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Continuous Opioid Infusions - Adult/Pediatric - Inpatient

Continuous Opioid Infusions - Adult/Pediatric - Inpatient - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Pain and Sedation


Continuous Opioid Infusions – Adult/Pediatric – Inpatient
Clinical Practice Guideline (CPG)
Cover Sheet
Target Population:
Adult and pediatric inpatients using continuous opioid infusions.
CPG Contact:
Name: P. Trapskin, Manager, Patient Care Services and Drug Policy Program
Phone Number: 608-265-0341
Email address: PTrapskin@uwhealth.org
Guideline Author(s):
Jordan Rush, PharmD
Coordinating Team Members:
Cindy Gaston, PharmD, BCPS
Review Individuals/Bodies:
Paul Hutson, PharmD; Peggy Riley,RN, MN, MPH; Janet Kunz, MS, RN, APNP,
FNP-BC; Ben Walker, MD; Toby Campbell, MD; Cindy Gaston, PharmD
Committee Approvals/Dates:
Medication Use Evaluation Committee – May 2014
Pharmacy & Therapeutics Committee – June 2014
Release Date:
June 2014
Next Schedule review:
June 2017
Copyright © 2014 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/201 4CCKM@uwhealth.org

1
Clinical Practice Guideline Executive Summary
Guideline Title:
UWHC Guidelines for continuous opioid infusions in adult and pediatric inpatients
Guideline Overview
These clinical practice guidelines are intended to guide clinicians in the use of continuous opioid
infusions in adult and pediatric patients. Graded recommendations for indications, dosing,
administration, and precautions for use are included.
Practice Recommendations
This guideline reviews the use of non-opioid therapies for pain relief as well as the use
continuous opioid infusions in both adults and pediatric patients. Dosing recommendations and
conversions between opioids are provided. The guideline also includes recommendations
regarding adult subcutaneous opioid infusions.
Pertinent UWHC Policies & Procedures
1. Meperidine Adult and Pediatric Inpatient Clinical Practice Guideline
2. Nursing Policy 10.12 Continuous Subcutaneous Opioid Infusion
3. Hospital Administrative Policy 8.76 for Pain Management
4. Administrative Policy 8.33 High Alert Medication Administration
5. UW Health Opioid Withdrawal Fast Fact
Copyright © 2014 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/201 4CCKM@uwhealth.org

Continuous Opioid Infusions – Adult and Pediatric– Inpatient – Clinical Practice Guideline
A. Scope
1. Guidance for the use of continuous opioid infusions in UWHC adult and pediatric inpatients. The
guideline does not cover treatment of neonate patients.
B. Methodology
1. A modified Grading of Recommendations Assessment, Development and Evaluation (GRADE)
developed by the American Heart Association and American College of Cardiology (Figure 1)
has been used to assess the Quality and Strength of the Evidence in this Clinical Practice
Guideline.1
2. Literature searches were conducted in PubMed, Google Scholar, and Google containing the
words pain, pain management, opioids, guideline, principles, continuous, and infusion in various
combinations during the month of October, 2013.
Figure1. Quality of Evidence and Strength of Recommendation Grading Matrix
C. Introduction
Pain is defined as an unpleasant, multidimensional, sensory, and emotional experience
associated with potential or actual tissue damage, or described in relation to such damage.2
Therefore, the goal of pain management is to improve patient comfort and function.3 While non-
opioids and oral opioids are preferred, if the pain is still uncontrolled or other routes of
administration are not tolerated or desirable then continuous opioid infusions may be
administered.4
Copyright © 2014 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/201 4CCKM@uwhealth.org

