Poor Glycemic Control During Hospitalization · Glucose and Post-CABG . Morbidity and Mortality . Diabetes and Coronary Artery Bypass Surgery . An examination of perioperative glycemic

Poor Glycemic Control During Hospitalization

Robert J. Rushakoff, MD Professor of Medicine

University of California, San Francisco

[email protected]

Rational Approach at a Time of Uncertainty

Disclosures

Speaker: Merck* Speaker: Novo-Nordisk* * Nonbranded

"Each blind man perceived the elephant as something different: a rope, a wall, tree trunks, a fan, a snake, a spear..."

Education Nurses

Physicians Students

Patient Education

Transitions Outpatient to Inpatient Inpatient to Inpatient

Inpatient to Outpatient

Data Collection

Medical Errors Glucometrics

Diabetes Management

Order Entry Smart Orders

Dosing Calculators

Jargon CQI

Patient Assessment of Skills, Education

Diabetes Assessment Form

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Page 1 of 6

Coordination of Outpatient Care

Home care services

Outpatient diabetes classes

Medical Errors JCAHO

ICU Protocols Periop Management Secondary Diagnosis

Insulin Administration Order Written Order Sent to Pharmacy Order Entry by Pharmacist Drug Preparation by pharmacy Insulin delivery to unit Medication Administration Documentation

Inpatient Diabetes Goals

Who Cares

Just get patient home

Sliding Scales are fine

Avoid that scary hypoglycemia


Normal glucoses for

everyone

A high glucose means failure

Sliding Scales are banned

Some hypoglycemia is acceptable


Who Cares





Normal glucoses for

everyone





Who Cares





Normal glucoses for

everyone





Who Cares





Normal glucoses for

everyone





Appropriate Glucose Control Based on

physiology and outcome studies

Target Glucose Levels

Alive

No DKA or Hyperosmolar Coma


No hypo- or hyperglycemia

•Prevent fluid and electrolyte abnormalities secondary to osmotic diuresis •Improve WBC function •Improve gastric emptying •Decrease surgical complications •Earlier hospital dischange

•Decreased post-MI mortality

•Decreased post-CABG morbidity and mortality


Normal Glucoses

Decreased Morbidity and Mortality


Problems With High Glucoses

Glucose and Post-CABG Morbidity and Mortality

Diabetes and Coronary Artery Bypass Surgery An examination of perioperative glycemic control and outcomes

• Retrospective review of 291 patients surviving 24 h post-op • 40% with retinopathy, nephropathy, or neuropathy

Inpatient complications: For each 1 mmol/l (18 mg/dL) increase in post-op day 1 over 6.1 mmol/l (110 mg/dL), a 17% increased risk of complications

McAlister FA et al. Diabetes Care. 2003; 26:1518-1524.

High Blood Glucose Levels Associated With Increased Mortality in ICU

● Retrospective review of 259,040 critically ill patients conducted by the Veterans Affairs Inpatient Evaluation Center based in Cincinnati

• Hyperglycemia was an independent predictor of mortality starting at 111 mg/dL

• Effect was greatest with acute myocardial infarction, unstable angina, and stroke – Raised MI risk from 1.7 to 6 times – Raised stroke risk from 1.8 to 29 times – Raised unstable angina from 1.4 to 3 times

Falciglia M et al. Crit Care Med. 2009; 37:3001-3009.

• A significant but weaker effect was seen in patients with sepsis, pneumonia, and pulmonary embolism

• Hyperglycemia was not found to be associated with mortality in diseases such as COPD and hepatic failure, hip fractures

• In diabetes patients, the increase in mortality risk was not seen until mean glucose was >146 mg/dL

Hyperglycemia–related mortality in critically ill patients varies with admission diagnosis

Falciglia M et al. Crit Care Med. 2009; 37:3001-3009.

TPN: Adverse Outcomes Hyperglycemia Is Associated With Adverse Outcomes in

Patients Receiving Total Parenteral Nutrition

Cheung et al: Diabetes Care, 28:2367-2371, 2005

Risk of complications in relation to mean daily blood glucose level

OR (95% CI) P

Any infection 1.40 (1.08–1.82) 0.01

Septicemia 1.36 (1.00–1.86) 0.05

Acute renal failure 1.47 (1.00–2.17) 0.05

Cardiac complications 1.61 (1.09–2.37) 0.02

Death 1.77 (1.23–2.52) <0.01

Any complication 1.58 (1.20–2.07) <0.01

Intervention Studies

Decreased Infections Insulin infusion improves neutrophil function in diabetic cardiac surgery patients

Perioperative IV insulin infusion

Neutrophil phagocytic activity

% baseline

Control 47

Insulin 75

Rassias AJ et al. Anesth Analg. 1999; 88:1011-1016.

