inpatient glycemic management: time to shed our scales? deric morrison oct. 2014

Inpatient Glycemic Management:

Time to shed our scales?Deric Morrison

Oct. 2014

Objectives• At the end of this presentation

you will:1. Understand the current guidelines for inpatient

glycemic management.2. Know the evidence that supports these

guidelines.3. Have an approach to managing inpatients with

hyperglycemia.

A word about Type 1 DM

• ALWAYS NEED basal insulin.

• Options:o Intermediate (NPH) SQ insulin q8-24hourso Long-acting (glargine/detemir) SQ insulin q12-

24ho Insulin pump basal rateo Intravenous Insulin Infusion

Why Do We Care?• Both Hyper and Hypo -glycemia are

associated with ↗ mortality and morbidity in-hospital.

• There has been little evidence to guide appropriate glycemic targets or glycemic management strategy in non-critically ill inpatients.

guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association

• Approximately 1/3 of in-patients have been found to have hyperglycemia

• Many have pre-existing diabetes prior to admission

Hyperglycemia

In-hospital Hyperglycemia is Common

What do you want to avoid

• In order of importance?oSevere hypoglycemic eventoDKAoSymptomatic hypo/hyperglycemiaoPersistent hyperglycemia

• Complications (association vs. causal)oThe “ready for discharge - except

requiring high doses of sliding scale insulin and has no long term diabetes management plan” syndrome

Why are sugars different in hospital?

• HigheroStress/concomitant illnessoNutrition (TPN, tube feeds, IV

dextrose)oDrugs (steroids)

• LoweroNutrition (diet, portions, NPO)oRenal failureo Liver failureoSevere illness


Hyperglycemia

Decreased immune

function, wound healing,

increased oxidative stress

Acute Illness

Increased stress hormones, use of glucocorticoids,

decreased level of activity

Inzucchi SE. NEJM 2006;355;1903

Hyperglycemia and Acute Ilness


Hyperglycemia

Increases risks of postoperative infections and

delirium

Prolonged hospital stay,

resource utilization

Increased renal dysfunction and renal allograft

rejection in transplant

Adverse Effects of Hyperglycemia

Armamentarium• Metformin• Sulfonylureas (Glyburide, Gliclazide)• Meglitinides (Repaglinide)• Alpha glucosidase inhibitor (Acarbose)• Incretins

• GLP-1 analogues (Exenatide, Liraglutide)• DPP-4 inhibitors (Sita/Lina/Saxa – gliptin)

• Thiazolidinediones (Rosi/Pio – glitazone)• SGLT2 inhibitors – cana (and other)

gliflozin(s) • Insulins

Insulins• Which ones do you know?

Guidelines• Canadian Diabetes Association –

2013• Endocrine Society – 2012

o Accompanied by Meta-Analysis

• American Diabetes Association – 2014

• American College of Physicians – 2011o Accompanied by Meta-Analysis

American College of Physicians

• Use of intensive insulin therapy for the management of glycemic control in Hospitalized patients: A CPG from the ACP: Feb. 2011.

• Intensive Insulin Therapy in Hospitalized Patients: A Systematic Review. Annals of Internal Medicine Feb. 2011.

• Organized into different clinical scenarios

Myocardial Infarction• 3 Trials (fair); 2 Trials (poor)• Target 4.0-11.0 mmol/L vs unspecified• Target 7.0-11.0 mmol/L + insulin on

dischargeo Mortality reduction o RR 0.69 (CI 0.49 – 0.96)

• Overall, no mortality reduction

Stroke• 2 Trials (fair); 2 Trials (poor)• Overall, no mortality reduction

Perioperative Control• 1 Trial (fair); 2 Trials (poor)• Target 3.9 – 10.0 mmol/L vs

unspecified

• No difference in health outcomeso Small studieso Low event rates

Infection Risk• 9 Trials (fair); 7 Trials (poor)• Sepsis

o Reduction of sepsis with Intensive Insulin o RR 0.79 (CI 0.62 – 1.00)

• Pooled result of wound infection, UTI, pneumonia or combinationo No significanceo RR 0.68 (CI 0.36 – 1.30)

Effects of intensive insulin therapy on rates of infection in various inpatient settings. We included inpatients in the MICU, SICU, and perioperative settings as well as patients with

stroke or acute brain injury.

Kansagara D et al. Ann Intern Med 2011;154:268-282

©2011 by American College of Physicians

sepsis

infx

General Medical Ward• 0 Trials

ACP• Recommendations deal with intensive

insulin in ICU (this presentation does not).

• Highlights lack of evidence regarding other hospitalized patient populations.

