Dosing Dilemmas in Sustained Low Efficiency

DialysisKellie L. Fortier, PharmD

Banner Baywood Medical Center

Mesa, AZ

Objectives

• Differentiate SLED from other CRRT modalities

• List the benefits to SLED

• Make antibiotic recommendations for patients receiving SLED

SLED

• Many names– Sustained Low Efficiency Dialysis– Slow Extended Daily Dialysis– Extended Daily Dialysis– Slow Low Efficiency Dialysis

• Hybrid modality• Uses diffusion and ultrafiltration

Types of CRRT

Heintz BH, et al. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy 2009; 29(5):562-77.

Advantages to SLED

• Hemodynamic stability• Uses same equipment as IHD• No need for customized solutions• Avoids interruption of therapy• Good solute removal• Generally no need for anti-

coagulation

Vancomycin• 11 ICU pts received 15 mg/kg• Vd 0.84 L/kg, t1/2 43.1 hrs, Cl 24.3

ml/min• 10 ICU pts 1 gm infused• Cl 35 ml/min, t1/2 = 11.2 while on

SLED and Cl 26 ml/min, t1/2 =37hrs off.

• Load with 15-25 mg/kg and check 24 hr level post infusion.

Ahern, JW, et al. Experience with vancomycin in patients receiving slow low-efficiency dialysis. Hosp Pharm 2004; 39:138-43.Kielstein JT, et al. Pharmacokinetics and total elimination of meropenem and vancomycin in ICU patients undergoing extended daily dialysis. Crit Care Med 2006; 34:51-6.

Linezolid

• Compared IHD, SLED, CVVH• Single dose 600 mg given to 5 ICU

pts receiving SLED (8hr run)• 34 % of dose removed• Recommendation to give at the end

of SLED

Fiaccadori E, et al. Removal of linezolid by conventional intermittent hemodialysis, sustained low-efficiency dialysis, or continuous venovenous hemofiltration in patients with acute renal failure. Cri Care Med 2004; 32:2437-42.

Daptomycin• 1 ICU pt received 6 mg/kg of

daptomycin, run time 12 hrs• t1/2 = 9 hrs comparable to nl fxn• 52% of dose was removed • Administer q24hr

Burkhardt O, et al. Elimination of daptomycin in a patient with acute renal failure undergoing extended daily dialysis. J Antimicrob Chemother 2008; 61:224-5.

Gentamicin• Single dose of 0.6 mg/kg base on

ABW (home CKD pts), 8 hr run• Vd = 0.28 L/kg, Cl = 76 ml/min,

t1/2 = 3.7 hrs while on SLED• 70% of drug removed• Authors recommend 2-2.5 mg/kg

post SLED• Not at steady state and single dose

Manley HJ, et al. Gentamicin pharmacokinetics during slow daily home hemodialysis. Kidney Int 2003; 63:1072-8.

Carbapenems• Meropenem – 10 ICU pts received 1

gm, 8 hr run • t1/2 = 3.7 hr, 51% of drug removed• Recommend 0.5 – 1 gm q8hr• Ertapenem- 6 ICU pts received 1 gm,

8 hr run time• Cl = 49.5 ml/min, t1/2 6.7 hrs • Recommend 1 gm q24

Kielstein JT, et al. Pharmacokinetics and total elimination of meropenem and vancomycin in ICU patients undergoing extended daily dialysis. Crit Care Med 2006; 34:51-6.Burkhardt O, et al. Pharmacokinetics of ertapenem in critically ill patients with acute renal failure undergoing extended daily dialysis. Nephrol Dial Transplant 2009; 24:267-71.

Fluoroquinolones• Levo – 5 ICU pts 500 mg dose with 8

hr run time • Fraction removed 17-27%, t1/2 = 10.3

on and 34.5 off.• Dose adjustment recommended• Moxi – 10 ICU pts 400 mg dose, 8 hr

run time• Kinetics similar to pt nl renal fxn• Give Moxifloxacin 400 q24 after

SLED

Czock D, et al. Pharmacokinetics of moxifloxacin and levofloxacin in intensive care unit patients who have acute renal failure and undergo extended daily dialysis. Clin J Am Soc Nephrol 2006; 1:1263-8.

