Diagnostic Considerations
A clinical continuum of severity exists, from sepsis to septic shock and multiple organ dysfunction syndrome (MODS). In a study that evaluated 2527 intensive care unit (ICU) patients with systemic inflammatory response syndrome (SIRS), 26% developed sepsis, 18% developed severe sepsis, and 4% developed septic shock. [55] The incidence of positive results on blood culture was 17% in patients with sepsis and 69% in patients with septic shock
The diagnosis of septic shock requires features of SIRS (eg, mental changes, hyperventilation, distributive hemodynamics, hyperthermia or hypothermia, or reduced, elevated, or left-shifted white blood cells [WBCs]) in addition to a potential source of infection.
Whenever a patient presents with shock, an early working diagnosis must be formulated, an approach to urgent resuscitation must be established, and steps must be taken to confirm the working diagnosis. The following points should be considered for early diagnosis of sepsis:
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Patients with sepsis may present in a myriad of ways, and high clinical suspicion is necessary to identify subtle presentations [56]
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Patients in a septic state should be screened for evidence of tissue hypoperfusion, such as cool or clammy skin, mottling, and elevated shock index (heart rate−to−systolic blood pressure >0.9)
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A lactic acid level higher than 4 mmol/dL has been used as an entry criterion for early goal-directed therapy (EGDT) and an indicator of severe tissue hypoperfusion
A patient with sepsis who is admitted to the ICU should be monitored carefully to facilitate prevention and treatment of the infectious complications that may perpetuate SIRS or trigger recurrent sepsis after the initial improvement. Such complications include sinusitis, urinary tract infection, urosepsis, intravascular catheter–related infections, acalculous cholecystitis, and translocation of bacteria or endotoxin from the gut. Several of these ailments may not manifest clinically; accordingly, a high index of suspicion is crucial for early diagnosis and treatment.
Important to note, three large prospective multicenter randomized clinical trials of EGDT in the management of septic shock (ProCESS [Protocolized Care for Early Septic Shock], [57] ARISE [Australasian Resuscitation In Sepsis Evaluation], [58] and ProMISe [Protocolised Management In Sepsis] [59] ) have all yielded the same negative results, namely that the use of strict protocolized monitoring (central venous catheterization, lactate and ScvO2 measures) and management (targeting a hemoglobin >8 g/dL, ScvO2 >70%) were no better than usual care as long as patients were managed closely.
Differential Diagnoses
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Heatstroke
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Neuroleptic Malignant Syndrome
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Strawberry tongue in a child with staphylococcal toxic shock syndrome. Reproduced with permission from Drage, LE. Life-threatening rashes: dermatologic signs of four infectious diseases. Mayo Clin Proc. 1999;74:68-72.
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Venn diagram showing the overlap of infection, bacteremia, sepsis, systemic inflammatory response syndrome (SIRS), and multiorgan dysfunction.
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A 26-year-old woman developed rapidly progressive shock associated with purpura and signs of meningitis. Her blood culture results confirmed the presence of Neisseria meningitidis. The skin manifestation seen in this image is characteristic of severe meningococcal infection and is called purpura fulminans.
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Gram stain of blood showing the presence of Neisseria meningitidis.
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Acute respiratory distress syndrome (ARDS), commonly observed in septic shock as a part of multiorgan failure syndrome, results in pathologically diffuse alveolar damage (DAD). This photomicrograph shows early stage (exudative stage) DAD.
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Acute respiratory distress syndrome (ARDS), commonly observed in septic shock as a part of multiorgan failure syndrome, results in pathologically diffuse alveolar damage (DAD). This is a high-powered photomicrograph of early stage (exudative stage) DAD.
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Photomicrograph showing delayed stage (proliferative or organizing stage) of diffuse alveolar damage (DAD). Proliferation of type II pneumocytes has occurred; hyaline membranes as well as collagen and fibroblasts are present.
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Photomicrograph showing delayed stage (proliferative or organizing stage) of diffuse alveolar damage (DAD). Fibrin stain depicts collagenous tissue, which may develop into fibrotic stage of DAD.
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Acute respiratory distress syndrome (ARDS) in a patient who developed septic shock secondary to toxic shock syndrome.
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Bilateral airspace disease and acute respiratory failure in a patient with gram-negative septic shock. The source of the sepsis was urosepsis.
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A 45-year-old woman was admitted to the intensive care unit with septic shock secondary to spontaneous biliary peritonitis. She subsequently developed acute respiratory distress syndrome (ARDS) and multiorgan failure.
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An 8-year-old boy developed septic shock secondary to Blastomycosis pneumonia. Fungal infections are rare causes of septic shock.
