6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
A) Gastrointestinal decontamination is not recommended because of the potential for abrupt onset of seizures and subsequent aspiration.
6.5.2) PREVENTION OF ABSORPTION
A) SUMMARY 1) Activated charcoal and orogastric lavage may be of benefit even several hours after ingestion, due to the anticholinergic effects of these drugs in overdose. However, because of the potential for seizure and CNS depression, endotracheal intubation for airway protection should be strongly considered prior to decontamination.
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).
C) GASTRIC LAVAGE 1) 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.
2) 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.
3) 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.
4) 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).
5) 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) SUPPORT 1) MANAGEMENT OF MILD TO MODERATE TOXICITY: Care is symptomatic and supportive.
2) MANAGEMENT OF SEVERE TOXICITY: Seizure should be treated aggressively with benzodiazepines. Seizures refractory to benzodiazepines should be treated with phenobarbital or propofol. If the above measures fail, treat with neuromuscular paralysis with continuous EEG monitoring. QRS widening should be treated with sodium bicarbonate and intubation/hyperventilation to achieve blood pH of 7.45 to 7.55. Early intubation is advised in any patient with CNS depression, seizures, QRS prolongation or ventricular dysrhythmia. Treat hyperthermia with control of seizures and external cooling measures. Treat hypotension with intravenous fluids, control of seizures and correction of severe acidosis. if hypotension persists, use vasopressors; norepinephrine is generally preferred to dopamine.
B) MONITORING OF PATIENT 1) Monitor vital signs and mental status.
2) Monitor serum electrolytes, renal function, arterial blood gases, and CPK in patients with seizure or severe CNS depression.
3) Obtain an ECG and institute continuous cardiac monitoring.
4) Serum drug concentrations are generally not useful in acute management.
5) In general, cyclic antidepressant concentrations greater than 1000 ng/mL are associated with coma, seizures, and dysrhythmias. However, significant and life-threatening toxicity may occur at serum concentrations less than 1000 ng/mL.
C) SEIZURE 1) Seizures in the setting of TCA overdose have been associated with abrupt deterioration of hemodynamic status (Ellison & Pentel, 1989) and should be aggressively controlled. Because of animal studies showing increased duration and frequency in ventricular tachycardia following the use of phenytoin in the setting of amitriptyline overdose (Callaham et al, 1988), phenobarbital is preferable to phenytoin in treating seizures refractory to benzodiazepines. 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).
8) RECURRING SEIZURES a) If seizures are not controlled by the above measures, patients will require endotracheal intubation, mechanical ventilation, continuous EEG monitoring, a continuous infusion of an anticonvulsant, and may require neuromuscular paralysis and vasopressor support. Consider continuous infusions of the following agents: 1) MIDAZOLAM: ADULT DOSE: An initial dose of 0.2 mg/kg slow bolus, at an infusion rate of 2 mg/minute; maintenance doses of 0.05 to 2 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: 0.1 to 0.3 mg/kg followed by a continuous infusion starting at 1 mcg/kg/minute, titrated upwards every 5 minutes as needed (Loddenkemper & Goodkin, 2011).
2) PROPOFOL: ADULT DOSE: Start at 20 mcg/kg/min with 1 to 2 mg/kg loading dose; maintenance doses of 30 to 200 mcg/kg/minute continuous infusion dosing, titrated to EEG; caution with high doses greater than 80 mcg/kg/minute in adults for extended periods of time (ie, longer than 48 hours) (Brophy et al, 2012); PEDIATRIC DOSE: IV loading dose of up to 2 mg/kg; maintenance doses of 2 to 5 mg/kg/hour may be used in older adolescents; avoid doses of 5 mg/kg/hour over prolonged periods because of propofol infusion syndrome (Loddenkemper & Goodkin, 2011); caution with high doses greater than 65 mcg/kg/min in children for extended periods of time; contraindicated in small children (Brophy et al, 2012).
