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Home , Norepinephrine, Synephrine

Norepinephrine Bitartrate

Brand names Levophed, generic

Medication error ISMP high-alert medication that has an increased risk of causing significant patient harm potential if it is used in error.(1) Look-alike, sound-alike drug names USP reports that has been confused with EPINEPHrine and nitroprusside. Norepinephrine has been confused with Neo- and and patient harm occurred. Levophed has been confused with Lopressor, and patient harm did not occur.(2)

Contraindications U.S. boxed warning: Extravasation may cause local ischemia and necrosis. Ali- and warnings quots of mesylate (0.1–0.2 mg/kg(7) up to 10 mg in 10–15 mL NS) should be injected using a fine hypodermic needle into the ischemic area. This should be done as soon as possible and within the first 12 hours of noting the extravasation.(3,4) (See the Infusion-Related Cautions section.) Contraindications: Norepinephrine should only be used in emergency situations prior to volume resuscitation. If used in hypotensive and volume-depleted patients prior to volume replacement, peripheral and visceral , decreased renal perfusion and urine output, decreased systemic blood flow, tissue hypoxia, and lactic acidosis may occur.(3,4) Do not use in patients with mesenteric or peripheral vascular thrombosis or in patients receiving cyclopropane and anesthetics.(3,4) Ventricular arrhythmias may result in patients with severe hypoxia or hypercarbia.(3,4) Warnings: Use with caution in patients receiving (MAO) inhibitors or triptyline or .(3,4) (See the Comments section.)

Infusion-related If possible, infuse via a central,(5,6) large vein, particularly antecubital or femoral vein, cautions using a plastic catheter inserted deep into the vein, to decrease the risk of necrosis of overlying skin. Gangrene has been reported after infusion via ankle vein.(3,4) See U.S. Boxed Warning in the Contraindications and Warnings section for extravasation antidote information. See Appendix E for additional information regarding extravasation treatment.

Dosage Correct intravascular volume depletion prior to starting norepinephrine.(3,4) /: 0.05–0.1 mcg/kg/min titrated to the desired up to usual maximum dose of 2 mcg/kg/min.(5-9,24) Starting doses of 0.5 mcg/kg/min have been used.(24,22) 2 mcg/m2/min has also been reported.(10) Continue norepinephrine dosing until adequate blood pressure and tissue perfusion are maintained.(9,10) Avoid abrupt withdrawal by gradually reducing the dose.(3,4) In adults, manufacturers recommend an initial dose of 8–12 mcg/min, which is then titrated to the desired blood pressure,(3,4) up to 30 mcg/min.(10) Norepinephrine is preferred as a first line agent in fluid-refractory vasodilated in adults.(20,23) Additionally, norepinephrine is recommended in adults immediately after cardiac arrest at a dose of 0.1–0.5 mcg/kg/min.(26) Persistent pulmonary of the newborn: A single observational prospec- tive study (n = 18) demonstrated a decrease in the requirement with norepineph- rine (initial dose 0.5 mcg/kg/min; titrated up to 3.3 mcg/kg/min based on mean systemic arterial pressure goal).(25)

Dosage adjustment No dosage adjustment is required in renal dysfunction.(11) in organ dysfunction  656 Norepinephrine Bitartrate

Maximum dosage 10.5 mcg/kg/min has been reported in a child.(22) 20.8 mcg/kg/min (for 11 hours) has been reported in a case report of an adult with meningococcemia.(27) Large doses up to 68 mg/day have been used in adults.(3,4)

Additives Some products contain sodium metabisulfite,(3) whereas others are preservative free.(4) (See Appendix C for more specific information about potential adverse effects of sulfites.) Sodium chloride is used to adjust to isotonicity.(3,4)

Suitable diluents D5W, D5NS, other D5-containing solutions,(3,4) LR.(12) Dilution with dextrose-containing solutions protects against significant loss of potency from oxidation.(3,4) Manufacturers do not suggest dilution with NS(3,4); however, tests suggest norepinephrine is stable in NS for 7 days (4 and 16 mcg/mL).(12)

Maximum Manufacturer does not give an absolute maximum concentration.(3,4) Concentrations up to concentration 64 mcg/mL have been shown to be stable in D5W.(12) 100 mcg/mL(18,24) and 128 mcg/mL(9) have also been reported.

Preparation and Parenteral products should be visually inspected for particulate matter and discoloration delivery before use. Refer to appropriate references for more information on compatibility with other drugs and solutions, compatibility following Y-site delivery, and suggested storage and extended stability.(12) Delivery: May be filtered through a 0.2-micron filter without significant norepinephrine loss.(12) Stability: Norepinephrine is easily destroyed by iron salts, oxidants, and in alkaline solu- tions(3) (i.e., sodium bicarbonate).(6) Protect from light. Do not infuse if solution is pink in color, darker than slightly yellow, or if a precipitate exists.(3,4)

IV push Not indicated

Intermittent infusion Not indicated

Continuous infusion 4–16 mcg/mL. Concentrations outside this range may be used dependent on the drug and fluid requirements of the individual patient.(3,4,13) The Joint Commission recommends the use of standardized concentrations of vasoactive medications.(15) The ISMP and Vermont Oxford Network recommend a standard concentration of 16 mcg/ mL for neonates.(16)

Other routes of IO(7,8,17) administration

Comments Norepinephrine may be considered in epinephrine-refractory cardiac arrest due to anaphylaxis.(21) Monitoring: Blood pressure,(3,4) ECG,(6) and central venous pressure monitoring. When possible, monitoring should occur continuously throughout therapy.(3,4) Drug interactions: Several drugs (e.g., tricyclic antidepressants, MAO inhibitors) may potentiate the pressor effects of norepinephrine.(3,4) Atropine may block the reflex brady- cardia and enhance the pressor response caused by norepinephrine.(10) Consult appropri- ate resources before combining any drug with norepinephrine. For hypotension due to tricyclic and other sodium channel blocker toxicity, norepinephrine and epinephrine have been shown to be superior to in elevating blood pressure. (See the Contraindications and Warnings section.)(8)  657