Intensive insulin ~ <7.8 pre-meal, <10 random

• This meta-analysis included observational studies (ACP did not)

• Main conclusion: Intensive Insulin may reduce risk of infection in non-critically ill patients (surgical)

• Low quality evidence• Intensive insulin ~ <7.8 acMeal, <10

random

Travel Plans• Now, that we’ve established we don’t

really know where we should go…

• How do we get there?


Patient Type Glucose Target (mmol/L)

Therapy of choice

Non-critically ill Fasting 5-8

Random <10

Pre-hospital regimen OR basal-bolus-correction

Critically ill 8-10 IV insulin infusion

CABG intraop 5.5-10 IV insulin infusion

Other periop 5-10 As appropriate

CABG = coronary artery bypass graft; IV = intravenous; Intraop = intraoperative; periop = perioperative

In-hospital Glycemic Targets

Targets (< 8 acMeal, < 10 Random)

Editorial

• No evidence for these targets in hospital (Outpatient targets)

• Reasonable place to start

• Safety first• Conservative dosing, avoid catastrophic hypos• Glucoses slightly above targets may be acceptable

• Try to maintain close to target• Symptomatic or severe hyperglycemia should

prompt action

• REASSESS targets and treatments daily


1. Provided that their medical conditions, dietary

intake, and glycemic control are acceptable, people

with diabetes should be maintained on their pre-

hospitalization oral anti-hyperglycemic agents or

insulin regimens [Grade D, Consensus]

Recommendation 1


Use BASAL + BOLUS + CORRECTION

In-hospital circumstances may warrant temporarily holding

other antihyperglycemic medications (eg. renal or

hepatic impairment)

Insulin = treatment of choice

BASAL + BOLUS + CORRECTION

Insu

lin

BOLUS + CORRECTION

BASAL

Breakfast Lunch Dinner


In the absence of routine

insulin, sliding scale insulin

regimen (bolus insulin on a prn

basis) is purely reactive rather

than proactive and allows for

hyperglycemia to occur before

responding

BG (mmol/L) Bolus insulin (U)

<4 Call MD

4.1 – 10.0 0

10.1 – 13.0 2

13.1 – 16.0 4

16.1 – 19.0 6

>19.0 Call MD

Queale WS. et al. Arch Int Med 1997;157

Sliding Scale Alone is Inefficient


4.0

10.0

Breakfast Lunch Dinner Bedtime


< 4 Call MD

4.1 – 10.0 0

10.1 – 13.0 2

13.1 – 16.0 4

16.1 – 19.0 6

> 19.0 Call MD

6.0

Bolus insulin QID

14.0

6.0

16.5

3.0

Sliding Scale alone

What do you do?

What do you do?

What do you do?

What do you do?

+4 U

0 U 0 U

+6 U

QID: four times daily; SSI: sliding-scale insulin; BG: blood glucose

Sliding Scale Insulin Alone Results in Variable Glucose Control

BG (mmol/L)


BASAL + BOLUS + CORRECTION Results in Smoother Glycemic Control

4.0

10.0

Breakfast Lunch Dinner Bedtime


< 4 Call MD

4.1 – 10.0 0

10.1 – 13.0 2

13.1 – 16.0 4

16.1 – 19.0 6

> 19.0 Call MD

6.0

12.0

6.0

Correctional Insulin AC meals

What do you do?

What do you do?

What do you do?

6+2 U

6+0 U

6U 6U

What do you do?

6+0 U

6.0

ROUTINE Bolus insulin

Basal insulin

6U

18 U

Routine Basal

Rabbit -2 Trial Medicine

• At 2 American Academic Hospitals • Open label, randomized study• 130 insulin naïve non-surgical

inpatients, known history of diabetes and initial BG 7.8 – 22.2.

• OHAs stopped, randomized to SSI or basal-bolus with glargine + glulisine.

• Admission BG = 12.7, A1c = 8.8%

Scheduled Dose

Sliding scale

Sliding scale/Supplemental

doses

7.8 – 10

>22.2

14.4 – 16.7

Comment on doses• Scheduled routine dosing

o 0.4 – 0.5 Units/kg/dayo 50% glargine, 50% glulisine

o E.g. 70 kg person• 30-35 Units/day• ~15 Units glargine• ~5/5/5 Units glulisine

o Conservative?

RABBIT 2 Results

10

13.3

5.6

Rabbit 2 Surgery 2011• Similar to Rabbit trial, similar glycemic results.


*

*

ŧŧ

††

RABBIT 2 RABBIT 2 Surgery

Adapted from: Umpierrez GE, et al. Diabetes Care 2007;30:2181-86. Adapted from: Umpierrez GE, et al. Diabetes Care 2011;34:256-61.