Decreased Infections Glucose control lowers the risk of wound infection in diabetics after open-heart operations

Perioperative IV insulin infusion Protocol to maintain glucoses <200 mg/dL

Incidence of Deep Wound Infections (%)

1997 1999 Routine Control 2.4 2.0 “Tight” Control 1.5 0.8

Zerr KJ et al. Ann Thorac Surg. 1997;63:356-361. Furnary AP et al. Ann Thorac Surg. 1999;67:352-360. Furnary AP et al. J Thorac Cardiovasc Surg. 2003;125:1007-1021.

Decreased Mortality Glucose control decreases mortality in diabetics after open heart

operations Furnary et al. J Thoracic Cardiovascular Surgery 2003, 125: 1007-1021

024

68

1012

1416

<150 150-175 175-200 200-225 225-250 >250

Mor

talit

y (%

)

Cardiac-relatedmortality

Noncardiac-related Mortality

0.9% 1.3%

2.3%

4.1%

6.0%

14.5%

Declining In-Hospital Mortality in Patients Undergoing Coronary Bypass Surgery in the United States Irrespective of Presence of Type 2 Diabetes or Congestive

Heart Failure

Clin Cardiol. 2012 Feb 23. (ahead online)

Steady decline in the coronary artery bypass grafting (CABG)-related total mortality in recent years.

Intensive Insulin Therapy in Critically Ill Patients

Decreased Morbidity and Mortality

● Patients (all) on mechanical ventilation in ICU

● Randomly assigned to IV insulin maintaining glucoses between 80-110 mg/dL or conventional treatment (IV insulin if glucose >215 mg/dL then maintain glucose between 180-200)

Van den Berghe G et al. N Engl J Med. 2001;345:1359-1367.

% given insulin 24-hour dose AM glucose

Intensive 99 71 units 103

Conventional 39 33 units 153

12 month mortality

Intensive 4.6%

Conventional 8.6%

Main effect on patients in ICU >5 days

Van den Berghe, G. et al. N Engl J Med 2006;354:449-461

Kaplan-Meier Curves for In-Hospital Survival

NICE-SUGAR

• 6104 adults who were expected to require treatment in the ICU on 3 or more consecutive days randomized to intensive blood glucose control (target range, 81 to 108 mg/dL) or conventional blood glucose control (<180 mg/dL)

• Primary endpoint death from any cause within 90 days after randomization

• Baseline characteristics similar

The NICE-SUGAR Study Investigators. N Engl J Med. 2009;360:1283-1297.

NICE- SUGAR: Data on Blood Glucose Level, According to Treatment Group

The NICE-SUGAR Study Investigators. N Engl J Med 2009;360:1283-1297

NICE-SUGAR: Probability of Survival and Odds Ratios for Death, According to Treatment Group


Problems With Low Glucoses

Hypoglycemia and Mortality in Insulin-treated vs Non–Insulin-treated

AMI Patients

Kosiborod M, et al. JAMA. 2009;301(15):1556-1564.

Hypoglycemia

No hypoglycemia P=.92 P<.001

Mor

talit

y, %

10.4

18.4

9.2 10.2

0

10

20

No Insulin Treatment Insulin Treatment

Hypoglycemia was a predictor of

higher mortality in patients not treated with insulin, but not

in patients treated with insulin

Hazard Ratio for Death According to the Occurrence of Hypoglycemia on 1 Day or More Than 1 Day and Receipt or Nonreceipt of Insulin Therapy at the Time of the First Hypoglycemic

Episode.


