6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
A) SUMMARY 1) Gastrointestinal decontamination may be indicated following a recent ingestion if the patient is not vomiting and the airway can be protected.
B) 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 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. Treat persistent diarrhea with antidiarrheals and treat nausea and/or vomiting with several antiemetics of different classes. Ensure adequate hydration and correct electrolyte abnormalities. Conduction abnormalities have occurred with panobinostat; obtain a baseline ECG and initiate continuous cardiac monitoring.
2) MANAGEMENT OF SEVERE TOXICITY a) Treatment is symptomatic and supportive. Administer colony stimulating factors (filgrastim or sargramostim) to patients with neutropenia. Hemorrhage (both gastrointestinal and pulmonary) has been reported with panobinostat therapy. Monitor platelet count and CBC frequently. Transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia, anemia, or hemorrhage. Severe nausea and vomiting may respond to a combination of agents from different drug classes. Significant systemic infections including pneumonia, bacterial, viral and invasive fungal infections have occurred with therapy. Monitor for signs and symptoms of infection and start anti-infective therapy as soon as possible.
B) MONITORING OF PATIENT 1) Monitor serial CBC (with differential) and platelet count until there is evidence of bone marrow recovery.
2) Monitor for clinical evidence of bleeding. Hemorrhage (both gastrointestinal and pulmonary) has been reported with panobinostat therapy. Monitor platelet count frequently along with CBC.
3) Monitor fluid status and serum electrolytes in patients with significant diarrhea and/or vomiting.
4) Monitor vital signs, including temperature.
5) Obtain a baseline ECG. Continuous cardiac monitoring is indicated in patients with evidence of conduction abnormalities. Correct any electrolyte abnormalities as needed.
6) Closely monitor liver enzymes, renal function, fluid status and electrolytes.
7) Monitor for clinical evidence of infection, with particular attention to: odontogenic infection, oropharynx, esophagus, soft tissues particularly in the perirectal region, exit and tunnel sites of central venous access devices, upper and lower respiratory tracts, and urinary tract.
8) Serum panobinostat concentrations are not clinically useful in guiding management following overdose, or widely available in clinical practice.
C) MYELOSUPPRESSION 1) Severe myelosuppression should be expected after overdose (primarily thrombocytopenia) based on the adverse events reported with panobinostat.
2) Monitor CBC with differential daily.
3) Severe thrombocytopenia has been reported in patients receiving panobinostat therapy. Although overdose has not been reported, it Is anticipated that hematologic events including thrombocytopenia and pancytopenia may develop (Prod Info FARYDAK(R) oral capsules, 2015). Transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia, anemia or hemorrhage.
4) If fever or infection develops during leukopenic phase, cultures should be obtained and appropriate antibiotics started.
5) Colony stimulating factors have been shown to shorten the duration of severe neutropenia in patients receiving cancer chemotherapy (Stull et al, 2005; Hartman et al, 1997). They should be considered in any patient following a panobinostat overdose.
6) Patients with severe neutropenia should be in protective isolation. Monitor CBC with differential daily. If fever or infection develops during leukopenic phase, cultures should be obtained and appropriate antibiotics started. Transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia, anemia or hemorrhage.
D) NEUTROPENIA 1) COLONY STIMULATING FACTORS a) DOSING 1) FILGRASTIM: The recommended starting dose for adults is 5 mcg/kg/day administered as a single daily subQ injection, by short IV infusion (15 to 30 minutes), or continuous IV infusion (Prod Info NEUPOGEN(R) subcutaneous injection, intravenous injection, 2015). According to the American Society of Clinical Oncology (ASCO), treatment should be continued until the ANC is at least 2 to 3 x 10(9)/L (Smith et al, 2006).
2) SARGRAMOSTIM: The recommended dose is 250 mcg/m(2) day administered intravenously over a 4-hour period OR 250 mcg/m(2)/day SubQ once daily (Prod Info LEUKINE(R) subcutaneous injection liquid, intravenous injection liquid, subcutaneous injection lyophilized powder for solution, intravenous injection lyophilized powder for solution, 2013). Treatment should be continued until the ANC is at least 2 to 3 x 10(9)/L (Prod Info LEUKINE(R) subcutaneous injection liquid, intravenous injection liquid, subcutaneous injection lyophilized powder for solution, intravenous injection lyophilized powder for solution, 2013; Smith et al, 2006).