D. Recommendations
1. Appropriate indications for use of continuous opioid infusions include persons: (Class I, level of
evidence C) 5
1.1. For whom oral, rectal, or other intermittent parenteral routes are not appropriate, tolerated,
or are contraindicated
1.2. Who require rapid opioid titration for severe continuous uncontrolled pain and are unable to
participate in IV Patient Controlled Analgesia
1.3. Require continuous opioid administration because of undesirable effects of repetitive bolus
dosing (e.g., hypotension).
2. Multimodal therapies
2.1. Multimodal therapies should be incorporated when appropriate into the treatment strategy
for pain (Class I, level of evidence C). 6
2.1.1. Add opioids onto non-opioid therapy to maximize pain relief (Class I, level of evidence
C) .4
2.1.2. Non-opioid pharmacological therapies include the use of NSAIDs, topical agents, and
anticonvulsants and antidepressants for neuropathic pain (Class I, level of evidence
C) .3,6
2.2. Non-drug therapy
2.2.1. Non-pharmacological therapies include heat/cold, music, acupuncture, electrical nerve
stimulation (TENS) , physical or restorative therapy, counseling, cognitive behavior
therapy, relaxation therapy (Class I, level of evidence C). 6
3. Baseline Assessment
3.1. Screen the patient for sensitivities and allergies to specific opioids (C lass I, level of
evidence C). 7
3.1.1. Allergies to opioid are extremely rare; however in the event of a true allergy, select an
agent in a different structural class (Class I, level of evidence C). 7
3.1.1.1. Phenylpiperidine class: meperidine, fentanyl, sufentanil, and remifentanil
3.1.1.2. Diphenylheptane class: methadone
3.1.1.3. Morphine class: codeine, morphine, hydrocodone, oxycodone, and
hydromorphone
3.2. Assess whether or not the patient is opioid-naïve (Class IIa , level of evidence C). 3
3.2.1. A patient is considered opioid tolerant if they have received at least 1 week of
morphine 60 mg/day oral, oxycodone 30 mg/day oral , hydromorphone 8 mg/day oral,
transdermal fentanyl 25 mcg/day, oxymorphone 25 mg/d oral or an equianalgesic
dose of any other opioid (Class IIa, level of evidence C). 3
4. Intravenous Infusion Drug of Choice
4.1. Hydromorphone, fentanyl, and morphine are the preferred parenteral analgesics in most
patients (Class IIa, level of evidence C). 8 (Table 1)
4.2. Cautions:
4.2.1. Avoid the use of morphine in patients with hypotension or severe asthma. (Class III,
level of evidence C) Histamine release can result in vasodilation and hypotension or
exacerbation of asthma. 9
4.2.2. Avoid morphine in moderate to severe renal dysfunction and in hemodynamic
instability (Class III, level of evidence C). 3,8
4.2.3. Do not use meperidine for the treatment of pain due to the potential toxicity. Refer to
the Meperidine Adult and Pediatric Inpatient Clinical Practice Guideline (Class III, level
of evidence C). 3
4.2.4. L ong-acting opioids (e.g., methadone) are rarely used as continuous infusions (Class
IIa, level of evidence C). 10
4.2.5. Methadone has been administered via patient controlled analgesia (PCA) with a basal
and bolus doses. This is only recommended in palliative care patients. (Class IIa ,
level of evidence C). 10
Copyright © 2014 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/201 4CCKM@uwhealth.org