Severe Hypoglycemia (glucose<40 mg/dl) 4 month audit

Unit Total Glucose Checks

# Low from report (% low)

False lows # of Actual Low (% low)

ICU (IV) 3378 3 (0.09%) 2/3 1 (0.03%) ICU (SQ) 5241 9 (0.17%) 8/9 1 (0.02%) Med/Surg 15661 18 (0.11%) 17/18 1 (<0.01%)

Unit Total False lows

Immediate repeat not low (and no rx

given)

No low glucose found (and no rx

noted)

ICU (IV) 2 2 0 ICU (SQ) 8 8 0 Med/Surg 17 12 5

False Low explanation

In ICU, both patients with lows did die within 24 hours, but on review, these patients were both end stage and plans were already being discussed for withdrawal of life support prior to the low glucose.

2013 Inpatient Glucose Goals

Organization ICU Non-ICU Prepandial

Non-ICU Maximum

AACE/ACE 140-180 mg/dl <140 mg/dl 180 mg/dl

ADA 140-180 mg/dl <140 mg/dl 180 mg/dl

ACP 140-200 mg/dl Avoid <140 mg/dl

Endocrine Society <140 mg/dl 180 mg/dl

Society of Critical Care Medicine 100-150 mg/dl

UCSF 100-160 mg/dl 100-180 mg/dl

Blood Glucose Levels During Isulin Treatment

Days of Therapy

Bloo

d gl

ucos

e (m

g/dL

)

100

120

140

160

180

200

220

240

Admit 1 2 3 4 5 6 7 8 9 10

SSRI

Lantus + glulisine

Mean Blood Glucose Levels During Insulin Therapy

* p<0.01 ¶ p<0.05

¶ * * *

¶ ¶ ¶

Day 3: P=0.06

Umpierrez GE Et al. Diabetes Care. 2007;30:2181–2186.

How to Obtain “Tight” Control

Bedside glucose monitoring IV insulin drips Diabetic Flow sheets Discourage the use of traditional Sliding Scale

insulin

INSULIN

SLIDING

SCALE

INSULIN

SLIDING

SCALE

Roller Coaster Effect of Insulin Sliding Scale

Mr. And Mrs. XXXXX are admitted for “Giants” fever.

Mr. XXXXX has Type 2 diabetes and takes a total of 75 Units insulin per day (2 shots). Glucoses at home are “poorly controlled.”

Mrs. XXXXX also has Type 2 diabetes but she has good control taking about 25 units of Lispro premeal and 40 Units glargine at night.

Fingerstick qid with regular insulin SQ coverage:

FSBG Action

< 50 1 amp D50 iv and call HO

51-80 give juice and repeat in 0.5-1 hr

81-150 no coverage

151-200 2U regular insulin SQ





>400 12U regular insulin SQ, call HO

Glucocorticoids and Diabetes Peripheral

Tissues (Muscle)

Glucose

Liver

Impaired insulin secretion

Increased glucose production

postreceptor defect

Insulin resistance

Pancreas

Glucocorticoids and Diabetes:

Breakfast Dinner Lunch Breakfast

Glucose

Bedtime



Glucose

Bedtime

Typical sliding scale insulin



Glucose

Bedtime

Typical sliding scale insulin



Glucose

Bedtime

Revved Up sliding scale insulin



Glucose

Bedtime

Revved Up sliding scale insulin



Glucose

Bedtime

NPH and

Regular



Glucose

Bedtime

NPH and

Regular



Glucose

Bedtime

Increase NPH and

Regular

INSULIN

SLIDING

SCALE

Use of Insulin

Physiologic Insulin Secretion: Basal/Bolus Concept

Breakfast Lunch Supper

Insu

lin

(µU

nits

/mL)

G

luco

se

(mg/

dL)

Basal Glucose

150

100

50

0 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9

A.M. P.M. Time of Day

Basal Insulin

50

25

0

Nutritional Glucose

Nutritional (Prandial) Insulin

Suppresses glucose production between meals & overnight

The 50/50 Rule

Relative Insulin Level

Time

Breakfast 12pm Lunch Dinner

Insulin Regimens


PM glargine

glargine

Insulin Regimens

Time

Breakfast 12pm Lunch Dinner


Time

Breakfast

TID lispro/aspart/glulisine and hs glargine

Lunch Dinner 12pm

glargine

Lispro/aspart/glulisine

Insulin Regimens

Past Paper Insulin Order Forms

● Adult – DKA – Adult SQ Insulin – Patient

eating – Adult SQ Insulin – NPO,

TPN, Tube Feeding – IV insulin – ICU protocol – IV insulin – Med-Surgical

Unit protocol – Adult Insulin pump

• Patient waver form – Adult SQ insulin algorithm

for NPO patients** – CV Surgery Specific orders

– PREO-OP Pathway**

● OB-GYN – SQ Insulin – Patient eating – IV Insulin form - delivery – Pump Form

• Pump waiver form

● Pediatrics – SQ Insulin – Patient eating – Pump Form

• Pump waiver – DKA – IV insulin

** under development

Order set

Adult SQ Insulin – Patient eating: set premeal dose

Premeal Dosing

Postmeal Dosing (based on amount consumed)

