Evidence-based critical care – Update 2006

Joel Peerless MD3 January 2006

Intensivist shortage

Experts predict that as the US population ages, the shortage of intensivists will become increasingly acute

By 2020, the supply of intensivists will meet only 22% of the demand for their services

The old way…

Intern/junior resident (Dr. X) was taughta concept by his/her:Senior residentChief residentFellowAttending

Dr. X practiced what he was taught…

The old way…

Dr. X went on to become:A senior residentA chief residentA fellowAn attending

And taught the same concept to his/her junior resident, and so on and so on….

The old way…”Why do you do it that way??” “Well, I learned this from Dr. X” “We’ve always done it this way” “We have good outcomes” “I have an article to prove it” (more on

this later…)

The old way… dopamine

Dopamine in low doses activates dopamine receptors in the kidney

Renal blood flow is increased Urine output is increased (sometimes) The assumption, and teaching,

became…

The old way… dopamine

Dopamine is indicated for:Preventing renal failureTreating renal failureReversing renal vasoconstriction when vasopressors are usedPreventing renal failure during aortic and renal cross-clamping

Dopamine flowed like water (often better than urine) in ICUs worldwide

Evidence-based critical care

THERE NOW EXISTS A MORE “SCIENTIFIC” METHOD TO PROVIDE CARE…

The new way…

Try to adapt practice based on the quality of clinical studies that support the test or intervention – “Evidence-based”

A careful evaluation of existing studies Type of trial Number of centers Number of patients Quality of the study

Evidence-based concepts

The best study is:ProspectiveRandomizedDouble Blinded – not always possibleMulticenter

Meta-analyses evaluate a number of similar studies

Evidence-based concepts

Surviving Sepsis Campaign Guidelines for the Management of Severe Sepsis and Septic Shock

11 critical care societies - international Initial document: CCM March, 2004 Evidence-based review: CCM

supplement November, 2004

Grading system

Grade A: At least 2 large, randomized trials with clearcut results

Grade B: At least 1 large, randomized trial with clearcut results

Grade C: Small, randomized trials, uncertain results

Grading system

Grade D: Nonrandomized, contemporaneous controls

Grade E: Nonrandomized, historical controls; case series; uncontrolled studies; expert opinion

Evidence-based critical care

VENTILATOR MANAGEMENT OF ARDSVt settingsLevel of PEEPUse of steroids in “late” ARDS

Low tidal volume strategy

Barotrauma High pressure generated with flow of air

into lungs Volume trauma (volutrauma)

Overdistention of alveoli can lead to further lung damage

Low tidal volume strategy

Classic practice: Vt 10-15 cc/kg Hypothesis: lower Vt is protective of

alveolar damage and outcome in ARDS ARDS-net trial, NEJM, 2000 Comparison of 6 ml/kg vs 12 ml/kg 861/1000 patients Mortality 31% vs 39.8% Reduction in mortality of 22%

Low tidal volume strategy

When ARDS diagnosed, adjust Vt for ideal body weight 60 kg x .6 cc/kg = 360 cc

pCO2 will likely increase – permissive hypercapnea

GRADE B

PEEP levels in ARDS

ARDS-net, NEJM, 2004 Comparison of low and high PEEP in

ARDS 549 patients Low versus high PEEP algorithm All patients had low Vt No difference in ventilator free days or

mortality

Steroids for “late” ARDS

Fibroproliferation can occur after 5-7 days of ARDS

This inflammatory process may present with worsening oxygenation, fever and leukocytosis (infection may present with same signs)

Case series of steroids to minimize the late inflammatory fibroproliferation

Steroids for “late” ARDS

ARDS-net randomized placebo-controlled trial

Goal 200 patients over 6-8 years No value in use of steroids in “late”

ARDS

Other ARDS modalities

We no longer consider:Prone positionInhaled nitric oxideSurfactantLiquid ventilation

Evidence-based critical care

Glucose control in critically ill patients

Intensive insulin therapy

NEJM, 2001, single center study 1,548 surgical patients Randomized to tight vs non tight control 80-120 mg/dl vs 150 mg/dl ICU mortality 4.6% vs 8.0% 43% risk reduction