Application to Practice• Assess risk vs. benefits (ADR’s,

severity of infection, etc.)• Most of these studies advocate for

more aggressive dosing compared to HD

• Consider aggressive tx for– residual renal fxn – longer run times

• TDM if able (Vanco, AG)

Recommendations• Work closely with nephrologist, ID,

dialysis staff• Educate RN’s to distinguish the

difference between SLEDD and HD• Q24 hr dosing administer after SLED• Consider dosing for CrCl 15-30

ml/min for run times 6-8 hours and 30-50 ml/min for longer run times.– Review article recommends CrCl 10-50

• Consistent timing for SLED

Mushatt D, et al. Antibiotic dosing in slow extended daily dialysis. CID 2009; 49:433-7.

Self Assessment• 1. A 78 y/o WM admitted with respiratory

failure and acute AKI. Pt is started on daily SLED therapy, run time 6 hours daily. Pharmacy consult for dosing of antibiotics is ordered. Pt is on Vancomycin 1 gm IV after each HD and Zosyn 3.375 gm IV q6 hr for empiric treatment of pneumonia . How would you adjust your antibiotics?

• a. Adjust for CrCl >50• b. Adjust for CrCl 30-50• c. Adjust for CrCl 15-29• d. Adjust for CrCl <15

Clinical Pearls: Propylene glycol toxicity associated

with lorazepam continuous infusion

Lindsay Davis, Pharm.D.

Introduction to propylene glycol 1, 2-propanediol

Vehicle used as a drug solubilizer in

hydrophobic topical, oral, & IV compounds

Common IV drugs containing PG:

Drug & Concentrations Amount of PG/ml

(volume/volume)

Etomidate 2 mg/ml 362.6 mg (35%)

Diazepam 5 mg/ml 413 mg (40%)

Esmolol 250 mg/ml 258 mg (25%)

Lorazepam 2mg/ml, 4mg/ml 830 mg (80%)

Nitroglycerin 5mg/ml 518 mg (30%)

Phenytoin 50 mg/ml 414.4 mg (40%)

Phenobarbital 65 mg/ml, 130mg/ml 702.4 mg (67.8%)

Why worry about propylene glycol?

Propylene glycol toxicity has been linked with:◦ Metabolic acidosis

◦ Lactic acidosis

◦ Nephrotoxicity (Acute tubular necrosis)

◦ Hemolysis

◦ Hypotension

◦ Central nervous system depression

◦ Seizures

◦ Arrhythmias

FDA considers PG safe for use in drugs & cosmetics◦ As a food additive, the maximum daily permissible intake

of PG is 25 mg/kg of body weight

◦ For a 70 kg patient, this limit would be met with only 4.2 mg IV lorazepam / day

Case Study 48 year old male with h/o alcohol abuse

Admitted for respiratory failure 2/2 aspiration PNA

VDRF continuous infusion lorazepam for sedation & alcohol

withdrawal

1st 7 days of hospitalization received 1,070 mg lorazepam (444 g PG)

Hospital days 6 & 7AG:19, HCO3- :13, pH:7.16, Cr:2.2

Sepsis considered as cause abx started

Despite abxAG:22, HCO3- : 10, pH:7.11

All cultures negative

Serum osmolality: 405 mOsm/kg (n: 285-295)

Lorazepam d/c’d midazolam started

Within 24 h, all metabolic abnormalities resolved

Serum PG level = 144 mg/dL (levels >18 associated with toxicity)

Wilson KC, Reardon C, Theodore AC, et al. Propylene glycol toxicity: A severe iatrogenic illness in ICU

patients receiving IV benzodiazepines. CHEST. 2005;128:1674-1681.

What did we learn?

This patient had PG toxicity, definitively diagnosed by serum PG level, but clinically manifested as AG metabolic acidosis & elevated SCr

Sepsis initially considered as cause for metabolic abnormalities

Elevated osmolality suspicion of PG in lorazepam

Rapid resolution of metabolic abnormalities with discontinuation of lorazepam

Assays to monitor PG concentrations are unavailable at most hospitals & results are often delayed

Use of osmol gap as surrogate marker of PG toxicity

Osmolality & Osmolarity

Terminology expressing calculated & measured

osmotic activity

Used to describe fluid movement between body

compartments

Can be used to detect foreign substances in the blood

Osmotically active compounds include ethanol,

methanol, isopropyl alcohol, & propylene glycol

Osmolality & Osmolarity

Osmolality (mOsm/kg of solvent)◦ Value derived by an osmometer in clinical laboratories

