Acute Liver Failure: Supporting Other Organsiltseducation.com/documents/_Gropper.pdf · UCSF...

Acute Liver Failure:Supporting Other Organs

Michael A. Gropper, MD, PhDProfessor of Anesthesia and Physiology

Director, Critical Care MedicineUniversity of California San Francisco

UCSF Department of Anesthesia and Perioperative Care

Acute Liver Failure

• Circulatory abnormalities and shock• Management of renal failure• Management of respiratory failure


Circulatory Abnormalities

• Diagnosis of shock• Resuscitation Goals• Choice of vasopressors• Goal directed therapy


Differentiation of Shock

SepticCardiogenic

andHypovolemic

Cardiac output Normal or high Low

Pulse pressure Decreased Decreased

SVR Decreased Increased

Temperature Up or down Unchanged or

Peripheralperfusion

Increased Decreased

WBC count Up or down Unchanged

Infection Suspected ordocumented

none

A-V DO2 Decreased Increased


• Increase O2 delivery• Optimize O2 content of blood• Improve cardiac output and

blood pressure• Match systemic O2 needs with O2

delivery• Reverse/prevent organ hypoperfusion

Therapeutic Goals in Shock


First, fill the tank…


PAOP versus CVP


CV Mechanics in Shock

cardiogenic shocknormal

End Diastolic Pressure

Car

diac

Out

put

hypovolemic


Schierhout, BMJ 1998

Crystalloid or

Colloid?


• Randomized, prospective trial of 4%albumin versus normal saline for fluidresuscitation

• 6997 patients randomized• Primary outcome was 28-day mortality

NEJM 2004


Albumin vs SalineSAFE Study: NEJM, 2004

• Prospective, randomized study of 6997 patients• Objective need (one): tachycardia, hypotension,

low PCWP, low Urine Output• Normal saline vs 4% albumin for resuscitation• All other management the same• Primary outcome: 28d mortality• Secondary outcomes: Survival time, new organ

failures, duration of mechanical ventilation, ICULOS


Albumin vs SalineSAFE Study: NEJM, 2004


FDA Medwatch on Albumin


If still hypotensive after fluidresuscitation, start pressors


Best Pressor: Dopamine?• No evidence of increased renal perfusion

at low doses• Tachycardia more common than with

norepinephrine• May impair splanchnic blood flow• Stimulates vasopressin secretion• Does not confer clinically significant

protection against renal dysfunction


Best Pressor: Norepinephrine?

• No evidence of worsening renalfunction

• Less tachycardia than dopamine

• More rapid and effective BP control

• May increase splanchnic perfusion


Best Pressor: Norepinephrine?• Effect of norepinephrine compared with high dose

dopamine and/or epinephrine on the outcome ofseptic shock– Prospective, observational cohort– N=97– Norepinephrine ↓ mortality

• 62% vs 82%• P<0.001• RR=0.68• 95% CI, 0.54-0.87

Martin et al, CCM 2000


Best Pressor: Epinephrine?• 30 adult patients with septic shock• MAP ≤60 mm Hg• Norepinephrine and dobutamine vs

epinephrine to MAP >80 mm Hg• Results

– Similar effect on hemodynamics– Epinephrine

• ↑ Lactate• ↑ Lactate/pyruvate ratio• ↓ Gastric pHi

Levy et al, Intens Care Med, 1997


Best Pressor: Phenylephrine?• 13 patients with septic shock• Treated with fluids and either low-dose dopamine

or dobutamine, but remained hypotensive• Phenylephrine added

– 0.5 to 9 µg/kg/min– MAP >70 mm Hg

• Results– Increased MAP, SVR, CI, stroke index, DO2, VO2

and urine output– No change in HR– Dose 3.7 (0.4-9.1) µg/kg/min– Mean duration 65 hours

Gregory et al, CCM, 1991


What about vasopressin?


Vasopressin mechanism ofaction


• Vasopressin plus NE versus NE alone• Randomized trial of 48 patients• Hemodynamic outcomes measured


Vasopressin administration resulted in:reduced heart rateincreased MAPincreased CIincreased SVIincreased LVSWIdecreased NE requirements

But:no difference in mortalityno difference in organ

dysfunctionIncreased bilirubin in AVP

group

Dunser et al, Circulation 2003.


What are the therapeuticgoals?


What is the BP Target?

• BP targets are arbitrary• Autoregulation is lost below MAP 55-

60 mmHg• What is the data that we should target

a MAP of 65 mmHg?


Crit Care Med 2005; 33:780 –786


How Much BP is Enough?Blood Lactate (meq/l) Oxygen Consumption (ml/min/m2)

Oxygen Delivery (ml/min/m2) Oxygen Extraction Ratio (%)


How Much BP is Enough?Urine Output (ml/h) Creatinine Clearance (ml/min)

Crit Care Med 2005; 33:780-786


Optimizing oxygen delivery:Early goal-directed therapy


• Randomized, prospective trial of early, goal-directed resuscitation of patients with severesepsis

• Patients randomized to 6 hours of goal-directed therapy vs standard therapy

• 260 patients randomized• In-hospital mortality was 30.5% with goal-

directed therapy vs 46.5% with standardtherapy

Rivers et al, NEJM, 2001;345:1368-77

Central Venous Oximetry


Inotropic agents

Supplemental oxygen +endotracheal intubation and

mechanical ventilation

Transfusion of red cellsUntil hematocrit > 30%ScvO2

<70%

>70%

<70%

>70%

Vasoactive agentsMAP< 65 mmHg>90 mmHg

>65 and <90 mmHg

< 8 mmHgCrystalloid

Colloid

CVP

8-12 mmHg

YesHospital admission GoalsAchieved

No

Central venous andarterial catheterization

Sedation, paralysis(if intubated), or both

Rivers et al, NEJM, 2001;345:1368-77


Evidence: The Importance ofEarly Goal Directed Therapy

• Early goal-directedtherapy in patients withsevere sepsisproduced:– 42% ↓ in relative risk

of in-hospital and 28-day mortality(P=0.009, =0.01)

– 33% in relative risk ofdeath at 60 days(P=0.03)

• NNT to prevent 1 event(death) = 6 to 8

Rivers E, et al. N Engl J Med 2001;345:1368-77.