Intensive insulin therapy

50% decrease in BSI, ARF requiring RRT, critical illness polyneuropathy and transfusion requirement

Shorter duration of mechanical ventilation and ICU care

Less multiple organ failure

Intensive insulin therapy

Mayo Clin Proc, 2004 800 critically ill medical-surgical patients

in a community ICU Hospital mortality decreased Decreased ICU LOS, ARF, transfusion

requirement Most benefit in septic patients

Intensive insulin therapy

GRADE D based on original study, (randomized but single center, mainly surgical patients), likely upgrade to C

German study (600 patients) – negative Two large scale randomized trials

underway European study – 3500 medical/surgical

patients Australia/NZ – 4500 medical/surgical

patients

Evidence-based critical care

Activated protein-C in sepsis (Xigris)

RH Activated Protein C

Prowess Study Recombinant human activated protein C

worldwide evaluation in severe sepsis Randomized, double blinded, placebo

controlled 96 hour infusion of activated protein C

(APC) Endpoint: death at 28 days

RH Activated Protein C

Prowess study 1690 patients (840 placebo; 850 APC) Mortality 30% vs 24.7%, p=0.005 6.1% reduction of death Serious bleeding 2% vs 3.5%, p=0.06 Similar number of blood transfusions

RH Activated Protein C

Prowess study The difference in outcome was greatest in

patients with an APACHE score >25 Address study

PRCT of RHAPC in patients with APACHE <25

No improvement in outcome May be worse outcome in SURGICAL

patients with single organ dysfunction

RH Activated Protein C

Contraindications Internal bleeding, hemorrhagic CVA, CHI,

neurosurgical procedures, surgery within 12 hours

Many patients with abdominal sepsis require repeat explorations

The drug is expensive ($100/kg)

RH Activated Protein C

GRADE B for patients with severe sepsis, multiple organ dysfunction, with APACHE >25

“Dear doctor” letter from Eli Lilly re: surgical patients with single organ dysfunction

Evidence-based critical care

CORTICOSTEROIDS AND SEPTIC SHOCK

Corticosteroids and sepsis

Old teaching: don’t give septic patients high dose steroids

New thought: patients with septic shock who are unresponsive to pressor agents may have adrenal insufficiency

Corticosteroids and sepsis

Incidence of adrenal insufficiency 30-50% in critically ill patients 50-60% in patients with septic shock

Clinical presentation resistant hypotension hyponatremia, hyperkalemia

Low or “normal” serum cortisol level

Corticosteroids and sepsis

JAMA, 2002; multicenter, RCT, 300 patients Septic shock, vasopressor therapy A baseline cortisol level of <25 mcg/dl Corticotropin stimulation test (cortrosyn) An increase in serum cortisol of 9 mcg/dl after

corticotropin – “responders” Unable to increase serum cortisol 9 mcg/dl –

“nonresponders”

Corticosteroids and sepsis

Nonresponders randomized to placebo vs hydrocortisone 50 mg IV every 6 hours + fludrocortisone

Mortality improved in patients with adrenal insufficiency

Faster time to vasopressor withdrawal No difference in patients with adequate

corticotropin response

Corticosteroids and sepsis

Should low doses of corticosteroids be used in the treatment of septic shock?

GRADE C SSC guidelines suggest steroids in

pressor-dependent patients with low serum cortisol (don’t even bother with the cortrosyn stimulation)

Evidence-based critical care

PULMONARY ARTERY CATHETER USE IN THE ICU

PA catheter use in the ICU

Old practice: any unstable patient who didn’t respond to fluids or who had possible cardiac dysfunction; “we didn’t know where we were…”

Preoperative “optimization” of high risk patients

Old practices questioned: Connors, et al, JAMA, 1996

Editorial: “abandon PACs until PRCT”

PA catheter use in the ICU

JAMA, 2005 Meta-analysis, 13 RCTs, 5051 patients Use of PA catheter neither increased

overall mortality or hospital days, nor conferred benefit

Use of the PA catheter was associated with a higher use of inotropes and vasodilators

