APPROACH TO SEPSIS MANAGEMENT
Thursday, September 17, 2015 1
WHAT THE PRIMARY PHYSICIAN SHOULD DO
Dr. A.P.Naveen Kumar
Chief Specialist (Gen. Med. )Visakha Steel General Hospital
Clinical impact of Severe Sepsis
†National Center for Health Statistics, 2001. §American Cancer Society, 2001. *American Heart Association. 2000. ‡Angus DC et al. Crit Care Med. 2001 (In Press).
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Polymicrobial sepsis shows higher risk for complication, length of stay and mortality than unimicrobial.
Thursday, September 17, 2015 3N Abed et al. Outcome of unimicrobial versus polymicrobial sepsis. Critical Care 2010, 14(Suppl 1):P62
(n=101) Unimicrobial infection Polymicrobial infection P value
Positive sputum 66% 71% 0.6
+ve blood culture 14% 51% 0.0001
UTI 6.3% 49.7% 0.0001
Wound infection 2.1% 20.7% 0.004
Acinetobacter/Candida/ E. coli
0.032
Mean hospital stay 17.4(+/- ) 9.3 days 26.9(+/- )15.4 days 0.001
Guide to Recommendations’ Strengths and Supporting Evidence: 1 = strong recommendation;1 = strong recommendation;
2 = weak recommendation or suggestion;2 = weak recommendation or suggestion;
A = good evidence from randomized trials;A = good evidence from randomized trials;
B = moderate strength evidence from small randomized trial(s) or B = moderate strength evidence from small randomized trial(s) or
multiple good observational trials;multiple good observational trials;
C = weak or absent evidence, mostly driven by consensus opinion.C = weak or absent evidence, mostly driven by consensus opinion.
Thursday, September 17, 2015 5Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Infection either
Bacteraemia (or viraemia/fungaemia/protozoan)is the presence of bacteria within the bloodstream
Septic focus (abscess / cavity / tissue mass)
SIRS –Systemic Inflammatory Response Syndrome
2/4 ofTemp >38 or <36
HR >90
Respiratory Rate >24 / mt.
WCC >12 or <4 or >10% bands (immature forms)
Definitions
SepsisSepsis is defined as the presence (probable or documented) of
infection together with systemic manifestations of infection(SIRS).
Thursday, September 17, 2015 8Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Definit ions
Severe sepsisSevere sepsis is defined as sepsis plus sepsis-induced
organ dysfunction or tissue hypoperfusion.
Thursday, September 17, 2015 9Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Organ System Involvement Circulation
Hypotension, increases in microvascular permeability Shock
Lung Pulmonary Edema, hypoxemia, ARDS
Hematologic DIC, coagulopathy (DVT)
Organ System Involvement GI tract
stress ulcer Translocation of bacteria, Liver Failure, Gastroparesis and ileus, Cholestasis
►Kidney Acute tubular necrosis, Renal Failure
Organ System Involvement Nervous System Encephalopathy
►Skeletal Muscle Rhabdomyolysis
Endocrine Adrenal insufficiency
1. Cardiovascular: Arterial systolic blood pressure < 90 mmHg or mean arterial pressure < 70 mmHg that responds to administration of intravenous fluid
2. Renal: Urine output <0.5 mL/kg per hour for 1 h despite adequate fluid resuscitation
3. Respiratory: PaO2/FIO2 < 250 or, if the lung is the
only dysfunctional organ < 200
Thursday, September 17, 2015 13
OXYGEN DELIVERY
FiO2 PaO2/FiO2
Room air 0.21 476
1 Litre / mt. 0.24 416
2 Litre/ mt. 0.28 357
3 Litre/ mt. 0.32 312
4 Litre/ mt. 0.36 277
5 Litre/ mt. 0.40 250
6 Litre/ mt. 0.44 227
7 Litre / mt. 0.48 208
8 Litre / mt. 0.52 192
4. Hematologic: Platelet count <80,000/L or 50% decrease in platelet count from highest value recorded over previous 3 days
5. Unexplained metabolic acidosis: A pH < 7.30 or a base deficit 5.0 mEq/L and a plasma lactate level >1.5 times upper limit of normal for reporting lab
6. Adequate fluid resuscitation: Pulmonary artery
wedge pressure < 12 mmHg or central venous pressure < 8 mmHg
Thursday, September 17, 2015 15
Definit ions
Sepsis-induced tissue hypoperfusion Sepsis-induced tissue hypoperfusion is
defined as infection-induced hypotension, elevated lactate, or
oliguria.