Table 1: Pharmacokinetic Parameters and Common Adverse Effects of Analgesics 9-12
Drug Onset Duration T1/2 Primary Route of Elimination Noteworthy Adverse Effects
Fentanyl <1 minute
30-60 minutes;
extended with
prolonged
infusions
2-4
hours
Hepatic CYP 3A4 metabolism to
inactivate metabolites. 10%
excreted unchanged in urine.
Case reports of chest wall rigidity
with high doses.13-18 Prolonged
sedation with continuous
infusions and obesity and/or
renal dysfunction.
Hydromorphone 3-5minutes
4-5 hours;
extended with
prolonged
infusions
2-3
hours
Hepatic glucuronidation to inactive
metabolites. 7% excreted
unchanged in urine.
Rare hypotension
Morphine 5 minutes
4-5 hours;
extended with
prolonged
infusions
3-5
hours
Hepatic glucuronidation to some
active metabolites. Renal
elimination of active metabolites as
well as small amount of
unchanged drug.
Metabolites accumulate in renal
insufficiency causing additional
prolonged sedation. Histamine
release can result in
hypotension.
5. Intravenous Infusion Initiation and Titration
5.1. Whenever possible, administer opioid infusions via a locked pump ( e.g., Alaris® PCA
module (Class I, Level C). 13
5.2. Avoid continuous infusions for opioid naïve patients (Class I, level of evidence C)
5.3. Adult intravenous infusion initiation
5.3.1. If the patient is not opioid naïve, administer an IV bolus that is 10 to 20% of the daily
IV morphine equivalent (Class IIa, level of evidence C). 3,9
5.3.2. Equivalent opioid doses can be calculated from Table 2; however these ratios
represent equivalencies for single doses, not continuous infusion.
5.3.2.1. If converting from one opioid to another, calculate the amount of opioids given
within a 24 hours period. Decrease the dose of the second opioid by 25-50% to
account for incomplete cross-tolerance. Refer to Table 2 for equivalencies.
(Class IIa, level of evidence C). 3
5.3.3. Monitor patients closely when switching to a continuous infusion for signs of efficacy
and toxicity.
5.4. Adult intravenous infusion titration
5.4.1. Infusion rates and changes must be specified by physician orders. Open infusion
UDWHV�VXFK�DV�³WLWUDWH�WR�SDLQ�UHOLHI´�DUH�QRW�DFFHSWDEOH��5Hfer to Policy 8.16 Patient
Care Orders .
5.4.2. Steady state is reached after 4 to 5 half-lives (Table 1) . Avoid adjusting infusions
until steady state is reached (Class I, level of evidence C). 3
5.4.3. Reassess the patient every 2 hours for efficacy and adverse effects (Class IIa, level
of evidence C). 3
5.4.4. Boluses can be administered every 5-15 minutes if given intravenously (Class IIa ,
level of evidence C). 3
5.4.4.1. If pain is mild, continue at the effective dose as needed over the initial 30
hours (Class IIa, level of evidence C). 3
5.4.4.2. If the pain is moderate, repeat the bolus dose (Class IIa, level of evidence
C) .3
5.4.4.3. If the pain is unchanged or increases, increase the bolus dose by 50-100%
(Class IIa , level of evidence C). 3
5.5. Pediatric intravenous infusion initiation and titration
5.5.1. Refer to Table 5 for continuous intravenous opioid infusions in children <50 kg (Class
IIa, level of evidence C). 14
5.5.2. Refer to Table 6 for continuous intravenous morphine infusions for infants (1- 3
months) (Class IIa, level of evidence C). 14
Copyright © 2014 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/201 4CCKM@uwhealth.org

Table 2. Opioid Equivalency Table for Adults- Approximate Equianalgesic Doses 3,15-17
Equ ianalgesic doses are approximate. Individual patient response must be observed. Doses and
LQWHUYDOV�EHWZHHQ�GRVHV�DUH�WLWUDWHG�DFFRUGLQJ�WR�WKH�SDWLHQW¶V�UHVSRQVH�
Drug Dose Parenteral
(mg)
Dose Oral
(mg)
Duration of
Analgesia
(hours)
morphine immediate-release 10 30 4 to 6
morphine sustained-release
(Oramorph ® , MS Contin® , Kadian ® ,
Avinza® )
- 30 8 to 24
hydromorphone
(Dilaudid ) 1.5 7.5 3 to 4
hydromorphone extended release
(Exalgo ® ) 7.5
codeine - 200 4 to 6
oxycodone immediate -release
(Percocet , Oxy IR ® , Roxicodone ,
Roxicet )
- 20-30 4 to 6
oxycodone sustained -release
(OxyContin ® ) - 20-30 8 to 12
hydrocodone
(Lortab , Vicodin , Norco® , Zohydro ® ) - 30 4 to 6
methadone*
(Dolophine ) See table 3
Ration of IV to
PO is 2:1 6 to 8
fentanyl
(Sublimaze, Duragesic ) 0.1
See table 4
(transdermal)
oxymorphone
(Opana ® - non-formulary) 1 10 3-6
tapentadol
(Nucynta ® ) - 75
tapentadol ER
(Nucynta ER ® ) 75
* The oral conversion ratio of morphine PO to methadone PO can range from 1: to 20:1 or higher (See Table 3 for
further details). Consult a pain or palliative care specialist if are unfamiliar with dosing methadone.
Equianalgesic dose and route for Equianalgesic dose and route for
currently administered opioid = desired new opioid
Total 24 hour dose and route for Total 24 hour dose with route for
currently administered opioid desired new opioid
Table 3. Methadone dosing18
Current Daily Oral Morphine
Equivalent Dose
Conversion ratio of
Morphine to Methadone
”�����PJ 3 to 1
101 – 300 mg 5 to 1
301 – 600 mg 10 to 1
601 – 800 mg 12 to 1
801 to 1000 mg 15 to 1
•������PJ 20 to 1
Copyright © 2014 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/201 4CCKM@uwhealth.org