Adult SQ Insulin – Patient eating: CHO Counting

Premeal Dosing CHO dependent

Postmeal Dosing (based on CHO consumed)

Adult SQ Insulin – NPO, TPN

Q4h nutrition and correction

Nutrition dose timed to cycle TPN, correction q4h

Adult SQ Insulin –Tube Feeding

Q4h nutrition and correction

Nutrition dose timed to cycle feedings, correction q4h

Adult Insulin Pump

IV Insulin protocol: ICU Specific initial rate for CVS/DKA/other

IV insulin protocol: Medical/surgical units Specific initial rate for CVS/DKA/other

DKA

Big Brother

Daily Reports: 2 or more glucoses>225 Glucose <60 On insulin pump Dx type 1 DM

Pharmacologic Classes of Agents to Control Hyperglycemia in Type 2 Diabetes

Thiazolidinediones—e.g., rosiglitazone, pioglitazone

Class

Biguanides—e.g., metformin

Alpha-glucosidase inhibitors—e.g., acarbose & miglitol

Insulin secretagogues—e.g., sulfonylureas (glyburide, glipizide); repaglinide

Takes 2-3 weeks to see initial effect. Effects continue for weeks or months after discontinuation of medication

Keep in mind the metabolic t1/2 of each drug. High risk for hypoglycemia

Withhold in conditions predisposing to renal insufficiency and/or hypoxia

CV collapse Acute MI or acute CHF Severe infection Use of iodinated contrast material Major surgical procedures

In case of hypoglycemia (due to sulfonylurea or insulin treatment)

Glucose (dextrose) must be administered

Sucrose and complex carbohydrates should not be administered

Special Considerations

Pharmacologic Classes of Agents to Control Hyperglycemia in Type 2 Diabetes

DDP 4 Inhibitor Class

SGLT-2 inhibitor

Other: Colesevelam Dopamine Agonist

GLP-1 Agonist

Minimal Data. Low risk of hypoglycemia

Minimal Data. GI side effects, delayed gastric emptying. Low risk of hypoglycemia

No Data. Risk of dehydration, urinary and yeast infections

No Data. GI side effects Colesvelam: binds medications

Special Considerations

What does it take to Implement Change?

Physicians Administration

Committee Members Physicians: Endocrinologist, Hospitalist Clinical Nurse Specialists: Diabetes, education Nurses: ICU Manager, at least one manager from

medical floor (or their representative) Clinical Pharmacist Administration presence – from level of quality

assurance or similar title Discharge Coordinator – not required for initial

discussions and implementation, but needed later Nutritional services – not required for initial design

and implementation of forms.

TASKS Formulary

Clean up insulin Clean up oral agents

Nursing Issues Policy on IV insulin use Policy on frequency of glucose monitoring

Forms Design forms

IV insulin forms SQ insulin forms ?DKA treatment forms

Other Committees To be Conquered Pharmacy and Therapeutics

Formulary issues Oral agents Insulins Insulin Forms – iv, sq

Forms Insulin forms – iv, sq

Quality Improvement Need buy in at this level to achieve administrative

support

Other People To be Conquered Smaller Hospitals

CEO Chief of Staff

Larger Institutions Chairs of Medicine, Surgery Heads of training programs from Medicine,

Surgery Chief of Staff, Chief Medical Officer, CEO Chairs of other Departments Chief Residents Dean for Education

Implementation Smaller Hospitals

Entire Institution Larger Institutions

? One unit at a time ? One service at a time

Make certain forms are available Unit clerks must be aware!!!! If orders written in ER, forms must be in ER If forms not available, this will fail.