Thursday, September 17, 2015 16Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Definit ions
Septic shockSeptic shock is defined as sepsis-induced hypotension
persisting despite adequate fluid resuscitation.
Thursday, September 17, 2015 17Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Sepsis - SIRS + Infection
Severe Sepsis- Sepsis+ Organ dysfunction
Septic shock– Sepsis+ Hypotension despite fluid resuscitation
Critical illness–related corticosteroid insufficiency (CIRCI)
Inadequate corticosteroid activity for the patient's severity of illness; should be suspected when hypotension is not relieved by fluid administration
Thursday, September 17, 2015 19
Thursday, September 17, 2015 21Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Multiple organ dysfunction syndrome Dysfunction of more than one organ,requiring
intervention to maintain hemostasis
Refractory Septic Shock
Septic shock that lasts for > 1 hr. and does not respond to fluids or pressor administration
Thursday, September 17, 2015 22
Case -1
51 year old male Presented with fever, cough and breathlessness h/o streaky hemoptysis h/o orthopnea+ Known case of COPD Ethanolic Non DM /non smoker
Examination
Conscious and coherent Febrile, HR- 140/mt.,RR – 40/mt ,BP 100/70 Lungs – Bil. Rhonchi and crepts. CVS – Tachycardia CNS- no deficit
Investigations Hb.-13.6 ,TC – 24100 , DC – P94 L04 , Pl. -2.1 FBS – 225 mgs /dl ,Sr. Crea. – 1.8 mgs/dl , Urea –
49 mgs/dl LFT – 1.8 / 53 / 48 /93 ECG – sinus tachycardia CXR – Lt.basal consolidation SPo2 – 66
CAP with Sepsis
Case -2
54 year old female Fever with breathlessness Dysuria and decreased urination DM , HTN Febrile , HR- 112/mt. ,BP – 80/60 Lungs –clear ,CVS -NAD
Hb.- 10.2 , TC -18600 , DC-P88 L10 E2 FBS – 224 ,PPBS -336 ,Crea. – 1.8 Urine –plenty of pus cells CXR –NAD ECG –WNL
UROSEPSIS
CASE 3
64 year old male HTN ,CAD ,DM, LV Dysfunction Presented with breathlessness –PND + Cough ,low grade fever Afebrile ,HR-122/mt. ,RR -32/mt. ,BP- 70/50 Lungs – bil. Crepts ,CVS – LVS3+ tach.,JVP -↑
Hb. -12.6 ,TC- 12400 ,DC –P72 L22 E6 ,Pl. -2.3 FBS- 168 ,PPBS -224 ,Crea. – 1.2 ,LFT –N ECG - T L1, Avl , V 2-6↓ CXR – s/o CCF SPo2 - 86
Case 4
70 yrs male Fever, chills ,altered sensorium HR 108 / mt. , RR – 28 /mt. ,BP – 90/ 50 Tc -12200 , FBS -144, Crea. – 2.2 Na – 118 , K -2.9
Metabolic encephalopathy
Thursday, September 17, 2015 30
Severe Sepsis: The Final Common Pathway
Endothelial Dysfunction and Microvascular Thrombosis
Hypoperfusion/Ischemia
Acute Organ Dysfunction (Severe Sepsis)
Death
High Risk Patients For Sepsis
Middle-aged, elderly Post op / post trauma Post splenectomy Transplant immune supressed Alcoholic / Malnourished Genetic predisposition Delayed appropriate antibiotics Comorbidities : AIDS, renal or liver failure, neoplasms
SYMPTOMS normo- or hypothermic,Hyperventilation
Disorientation, confusion, encephalopathy
Hypotension and DIC predispose to acrocyanosis and ischemic necrosis of peripheral tissues, most commonly the digits
Cellulitis, pustules, bullae, or hemorrhagic lesions may develop when hematogenous bacteria or fungi seed the skin or underlying soft tissue
vomiting, diarrhea, and ileus ,Stress ulceration , Cholestatic jaundice, acute hepatic injury or ischemic bowel necrosis
Thursday, September 17, 2015 34
Init ial Resuscitation, Diagnosis, and Antibiotic Therapy
Recommend early goal-directed therapy:Recommend early goal-directed therapy:
Give early appropriate antibioticsGive early appropriate antibiotics
Give early appropriate fluidsGive early appropriate fluids
Give appropriate inotropic supportGive appropriate inotropic support
Take early culturesTake early cultures
Take early lactate levelTake early lactate level
Take early central venous oxygen saturation(SVO2) – pending the Take early central venous oxygen saturation(SVO2) – pending the
results of numerous ongoing trials.results of numerous ongoing trials.
