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DEXMEDETOMIDINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Dexmedetomidine is the S-enantiomer of medetomidine and is a selective alpha-2-adrenoceptor agonist with sedative properties.

Specific Substances

    1) Dexmedetomidine
    2) CAS 113775-47-6 (dexmedetomidine)
    3) CAS 145108-58-3 (dexmedetomidine hydrochloride)
    4) ATC: N05CM18
    5) Molecular Formula: C(13)H(16)N(2)(HCl)
    1.2.1) MOLECULAR FORMULA
    1) C13H16N2(HCl)

Available Forms Sources

    A) FORMS
    1) Dexmedetomidine is available as 100 mcg/mL in 2 mL clear glass vials, and as 4 mcg/mL in 20 mL, 50 mL, and 100 mL glass bottles, mixed with 0.9% sodium chloride, for intravenous infusion (Prod Info Precedex(TM) intravenous injection, 2016).
    B) USES
    1) Dexmedetomidine is indicated for short term (24 hours or less) sedation of patients requiring intubation and mechanical ventilation during medical care in an intensive care setting. It is also used for sedating non-intubated patients either before and/or during surgical and non-surgical procedures (Prod Info Precedex(TM) intravenous injection, 2016). Multiple studies have utilized dexmedetomidine for greater than 24 hours; therefore, it may be a safe and effective sedative when used for longer than 24 hours (Shehabi et al, 2004; Venn et al, 2003).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Indicated for short term (24 hours or less) sedation of patients requiring intubation and mechanical ventilation in an intensive care setting. It is also used for sedating non-intubated patients either before and/or during surgical and non-surgical procedures. Multiple studies have utilized dexmedetomidine for greater than 24 hours; therefore, it may be a safe and effective sedative when used for longer than 24 hours.
    B) PHARMACOLOGY: Dexmedetomidine is a specific and selective alpha-2 adrenoceptor agonist. It has a significantly higher alpha-2/alpha-1 selectivity ratio than does clonidine.
    C) TOXICOLOGY: It is anticipated that dexmedetomidine can produce hypotension and bradycardia induced by vagal stimuli and sympathetic outflow.
    D) EPIDEMIOLOGY: Overdose is rare.
    E) WITH THERAPEUTIC USE
    1) COMMON: The most frequently reported adverse events include: hypotension (28%), hypertension (16%) {associated with loading dose administration}, bradycardia (7%), tachycardia (3%) and hypoxia (4%). Dexmedetomidine decreases sympathetic nervous system activity, therefore, bradycardia and hypotension may be profound in some patients including the elderly, hypovolemic patients or patients with significant comorbidity (e.g., diabetes mellitus or chronic hypertension). Respiratory depression is rare, despite doses that produce marked sedation. Other events include atrial fibrillation (4%), fever (5%), vomiting (4%), hemorrhage (3%), and anemia (3%). INFREQUENT EVENTS: Hyperpyrexia, pain, hyperglycemia, acidosis, pleural effusion, oliguria and thirst may develop.
    2) WITHDRAWAL SYNDROME: Withdrawal symptoms may occur following abrupt dose reduction or sudden cessation of therapy, similar to clonidine and other centrally acting antihypertensive agents. Symptoms include, but are not limited to, nausea, vomiting, agitation, palpitations, and hypertension.
    F) WITH POISONING/EXPOSURE
    1) Limited data exists on overdose. It is anticipated that overdose events may be an extension of the adverse events observed. Overdose may result in oversedation, bradycardia and hypotension. In a series of 3 inadvertent overdoses, deep hypnosis developed, which resolved within one hour of drug discontinuation. First and second degree AV block were reported in volunteers receiving supratherapeutic doses. Bradycardia and hypotension developed in two patients who received 2 mcg/kg over 10 minutes. Cardiac arrest developed in a patient after a bolus loading dose of undiluted dexmedetomidine (19.4 mcg/kg; normal loading dose 1 mcg/kg); recovery was uneventful.
    0.2.3) VITAL SIGNS
    A) WITH THERAPEUTIC USE
    1) Fever may occur with therapeutic use. Bradycardia and hypotension can occur with therapy, but may not produce hemodynamic instability. Transient, mild hypertension has also developed during initial treatment.
    0.2.20) REPRODUCTIVE
    A) Dexmedetomidine is classified as FDA pregnancy category C. Embryo and fetal toxicity, but no teratogenicity, were reported in animal studies. It is not known if dexmedetomidine is secreted in human breast milk, although animal studies reported the drug in the milk of lactating rats.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no studies were found on the possible carcinogenic activity of dexmedetomidine in humans.

Laboratory Monitoring

    A) Monitor vital signs and pulse oximetry. Hypotension, bradycardia and respiratory depression may develop. Institute continuous cardiac monitoring and obtain an ECG.
    B) Monitor neurologic function.
    C) Specific laboratory tests are not necessary following inadvertent exposure, unless otherwise clinically indicated.

Treatment Overview

    0.4.6) PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Manage mild hypotension with IV fluids. Transient hypertension may develop after exposure; treatment is usually not indicated.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. Symptomatic bradycardia can be treated with atropine.
    C) DECONTAMINATION
    1) Not indicated. Drug administered via the intravenous route.
    D) AIRWAY MANAGEMENT
    1) A decrease in respiratory function is generally not anticipated with dexmedetomidine when given alone, but it may produce significant respiratory depression when combined with centrally acting depressant agents (eg, opioids). Assess respiratory rate and effort closely following exposure; administer oxygen, assist ventilation and intubate if clinically indicated.
    E) ANTIDOTE
    1) None.
    F) ENHANCED ELIMINATION PROCEDURE
    1) Hemodialysis is UNLIKELY to be of value because of the high degree of protein binding and large volume of distribution.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: There is no data to support home management; dexmedetomidine is generally only used in the hospital setting.
    2) OBSERVATION CRITERIA: Patients who are symptomatic should be observed with frequent monitoring of vital signs.
    3) HOSPITAL ADMISSION: Patients with dysrhythmias or severe respiratory distress require ICU admission.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    H) PITFALLS
    1) Be mindful of abrupt dose reduction or sudden cessation of therapy with dexmedetomidine infusions greater than 24 hours in duration. Withdrawal symptoms (eg, nausea, vomiting, agitation, palpitations, and hypertension) have developed.
    I) PHARMACOKINETICS
    1) Dexmedetomidine is 94% protein bound. Volume of distribution is 118 L; distribution half-life is approximately 6 minutes. Almost completely metabolized via direct glucuronidation and cytochrome P450 enzymes. Approximately 85% of a radiolabeled dexmedetomidine dose was recovered in the urine 24 hours following IV infusion. Clearance is approximately 39 L/hour and terminal elimination half-life is approximately 2 hours.
    J) PREDISPOSING CONDITIONS
    1) Dexmedetomidine decreases sympathetic nervous system activity, therefore bradycardia and hypotension may be profound in some patients including the elderly, hypovolemic patients or patients with significant comorbidity (e.g., diabetes mellitus or chronic hypertension).
    K) DIFFERENTIAL DIAGNOSIS
    1) Overdose with other alpha-2 adrenoreceptor agonists (eg, clonidine, guanfacine).