Basal-Bolus (BBI) Regimen Achieves Better Control than Sliding Scale (SSI) Alone

Blo

od

glu

cose

(m

mo

l/L

)

¶

¶

¶

***

Admit 1 2 3 4 5 6 7 8 9 10

Duration of treatment (days)

5.6

6.7

7.8

8.9

10.0

11.1

12.2

13.3

*p < 0.01; ¶p < 0.05.

¶

SSI

BBI

1Randomi-zation

2 3 4 5 6 7 8 9

Duration of treatment (days)

6.7

7.8

8.9

10.0

11.1

13.3

*p < 0.001, ŧp = 0.02, †p = 0.01

SSI

BBI

RABBIT 2 Results• End point:

o Target BG <7.8; o 66% in Basal/Bolus, 38% SSI

• No differences in hospital stay or hypoglycemia

Basal Plus Trial• Umpierrez GE, et al. Randomized

Study Comparing a Basal Bolus With a Basal Plus Correction Insulin Regimen for the Hospital Management of Medical and Surgical patients With Type 2 Diabetes: Basal Plus Trial. Diabetes Care. 2013 Feb 22. [Epub ahead of print].

http://www.ncbi.nlm.nih.gov/m/pubmed/23435159/?i=1&from=/23435159/related







Basal Plus• Multicentre, 375 DM2 patients• Home regimen: diet, oral agents, or

low dose insulin, randomized 2:2:1

1. Basal-Bolus-Correction [glargine-glulisine]

2. Basal Plus (sliding scale) [glar-glu]3. Sliding Scale (alone) [regular]

Basal-Bolus-Correction

Basal Plus

Sliding Scale – Added to Basal

bolus or Plus (glulisine) OR alone

SSI (R)

Insulin adjustment• Basically increase insulin by 10%

if mildly high, 20% if high.

• Reduce by 20% if low.

Basal Plus Trial• Treatment Failure (mean glucose

or 2 consecutive > 13.3)o Basal Bolus 0, Basal Plus 2%, SSI 19%

• Hypoglycemiao Less than 3.8

• Significantly less in SSIo Less than 3.3

• Trend to less in SSIo Less than 2.2

• 1 event each in basal bolus and basal plus, 0 in SSI

Basal Plus Trial Conclusions

• DM2 patients who are not on high doses of insulin can be managed by a Basal Plus (SSI) routine

• Basal Plus controls hyperglycemia = Basal Bolus, and better than a SSI with Insulin R

• Concern about hypoglycemia risk in basal bolus/basal plus.o Assumption is risk is low and outweighed by risks of

hyperglycemia with SSI• Evidence?


CONTINUE pre-hospital diabetes regimen if

appropriate, otherwise …

USE insulin as the treatment of choice

DO NOT use sliding scale insulin alone

DO use BASAL + BOLUS + CORRECTION insulin

regimen

AVOID hypoglycemia

2013In-hospital Management Checklist


Recommendation 2

2. For hospitalized patients with diabetes treated with

insulin, a proactive approach that includes basal,

bolus, and correction (supplemental) insulin,

along with pattern management, should be used to

reduce adverse events and improve glycemic

control, instead of the reactive sliding-scale

insulin approach that uses only short- or rapid-acting

insulin [Grade B, Level 2]


3. For the majority of non critically ill patients treated

with insulin, pre-meal BG targets should be 5.0 to

8.0 mmol/L in conjunction with random BG values

<10.0 mmol/L, as long as these targets can be

safely achieved [Grade D, consensus]

4. For most medical/surgical critically ill patients

with hyperglycemia, a continuous IV insulin

infusion should be used to maintain glucose levels

between 8.0-10.0 mmol/L [Grade D, consensus]

2013

2013

Recommendations 3 and 4


5. To maintain intraoperative glycemic levels between

5.5-10.0 mmol/L for patients with diabetes

undergoing CABG, a continuous IV insulin infusion

protocol administered by trained staff, [Grade C, Level 3]

should be used

6. Perioperative glycemic levels should be maintained

between 5.0-10.0 mmol/L for most other surgical

situations, with appropriate protocol and trained staff

to ensure safe and effective implementation of

therapy and to minimize the likelihood of

hypoglycemia [Grade D, Consensus]

2013

Recommendations 5 and 6


7. In hospitalized patients, hypoglycemia should be

avoided:

– Protocols for hypoglycemia avoidance, recognition

and management should be implemented with nurse

–initiated treatment, including glucagon for severe

hypoglycemia when IV access is not readily available [Grade D, consensus]