Thursday, September 17, 2015 35Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
The Bundles To be completed within 3 hrs
Measure lactate level
Obtain blood culture samples prior to administration of antibiotics.
Administer broad spectrum antibiotics.
Administer 30mL/Kg crystalloids for hypotension or lactate >/= 4
mmol/L.
Thursday, September 17, 2015v 36Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
The Bundles
To be completed within 6 hrs Apply vasopressors (for hypotension that does not respond to
initial fluid resuscitation) to maintain a mean arterial pressure (MAP) 65 mm Hg.
In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate 4 mmol/L (36 mg/dL):Measure central venous pressure (CVP)Measure central venous oxygen saturation (ScvO2)
Remeasure lactate if initial lactate was elevated
Targets for quantitative resuscitation included in the guidelines are CVP of 8 mm Hg, ScvO2 of 70%, and normalization of lactate
Thursday, September 17, 2015 37Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Screening for and Diagnosis of Sepsis
• Routine screening is recommended of potentially infected seriously ill
patients for severe sepsis to increase the early identification of sepsis
and allow implementation of early sepsis therapy (grade 1C).
• Obtaining appropriate cultures before antimicrobial therapy is
initiated if such cultures do not cause significant delay (> 45
minutes) in the start of antimicrobial(s) administration (grade 1C).
Thursday, September 17, 2015 38Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Currently available Biomarkers
WBC Lactate levels C-Reactive protein (CRP) Procalcitonin Cytokines New markers
Thursday, September 17, 2015 39
LACTATE LEVELS
0.5-1 mmol/l – normal > 4 mmol/l - lactic acidosis Useful for monitoring response of septic patients Higher the lactate clearance better the prognosis
Thursday, September 17, 2015 40
PROCALCITONIN LEVELS
Rises within 2-4 hrs. – peak - 8-24 hrs. Short half life of 24 hrs. independent of renal
function Normal - < 0.05 ng /l Tend to be low in viral infections Guidelines advocate PCT levels for
starting,continuing or stopping antibiotics
Thursday, September 17, 2015 41
PCT LEVELS
Thursday, September 17, 2015 42
Thursday, September 17, 2015 43
Thursday, September 17, 2015 44
NEWER MARKERS
Soluble CD 14 subtype ( Presepsin )
Heparin binding protein
Pentraxin
Macrophage migration inhibitory factor ( MIF )
Cytokine / Chemokine Biomarkers
Thursday, September 17, 2015 45
Screening for and Diagnosis of Sepsis
No recommendation given for the use of procalcitonin
levels or other biomarkers (such as C-reactive protein) to
distinguish between severe infection and other acute inflammatory
states.
When no infection can be found during empiric antibiotic
therapy, consider using a low procalcitonin level as a supportive
tool for the decision to stop antibiotics (Grade 2C).
Thursday, September 17, 2015 46Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Screening for and Diagnosis of Sepsis
For patients at risk for fungal infection as a source for severe
sepsis, checking one of the newer tests for IFIs such as 1,3-
beta-D-glucan, galactomannan, or anti-mannan ELISA antibody
testing (Grade 2B/C).
Imaging studies be performed promptly in attempts to
confirm a potential source of infection(UG).