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A 28-year-old woman who was a former intravenous drug user (human immunodeficiency virus [HIV] status: negative) developed septic shock secondary to bilateral pneumococcal pneumonia.
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Diagram depicting the pathogenesis of sepsis and multiorgan failure. DIC = disseminated intravascular coagulation; IL = interleukin.
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Soft-tissue infection secondary to group A streptococci, leading to toxic shock syndrome.
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Necrotizing cellulitis of toxic shock syndrome.
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Necrosis of the little toe of the right foot and cellulitis of the foot secondary to group A streptococcal infection.
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Group A streptococci cause beta hemolysis on blood agar.
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Gram stain of blood showing group A streptococci that was isolated from a patient who developed toxic shock syndrome. Image courtesy of T. Matthews.
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A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome. The leg was incised to exclude underlying necrotizing infection. Image courtesy of Rob Green, MD.
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A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome (same patient as in previous image). This patient also had streptococcal pharyngitis. Image courtesy of Rob Green, MD.
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A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome (same patient as in previous image). The patient had diffuse erythroderma, a characteristic feature of the syndrome. Image courtesy of Rob Green, MD.
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A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome (same patient as in previous image). The patient had diffuse erythroderma, a characteristic feature of the syndrome. He improved with antibiotics and intravenous gammaglobulin therapy. Several days later, a characteristic desquamation of the skin occurred over his palms and soles. Image courtesy of Rob Green, MD.
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Progression of soft-tissue swelling to vesicle or bullous formation is an ominous sign and suggests streptococcal shock syndrome. Image courtesy of S. Manocha.
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Extensive debridement of necrotizing fasciitis of the hand.
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Healing of the hand after aggressive surgical debridement of necrotizing fasciitis (same patient as in previous image).
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A 58-year-old patient presented in septic shock. On physical examination, progressive swelling of the right groin was observed. On exploration, necrotizing cellulitis, but not fasciitis, was present. The wound cultures grew group A streptococci. The patient developed severe shock (toxic shock syndrome). Computed tomography (CT) scanning helped to evaluate the extent of the infection and to exclude other pathologies (eg, psoas abscess, osteomyelitis, inguinal hernia).
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Computed tomography (CT) scan from a 58-year-old patient who presented in septic shock (same patient as in previous image). Progressive swelling of the right groin was noted, and necrotizing cellulitis, but not fasciitis, was present. The wound cultures grew group A streptococci. The patient developed severe shock (toxic shock syndrome). CT scanning helped in the evaluation of the extent of the infection and in the exclusion of other pathologies (eg, psoas abscess, osteomyelitis, inguinal hernia).
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Computed tomography (CT) scan from a 58-year-old patient who presented in septic shock (same patient as in previous image). Progressive swelling of the right groin was noted, and necrotizing cellulitis, but not fasciitis, was present. The wound cultures grew group A streptococci. The patient developed severe shock (toxic shock syndrome). CT scanning helped in the evaluation of the extent of the infection and in the exclusion of other pathologies (eg, psoas abscess, osteomyelitis, inguinal hernia).
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Space-occupying lesion correlating with left temporoparietal metastatic infiltration associated with peritumoral edema.
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Space-occupying lesion correlating with left temporoparietal metastatic infiltration associated with peritumoral edema (same lesion as shown in previous computed tomography image).
Tables
System |
0 Points |
1 Point |
2 Points |
3 Points |
4 Points |
Respiration PaO2a/FiO2b |
≥400 mm Hg |
< 400 mm Hg |
< 300 mm Hg |
< 200 mm Hg (with respiratory support) |
< 100 mm Hg (with respiratory support) |
Coagulation Platelet count |
≥150 x 103/µL |
< 150 x 103/µL |
< 100 x 103/µL |
< 50 x 103/µL |
< 20 x 103/µL |
Liver Bilirubin level |
< 1.2 mg/dL |
1.2-1.9 mg/dL |
2-5.9 mg/dL |
6-11.9 mg/dL |
>12 mg/dL |
Cardiovascular |
MAPc ≥70 mm Hg |
MAP >70 mm Hg |
Dopamine < 5 or dobutamine (any dose)e |
Dopamine 5.1-15 or epinephrine ≤0.1 or norepinephrine ≤0.1e |
Dopamine >15 or epinephrine >0.1 or norepinephrine >0.1e |
Central nervous system GCSd score |
15 |
13-14 |
10-12 |
6-9 |
