6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
A) ACTIVATED CHARCOAL 1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION 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). 1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
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).
6.5.2) PREVENTION OF ABSORPTION
A) Activated charcoal can be used if the patient presents early and is able to protect their airway. B) 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).
6.5.3) TREATMENT
A) SUPPORT 1) MANAGEMENT OF MILD TO MODERATE TOXICITY a) Treatment is symptomatic and supportive. Overdose has not been reported. HYPOTENSION: Monitor vital signs. Assess fluid status; osmotic diuresis and intravascular depletion may develop. Replace fluids (oral or IV fluids) as indicated. HYPOGLYCEMIA: Ingestion of dapagliflozin alone is not expected to cause severe hypoglycemia, but when combined with insulin or insulin secretogogues severe hypoglycemia may develop. In patients with dapagliflozin overdose who are also taking insulin or insulin secretogogues, obtain hourly blood glucose and monitor for clinical evidence of hypoglycemia for 8 to 12 hours. DIET: If the patient is awake and alert, offer carbohydrates. If hypoglycemia persists or becomes severe, treat hypoglycemia with IV dextrose boluses as needed. May need to repeat in patients with profound hypoglycemia. A dextrose infusion may be needed in patients in whom recurrent hypoglycemia develops, despite feeding and dextrose boluses. Titrate carefully to reduce the potential for reactive hypoglycemia. NOT RECOMMENDED: Prophylactic dextrose administration is not recommended in patients who do not become hypoglycemic, as it may make it difficult to distinguish patients who become hypoglycemic and require prolonged hospitalization from those who remain asymptomatic and may be discharged sooner.
2) MANAGEMENT OF SEVERE TOXICITY a) Treatment is symptomatic and supportive. HYPOTENSION: Treat moderate to severe hypotension with IV fluids, dopamine or norepinephrine as necessary. HYPOGLYCEMIA: Ingestion of dapagliflozin alone is not expected to cause severe hypoglycemia, but when combined with insulin or insulin secretogogues severe hypoglycemia may develop. In patients with dapagliflozin overdose who are also taking insulin or insulin secretogogues, obtain hourly blood glucose and monitor for clinical evidence of hypoglycemia for 8 to 12 hours. Treat hypoglycemia with IV dextrose boluses as needed. May need to repeat in patients with profound hypoglycemia. A dextrose infusion may be needed in patients in whom recurrent hypoglycemia develops, despite feeding and dextrose boluses. Titrate carefully to reduce the potential for reactive hypoglycemia.
B) MONITORING OF PATIENT 1) Monitor vital signs.
2) Ingestion of dapagliflozin alone is not expected to cause severe hypoglycemia, but when combined with insulin or insulin secretogogues severe hypoglycemia may develop. In patients with dapagliflozin overdose who are also taking insulin or insulin secretogogues, obtain hourly blood glucose and monitor for clinical evidence of hypoglycemia for 8 to 12 hours.
3) Monitor fluid and electrolyte balance in symptomatic patients.
4) Plasma levels are not clinically useful for managing overdose.
C) HYPOGLYCEMIA 1) SUMMARY a) There is little clinical experience with dapagliflozin in overdose. Treatment is symptomatic and supportive. Severe hypoglycemia may develop when dapagliflozin is combined with insulin or sulfonylureas, but is not expected after ingestion of dapagliflozin alone.
b) DIET: If the patient is awake and alert, offer carbohydrates.
2) DEXTROSE a) Treat patients who develop laboratory evidence of hypoglycemia (blood glucose less than 60 mg/dL) or significant clinical effects (altered mental status, seizures) with IV dextrose. b) DOSE 1) ADULT a) BOLUS: Symptomatic patients require immediate treatment with 0.5 to 1 g/kg of D50W (50% dextrose) IV push (Bosse, 2006). Patients with profound hypoglycemia may require a second dose. b) INFUSION: Initiation of a continuous 10% to 20% dextrose intravenous infusion is recommended in any patient who develops recurrent hypoglycemia (Sonnenblick & Shilo, 1986; Palatnick et al, 1991). 1) Do not stop IV dextrose infusion abruptly. Intravenous dextrose may need to be prolonged or repeated, depending upon the amount ingested.
2) Slowly decrease the rate of the dextrose infusion with hourly monitoring of blood glucose after blood glucose levels have been stable for 6 to 8 hours.
3) Prophylactic dextrose administration is NOT recommended in patients who do not become hypoglycemic, as it may make it difficult to distinguish patients who become hypoglycemic and require prolonged hospitalization from those who remain asymptomatic and may be discharged sooner .
2) PEDIATRIC a) NEONATE: BOLUS: 0.2 g/kg IV (2 mL/kg) of D10W (10% dextrose) (Committee on Fetus and Newborn & Adamkin, 2011; Jain et al, 2008; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008). b) INFANTS AND CHILDREN: BOLUS: 0.5 to 1 g/kg IV (usually given as 2 to 4 mL/kg/dose) D25W (25% dextrose) (Kleinman et al, 2010; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008). c) ADOLESCENTS: BOLUS: 0.5 to 1 g/kg IV (usually give as 1 to 2 mL/kg/dose) D50W (50% dextrose) (Kleinman et al, 2010; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008). d) INFUSION: Initiation of a continuous 10% to 20% dextrose in 0.2% normal saline intravenous infusion is recommended in any patient who develops recurrent hypoglycemia (Sonnenblick & Shilo, 1986; Palatnick et al, 1991). Titrate to maintain blood glucose above 100 mg/dL. 1) Do not stop the IV dextrose infusion abruptly. Intravenous dextrose may need to be prolonged or repeated, depending upon the amount of ingested.
2) Slowly decrease the rate of dextrose infusion with hourly monitoring of blood glucose after blood glucose levels have been stable for 6 to 8 hours.
3) Prophylactic dextrose administration is not recommended in patients who do not become hypoglycemic, as it may make it difficult to distinguish patients who become hypoglycemic and require prolonged hospitalization from those who remain asymptomatic and may be discharged sooner .
c) PRECAUTIONS 1) Avoid subcutaneous administration.
2) Avoid fluid overload with intravenous infusion.
3) Be cautious in using an IV infusion in patients with congestive heart failure.
4) Hyperosmolar coma may occur in diabetics receiving an intravenous infusion.
5) Do not stop the intravenous glucose abruptly.
D) 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).
E) ACUTE ALLERGIC REACTION 1) SUMMARY a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
2) BRONCHOSPASM a) ALBUTEROL 1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
3) CORTICOSTEROIDS a) Consider systemic corticosteroids in patients with significant bronchospasm.
b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
4) MILD CASES a) DIPHENHYDRAMINE 1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
5) MODERATE CASES a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
6) SEVERE CASES a) EPINEPHRINE 1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared 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). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).
7) AIRWAY MANAGEMENT a) OXYGEN: 5 to 10 liters/minute via high flow mask.
b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
8) MONITORING a) CARDIAC MONITOR: All complicated cases.
b) IV ACCESS: Routine in all complicated cases.
9) HYPOTENSION a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension. 1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
10) H1 and H2 ANTIHISTAMINES a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010). 1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010). c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010). 11) DYSRHYTHMIAS a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
12) OTHER THERAPIES a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).
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