2) HIGH-DOSE THERAPY a) Higher doses of filgrastim, such as those used for bone marrow transplant, may be indicated after overdose. b) FILGRASTIM: In patients receiving bone marrow transplant (BMT), the recommended dose of filgrastim is 10 mcg/kg/day given as an IV infusion no longer than 24 hours. The daily dose of filgrastim should be titrated based on neutrophil response (ie, absolute neutrophil count (ANC)) as follows (Prod Info NEUPOGEN(R) subcutaneous injection, intravenous injection, 2015): 1) When ANC is greater than 1000/mm(3) for 3 consecutive days; reduce filgrastim to 5 mcg/kg/day.
2) If ANC remains greater than 1000/mm(3) for 3 more consecutive days; discontinue filgrastim.
3) If ANC decreases again to less than 1000/mm(3); resume filgrastim at 5 mcg/kg/day.
c) In BMT studies, patients received up to 138 mcg/kg/day without toxic effects. However, a flattening of the dose response curve occurred at daily doses of greater than 10 mcg/kg/day (Prod Info NEUPOGEN(R) subcutaneous injection, intravenous injection, 2015). d) SARGRAMOSTIM: This agent has been indicated for the acceleration of myeloid recovery in patients after autologous or allogenic BMT. Usual dosing is 250 mcg/m(2)/day as a 2-hour IV infusion over a 2-hour period. Duration is based on neutrophil recovery (Prod Info LEUKINE(R) subcutaneous injection liquid, intravenous injection liquid, subcutaneous injection lyophilized powder for solution, intravenous injection lyophilized powder for solution, 2013). 3) SPECIAL CONSIDERATIONS a) In pediatric patients, the use of colony stimulating factors (CSFs) can reduce the risk of febrile neutropenia. However, this therapy should be limited to patients at high risk due to the potential of developing a secondary myeloid leukemia or myelodysplastic syndrome associated with the use of CSFs. Careful consideration is suggested in using CSFs in children with acute lymphocytic leukemia (ALL) (Smith et al, 2006).
4) ANTIBIOTIC PROPHYLAXIS a) Treat high risk patients with fluoroquinolone prophylaxis, if the patient is expected to have prolonged (more than 7 days), profound neutropenia (ANC 100 cells/mm(3) or less). This has been shown to decrease the relative risk of all cause mortality by 48% and or infection-related mortality by 62% in these patients (most patients in these studies had hematologic malignancies or received hematopoietic stem cell transplant). Low risk patients usually do not routinely require antibacterial prophylaxis (Freifeld et al, 2011).
E) FEBRILE NEUTROPENIA 1) SUMMARY a) Severe neutropenia has been reported with panobinostat therapy in patients with advanced cancer (Prod Info FARYDAK(R) oral capsules, 2015). All patients should be monitored for the development of febrile neutropenia following overdose with panobinostat.
2) CLINICAL GUIDELINES FOR ANTIMICROBIAL THERAPY IN NEUTROPENIC PATIENTS WITH CANCER a) SUMMARY: The following are guidelines presented by the Infectious Disease Society of America (IDSA) to manage patients with cancer that may develop chemotherapy-induced fever and neutropenia (Freifeld et al, 2011). b) DEFINITION: Patients who present with fever and neutropenia should be treated immediately with empiric antibiotic therapy; antibiotic therapy should broadly treat both gram-positive and gram-negative pathogens (Freifeld et al, 2011). c) CRITERIA: Fever (greater than or equal to 38.3 degrees C) AND neutropenia (an absolute neutrophil count (ANC) of less than or equal to 500 cells/mm(3)). Profound neutropenia has been described as an ANC of less than or equal to 100 cells/mm(3) (Freifeld et al, 2011). d) ASSESSMENT: HIGH RISK PATIENT: Anticipated neutropenia of greater than 7 days, clinically unstable and significant comorbidities (ie, new onset of hypotension, pneumonia, abdominal pain, neurologic changes). LOW RISK PATIENT: Neutropenia anticipated to last less than 7 days, clinically stable with no comorbidities (Freifeld et al, 2011). e) LABORATORY ANALYSIS: CBC with differential leukocyte count and platelet count, hepatic and renal function, electrolytes, 2 sets of blood cultures with a least a set from a central and/or peripheral indwelling catheter site, if present. Urinalysis and urine culture (if urinalysis positive, urinary symptoms or indwelling urinary catheter). Chest x-ray, if patient has respiratory symptoms (Freifeld et al, 2011). f) EMPIRIC ANTIBIOTIC THERAPY: HIGH RISK patients should be admitted to the hospital for IV therapy. Any of the following can be used for empiric antibiotic monotherapy: piperacillin-tazobactam; a carbapenem (meropenem or imipenem-cilastatin); an antipseudomonal beta-lactam agent (eg, ceftazidime or cefepime). LOW RISK patients should be placed on an oral empiric antibiotic therapy (ie, ciprofloxacin plus amoxicillin-clavulanate), if able to tolerate oral therapy and observed for 4 to 24 hours. IV therapy may be indicated, if patient poorly tolerating an oral regimen (Freifeld et al, 2011). 1) ADJUST THERAPY: Adjust therapy based on culture results, clinical assessment (ie, hemodynamic instability or sepsis), catheter-related infections (ie, cellulitis, chills, rigors) and radiographic findings. Suggested therapies may include: vancomycin or linezolid for cellulitis or pneumonia; the addition of an aminoglycoside and switch to carbapenem for pneumonia or gram negative bacteremia; or metronidazole for abdominal symptoms or suspected C. difficile infection (Freifeld et al, 2011).
