Sepsis, Severe Sepsis, and Septic Shock (Dr. J. Tavares ...

SEPSIS ,SEVERE SEPSIS AND SEPTIC SHOCK

2008 UPDATE

J.TAVARES,MD,FCCP,FAASM

Rivers E et al. N Engl J Med 2001;345:1368-1377

Protocol for Early Goal-Directed Therapy

• SEPSIS RESUSCITATION BUNDLE:• 1-Serum Lactate• 2-Blood Cultures• 3-Antibiotics within 3 hours/1 hr• 4-IVF • 5-CVP 8-12 or 12-15mmHg• 6-Scv02>70%

LACTIC ACID

• High Lactate levels due to liver failure.

• Cutoff value still 4mmol/L .• Rapid turnaround time (ABG

analyzer).

FLUID MANAGEMENT

• 1-Crystalloids comparable to Colloids(SAFE Trial:NEJM,2004)

• 2-May use Albumin in individuals with Albumin less than 4.

• 3- ?Hydroxyethyl starch(HES )

PENTASTARCH

• NEJM(358;2; jan 10/08)• Ringer’s Lactate vs Pentastarch• Mortality: no diference at 28

days(24.1% vs 26.7%) ; higher in the Pentastarch group at 90 days(33.9% vs 41.0%; P=0.09)

PENTASTARCH

• MORBIDITY:

• Higher rate of acute renal failure(22.8% vs 34.9%)

• Lower platelets count• More PRBC transfusions

Brunkhorst F et al. N Engl J Med 2008;358:125-139

Kaplan-Meier Curves for Overall Survival

CVP 8-12:?for how long

• Comparison of 2 fluid mngt strategies in ALI(nejm;354,2006

• 1000 Pts(500 conservative fluid mangt;497 liberal)

• No difference in 60 day mortality,but less lung injury, faster weaning and fewer days in ICU for conservative.

Rivers E et al. N Engl J Med 2001;345:1368-1377

Protocol for Early Goal-Directed Therapy

RBC Transfusion

• Controversies in RBC transfusion in the critically ill(chest/131/5/may,2007)

• TRICC trial(NEJM 1999;340)• Lack of benefit of RBC

transfusions:1-immune suppression(leukocytes);2-prolonged RBC storage

RBC TransfusionClinical Recommendations)• 1-general critically ill:Hb=7g/dl• 2-critically ill with septic shock(<6h):8-

10• 3-critically ill with septic

shock(>6h):7g/dl• 4-critically ill with chronic cardiac

disease:7g/dl• 5-critically ill with acute cardiac

disease:8-10g/dl

Sepsis management bundle• 1-Tight blood sugar control

• 2-Low dose steroids

• 3-Drotrecogin alfa

• 4-Plateau pressures<30cm H2O

• 5-Extubation readiness.

Intensive insulin therapy in the ICU• Leuven study(nejm;nov2001)• 1-BG<110 2-mortality reduced from 8% to

4.6%• 3-Severe hypoglycemia(<40): 0.8%

in the conventional group and 5.1% in the intensive treatment group.

• 4-Surgical ICU patients.

Van den Berghe G et al. N Engl J Med 2001;345:1359-1367

Kaplan-Meier Curves Showing Cumulative Survival of Patients Who Received Intensive Insulin Treatment or Conventional Treatment in the Intensive Care Unit (ICU)

IIT in the ICU

• Leuven 2(nejm 2006;354)• 1-Blood glucose 80-110• 2- patients staying in ICU for 3 or

more days: mortality decreased from 52.3% to 43%

• 3-Severe hypoglycemia(<40): 3.1% in the conventional group and 18.7% in the treatment group.

• 4-medical IICU patients.

IIT in the ICU

• VISEP studies and Glucocontrol studies both in Europe(stopped because of increased risk of hypoglycemia).

• Both criticized for not having enough number of patients.

• Ongoing clinical trial by NIH(NICE-SUGAR) trial may have sufficient statistical power to address the above issues.

Brunkhorst F et al. N Engl J Med 2008;358:125-139

Kaplan-Meier Curves for Overall Survival

ITT in the ICU

• Glycemic control needs to be done safely.