Range Of Toxicity

    A) TOXICITY: Limited data. Three patients received an inadvertent overdose in the perioperative setting: one patient received a dose of 192 mcg (2.6 times the prescribed dose) over 20 minutes; one received 4 and 2 mcg/kg/hr instead of 0.4 and 0.2 mcg/kg/hr and the third patient received 0.5 mcg/kg/min rather than 0.5 mcg/kg/hr. The major clinical effect in all three was oversedation, which resolved with the discontinuation of the infusion. In a study of healthy subjects receiving doses approximately 13 times the upper limit of therapeutic range, transient AV block (first and second degree) developed which resolved spontaneously. One patient received a bolus dose of 19.4 mcg/kg undiluted dexmedetomidine and had a cardiac arrest from which he was successfully resuscitated.
    B) THERAPEUTIC DOSE: For sedation, intubated/mechanically ventilated ICU patients: ADULT: Initial dose: 1 mcg/kg over 10 min; Maintenance: 0.2 to 0.7 mcg/kg/hr infusion for a maximum of 24 hours. Procedural sedation: ADULT: Initial dose: 0.5 to 1 mcg/kg over 10 min; Maintenance: 0.6 mcg/kg/hr initially and adjust to 0.2 to 1 mcg/kg/hr for a maximum of 24 hours. PEDIATRIC: Safety and efficacy in children less than 18 years of age have not been established.

Clinical Effects

Summary Of Exposure

    A) USES: Indicated for short term (24 hours or less) sedation of patients requiring intubation and mechanical ventilation in an intensive care setting. It is also used for sedating non-intubated patients either before and/or during surgical and non-surgical procedures. Multiple studies have utilized dexmedetomidine for greater than 24 hours; therefore, it may be a safe and effective sedative when used for longer than 24 hours.
    B) PHARMACOLOGY: Dexmedetomidine is a specific and selective alpha-2 adrenoceptor agonist. It has a significantly higher alpha-2/alpha-1 selectivity ratio than does clonidine.
    C) TOXICOLOGY: It is anticipated that dexmedetomidine can produce hypotension and bradycardia induced by vagal stimuli and sympathetic outflow.
    D) EPIDEMIOLOGY: Overdose is rare.
    E) WITH THERAPEUTIC USE
    1) COMMON: The most frequently reported adverse events include: hypotension (28%), hypertension (16%) {associated with loading dose administration}, bradycardia (7%), tachycardia (3%) and hypoxia (4%). Dexmedetomidine decreases sympathetic nervous system activity, therefore, bradycardia and hypotension may be profound in some patients including the elderly, hypovolemic patients or patients with significant comorbidity (e.g., diabetes mellitus or chronic hypertension). Respiratory depression is rare, despite doses that produce marked sedation. Other events include atrial fibrillation (4%), fever (5%), vomiting (4%), hemorrhage (3%), and anemia (3%). INFREQUENT EVENTS: Hyperpyrexia, pain, hyperglycemia, acidosis, pleural effusion, oliguria and thirst may develop.
    2) WITHDRAWAL SYNDROME: Withdrawal symptoms may occur following abrupt dose reduction or sudden cessation of therapy, similar to clonidine and other centrally acting antihypertensive agents. Symptoms include, but are not limited to, nausea, vomiting, agitation, palpitations, and hypertension.
    F) WITH POISONING/EXPOSURE
    1) Limited data exists on overdose. It is anticipated that overdose events may be an extension of the adverse events observed. Overdose may result in oversedation, bradycardia and hypotension. In a series of 3 inadvertent overdoses, deep hypnosis developed, which resolved within one hour of drug discontinuation. First and second degree AV block were reported in volunteers receiving supratherapeutic doses. Bradycardia and hypotension developed in two patients who received 2 mcg/kg over 10 minutes. Cardiac arrest developed in a patient after a bolus loading dose of undiluted dexmedetomidine (19.4 mcg/kg; normal loading dose 1 mcg/kg); recovery was uneventful.

