Sepsis Management

SEPSIS

Steffen Rex Department of Anesthesiology University Hospitals Leuven steffen.rex@uzleuven.be

Sepsis Management

Dombrowskiy V Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: A trend analysis from 1993 to 2003. Crit Care Med 2007; 35:1244–1250

Epidemiology

Sepsis Management

Epidemiology: Current trends in incidence

Lagu T et al. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med 2012; 40:754–761

Sepsis Management

Germany: ~154.000 / year

Engel C et al. Epidemiology of sepsis in Germany: results from a national prospective multicenter study. ICM 2007; 33(4):606-18

Epidemiology: Prevalence

Sepsis Management

1 Angus DC et al; Crit Care Med 2001; 29: 1303-1310 2 Martin GS et al, N Engl J Med 2003;348:1546-54

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Epidemiology: Incidence in the USA

Sepsis Management

!  1,5 million patients with severe sepsis

Today

•  Increasing number of older patients

•  Life-sustaining technologies •  Invasive techniques and

procedures •  Nosocomial infections •  Antibiotic resistance

Future

Linde-Zwirble et al. Crit Care Med 1999; 27: A33 Opal und Cohen, Crit Care Med 1999; 27: 1608

Epidemiology: Incidence in the future

Sepsis Management

For comparison: Myocardial infarction: 4-10%

Epidemiology: Mortality

Engel C et al. Epidemiology of sepsis in Germany: results from a national prospective multicenter study. ICM 2007; 33(4):606-18

Sepsis Management

Epidemiology: Mortality USA vs. Europe

Levy MM et al. Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study. Lancet Infect Dis 2012;12: 919–24

Sepsis Management

Epidemiology: Current trends in severity / mortality

Lagu T et al. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med 2012; 40:754–761

Sepsis Management

"  Dysregulation of the immune response

"  Endothelial dysfunction: "  Capillary leak "  Vasoplegia

"  Dysregulation of the coagulation system

"  Cardiovascular Dysfunction: "  Relative/absolute hypovolemia "  Septic cardiomyopathy

"  Microcirculatory failure

"  Cytopathic hypoxia, endocrine dysregulation, ...

Pathophysiology: Hallmarks

Sepsis Management

Riedemann N. Novel strategies for the treatment of sepsis. Nature Medicine 2003

Vasodilation Endothelial Dysfunction Capillary Leakage DIC Cardiovascular Dysfunction Cytopathic Hypoxia Apoptosis

MODS

Failure of local control mechanisms

Sepsis: Pathophysiology

Sepsis Management

�Eine Sepsis liegt dann vor, wenn sich innerhalb des Körpers ein Herd gebildet hat, von dem aus konstant oder periodisch pathogene Bakterien in den Blutkreislauf gelangen, derart, daß durch diese Invasion subjektiv oder objektiv Krankheits-erscheinungen ausgelöst werden.�

Trias of Schottmüller: Source – Spreading – Systemic effect

H. Schottmüller, 1914

Diagnosis and Definition

Sepsis Management

SIRS (>2 of the following) " Temperature >38°C or < 36°C " HR > 90/min " Respiratory rate

> 20/min or PaCO2 < 33mmHg

" Leucocytes >12.000/mm3 or < 4000/mm3 or >10% immature forms

Infection Suspected or proven

Diagnosis and Definition

+

SEPSIS =

Sepsis Management

Infection Suspected/proven

SEPSIS +

Inflammation SIRS

+ Organ dysfunction

SEVERE SEPSIS

Diagnosis and Definition

Sepsis Management

Diagnosis and Definition: Organ Failure

Septic encephalopathy

Wer reitet so spät durch Nacht und Wind?

Es ist der Vater mit seinem Kind.

Er hat den Knaben wohl in dem Arm,

Er faßt ihn sicher, er hält ihn warm.

Mein Sohn, was birgst du so bang dein Gesicht? -

Siehst Vater, du den Erlkönig nicht!

Den Erlenkönig mit Kron� und Schweif? -

Mein Sohn, es ist ein Nebelstreif. -

„Du liebes Kind, komm geh� mit mir!