UCSF Implementation Committee: Endocrinologists, Hospitalist,

Diabetes Nurse Specialist, Clinical Pharmacists, QA administrators, others

Formulary Limited number of insulins now available

Forms IV insulin forms – ICU, Floor SQ insulin form DKA treatment forms

Physicians Robert Rushakoff Umesh Masharani Melissa Weinberg Sarah Kim Aaron Neinstein Bonnie Kimmel Saleh Adi Stephen Gitelman Jan Hirsch Kathryn Rouine-Rapp David Robinowitz Michael Hwa Heather Nye Steve Pantilat

Pharmacists Heidemarie Windham Lisa Kroon Kethen So Thomas Bookwalter Anna Seto

Administration Rosanne Rappazini Jennifer Pacholuk Joy Pao

Dietary Marian Devereaux

Nurses Mary Sullivan Pauline Chin Marlene Bedrich Craig Johnson Molly Killion Jeanne Buchanan Noraliza Salazar Lynn Dow

PEOPLE CHANGING INPATIENT DM MANAGEMENT AT UCSF

UCSF Implementation Nursing Education

Diabetes Nurse Specialist Intranet Training

UCSF Implementation Nursing Education

Diabetes Nurse Specialist Intranet Training

Physician Training Small group sessions Internet training

Pediatric Nursing Training

Pre-implementation

N=24

Post-implementation

N=22

Test of significance

Total errors 127 17

Total possible errors

882 1107

Mean # errors/pt 5.29 0.77 2-tailed t, independent samples with

unequal variance p.=.004

Error rate Denominator = possible errors

0.14 0.02 Z-test, 2-tail p=0.02

Community Hospital Physician Training

Annenberg Project

Robert J. Rushakoff, MD Director Inpatient Diabetes, UCSF

Cheryl W. O’Malley, MD Program Director, Internal Medicine Banner Good Samaritan Medical, Phoenix, Arizona

Kendall M. Rogers, MD Chief, Hospital Medicine University of New Mexico Health

Sciences Center Albuquerque, New Mexico

Archana Sadhu, MD Director, Inpatient Diabetes Program, The Methodist

Hospital System Houston, Texas

Carol Manchester, MSN, ACNS, BC-ADM, CDE University of Minnesota Medical Center, Minneapolis, Minnesota

Jane Jeffrie Seley, DNP, MPH, BC-ADM, CDE New York Presbyterian/Weill Cornell Medical Center

Mary M. Sullivan, RN, DNP, ANP-BC, CDE University of California, San Francisco

Eric D. Peterson, EdM, FACME Annenberg Center for Health Sciences at Eisenhower

Faculty team visits each site 1 physician (inpatient endocrinologist or hospitalist)

1 nurse with inpatient glycemic control experience

Team Meeting Review experience, goals, barriers

Refine the team project who they need to involve Data collection to characterize their current performance Common barriers that they are likely to face and strategies that have been used by other

institutions to overcome them Implementation and measurement that they may want to consider to evaluate both process and

outcome

Presentation to other stakeholder groups Physician or nursing staff forums

3 Web conferences planned #1 Sites share their project plans

#2 Sites present interim progress and challenges

#3 Sites present data generated from their project

Primarily intended as a tactic to keep sites “on task” and to facilitate interaction between sites

Community, non-teaching; No Endocrinology

Lots of forms – main was self adjusting SS

Many MD groups, hospitalist group

No education, Meal timing

Lots of forms – main was self adjusting SS SS form gone; BB mainly used (CHO based postmeal for

meals on demand) Many MD groups, hospitalist group Hospitalist contract dispute

No education Case studies – CDs, in person for specific populations

Meals Refreshment centers closed Still get meals on demand

CDE Involvement Assist with insulin orders Call MDs for consistently high numbers

Hyperglycemia in Hospitalized Patients

ucsf.logicnets.com

Transition from Home to Hospital

http://ucsf.logicnets.com/

Issues at Discharge ● Patient new to diabetes ● Patient new to insulin or other medications ● Not metabolically stable (eg, steroid taper), unclear

what any requirement will be ● Oral agents, incretins - when, how, why ● Changing medications (TPN, etc.) on the day of

discharge ● Inability to perform self management ● Who follows patient ● Communication of inpatient care plan to outpatient

providers ● Short-term and long-term goals

UCSF Survey of Patients on Insulin Discharged to Home

Documents

Poor Glycemic Control During Hospitalization · Glucose and Post-CABG . Morbidity and Mortality . Diabetes and Coronary Artery Bypass Surgery . An examination of perioperative glycemic