Vital Signs

    3.3.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Fever may occur with therapeutic use. Bradycardia and hypotension can occur with therapy, but may not produce hemodynamic instability. Transient, mild hypertension has also developed during initial treatment.
    3.3.2) RESPIRATIONS
    A) WITH THERAPEUTIC USE
    a) Dexmedetomidine does not cause clinically significant respiratory depression, despite doses that produce marked sedation (Arain & Ebert, 2002; Peden & Prys-Roberts, 1992a). In a study of healthy volunteers administered an initial bolus of dexmedetomidine followed by a maintenance dose of 0.2 or 0.6 mcg/kg/hr, respiratory function remained normal with no dose effect on respiratory rate or oxygen saturation (Hall et al, 2000). It may, however, potentiate the respiratory depressant effects of other agents (i.e., opioids) when used in conjunction for general anesthesia (Ho et al, 2005).
    3.3.3) TEMPERATURE
    A) WITH THERAPEUTIC USE
    1) FEVER
    a) Fever was reported in 5% of ICU patients (n=387) sedated with dexmedetomidine during clinical trials (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    2) HYPOTHERMIA
    a) CASE REPORT: Hypothermia-induced bradycardia occurred in a 2-day-old female neonate who underwent primary repair of bladder exstrophy; the effect thought to be secondary to the alpha-2-agonist activity of dexmedetomidine. Although dexmedetomidine decreases lipolysis and can prevent thermogenesis in infants, multiple other medications including opioids, and anesthetics were given in this case, so causality is unclear (Finkel & Quezado, 2007).
    3.3.4) BLOOD PRESSURE
    A) WITH THERAPEUTIC USE
    1) Hypotension can occur with dexmedetomidine, in certain clinical settings (i.e., hypovolemia, diabetes, the elderly). Transient, mild hypertension may develop during initial therapy (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    3.3.5) PULSE
    A) WITH THERAPEUTIC USE
    1) Bradycardia may develop with therapeutic use, and may be more likely in some settings (ie, hypovolemia, diabetes, the elderly). Sinus arrest has been reported in young, healthy volunteers with high vagal tone or following rapid administration (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypotension (reduction in excess of 20% from baseline) has been reported in 28% to 30% of patients sedated with dexmedetomidine during clinical trials (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013; Gerlach & Dasta, 2007). Hypotension has also been observed during surgery in patients premedicated with intravenous dexmedetomidine (Jaakola et al, 1992).
    b) Dexmedetomidine decreases sympathetic nervous system activity, therefore bradycardia and hypotension may be profound in a selected patient population including the elderly, hypovolemic patients, or patients with multiple co-morbidities (eg, diabetes mellitus or chronic hypertension) (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    2) WITH POISONING/EXPOSURE
    a) Three surgical patients received inadvertent overdoses of dexmedetomidine. One received 192 mcg over 20 minutes, another received an infusion of 4 mcg/kg/hr for 2 hours followed by 2 mcg/kg/hr for 6 hours 15 minutes (intended infusion was 0.4 mcg/kg/hr and 0.2 mcg/kg/hr, respectively), and the third received 1600 mcg (a 60 fold overdose) over an unclear time period (probably 15 minutes). The major clinical effect was oversedation, with only minor decreases in heart rate and blood pressure. Symptoms resolved within one hour of discontinuation of the infusion, and all three patients remained hemodynamically stable. Recovery was uneventful (Jorden et al, 2004).
    b) In healthy male subjects, administration of 5 mcg/mL of dexmedetomidine did not seriously attenuate myocardial perfusion compared to 0.5 mcg/mL (therapeutic dose) (Snapir et al, 2006).
    c) CASE REPORTS: In a series of 5 patients receiving inadvertent overdoses of dexmedetomidine during an ICU sedation study, 2 patients developed no symptoms. Bradycardia and hypotension developed in 2 other patients receiving a 2 mcg/kg (1 mcg/kg recommended) loading dose over 10 minutes (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    B) BRADYCARDIA
    1) WITH THERAPEUTIC USE
    a) Sinus bradycardia (less than 45 beats/minute) requiring atropine administration has occurred after intravenous and intramuscular doses of dexmedetomidine (Aho et al, 1991aa; Aho et al, 1991a; Kallio et al, 1989; Jaakola et al, 1991a; Aantaa et al, 1991a; Aantaa et al, 1991). This has been a particular problem with intramuscular doses of 1 mcg/kg or greater (Aantaa et al, 1991; Aantaa et al, 1991a).
    b) Dexmedetomidine decreases sympathetic nervous system activity, therefore bradycardia and hypotension may be profound in some patients including the elderly, hypovolemic patients, or patients with significant comorbidity (e.g., diabetes mellitus or chronic hypertension) (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    1) INCIDENCE: Bradycardia developed in 7% of patients (n=387) sedated with dexmedetomidine during clinical trials (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    c) Bradycardia of 31 beats/minute as well as a systolic blood pressure of 65 mmHg occurred about 9 hours after application of a transdermal patch during pharmacokinetic studies in healthy volunteers; fluids and atropine were administered for reversal (Kivisto et al, 1994).
    d) Administration of glycopyrrolate has minimized the bradycardic effects of dexmedetomidine (Aho et al, 1991a; Scheinin et al, 1992a); atipamezole, a selective alpha-2 adrenoceptor antagonist, has effectively reversed dexmedetomidine-induced hypotension (Karhuvaara et al, 1991).
    e) CASE SERIES: In a study of 10 healthy men receiving sequential 40-minute infusions of dexmedetomidine (0.5 to 8.0 ng/mL doses), progressive decreases in heart rate and cardiac output were found with higher doses of dexmedetomidine. Dexmedetomidine produces both an inhibition of sympathetic effect and an increase in cardiac vagal activity which results in a decrease in heart rate (Ebert et al, 2000).
    f) CASE REPORT (PEDIATRIC): Bradycardia, resulting in vasovagal syncope, occurred in an 11-year-old girl who received dexmedetomidine, 100 mcg intranasally (2.4 mcg/kg), for sedation prior to a voiding cystourethrogram procedure. Following the procedure, the patient's blood pressure and heart rate were 97/38 mmHg and 74 beats per minute. However, after leaving the sedation area, the patient experienced a syncopal episode. Repeat monitoring of vital signs revealed a blood pressure of 78/51 mmHg and a heart rate of 36 beats per minute. An ECG demonstrated sinus bradycardia. Following continued observation and cardiac monitoring over the next 2 hours, the patient's heart rate normalized spontaneously and she was discharged the next day without sequelae (Patel et al, 2014).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORTS: In a series of 5 patients receiving inadvertent overdoses of dexmedetomidine during an ICU sedation study, 2 patients developed no symptoms. Bradycardia and hypotension developed in 2 other patients receiving a 2 mcg/kg (1 mcg/kg recommended) loading dose over 10 minutes (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    b) Three surgical patients received inadvertent overdoses of dexmedetomidine. One received 192 mcg over 20 minutes, another received an infusion of 4 mcg/kg/hr for 2 hours followed by 2 mcg/kg/hr for 6 hours 15 minutes (intended infusion was 0.4 mcg/kg/hr and 0.2 mcg/kg/hr respectively), and the third received 1600 mcg (a 60 fold overdose) over an unclear time period (probably 15 minutes). The major clinical effect was oversedation, with only minor decreases in heart rate and blood pressure. Symptoms resolved within one hour of discontinuation of the infusion, and all three patients remained hemodynamically stable. Recovery was uneventful (Jorden et al, 2004).