PA catheter use in the ICU

RCT in progress ARDS-net, 1000 patient goal FACTT Study: PRMCT of PAC vs CVP

for management of ALI and ARDS and PRMCT of “fluid conservative” vs “fluid

liberal” management of ALI and ARDS

Evidence-based critical care

EARLY GOAL-DIRECTED THERAPY IN SEPSIS

Early goal-directed therapy

“Standard” goals for sepsis (resuscitation) MAP >65 CVP 8-12 Urine output >0.5 cc/hr

Early goal-directed therapy

DO2 = Hgb (SaO2) x 1.34 x CI x 10 “Supranormal” goals for PAC (1980s)

CI > 4.5 L/min/m2

DO2I > 600 ml O2/min/m2

VO2I > 170 ml 02/min/m2

Fluids, blood, inotropes, pressors… We could measure our progress with a

calculator!!

Early goal-directed therapy

Supranormal goals disproven in established sepsis (NEJM x2)

Will this theory work if we get to the patient earlier?

Early goal-directed therapy

NEJM, 2001, Henry Ford Hospital 263 ED patients Control group: MAP, CVP, UO Protocol group: MAP, CVP, UO,

SCVO2 >70 Mortality 46.5 vs 30.5%, p=.009

Early goal-directed therapy

There IS value to optimizing cardiac output, oxygen delivery and SVO2 if you intervene early enough

(Is it really the SVO2 that makes the difference, or is it resuscitation??)

Evidence-based critical care

ANTIBIOTICS and INFECTION CONTROLWHO NEEDS TREATMENT AND FOR HOW LONGVENTILATOR ASSOCIATED PNEUMONIACATHETER-RELATED BACTERIAL STREAM INFECTIONC-DIFFICILE COLITIS

Who needs antibiotics?

Systemic inflammatory response syndrome (SIRS)

Fever means inflammation, not necessarily infection

Emergence of multiresistant bacteria Treating fever alone or fever + WBC

without a source of infection is usually not in the best interest of the patient

Duration of antibiotic coverage

Minimal data over duration of antibiotic usage for most infections Bacteremia – 2 weeks Endocarditis – 6 weeks

What about “double coverage” for pneumonia SPACE bugs: Serratia, Pseudomonas,

Acinetobacter, Citrobacter, Enterobacter VAP coverage was always 2 weeks

SICU antibiotic usage

Perioperative coverage – single dose or 24 hours of coverage

UTI – 5 days Sinusitis – 5-7 days Bacteremia – 10 days

Evidence-based critical care

VENTILATOR-ASSOCIATED PNEUMONIADIAGNOSISTREATMENTPREVENTION

Ventilator-associated pneumonia - diagnosis Classic teaching: Fever, WBC, purulent

sputum, + culture, infiltrate 75% of intubated patients are colonized

with GNB after 3 days in the ICU You could have bronchitis or sinusitis +

atelectasis, or pulmonary edema Endotracheal aspirate vs BAL

BAL samples give quantitative cultures

Ventilator-associated pneumonia - diagnosis Fever/WBC, + culture without purulent

sputum or CXR – NO ANTIBIOTICS Fever/WBC, purulent sputum or

changing CXR, + sputum culture → empiric therapy

Fever/WBC, purulent sputum or changing CXR, + sputum culture → BAL + empiric therapy

Ventilator-associated pneumonia treatment JAMA, 2003 PRCDBT, 51 French ICUs, 401 patients VAP treatment for 8 vs 15 days No excess mortality, recurrent infections,

ventilator days, ICU LOS with 8 day treatment

But, recurrence of VAP was higher with PSD

Ventilator-associated pneumonia prevention Subglottic suctioning of secretions

Additional suction port above the ETT cuff Some studies suggest decreased VAP Who will get them, will you risk changing

the tube?? Role of gastric contents

Gastric residuals: not shown to correlate with VAP (a major cause of poor nutrition)

Ventilator-associated pneumonia What is known

More likely from mouth contents than from regurgitation of stomach contents

Head of bed 30 degrees up is the only proven preventive technique!!

Early effective antibiotic therapy is essential !!