– Patients at risk of hypoglycemia should have ready

access to an appropriate source of glucose (oral or

IV) at all times, particularly when NPO or during

diagnostic procedures [Grade D, Consensus]

2013Recommendation 7


8. Healthcare professional education, insulin

protocols and order sets may be used to improve

adherence to optimal insulin use and glycemic

control [Grade C, Level 3]

9. Measures to assess, monitor, and improve glycemic

control within the inpatient setting should be

implemented, as well as diabetes-specific

discharge planning [Grade D, Consensus]

2013Recommendation 8 and 9


CONTINUE pre-hospital diabetes regimen if

appropriate, otherwise …

USE insulin as the treatment of choice

DO NOT use sliding scale insulin alone

DO use BASAL + BOLUS + CORRECTION insulin

regimen

AVOID hypoglycemia

2013In-hospital Management Checklist

Question• 55 yr old person with Type 2 DM on

oral agents (metformin and gliclazide) who will be NPO for an indefinite period of time.

• What are your options for in hospital treatment?

DM2: NPO on Gliclazide and Metformin

What do you want to avoid

• In order of importance?oSevere hypoglycemic eventoDKAoSymptomatic hypo/hyperglycemiaoPersistent hyperglycemiao The “ready for discharge except

requiring high doses of sliding scale insulin and has no long term diabetes management plan” syndrome

• Hold Oral agents when NPO

Insulin Strategies• Basal Bolus

o Scheduled bolus inappropriate if NPOo Risk of hypoglycemia

• Basal Plus (SSI)o Reasonable

• Basal dose ~0.1-0.25 U/kg (half of a total estimated daily dose of ~0.2-0.5 U/kg)

• SSI aloneo Reasonable – IF TEMPORARY

• If very concerned about hypoglycemia, can use gentle DOSE FINDING sliding scale.

• REASSESS in 12-24 hours consider basal insulin

If Not NPO - Insulin• Basal Bolus

o Reasonable• Total daily dose ~0.2-0.5 U/kg/day

o 50% Basalo 50% Bolus (divided by 3 to be given at 3 meals)

• I would use gentle sliding scale option to start, but reassess often

• Basal Plus (SSI)o Reasonable

• 50% of total daily dose as basal• ~0.1-0.25 U/kg/day• Consider more aggressive sliding scale option

• Sliding Scale Aloneo Only if high concern for hypoglycemiao If requires sliding scale doses in first ~12 hours strongly

reconsider strategy

If Not NPO – Oral agents

• Discontinue Metformin if:o Liver failureo Heart Failureo Renal Failureo Radiocontrast dyeo Acidosis

• Usually discontinue gliclazide (sulfonylurea) re: hypoglycemiao Consider re-instituting if no hypoglycemia and clinically

stableo Renal/liver/cardiac function stableo Not expected to be NPOo Want to try transitioning off insulin before d/c

Rational Sliding Scale• Reassess DAILY!

o If no or very few sliding scale doses sugars are <10 and no change required.

o If sliding scale is being used blood sugars are >10

• i.e. add OHA, add Basal, premix or MDI insulin

• Unless expect insulin requirements to decrease

Ac Breakfast

Ac Lunch Ac Supper qhs

13 – 4 Units

11 – 2 Units

17 – 8 Units

13 – 4 Units

10 – 0 Units

15 – 6 Units

Rational Sliding Scale• Reassess DAILY!

o In addition to assessing need for DM mgmt plan assess scale

• If constantly increasing and very high sugar then consider tightening scale

• If there are BGs <6 reassess scaleo Risk of hypos – consider loosening

• If there are BGs less than 4 decrease insulino Scale, scheduled, OHAs or a combination

acBreakfast

acLunch acSupper Bedtime

9 – 0 Units 12 – 2 Units

14 – 4 Units

18 – 8 Units

13 – 4 Units

16 – 8 Units

Consider DM1 made NPO

• Home insulin lispro 6/6/8 U and glargine 20 U

• Options?o IV insulin infusion = “Right” answero Glargine (usual, slight decrease, slight increase?) + scale if

sugars stable/easy to manageo Can stabilize with IV insulin infusion then when stable

transition to basal insulin based on requirements• E.g. add up 24 hour insulin requirement and deliver slightly

less as basal SQ + corrective scale for highs (remember may be insulin sensitive if requirements are low)

• Bottom line – DO NOT interrupt insulin delivery!o Sliding scale only is WRONG!