    c) CASE REPORT (PEDIATRIC): A 20-month-old, 10.7 kg, toddler received dexmedetomidine during a patent ductus arteriosus closure procedure. The intended infusion rate was 1 mcg/kg/hr, but the toddler was inadvertently administered 1 mcg/kg/min for a period of 36 minutes. In total, a dose of 380 mcg (36 mcg/kg) was given. During the infusion, the toddler experienced bradycardia (nadir = 84 beats/min) which responded to atropine. Hypertension and hypoglycemia were also complications of the overdose. The toddler was treated symptomatically and made a full recovery (Bernard et al, 2009).
    C) CONDUCTION DISORDER OF THE HEART
    1) WITH THERAPEUTIC USE
    a) Atrial fibrillation has been reported during clinical trials in 4% of patients (n=387) sedated with dexmedetomidine (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    2) WITH POISONING/EXPOSURE
    a) First and second degree AV block developed in volunteers with dexmedetomidine blood concentrations up to 13 times the upper limit of therapeutic range. Hemodynamic compromise was not observed, and the effects resolved spontaneously within one minute (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    D) CARDIAC ARREST
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 52-year-old healthy woman newly diagnosed with myasthenia gravis underwent surgery to remove a thymoma, and developed progressive bradycardia and asystole intraoperatively. During the preoperative period, the patient was given midazolam and a loading dose of 1 mcg/kg dexmedetomidine followed by an infusion at 0.2 mcg/kg/hr. General anesthesia was induced with fentanyl and propofol IV with no neuromuscular blockade. Anesthesia was maintained with isoflurane and a dexmedetomidine infusion. Upon sternal retraction, the patient's heart rate dropped into the 30's (heart rate 46-50 BPM during initiation of surgery) progressing to asystole. Immediate cardiac massage and 300 mcg IV epinephrine restored her heart rate and blood pressure. Dexmedetomidine was stopped and the surgery was completed. The patient was extubated successfully with no evidence of cardiac or neurologic compromise. The patient was discharged on postoperative day 4.
    1) The authors suggested that the development of asystole in this patient was multifactorial, but the primary factors were likely due to the centrally mediated decrease in sympathetic outflow and increase in parasympathetic outflow from dexmedetomidine, and the patient's autonomic response to abrupt surgical stimulation. An increase in vagal tone at baseline may have also contributed to the development of asystole (Ingersoll-Weng et al, 2004).
    2) It has been further suggested that the dose of dexmedetomidine in this setting was excessive given the concomitant use of other agents including anesthetics, sedatives, hypnotics, and opioids. The patient may have also been at greater risk for developing progressive bradycardia and hypotension due to an increase in vagal activity due to vigorous exercise and the use of pyridostigmine preoperatively to treat her myasthenia gravis. The authors concluded that an excessive dose of dexmedetomidine, along with delayed treatment of initial bradycardia and possible inadequate hydration led to cardiac arrest in this patient (Muntazar & Kumar, 2004).
    b) CASE REPORT: A 76-year-old woman with a history of hypertension, hyperlipidemia, chronic atrial fibrillation and diabetes, developed a staphylococcal bacteremia from an infected pacemaker. She was started on a vancomycin infusion and was sedated with 1 mcg/kg of dexmedetomidine. After 15 minutes with an estimated dose of 71.25 mcg the patient coughed, became dyspneic and lost consciousness. Standard resuscitative measure were initiated; however, the patient expired. Autopsy results were significant for cardiomegaly and diffuse calcific atherosclerosis. The authors concluded that the patient died secondary to the hemodynamic and arrhythmogenic effects of dexmedetomidine (Shah et al, 2007).
    2) WITH POISONING/EXPOSURE
    a) Cardiac arrest developed in a patient receiving a bolus loading dose of undiluted dexmedetomidine of 19.4 mcg/kg, instead of the recommended loading dose of 1 mcg/kg; recovery was uneventful (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    E) HYPERTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) During clinical trials, transient hypertension occurred in 16% of patients sedated with dexmedetomidine (n=387). This event has primarily been associated with the loading dose phase (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013). It has been suggested that the activation of postsynaptic alpha-2 adrenoceptors in vascular smooth muscle produces the effect (Kallio et al, 1989).
    b) Significant, sustained hypertension has been observed in healthy subjects whose plasma concentration levels of dexmedetomidine attained or exceeded 1.9 ng/mL. The change in mean arterial pressure (MAP) was biphasic, with an initial decline in MAP followed by linear, dose-related increases in pressure. The increase in MAP was accompanied by significant elevations of central venous pressure (mean increase of 195%), pulmonary capillary wedge pressure (mean increase of 89%), pulmonary artery pressure (mean increase of 44%), and pulmonary vascular resistance (mean increase of 155%). A mean decrease of 35% in cardiac output was also associated with administration of higher doses of dexmedetomidine (Ebert et al, 2000a).
    c) CASE REPORT (PEDIATRIC): A 2-year-old boy with traumatic brain injury was administered dexmedetomidine for sedation at an initial dose of 2 mcg/kg/hr. The dose was increased to 4 mcg/kg/hr over the next 12 hours secondary to agitation. Hypertension developed (range = 130-140/60-70 mmHg) despite the patient showing no signs of agitation or pain and heart rate maintaining at 60 to 70 beats/minute. The dexmedetomidine infusion was decreased to 2 mcg/kg/hr, and the patient's blood pressure normalized (range = 90-100/50-60 mmHg) within 20 minutes. The dexmedetomidine infusion was weaned over the next few days with no other hypertensive episodes (Erkonen et al, 2008).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT (PEDIATRIC): A 20-month-old, 10.7 kg, toddler received dexmedetomidine during a patent ductus arteriosus closure procedure. The intended infusion rate was 1 mcg/kg/hr, but the toddler was inadvertently administered 1 mcg/kg/min for a period of 36 minutes. In total, a dose of 380 mcg (36 mcg/kg) was given. During the infusion, the toddler experienced hypertension (peak = 152/85 mm Hg) and bradycardia. Hypoglycemia was also a complication of the overdose. The toddler was treated symptomatically and made a full recovery (Bernard et al, 2009).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) HYPOXIA
    1) WITH THERAPEUTIC USE
    a) During clinical trials, hypoxia was observed in 4% of patients sedated with dexmedetomidine (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    b) Dexmedetomidine does not induce significant ventilatory depression, despite doses that produce marked sedation (Ebert et al, 2000; Arain & Ebert, 2002; Peden & Prys-Roberts, 1992a). In a study of healthy volunteers administered an initial bolus of dexmedetomidine followed by a maintenance dose of 0.2 or 0.6 mcg/kg/hr, respiratory function remained normal with no dose effect on respiratory rate or oxygen saturation (Hall et al, 2000). The use of dexmedetomidine may reduce postoperative respiratory depression by decreasing opioid requirements (Peden & Prys-Roberts, 1992a).
    B) APNEA
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 69-year-old woman underwent genitourinary surgery requiring general anesthesia including opioids and dexmedetomidine and became apneic approximately one minute after being extubated in the recovery room. No respiratory effort was observed, and oxygen saturation declined. The patient was ventilated for approximately 5 minutes along with discontinuation of the dexmedetomidine infusion; she began to breathe on her own and recovered without sequelae (Ho et al, 2005). The authors suggested that dexmedetomidine may have potentiated the respiratory depressant effects of the opioids given, along with the patient's age and lack of habituation to sedative use.

