sepsis edited

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 1/35

Sepsis

Hippocrates (460-377 B.C.), the most famous

doctor in ancient Greece, was titled as Father

of Medicine, who used "sepsis" to describeputrefaction and a bad smell.

Ubi pus, ibi evacua-"Where there is pus, thereevacuate it"

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 2/35

Inflammation

Calor Rubor Tumor Dolor Functio laesa

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 3/35

Incidence of diseases in Germany

§ AIDS 17/100.000

§ Bowel-Ca 50/100.000

§ Mamma-Ca 110/100.000

§ Sepsis 300/100.000*

Deutsche Sepsisgesellschaft 2004

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 4/35

Sepsis in United States

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 5/35

Two or mor e of the f ollowing:

Temp >38°C or <36 °C

Hear t r ate > 90 bpm

Resp r ate > 20 bpm or PCO2 < 32 mm HgWBC >12 or  < 4 Gpt/l

Early LAB Clues

Glucose > 7 mmol/l

Cr eatinine incr ease > 0.5 mg/dLINR > 1.5 or aPTT > 60s

Thrombocytopenia < 100,000

Hyper bilir ubinemia > 34 umol/l

Lactate level > 2mmol/L

Diagnosis SIRS

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 6/35

Definitions and Ter ms

Sepsis

 ± SIRS plus systemic manifestations of infection

Severe sepsis

 ± Sepsis plus sepsis-induced or gan dysfunction or  tissue

hypoper fusion (Eg Oligur ia, elevated lactate, shock)

Septic shock-- Sepsis induced hypotension defined as

SBP < 90 mm Hg or 

>40 mm Hg drop f rom baseline not r elieved with fluids

MAP < 70 mm Hg

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 7/35

Organ Dysfunction

CNS (Confusion)

Renal (ARF) Respiratory (ARDS)

Haematologic (DIC)

Metabolic (Acidosis)

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 8/35

Source of Infection

Lungs (41%) Abdomen (32%)

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 9/35

Urinary tract (11%) Wounds + Soft tissue (5%) Tubes+Drains (5%)

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 10/35

Sepsis

Obtain 2 sets of blood cultures, and other

appropriate cultures (eg urine, sputum,

wounds).

Administer appropriate antibiotics

immediately after obtaining blood cultures.

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 11/35

Empirical AB treatment

di/flucloxacillin 2 g IV, 4- to 6-hourly

PLUS

gentamicin 4 to 6 mg/kg IV, for 1 dose, then adjust

subsequent dose for renal function

Penicillin-allergy

cephalothin 2 g IV, 6-hourly OR

cephazolin 2 g IV, 8-hourly.

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 12/35

Febrile neutropenic patients

ticarcillin+clavulanate 3+0.1 g IV, 6-hourly

PLUS

gentamicin 4 to 6 mg/kg daily OR

ceftazidime 2 g IV, 8-hourly

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 13/35

Goals

Search for a source and control it ASAP

Drain any infected fluid

Debride infected tissueRemove infected devices

Recommendations

Administer antibiotics in the ED within 1 hour of sepsisdiagnosis (after culturing!!!)

Initial broad coverage tailored to the potential source

Consider resistance patterns in nursing home patients

and patients on prior antibiotics

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 14/35

The Tarragona Strategy

Hit hard with a high dose of broad-spectrum antibiotic.

Get to the point: use antibiotics according to their

pharmacodynamic response.

Focus, focus, focus: de-escalate when it is possible, according

to microbiological findings and do not prolong antibiotic therapy

unnecessarily.

Listen to your hospital: tailor the antibiotic policy according

to regularly updated information on the resistance patterns of local pathogens.

Look at your patient: individualise the initial antibiotic

therapy on the basis of the patients comorbidities, intubation

period and previous antibiotic exposure.

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 15/35

Each hour  

without adequate

 AB Rx incr eases

mor tality by

7.6%.

82%, if AB initiated within 30 minutes, after 1-2 hour s sur vival r ate: 77%,

after 5-6 hour s: 50%

Duration of hypotension before initiation of effective

antimicrobial therapy is the critical determinant of survival in

septic shock

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 16/35

Antibiotics

CeftriaxoneGood, broad spectrum 3rd generation cephalosporin with activity against mostGram-neg other than P. aeruginosa. Activity vs. anaerobes is not wellestablished.

Timentin (ticarcillin+clavulanic acid) good broad spectrum activity against awide range of Gram-positive and Gram-negative aerobic and anaerobicbacteria, Pseudomonas

Gentamicin

Gram-neg, Pseudomonas, ototoxicity as well as nephrotoxicity, the tendency tounderdose & the need to monitor levels.

Azithromycin

atypical pneumonia, gram-pos

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 17/35

Antibiotics

MeropenemVery similar to imipenem (favored drug for serious infections which requirea broad spectrum agent, active against almost all gram-pos and gram-negorganism). Probably less seizure potential.

Di/Flucloxacillin

Staphylocooci, gram pos cocci

Vancomycin

Is active against most gram-positive cocci and bacilli, including almost all S.

aureus and coagulase-negative staphylococcal strains that are resistant topenicillins and cephalosporins (MRSA). Oto-, nephrotoxicity

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 18/35

Activated Protein C

Drotregonin alfa (Xigris)-modulation of the systemicinfection response, limits thrombin formation

represents the only specific therapeutic modality

apart from antibiotics that has been shown toimprove mortality in severe sepsis and septic shock.

