For intravenous administration

Pediatric Patients 

Most patients aged 3 years through 16 years and classified ASA-PS I or II require 2.5 to  

3.5 mg/kg of DIPRIVAN Injectable Emulsion for induction when unpremedicated or when 

lightly premedicated with oral benzodiazepines or intramuscular opioids.  Within this dosage 

range, younger pediatric patients may require higher induction doses than older pediatric 

patients.  As with other sedative-hypnotic agents, the amount of intravenous opioid and/or 

benzodiazepine premedication will influence the response of the patient to an induction dose 

of DIPRIVAN Injectable Emulsion.  A lower dosage is recommended for pediatric patients 

classified as ASA-PS III or IV.  Attention should be paid to minimize pain on injection when 

administering DIPRIVAN Injectable Emulsion to pediatric patients.  Boluses of DIPRIVAN 

Injectable Emulsion may be administered via small veins if pretreated with lidocaine or via 

antecubital or larger veins (see PRECAUTIONS,_General'>PRECAUTIONS, General). 

Neurosurgical Patients 

Slower induction is recommended using boluses of 20 mg every 10 seconds.  Slower boluses 

or infusions of DIPRIVAN Injectable Emulsion for induction of anesthesia, titrated to clinical 

responses, will generally result in reduced induction dosage requirements (1 to  

2 mg/kg) (see PRECAUTIONS and DOSAGE AND ADMINISTRATION). 

Cardiac Anesthesia 

DIPRIVAN Injectable Emulsion has been well-studied in patients with coronary artery 

disease, but experience in patients with hemodynamically significant valvular or congenital 

heart disease is limited.  As with other anesthetic and sedative-hypnotic agents, DIPRIVAN 

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Injectable Emulsion in healthy patients causes a decrease in blood pressure that is secondary 

2 

to decreases in preload (ventricular filling volume at the end of the diastole) and afterload 

3 

(arterial resistance at the beginning of the systole).  The magnitude of these changes is 

4 

proportional to the blood and effect site concentrations achieved.  These concentrations 

5 

depend upon the dose and speed of the induction and maintenance infusion rates. 

6 

In addition, lower heart rates are observed during maintenance with DIPRIVAN 

7 

Injectable Emulsion, possibly due to reduction of the sympathetic activity and/or resetting of 

8 

the baroreceptor reflexes.  Therefore, anticholinergic agents should be administered when 

9 

increases in vagal tone are anticipated. 

10 

As with other anesthetic agents, DIPRIVAN Injectable Emulsion reduces myocardial 

11 

oxygen consumption.  Further studies are needed to confirm and delineate the extent of these 

12 

effects on the myocardium and the coronary vascular system.   

13 

Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been 

14 

shown to decrease the necessary DIPRIVAN Injectable Emulsion maintenance infusion rates 

15 

and therapeutic blood concentrations when compared to non-narcotic (lorazepam) 

16 

premedication.  The rate of DIPRIVAN Injectable Emulsion administration should be 

17 

determined based on the patient's premedication and adjusted according to clinical responses.   

18 

A rapid bolus induction should be avoided.  A slow rate of approximately 20 mg every 

19 

10 seconds until induction onset (0.5 to 1.5 mg/kg) should be used.  In order to assure 

20 

adequate anesthesia, when DIPRIVAN Injectable Emulsion is used as the primary agent, 

21 

maintenance infusion rates should not be less than 100 mcg/kg/min and should be 

22 

supplemented with analgesic levels of continuous opioid administration.  When an opioid is 

23 

used as the primary agent, DIPRIVAN Injectable Emulsion maintenance rates should not be 

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less than 50 mcg/kg/min, and care should be taken to ensure amnesia.  Higher doses of 

2 

DIPRIVAN Injectable Emulsion will reduce the opioid requirements (see Table 4).  When 

3 

DIPRIVAN Injectable Emulsion is used as the primary anesthetic, it should not be 

4 

administered with the high-dose opioid technique as this may increase the likelihood of 

5 

hypotension (see PRECAUTIONS, Cardiac Anesthesia). 

6 

Table 4.  Cardiac Anesthesia Techniques 

Primary Agent 

Rate 

Secondary Agent/Rate 

       (Following Induction with Primary Agent) 

DIPRIVAN Injectable Emulsion 

OPIOID

a

/0.05 to 0.075 mcg/kg/min (no bolus)

 Preinduction 

 Anxiolysis 

25 mcg/kg/min 

Induction 

0.5 to 1.5 mg/kg 

over 60 sec 

Maintenance 

(Titrated to Clinical 

Response) 

100 to 150 mcg/kg/min 

OPIOID

b 

DIPRIVAN Injectable Emulsion/50 to 100 mcg/kg/min 

(no bolus) 

Induction 

25 to 50 mcg/kg 

Maintenance 

0.2 to 0.3 mcg/kg/min 

7 

a

OPIOID is defined in terms of fentanyl equivalents, i.e., 

8 

1 mcg of fentanyl  =  5 mcg of alfentanil (for bolus) 

9 

=  10 mcg of alfentanil (for maintenance) 

10 

or 

11 

=  0.1 mcg of sufentanil 

12 

b

Care should be taken to ensure amnesia. 