Gar schöne Spiele, spiel ich mit dir,

Manch bunte Blumen sind an dem Strand,

Meine Mutter hat manch gülden Gewand.�

Mein Vater, mein Vater, und hörest du nicht,

Was Erlenkönig mir leise verspricht? -

Sei ruhig, bleibe ruhig, mein Kind,

In dürren Blättern säuselt der Wind. -

„Willst feiner Knabe du mit mir geh�n?

Meine Töchter sollen dich warten schön,

Meine Töchter führen den nächtlichen Reihn

Und wiegen und tanzen und singen dich ein.�

Mein Vater, mein Vater, und siehst du nicht dort

Erlkönigs Töchter am düsteren Ort? -

Mein Sohn, mein Sohn, ich seh� es genau:

Es scheinen die alten Weiden so grau. -

„Ich liebe dich, mich reizt deine schöne Gestalt,

Und bist du nicht willig, so brauch ich Gewalt!�

Mein Vater, mein Vater, jetzt faßt er mich an,

Erlkönig hat mir ein Leids getan. -

Dem Vater grauset�s, er reitet geschwind,

Er hält in den Armen das ächzende Kind,

Erreicht den Hof mit Mühe und Not,

In seinen Armen das Kind war tot.

Sepsis Management

Diagnosis and Definition: Organ Failure

Ware LB and Matthay MA The Acute Respiratory Distress Syndrome.

NEJM 2000, 342: 1334-1349

Levy MM et al. Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study. Lancet Infect Dis 2012;12: 919–24

USA Europe

Sepsis Management

Diagnosis and Definition: Organ Failure

Schrier RW, Wang W Acute Renal Failure and Sepsis.

N Engl J Med 2004;351:159-69.

USA Europe

Levy MM et al. Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study. Lancet Infect Dis 2012;12: 919–24

Prerenal AKF

Renal AKF

Sepsis Management

Diagnosis and Definition

Dellinger RP et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012 Crit Care Med 2013; 41:580–637

Sepsis Management

Diagnosis and Definition

Infection Suspected/proven

SEPSIS

Inflammation +

+ Organ dysfunction SEVERE SEPSIS

+ Hypotension > 1h " SAP < 90mmHg " MAP < 70mmHg " Despite adequate fluid

resuscitation SEPTIC SHOCK

Sepsis Management

Sepsis Management: The Guidelines

: 2004

Goal: Decrease in sepsis mortality

by 25% in 5 years

Sepsis Management

Sepsis Management: SSC-Guidelines Initial Resuscitation

1. Protocolized, quantitative resuscitation of patients with sepsis-induced tissue hypoperfusion (defined as hypotension persisting after initial fluid challenge or blood lactate concentration ≥ 4 mmol/L).

Goals during the first 6 hrs of resuscitation: a) Central venous pressure 8–12 mm Hg (12-15mmHg in ventilated patients) b) Mean arterial pressure (MAP) ≥ 65 mm Hg c) Urine output ≥ 0.5 mL/kg/hr d) Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively (grade 1C).

2. In patients with elevated lactate levels targeting resuscitation to normalize lactate (grade 2C).

Sepsis Management

Sepsis Management: SSC-Guidelines Initial Resuscitation: MAP

Urinary !output (mL)! 49 +18! 56 + 21! 43 +13! .60/.71!

Capillary blood flow (mL/min/100 g)! 6.0 + 1.6! 5.8 + 11! 5.3 + 0.9! .59/.55!

Red Cell !Velocity (au)! 0.42 + 0.06! 0.44 +016! 0.42 + 0.06! .74/.97!

Pico2 (mm Hg)! 41 + 2! 47 + 2! 46 + 2! .11/.12!

Pa-Pico2 (mm Hg)! 13 + 3! 17 + 3! 16 + 3! .27/.40!

75 mm Hg!65 mm Hg! 85 mm Hg! F/LT!MAP

LeDoux et al. Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 2000; 28:2729-2732

Sepsis Management

Sepsis Management: SSC-Guidelines Initial Resuscitation

Howell et al. Occult hypoperfusion and mortality in patients with suspected infection.

Intensive Care Med (2007) 33:1892–1899

Pressure is not enough!!!