Osmolarity (mOsm/L of solution)◦ Bedside calculation of osmotic activity by clinicians using

patient’s laboratory data

Osmol gap◦ Mathematical difference between the osmolality & osmolarity

Serum osmolarity = (2 x serum Na+) + (BUN / 2.8) + (glucose / 18)

Normal osmolarity: 285 – 295 mOsm/L

Osmol gap = osmolality (measured) – osmolarity (calculated)

Normal osmol gap is defined as < 10

Normal osmolality: 285 – 295 mOsm/kg

Propylene Glycol Metabolism

Renal elimination (12-50%)

Hepatic metabolism (50+%)

◦ via alcohol dehydrogenase oxidized to lactic

or pyruvic acid

t ½ = 2 – 4 hours (adults)

Propylene glycol toxicity

Serum PG concentrations > 18 mg/dL are

associated with ADE/toxicity

◦ Predominant manifestation of PG accumulation is an AG

metabolic acidosis with corresponding elevated osmol gap

The portion of the serum osmolality contributed

by presence of PG can be calculated

◦ osmolality due to PG = [PG] / 7.6

◦ If this component explains an osmolar gap > 10, then no

other osmotically active particles are contributing to the gap

Lorazepam dose > 1 mg/kg/day

Yahwak JA, Riker RR, Fraser GL, et al. Determination of a lorazepam dose threshold for using the osmol

gap to monitor for propylene glycol toxicity. Pharmacotherapy. 2008; 28(8):984-991.

Lorazepam dose > 1 mg/kg/day

Results:

9/14 (64%) had PG concentrations > 18 mg/dL

6/9 (67%) developed transient AKI and/or metabolic acidosis

Conclusions:

Osmol gap > 10 was predictive of elevated PG concentrations

Osmol gap > 12 was predictive of clinical changes suggestive of PG toxicity

Consider screening for PG toxicity when doses > 1 mg/kg/day are required

Yahwak JA, Riker RR, Fraser GL, et al. Determination of a lorazepam dose threshold for using the osmol

gap to monitor for propylene glycol toxicity. Pharmacotherapy. 2008; 28(8):984-991.

Summary: Propylene glycol toxicity

Large volume of drug large volume of diluent

PG toxicity is potentially life-threatening

PG toxicity is likely common & is preventable

Consider PG toxicity when a patient has: - unexplained anion gap - metabolic acidosis

- hyperosmolality - clinical deterioration

A threshold dose of lorazepam that does NOT result in PG accumulation has yet to be defined

The osmol gap may represent a surrogate marker for PG toxicity especially if lorazepam dose exceeds 1mg/kg/day

References1. Arroliga AC, Shehab N, McCarthy K, et al. Relationship of continuous infusion

lorazepam to serum propylene glycol concentration in critically ill adults. Crit Care Med. 2004; 32(8):1709-1714.

2. Erstad BL. Osmolality and osmolarity: Narrowing the terminology gap. Pharmacotherapy. 2003; 23(9):1085-1086.

3. Glover ML, Reed MD. Propylene glycol: The safe diluents that continues to harm. Pharmacotherapy. 1996; 16(4):690-693.

4. Reynolds HN, Teiken P, Regan ME, et al. Hyperlactatemia, increased osmolar gap, and renal dysfunction during continuous lorazepam infusion. Crit Care Med. 2000; 28(5):1631-1634.

5. Wilson KC, Reardon C, Theodore AC, et al. Propylene glycol toxicity: A severe iatrogenic illness in ICU patients receiving IV benzodiazepines. A case series and prospective, observational pilot study. CHEST. 2005; 128:1674-1681.

6. Yahwak JA, Riker RR, Fraser GL, et al. Determination of a lorazepam dose threshold for using the osmol gap to monitor for propylene glycol toxicity. Pharmacotherapy. 2008; 288(8):984-991.

7. Yaucher NE, Fish JT, Smith HW, et al. Propylene glycol-associated renal toxicity from lorazepam infusion. Pharmacotherapy. 2003; 23(9):1094-1099.