3) PENTOBARBITAL: ADULT DOSE: A loading dose of 5 to 15 mg/kg at an infusion rate of 50 mg/minute or lower; may administer additional 5 to 10 mg/kg. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: A loading dose of 3 to 15 mg/kg followed by a maintenance dose of 1 to 5 mg/kg/hour (Loddenkemper & Goodkin, 2011).
4) THIOPENTAL: ADULT DOSE: 2 to 7 mg/kg, at an infusion rate of 50 mg/minute or lower. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusing dosing, titrated to EEG (Brophy et al, 2012)
b) Endotracheal intubation, mechanical ventilation, and vasopressors will be required (Brophy et al, 2012) and consultation with a neurologist is strongly advised. c) Neuromuscular paralysis (eg, rocuronium bromide, a short-acting nondepolarizing agent) may be required to avoid hyperthermia, severe acidosis, and rhabdomyolysis. If rhabdomyolysis is possible, avoid succinylcholine chloride, because of the risk of hyperkalemic-induced cardiac dysrhythmias. Continuous EEG monitoring is mandatory if neuromuscular paralysis is used (Manno, 2003). 9) PROPOFOL a) A 30-year-old woman developed status epilepticus unresponsive to 15 milligrams of diazepam, 20 milligrams of lorazepam and one gram of phenytoin after ingesting 9.6 grams of amoxapine, 220 milligrams of fluphenazine and 4.5 grams of diphenhydramine. Seizures stopped after she received propofol 2.5 milligrams/kilogram bolus followed by an infusion of 0.2 milligram/kilogram/minute (Merigian et al, 1995).
D) WIDE QRS COMPLEX 1) SUMMARY: Conduction defects and dysrhythmias are not common with amoxapine and loxapine overdoses. Recommended therapy is based on treatment of traditional tricyclic antidepressant overdoses. Serum alkalinization using intravenous boluses of sodium bicarbonate and intubation/hyperventilation is the treatment of choice. 2) SODIUM BICARBONATE a) SUMMARY: Sodium bicarbonate administration appears to have a beneficial effect on TCA-induced conduction defects and dysrhythmias in humans and in animal models (Nattel et al, 1984; Nattel & Mittleman, 1984; Hedges et al, 1985; Hoffman et al, 1993). Animal studies and in vitro studies have suggested that this effect may be secondary to increased pH (Brown et al, 1973; Brown, 1976; Nattel & Mittleman, 1984), increased concentration of sodium ion (Pentel & Benowitz, 1984; Hoffman et al, 1993; McCabe et al, 1993), or both (Sasyniuk et al, 1986). 1) Serum alkalinization to a pH of 7.45 to 7.55 should be achieved using intravenous boluses of sodium bicarbonate and intubation/hyperventilation as necessary. Simultaneous hyperventilation and bicarbonate administration may result in profound alkalemia (Wrenn et al, 1992) and should only be done with extreme caution and careful monitoring of pH.
b) MECHANICAL HYPERVENTILATION: Induction of respiratory alkalosis by mechanical hyperventilation may be as effective as intravenous sodium bicarbonate. A pH greater than 7.60 or a pCO2 less than 20 mmHg is probably undesirable (Bessen et al, 1983; Bessen & Niemann, 1985-86). 1) CASE REPORTS: Several case reports describe reversal of dysrhythmias and improvement in conduction delay in patients with severe TCA overdose treated with hyperventilation (Kingston, 1979; Bessen et al, 1983; Bessen & Niemann, 1985-86).
2) ANIMAL DATA: In a dog model of amitriptyline overdose, treatment with either hyperventilation or sodium bicarbonate reduced dysrhythmias and conduction slowing, while infusion of isotonic or hypertonic sodium chloride did not (Nattel & Mittleman, 1984).
