Transcript Inpatient Glycemic Management in Non Critically Ill patients

Inpatient Glycemic
Management:
Time to shed our scales?
Deric Morrison
Oct. 2014
Objectives
• At the end of this presentation you will:
1.
2.
3.
Understand the current guidelines for inpatient glycemic
management.
Know the evidence that supports these guidelines.
Have an approach to managing inpatients with
hyperglycemia.
A word about Type 1 DM
• ALWAYS NEED basal insulin.
• Options:
o
o
o
o
Intermediate (NPH) SQ insulin q8-24hours
Long-acting (glargine/detemir) SQ insulin q12-24h
Insulin pump basal rate
Intravenous Insulin Infusion
Why Do We Care?
• Both Hyper and Hypo -glycemia are
associated with ↗ mortality and morbidity inhospital.
• There has been little evidence to guide
appropriate glycemic targets or glycemic
management strategy in non-critically ill
inpatients.
In-hospital Hyperglycemia is Common
•
Approximately 1/3 of
in-patients have been
found to have
hyperglycemia
•
Many have preexisting diabetes prior
to admission
Hyperglycemia
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What do you want to
avoid
• In order of importance?
o Severe hypoglycemic event
o DKA
o Symptomatic hypo/hyperglycemia
o Persistent hyperglycemia
• Complications (association vs. causal)
o The “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?
• Higher
o Stress/concomitant illness
o Nutrition (TPN, tube feeds, IV dextrose)
o Drugs (steroids)
• Lower
o Nutrition (diet, portions, NPO)
o Renal failure
o Liver failure
o Severe illness
Hyperglycemia and Acute Ilness
Hyperglycemia
Increased stress
hormones, use of
glucocorticoids,
decreased level of
activity
Decreased
immune
function, wound
healing,
increased
oxidative stress
Acute Illness
Inzucchi SE. NEJM 2006;355;1903
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Adverse Effects of Hyperglycemia
Hyperglycemia
Increases risks
of postoperative
infections and
delirium
Prolonged
hospital stay,
resource
utilization
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Increased renal
dysfunction and
renal allograft
rejection in
transplant
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 – 2011
o 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 discharge
o 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 outcomes
o Small studies
o 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 combination
o No significance
o 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.
sepsis
infx
Kansagara D et al. Ann Intern Med 2011;154:268-282
©2011 by American College of Physicians
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?
Cases
In-hospital Glycemic Targets
Patient Type
Non-critically ill
Glucose Target
(mmol/L)
Therapy of
choice
Fasting 5-8
Pre-hospital
regimen OR
basal-boluscorrection
Random <10
Critically ill
CABG intraop
Other periop
8-10
IV insulin infusion
5.5-10
IV insulin infusion
5-10
As appropriate
CABG = coronary artery bypass graft; IV = intravenous; Intraop = intraoperative;
periop = perioperative
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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
Recommendation 1
1. Provided that their medical conditions, dietary
intake, and glycemic control are acceptable, people
with diabetes should be maintained on their prehospitalization oral anti-hyperglycemic agents or
insulin regimens [Grade D, Consensus]
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Use BASAL + BOLUS + CORRECTION
Insulin
BOLUS + CORRECTION
In-hospital circumstances may
warrant temporarily holding
other antihyperglycemic
medications (eg. renal or
hepatic impairment)
Insulin = treatment of choice
BASAL
Breakfast
Lunch
Dinner
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BASAL + BOLUS +
CORRECTION
Sliding Scale Alone is Inefficient
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
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
Queale WS. et al. Arch Int Med 1997;157
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Sliding Scale Insulin Alone Results in
Variable Glucose Control
BG (mmol/L)
16.5 What do you do?
What do you do?
+6 U
14.0 +4 U
Sliding Scale alone
10.0
6.0
6.0
4.0 What do you do? What do you do?
0U
0U
Breakfast
Lunch
Dinner
Bolus insulin QID
QID: four times daily; SSI: sliding-scale insulin; BG: blood glucose
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3.0
Bedtime
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
BASAL + BOLUS + CORRECTION Results in
Smoother Glycemic Control
6+2 U
Correctional Insulin AC meals
What do you do?
12.0
BG (mmol/L)
Bolus insulin
(U)
<4
Call MD
4.1 – 10.0
0
10.1 – 13.0
2
6.0
13.1 – 16.0
4
18 U
16.1 – 19.0
6
> 19.0
Call MD
10.0
6+0 U
What do
you do?
