Sterile Drug Products Used in the Anesthesia Practice Setting: Part 2 PharMEDium Lunch and Learn Series

LUNCH AND LEARN

Sterile Drug Products Used in the Anesthesia Practice Setting: Part 2 February 10, 2017

Featured Speaker: Julie A. Golembiewski, PharmD Clinical Associate Professor, Department of Pharmacy Practice Clinical Associate Professor of Anesthesiology University of Illinois at Chicago Colleges of Pharmacy and Medicine

CE Activity Information & Accreditation

ProCE, Inc. (Pharmacist and Tech CE) 1.0 contact hour

Funding: This activity is self‐funded through PharMEDium.

It is the policy of ProCE, Inc. to ensure balance, independence, objectivity and scientific rigor in all of its continuing education activities. Faculty must disclose to participants the existence of any significant financial interest or any other relationship with the manufacturer of any commercial product(s) discussed in an educational presentation. Dr. Golembiewski has no relevant commercial and/or financial relationships to disclose. 2

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Online Evaluation, Self-Assessment and CE Credit

. Submission of an online self‐assessment and evaluation is the only way to obtain CE credit for this webinar . Go to www.ProCE.com/PharMEDiumRx . Print your CE Statement online . Live CE Deadline: March 10, 2017 . CPE Monitor – CE information automatically uploaded to NABP/CPE Monitor upon completion of the self‐assessment and evaluation (user must complete the “claim credit” step) Attendance Code Code will be provided at the end of today’s activity Attendance Code not needed for On‐Demand 3

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Resources

. Visit www.ProCE.com/PharMEDiumRx to access: – Handouts – Activity information – Upcoming live webinar dates – Links to receive CE credit

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Sterile Drug Products Used in the Anesthesia Setting – Part 2

Julie Golembiewski PharmD February 10, 2017

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THE OPERATING ROOM

Anesthesia Care Provider

Surgeon 7

CARDIOVASCULAR DRUGS ADRENERGIC RECEPTORS Receptor Location Response (Agonist activity) Alpha 1 Vascular smooth muscle, Contraction heart

Alpha 2 Vascular smooth muscle Contraction Beta 1 Heart Increased force and rate of contraction

Beta 2 Smooth muscle (lungs, Relaxation vascular)

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CLASSIFICATION OF BETA-BLOCKERS Classification Agent Non-selective Propranolol (blocks beta 1 and beta 2  decreases HR) Beta 1 selective Esmolol, metoprolol (decreases force and rate of contraction  decreases HR) Alpha-blocking activity Labetolol >> beta-blocking activity (relaxes vascular smooth muscle  decreases BP)

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Beta Blockers

Property Esmolol Metoprolol Pharma- Beta 1 antagonist Beta 1 antagonist cology Reduces HR and, Reduces HR and, to a much lesser to a much lesser extent, BP extent, BP Peak effect ̴ 5 minutes ̴ 10 minutes (IV) Duration (IV) 10 – 30 minutes ̴ 6 hours Usual dose 10 - 20 mg, 2 mg up to 0.5 mg/kg

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Antihypertensives Property Hydralazine Labetolol Pharmacology Direct relaxation of Alpha 1 blocker, vascular smooth nonselective beta muscle antagonist

Reduces BP Reduces BP, less effect on HR than propranolol Peak effect (IV) 5 – 20 minutes 5 – 15 minutes Duration (IV) 1 – 4 hours 2 – 18 hours Clinical Reflex tachycardia Less reflex Considerations tachycardia due to beta blocker effects Usual dose 5 mg 5 – 10 mg

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VASOPRESSORS

Property Phenylephrine Norepinephrine Pharmacology Alpha 1 agonist Alpha 1 agonist (vasoconstriction) (vasoconstriction)

Beta 1 and some Beta 2 effects Relaxing effect on venous resistance  enhanced venous return to heart  increased CO with little effect on HR BP Increased Increased HR Decreased No change or increased Contractility No change or Increased decreased Venous return Increased Decreased Cardiac output Decreased Increased Typical IV bolus 40 – 100 mcg 2 – 8 mcg dose

Norepinephrine increases BP by arterial vasoconstriction and an increase or maintenance of HR, stroke volume and cardiac output 12

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EPHEDRINE VS. EPINEPHRINE

Property Ephedrine Epinephrine Pharmacology Indirect stimulation Beta 1, beta 2 and of alpha 1 and in higher doses, beta 1 receptors alpha 1

Increases BP, HR, Increases HR, contractibility and cardiac output, BP cardiac output (less than others) bronchodilator

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OPIOIDS

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OPIOIDS

Indications Agents • Blunt hemodynamic Fentanyl, sufentanil, response to: remifentanil, morphine, hydromorphone • Laryngoscopy • Surgical stimulation • Provide analgesia Considerations • Reduce anesthetic Onset requirement Duration Route of elimination