3) IN VITRO: Alkalinization therapy may work by affecting plasma protein binding of tricyclics (Brown et al, 1973; Levitt et al, 1986).
c) SODIUM BICARBONATE DOSE: 1 to 2 milliequivalents/kilogram as needed to achieve a physiologic pH or slightly above (7.45 to 7.55) (Nattel et al, 1984). In some cases alkalinization of blood to a pH above physiologic may be necessary to reverse dysrhythmias (Sasyniuk et al, 1986). 1) CASE REPORTS: Several case reports describe reversal of dysrhythmias and improvement in hemodynamic status in patients with severe TCA overdose treated with sodium bicarbonate (Hoffman & McElroy, 1981; Molloy et al, 1984).
2) ANIMAL DATA: Hyperventilation, which increased arterial pH to above 7.50, did not cause QRS narrowing in a rat model of desipramine overdose. Injection of 3 to 6 milliequivalents/kilogram of NaCl or high doses of sodium bicarbonate (3 milliequivalents/kilogram) reduced cardiac toxicity in acidotic and normal animals. The beneficial effects of NaHCO3 may therefore be due to its sodium content, not in its ability to change pH (Pentel & Benowitz, 1984).
E) VENTRICULAR ARRHYTHMIA 1) Ventricular dysrhythmias (multifocal PVCs, ventricular tachycardia, flutter and fibrillation) may respond to serum alkalinization therapy to pH 7.45 to 7.55 by intravenous boluses of sodium bicarbonate and intubation/hyperventilation. Dysrhythmias unresponsive to this therapy may respond to lidocaine. 2) CONTRAINDICATIONS: Quinidine, disopyramide, and procainamide are contraindicated as their effects on myocardial conduction are similar to that of the tricyclic antidepressants. 3) LIDOCAINE a) 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). b) 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).
c) LIDOCAINE/MONITORING PARAMETERS 1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).
F) HYPOTENSIVE EPISODE 1) SUMMARY a) If alkalinization and volume repletion are ineffective in reversing hypotension, consider the use of pressor or inotropic agents (Frommer et al, 1987). Hemodynamic interventions may be guided by right-sided heart catheterization (Frommer et al, 1987). b) Dopamine and norepinephrine are the most commonly used agents. Animal data support the use of either agent (Vernon et al, 1991). c) Intra-aortic balloons have been used successfully when pressors have failed (Frommer et al, 1987). d) SUMMARY 1) 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.
e) DOPAMINE 1) 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).
2) 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).
f) NOREPINEPHRINE 1) 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). 2) DOSE a) 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).
b) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
c) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
2) DOPAMINE a) While there are reports of patients whose TCA-induced shock was refractory to dopamine, but not to other agents (Heath et al, 1984; Teba et al, 1988; Hagerman & Hanashiro, 1981), most patients respond adequately to dopamine. Animal studies have yielded conflicting results regarding the efficacy of dopamine for TCA-induced hypotension; dosages used and varying experimental conditions limit the usefulness of these studies. b) ANIMALS 1) Vernon et al (1991), using a dog amitriptyline model, found that dosing with dopamine 30 micrograms/kilogram/minute or with norepinephrine 0.25 microgram/kilogram/minute significantly improved cardiac output, heart rate, peak left ventricular pressure change, mean arterial pressure, and mixed venous oxygen saturation. They concluded that both norepinephrine and dopamine were efficacious in this study (Vernon et al, 1991).
2) Studies performed on a cat model of TCA toxicity showed minimal or even deleterious effects of dopamine (10 to 40 micrograms/kilogram/minute) and dobutamine (Jackson & Banner, 1981).
3) Follmer & Lum (1982) refuted this finding; in a cat model, they compared several agents and found that dopamine (20 microgram/kilogram/minute) was superior to norepinephrine (0.2 to 0.4 microgram/kilogram/minute) in reversing hypotension and in preventing death (Follmer & Lum, 1982).
3) NOREPINEPHRINE a) Hypotension may be a result of antidepressant-induced depletion of norepinephrine due to inhibition of neuronal uptake. Theoretically, norepinephrine and phenylephrine may be more effective agents due to their alpha-stimulating effects (Frommer et al, 1987).
b) Norepinephrine, in doses of 15 and 30 micrograms/minute for 5 and 24 hours respectively, was successful in reversing circulatory shock refractory to dopamine in two adults with tricyclic antidepressant overdose (Teba et al, 1988).
c) Disadvantages of using norepinephrine include the need for continuous nursing supervision, a central venous line, and the tissue damage caused by extravasation.