• Use of computerized systems:

• Glucommander(can be loaded in a bedside computer,hanheld computer or nursing station computer

Glucommander

• 5 parameters: • 1-low end of target range for blood

glucose• 2-high end of target range for glucose• 3-the initial multiplier(adjusted for

insulin sensitivity)• 4-the maximum time interval between

measurements• 5-the insulin concentration



• 3-Drotrecogin alfa



Adrenal Insufficiency

• 2002:Annane et al(JAMA;288):299 patients-76% of nonresponders to cosyntropin stimulation test,on ventilator were randomized to hydrocortisone plus fludrocortisone for 7 days:13% reduction in mortality for those treated


• The CORTICUS trial(double-blinded,randomized,placebo-controlled multicenter European trial)( Goal:800 patients):

• Comparing hydrocortisone(50mg IV q6h for 5 days,taper to 50mg IV q12h for 3 days,then 50mg daily for 3 days)with placebo in septic shock.


• The retrospective Corticus cohort study(Critical Care Medicine:Volume 35(4) April 2007pp 1012-1018)

• Total of 562 patients(after exclusion:477pts were left)

Sprung C et al. N Engl J Med 2008;358:111-124

Enrollment and Outcomes

CORTICUS

• 1-Hydrocortisone did not improve survival or reversal of shock even in patients who did not respond to Cosyntropin test

• 2- Hydrocortisone hastened reversal of shock.



• 3-Drotrecogin alpha



Bernard G et al. N Engl J Med 2001;344:699-709

Proposed Actions of Activated Protein C in Modulating the Systemic Inflammatory, Procoagulant, and Fibrinolytic Host Responses to Infection

Drotrecogin Alfa

• 1-PROWESS trial:NEJM 2001;344:699-709.

• 2-ADDRESS trial:(APACHE<25 or only one organ dysfunction at baseline)-NEJM 2005;353:1332-1341.:no significant reduction in 28-day mortality.

• 3-ADDRESS one year follow-up(critical care medicine 2007;35:1457-1463):no increased risk of death or evidence of harm at 1 year.


Kaplan-Meier Estimates of Survival among 850 Patients with Severe Sepsis in the Drotrecogin Alfa Activated Group and 840 Patients with Severe Sepsis in the Placebo Group


Incidence of Serious Adverse Events

How do I do it(Resuscitation Phase)• Septic shock:• 1-IVF (up to 20cc/kg bolus to keep

MAP>=65• 2-if unable to achieve above,place

central line for CVP monitoring:keep CVP 8-12mmHg(12-15 if PPV).

• 3-If CVP goal achieved but MAP<65,start vasopressors

How do I do it(Resuscitation Phase)

• 4-NE,DA,PE,Vasopressin• 5-follow serial lactate levels 6-If MAP>65,check ScVo2(goal is

ScVo2>70%). 7-If ScVo2<70% and

Ht<30%,transfuse PRBC

How do I do it(Resuscitation Phase)

• 9-If Ht>30% and ScVo2 still <70%,start Dobutamine.

If ScVo2>70%,goal achieved

FLUIDS

• Normal Saline:500 cc boluses

• Albumin:25g iv x 3 doses

• Avoid Hespan

Vasopressin

• 0.01-0.04 units/mn IV

• Do not titrate.

How do I do it(Management Phase)

• STEROIDS• 1-No need for baseline cortisol

level or Cosyntropin test: If BP is not responding to IVF and Vasopressors after 1 to 2 hours,start HYDROCORTISONE at 50mg IV every 6 hours for 5 days(do not taper)

How do I do it(Management)• ACTIVATED PROTEIN C

• 2-APACHE>25 or at least two organs failure,start drotrecogin alpha.

• 3-If APACHE<25 or only one organ failure,may consider drotrecogin.

How do I do it(management)

• BLOOD GLUCOSE• 4-Tight Blood Sugar control: use

hospital protocol). Acceptable to keep blood sugar less than 150.

How do I do it(Management)

• Mechanical ventilation

• 5-keep plateau pressure below 30 cmH20

• 6-Spontaneous Awakening Trials• 7-Spontaneous Breathing Trials

Antibiotics

• USE HOSPITAL PROTOCOL

Goal for 2009

• DECREASE SEPSIS MORTALITY BY 25%

Material for Research

• 1-Procalcitonin

• 2-C Reactive Protein

• 3-Statins

Sepsis, Severe Sepsis, and Septic Shock (Dr. J. Tavares ...

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