Thursday, September 17, 2015 47Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
I.V. antibiotics Initiated as soon as cultures are drawn
Severe sepsis should receive broadspectrum antibiotic.
Empiric antifungal drug; Neutropenic patients, DM, chronic steroids.
Antibiotics
• Abx within 1 hr hypotension: 79.9% survival
• Survival decreased 7.6% with each hour of delay
• Mortality increased by 2nd hour post hypotension
• Time to initiation of Antibiotics was the single strongest predictor of outcome
Dosage for IV administration (N renal function)
Imipenem-cilastin 0.5g q 6h Meropenem 1.0g q 8h Piperacillin-tazobactam 3.375gq 4h or 4.5 g q 6h Cefepime 2 gms. 12 hr
Patients allergic to B lactums
Gatifloxacin 400mg iv q d Levofloxacin 500-750 mg 12 hrly.
plus clindamycin (600 mg q8h).Vancomycin (15 mg/kg q 12 hrly ) added to each of the
above regimes
Neutropenia (<500 neut./ L)
imipenem-cilastatin (0.5 g q6h) meropenem (1 g q8h) cefepime (2 g q8h);
piperacillin/tazobactam (3.375 g q4h) plus tobramycin (5–7 mg/kg q24h).
Vancomycin (15 mg/kg q 12 hrly ) added to each of the above regimes
Empirical anti fungal therapy 51
Splenectomy Cefotaxime (2 g q6–8h) or ceftriaxone (2 g q12h) B- lactum allergy - vancomycin (15 mg/kg q12h)
plus either moxifloxacin (400 mg q24h) or levofloxacin (750 mg q24h) or aztreonam (2 g q8h) should be used
IV drug user Vancomycin (15 mg/kg q12h)
AIDSCefepime (2 g q8h) or piperacillin-tazobactam
(3.375 g q4h) plus tobramycin (5–7 mg/kg q24h)Thursday, September 17, 2015 52
For patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is for P. aeruginosa bacteremia (grade 2B).
A combination of beta-lactam and macrolide for patients with septic shock from bacteremic
Streptococcus pneumoniae infections (grade 2B).
Thursday, September 17, 2015 53
Antimicrobial Therapy
The administration of effective intravenous antimicrobials within
the first hour of recognition of septic shock and severe sepsis
without septic shock (grade 1B/ 1C) should be the goal of therapy.
The initial empiric anti-infective therapy include one or more
drugs that have activity against all likely pathogens and that
penetrate in adequate concentrations into the tissues
presumed to be the source of sepsis (grade 1B).
Thursday, September 17, 2015 54Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Mortality associated with Sensitive vs Resistant GNB*
11.7 10.1 18.9 8 190
20
63.620 41
18.414.3
0
20
40
60
80
100
Klebs
iella
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E. c
oli (
n=19
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Pse
udom
onas
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Acine
toba
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)
Ent
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Sensitive Resistant
Bochem PY, Intensive Care Med 2001
Mor
talit
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tes
(% p
atie
nts)
*GNB-gram-negative bacilli
Enterobacteriacae
Pseudomonas
Anaerobes
Renal/hepatic function
Patient
condition
Co-existing medical illness
So many factors to consider
?Abscess
Resistance
patterns
Community vs hospital acquired infection
Monotherapy vs Combination
?Candida
Solomkin JS, Mazuski JE, et al. Clinical Infectious Diseases 2003 Mazuski JE, Sawyer RG et al. Surgical Infections 2002
% patients of sepsis with renal failure
Thursday, September 17, 2015 57Singh M et al. Pharmacologyonline . 2009;3: 597-605
Higher doses warranted in critical patients
Recent evidence states beta-lactam antibiotics should be above the MIC for > 70% dosing interval in serious infections
Antimicrobial Therapy
The antimicrobial regimen should be reassessed daily for
potential de-escalation to prevent the development of
resistance, to reduce toxicity, and to reduce costs (grade 1B).
Low procalcitonin levels or similar biomarkers should be used
to assist the clinician in the discontinuation of empiric
antibiotics in patients who appeared septic, but have no
subsequent evidence of infection (grade 2C).