2) DURATION OF THERAPY: Dependent on the particular organism(s), resolution of neutropenia (until ANC is equal or greater than 500 cells/mm(3)), and clinical evaluation. Ongoing symptoms may require further cultures and diagnostic evaluation, and review of antibiotic therapies. Consider the use of empiric antifungal therapy, broader antimicrobial coverage, if patient hemodynamically unstable. If the patient is stable and responding to therapy, it may be appropriate to switch to outpatient therapy (Freifeld et al, 2011).
g) COMMON PATHOGENS frequently observed in neutropenic patients (Freifeld et al, 2011): 1) GRAM-POSITIVE PATHOGENS: Coagulase-negative staphylococci, S. aureus (including MRSA strains), Enterococcus species (including vancomycin-resistant strains), Viridans group streptococci, Streptococcus pneumoniae and Streptococcus pyrogenes.
2) GRAM NEGATIVE PATHOGENS: Escherichia coli, Klebsiella species, Enterobacter species, Pseudomonas aeruginosa, Citrobacter species, Acinetobacter species, and Stenotrophomonas maltophilia.
h) HEMATOPOIETIC GROWTH FACTORS (G-CSF or GM-CSF): Prophylactic use of these agents should be considered in patients with an anticipated risk of fever and neutropenia of 20% or greater. In general, colony stimulating factors are not recommended for the treatment of established fever and neutropenia (Freifeld et al, 2011). F) DIARRHEA 1) Severe diarrhea has developed in patients receiving panobinostat (Prod Info FARYDAK(R) oral capsules, 2015). Persistent diarrhea should be treated with antidiarrheals. Ensure adequate hydration and correct any electrolyte abnormalities.
G) VOMITING 1) TREATMENT OF BREAKTHROUGH NAUSEA AND VOMITING a) Treat patients with high-dose dopamine (D2) receptor antagonists (eg, metoclopramide), phenothiazines (eg, prochlorperazine, promethazine), 5-HT3 serotonin antagonists (eg, dolasetron, granisetron, ondansetron), benzodiazepines (eg, lorazepam), corticosteroids (eg, dexamethasone), and antipsychotics (eg, haloperidol, olanzapine); diphenhydramine may be required to prevent dystonic reactions from dopamine antagonists, phenothiazines, and antipsychotics. It may be necessary to treat with multiple concomitant agents, from different drug classes, using alternating schedules or alternating routes. In general, rectal medications should be avoided in patients with neutropenia.
b) DOPAMINE RECEPTOR ANTAGONISTS: Metoclopramide: Adult: 10 to 40 mg orally or IV and then every 4 or 6 hours, as needed. Dose of 2 mg/kg IV every 2 to 4 hours for 2 to 5 doses may also be given. Monitor for dystonic reactions; add diphenhydramine 25 to 50 mg orally or IV every 4 to 6 hours as needed for dystonic reactions (None Listed, 1999). Children: 0.1 to 0.2 mg/kg IV every 6 hours; MAX 10 mg/dose (Dupuis & Nathan, 2003).
