23 taylor- endocrine in icu 0509jt

8/8/2019 23 Taylor- Endocrine in ICU 0509jt

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Endocrine Controversiesin the ICU

John M. Taylor, M.D.

University of California, San FranciscoAnesthesia and Critical Care Medicine


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Intensive Insulin Therapy

How intense should we be?


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Pathophysiology of hyperglycemia

LipshutzAK,GropperMA;Anesthesiology2009;110:408


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Risks associated with hyperglycemia

Impaired vasodilation Decreased nitric oxide synthase activity

Elevated cytokines and TNF leading toinflammation

Decreased phagocytosis and immunity

Increased incidence of critical caremyopathy and polyneuropathy


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Risks associated with hypoglycemia

Hypoglycemia produces brain injury Hypoglycemia results in increased levels of

norepinephrine / epinephrine and glucagon


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So is tight control good or evil?

Many studies Many outcomes


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Van den Berghe, et al, NEJM 2001

1548 Surgical ICU pts, ICU stay > 5 days

Non-blinded study

Randomized to 2 Insulin Treatment Groups:

Conventional: insulin gtt to maintain blood glucose180-200 mg/dl

Intensive: insulin gtt to maintain blood

glucose 80-110 mg/dl


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For patients in a medical ICU > 5days -

IIT group had 34% decrease in mortality

IIT group also has marked decrease in sepsis, acute

renal failure requiring dialysis, blood component

transfusions, ICU polyneuropathy, duration ofintubation and ICU stay.

IIT correlated with better ICU outcomes

But, question raised of insulin toxicity for pts in

ICU < 3 days


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Intention to treat 1200 pts, 767 pts enrolled

Multicenter, Medical ICU, pts >3 day in ICU

Same treatment groups as in VDB 2001 study

IIT group had significant decrease in morbidity due to

new ARF, shorter mechanical ventilation and shorter

ICU and hospital stay

Trends suggest improved mortality in IIT pts with ICU

stay > 3 days

However, found increased mortality in IIT pts with

ICU stay < 3 days


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Van den Berghe, et al, Summary

Hyperglycemia and hypoglycemia are linked toadverse outcomes

Glucose control with insulin does not affect

mortality in all critically ill patients IIT may be effective in lowering the risk of death

among surgical ICU patients

Differences in study outcomes are multifactorial

Further research is needed


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NICE-SUGAR 2009

6104 patients with expected ICU stay of >3

days randomized to 2 groups;intensive vs. conventional treatment

IIT showed an increase in mortality Blood glucose target < 180 mg/dl

(conventional) showed mortality benefit

No difference in ICU LOS, hospital LOS, needfor mechanical vent or dialysis

Significant increase in hypoglycemia in IIT


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NICE-SUGAR 2009

Intensive versus Conventional Glucose Control in Critically Ill Patients; NEJM 2009; 360;13:1283


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NICE-SUGAR 2009

Intensive versus Conventional Glucose Control in Critically Ill Patients; NEJM 2009; 360;13:1283


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IMADIM 2004 - UCSF Study

33 Medical & surgical critically ill pts 69% with DM & 31% without DM

136 mg/dl average BG level 119 median BG level

19 (0.08%) episodes of hypoglycemiatreated & without clinical harm


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Incidence of HypoglycemiaStudy Hypoglycemia

Conventional

Hypoglycemia

ITT

p value

VDB 2001 0.8% 5.1% p < 0.001

VDB 2006 3.1% 18.7% p < 0.001

VISEP 2005 * 2.1% 12.1% p < 0.001

GLUCONTROL 2006 * 2.4% 8.6% p < 0.001

NICE-SUGAR 2009 0.5% 6.8% p < 0.001

IMADIM 2004 (UCSF) n/a 0.08% n/a

* trial stopped early due to lack of efficacy and safety concerns due to severe hypoglycemia (blood glucose < 40 mg/dl)


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Things we dont know

Intensive insulin therapy (IIT) in diabetic vs.

non-diabetic patients

Timing of IIT (preop, intraop, postop)

Most appropriate target serum glucose How blood glucose should be measured

How should insulin be given

Is the benefit of IIT the result of giving insulin

or maintaining blood glucose < 150 mg/dl?