Thursday, September 17, 2015 60Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Antimicrobial Therapy
Combination therapy, when used empirically in patients with severe
sepsis, should not be administered for longer than 3 to 5 days.
De-escalation to the most appropriate single-agent therapy should be
performed as soon as the susceptibility profile is known (grade 2B).
Exceptions would include aminoglycoside monotherapy, which
should be generally avoided, particularly for P. aeruginosa sepsis,
and for selected forms of endocarditis, where prolonged courses of
combinations of antibiotics are warranted.
Thursday, September 17, 2015 61Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Antimicrobial Therapy
the duration of therapy typically be 7 to 10 days if clinically
indicated.
Longer courses may be appropriate in patients who have a slow
clinical response, undrainable foci of infection, bacteremia with S.
aureus; some fungal and viral infections, or immunologic
deficiencies, including neutropenia (grade 2C).
Thursday, September 17, 2015 62Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Fluid Resuscitation Recommendations
Strong 1A recommendation for the use of crystalloids like
normal saline as the initial fluid resuscitation for people with severe
sepsis.
The initial fluid challenge should be 1L or more of crystalloid,
and a minimum of 30 mL/kg of crystalloid (2.1 L in a 70 kg or 154-
pound person) in the first 4-6 hours.
Thursday, September 17, 2015 63Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Fluid Resuscitation Recommendations
Incremental fluid boluses should be continued as long as
patients continue to improve hemodynamically (Grade 1C).
Weak recommendation adding albumin to initial fluid
resuscitation with crystalloid for severe sepsis and septic shock
(Grade 2B).
Thursday, September 17, 2015 64Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Fluid Resuscitation Recommendations
Authors strongly recommended not using hetastarches/
hydroxyethyl starches greater than 200 kDa in molecular
weight (Grade 1B).
They did not comment on the use of lower molecular
weight hetastarches or the use of gelatins; trials are ongoing
to evaluate these resuscitative agents.
Thursday, September 17, 2015 65Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Sepsis-induced hypotensionsystolic less than 90 mm Hg
or a reduction of more than 40 mm Hg from baseline in the absence of other causes of hypotension.”
1.A loss of plasma volume into the interstitial space,
2. Decreases in vascular tone, 3. myocardial depression.
Goals for initial resuscitation
Central venous pressure 8 to 12 mmHg.
Mean arterial pressure > 65 mmHg.
Urine output 0.5 mL per kg per hr.
Pulmonary capillary wedge pressure exceeds 18 mmHg
Treatment of Hypotension Intravenous fluids : Crystalloids vs. Colloids. need more than ‘maintenance’ + replace losses
Fluid Therapy
No mortality difference between;
colloid vs. crystalloid
Vasopressors and Inotrophic Therapy
The researchers recommend using norepinephrine as the first
choice vasopressor (Grade 1B)
Adding or substituting epinephrine when an additional drug is needed
to maintain adequate blood pressure (Grade 2B).
Vasopressin 0.03 units per minute may be added or
substituted for norepinephrine (Grade 2A).
Thursday, September 17, 2015 71Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Vasopressors and Inotrophic Therapy Dopamine was suggested as an alternative vasopressor, but only
in highly selected patients at very low risk of arrhythmias and with a low
cardiac output and/or low heart rate (Grade 2C).
Dobutamine infusion be started or added to a vasopressor in
myocardial dysfunction (elevated cardiac filling pressure and low cardiac
output) or ongoing signs of hypoperfusion, even after adequate
intravascular volume and mean arterial pressure are achieved (Grade 1C).
Low dose dopamine should not be used for renal protection
(grade 1A).
Thursday, September 17, 2015 72Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Source Control
A specific anatomical diagnosis of infection requiring
consideration for emergent source control should be sought and
diagnosed or excluded as rapidly as possible, and intervention
be undertaken for source control within the first 12 hr after
the diagnosis is made, if feasible (grade 1C).
In infected peripancreatic necrosis, definitive intervention is
best delayed until adequate demarcation of viable and
nonviable tissues has occurred (grade 2B).
Thursday, September 17, 2015 73Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Source Control
When source control in a severely septic patient is required, the
effective intervention associated with the least physiologic
insult should be used (eg, percutaneous rather than surgical
drainage of an abscess) (UG).