Management of Renal Failure


Impact of ARF on Mortality in Critically IllPatients

Metnitz et al, Critical Care Medicine, 2002


Decreasedeffective

Blood volume

Obstruction ofcollectingsystem

Prerenal Failure Intrinsic Renal Postrenal Failure

Acute Renal Failure

Vascular AcuteGlomerulo-nephritis

AcuteTubular Necrosis

Ischemic Nephrotoxic

AcuteInterstitialnephritis

EndogenousExogenous

HRS

HR

S


Acute Tubular Necrosis

Lamiere et al, Lancet: 2005


Hepatorenal Syndrome:Consensus Definition, International Ascites Club

Major Criteria• Acute/chronic liver disease with hepatic failure and portal hypertension• Low GFR: serum Cr > 1.5 mg/dl or 24 hour creatinine clearance < 40

cc/min• Absence of shock, ongoing infection, fluid loss, treatment with

nephrotoxins• No improvement in renal function following withdrawal of diuretics,

expansion of plasma volume with 1.5 L isotonic saline• Proteinuria < 500 mg/d and no ultrasonographic evidence of

obstructive uropathy or parenchymal disease

Minor Criteria• Urine volume < 500 cc/d• Urine Na < 10 meQ/d• Urine osm > Plasma osm• Urine RBC < 50/hpf• Serum Na < 130 meQ/L

Arroyo et al, Hepatology 23(1996): 164-176


Hepatorenal Syndrome

Type I:Doubling of serum Cr to > 2.5 mg/dL or a 50%reduction of initial GFR to less than 20 cc/minwithin 2 weeks

Type II:Moderate and stable reduction in GFR withouta rapidly progressive course


When To Initiate CRRT?

Drug overdose with dialysable toxinHyperthermiaPlasma sodium >155 mmol/L or <120mmol/LUremic pericarditisUremic neuropathy/myopathyUremic encephalopathyAzotemia: urea concentration >30mmol/LSevere acidemia: pH<7.0Hyperkalemia: potassium >6.5 mmol/LAnuria: urine output <50mL in 12hOliguria with <200 mL in 12h


Hemodialysis

Forni. NEJM, 1997Movement of small moleculesacross a selective membrane


Hemofiltration

Forni. NEJM, 1997

Movement of water and small moleculesacross a selective membrane, with selective fluidreplacment


IHD vs CRRT

Lamiere et al, Lancet: 2005


Continuous RenalReplacement Therapy


Slow removal of excess intra/extravascular volume


Convective solute clearance without dialysis


Dialysis with solute and nitrogen removal


Solute and nitrogen clearance, with fluid replacement


Does dialysis dose matter? Ronco et al, Lancet: 2000


Dialysis Dose and MortalityRonco et al, Lancet: 2000


Management of RespiratoryFailure


Respiratory Abnormalities in ALF

• Hepatopulmonary syndrome (HPS)

• Portopulmonary hypertension (PPH)

• Acute lung injury and the acuterespiratory distress syndrome (ALI/ARDS)


Hepatopulmonary vs Pulmonary Hypertension

Herve et al, Eur Resp J, 1998


Hepatopulmonary Syndrome

• Defined as:–Presence of liver disease–Hypoxemia on room air–Intrapulmonary vascular dilation


Portopulmonary Hypertension

• Defined as:– Histologic changes in the pulmonary

circulation leading to increased vascularresistance.

– Mean PAP > 25 mmHg, with PCWP > 15mmHg

– Evidence of portal hypertension


Definition of ARDS• Clinical syndrome characterized by:

– oxygenation defect (PaO2/FiO2<200mmHg)– bilateral infiltrates on CXR– No evidence of CHF

• PCWP < 18 mmHg

• Acute Lung Injury (ALI)– above, except (PaO2/FiO2<300mmHg)


Pressure-volume relationship

Paw

V

appropriateVt

excessiveVt

Pflex

protectiveVt

Normal lung

Consolidatedlung

PleuralEffusion

CT in Early ARDS


PaOPaO22 / FiO / FiO22

120

140

160

180

200

0 1 2 3 4Study Day

P/F

6 ml/kg

12 ml/kg

* *

ARDSnet, NEJM 2000

Median Organ Failure Free DaysMedian Organ Failure Free Days

*

*

*

*

= 6 ml/kg= 12 ml/kg

ARDSnet, NEJM 2000


Ventilator-Free DaysVentilator-Free Days

0

2

4

6

8

10

12

14

6 ml/kg 12 ml/kg

6 ml/kg

12 ml/kg

ARDSnet, NEJM 2000


Mortality Prior to HospitalMortality Prior to HospitalDischargeDischarge

0

10

20

30

40

50

Mortality (Percent)

6 ml/kg 12 ml/kg

P=0.0054

ARDSnet, NEJM 2000


Conclusions• Shock resuscitation is time-sensitive• Consider central venous oxygen saturation

as a resuscitation target• Continuous renal replacement therapy is a

powerful tool for achieving homeostasis inacute renal failure

• Use a protective ventilation strategy inpatients with acute lung injury

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