What do
you do?
6.0
4.0
6.0
What do you do?
6+0 U
Breakfast
6U
Lunch
Dinner
6U
6U
ROUTINE Bolus insulin
Bedtime
Basal
insulin
Routine Basal
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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 basalbolus with glargine + glulisine.
• Admission BG = 12.7, A1c = 8.8%
Scheduled Dose
Sliding scale
Sliding
scale/Supplemental doses
7.8 – 10
14.4 – 16.7
>22.2
Comment on doses
• Scheduled routine dosing
o 0.4 – 0.5 Units/kg/day
o 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
13.3
10
5.6
Rabbit 2 Surgery 2011
• Similar to Rabbit trial, similar glycemic results.
Basal-Bolus (BBI) Regimen Achieves Better
Control than Sliding Scale (SSI) Alone
RABBIT 2
RABBIT 2 Surgery
Blood glucose (mmol/L)
13.3
13.3
*
12.2
*
11.1
11.1
*
*
¶
SSI
¶
10.0
¶
10.0
ŧ
¶
8.9
SSI
*
ŧ
†
†
8.9
7.8
7.8
6.7
*p < 0.01; ¶p < 0.05.
*p < 0.001, ŧp = 0.02, †p = 0.01
BBI
BBI
6.7
5.6
Admit 1
2
3
4
5
6
7
8
9
10
Duration of treatment (days)
Adapted from: Umpierrez GE, et al. Diabetes Care 2007;30:2181-86.
Adapted from: Umpierrez GE, et al. Diabetes Care 2011;34:256-61.
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Randomi 1
-zation
2
3
4
5
6
7
8
Duration of treatment (days)
9
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].
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%
• Hypoglycemia
o Less than 3.8
• Significantly less in SSI
o Less than 3.3
• Trend to less in SSI
o 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?
In-hospital Management Checklist
2013
 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
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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]
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Recommendations 3 and 4
3. For the majority of non critically ill patients treated
with insulin, pre-meal BG targets should be 5.0 to
2013 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
2013
infusion should be used to maintain glucose levels
between 8.0-10.0 mmol/L [Grade D, consensus]
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Recommendations 5 and 6
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
2013
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]
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Recommendation 7
2013
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]
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Recommendation 8 and 9
2013
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]
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In-hospital Management Checklist
2013
 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
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Copyright © 2013 Canadian Diabetes Association
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?
o Severe hypoglycemic event
o DKA
o Symptomatic hypo/hyperglycemia
o Persistent hyperglycemia
o 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 NPO
o 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 alone
o 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% Basal
o 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 Alone
o Only if high concern for hypoglycemia
o If requires sliding scale doses in first ~12 hours strongly reconsider strategy
If Not NPO – Oral agents
• Discontinue Metformin if:
o
o
o
o
o
Liver failure
Heart Failure
Renal Failure
Radiocontrast dye
Acidosis
• Usually discontinue gliclazide (sulfonylurea)
re: hypoglycemia
o
o
o
o
Consider re-instituting if no hypoglycemia and clinically stable
Renal/liver/cardiac function stable
Not expected to be NPO
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
acBreakfast
acLunch
acSupper
Bedtime
9 – 0 Units
12 – 2 Units
14 – 4 Units
18 – 8 Units
13 – 4 Units
16 – 8 Units
• If there are BGs <6 reassess scale
o Risk of hypos – consider loosening
• If there are BGs less than 4 decrease insulin
o Scale, scheduled, OHAs or a combination
Consider DM1 made NPO
• Home insulin lispro 6/6/8 U and glargine 20 U
• Options?
o IV insulin infusion = “Right” answer
o Glargine (usual, slight decrease, slight increase?) + scale if sugars
stable/easy to manage
o 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 op
o 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 SC
o Consider change to IV insulin infusion
o SC insulin may be poorly absorbed due to
edema poor perfusion etc
Feeds/TPN
• May consider adding regular insulin to
TPN bag
o Will decrease risk of hypoglycemia if TPN held
o 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 Insulin
o 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
Transition from IV to SC
• 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 insulin
o Stop feeds while continuing with the IV infusion
o 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 meals
o 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
Transition from IV to SC
• 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 previously
o 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 feeds
o Adjust as required
o If patient eating during the day assess BG levels
and treat if required
• If bolus feeds
o Add fast acting insulin at the time of
planned feeds
o Base 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 highs
o Consider whether to continue or stop orals
• Insulin Strategy
o Basal +/- Bolus
o 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