Start with broad-spectrum coverage, then taper antibiotics based on EA/BAL results

Catheter-related BSI

Prevention – what doesn’t work Changing lines every three days Performing wire changes Putting antibiotic solutions (goop) on the

site Antibiotic lock solutions

Catheter-related BSI

Prevention – what DOES work Subclavian site Prep: Chlorhexidine (not povidone) Barrier precautions: Hat, mask, gown,

gloves, FULL body drape Antiseptic coated catheters ($$$; beware

of hospital administrators) Management of stopcocks: alcohol prior to

injections, keep ports closed

C-difficile colitis

Related to indiscriminate antibiotic usage May occur with only a single dose of

antibiotics (even perioperative coverage) May require colectomy May be fatal A huge topic in the lay press and

certainly will be seized on by the legal community

Infection control techniques

We all have the power to limit the occurrence of hospital acquired infections

Hand washing is the most effective method of limiting hospital acquired infections

Infection control techniques

Soap and water Hand disinfectant solutions : Steris

product, Purell Remember: C-difficile toxin spores are

not killed by hand solutions; use soap and water

Wear protective gowns and mask when examining c-diff patients

EBM in perspective

EBM in perspective

We have very good data (A) DVT prophylaxis Stress ulcer prophylaxis Spontaneous breathing trials Preventive practices for CR-BSI

EBM in perspective

We have good data (B), but these studies can likely never be repeated Early goal-directed therapy in septic shock Activated protein-C for severe sepsis Low Vt in ARDS

EBM in perspective

We have good data (B) that will probably never get better despite further studies Crystalloids vs colloids, albumin Bicarbonate in acidosis

We are able to eliminate unproven or potentially unsafe practices NO for ARDS Prone positioning for ARDS

EBM in perspective

We practice with lots of E’s – these probably can’t ethically be studied Use of antibiotics early in sepsis Draining abscesses Giving fluids for hypovolemia Vasopressors in septic shock Mechanical ventilation in respiratory failure

EBM in perspective – the good

We know the quality of the data Development of consensus statements

ASA, SCCM, ACCP, EAST www.guideline.gov

Guidelines and protocols Keep us current and consistent in our care Allows ongoing monitoring of practices Educate our trainees

EBM in perspective – the bad Extending data to non-studied or non-

proven conditions:Low tidal volumes for all: There is no data that patients who do not have ARDS should be ventilated with low tidal volumesDaily breaks in sedation: It is not reasonable to break sedation in some patients: ARDS, elevated ICP, etc

EBM in perspective – the bad

Blanket referrals to EBM:PAC usage in critically ill patients: A PAC may still be useful in managing your patientThe anti-dopamine conspiracy: Lancet, 2000: 328 patients; 23 ICUs; no effect on renal dysfunction, LOS or mortality

EBM in perspective: the bad

There are patients with low urine output or impending renal failure secondary to low cardiac output who may benefit from the use of low dose dopamine

EBM in perspective – the scary

OUTCOMES RELATED TO EVIDENCE-BASED CARE WILL BE MONITORED AND WILL BECOME A MEASURE OF QUALITY AND POTENTIALLY A SOURCE OF MEDICOLEGAL LIABILITY

EBM in perspective – keep reading The data may change !! JAMA, July 13, 2005 Contradicted findings (16%)

Hormone therapy and CAD risk Vitamin E and CAD risk Vit A and breast cancer Monoclonal AB to endotoxin (HA1A) Nitric oxide in ARDS

EBM in perspective – keep reading Studies with initially stronger effects

(16%) Zidovudine in HIV Angioplasty vs TPA in AMI TPA in CVA CEA and risk reduction of CVA or death Acetylcysteine preventing contrast

nephropathy

EBM in perspective – reading the literature Cautious use of “the literature”,

“landmark” articles It’s easy to quote the last line of the

abstract LOOK FOR THE EDITORIAL

Comments on the quality and limitations of the study

“This study raises more questions than it answers”

“Large, randomized trials are needed”

Summary

We should use EBM consensus statements to keep our knowledge current

Reaching the highest rankings (grade A) may be limited by ethics, resource restrictions and marketing strategies

Be watchful for “new” data or negation of previously accepted data

Summary

Realize that the public is watching our adherence to practice guidelines

Accept the fact that external monitoring of evidence-based practices and outcomes will be standard in the future

Be proactive in maintaining high standards of care