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Summary recommendations

Start IIT when glucose is >180 mg/dl Goal blood glucose < 150 mg/dl

Use IIT in a stepwise fashion to avoid

hypoglycemia

Be prepared to give more insulin to patients

with insulin resistance (type II diabetics) Hypoglycemia is a very real and dangerous

complication monitor frequently!


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Corticosteroids in the ICU

Should they be used in septic shock?

And a brief word on ARDS.


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History of corticosteroid therapyin the ICU

Ingle 1940s described biologic activity of steroids Hench 1949 tx of rheumatoid arthritis

1950 Nobel prize awarded to Kendall & Hench

Hahn 1951 suggested steroids for sepsis

1963 Renewed interest for treatment of sepsis

1970s Studies showed fluid and vasopressors superiorto steroid treatment

1975 Suggested for treatment of ARDS


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So, where are we now?


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Effects of steroid therapy

Pros

Decrease duration of mechanical ventilation

Decrease duration of significant hypotension

Reduction in inflammatory mediators

Cons

Impaired immunity

Increased glycemic levels

No proven morbidity or mortality benefits


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Regarding Sepsis:What do the studies say?

Annane study 2002

CORTICUS 2008

Surviving Sepsis Campaign 2008


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Annane, et. al., JAMA 2002

300 pts with septic shock

Randomized double-blind placebo-control

study after cortisol stimulation test

Low dose hydrocortisone + fludrocortisonevs. placebo for 7 days

Treatment group had significant decrease in 28

day mortality and duration vasopressors

NNT 7 pts to save 1 life


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Sprung, et.al., CORTICUS, NEJM, 2008

500 pts, multicenter, randomized, double-blind,

placebo-control

Low dose hydrocortisone vs. placebo

Primary end point 28 day mortality No difference in cortisol stim between groups

No difference in 28 day mortality

Steroid group had more rapid reversal of shock,

but also more superinfections and new sepsis


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Sprung, et.al., CORTICUS, NEJM, 2008


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Surviving Sepsis Campaign 2008

Steroids:

Consider IV hydrocortisone for adult septic shock when hypotensionis refractory to adequate fluid resuscitation and vasopressors. (2C)

ACTH stim test is not recommended to identify the subset of adults

with septic shock who should receive hydrocortisone. (2B) Hydrocortisone is preferred to dexamethasone. (2B)

Fludrocortisone is optional if hydrocortisone is used. (2C)

Wean steroids once vasopressors are no longer required. (2D)

Hydrocortisone dose should be 300 mg/day. (1A)

Do not use corticosteroids to treat sepsis in the absence of shock

unless the patients endocrine or corticosteroid history warrants. (1D)


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Steroids in the Treatment of

ARDS

A brief word


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Steroids in the Treatment of ARDS

Meduri 2008, review Correct use of prolonged glucocorticoid

treatment is associated with a substantial

and significant improvement in meaningfulpatient-centered outcome variables, and a

distinct survival benefit when treatment is

initiated before day 14 of ARDS

Meduri, et. al; Intensive Care Med 2008; 34: 61-69.


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Steroids in the Treatment of ARDS

Peter 2008 meta-analysis steroids in ARDS Some evidence exists for the efficacy of

steroid use after the onset of ARDS, without

notable side effects such as new infection.

Definitive treatment recommendations would

seem to depend on further randomized trials ormeta-analysis of individual patient data.

Peter, et. al.; Corticosteroids in the prevention and treatment of ARDS in adults: meta-analysis; BMJ 2008; 336: 1006.


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Recommendations, as I see them

For sepsis, no evidence that steroids arebeneficial. They may be appropriate as a

rescue medication if sepsis is associated

with life-threatening hypotension.

For ARDS, steroids may be beneficial for

ARDS that is lasting (>7 days). Therapy

should be continued for 14 21 days.


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thank you for your time

questions or comments:

[email protected]


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References

Agarwal Ret. al.; Do glucocorticoids decrease mortality in acute

respiratory distress syndrome? A meta-analysis.; Respirology. 2007

Jul;12(4):585-90.