Sepsis Management

Sepsis Management: SSC-Guidelines Initial Resuscitation: ScvO2

Adequacy of DO2 (= CO * caO2)

DO2 ↓

O2-ER ↑

S(c)vO2 ↓

Diuresis ↓ Lactate ↑

Sepsis Management

Rivers E et al.

New Engl J Med 2001

345:1368-77

EGDT

Rivers E. et al. EARLY GOAL-DIRECTED THERAPY IN THE TREATMENT OF SEVERE SEPSIS AND SEPTIC SHOCK. N Engl J Med 2001;345:1368-77

ScvO2

PreSep™ Katheter

Sepsis Management

Mortality

49,2

Patients (%)

49,2 %

33,3 %

56,9 %

46,5 %

30,5 %

44,3 %

50 30 10 0

In-Hospital

28-days

60-days

*

*

*

Standard EGDT

Sepsis Management: SSC-Guidelines Initial Resuscitation: ScvO2

Rivers E. et al. EARLY GOAL-DIRECTED THERAPY IN THE TREATMENT

OF SEVERE SEPSIS AND SEPTIC SHOCK. N Engl J Med 2001;345:1368-77

Sepsis Management

CO = VO2 / avDO2

VO2 = CO · avDO2

CO = VO2

caO2 – cvO2

CO ≈ VO2

(SaO2 • Hb • 1,39) – (SvO2 • Hb • 1,39)

SvO2 ≈ VO2

HR • SV • Hb • 1,39 SaO2 -

Sepsis Management: SSC-Guidelines Initial Resuscitation: ScvO2: Limitations

Significantly decreased during anesthesia/sedation

S(c)vO2: reflects adequacy of oxygen delivery but: not a „poor man‘s CO-monitor“

Sepsis Management

Sepsis Management: SSC-Guidelines Initial Resuscitation: ScvO2: Limitations

Trzeciak S et al. Clinical manifestations of disordered microcirculatory perfusion in severe sepsis. Critical Care 2005 Vol 9 Suppl 4

Sepsis: No oxygen debt ! instead: Capillary shunting (# increase in ScvO2)

Sepsis Management

Sepsis Management: SSC-Guidelines Initial Resuscitation: ScvO2: Limitations

Van Beest P. et al. The incidence of low venous oxygen saturation on admission to the intensive care unit: a multi-center observational study in The Netherlands. Critical Care 2008, 12:R33

Sepsis Management

Jones A.E. et al. Lactate Clearance vs Central Venous Oxygen Saturation as Goals

of Early Sepsis Therapy. JAMA. 2010;303(8):739-746

Sepsis Management: SSC-Guidelines Initial Resuscitation: Lactate clearance

Sepsis Management

Jones A.E. et al. Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy. JAMA. 2010;303(8):739-746

Sepsis Management: SSC-Guidelines Initial Resuscitation: Lactate clearance

Sepsis Management

Osman D. et al. Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge. Crit Care Med 2007; 35:64–68

Pre-

Infu

sion

ΔCI > 15% ΔCI < 15%

Sepsis Management: SSC-Guidelines Initial Resuscitation: CVP

Sepsis Management

Marik P et al.

Does Central Venous Pressure Predict Fluid Responsiveness? A Systematic Review of the Literature and the Tale of Seven Mares.

CHEST 2008; 134:172–178

Sepsis Management: SSC-Guidelines Initial Resuscitation: CVP

Sepsis Management

Sepsis Management: Diagnosis

1. Cultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins) in the start of antimicrobial(s) (grade 1C). At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently (<48 hrs) inserted (grade 1C). 2. Use of the 1,3 beta-D-glucan assay (grade 2B), mannan and anti-mannan antibody assays (2C), if available and invasive candidiasis is in differential diagnosis of cause of infection. 3. Imaging studies performed promptly to confirm a potential source of infection (UG).

Sepsis Management

Sepsis Management: Antimicrobial Therapy

Kumar A. et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock Crit Care Med 2006; 34:1589–1596

Each hour of delay in antimicrobial administration: Average decrease in survival of 7.6%

Sepsis Management

Sepsis Management: Source Control

There is no medicine for bad surgery.