G) SUPRAVENTRICULAR ARRHYTHMIA 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).
H) PHYSOSTIGMINE 1) Use of physostigmine in the setting of tricyclic antidepressant overdose has been associated with the development of seizures and fatal dysrhythmias. It is NOT recommended
I) FLUMAZENIL 1) CONTRAINDICATED: Flumazenil is NOT INDICATED even if benzodiazepines are known coingestants; use of flumazenil in the setting of tricyclic antidepressant overdose has been associated with the onset of seizures and ventricular dysrhythmias (Burr et al, 1989; Marchant et al, 1989; Mordel et al, 1992; Geller et al, 1991).
2) ANIMAL STUDY: Dogs treated with flumazenil 0.2 milligram/kilogram after intoxication with amitriptyline and midazolam or amitriptyline alone developed worsening dysrhythmias whereas intoxicated dogs treated with normal saline did not (Lheureux et al, 1992). Two of the dogs treated with flumazenil died compared with none in the saline treated groups.
J) RHABDOMYOLYSIS 1) SUMMARY: Early aggressive fluid replacement is the mainstay of therapy and may help prevent renal insufficiency. Diuretics such as mannitol or furosemide may be added if necessary to maintain urine output but only after volume status has been restored as hypovolemia will increase renal tubular damage. Urinary alkalinization is NOT routinely recommended.
2) Initial treatment should be directed towards controlling acute metabolic disturbances such as hyperkalemia, hyperthermia, and hypovolemia. Control seizures, agitation, and muscle contractions (Erdman & Dart, 2004).
3) FLUID REPLACEMENT: Early and aggressive fluid replacement is the mainstay of therapy to prevent renal failure. Vigorous fluid replacement with 0.9% saline (10 to 15 mL/kg/hour) is necessary even if there is no evidence of dehydration. Several liters of fluid may be needed within the first 24 hours (Walter & Catenacci, 2008; Camp, 2009; Huerta-Alardin et al, 2005; Criddle, 2003; Polderman, 2004). Hypovolemia, increased insensible losses, and third spacing of fluid commonly increase fluid requirements. Strive to maintain a urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hour) (Walter & Catenacci, 2008; Camp, 2009; Erdman & Dart, 2004; Criddle, 2003). To maintain a urine output this high, 500 to 1000 mL of fluid per hour may be required (Criddle, 2003). Monitor fluid input and urine output, plus insensible losses. Monitor for evidence of fluid overload and compartment syndrome; monitor serum electrolytes, CK, and renal function tests.
4) DIURETICS: Diuretics (eg, mannitol or furosemide) may be needed to ensure adequate urine output and to prevent acute renal failure when used in combination with aggressive fluid therapy. Loop diuretics increase tubular flow and decrease deposition of myoglobin. These agents should be used only after volume status has been restored, as hypovolemia will increase renal tubular damage. If the patient is maintaining adequate urine output, loop diuretics are not necessary (Vanholder et al, 2000).
5) URINARY ALKALINIZATION: Alkalinization of the urine is not routinely recommended, as it has never been documented to reduce nephrotoxicity, and may cause complications such as hypocalcemia and hypokalemia (Walter & Catenacci, 2008; Huerta-Alardin et al, 2005; Brown et al, 2004; Polderman, 2004). Retrospective studies have failed to demonstrate any clinical benefit from the use of urinary alkalinization (Brown et al, 2004; Polderman, 2004; Homsi et al, 1997).
K) ACIDOSIS 1) METABOLIC ACIDOSIS: Treat severe metabolic acidosis (pH less than 7.1) with sodium bicarbonate, 1 to 2 mEq/kg is a reasonable starting dose(Kraut & Madias, 2010). Monitor serum electrolytes and arterial or venous blood gases to guide further therapy.
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