c) PHENOTHIAZINES: Prochlorperazine: Adult: 25 mg suppository as needed every 12 hours or 10 mg orally every 4 or 6 hours as needed. IV dose: 2.5 to 10 mg by slow IV injection or infusion not to exceed 5 mg per minute (MAX 40 mg/day); Children (2 yrs or older): 20 to 29 pounds: 2.5 mg orally 1 to 2 times daily (MAX 7.5 mg/day); 30 to 39 pounds: 2.5 mg orally 2 to 3 times daily (MAX 10 mg/day); 40 to 85 pounds: 2.5 mg orally 3 times daily or 5 mg orally twice daily (MAX 15 mg/day) OR 2 yrs or older and greater than 20 pounds: 0.06 mg/pound IM as a single dose (Prod Info COMPAZINE(R) oral tablets, 2013; Prod Info prochlorperazine edisylate intramuscular intravenous injection, 2011; Prod Info COMPAZINE(R) rectal suppositories, 2013). Promethazine: Adult: 12.5 to 25 mg orally or IV every 4 to 6 hours; Children (2 yr and older) 12.5 to 25 mg OR 0.5 mg/pound orally every 4 to 6 hours as needed. Monitor children closely for respiratory depression or apnea (Prod Info promethazine HCl oral tablets, 2013). Chlorpromazine: Children: Greater than 6 months of age, 0.55 mg/kg orally every 4 to 6 hours, or IV every 6 to 8 hours; max of 40 mg per dose if age is less than 5 years or weight is less than 22 kg (None Listed, 1999).
d) SEROTONIN 5-HT3 ANTAGONISTS: The following antiemetic dosing is based on high emetic risk. Dolasetron: Adult: 100 mg orally ONLY. Granisetron: Adult: 2 mg orally daily or 1 mg or 0.01 mg/kg (maximum 1 mg) IV. Ondansetron: Adult: 8 mg orally twice daily; 8 mg or 0.15 mg/kg IV. Palonosetron: Adult: 0.5 mg oral; 0.25 mg IV. Tropisetron: Adult: 5 mg oral; 5 mg IV. Ramosetron: 0.3 mg IV (Basch et al, 2011); Ondansetron: Children (older than 3 years of age): 0.15 mg/kg IV 4 and 8 hours after chemotherapy (None Listed, 1999).
e) BENZODIAZEPINES: Lorazepam: Adult: 1 to 2 mg orally or IM/IV every 6 hours; Children: 0.05 mg/kg, up to a maximum of 3 mg, orally or IV every 8 to 12 hours as needed (None Listed, 1999).
f) STEROIDS: Dexamethasone: Adult: 10 to 20 mg orally or IV every 4 to 6 hours; Children: 5 to 10 mg/m(2) orally or IV every 12 hours as needed; methylprednisolone: children: 0.5 to 1 mg/kg orally or IV every 12 hours as needed (None Listed, 1999).
g) ANTIPSYCHOTICS: Haloperidol: Adult: 1 to 4 mg orally or IM/IV every 6 hours as needed (None Listed, 1999).
H) CONDUCTION DISORDER OF THE HEART 1) Significant cardiac events including ischemia, severe dysrhythmias (ie, atrial and ventricular) have been reported with panobinostat therapy in patients with advanced cancer.
I) VENTRICULAR ARRHYTHMIA 1) 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.
2) 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).
3) 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).
J) TACHYARRHYTHMIA 1) TACHYCARDIA SUMMARY a) Evaluate patient to be sure that tachycardia is not a physiologic response to dehydration, anemia, hypotension, fever, sepsis, or hypoxia. Sinus tachycardia does not generally require treatment unless hemodynamic compromise develops. b) If therapy is required, a short acting, cardioselective agent such as esmolol is generally preferred (Prod Info BREVIBLOC(TM) intravenous injection, 2012). c) ESMOLOL/ADULT LOADING DOSE 1) Infuse 500 micrograms/kilogram (0.5 mg/kg) IV over 1 minute (Neumar et al, 2010).
d) ESMOLOL/ADULT MAINTENANCE DOSE 1) Follow loading dose with infusion of 50 mcg/kg per minute (0.05 mg/kg per minute) (Neumar et al, 2010).
2) EVALUATION OF RESPONSE: If response is inadequate, infuse second loading bolus of 0.5 mg/kg over 1 minute and increase the maintenance infusion to 100 mcg/kg (0.1 mg/kg) per minute. Reevaluate therapeutic effect, increase in the same manner if required to a maximum infusion rate of 300 mcg/kg (0.3 mg/kg) per minute (Neumar et al, 2010).
3) The manufacturer recommends that a maximum of 3 loading doses be used (Prod Info BREVIBLOC(TM) intravenous injection, 2012).
4) END POINT OF THERAPY: As the desired heart rate or blood pressure is approached, omit loading dose and adjust maintenance infusion as required (Prod Info BREVIBLOC(TM) intravenous injection, 2012).
e) CAUTION 1) Esmolol is a short acting beta-adrenergic blocking agent with negative inotropic effects. Esmolol should be avoided in patients with asthma, obstructive airway disease, decompensated heart failure and pre-excited atrial fibrillation (wide complex irregular tachycardia) or atrial flutter (Neumar et al, 2010).
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