Clinical significance and methods
Category, grade | Definition |
---|---|
Strength of recommendation | |
A | Good evidence to support a recommendation for use |
B | Moderate evidence to support a recommendation for use |
C | Poor evidence to support a recommendation |
D | Moderate evidence to support a recommendation against use |
E | Good evidence to support a recommendation against use |
Quality of evidence | |
I | Evidence from ≥1 properly randomized, controlled trial |
II | Evidence from ≥1 well-designed clinical trial, without randomization; from cohort or case-controlled analytic studies (preferably from >1 centre); from multiple time-series; or from dramatic results from uncontrolled experiments |
III | Evidence from opinions of respected authorities, based on clinical experience, descriptive studies or reports of expert committees |
Definitions
General parameters |
Fever (core temperature >38.3 °C) |
Hypothermia (core temperature <36.0 °C) |
Heart rate (>90 bpm or >2 SD above the normal value for age) |
Tachypnoea (>30 bpm) |
Altered mental status |
Significant edema or positive fluid balance (>20 mL/kg over 24 h) |
Hyperglycaemia (plasma glucose >110 mg/dL or >7.7 mmol/L) in the absence of diabetes |
Inflammatory parameters |
Plasma C reactive protein or plasma procalcitonin (>2 SD above the normal value) |
Haemodynamic parameters |
Arterial hypotension (systolic blood pressure <90 mmHg, mean arterial pressure <70 mmHg, or a systolic blood pressure decrease >40 mmHg in or <2 SD below normal for age) |
Mixed venous oxygen saturation (>70 %) |
Cardiac index (>3.5 L/min/m2) |
Organ dysfunction parameters |
Arterial hypoxaemia (PaO2/FIO2 <300) |
Acute oliguria (urine output <0.5 mL/kg/h for ≥2 h) |
Creatinine increase (≥0.5 mg/dL) |
Coagulation abnormalities (international normalized ratio >1.5 or activated partial thromboplastin time >60 s) |
Ileus (absent bowel sounds) |
Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 mmol/L) |
Tissue perfusion parameters |
Hyperlactataemia (>3 mmol/L) |
Decreased capillary refill or mottling |
Severe sepsis | Sepsis with new signs of organ dysfunction or a decrease in organ perfusion (lactate acidosis, oliguria (<30 mL/h or <0.5 mL/kg/h), hypotension (<90 mmHg or decrease of >40 mmHg), mental alteration) |
Septic shock | Severe sepsis and hypotension persistent despite adequate fluid substitution and exclusion for other reasons for hypotension |
Incidence
Risk factors and prognosis
Risk factors for bacteraemia
Risk factors for development of severe sepsis
Prognosis
Microbiology
Origin | Frequent pathogens |
---|---|
Unknown | Coagulase-negative Staphylococci, Escherichia coli, Enterococcus species |
Lung |
Pseudomonas aeruginosa, Streptococcus pneumoniae (pneumococci), Viridans (alpha-haemolytic) streptococci, Acinetobacter species
|
Abdomen |
Escherichia coli, P. aeruginosa, Clostridium spp., Enterococcus spp., Klebsiella species |
Urogenital |
Escherichia coli, Klebsiella species, Pseudomonas aeruginosa
|
Soft tissue |
Staphylococcus aureus, alpha-haemolytic streptococci
|
CVC | Coagulase-negative Staphylococci, Coryneform bacteria, Propionibacterium species, Candida albicans, Candida tropicalis, Candida parapsilosis, Stenotrophomonas maltophilia
|
Treatment
Antimicrobial treatment
Treatment of cardiovascular insufficiency
Treatment of pulmonary failure
Management of renal dysfunction
Nutrition and control of metabolic functions
Caloric intake
Supplements
Hyperglycaemia
Treatment with corticosteroids
High-dose corticosteroid treatment (>300 mg hydrocortisone per day)
Low-dose corticosteroid treatment (≤300 mg hydrocortisone per day)
Treatment with coagulation inhibitors
Heparin
Antithrombin
Activated protein C (APC)
Thrombomodulin
Cytokines and haematopoietic growth factors (G-CSF, GM-CSF)
Immunoglobulins
Granulocyte transfusions
Transfusion management in sepsis
Summary of recommendations
Recommendation | Evidence level |
---|---|
Antimicrobial treatment | |
Initial treatment with meropenem or with imipenem/cilastatin or with piperacillin/tazobactam | AIII |
A combination treatment with an aminoglycoside in neutropenic patients with septic shock and severe sepsis may be considered | BIII |
Cardiovascular insufficiency | |
Albumin-containing solutions may be used in patients with sepsis and septic shock | CII |
The drug of choice to elevate the vasotonus is norepinephrine | BII |
In case of sepsis-related myocardial depression leading to low cardiac output despite adequate volume substitution, vasopressor treatment with dobutamine should be instituted | AII |
Treatment of pulmonary failure | |
Non-invasive positive pressure ventilation (CPAP or bilevel positive airway pressure) should be preferred if possible in patients without hypotension or altered mental status | AII |
An early start of non-invasive ventilation, prior to development of severe hypoxaemia, is favourable | BII |
Management of renal dysfunction | |
Intermittent haemodialysis and continuous renal replacement therapies are equivalent | BI |
No firm recommendations can be given for the use of increased doses of renal replacement therapy | CI |
Low-dose dopamine for protection of renal function is not recommended | EI |
Nutrition and control of metabolic functions | |
Enteral nutrition is preferred over parenteral nutrition | BII |
During initial phase of sepsis, energy supply should not exceed 20–25 kcal/kg ideal bodyweight (IBW) | DIII |
During recovery, 25–30 kcal/kg IBW should be provided | BIII |
We do not recommend general use of arginine, omega-3 fatty acids and combined formulations in patients with severe sepsis and septic shock | DII |
Glutamine substitution cannot be recommended in patients with severe sepsis and septic shock | EI |
Further clinical trials regarding the adequate dosing and treatment duration are needed before treatment with selenium can be recommended | DI |
Aiming at strictly normal blood glucose level of 4.4–6.6 mmol/L (80–120 mg/dL) is not recommended | EI |
Blood glucose levels should be kept ≤9.9 mmol/L (≤180 mg/dL) in septic neutropenic patients | BIII |
A high variability of blood glucose levels in septic patients should be avoided, as this is associated with increased mortality | BIII |
Corticosteroids | |
High-dose corticosteroids should not be used in neutropenic or non-neutropenic septic patients | EI |
The routine use of substitutive doses of hydrocortisone in neutropenic patients with sepsis is not recommended | DI |
Low-dose corticoid treatment may be considered in patients with insufficient restoration of blood pressure levels despite adequate fluid resuscitation and vasopressor treatment | BII |
Treatment with coagulation inhibitors | |
Further trials on the use of low-dose heparin (500 IU/h for 7 days) are needed before recommendations can be made | CI |
Routine use of antithrombin is not recommended as treatment of sepsis in neutropenic patients antithrombin may be considered during DIC and sepsis | DI |
BII | |
Growth factors and immunoglobulins | |
The routine additional use of G-CSF or GM-CSF as standard treatment of sepsis in neutropenia is not recommended | DI |
There is moderate degree of evidence to support the use of i.v. immunoglobulins in sepsis | BII |
Transfusion management | |
The cut-off for substitution of platelets is often set to a higher value (platelets 20,000/μL instead of 10,000/μL during sepsis) | BIII |
A transfusion trigger of <9 g/dL haemoglobin during neutropenic sepsis is recommended | BIII |