Sepsis Management

Sepsis Management: Fluid Therapy

1. Crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock (grade 1B).

2. Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and septic shock (grade 1B).

3. Albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids (grade 2C).

4. Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (a portion of this may be albumin equivalent). More rapid administration and greater amounts of fluid may be needed in some patients (grade 1C).

5. Fluid challenge technique be applied wherein fluid administration is continued as long as there is hemodynamic improvement either based on dynamic (eg, change in pulse pressure, stroke volume variation) or static (eg, arterial pressure, heart rate) variables (UG).

Sepsis Management

Sepsis Management: Fluid Therapy

Zarychanski R. et al. Association of Hydroxyethyl Starch Administration With Mortality and Acute Kidney Injury in Critically Ill Patients Requiring Volume Resuscitation. A Systematic Review and Meta-analysis. JAMA. 2013;309(7):678-688

Sepsis Management

Sepsis Management: Fluid Therapy

Zarychanski R. et al. Association of Hydroxyethyl Starch Administration With Mortality and Acute Kidney Injury in Critically Ill Patients Requiring Volume Resuscitation. A Systematic Review and Meta-analysis. JAMA. 2013;309(7):678-688

Sepsis Management

Sepsis Management: Fluid Therapy

Finfer S. et al. A Comparison of Albumin and Saline for Fluid

Resuscitation in the Intensive Care Units. N Engl J Med 2004;350:2247-56

Sepsis Management

Sepsis Management: Vasopressors

1. Vasopressor therapy initially to target a mean arterial pressure (MAP) of 65 mm Hg (grade 1C).

2. Norepinephrine as the first choice vasopressor (grade 1B).

3. Epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure (grade 2B).

4. Vasopressin 0.03 units/minute can be added to norepinephrine (NE) with intent of either raising MAP or decreasing NE dosage (UG).

5. Low dose vasopressin is not recommended as the single initial vasopressor for treatment of sepsis-induced hypotension and vasopressin doses higher than 0.03-0.04 units/minute should be reserved for salvage therapy (failure to achieve adequate MAP with other vasopressor agents) (UG).

6. Dopamine as an alternative vasopressor agent to norepinephrine only in highly selected patients (eg, patients with low risk of tachyarrhythmias and absolute or relative bradycardia) (grade 2C).

7. Phenylephrine is not recommended in the treatment of septic shock except in circumstances where (a) norepinephrine is associated with serious arrhythmias, (b) cardiac output is known to be high and blood pressure persistently low or (c) as salvage therapy when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP target (grade 1C).

8. Low-dose dopamine should not be used for renal protection (grade 1A).

9. All patients requiring vasopressors have an arterial catheter placed as soon as practical if resources are available (UG).

Sepsis Management

De Backer et al. Comparison of Dopamine and Norepinephrine in the Treatment of Shock. N Engl J Med 2010;362:779-89

Sepsis Management: Vasopressors

Sepsis Management

Landry et al. THE PATHOGENESIS OF VASODILATORY SHOCK. N Engl J Med, Vol. 345, No. 8 August 23, 2001

Vasopressin Rationale: • Endogenous hormone • Released from pituitary gland during hypotension • Depletion of neurohypophyseal stores in sepsis

Normal 1 h of shock

Sepsis Management: Vasopressors

Sepsis Management

N = 778 Dosis: 0.01-0.03 U/min

Sepsis Management: Vasopressors

Sepsis Management

Sepsis Management: Inotropic Therapy

1. A trial of dobutamine infusion up to 20 micrograms/kg/min be administered or added to vasopressor (if in use) in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate MAP (grade 1C).

2. Not using a strategy to increase cardiac index to predetermined supranormal levels (grade 1B).

* p <0.05

7,1 7,2 7,3 7,4

0 1 6 12 24

pHi

* * *

50 60 70 80 90

100 110

0 1 6 12 24

MAP (mmHg)

Time (h)

3,5 4

4,5 5

5,5

0 1 6 12 24

CI (l/min/m2)

NA/Dobutamine Adrenaline

Levy et al (1997) Intensive Care Med 23:282

Sepsis Management

Annane D. et al. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial Lancet 2007; 370: 676–84

Articles

680 www.thelancet.com Vol 370 August 25, 2007

coronary events, limb ischaemia or skin necrosis, and acute cerebrovascular events (whether haemorrhagic or ischaemic). These events were deemed to be related to catecholamine infusion when they occurred while patients were receiving study drugs.