Protein C is approved only for use in patients withsepsis who have the most severe organ

compromise and the highest likelihood of death.

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 19/35

Volume Resuscitation

Early aggressive therapy that optimized cardiac preload,afterload, and contractility in patients with severe sepsis andseptic shock improved the likelihood of survi val.

Duringthe first 6 hrs of resuscitation, the goals of initial

resuscitation of sepsis-induced hypoperfusion should include:

CVP of 8 to 12 mm Hg,

MAP between 65 to 90 mm Hg central venous oxygen saturations > 70%.

Urine output 0.5mL.kg/hr

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 20/35

Vasopressors

Dobutamine is useful in patients with myocardial depressionwith persistent low cardiac output following adequate fluidresuscitation.

A combination of dobutamine and norepinephrine, exertedbeneficial effect on gastrointestinal blood flow.

Norepinephrine may yield superior results clinically comparedwith dopamine.

Vasopressin, a potent vasoconstrictor, has an established rolein systemic arterial pressure maintenance.

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 21/35

Australasian Practice

Noradrenaline is usually first agent used

Adrenaline also commonly used in resus

Dopamine seldom used any more (Renal dosedopamine does not work!!!)

Metaraminol (Aramine) commonly used

during anaesthesia for hypotension Dobutamine is used in low cardiac output states

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 22/35

Intensive Insulin Therapy for Hyperglycemia

Insulin therapy reduced the rate of death frommultiple-organ failure among patients with

sepsis, regardless of whether they had ahistory of diabetes.

BSL 80 to 110 mg /dl (4.4 to 6.1 mmol per liter)  but risk of hypoglycemia followed by

increased mortality BSL 120 to 160 mg/dl (6.7 to 8.9 mmol per

liter)   same benefit?

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 23/35

Corticosteroids

 Administr ation of high doses of cor ticosteroids (e.g., 30

mg of methylpr ednisolone/kg BW) does not improve

sur vival among patients with sepsis and may wor senoutcomes by incr easing the f r equency of secondar y

infections.

Patients with sepsis who ar e extremely ill and have persistent shock r equir ing vasopr essor s and prolonged

mechanical ventilation may benefit f rom "physiologic"

doses of cor ticosteroids (Hydrocortisone 50-mg

intravenous bolus four times per day) andfludrocor tisone 50 er da

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 24/35

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 25/35

Nutrition Support

Early je junal feeding may help maintain the normal bacterialmicroflora and the barrier function of intestines, thus,minimizing bacterial and endotoxin translocation. Incombination with pancreatitis, lack of enteral nutrition can

produce mucosal atrophy and increased permeability of intestinal barrier leading to failure of intestinal barrierfunction, which plays a pivotal role in bacterial translocation.In a recent study, approximately 3-6% of all patients with acutepancreatitis developed SIRS, sepsis, and MOF, likely as a resultof colonization and infection of the necrotic tissue. The rate of septic complications, including infected pancreatic necrosisand abscess, was lower in a group of patients treated withearly jejunal feeding compared with the conventionalparenteral nutrition.

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 26/35

Hemodialysis

Acute renal failure in critically ill patients is

often associated with extra renal

complications that may instigate MOF and

high mortality. Renal replacement therapy

with intermittent hemodialysis is the current

standard, but an adequate dose of 

maintenance hemodialysis is not currentlyknown.

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 27/35

Potential Therapies for Sepsis

antibodies against complement-activation

product C5a decreased the frequency of 

bacteremia, prevented apoptosis, and

improved survival

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 28/35

Procalcitonin

PCT is not a better marker of bacterial

infection than CrP for adult emergency

department patients, but it is a useful markerof the severity of infection.

Normal <0,5 ng/ml Sepsis >2,0 ng/ml

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 29/35

Age-specific incidence (per 1000 population) of 

severe sepsis patients with and without cancer.

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 30/35

Systemic Inflammator y Response Syndrom

Inflammatorische Parameter

Leukocytose (> 12000 /l)

Leukopenie (< 4000 /l)

Normale Leukozytenzahl mit > 10% unreifen

Formen im Differentialblutbild

CRP > 2 SD über Normwert

Procalcitonin (ProCT) > 2 SD über Normwert

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 31/35

Initial choice of vasopressor

Noradrenaline

Via CVC

To maintain MAP > 65 mmHg

Adrenaline, phenylephrine, or vasopressin NOT first line (2C)

Adrenaline as first alternative agent when BP poorly

responsive

Low-dose dopamine for renal protection doesnt work

Insert an arterial catheter as soon as practical

Use dobutamine in patients with myocardial dysfunction

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 32/35

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 33/35

Early goal-directed therapy (EGDT

Otero, R. M. et al. Chest 2006;130:1579-1595

Algorithm of EGDT

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 34/35

Activated protein C

represents the only specific therapeutic

modality apart from antibiotics that has

been shown to improve mortality in severesepsis and septic shock. In contrast, recent

phase III trials of related therapies such as

antithrombin III and tissue factor pathway

inhibitor have failed to demonstrate

improved survival.

8/8/2019 Sepsis Edited

http://slidepdf.com/reader/full/sepsis-edited 35/35

Cor ticosteroids