1

Does Your Patient Have Unexplained Abdominal Pain?A Review of Porphyria

Mindy Throm Burnworth, PharmD, BCPSMidwestern University College of Pharmacy – Glendale Associate Professor – Pharmacy Practicemburnw@midwestern.edu

6th Annual AzPA Annual MeetingBiltmore Resort & Spa, Phoenix, ArizonaSunday, July 18, 2010

Objectives/Disclosure

To review the pathophysiology, clinical signs and symptoms, diagnosis, treatment, and management of porphyriaNo disclosures

2

28 yo F with severe abdominal painHPI: 3 days ago pt developed severe N/V (~ 5/day), diffuse abdominal pain, constipation, & fatigue. States urine is dark tinged (no burning on urination). Reports hearing voices.PMH: dysmenorrhea (estrogen)SH: smoking (+), alcohol (social), no IVDAVS: AF, BP 150/90, HR 88 Labs: Amylase/lipase, LFTs, CBC WNL; UA unremarkable/urine cx NGTD; CDT (-), O/P (-); impaction ruled out; BMP WNL except Na 131, K 3.2

What is porphyria?

“well-defined genetic disorders of heme biosynthesis”

Anderson KE et al. Ann Intern Med 2005;142:439-50

Disease Deficient % NormalEnzyme Activity

Acute intermittent Porphobilinogen ~50porphyria (AIP) deaminase

Hereditary coproporphyria Coproporphyrinogen ~50(HCP) oxidase

Variegate porphyria Protoporphyrinogen ~50(VP) oxidase

5-aminolevulinic acid [ALA] ALA dehydratase ~5dehydratasedeficient porphyria (ADP)

3

Heme Biosynthetic Pathwayw

ww

.por

phyr

ia-e

urop

e.co

m

What causes acute attacks of porphyria?

Fasting, dieting, smoking/alcohol, stress from illnessMedications

Barbituates, carbamazepine, ethosuximide, phenytoin, primidone, valproic acidCarisoprodolClonazepam (high doses)DanazolDiclofenac/NSAIDsErgotsEstrogen, progesteroneMetoclopramidePyrazinamide, rifampinSulfonamide antibiotics

Anderson KE et al. Ann Intern Med 2005;142:439-50

www.porphyriafoundation.comwww.porphyria-europe.comwww.drugs-porphyria.comwww.cpf-inc.cawww.porphyria.uct.ac.za

4

What are signs and symptoms of porphyria?

Women of reproductive ageAbdominal painMuscle weaknessHyponatremiaDark or reddish urine

Anderson KE et al. Ann Intern Med 2005;142:439-50

What are signs and symptoms of porphyria?

And

erso

n K

E e

t al.

Ann

Inte

rn M

ed 2

005;

142:

439-

50

Signs & Symptoms Incidence (%)GASTROINTESTINALAbdominal pain 85-95Vomiting 43-88Constipation 48-84Diarrhea 5-12

NEUROLOGICPain in extremities, back, chest, neck, or head 50-70Paresis 42-68Respiratory paralysis 9-20Mental symptoms 40-58Convulsions 10-20

CARDIOVASCULARTachycardia 28, 64-85Systemic arterial HTN 36-55

5

How is porphyria diagnosed?

Anderson KE et al. Ann Intern Med 2005;142:439-50

Porphobilinogen/Porphyrin LevelsDisease Erythrocyte Urine Fecal PlasmaAcute intermittent ▼ ▲ ►◄,▲ ►◄,▲

porphyria (AIP)

Hereditary ►◄ ▲ ▲ ►◄coproporphyria(HCP)

Variegate porphyria ►◄ ▲ ▲ ▲(VP)

How is porphyria treated?

Withdraw unsafe medicationsNutritional support & symptomatic treatment

Seizure (gabapentin, vigabatrin, BZD)IVF/electrolytesNarcotic analgesics Phenothiazinesβ-blockers

IV glucose (10%, 300 g/day)Hemin 3-4 mg/kg IV daily x 4 days ($8K)

Anderson KE et al. Ann Intern Med 2005;142:439-50

6

What should the pharmacist know?Screen the patient’s medication profile for drugs that may precipitate and/or exacerbate porphyriaBe familiar with porphyria references (electronic)Add porphyria to “allergy” or “drug-disease”database

28 yo F with severe abdominal pain, N/V, weakness, dark tinged urine, hearing voices, HTN/tachycardiaDysmenorrhea (estrogen), smoking/alcohol (+)Tests/Labs: All negative except Na 131 (no seizures), urine porphobilinogen level 100 mg/d (0-4 mg/d) [Trace PBG Kit], erythrocyte/fecal/plasma pendingPharmD consult (stop estrogen, smoke/EtOH)Carbohydrate load, IVF with KPRN IV morphine, promethazine, metoprolol, lorazepam