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH THERAPEUTIC USE
    a) Adverse central nervous system effects of dexmedetomidine include fatigue, headache, restlessness, and dizziness (Scheinin et al, 1992a; Aantaa et al, 1990a; Aantaa et al, 1991a; Jaakola et al, 1991a).
    B) SEDATED
    1) WITH THERAPEUTIC USE
    a) Sedation is a prominent effect of dexmedetomidine, and is considered beneficial when used as an anesthesia adjunct (Kallio et al, 1989; Karhuvaara et al, 1991; Scheinin et al, 1992a; Aho et al, 1991a; Aantaa et al, 1990a). However, excessive and prolonged sedation has limited the use of intravenous dexmedetomidine for postoperative pain (Aho et al, 1991aa) and intramuscular dexmedetomidine for anesthetic premedication (Aantaa et al, 1991; Aantaa et al, 1991a). Atipamezole, a selective alpha-2 adrenoceptor antagonist, is capable of reversing dexmedetomidine-induced sedation (Karhuvaara et al, 1991).
    b) In a study of healthy volunteers administered an initial bolus of dexmedetomidine followed by a maintenance dose of 0.2 (small) or 0.6 (moderate) mcg/kg/hr, significant sedation developed. Sedation levels after a 60 minute infusion were similar between doses resulting in sedation rates of 61% and 76% in small and moderate dose groups, respectively (Hall et al, 2000).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORTS: In a series of 3 inadvertent overdoses, deep hypnosis developed, which resolved within one hour of drug discontinuation (Jorden et al, 2004).
    C) COGNITIVE FUNCTION FINDING
    1) WITH THERAPEUTIC USE
    a) In a study of healthy volunteers administered an initial bolus of dexmedetomidine followed by a maintenance dose of 0.2 (small) or 0.6 (moderate) mcg/kg/hr, produced a reduction in word recall of 37% and 46%, respectively as compared with a 6% decrease in the placebo group. Psychomotor performance was also decreased in the treatment groups. However, symptoms resolved once the infusion was stopped (Hall et al, 2000).
    D) SYNCOPE
    1) WITH THERAPEUTIC USE
    a) CASE REPORT (PEDIATRIC): Vasovagal syncope secondary to bradycardia occurred in an 11-year-old girl who received dexmedetomidine, 100 mcg intranasally (2.4 mcg/kg), for sedation prior to a voiding cystourethrogram procedure. Following the procedure, the patient's blood pressure and heart rate were 97/38 mmHg and 74 beats per minute. However, after leaving the sedation area, the patient experienced a syncopal episode. Repeat monitoring of vital signs revealed a blood pressure of 78/51 mmHg and a heart rate of 36 beats per minute. An ECG demonstrated sinus bradycardia. Following continued observation and cardiac monitoring over the next 2 hours, the patient's heart rate normalized spontaneously and she was discharged the next day without sequelae (Patel et al, 2014).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) During clinical trials, nausea was reported in 11% of patients (n=387) sedated with dexmedetomidine, and vomiting occurred in 4% (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    B) GASTROINTESTINAL TRACT FINDING
    1) WITH THERAPEUTIC USE
    a) Post-marketing surveillance has reported the occurrence of abdominal pain and diarrhea with therapeutic dexmedetomidine use (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    b) XEROSTOMIA is a prominent effect of dexmedetomidine (Kallio et al, 1989; Jaakola et al, 1991a; Aantaa et al, 1990a).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) DIURESIS
    1) WITH THERAPEUTIC USE
    a) In one study, dexmedetomidine was administered as a supplement to epidural analgesia and induced diuresis in post-thoracotomy patients (Frumento et al, 2006).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH THERAPEUTIC USE
    a) A generalized urticarial reaction with mild temperature elevation occurred 30 hours after transdermal patch application (about 20 hours after patch removal) in a healthy volunteer participating in pharmacokinetic studies of this dosage form. Given the time delay, the reaction was attributed to a component of the patch other than dexmedetomidine (Kivisto et al, 1994).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HYPOGLYCEMIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT (PEDIATRIC): A 20-month-old, 10.7 kg, toddler received dexmedetomidine during a patent ductus arteriosus closure procedure. The intended infusion rate was 1 mcg/kg/hr, but the toddler was inadvertently administered 1 mcg/kg/min for a period of 36 minutes. In total, a dose of 380 mcg (36 mcg/kg) was given. During the infusion, the toddler experienced bradycardia (nadir = 84 beats/min) which responded to atropine and hypertension (peak = 152/85 mmHg). Three hours after the infusion was stopped, a peripheral blood sugar level was 26 mg/dL. The patient was treated symptomatically with dextrose infusions and made a full recovery (Bernard et al, 2009). The authors suggested that the hypoglycemia observed in this child was likely due to substrate deficiency, with a possible dexmedetomidine effect.

