CARDIOPULMONARY RESUSCITATION: INTRAVENOUS/INTRAOSSEOUS: OLDER INFANTS/CHILDREN: 0.01 mg/kg (0.1 mL/kg of 1:10,000 (0.1 mg/mL) solution); maximum 1 mg/dose. May repeat dose every 3 to 5 minutes (Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sorrentino, 2005). ENDOTRACHEAL: OLDER INFANTS/CHILDREN: 0.1 mg/kg (0.1 mL/kg of 1:1000 (1 mg/mL) solution). Maximum 2.5 mg/dose (maximum total dose: 10 mg). May repeat every 3 to 5 minutes (Kleinman et al, 2010; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008). Follow ET administration with saline flush or dilute in isotonic saline (1 to 5 mL) based on the child's size (Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
2) INFUSION: Used for the treatment of refractory hypotension, bradycardia, severe anaphylaxis. DOSE: 0.1 to 1 mcg/kg/min, titrate dose; start at lowest dose needed to reach desired clinical effects. Doses as high as 5 mcg/kg/min may sometimes be necessary. High dose epinephrine infusion may be useful in the setting of beta blocker poisoning (Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) CAUTION 1) Extravasation may cause severe local tissue ischemia (Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008); infusion through a central venous catheter is advised.
F) EXPERIMENTAL THERAPY 1) INSULIN/DEXTROSE a) CASE REPORT: A 15-year-old girl presented with impaired consciousness 15 minutes after ingesting about 40 propafenone tablets (150 mg each; total dose: 6000 mg). During transport to the hospital, she developed cardiopulmonary arrest. Despite continuous cardiopulmonary resuscitation, she did not respond to treatment. Following arrival to the hospital, a blood gas test revealed metabolic acidosis. She also did not respond to therapy with sodium bicarbonate during CPR. At this time, she received 1 unit/kg of insulin and 500 mL of 10% dextrose, which resulted in a pulse within 15 minutes. In addition, a dopamine infusion was started for hypotension and a transvenous transient pacemaker was added for an ongoing wide QRS with bradycardia. Laboratory analysis revealed respiratory alkalosis, elevated transaminases with creatinine kinase (CK) and CK-MB, and hypokalemia. She also developed an elevated plasma amylase concentration 3 days after admission. Following further supportive care, her condition improved and she was extubated 2 days after resuscitation and remained conscious until discharge 3 weeks after admission. No permanent sequelae occurred (Bayram et al, 2013). 1) Insulin increases catecholamine discharge and calcium uptake by heart cells, resulting in increases in cardiac output and heart rate. It increases the rate of carbohydrate oxidation, resulting in an increase in the myocardial mechanism and contractility. As a powerful positive inotropic agent, insulin has been used in beta-adrenergic receptor antagonists and calcium channel antagonist overdoses (Bayram et al, 2013).
G) SEIZURE 1) SUMMARY: PHENYTOIN shares some of the same cardiovascular effects as propafenone and may have contributed to toxicity in a child (McHugh & Perina, 1987). 2) SUMMARY 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).
3) DIAZEPAM 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 .
4) NO INTRAVENOUS ACCESS 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).
5) LORAZEPAM 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).
6) PHENOBARBITAL 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).
7) OTHER AGENTS 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): 1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
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