7

Mindy Throm Burnworth, PharmD, BCPSMidwestern University College of Pharmacy – Glendale Associate Professor – Pharmacy Practicemburnw@midwestern.edu

6th Annual AzPA Annual MeetingBiltmore Resort & Spa, Phoenix, ArizonaSunday, July 18, 2010

Does Your Patient Have Unexplained Abdominal Pain?A Review of Porphyria

USP <797>: Improving Patient Outcomes Through Compliance

Christi Larson, Pharm. D.Infusion PharmacistChief Consultant, I.V. Insights

www.IVinsights.com

MAIN OBJECTIVE

• Identify the most common cause of contamination when preparing sterile products for patient use.

At the end of this presentation you will be able to:

OBJECTIVES

• What is USP 797?

• Who does USP 797 really apply to?

• Why should you be familiar with USP 797?

You will also learn:

What is USP 797?

• The 797th chapter of US Pharmacopeia

• Chapter became effective January 1, 2004

• Revisions June 2008

• USP 797 is a set of enforceable sterile compounding standards

What Does USP 797 Entail:

• Clean room operation and construction• Aseptic technique and compounding procedures• Facility cleaning and maintenance procedures• Staff training and demonstration of ongoing competency• Policies, procedures, documentation and action plans

*Being compliant with USP 797 means being able to demonstrate through policies, procedures, documentation and actions plans that

all aspects of USP 797 are being met and the highest standards of sterile compounding practices are being upheld*

Who Does USP 797 Apply ?• “ALL persons who prepare

CSPs (compounded sterile

products and all places

where CSPs are prepared

(e.g. hospitals and other

healthcare institutions,

patient treatment clinics,

pharmacies, physician’s

practice facilities, and other

locations and facilities in

which CSPs are prepared,

stored and transported).”

Who Does USP 797 Apply (cont.)?

• “ Compounded biologics, diagnostics, drugs, nutrients, and radiopharmaceuticals, including…dosage forms that must be sterile when they are administered to patients: aqueous bronchial and nasal inhalations, baths and soaks for live organs and tissues, injections, irrigations for wounds and body cavities, ophthalmic drops and ointments, and tissue implants.”

Who Does USP 797 NOT apply to?

• USP 797 only pertains to the “preparation, storage and handling of (CSPs) up to the point before administration to patients.”

• “Compounding does not include mixing, reconstituting, or similar acts that are performed in accordance with the directions consistent with that labeling.”

Q: Why Should I be Familiar with USP 797?

A: Because Patient Outcomes are at Stake!

Q&A

Need More Reasons to be Familiar with USP 797…?

• Opportunity for pharmacy to contribute to infection control efforts.

• Reimbursement for services may be affected.

Why Does Compliance Matter?

1. Clinical patient outcomes (i.e. decreased infection, decreased length of stay…etc)

2. The bottom line (i.e. $$$$$)

2 Simple Reasons:

Improved Patient Outcomes• There is currently no single study that concludes that,

“Following USP 797 will undoubtedly decrease contamination and reduce infection rates in patients.”

• There are studies that have demonstrated that NOT following certain aspects of USP 797 (hand hygiene, aseptic technique) can lead to negative patient outcomes.

• USP 797 is an important tool, perhaps the most important and comprehensive resource we have available that we can look to to provide a model of how we should be compounding sterile products to reduce the risk of infection.

What We Do Know…• Touch contamination presents the most common cause of

product contamination when preparing sterile compounded products.

• Therefore ensuring proper aseptic technique through the recommendations set forth in USP<797> is critical.

• Ensuring ongoing compliance with aseptic practices through proper training, competency testing and documentation is key.

• Proper cleanroom layout, cleaning and disinfecting procedures, and proper product storage only further contribute to decreasing the risk of product contamination.

Improved Patient Outcomes:

1. Archibald LK, Ramos M, Arduino MJ et al, Enterobacter cloacae and Pseudomonas aeruginosa polymicrobial bloodstream infections traced to extrinsic contamination of a dextrose multidose vial. J Pediatr 1998: 133(5): 640-644.