Table 4. Dose Conversion from Morphine to Transdermal Fentanyl19,20
Table 5. Intravenous opioid infusion dosing for children <50 kg 9,14
Drug Loading Dose Start Rate
Infusion
Dose Bolus Dose
Morphine 50-100mcg/kg
20
mcg/kg/hr
10-40
mcg/kg/hr
10-20 mcg/kg each 10 -30 minutes as
required
Hydromorphone 10-20mcg/kg 3 mcg/kg/hr 6 mcg/kg/hr 2-4 mcg/kg each 10 min as required
Fentanyl 0.6-1 mcg/kg 0.5 mcg/kg/hr
0.1-2
mcg/kg/hr
0.3 mcg/kg each 5 -10 min as
required
Table 6. Continuous intravenous morphine infusions for infants (1-3 months) 14
Drug Loading Dose Start Rate Infusion Range Bolus Dose
Morphine 25-50 mcg/kg 10 mcg/kg/hr 5-20 mcg/kg/hr 10 mcg/kg each 30 min
6. Adult Subcutaneous Infusions
6.1. Subcutaneous opioid infusions are as effective as the intravenous route and have been
shown to be superior in the palliative care setting (Class I, level of evidence A). 13,15,19,21
6.2. Drug Selection
6.2.1. The most commonly used medications for this route of administration are morphine
and hydromorphone. Fentanyl can also be given subcutaneously. (Class I, level of
evidence C). 16
6.2.2. Methadone can cause tissue irritation and is therefore not recommended to
administer via subcutaneous infusions (Class III, level of evidence C). 16
6.3. A single subcutaneous infusion site can usually accept up to 2 mL per hour. Because of
this, continuous subcutaneous infusions generally need to be a highly concentrated solution
(e.g., morphine 10 mg or more per mL) . Refer to Nursing Policy 10.12 Continuous
Subcutaneous Opioid Infusion (Class I, level of evidence C). 2
6.4. The peak effect of medications administered subcutaneously is usually 30 minutes
compared to 15 minutes as seen with intravenous administration (Class IIa, level of
evidence C). 3
6.5. Site Preparation
6.5.1. A 25- or 27-gauge butterfly needed can be inserted into the anterior thighs,
abdomen, upper arms, subclavicular area, and upper back. The site should be
rotated every 7 days (Class I, level of evidence C). 22 [UWHC carries MiniMed® Sof-
set subcutaneous needle model number MMT-111]
7. Subcutaneous Infusion Initiation and Titration for Adults
7.1. Adult Initiation
Morphine
Transdermal Fentanyl
IV/ Subcutaneous
<10 mg per 24 hours 12 mcg/hr
10-22 mg per 24 hours 25 mcg/hr
23-37 mg per 24 hours 50 mcg/hr
38-52 mg per 24 hours 75 mcg/hr
53-67 mg per 24 hours 100 mcg/hr
Copyright © 2014 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/201 4CCKM@uwhealth.org