Approach to Hospitalized Patient with severe insulin

resistance

• J Clin Endocrinol Metab Sept 2011

Causes of insulin resistance in hospitalized patients

• Stress response• Obesity• Electrolyte disturbance: low K/Ca/Mg or high Ca• Feeds• Fatty emulsion eg. Propofol• Steroids/Tacrolimus/Sirolimus• Anesthetic Agents: volatile agents• Hormonal agents: octreotide, leuprolide, bicalutamide• Hormonal disorders: Cushing’s Syndrome,

Acromegaly, Hyperaldosteronism, Pheochromocytoma

Approach to Patient• Rule-out pseudo-resistance

o Check IV bag, tubing, IV site

• Review medications• Assess for concurrent diseases• Check electrolytes• Check if dextrose is used• Assess feeds

Case• 62 Male DM2 on 30/70 20 scB, 30acS at home.• Liver transplant• NPO on TPN

• Sliding scale post opo 2 U for 10, 4 for 13, 6 for 16…

Ac Breakfast

Ac Lunch Ac Supper qhs

18 – 6 Units

17 – 4 Units

23– 10 Units

19– 8 Units

14– 4 Units 24– 10 Units

21 – 10 Units

• If patient receiving SCo Consider change to IV insulin infusiono SC insulin may be poorly absorbed due to

edema poor perfusion etc

Feeds/TPN• May consider adding regular insulin

to TPN bago Will decrease risk of hypoglycemia if TPN heldo Max dose 50% of daily requirement of insulin

• Change feed to enteral feeds• Decrease or hold TPN with

consultation • Decrease Intralipid

o Changing from FFA infusion to soybean fat

Transition from IV to SC

• Patient on and staying on continuous feeds?

• IV insulin 3-5 U/hr over last 24 hours

Patient on and staying on continuous feeds

• Requirement for Basal and Supplemental Insulino Estimates 24hr insulin requirements from the IV infusion

(eg. units/hr x 24 hrs)o Options:

• 1/3 dose as NPH q8h• ½ dose as glargine or detemir q12h• Full dose as glargine or detemir q24h

• Overlap IV with SC for 3 hrs; sorter if glucose falls < 5.5 mmol/L

• Change BG checks to q4h once IV is off

• Add fast acting analog or regular insulin q4h

• Reassess and adjust


• Currently on continuous feeds with plans to stop and advance diet?

• On 3-5U/hr IV

Currently on continuous feeds with plans to stop and advance

diet• Requirement for Basal, Bolus and

Supplemental insulino Stop feeds while continuing with the IV infusiono After 4-5 hrs estimate basal requirements

• New rate while off feeds eg. 2 units/hr • ~24hr req 48 units

o Options• Give entire basal dose as once daily glargine or detemir or

use split dosing half in the morning, half at HS• Use NPH: 2/3 ACB and 1/3 evening or 50:50 split

• Estimate requirement for mealso Give fast acting analog or regular using a CHO ratio with

meals, if previous ratio unknown start with 1:15; if resistant use 1:7 1:5

o Use fixed dose approx 50% of basal insulin dose divided for each meal

• (units of basal/3 = units for each meal)o If limited intake may need small doses with adjustment as

intake improves

• Overlap IV insulin• Blood glucose checks AC meals and HS,

consider 3 AM checks


• Currently on continuous feeds with plan for intermittent or overnight feeds?

• On 3-5U/hr IV

Currently on continuous feeds

with plan for intermittent or

overnight feeds• Scheduled overnight feeds

o Calculate 24hr requirements as previouslyo At initiation of feeds: administer NPH in the

evening with additional 5-10 units of fast acting analog or regular insulin

o Check BG at 3AM and at the end of the feedso Adjust as requiredo If patient eating during the day assess BG

levels and treat if required

• If bolus feedsoAdd fast acting insulin at the time of

planned feedsoBase dose on CHO count and use a ratio

or fixed dose insulin

Steroids• May need additional insulin• NPH may be used in the AM when steroids

are given and adjusted as the dose of steroids is tapered

• Meal time insulin may also need to be increased for 4 – 8 hrs after the steroid is given

• Multiple doses of dex have a long T1/2

Take Home Messages• Safety first

o Avoid lows and significant highso Consider whether to continue or stop orals

• Insulin Strategyo Basal +/- Boluso Almost never should use Sliding scale alone

• Reassess and adjust• Plan for discharge

o When medically stable consider• Taper insulin/re-introduce orals• Plan for discharge on insulin with appropriate education

and follow up

inpatient glycemic management: time to shed our scales? deric morrison oct. 2014

Documents

hours o

causal o

common slide

hospital hyperglycemia

metaanalysis slide

acute ilness slide

admission hyperglycemia

basal insulin