If intravascular access devices are a possible source of severe
sepsis or septic shock, they should be removed promptly
after other vascular access has been established (UG).
Thursday, September 17, 2015 74Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Infection Prevention
Selective oral decontamination (SOD) and selective digestive
decontamination (SDD) should be introduced and investigated as a
method to reduce the incidence of ventilator-associated pneumonia
(VAP); this infection control measure can then be instituted in
healthcare settings and regions where this methodology is found to
be effective (grade 2B).
Oral chlorhexidine gluconate (CHG) should be used as a form of
oropharyngeal decontamination to reduce the risk of VAP in ICU
patients with severe sepsis (grade 2B).
Thursday, September 17, 2015 75Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Blood Product Administration
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).
Thursday, September 17, 2015 76
Not using erythropoietin as a specific treatment of anemia associated with severe sepsis (grade 1B).
Fresh frozen plasma not be used to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures (grade 2D).
• Not using antithrombin for the treatment of severe sepsis and septic shock (grade 1B).
Thursday, September 17, 2015 77
Platelets
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).
Thursday, September 17, 2015 78
Supportive therapy for severe sepsis
Thursday, September 17, 2015 79
Sedation, Analgesia, and neuromuscular Blockade
Either continuous or intermittent sedation should be minimized
in mechanically ventilated sepsis patients, targeting specific
titration endpoints (grade 1B).
NMBAs should be avoided if possible in the septic patient without
ARDS due to the risk of prolonged neuromuscular blockade
following discontinuation.
If NMBAs must be maintained, either intermittent bolus as
required or continuous infusion with monitoring of the depth of
blockade should be used (grade 1C).
A short course of an NMBA (≤ 48 hours) for patients with early,
sepsis-induced ARDS and Pao2/Fio2 < 150 mm Hg (grade 2C).Thursday, September 17, 2015 80
Steroids in Sepsis and Sepsis-Induced ARDS
In adult septic shock patients, it is suggested not to use IV
corticosteroids if fluid resuscitation or vasopressor therapy is able to
restore the patient to hemodynamic stability.
When hemodynamic stability cannot be achieved, the researchers
recommend IV hydrocortisone 200 mg daily given with
continuous infusion (Grade 2C).
Thursday, September 17, 2015 81Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Steroids in Sepsis and Sepsis-Induced ARDS ACTH stimulation test should not be used to identify adults with septic
shock who should receive hydrocortisone (grade 2B).
In treated patients hydrocortisone should be tapered when vasopressors
are no longer required (grade 2D).
Corticosteroids not to be administered for the treatment of sepsis in the
absence of shock (grade 1D).
When HC is given, continuous flow should be used(grade 2D).Thursday, September 17, 2015 82Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Mechanical Ventilation of Sepsis-Induced ARDS It is Suggested that clinicians target a tidal volume of 6 mL/kg predicted
body weight in pt with sepsis induced ARDS(grade1A) vs. 12 mL/kg.
Higher levels of PEEP in patients with severe ARDS (grade 2C).
The researchers suggest recruitment maneuvers in patients with severe
refractory hypoxemia (Grade 2C).
They also suggest prone positioning for patients with severe ARDS whose
PaO2 /FiO2 rates are less than 100 despite such maneuvers (Grade 2C).
Thursday, September 17, 2015 83Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Mechanical Ventilation of Sepsis-Induced ARDS It is suggested that noninvasive mask ventilation (NIV) be
used in that minority of sepsis-induced ARDS patients in whom the
benefits of NIV have been carefully considered and are thought to
outweigh the risks (grade 2B).
That a weaning protocol be in place.
Against the routine use of the pulmonary artery catheter
for patients with sepsis-induced ARDS (grade 1A).
Thursday, September 17, 2015 84Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Glucose Control
A protocolized approach when 2 consecutive blood glucose
levels are >180 mg/dL.
Should target an upper blood glucose ≤180 mg/dL rather
than an upper target blood glucose ≤ 110 mg/dL (grade 1A).
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).