7.1.1. Conversions between subcutaneous and intravenous opioids are 1:1 (Class IIa,
level of evidence C). 3
7.1.2. When initiating a subcutaneous infusion, administer a bolus dose equal to one-half
of the opioid starting hourly rate (Class I, level of evidence C). 16
7.2. Adult Titration
7.2.1. A rescue bolus dose may be administered every 30 minutes and should be 50% of
the hourly opioid dose (Class I, level of evidence C). 16
7.2.2. Increase or decrease the dose based on patient response (Class I, level of evidence
C) .16
8. Adult Tapering the Intravenous or Subcutaneous Infusion or Converting to the Oral/Transdermal
Route
8.1. Converting from one opioid to another
8.1.1. If converting from one opioid to another, calculate the amount of opioids given within
a 24 hours period. Decrease the dose of the second opioid by 25-50% to account
for incomplete cross-tolerance. Refer to Table 2 above for equivalencies. (Class I Ia,
level of evidence C). 3
8.2. Tapering the intravenous or subcutaneous infusion
8.2.1. Tapering the dose more quickly than 25% every 24 hours without replacement
opioid therapy may result in symptoms of withdrawal. Refer to Pain Care Fast Facts:
Opioid Withdrawal . (Class IIa, level of evidence C). 3,8
8.3. Converting from the intravenous or subcutaneous infusion to the oral or transdermal route
8.3.1. When pain is controlled on a stable dose of the infusion for at least 24 hours,
consider converting back to an oral or transdermal opioid formulation for discharge.
8.3.2. Use the Opioid Equivalency Table (Table 2) to convert the current total 24 hours
intravenous opioid consumption to oral or transdermal equivalents. Decrease the
dose of the second opioid by 25-50% to account for cross-tolerance. For oral
opioids, divide the total daily dose needed by the number of doses per day (Class IIa ,
level of evidence C). 3
8.3.3. For the conversion of morphine to transdermal fentanyl, refer to Table 4 (Class I,
level of evidence C). 19
8.3.4. The opioid infusion can be stopped 1 to 2 hours after administration of the first oral
dose (depending on whether the patient is given a short acting or extended release
formulation). If the patient is switching to transdermal fentanyl (Duragesic®), a two-
step taper should be completed with a 50% dose reduction in the infusion rate 6-
hours after application of the patch, followed by completely discontinuing the infusion
12 hours after application of the patch (Class I, level of evidence C). 9,13,18
8.3.5. See UW Health Opioid Withdrawal Fast Fact for more information of withdrawal
symptoms and non-opioid treatment.
9. Risks of Continuous Infusions and Concentrated Syringes
9.1. Opioid side effects should be anticipated and treated. Monitor and reassess per Hospital
Administrative Policy 8.76 for Pain Management.
9.2. If side effects cannot be controlled with adjuvant drugs, consider switching to an infusion
with a different opioid or an alternative method of analgesia (Class I, level of evidence C). 3,8
Due to the risk of addiction, misuse, abuse, overdose, and death, prescribers should
establish opioid analgesic goals of therapy for each patient and regularly assess the patient
in order to guide therapy (Class IIa, level of evidence C). 3
E. Internal References
1. Meperidine Adult and Pediatric Inpatient Clinical Practice Guideline
2. Nursing Policy 10.12 Continuous Subcutaneous Opioid Infusion
3. Pain Care Fast Facts: Opioid Withdrawal
4. Hospital Administrative Policy 8.76 for Pain Management
5. Administrative Policy 8.33 High Alert Medication Administration
Copyright © 2014 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/201 4CCKM@uwhealth.org