Reproductive

    3.20.1) SUMMARY
    A) Dexmedetomidine is classified as FDA pregnancy category C. Embryo and fetal toxicity, but no teratogenicity, were reported in animal studies. It is not known if dexmedetomidine is secreted in human breast milk, although animal studies reported the drug in the milk of lactating rats.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent (Prod Info PRECEDEX(R) intravenous injection, 2008).
    B) ANIMAL STUDIES
    1) RATS, RABBITS: Animal studies reported no teratogenic effects in rats given dexmedetomidine in subQ doses up to 200 mcg/kg (about twice the human dose) from days 5 to 16 of gestation, or in rabbits given IV doses up to 96 mcg/kg (about equal the human dose) from days 6 to 18 of gestation (Prod Info PRECEDEX(R) intravenous injection, 2008).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) The manufacturer has classified dexmedetomidine as FDA pregnancy category C (Prod Info PRECEDEX(R) intravenous injection, 2008).
    B) ANIMAL STUDIES
    1) RATS: Fetal toxicity (increased post-implantation losses and reduced live pups) was reported in rats given subQ doses of 200 mcg/kg (about twice the human dose) from days 5 to 16 of gestation. A no-effect dose of 20 mcg/kg was reported. Another study reported low birth weights in the offspring of rats given 8 and 32 mcg/kg doses of dexmedetomidine from day 16 of gestation through nursing. At 32 mcg/kg (less than the maximum recommended human IV dose), rat offspring also showed delayed motor development. Rat embryo and fetal toxicity were observed in second-generation offspring at the daily 32 mcg/kg dosage. In pregnant rats, dexmedetomidine crossed the placental barrier (Prod Info PRECEDEX(R) intravenous injection, 2008).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation in humans (Prod Info PRECEDEX(R) intravenous injection, 2008).
    B) ANIMAL STUDIES
    1) RATS: Dexmedetomidine is excreted in the milk of lactating rats following subQ administration (Prod Info PRECEDEX(R) intravenous injection, 2008).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) RATS: There was no effect on fertility in both sexes after subQ injections of dexmedetomidine at doses up to 54 mcg/mg daily (less than the maximum recommended IV dose in humans) for 10 weeks before mating in males and 3 weeks before mating, and during mating, in females (Prod Info PRECEDEX(R) intravenous injection, 2008).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no studies were found on the possible carcinogenic activity of dexmedetomidine in humans.
    3.21.4) ANIMAL STUDIES
    A) LACK OF INFORMATION
    1) Animal studies to determine the possible carcinogenic activity of dexmedetomidine have not been performed (Prod Info PRECEDEX(R) intravenous injection, 2008).

Genotoxicity

    A) Dexmedetomidine was found to be clastogenic in an in vitro human lymphocyte chromosome aberration test with (but not without) rat S9 metabolic activation and in the in vivo mouse micronucleus test in NMRI mice. However, an vitro human lymphocyte chromosome aberration test with or without human S9 metabolic activation and the in vivo mouse micronucleus test in CD-1 mice did not find dexmedetomidine to be clastogenic (Prod Info PRECEDEX(R) intravenous injection, 2008).
    B) In vitro studies did not find dexmedetomidine to be mutagenic in either the bacterial reverse mutation assay (E coli and Salmonella typhimurium) or the mammalian cell forward mutation assay (mouse lymphoma) (Prod Info PRECEDEX(R) intravenous injection, 2008).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and pulse oximetry. Hypotension, bradycardia and respiratory depression may develop. Institute continuous cardiac monitoring and obtain an ECG.
    B) Monitor neurologic function.
    C) Specific laboratory tests are not necessary following inadvertent exposure, unless otherwise clinically indicated.
    4.1.2) SERUM/BLOOD
    A) Specific laboratory tests are not necessary following inadvertent exposure, unless otherwise clinically indicated.
    B) Monitor hepatic and renal function in patient's with a history of hepatic insufficiency; decreased drug clearance may develop with severe hepatic impairment.
    4.1.4) OTHER
    A) OTHER
    1) Cardiac Monitoring
    a) Continuous cardiac monitoring is indicated during infusion. Bradycardia and sinus arrest have been associated with dexmedetomidine administration (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013). Asystole may develop in overdose (Jorden et al, 2004).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.2) DISPOSITION/PARENTERAL EXPOSURE
    6.3.2.1) ADMISSION CRITERIA/PARENTERAL
    A) Patients with dysrhythmias or severe respiratory distress require ICU admission.
    6.3.2.2) HOME CRITERIA/PARENTERAL
    A) There is no data to support home management; dexmedetomidine is generally only used in the hospital setting.
    6.3.2.3) CONSULT CRITERIA/PARENTERAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.2.5) OBSERVATION CRITERIA/PARENTERAL
    A) Patients who are symptomatic should be observed with frequent monitoring of vital signs.

Monitoring

    A) Monitor vital signs and pulse oximetry. Hypotension, bradycardia and respiratory depression may develop. Institute continuous cardiac monitoring and obtain an ECG.
    B) Monitor neurologic function.
    C) Specific laboratory tests are not necessary following inadvertent exposure, unless otherwise clinically indicated.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Decontamination is not indicated, since the drug is administered parenterally.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Treatment should include recommendations listed in the PARENTERAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) HEMODIALYSIS
    1) Hemodialysis is UNLIKELY to be of value because of the high degree of protein binding (94%) and large volume of distribution (118 liters) (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).