Pharmacoeconomic analysis was done on the basis of a model that computes the medical cost of patients in intensive care.18 This model takes into account the rate of invasive or surgical procedures and estimates the mean medical cost per patient in intensive care.

The data and safety monitoring board met three times during the study to analyse the conduct of the study, the results of interim analyses, and to review serious adverse events. Interim analyses were done on Nov 18, 2002, and Oct 1, 2003, after the assessment of 185 and 232 patients, respectively. After each analysis, the independent data and safety monitoring board advised the study chairmen to continue the study. A diagnosis validation committee also met three times during the study to grade, without knowledge of treatment allocation, the patients as having defi nite septic shock, probable septic shock, and probable non-septic shock,19 and to assess the appropriateness of antibiotic treatments.

Statistical analysisWe expected an all-cause mortality rate at day 28 of 60% in the epinephrine group, on the basis of data from another trial we were doing in patients with septic shock when we planned this protocol.20 We calculated that we would need a sample size of 340 patients to be able to detect, in a two-sided test done with a 0·05 type I error, an absolute reduction of 20% in the mortality rate at day 28 with 95% probability.

The two interim analyses were planned with an O’Brien and Fleming stopping boundary.21 With this

procedure, the diff erences between the two groups were considered signifi cant if the critical Z values were higher than 3·471, 2·454, and 2·004 at the fi rst, second, and fi nal analyses, respectively (corresponding to nominal two-sided p values of <0·0005, <0·0141, and <0·0451).

The statistical analysis, prospectively defi ned, was done by intention to treat (ie, in all analyses, patients were grouped according to their original randomised treatment) with SAS statistical software (version 8.2; Cary, NC, USA). For continuous variables, the means and SD or the median (IQR), in case of signifi cant non-normality of the distribution, are reported. The number of patients in each category and the corresponding percentages are given for categorical variables.

The eff ects of treatments on the frequency of fatal events (mortality rates at day 7, day 14, day 28, at discharge from intensive care or from hospital, and day 90) were compared between groups by χ² tests. Corresponding relative risks (RR), together with their 95% CI, were estimated. Cumulative event curves (censored endpoints) were estimated with the Kaplan-Meier procedure. The eff ects of treatments on these endpoints were compared between groups with the log-rank test. For the primary endpoint, we did additional analyses with logistic and Cox regression models, adjusting for the main baseline factors that predict outcomes22 (ie, McCabe and Jackson classifi cation, SAPS II, SOFA, arterial lactate concentrations, and appropriateness of antibiotic treatments).23 For these analyses, continuous variables were broken into two classes on the basis of their median values. Odds ratios (OR) and hazard ratios (HR), together with 95% CI, were estimated with these models. For day 90 survival, patients who were still alive at 90 days were treated as censored. For time to vasopressor therapy withdrawal, among patients who had more than one outcome event during the 28 days from randomisation, time to fi rst event was used in the analyses. For this endpoint, the patients who died before vasopressor therapy could be withdrawn and those for whom vasopressor therapy could not be withdrawn during the 28 days from randomisation were treated as censored. The frequency of serious adverse events was compared between groups with the χ² test or Fisher’s exact test as appropriate. In the pharmacoeconomic analysis, the rates of invasive or surgical procedures were compared between groups by the χ² test and the mean medical costs per patient in intensive care were compared between groups by the Wilcoxon test. All reported p values are two-sided.

This trial is registered with ClinicalTrials.gov, number NCT00148278.

Role of the funding sourceThe funding source had no role in the conduct of the study, the collection and interpretation of the data, or in the drafting of the report. All authors had full access to all the data of the study, and all agreed to submit the fi nal manuscript for publication.

