Adult Patients

(See  WARNINGS and DOSAGE AND ADMINISTRATION, Handling Procedures.) The administration of DIPRIVAN should be initiated as a continuous infusion and changes in the rate of administration made slowly (greater than 5 min) in order to minimize hypotension and avoid acute overdosage (see DOSAGE AND ADMINISTRATION).

Patients should be monitored for early signs of significant hypotension and/or cardiovascular depression, which may be profound. These effects are responsive to discontinuation of DIPRIVAN, IV fluid administration, and/or vasopressor therapy. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus administration should not be used during sedation in order to minimize undesirable cardiorespiratory depression, including hypotension, apnea, airway obstruction, and oxygen desaturation.

As with other sedative medications, there is wide interpatient variability in DIPRIVAN dosage requirements, and these requirements may change with time.

Failure to reduce the infusion rate in patients receiving DIPRIVAN for extended periods may result in excessively high blood concentrations of the drug. Thus, titration to clinical response and daily evaluation of sedation levels are important during use of DIPRIVAN infusion for ICU sedation, especially when it is used for long durations.

Opioids and paralytic agents should be discontinued and respiratory function optimized prior to weaning patients from mechanical ventilation. Infusions of DIPRIVAN should be adjusted to maintain a light level of sedation prior to weaning patients from mechanical ventilatory support. Throughout the weaning process, this level of sedation may be maintained in the absence of respiratory depression. Because of the rapid clearance of DIPRIVAN, abrupt discontinuation of a patient's infusion may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation, making weaning from mechanical ventilation difficult. It is therefore recommended that administration of DIPRIVAN be continued in order to maintain a light level of sedation throughout the weaning process until 10 minutes to 15 minutes prior to extubation, at which time the infusion can be discontinued.

Since DIPRIVAN is formulated in an oil-in-water emulsion, elevations in serum triglycerides may occur when DIPRIVAN is administered for extended periods of time. Patients at risk of hyperlipidemia should be monitored for increases in serum triglycerides or serum turbidity. Administration of DIPRIVAN should be adjusted if fat is being inadequately cleared from the body. A reduction in the quantity of concurrently administered lipids is indicated to compensate for the amount of lipid infused as part of the DIPRIVAN formulation; 1 mL of DIPRIVAN contains approximately 0.1 g of fat (1.1 kcal).

EDTA is a strong chelator of trace metals – including zinc. Although with DIPRIVAN there are no reports of decreased zinc levels or zinc deficiency-related adverse events, DIPRIVAN should not be infused for longer than 5 days without providing a drug holiday to safely replace estimated or measured urine zinc losses. 

In clinical trials mean urinary zinc loss was approximately 2.5 mg/day to 3 mg/day in adult patients and 1.5 mg/day to 2 mg/day in pediatric patients. 

In patients who are predisposed to zinc deficiency, such as those with burns, diarrhea, and/or major sepsis, the need for supplemental zinc should be considered during prolonged therapy with DIPRIVAN.

At high doses (2 grams to 3 grams per day), EDTA has been reported, on rare occasions, to be toxic to the renal tubules. Studies to date in patients with normal or impaired renal function have not shown any alteration in renal function with DIPRIVAN containing 0.005% disodium edetate. In patients at risk for renal impairment, urinalysis and urine sediment should be checked before initiation of sedation and then be monitored on alternate days during sedation.

The long-term administration of DIPRIVAN to patients with renal failure and/or hepatic insufficiency has not been evaluated.

Neurosurgical Anesthesia

When DIPRIVAN is used in patients with increased intracranial pressure or impaired cerebral circulation, significant decreases in mean arterial pressure should be avoided because of the resultant decreases in cerebral perfusion pressure. To avoid significant hypotension and decreases in cerebral perfusion pressure, an infusion or slow bolus of approximately 20 mg every 10 seconds should be utilized instead of rapid, more frequent, and/or larger boluses of DIPRIVAN. Slower induction, titrated to clinical responses, will generally result in reduced induction dosage requirements (1 mg/kg to 2 mg/kg). When increased ICP is suspected, hyperventilation and hypocarbia should accompany the administration of DIPRIVAN (see DOSAGE AND ADMINISTRATION).

Cardiac Anesthesia

Slower rates of administration should be utilized in premedicated patients, geriatric patients, patients with recent fluid shifts, and patients who are hemodynamically unstable. Fluid deficits should be corrected prior to administration of DIPRIVAN. In those patients where additional fluid therapy may be contraindicated, other measures, e.g., elevation of lower extremities, or use of pressor agents, may be useful to offset the hypotension which is associated with the induction of anesthesia with DIPRIVAN.