13 

14 

Maintenance of General Anesthesia 

15 

DIPRIVAN Injectable Emulsion has been used with a variety of agents commonly used in 

16 

anesthesia such as atropine, scopolamine, glycopyrrolate, diazepam, depolarizing and 

17 

nondepolarizing muscle relaxants, and opioid analgesics, as well as with inhalational and 

18 

regional anesthetic agents. 

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In the elderly, debilitated, or ASA-PS III or IV patients, rapid bolus doses should not 

2 

be used, as this will increase cardiorespiratory effects including hypotension, apnea, airway 

3 

obstruction, and oxygen desaturation. 

4 

Adult Patients 

5 

In adults, anesthesia can be maintained by administering DIPRIVAN Injectable Emulsion by 

6 

infusion or intermittent IV bolus injection.  The patient's clinical response will determine the 

7 

infusion rate or the amount and frequency of incremental injections. 

8 

Continuous Infusion 

9 

DIPRIVAN Injectable Emulsion 100 to 200 mcg/kg/min administered in a variable rate 

10 

infusion with 60% to 70% nitrous oxide and oxygen provides anesthesia for patients 

11 

undergoing general surgery.  Maintenance by infusion of DIPRIVAN Injectable Emulsion 

12 

should immediately follow the induction dose in order to provide satisfactory or continuous 

13 

anesthesia during the induction phase.  During this initial period following the induction dose, 

14 

higher rates of infusion are generally required (150 to 200 mcg/kg/min) for the first  

15 

10 to 15 minutes.  Infusion rates should subsequently be decreased 30% to 50% during the 

16 

first half-hour of maintenance.  Generally, rates of 50 to 100 mcg/kg/min in adults should be 

17 

achieved during maintenance in order to optimize recovery times.   

18 

Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, 

19 

and opioids) can increase the CNS depression induced by propofol.   

20 

Intermittent Bolus 

21 

Increments of DIPRIVAN Injectable Emulsion 25 mg (2.5 mL) to 50 mg (5 mL) may be 

22 

administered with nitrous oxide in adult patients undergoing general surgery.  The 

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incremental boluses should be administered when changes in vital signs indicate a response to 

2 

surgical stimulation or light anesthesia. 

3 

Pediatric Patients 

4 

DIPRIVAN Injectable Emulsion administered as a variable rate infusion supplemented with 

5 

nitrous oxide 60% to 70% provides satisfactory anesthesia for most children 2 months of age 

6 

or older, ASA-PS I or II, undergoing general anesthesia. 

7 

In general, for the pediatric population, maintenance by infusion of DIPRIVAN 

8 

Injectable Emulsion at a rate of 200 to 300 mcg/kg/min should immediately follow the 

9 

induction dose.  Following the first half-hour of maintenance, infusion rates of 125 to  

10 

150 mcg/kg/min are typically needed.  DIPRIVAN Injectable Emulsion should be titrated to 

11 

achieve the desired clinical effect.  Younger pediatric patients may require higher 

12 

maintenance infusion rates than older pediatric patients.  (See Table 2 Clinical Trials.) 

13 

Monitored Anesthesia Care (MAC) Sedation 

14 

Adult Patients 

15 

When DIPRIVAN Injectable Emulsion is administered for MAC sedation, rates of 

16 

administration should be individualized and titrated to clinical response.  In most patients, the 

17 

rates of DIPRIVAN Injectable Emulsion administration will be in the range of 25 to  

18 

75 mcg/kg/min. 

19 

During initiation of MAC sedation, slow infusion or slow injection techniques are 

20 

preferable over rapid bolus administration.  During maintenance of MAC sedation, a variable 

21 

rate infusion is preferable over intermittent bolus dose administration.  In the elderly, 

22 

debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration 

23 

should not be used for MAC sedation (see WARNINGS).  A rapid bolus injection can result 

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in undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, 

2 

and oxygen desaturation. 

3 

Initiation of MAC Sedation 

4 

For initiation of MAC sedation, either an infusion or a slow injection method may be utilized 

5 

while closely monitoring cardiorespiratory function.  With the infusion method, sedation may 

6 

be initiated by infusing DIPRIVAN Injectable Emulsion at 100 to 150 mcg/kg/min (6 to  

7 

9 mg/kg/h) for a period of 3 to 5 minutes and titrating to the desired clinical effect while 

8 

closely monitoring respiratory function.  With the slow injection method for initiation, 

9 

patients will require approximately 0.5 mg/kg administered over 3 to 5 minutes and titrated to 

10 

clinical responses.  When DIPRIVAN Injectable Emulsion is administered slowly over  

11 

3 to 5 minutes, most patients will be adequately sedated, and the peak drug effect can be 

12 

achieved while minimizing undesirable cardiorespiratory effects occurring at high plasma 

13 

levels. 