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Mortality at 3 monthsEpinephrine: 84/161 (52%)Norepinephrine plus dobutamine: 85/169 (50%)χ²=0·12p=0·73

Log-rankχ²=0·39p=0·53

20 30 40 50 60 70 80 90

Number at risk Epinephrine 161 117 102 96 88 84 81 79 79 74Norepinephrine 169 131 117 108 98 92 91 85 84 84plus dobutamine

Time (days)

EpinephrineNorepinephrine plus dobutamine

Figure 3: Survival from randomisation to day 90

Sepsis Management: Inotropic Therapy

Sepsis Management

Sepsis Management: Corticosteroids

1. Not using intravenous hydrocortisone to treat adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (see goals for Initial Resuscitation). In case this is not achievable, we suggest intravenous hydrocortisone alone at a dose of 200 mg per day (grade 2C).

2. Not using the ACTH stimulation test to identify adults with septic shock who should receive hydrocortisone (grade 2B).

3. In treated patients hydrocortisone tapered when vasopressors are no longer required (grade 2D).

4. Corticosteroids not be administered for the treatment of sepsis in the absence of shock (grade 1D).

5. When hydrocortisone is given, use continuous flow (grade 2D).

Sprung C. et al. Hydrocortisone Therapy for Patients with Septic Shock.

N Engl J Med 2008;358:111-24

Sepsis Management

Sepsis Management: Blood Product Administration

1. Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances, such as myocardial ischemia, severe hypoxemia, acute hemorrhage, or ischemic heart disease, we recommend that red blood cell transfusion occur only when hemoglobin concentration decreases to <7.0 g/dL to target a hemoglobin concentration of 7.0 –9.0 g/dL in adults (grade 1B).

2. Not using erythropoietin as a specific treatment of anemia associated with severe sepsis (grade 1B).

3. Fresh frozen plasma not be used to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures (grade 2D).

4. Not using antithrombin for the treatment of severe sepsis and septic shock (grade 1B).

5. In patients with severe sepsis, administer platelets prophylactically when counts are <10,000/mm3 (10 x 109/L) in the absence of apparent bleeding. We suggest prophylactic platelet transfusion when counts are < 20,000/mm3 (20 x 109/L) if the patient has a significant risk of bleeding. Higher platelet counts (≥50,000/mm3 [50 x 109/L]) are advised for active bleeding, surgery, or invasive procedures (grade 2D).

Sepsis Management

Sepsis Management: Mechanical Ventilation

Sepsis Management

Sepsis Management: Glucose Control

1. A protocolized approach to blood glucose management in ICU patients with severe sepsis commencing insulin dosing when 2 consecutive blood glucose levels are >180 mg/dL. This protocolized approach should target an upper blood glucose ≤180 mg/dL rather than an upper target blood glucose ≤ 110 mg/dL (grade 1A).

2. Blood glucose values be monitored every 1–2 hrs until glucose values and insulin infusion rates are stable and then every 4 hrs thereafter (grade 1C).

3. Glucose levels obtained with point-of-care testing of capillary blood be interpreted with caution, as such measurements may not accurately estimate arterial blood or plasma glucose values (UG).

< 180 mg/dl

< 81 - 108 mg/dl

Finfer S. et al. Intensive versus Conventional Glucose Control

in Critically Ill Patients. N Engl J Med 2009;360:1283-97

Sepsis Management

SEPSIS

Antimicrobial therapy

Adjunctive

Therapy

Supportive

Therapy

Source control

"  Debridement of infected tissue

"  Removal of invasive devices

"  Absces drainage

"  Hydrocortisone?

"  rhAPC

"  Selenium

"  Immunemodulators

"  Empirical

"  Calculated

"  Targeted

"  Volume resuscitation

"  Vasopressors/Inotropes

"  Lung-protective

ventilation

"  Nutrition

"  Glucose homeostasis

"  RRT

Sepsis Management The cornerstones

Sepsis Management

Sepsis Management: Summary: Protocolized Approach

Sepsis Management

Sepsis Management: Summary: Protocolized Approach

Levy M.M. et al. The Surviving Sepsis Campaign: results of an

international guideline-based performance improvement program targeting severe sepsis.

Intensive Care Med (2010) 36:222–231

Sepsis Management Thank you very much for your attention