Range Of Toxicity

Summary

    A) TOXICITY: Limited data. Three patients received an inadvertent overdose in the perioperative setting: one patient received a dose of 192 mcg (2.6 times the prescribed dose) over 20 minutes; one received 4 and 2 mcg/kg/hr instead of 0.4 and 0.2 mcg/kg/hr and the third patient received 0.5 mcg/kg/min rather than 0.5 mcg/kg/hr. The major clinical effect in all three was oversedation, which resolved with the discontinuation of the infusion. In a study of healthy subjects receiving doses approximately 13 times the upper limit of therapeutic range, transient AV block (first and second degree) developed which resolved spontaneously. One patient received a bolus dose of 19.4 mcg/kg undiluted dexmedetomidine and had a cardiac arrest from which he was successfully resuscitated.
    B) THERAPEUTIC DOSE: For sedation, intubated/mechanically ventilated ICU patients: ADULT: Initial dose: 1 mcg/kg over 10 min; Maintenance: 0.2 to 0.7 mcg/kg/hr infusion for a maximum of 24 hours. Procedural sedation: ADULT: Initial dose: 0.5 to 1 mcg/kg over 10 min; Maintenance: 0.6 mcg/kg/hr initially and adjust to 0.2 to 1 mcg/kg/hr for a maximum of 24 hours. PEDIATRIC: Safety and efficacy in children less than 18 years of age have not been established.

Therapeutic Dose

    7.2.1) ADULT
    A) ICU SEDATION
    1) LOADING DOSE: 1 mcg/kg over 10 minutes using a controlled infusion device (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013)
    2) MAINTENANCE DOSE: 0.2 to 0.7 mcg/kg/hour, not to exceed 24 hours (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013)
    B) PROCEDURAL SEDATION
    1) LOADING DOSE: 0.5 to 1 mcg/kg over 10 minutes using a controlled infusion device (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013)
    2) MAINTENANCE DOSE: Initiate at 0.6 mcg/kg/hour and adjust to 0.2 to 1 mcg/kg/hour, not to exceed 24 hours (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013)
    7.2.2) PEDIATRIC
    A) Safety and efficacy in the pediatric or adolescent population have not been established (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013)

Maximum Tolerated Exposure

    A) Three patients received an inadvertent overdose in the perioperative setting. One patient received a dose of 192 mcg (2.6 times the prescribed dose) over 20 minutes. The other two patients received 4 and 2 mcg/kg/hr instead of 0.4 and 0.2 mcg/kg/hr and 0.5 mcg/kg/min rather than 0.5 mcg/kg/hr, respectively. The major clinical effect was oversedation, which resolved with the discontinuation of the infusion (Jorden et al, 2004).
    B) In a study of healthy subjects receiving doses approximately 13 times the upper limit of therapeutic range, transient AV block (first and second degree) developed, which resolved spontaneously (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    C) One patient received a bolus dose of 19.4 mcg/kg undiluted dexmedetomidine and had a cardiac arrest from which he was successfully resuscitated (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013).
    D) PROLONGED THERAPY/CASE REPORTS: Although dexmedetomidine is recommended for only 24 hours of continuous infusion for sedation (Prod Info Precedex(TM) intravenous injection, intravenous injection concentrate , 2013), two ICU patients were successfully maintained on a dexmedetomidine infusion for 36 hours and 7 days, respectively. In the first patient experiencing cocaine withdrawal, the dose was titrated to maintain a motor activity level in which the patient was calm, followed commands, and had purposeful movement . The second patient was mechanically ventilated and had developed sedative-analgesic withdrawal following a protracted course in the ICU. The patient was maintained on dexmedetomidine for 7 days at 0.7 mcg/kg/hr and was gradually weaned, with no further withdrawal symptoms observed (Maccioli, 2003).
    E) INTRA-ARTERIAL INJECTION: A 43-year-old woman inadvertently received a bolus dose of 50 mcg of dexmedetomidine (0.7 mcg/kg) through a canula in her ulnar artery for post-operative sedation. The bolus was administered over 10 minutes. Other than slight decreases in heart rate (90 to 65 beats/min) and blood pressure (10% decrease in mean systolic pressure) during dexmedetomidine administration, the patient remained asymptomatic. Color, temperature and peripheral arterial pulses remained similar in both hands. Serial Doppler studies demonstrated normal blood flow to the affected artery and no evidence of a thrombus. There were no sequelae at the 3-month follow-up (Ghatak & Samanta, 2013).
    F) PEDIATRIC: A 20-month-old, 10.7 kg, toddler received dexmedetomidine during a patent ductus arteriosus closure procedure. The intended infusion rate was 1 mcg/kg/hr, but the toddler was inadvertently administered 1 mcg/kg/min for a period of 36 minutes. In total, a dose of 380 mcg (36 mcg/kg) was given. The patient experienced bradycardia (nadir = 84 beats/min) which responded to atropine and hypertension (peak = 152/85 mm Hg) during the infusion. Three hours after the infusion had been stopped, a peripheral blood sugar level was 26 mg/dL. The patient responded well to dextrose infusions and a full recovery was noted (Bernard et al, 2009).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Dexmedetomidine is a specific and selective alpha-2 adrenoceptor agonist (Peden & Prys-Roberts, 1992; Kharasch et al, 1991; Scheinin et al, 1992). This compound is an imidazole derivative and the active d-isomer of medetomidine, an agent which has been used in veterinary medicine as a hypnotic, sedative, and analgesic (Maze & Tranquilli, 1991; Peden & Prys-Roberts, 1992). The clinical effects of racemic medetomidine are attributed exclusively to dexmedetomidine (Kharasch et al, 1991).
    B) The mechanism of action of dexmedetomidine resembles that of clonidine, although its affinity for the alpha-2 adrenoceptor is approximately 8 times that of clonidine (Peden & Prys-Roberts, 1992). Dexmedetomidine has a significantly higher alpha-2/alpha-1 selectivity ratio than does clonidine (Aantaa et al, 1990; Jaakola et al, 1991).
    C) Parenterally administered dexmedetomidine produces clinical actions similar to those of clonidine, including sedation, reduced salivation, reduced blood pressure and heart rate, and tiredness (Kallio et al, 1990). Like clonidine, dexmedetomidine has been used in anesthesia to reduce anesthetic and opioid requirements, attenuate the tachycardic response to endotracheal intubation, and provide intraoperative hemodynamic stability (Scheinin et al, 1992; Peden & Prys-Roberts, 1992; Aho et al, 1991). Dexmedetomidine itself has anesthetic properties and has been used as a sole anesthetic in animal studies (Segal et al, 1988; Peden & Prys-Roberts, 1992). Data from animal studies suggest that dexmedetomidine may reduce volatile anesthetic requirements to a greater extent than does clonidine (Peden & Prys-Roberts, 1992). Analgesic effects of dexmedetomidine have also been demonstrated in healthy volunteers and surgical patients (Aho et al, 1991a; Jaakola et al, 1991).
    D) The sympatholytic effects of dexmedetomidine attenuate the stress response in patients emerging from anesthesia. Patients who receive dexmedetomidine during surgery do not experience increases in heart rate, systolic blood pressure, or in plasma norepinephrine concentrations (Talke et al, 2000).
    E) Precise mechanisms of anesthetic effect of dexmedetomidine are unknown but are presumed to be related to stimulation of central postsynaptic (and possibly presynaptic) alpha-2 receptors (Peden & Prys-Roberts, 1992; Aantaa et al, 1990); anesthetic and hypnotic effects of the drug have been reversed with alpha-2 adrenoceptor antagonists that cross the blood-brain barrier (atipamezole, idazoxan), whereas antagonism was not achieved with a peripheral alpha-2 antagonist (L-659-066) (Peden & Prys-Roberts, 1992). The analgesic effects of dexmedetomidine (and clonidine) appear to be mediated via both spinal and supraspinal mechanisms, although peripheral antinociception via release of an enkephalin-like substance has also been postulated (Aho et al, 1991a; Peden & Prys-Roberts, 1992; Jaakola et al, 1991). Analgesic effects of dexmedetomidine have been blocked by atipamezole but not by naloxone (Peden & Prys-Roberts, 1992). A close relationship between opioid mu and alpha-2 adrenergic actions in the modulation of pain pathways has recently been suggested (Peden & Prys-Roberts, 1992).