14 

In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) 

15 

bolus dose administration should not be used for MAC sedation (see WARNINGS).  The rate 

16 

of administration should be over 3 to 5 minutes and the dosage of DIPRIVAN Injectable 

17 

Emulsion should be reduced to approximately 80% of the usual adult dosage in these patients 

18 

according to their condition, responses, and changes in vital signs (see DOSAGE AND 

19 

ADMINISTRATION). 

20 

Maintenance of MAC Sedation 

21 

For maintenance of sedation, a variable rate infusion method is preferable over an intermittent 

22 

bolus dose method.  With the variable rate infusion method, patients will generally require 

23 

maintenance rates of 25 to 75 mcg/kg/min (1.5 to 4.5 mg/kg/h) during the first 10 to 

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15 minutes of sedation maintenance.  Infusion rates should subsequently be decreased over 

2 

time to 25 to 50 mcg/kg/min and adjusted to clinical responses.  In titrating to clinical effect, 

3 

allow approximately 2 minutes for onset of peak drug effect. 

4 

Infusion rates should always be titrated downward in the absence of clinical signs of 

5 

light sedation until mild responses to stimulation are obtained in order to avoid sedative 

6 

administration of DIPRIVAN Injectable Emulsion at rates higher than are clinically 

7 

necessary. 

8 

If the intermittent bolus dose method is used, increments of DIPRIVAN Injectable 

9 

Emulsion 10 mg (1 mL) or 20 mg (2 mL) can be administered and titrated to desired clinical 

10 

effect.  With the intermittent bolus method of sedation maintenance, there is increased 

11 

potential for respiratory depression, transient increases in sedation depth, and prolongation of 

12 

recovery. 

13 

In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) 

14 

bolus dose administration should not be used for MAC sedation (see WARNINGS).  The rate 

15 

of administration and the dosage of DIPRIVAN Injectable Emulsion should be reduced to 

16 

approximately 80% of the usual adult dosage in these patients according to their condition, 

17 

responses, and changes in vital signs (see DOSAGE AND ADMINISTRATION). 

18 

DIPRIVAN Injectable Emulsion can be administered as the sole agent for 

19 

maintenance of MAC sedation during surgical/diagnostic procedures.  When DIPRIVAN 

20 

Injectable Emulsion sedation is supplemented with opioid and/or benzodiazepine medications, 

21 

these agents increase the sedative and respiratory effects of DIPRIVAN Injectable Emulsion 

22 

and may also result in a slower recovery profile (see PRECAUTIONS,_Drug_Interactions'>PRECAUTIONS, Drug Interactions). 

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ICU Sedation 

2 

(See WARNINGS and DOSAGE AND ADMINISTRATION, Handling Procedures.) 

3 

Abrupt discontinuation of DIPRIVAN Injectable Emulsion prior to weaning or for daily 

4 

evaluation of sedation levels should be avoided.  This may result in rapid awakening with 

5 

associated anxiety, agitation, and resistance to mechanical ventilation.  Infusions of 

6 

DIPRIVAN Injectable Emulsion should be adjusted to assure a minimal level of sedation is 

7 

maintained throughout the weaning process and when assessing the level of sedation (see 

8 

PRECAUTIONS). 

9 

Adult Patients 

10 

For intubated, mechanically ventilated adult patients, Intensive Care Unit (ICU) sedation 

11 

should be initiated slowly with a continuous infusion in order to titrate to desired clinical 

12 

effect and minimize hypotension (see DOSAGE AND ADMINISTRATION). 

13 

Most adult ICU patients recovering from the effects of general anesthesia or deep 

14 

sedation will require maintenance rates of 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/h) 

15 

individualized and titrated to clinical response (see DOSAGE AND ADMINISTRATION). 

16 

With medical ICU patients or patients who have recovered from the effects of general 

17 

anesthesia or deep sedation, the rate of administration of 50 mcg/kg/min or higher may be 

18 

required to achieve adequate sedation.  These higher rates of administration may increase the 

19 

likelihood of patients developing hypotension.  Administration should not exceed  

20 

4 mg/kg/hour unless the benefits outweigh the risks (see WARNINGS). 

21 

Dosage and rate of administration should be individualized and titrated to the desired 

22 

effect, according to clinically relevant factors including the patient’s underlying medical 

23 

problems, preinduction and concomitant medications, age, ASA-PS classification, and level 

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of debilitation of the patient.  The elderly, debilitated, and ASA-PS III or IV patients may 

2 

have exaggerated hemodynamic and respiratory responses to rapid bolus doses (see 

3 

WARNINGS). 