2. Anon. US Department of Health and Human Services. Centers for Disease Control and Prevention. Exophiala infection from contaminated steroids prepared by a compounding pharmacy—United States, July-November 2002. Morbidity and Mortality Weekly Report (MMWR) (serial online) 2002; 51(49): 1109-1112. Available at: www.cdc.gov/mmw.

3. Anon. US Department of Health and Human Services. Centers for Disease Control and Prevention. Pseudomonas bloodstream infections associated with a heparin/saline flush—Missouri, New York, Texas and Michigan, 2004-2005. Morbidity and Mortality Weekly Report (MMWR) (serial online) 2005; 54(11): 269-272. Available at: www.cdc.gov/mmw.

4. Hallisy E, Russell S. Who’s mixing your drugs? Bad medicine: Pharmacy mix-ups a recipe for misery, some drugstores operate with very little oversight. San Francisco Chronicle. June 23, 2002: A-1.

5. Selenic D, Dodson DR, Jensen B et al. Enterobacter cloacae bloodstream infections in pediatric patients traced to a hospital pharmacy. Am J Health Syst Pharm 2003; 60(14):1440-1446.

6. Thomas M, Sanborn MD, Couldry R I.V. admixture contamination rates. Traditional practice site versus a class 1000 cleanroom Am J Health Syst Pharm 2005; 62(22): 2386-2392.

7. Vos MC, de Haas PE, Verbrugh HA et al. Nosocomial Mycobacterium bovisbacille Calmette-Guerin infections due to contamination of chemotherapeutics: Case findings and route of transmission. J Infect Dis 2003; 188(9): 1332-1335.

8. And the list goes on and on…etc

$$$$: The Universal Language

• Not complying with USP 797 can indirectly affect your

bottom line in several different ways

1. Mandatory infection rate reporting

2. Increased length of stay

3. Added cost of treating preventable infections

4. Non-compliance with USP 797 can affect a

facility’s ability to become accredited

Tips

• Steps to compliance:

• Define compounding risk level

• Perform gap analysis

• Come up with an action plan

• Implement/monitor action plan

• Adjust action plan and monitor criteria as

needed.

Tips (cont.)

• Reach for ‘low hanging fruit’ first (i.e. documentation, training, cleaning procedures) then tackle reconstruction if you like.

• If one does not want to spend money on clean room construction, you can focus on ‘immediate use’ meds in the facility when they you able and outsource the rest.

• When compounding chemotherapy, one may consider using Closed System Transfer Devices (CSTD) if you are not able to provide a properly constructed chemo compounding area.

USP 797 Resources

• www.USP.org

• www.USP797.org

• www.ashp.org

• www.nhia.org

• www.ascp.org

• www.IVInsights.com

The Bottom Line•Not complying with USP 797 can compromise patient health

•Not complying with USP 797 can impact the bottom line

•You have the power to impact patient outcomes and improve the bottom line.

1

You're Getting Very Sleepy:You're Getting Very Sleepy:Assessment and prevention of Assessment and prevention of

opioidopioid--induced sedationinduced sedation..

Rachel S Smallwood, Rachel S Smallwood, PharmDPharmD, BCPS, BCPSBanner Banner BaywoodBaywood Medical CenterMedical Center

ObjectiveObjective

Upon completion of this activity, the Upon completion of this activity, the participant should be able to identify participant should be able to identify risk factors for risk factors for opioidopioid--induced sedationinduced sedation

2

OpioidOpioid--Induced SedationInduced Sedation

Definition Definition ““sedationsedation””: depression of : depression of brain functioning by a medication, brain functioning by a medication, manifested by sleepiness, drowsiness, manifested by sleepiness, drowsiness, fatigue, slowed brain activity, reduced fatigue, slowed brain activity, reduced wakefulness, and wakefulness, and impaired performance.impaired performance.