Opioids alone do NOT provide anesthesia 15

Property Morphine Hydromorphone Fentanyl (Dilaudid) Onset 5 min ≤ 5 min ≤ 2 min

Peak 15 - 20 min 10 – 20 min 5 – 7 min

Duration ̴ 3 – 4 hours ̴ 2 – 3 hours 30 – 60 min

Renal dysfunction Active metabolite OK OK can accumulate Equianalgesic 1 mg 0.2 mg 12.5 mcg dose

(plasma) (brain)

Anesthesiology. 2010;112:226. 16

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Sufentanil – 5 – 10 times more potent than fentanyl • Usual dose: 5 – 20 mcg IV bolus – Similar onset and peak, but more rapidly eliminated than fentanyl when multiple doses (or infusion) administered

Remifentanil – Slightly more potent than fentanyl • Usual dose: 12.5 – 25 mcg IV bolus – Rapidly eliminated by nonspecific plasma and tissue esterases – Shortest duration of action ( ̴ 10 minutes) • Infusion (usual range: 0.025 mcg/kg/min – 0.2 mcg/kg/min)

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Context-Sensitive Halftime

Anesthesiology. 1993;79:881–892 . 18

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OPIOID ADVERSE EFFECTS

• Nausea, vomiting, constipation • Sedation, dizziness • Itching • Bradycardia (intra-op boluses) • Apnea, respiratory depression

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LOCAL ANESTHETICS

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Local Anesthetics

Agent Onset Duration Max Dose * Comments Chloroprocaine Fastest Short 800 (1,000) Epidural Lidocaine Rapid Intermediate 300 (500) Most frequently used Mepivacaine Moderate Intermediate 300 (500) Nerve block, epidural Bupivacaine Slow Long ** 175 (225) Local infiltration, (up to 12 nerve block, hrs) epidural, spinal Bupivacaine Slow Longest 266 Local infiltration liposome (up to 72 only hrs) Ropivacaine Slow Long ** 200 (200) Local infiltration, (up to 12 nerve block, hrs) epidural * In milligrams; epinephrine containing solution in parenthesis ** May be given as a continuous infusion for local infiltration, epidural, peripheral nerve block 21

SPINAL AND EPIDURAL ANESTHESIA

Spinal needle

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NERVE BLOCK ANESTHESIA

Femoral nerve block Sciatic nerve block

Source: http://www.privatehealth.co.uk/private-operations/Anaesthesia/femoral-nerve-block/ http://www.privatehealth.co.uk/private-operations/Anaesthesia/sciatic-nerve-block/ 23

LOCAL INFILTRATION (SURGEON)

Source: 24

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Local Anesthetic Infusions

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PERIOPERATIVE ROUTES OF ADMINISTRATION OF LOCAL ANESTHETICS Surgeon Anesthesia Topical* Spinal Subcutaneous, deep tissue Epidural Transversus Intravenous abdominal plane* (lidocaine only) Tumescent Peripheral technique nerve block Intra- or periarticular

* Surgeon or Anesthesia 26

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PERIOPERATIVELidocaine ROUTES OF ADMINISTRATION FastOF LOCAL onset, ANESTHETICS

Topical Short duration (1 - 3 hrs) Spinal Subcutaneous, deep tissue Epidural Transversus Intravenous abdominal plane

Tumescent Peripheral technique nerve block Intra- or periarticular

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BupivacainePERIOPERATIVE or Ropivacaine ROUTES OF ADMINISTRATION OF LOCAL ANESTHETICS Slow onset, long duration (4 – 18 hrs)

Topical Spinal Subcutaneous, (bupivacaine only) deep tissue Epidural Transversus Intravenous abdominal plane

Tumescent Peripheral technique nerve block Intra- or periarticular

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PERIOPERATIVE ROUTES OF ADMINISTRATIONLiposome Bupivacaine OF LOCAL ANESTHETICSFast onset, long duration (up to 72 hrs) Topical Spinal Subcutaneous, (bupivacaine only) deep tissue Epidural Transversus Intravenous abdominal plane

Tumescent Peripheral technique nerve block Intra- or periarticular

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EPIDURAL ANALGESIA • Indication – Postoperative pain, labor pain, pain unrelieved by systemic analgesics • Agents – Local anesthetic + opioid • Bupivacaine 0.1% + fentanyl 2 mcg/ml • Bupivacaine 0.1% + hydromorphone 10 mcg/ml • Others (ropivacaine, sufentanil) – Local anesthetic alone – Opioid alone • Administered as a: – Single bolus dose – Continuous infusion +/- patient-controlled bolus doses

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LOCAL ANESTHETIC TOXICITY – CLASSIC TEACHING

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HOWEVER …

• Nearly half of reports of local anesthetic systemic toxicity are in patients either < 16 years old (16%) or > 60 years old (30%)