4 

DIPRIVAN Injectable Emulsion should be individualized according to the patient's 

5 

condition and response, blood lipid profile, and vital signs (see PRECAUTIONS, Intensive 

6 

Care Unit Sedation).  For intubated, mechanically ventilated adult patients, Intensive Care 

7 

Unit (ICU) sedation should be initiated slowly with a continuous infusion in order to titrate to 

8 

desired clinical effect and minimize hypotension.  When indicated, initiation of sedation 

9 

should begin at 5 mcg/kg/min (0.3 mg/kg/h).  The infusion rate should be increased by 

10 

increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/h) until the desired level of sedation is 

11 

achieved.  A minimum period of 5 minutes between adjustments should be allowed for onset 

12 

of peak drug effect.  Most adult patients require maintenance rates of 5 to 50 mcg/kg/min (0.3 

13 

to 3 mg/kg/h) or higher.  Administration should not exceed 4 mg/kg/hour unless the benefits 

14 

outweigh the risks (see WARNINGS).  Dosages of DIPRIVAN Injectable Emulsion should 

15 

be reduced in patients who have received large dosages of narcotics.  The DIPRIVAN 

16 

Injectable Emulsion dosage requirement may also be reduced by adequate management of 

17 

pain with analgesic agents.  As with other sedative medications, there is interpatient 

18 

variability in dosage requirements, and these requirements may change with time (see 

19 

SUMMARY OF DOSAGE GUIDELINES).  Evaluation of level of sedation and assessment 

20 

of CNS function should be carried out daily throughout maintenance to determine the 

21 

minimum dose of DIPRIVAN required for sedation (see Clinical Trials, Intensive Care Unit 

22 

(ICU) Sedation).  Bolus administration of 10 or 20 mg should only be used to rapidly 

23 

increase depth of sedation in patients where hypotension is not likely to occur.  Patients with 

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compromised myocardial function, intravascular volume depletion, or abnormally low 

2 

vascular tone (e.g., sepsis) may be more susceptible to hypotension (see PRECAUTIONS). 

3 

SUMMARY OF DOSAGE GUIDELINES: 

4 

Dosages and rates of administration in the following table should be individualized and 

5 

titrated to clinical response.  Safety and dosing requirements for induction of anesthesia in 

6 

pediatric patients have only been established for children 3 years of age or older.  Safety and 

7 

dosing requirements for the maintenance of anesthesia have only been established for children 

8 

2 months of age and older.   

9 

For complete dosage information, see DOSAGE AND ADMINISTRATION. 

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INDICATION  DOSAGE 

AND 

ADMINISTRATION  

Induction of General Anesthesia: 

Healthy Adults Less Than 55 Years of Age: 

40 mg every 10 seconds until induction onset (2 to 2.5 mg/kg). 

Elderly, Debilitated, or ASA-PS III or IV Patients: 

20 mg every 10 seconds until induction onset (1 to 1.5 mg/kg). 

Cardiac Anesthesia: 

20 mg every 10 seconds until induction onset  (0.5 to 1.5 mg/kg). 

Neurosurgical Patients: 

20 mg every 10 seconds until induction onset (1 to 2 mg/kg). 

Pediatric Patients - healthy, from 3 years to 16 years of age: 

2.5 to 3.5 mg/kg administered over 20 to 30 seconds. 

(see PRECAUTIONS, Pediatric Use and CLINICAL 

PHARMACOLOGY, Pediatrics) 

Maintenance of General Anesthesia:  

Infusion 

Healthy Adults Less Than 55 Years of Age: 

100 to 200 mcg/kg/min (6 to 12 mg/kg/h). 

Elderly, Debilitated, ASA-PS III or IV Patients: 

50 to 100 mcg/kg/min (3 to 6 mg/kg/h). 

Cardiac Anesthesia:  Most patients require:  

Primary DIPRIVAN Injectable Emulsion with Secondary Opioid –  

100 to 150 mcg/kg/min. 

Low-Dose DIPRIVAN Injectable Emulsion with Primary Opioid –  

50 to 100 mcg/kg/min.  

(see DOSAGE AND ADMINISTRATION, Table 4)  

Neurosurgical Patients: 

100 to 200 mcg/kg/min (6 to 12 mg/kg/h). 

Pediatric Patients - healthy, from 2 months of age to 16 years of age: 

125 to 300 mcg/kg/min (7.5 to 18 mg/kg/h).  

Following the first half hour of maintenance, if clinical signs of light  

anesthesia are not present, the infusion rate should be decreased.  

(see PRECAUTIONS, Pediatric Use and CLINICAL  

PHARMACOLOGY, Pediatrics)