OpioidOpioid--Induced SedationInduced Sedation

2020--60% patient taking 60% patient taking opioidsopioidsOpioid naOpioid naïïve ve vsvs opioid tolerantopioid tolerantAcute pain Acute pain vsvs chronic painchronic painTolerance within a few daysTolerance within a few daysDoseDose-- dependent effectsdependent effectsPrecursor to respiratory depressionPrecursor to respiratory depression

3

Assessment of sedationAssessment of sedation

PaseroPasero OpioidOpioid--Induced Sedation Induced Sedation Scale (POSS)Scale (POSS)

–– Appropriate Appropriate vsvs inappropriate levels of inappropriate levels of sedationsedation

When is it safe to give dosesWhen is it safe to give dosesWhen is it safe to increase doses When is it safe to increase doses

–– DocumentationDocumentationConsistency among caregiversConsistency among caregivers

Nisbet and Mooney-Cotter. Pain Management Nursing 2009;10(3):154-164

S = Sleep, easy to arouseS = Sleep, easy to arouseAcceptable, no action necessary, may Acceptable, no action necessary, may increase doseincrease dose

1. Awake and alert1. Awake and alertAcceptable, no action necessary, may Acceptable, no action necessary, may increase doseincrease dose

2. Slightly drowsy, easily aroused2. Slightly drowsy, easily arousedAcceptable, no action necessary, may Acceptable, no action necessary, may increase doseincrease dose

PaseroPasero OpioidOpioid--Induced Induced Sedation Scale (POSS)Sedation Scale (POSS)

Pasero. Journal of PeriAnesthesia Nursing 2009;24:186-90

4

PaseroPasero OpioidOpioid--Induced Sedation Induced Sedation Scale (POSS)Scale (POSS)

3. Frequently drowsy, 3. Frequently drowsy, arousablearousable, drifts to , drifts to sleep during conversationsleep during conversation

Unacceptable, monitor respiratory status until Unacceptable, monitor respiratory status until sedation level<3, decrease dose 25sedation level<3, decrease dose 25--50% or notify 50% or notify prescriberprescriber

4. Somnolent, minimal or no response to 4. Somnolent, minimal or no response to verbal or physical stimulationverbal or physical stimulation

Unacceptable, stop opioid, consider administering Unacceptable, stop opioid, consider administering naloxonenaloxone if respiratory status is compromised, if respiratory status is compromised, notify prescriber, monitor until sedation level<3notify prescriber, monitor until sedation level<3

Prevention of sedationPrevention of sedation

Identify patients at riskIdentify patients at riskComplete/accurate patient historyComplete/accurate patient history–– Disease that affect drug metabolismDisease that affect drug metabolism

Renal/hepatic/respiratory failureRenal/hepatic/respiratory failure

–– Look for signs of undiagnosed conditionsLook for signs of undiagnosed conditionsSnoring= OSASnoring= OSA

–– History of complications with anesthesia History of complications with anesthesia or narcoticsor narcotics

Medication ReviewMedication Review

5

Risk FactorsRisk Factors

Opioid naOpioid naïïveveRapid dose escalation Rapid dose escalation Drug accumulation/additive effectDrug accumulation/additive effectDose conversionsDose conversionsOSA or undiagnosed sleep disordersOSA or undiagnosed sleep disordersPolypharmacyPolypharmacy/Drug interactions/Drug interactionsObesityObesity

Nisbet and Mooney-Cotter. Pain Management Nursing 2009;10(3):154-164

Drug InteractionsDrug Interactions

SedativesSedatives–– BZD, hypnotics, BZD, hypnotics, diphenhydraminediphenhydramine

AnticholinergicsAnticholinergics–– DicyclomineDicyclomine, TCA, , TCA, hyoscaminehyoscamine, ,

phenothiazinesphenothiazines

OthersOthers–– AntiparkinsonAntiparkinson’’ss agents, antipsychotics, agents, antipsychotics,

muscle relaxants.muscle relaxants.

Pattinson KTS. Br J Anaesthia 2008;100(6):747-758

6

SummarySummary

Assessment of sedation using POSS Assessment of sedation using POSS can increase patient safetycan increase patient safetyPrevention is key to minimizing opioidPrevention is key to minimizing opioid--induced sedationinduced sedation–– Identify risk factorsIdentify risk factors–– Complete patient historyComplete patient history–– Minimize drug interactionsMinimize drug interactions

Advocate nonAdvocate non--narcotic medicationsnarcotic medications

Assessment QuestionAssessment Question

Which of the following is NOT a risk Which of the following is NOT a risk factor for factor for opioidopioid--induced sedation?induced sedation?–– A) Obstructive Sleep ApneaA) Obstructive Sleep Apnea–– B) Rapid dose escalationB) Rapid dose escalation–– C) Concurrent use of C) Concurrent use of promethazinepromethazine and and

dicyclominedicyclomine–– D) No previous history of narcotic useD) No previous history of narcotic use–– E) None of the aboveE) None of the above