Near-Target Caloric Intake in Critically Ill Medical-Surgical Patients

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Near-Target Caloric Intake in Critically Ill Medical-

Surgical Patients Is Associated With Adverse

OutcomesYaseen M. Arabi, et.al.JPEN J Parenter Enteral Nutr 2010

34

MarniarPembimbing :

dr. Agussalim Bukhari, M.Med., Ph.D, SpGK

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ABSTRACT

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Background

The objective of this study was to determine whether caloric intake independently influences mortality and morbidity of critically ill patients.

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MethodsThe study was conducted as a nested cohort study within a randomized controlled trial in a tertiary care intensive care unit (ICU). The main exposure in the study was average caloric intake/target for the first 7 ICU days.The primary outcomes were ICU and hospital mortality. Secondary outcomes included ICU-acquired infections, ventilator-associated pneumonia (VAP), duration of mechanical ventilation days, and ICU and hospital length of stay (LOS).

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MethodsThe authors divided patients (n = 523) into 3 tertiles according to the percentage of caloric intake/ target: tertile I <33.4%, tertile II 33.4%–64.6%, and tertile III >64.6%.To adjust for potentially confounding variables, the authors assessed the association between caloric intake/target and the different outcomes using multivariate logistic regression for categorical outcomes (tertile I was used as reference) and multiple linear regression for continuous outcomes.

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ResultsTertile III was associated with higher adjusted hospital mortality, higher risk of ICU-acquired infections, and a trend toward higher VAP rate.

Increasing caloric intake was independently associated with a significant increase in duration of mechanical ventilation, ICU LOS, and hospital LOS.

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ConclusionsThe data demonstrate that near-target caloric intake is associated with significantly increased hospital mortality, ICU-acquired infections, mechanical ventilation duration, and ICU and hospital LOS.Further studies are needed to explore whether reducing caloric intake would improve the outcomes in critically ill patients.

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INTRODUCTION

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MALNUTRITIONcommon problem in ICU

patients

associated withincreased morbidity and

mortality

Nutrition support has become an

integral component of critical care

Several studies have demonstrated improved patient outcomes with early nutrition

support and with achieving the target caloric dose

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On the other hand…CALORIC RESTRICTION

extends life span in a variety of species

improves biomarkers of longevity in humans

probably related to :• reduction in metabolic rate and oxidative stress • improvement in insulin sensitivity• modification of cardiovascular risk• alterations in neuroendocrine and sympathetic

nervous system function

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hypercatabolic state

augmented oxidative stress

insulin

resistance

CRITICAL ILLNESS

Some researchers recommend the provision of reduced energy to avoid

accentuating these adaptive or maladaptive

responses to stress

supported by someevidence

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Therefore…

it remains unclear what constitutes an appropriate dose of caloric intake for

critically ill patients

Professional societies recommended achieving

nutrition targets early in the course of critical illness,

although such a recommendation is not

based on strong evidence

The purpose of this study was to determine whether the dose of caloric intake independently influences

the mortality and morbidity of critically ill

patients

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METHODS

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Setting

a nested cohort study of all patients (n = 523)

who were enrolled in a RCT that compared intensive insulin therapy to conventional

insulin therapy

January 2004 - March 2006

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Nutrition

•The caloric target was estimated by a dietitian using the Harris-Benedict equation and adjusting for stress factors.•Protein target was calculated as 0.8–1.5 g/kg based on the patient condition and underlying diseases

Prescribed by the treating intensivists

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Data Collectionpatients’

demographicsAPACHE II score

admission category

vasopressor therapy

BG on admission

history of diabetes

mechanical ventilation

serumcreatinine

daily dose of insulin

average BG levels

daily total caloric intake

caloric intake/targ

et

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Data Collection

•ICU mortality•Hospital mortality

primary endpoint

s

•Nosocomial infection•VAP•Duration of mechanical ventilation•ICU and hospital LOS

secondary endpoints

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Statistical Analysis

SAS P values (x² test)

ANOVAmultivariate

logistic regression

multiple linear

regression

To discern whether there was a dose-effect relationship between the caloric intake/target and mortality, the

authors further stratified patients into 10 deciles and evaluated the association with the different outcomes

considered in this study.

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RESULTS

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Patient Characteristics

40% of patients were diabetic

83% were admitted for medical indications

85% were mechanically ventilated

APACHE II score was 22.8 ± 8.1

85% were mechanically ventilated

83% were admitted for medical indications

40% of patients were diabetic

APACHE II score was 22.8 ± 8.1

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Patient Characteristics

BMI, blood glucose on admission, and calculated caloric targets were

similar in the 3 tertiles

patients in tertile III required higher doses of insulin to maintain

target blood glucose level

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Outcomes

patients in tertile III had increased ICU mortality, hospital

mortality, ICU-acquired infections, VAP, mechanical

ventilation duration, and ICU and hospital LOS

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Outcomes

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Outcomes

25

Outcomes

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Outcomes

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Tabel 4

Tertile III

↑ hospital mortality

↑ ICU LOS↑ ICU-acq.inf

↑ hospital LOS

↑ VAP↑ duration

of mech.vent

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DISCUSSION

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THE MAIN FINDING : near-target caloric intake in critically ill