Thursday, September 17, 2015 85Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Tight Glycemic control
Continuous insulin infusion
Maintaining serum glucose levels between 120 and 180 mg/dl
Decreased mortality development of renal failure
Renal Replacement Therapy
Continuous renal replacement therapies and intermittent
hemodialysis are equivalent in patients with severe sepsis and
acute renal failure (grade 2B).
Use continuous therapies to facilitate management of fluid
balance in hemodynamically unstable septic patients (grade
2D).
Thursday, September 17, 2015 87Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Bicarbonate Therapy
Not using sodium bicarbonate therapy for the purpose of
improving hemodynamics or reducing vasopressor requirements in
patients with hypoperfusion-induced lactic acidemia with pH ≥7.15
(grade 2B).
Thursday, September 17, 2015 88Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Deep Vein Thrombosis Prophylaxis Patients with severe sepsis receive daily pharmacoprophylaxis
against venous thromboembolism (VTE) (grade 1B).
This should be accomplished with daily subcutaneous low-
molecular weight heparin (LMWH).
If creatinine clearance is <30 mL/min, use Dalteparin (grade
1A) or another form of LMWH that has a low degree of renal
metabolism (grade 2C) or UFH (grade 1A).
Thursday, September 17, 2015 89Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Deep Vein Thrombosis Prophylaxis Patients with severe sepsis be treated with a combination of
pharmacologic therapy and intermittent pneumatic
compression devices whenever possible (grade 2C).
Septic patients who have a contraindication for heparin use not
receive pharmacoprophylaxis (grade 1B), but receive mechanical
prophylactic treatment, (grade 2C), unless contraindicated.
When the risk decreases start pharmacoprophylaxis
(grade 2C).
Thursday, September 17, 2015 90Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Stress Ulcer Prophylaxis
Stress ulcer prophylaxis using H2 blocker or proton pump
inhibitor be given to patients with severe sepsis/septic shock who
have bleeding risk factors (grade 1B).
When stress ulcer prophylaxis is used, proton pump inhibitors
rather than H2RA (grade 2D)
Patients without risk factors do not receive prophylaxis (grade 2B).
Thursday, September 17, 2015 91Dellinger R P et al. Critical Care Medicine. 2013;41(2):580-637
Nutrit ion
Administer oral or enteral (if necessary) feedings, as
tolerated, rather than either complete fasting or provision of only
intravenous glucose within the first 48 hours after a diagnosis of
severe sepsis/septic shock (grade 2C).
Avoid mandatory full caloric feeding in the first week but
rather suggest low dose feeding (eg, up to 500 calories per day),
advancing only as tolerated (grade 2B).
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Nutrit ion
Use intravenous glucose and enteral nutrition rather than total parenteral
nutrition (TPN) alone or parenteral nutrition in conjunction with enteral
feeding in the first 7 days after a diagnosis of severe sepsis/septic shock
(grade 2B).
Use nutrition with no specific immunomodulating
supplementation rather than nutrition providing specific
immunomodulating supplementation in patients with severe sepsis (grade
2C).
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Setting Goals of Care
It is recommended that the goals of care and prognosis be
discussed with patients and families (grade 1B).
The goals of care be incorporated into treatment and end-of-
life care planning, utilizing palliative care principles where
appropriate (grade 1B).
The goals of care be addressed as early as feasible, but no
later than within 72 hrs of ICU admission (grade 2C).
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SurgeryGet the pus out ofabscesses or foci of infection should be drained
Early definitive care ;e,.g; ruptured appendix, cholecystitis
Mortality
Sepsis: 30% - 50%
Septic Shock: 50% - 60%
SUMMARY AND FUTURE DIRECTIONS Though this document is static, the optimum treatment of severe
sepsis and septic shock is a dynamic and evolving process.
Additional evidence that has appeared since the publication of the 2008 guidelines allows more certainty in making severe sepsis recommendations; however, further programmatic clinical research in sepsis is essential to optimize these evidence-based medicine recommendations.
New interventions will be proven and established interventions may need modification.
This publication represents an ongoing process.
The Surviving Sepsis Campaign and the consensus committee members are committed to updating the guidelines regularly as new interventions are tested and results published.
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