< 6 |
Renal Creatinine Urine output |
< 1.2 mg/dL |
1.2-1.9 mg/dL |
2-3.4 mg/dL |
3.5-4.9 mg/dL < 500 mL/day |
>5 mg/dL < 200 mL/day |
aPaO2=Partial pressure of oxygen. bFiO2=Fraction of inspired oxygen. cMAP=Mean arterial pressure. dGCS=Glasgow Coma Scale (range, 3-15, with higher indicating better function). eCatecholamine doses administered as µg/kg/min for ≥1 hour. |
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Organ System |
Sepsis Criteria |
Severe Sepsis Criteria |
Pulmonary |
Arterial hypoxemia: PaO2/FIO2< 300 |
Arterial hypoxemia: PaO2/FIO2< 250 in absence of pneumonia and < 200 in presence of pneumonia |
Hepatic |
Hyperbilirubinemia: Plasma total bilirubin >4 mg/dL or 70 µmol/L |
Hyperbilirubinemia: Plasma total bilirubin >2 mg/dL or 34.2 µmol/L |
Renal |
Creatinine increase >0.5 mg/dL or 44.2 µmol/L Acute oliguria: Urine output < 0.5 mL/kg/hr for ≥2 hr despite adequate fluid resuscitation |
Creatinine >2 mg/dL or 176.8 µmol/L Acute oliguria: Urine output < 0.5mL/kg/hr for ≥2 hr despite adequate fluid resuscitation |
Gastrointestinal |
Ileus: Absent bowel sounds |
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Hematologic |
INR >1.5, aPTT >60 s, or platelets < 100,000/µL |
INR >1.5 or platelets < 100,000/µL |
Cardiovascular |
Hyperlactatemia >1 mmol/L; decreased capillary refill or mottling Hemodynamic status: SBP < 90 mm Hg, MAP < 70 mm Hg, or SBP decrease >40 mm Hg |
Hyperlactatemia: Above upper limits of laboratory normal Hemodynamic status: SBP < 90 mm Hg, MAP < 70 mm Hg, or SBP decrease >40 mm Hg |
Central nervous system |
Confusion, lethargy, coma |
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aPTT = activated partial thromboplastin time; FIO2 = fraction of inspired oxygen; INR = international normalized ratio; MAP = mean arterial pressure; PaO2 = partial pressure of oxygen; PEEP = positive end-expiratory pressure; PT = prothrombin time; SBP = systolic blood pressure. Source: Dellinger RP, Levy MM, Rhodes A, et al, for the Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. [11] |
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Type |
Mediator |
Activity |
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Cellular mediators |
LPS |
Activation of macrophages, neutrophils, platelets, and endothelium releases various cytokines and other mediators |
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Lipoteichoic acid |
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Peptidoglycan |
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Superantigens |
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Endotoxin |
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Humoral mediators |
Cytokines |
Activate inflammatory pathways |
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Potent proinflammatory effect |
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Acts as pyrogen, stimulates B- and T-cell proliferation |
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Neutrophil chemotactic factor, activation and degranulation of neutrophils |
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Inhibits cytokine production, induces immunosuppression |
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Activates macrophages and T cells |
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Promotes neutrophil and macrophage, platelet activation |
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Complement |
Promotes neutrophil and macrophage, platelet activation and chemotaxis, other proinflammatory effects |
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Nitric oxide |
Involved in hemodynamic alterations of septic shock; cytotoxic, augments vascular permeability, contributes to shock |
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Lipid mediators |
Enhance vascular permeability and contribute to lung injury |
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Arachidonic acid metabolites |
Augment vascular permeability |
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Adhesion molecules |
Enhance neutrophil-endothelial cell interaction, regulate leukocyte migration and adhesion, and play a role in pathogenesis of sepsis; increased levels of VAP-1 activity and anchor protein SDC-1 content have been found in critically ill patients with septic shock [12] |
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Late mediator of endotoxin-induced lethality and tissue repair |
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G-CSF = granulocyte colony-stimulating factor; IL = interleukin; LPS = lipopolysaccharide; MIF = macrophage inhibitory factor; PAF = platelet-activating factor; SDC-1 = syndecan-1; TNF = tumor necrosis factor; VAP-1 = vascular adhesion protein–1. Source: Cinel I, Opal SM. Molecular biology of inflammation and sepsis: a primer. Crit Care Med. 2009 Jan;37(1):291-304. [13] |
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- Overview
- Presentation
- DDx
- Workup
- Treatment
- Approach Considerations
- General Treatment Guidelines in Septic Shock
- Goals of Hemodynamic Support
- Fluid Resuscitation
- Vasopressor Therapy
- Inotropic Therapy and Augmented Oxygen Delivery
- Empiric Antimicrobial Therapy
- Corticosteroid Therapy
- Glycemic Control
- DVT Prophylaxis and Management of DIC
- Management of Acute Respiratory Distress Syndrome
- Surgical Treatment
- Prevention
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- Questions & Answers
- Media Gallery
- Tables
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