Toxicologic Mechanism

    A) Based on its mechanism of action, its anticipated that dexmedetomidine can produce hypotension and bradycardia induced by vagal stimuli and sympathetic outflow (Prod Info Precedex(TM) intravenous injection, 2016; Ebert et al, 2000). Interventions may include the administration of atropine to alter vagal tone and increase heart rate. Decreases in sympathetic nervous system activity may also result in more severe episodes of bradycardia and/or hypotension in patients with hypovolemia, a history of significant co-morbidities (eg, diabetes, chronic hypertension), and the elderly (Prod Info Precedex(TM) intravenous injection, 2016).

Physicochemical

Physical Characteristics

    A) Dexmedetomidine hydrochloride is a off-white to white powder, freely soluble in water; the pKa is 7.1 (Prod Info PRECEDEX(R) intravenous injection, 2008).

Ph

    A) 4.5 to 7 (Prod Info PRECEDEX(R) intravenous injection, 2008)

Molecular Weight

    A) 236.7 (Prod Info PRECEDEX(R) intravenous injection, 2008)

References

General Bibliography

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    2) Aantaa R, Kanto J, & Scheinin M: Intramuscular dexmedetomidine, a novel alpha(2)-adrenoceptor agonist, as premedication for minor gynaecological surgery. Acta Anaesthesiol Scand 1991a; 35:283-288.
    3) Aantaa R, Kanto J, Scheinin M, et al: Dexmedetomidine, an alpha(2)-adrenoceptor agonist, reduces anesthetic requirements for patients undergoing minor gynecologic surgery. Anesthesiology 1990; 73:230-235.
    4) Aantaa R, Kanto J, Scheinin M, et al: Dexmedetomidine, an alpha(2)-adrenoceptor agonist, reduces anesthetic requirements for patients undergoing minor gynecologic surgery. Anesthesiology 1990a; 73:230-235.
    5) Aho MS, Erkola OA, Scheinin H, et al: Effect of intravenously administered dexmedetomidine on pain after laparoscopic tubal ligation. Anesth Analg 1991a; 73:112-118.
    6) Aho MS, Erkola OA, Scheinin H, et al: Effect of intravenously administered dexmedetomidine on pain after laparoscopic tubal ligation. Anesth Analg 1991aa; 73:112-118.
    7) Aho MS, Lehtinen AM, Erkola O, et al: The effect of intravenously administered dexmedetomidine on perioperative hemodynamics and isoflurane requirements in patients undergoing abdominal hysterectomy. Anesthesiology 1991; 74:997-1002.
    8) Aho MS, Lehtinen AM, Erkola O, et al: The effect of intravenously administered dexmedetomidine on perioperative hemodynamics and isoflurane requirements in patients undergoing abdominal hysterectomy. Anesthesiology 1991a; 74:997-1002.
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    40) Product Information: PRECEDEX(R) injection, dexmedetomidine hcl injection. Hospira,Inc., Lake Forest, IL, 2004.
    41) Product Information: PRECEDEX(R) intravenous injection, dexmedetomidine hydrochloride intravenous injection. Hospira,Inc, Lake Forest, IL, 2008.
    42) Product Information: Precedex(TM) intravenous injection, dexmedetomidine HCl intravenous injection. Hospira, Inc. (per FDA), Lake Forest, IL, 2016.
    43) Product Information: Precedex(TM) intravenous injection, intravenous injection concentrate , dexmedetomidine HCl intravenous injection, intravenous injection concentrate . Hospira, Inc. (per FDA), Lake Forest, IL, 2013.
    44) Product Information: dopamine hcl, 5% dextrose IV injection, dopamine hcl, 5% dextrose IV injection. Hospira,Inc, Lake Forest, IL, 2004.
    45) Product Information: norepinephrine bitartrate injection, norepinephrine bitartrate injection. Sicor Pharmaceuticals,Inc, Irvine, CA, 2005.
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