Annane D, et. al.; Effect of treatment with low doses of hydrocortisone

and fludrocortisone on mortality in patients with septic shock.; JAMA.

2002 Aug 21;288(7):862-71.

Bailey GL, Strub RL.; Gram-negative septic shock: the new approach.;

South Med J. 1966 Nov;59(11):1327-32.

CORTICUS Study Group.; Sprung CL, et . al.; Hydrocortisone therapy

for patients with septic shock.; N Engl J Med. 2008 Jan 10;358(2):111-24.

Dellinger RP, et. al.; Surviving Sepsis Campaign: international

guidelines for management of severe sepsis and septic shock: 2008.;

Intensive Care Med. 2008 Jan;34(1):17-60.


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References

Lipshutz AK, Gropper MA.; Perioperative glycemic control: an

evidence-based review.; Anesthesiology. 2009 Feb;110(2):408-21.

Marik PE.; Critical illness-related corticosteroid insufficiency.; Chest.

2009 Jan;135(1):181-93.

Meduri GU, et. al.; Methylprednisolone infusion in early severe

ARDS: results of a randomized controlled trial.; Chest. 2007

Apr;131(4):954-63.

NICE-SUGAR Study Investigators; Finfer S, et. al; Intensive versus

conventional glucose control in critically ill patients.; N Engl J Med.

2009 Mar 26;360(13):1283-97. Richardson L, Hunter S.; Is steroid therapy ever of benefit to patients

in the intensive care unit going into septic shock.; Interact Cardiovasc

Thorac Surg. 2008 Oct;7(5):898-905. Epub 2008 Jul 21.


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References

Sprung CL, et. al.; The effects of high-dose corticosteroids in patients

with septic shock. A prospective, controlled study.; N Engl J Med.

1984 Nov 1;311(18):1137-43.

Van den Berghe G, et. al.; Intensive insulin therapy in the critically ill

patients.; N Engl J Med. 2001 Nov 8;345(19):1359-67.

Van den Berghe G, et. al.; Intensive insulin therapy in the medicalICU.; N Engl J Med. 2006 Feb 2;354(5):449-61.

Vincent JL, et. al.; Reducing mortality in sepsis: new directions.; Crit

Care. 2002 Dec.


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Grades of EvidenceGrade Explanation

1A Highqualitymetaanalyses,systematicreviewsofRCTs,orRCTswithaverylowriskof

bias

1B Wellconductedmetaanalyses,systematicreviewsofRCTs,orRCTswithalowriskofbias

1C Metaanalyses,systematicreviewsofRCTs,orRCTswithahighriskofbias

2A Highqualitysystematicreviewsofcasecontrolorcohortstudies

Highquality

case

control

or

cohort

studies

with

avery

low

risk

of

confounding,

bias,

or

chanceandahighprobabilitythattherelationshipiscausal

2B Wellconductedcasecontrolorcohortstudieswithalowriskof confounding,bias,or

chanceandamoderateprobabilitythattherelationshipiscausal

2C Casecontrolorcohortstudieswithahighriskofconfounding,bias,orchanceanda

significantrisk

that

the

relationship

is

not

causal

3 Nonanalyticstudies,e.g.casereports,caseseries

4 Expertopinion


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Grades of RecommendationGrade Explanation

A Atleastonemetaanalysis,systematicreview,orRCTratedas1A,anddirectly

applicableto

the

target

population;

or

AsystematicreviewofRCTsorabodyofevidenceconsistingprincipallyof

studiesratedas1B,directlyapplicabletothetargetpopulation,and

demonstratingoverallconsistencyofresults

B Abodyofevidenceincludingstudiesratedas2A,directlyapplicabletothe

targetpopulation,anddemonstratingoverallconsistencyofresults;or

Extrapolatedevidencefromstudiesratedas1Aor1B

C Abodyofevidenceincludingstudiesratedas2B,directlyapplicabletothe

targetpopulationanddemonstratingoverallconsistencyofresults;or

Extrapolatedevidence

from

studies

rated

as

2A

D Evidencelevel3or4;orExtrapolatedevidencefromstudiesratedas2B

23 taylor- endocrine in icu 0509jt

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