medical-surgical patients is associated with increased mortality as well as morbidity, including ICU-acquired infections, VAP

rate, duration of mechanical ventilation, and ICU and hospital LOS

Although there was universal agreement about the

importance of nutrition support to critically ill patients, considerable controversy exists

over the appropriate caloric dose, as different studies have yielded different

results

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Studies suggested that low caloric intake may

be detrimental and that higher caloric intake may be associated with improved

outcomes :• cumulative energy deficit was associated with longer ICU LOS, longer mechanical ventilation

duration, and more complications

Villet et al

• patients receiving <25% of prescribed energy requirements had higher risk for bloodstream

infection than other patients

Rubinson et al

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Studies suggested that low caloric intake may

be detrimental and that higher caloric intake may be associated with improved

outcomes :• Patients in the enhanced nutrition group had a trend

toward better neurologic outcome 3 months postinjury and fewer

overall complications, including infections

Taylor et al

• Patients in the intervention hospitals had a significantly

shorter hospital LOS and a trend toward reduced mortality

ACCEPT

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Evidence to support lowerthan-target :

• Moderate caloric intake was associated with better outcomes

in terms of mechanical ventilation duration, ICU LOS, and hospital mortality than higher levels of

caloric intake

Krishnan et al

• Patients who received lower calories had decreased ICU LOS, reduced duration of antibiotic therapy, and a trend toward

decreased mechanical ventilation duration

Dickerson et al

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Evidence to support lowerthan-target :

• Patients in the early feeding group had higher incidences of VAP and Clostridium difficile– associated diarrhea and longer

ICU and hospital LOS

Ibrahim et

al

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This study :

within this population, increasing caloric intake closer to target was associated with increasing mortality

and morbidity

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Several potential mechanisms :

nutrition support

hyperglycemia

requires

higher insuli

n dosin

gASSOCIATED WITH

WORSE OUTCOME

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Several potential mechanisms : ↑↑

enteral

feeding

↑↑ gastric

residuals

↑↑ risk of

aspiration

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Several potential mechanisms :

reduces oxidative stress

attenuatesinflammatory response

affects the cardiovascular risk profile

alters several neuroendocrine and sympathetic nervous system functions

CALORIC RESTRIC

TION

THESE MECHANISMS DURING CRITICAL

ILLNESS ISUNCLEAR AT

PRESENT

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The strengths & weaknesses of this study :

• the data extraction from an original prospective RCT

• the setting of a closed ICU with continuous coverage by critical care board-certified intensivists

• the nutrition assessment by full-time board-certified clinical dietician

STRENGTHS

• its being conducted in a single center• this study could not answer whether

patients should be “underfed” for a defined period of time or for the entire ICU stay

• the 3 tertile groups were different in their baseline characteristics

WEAKNESSE

S

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CONCLUSIONThis study demonstrated that near-target

caloric intake is ASSOCIATED with significantly increased hospital mortality,

ICU-acquired infections, mechanical ventilation duration,

and ICU and hospital LOSThere is a need for a large RCT to examine the effects of permissive underfeeding vs

eucaloric/hypercaloric diet and also to identify the appropriate caloric needs

for critically ill patients

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TELAAH KRITIS JURNAL

Near-Target Caloric Intake in Critically Ill Medical-Surgical Patients Is Associated

With Adverse Outcomes

Yaseen M. Arabi, Samir H. Haddad, Hani M. Tamim, Asgar H. Rishu, Maram H. Sakkijha, Salim H. Kahoul and

Riette J.BrittsJPEN J Parenter Enteral Nutr 2010 34: 280

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1. UMUMHAL YANGDINILAI

CHECK LIST PENILAIAN YA TIDAK

JudulMakalah

a. Apakah judul tidak terlalu panjang atau terlalu pendek ?

b. Apakah judul menggambarkan isi utama penelitian ?

c. Apakah judul cukup menarik ?d. Apakah judul menggunakan singkatan

selain yang baku ?

√Tdk ada singk.

Abstrak a. Apakah merupakan abstrak satu paragraf atau abstrak terstruktur ?

b. Apakah sudah tercakup komponen IMRAC (Introduction, Methods, Result, Conclusion) ?

c. Apakah secara keseluruhan abstrak informatif ?

d. Apakah abstrak lebih dari 200 kata dan kurang dari 250 kata?

Terstruktur

√ 241

45

Pendahuluan a. Apakah mengemukakan alasan dilakukannya penelitian ?

b. Apakah menyatakan hipotesis atau tujuan penelitian ?

c. Apakah pendahuluan didukung oleh pustaka yang kuat dan relevan ?