6. UW Health Opioid Withdrawal Fast Fact
F. External References
1. Tricoci P, Allen J, Kramer J, Califf R, Smith S. Scientific evidence underlying the ACC/AHA Clinical Practice
Guidelines. JAMA. 2009;301(8):831-841.
2. Merskey H, Bugduk N. Classification of Chronic Pain. 2nd ed. Seattle, WA: IASP Press;1994.
3. Adult Cancer Pain Clinical Practice Guidelines. NCCN Web Site.
http://www.nccn.org/professionals/physician_gls/pdf/pain.pdf . Accessed November 13, 2013.
4. :+2¶V�3DLQ�5HOLHI�/DGGHU��World Health Organization Web Site .
http://www.who.int/cancer/palliative/painladder/en . Updated 1986. Accessed November 6, 2013.
5. Latimer E, Burge F. Continuous intravenous infusion of opioid analgesics for severe pain. Can Fam
Physician. 1989;35:1788-1792.
6. American Society of Anesthesiologists Task Force on Chronic Pain Management and the American Society
of Regional Anesthesia and Pain Medicine. Practice Guidelines for Chronic Pain Management.
Anesthesiology. 2010;112:1-1
7. Analgesic Options for Patients with Allergic-Type Opioid Reactions. Pharmacists Letter / Prescribers Letter.
2006;22:220201.
8. Levy MH. Pharmacologic treatment of cancer pain. N Engl J Med. 1996;335:1124-1132.
9. Lexi-Comp Online, Lexi-Drugs Online, Hudson Ohio: Lexi-Comp, Inc.; 2012; accessed October 2013.
10. Shaiova L, Berger A, Blinderman CD, et al. Consensus guideline on parenteral methadone use in pain and
palliative care. Palliat Support Care. 2008;6;165-176.
11. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and
delirium in adult ICU patients. Crit Care Med. 2013;41(1):263-306.
12. Micromedex 1.0 Healthcare Series, [Internet database] . Greenwood Village Colo; Thomson Healthcare.
Updated periodically.
13. Elsner F, Radbruch L, Loick G, et al.: Intravenous versus subcutaneous morphine titration in patients with
persisting exacerbation of cancer pain. J Palliat Med. 2005;8(4):743- 50.
14. Twycross A, Dowden S, Bruce L. Managing Pain in Children: A Clinical Guide. West Sussex, United
Kingdom: John Wiley & Sons, 2009.
15. Hagen NA, Wasylenki E. Methadone:outpatient titration and monitoring strategies in cancer patients. J Pain
Symptom Manage. 1999;18(5):369-75.
16. Pasero C. Subcutaneous opioid infusion. Am J Nurs. 2002;102(7):61-62.
17. Pain (PDQ®). National Cancer Institute Web Site.
http://www.cancer.gov/cancertopics/pdq/supportivecare/pain/HealthProfessional/page3 . Updated
September 25, 2013. Accessed October 2013.
18. Toombs JD, Kral LA. Methadone treatment for pain states. Am Fam Physician. 2005;71:1353-1358.
19. Hanks GW, Conno F, Cherny N, et al.: Morphine and alternative opioids in cancer pain: the EAPC
recommendations. Br J Cancer. 84 (5): 587-93, 2001
20. Duragesic (package insert). [Prescribing information]. Vacaville, CA. Janssen Pharmaceuticals;2009.
21. Gazelle G, Fine PG. Fast fact and concept #075 Methadone for Pain. End- of-Life Physician Resource
Center Website. http://www.eperc.mcw.edu. Updated September 2002. Accessed November 12, 2005.
22. Toombs JD, Kral LA. Methadone treatment for pain states. Am Fam Physician. 2005;71:1353-1358.
G. Benefits / Harms of Implementation
Implementation of this clinical practice guideline will provide a consistent approach to ensuring
the safe and efficacious use of continuous opioid infusions.
H. Implementation Strategy
This clinical practice guideline will be disseminated to clinical staff and posted electronically to
UConnect.
I. Implementation Tools / Plan
This clinical practice guideline will be posted on UConnect and associated with medication order
records for continuous opioid infusions.
Copyright © 2014 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/201 4CCKM@uwhealth.org

J. Disclaimer
This clinical practice guideline provides an evidence-based approach to managing continuous
opioid infusions. It is understood that occasionally patients will not match the conditions
considered in the guideline.
Copyright © 2014 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 06/201 4CCKM@uwhealth.org