• More than one third of reports of toxicity involved patients with underlying cardiac, neurologic, renal, hepatic, pulmonary or metabolic disease

• Dose reduction and heightened vigilance may be warranted in such patients, particularly if they’re at the extremities of age

Neal et. al. Reg Anesth Pain Med. 2010;35:152. Rosenberg et. al. Reg Anesth Pain Med. 2004;29:564. 32

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ASRA Checklist for Treatment of Local Anesthetic Systemic Toxicity 2012

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METHEMOGLOBINEMIA • LAs are indirect oxidizers of iron within hemoglobin  methemoglobin  unable to transport oxygen • As methemoglobin levels rise, may see: – Cyanosis, altered mental status, seizures – Tachypnea, tachycardia, respiratory compromise – Skin and mucous membranes appear bluish, gray or pale; blood may be chocolate-colored • Because pulse ox cannot detect > 2 wavelengths of light, high concentrations of methemoglobin cause incorrect readings in O2 saturation reported by pulse ox • Although four local anesthetics have been implicated (prilocaine, benzocaine, lidocaine, tetracaine), benzocaine and prilocaine most common

Guay J. Anesth Analg 2009;108:837 34

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Medication Safety

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Wahr et. al. • Literature review to identify those medication safety recommendations that “at least are based on the opinions of respected authorities” • 197 articles reviewed • 78 articles met inclusion criteria – Data extracted, recommendations graded • Results – 128 specific, unique recommendations made

Br J Anaesth. 2017;118(1):32-43. 36

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MEDICATION SAFETY - STRATEGY CATEGORIES

• Patient information • Drug information • Anesthesia cart medication inventory • Medication administration •Culture • Pharmacy

Br J Anaesth. 2017;118(1):32-43. 37

SELECT STRATEGIES • Anesthesia medication trays – Standardized across all locations – Tray divisions labeled clearly – Drugs placed to minimize confusion – Modular system – Pharmacy manages drug trays • Single use vials preferable; if multidose is required, discard at end of case • Only one standard concentration on cart • Pharmacy – Provides diluted, high-risk drugs – Prepares compounded drugs – Prepares infusions – Alerts anesthesia/OR staff when there are changes in drugs supplied (new labels, new concentrations, etc.) • Regional anesthetic solutions (spinal, epidural and nerve block medications) clearly segregated from IV medications

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MEDICATION TRAY REDESIGN EXAMPLE 1

Gemensky J. US Pharm. 2015;40(3):HS8-HS12. 39

MEDICATION TRAY REDESIGN EXAMPLE 2

Problems Solutions

Problems Identified: A – slots covered entire medication vial; cannot read label B – slots are rigid and cannot accommodate vial size changes C – trays are similar in size; possible erroneous placement of same tray side by side D – nonintuitive placement of medications (have to search for desired med) E – syringe location inconsistent; boxes moved The Joint Commission Journal of Quality and Patient Safety. 2016;42(10)473-477. 40

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ASA Statement on Creating Levels of Pharmaceuticals for use in Anesthesiology Last amended October 28, 2015 42

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Label Enhancements to Reduce Drug Administration Errors:

 Bar coding: Essential information, including the drug’s generic name and concentration could be bar coded at a location on the label which will not interfere with the label’s legibility, as specified in Section 8 of ASTM D6398.  Label material shall allow the user to write information on it using a ball-point pen or felt-tip marker without smudging or blurring as specified in Section 2.3 of ISO 26825:2008.  Printing: Allprintingisinblackboldtypewith the exception of succinylcholine and epinephrine which are printed against the background color as reverse plate letters within a black bar running from edge to edge of the label.  Tall Man Letters: The FDA Office of Generic Drugs requested manufacturers of sixteen look- alike name pairs to voluntarily revise the appearance of their established names in order to minimize medication errors resulting from look-alike confusion. Letters from the FDA encouraged manufacturers to revise labels and labeling that visually differentiated their established names with the use of "Tall Man" letters. The following are Tall Man drug names from lists of easily confused medications compiled by the FDA and the ISMP that may be administered by the anesthesia care team during a procedure.

ASA Statement on Creating Levels of Pharmaceuticals for use in Anesthesiology Last amended October 28, 2015 43

SUMMARY

• In addition to drugs discussed in part 1 of this CE program, drugs used by anesthesia include: – Vasoactive drugs • Increase and decrease blood pressure and heart rate • Generally bolus doses rather than infusions – Opioids • Analgesic, blunt response to laryngoscopy and surgical stimulation and reduce anesthetic requirements • Short vs. longer-acting agents intra- vs. post-op – Local anesthetics • Administered by anesthesia and surgeon • Many routes of administration • Toxicity • Medication safety strategies – Anesthesia medication tray contents and design – Single vs. multiple dose vials, concentration, labeling – Role of pharmacy 44

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