Metode a. Apakah disebutkan desain, tempat dan waktu penelitian ?

b. Apakah disebutkan populasi sumber (populasi terjangkau) ?

c. Apakah kriteria pemilihan (inklusi dan eksklusi) dijelaskan ?

d. Apakah cara pemilihan subyek (teknik sampling) disebutkan ?

e. Apakah perkiraan besar sampel disebutkan dan disebut pula alasannya?

f. Apakah perkiraan sampel dihitung dengan rumus yang sesuai ?

√d/w

46

g. Apakah observasi, pengukuran serta intervensi dirinci sehingga orang lain dapat mengulanginya ?

h. Apakah defenisi istilah dan variabel penting dikemukakan ?

i. Apakah ethical clearance diperoleh ?

j. Apakah disebutkan rencana analisis, batas kemaknaan dan power penelitian ?

√Tdk

dijelaskan

Hasil a. Apakah disertakan tabel deskripsi subyek penelitian ?

b. Apakah karakteristik subyek yang penting (data awal) dibandingkan kesetaraannya ?

c. Apakah dilakukan uji hipotesis untuk kesetaraan ini ?

d. Apakah disebutkan jumlah subyek yang diteliti ?

47

e. Apakah dijelaskan subyek yang drop out dengan alasannya ?

f. Apakah semua hasil di dalam tabel disebutkan dalam naskah ?

g. Apakah semua outcome yang penting disebutkan dalam hasil ?

h. Apakah disertakan hasil uji statistik (x2,t) derajat kebebasan (degree of freedom), dan nilai p ?

i. Apakah dalam hasil disertakan komentar dan pendapat ?

Tidak ada DO

Diskusi a. Apakah semua hal yang relevan dibahas ?

b. Apakah dibahas keterbatasan penelitian dan kemungkinan dampaknya terhadap hasil ?

c. Apakah disebutkan kesulitan penelitian, penyimpangan dari protokol dan kemungkinan dampaknya terhadap hasil ?

48

d. Apakah pembahasan dilakukan dengan menghubungkannya dengan teori dan hasil penelitian terdahulu ?

e. Apakah dibahas hubungan hasil dengan praktek klinis ?

f. Apakah disertakan kesimpulan utama penelitian ?

g. Apakah kesimpulan didasarkan pada data penelitian ?

h. Apakah disebutkan hasil tambahan selama diobservasi ?

i. Apakah disebutkan generalisasi hasil penelitian ?

j. Apakah disertakan saran penelitian selanjutnya, dengan anjuran metodologis yang tepat ?

√√

49

KHUSUSValidity

Apakah awal penelitian didefenisikan dengan jelas ?

Ya. “…was conducted between January 2004 and March 2006…”

Apakah desain penelitian dinyatakan dengan jelas ?

Ya. ”This was a nested cohort study…”

Apakah ada pembanding yang jelas ?

Ya. ” The authors divided patients (n = 523) into 3 tertiles according to the percentage of caloric intake/target: tertile I <33.4%, tertile II 33.4%–64.6%, and tertile III >64.6%..”

Apakah follow up pasien dilakukan cukup panjang dan lengkap ?

Ya. “…was conducted between January 2004 and March 2006…”

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Apakah faktor kausal dikemukakan ?

Ya. “…Therefore, it remains unclear what constitutes an appropriate dose of caloric intake for critically ill patients…”

Apakah kelompok-kelompok yang dibandingkan sebanding pada tahap awal ?

Tidak. “BMI, blood glucose on admission, and calculated caloric targets were similar in the 3 tertiles. Patients in tertile III had higher APACHE II scores and were more likely to be admitted for nonoperative reasons and to bemechanically ventilated. Although there was no significant difference in average blood glucose, patients in tertile III required higher doses of insulin to maintain target blood glucose level. Patients in tertile I received fewer calories from enteral feeding and propofol and more calories from intravenous glucose as compared to tertiles II and III.”

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ImportantApakah outcome/hasil dipaparkan secara jelas (hasil uji statistik dengan nilai p) ?

Ya, sebagaimana yang telah ditampilkan pada Tabel 2, 3 dan 4, dan Figure 1 dan 2.

ApplicabilityApakah pasien kita mirip dengan subyek yang diteliti ?

Ya, pada pasien yang di rawat di ICU.

Apakah bukti ini akan mempunyai pengaruh yang penting secara klinis terhadap kesembuhan pasien kita tentang apa yang telah ditawarkan/diberikan kepada pasien kita ?

Ya, pemberian kalori yang tepat pada pasien-pasien ICU akan menurunkan morbiditas dan mortalitas.

52

53

Outcomes

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Lancet 2009; 373: 1798–807

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In the hospital setting, a combination of factors aff ect the development of stress hyperglycaemia (fi gure 2). The mechanisms for this disorder probably vary with the patients’ underlying glucose tolerance, type and severity of disease, and stage of illness. The cause of hyperglycaemia in type 2 diabetes is a combination of insulin resistance and β-cell secretory defects. However, the development of stress hyperglycaemia is caused by a highly complex interplay of counter-regulatory hormones such as catecholamines, growth hormone, cortisol, and cytokines (fi gure 3).

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HPA axis

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