How does multiple organ dysfunction syndrome (MODS) develop and progress in sepsis/septic shock?

Updated: Oct 07, 2020
  • Author: Andre Kalil, MD, MPH; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, FAPS, MCCM  more...
  • Print

Two well-defined forms of MODS exist. In either, the development of ALI or ARDS is of key importance to the natural history, though ARDS is the earliest manifestation in all cases.

In the more common form of MODS, the lungs are the predominant, and often the only, organ system affected until very late in the disease. Patients with this form of MODS most often present with a primary pulmonary disorder (eg, pneumonia, aspiration, lung contusion, near-drowning, chronic obstructive pulmonary disease [COPD] exacerbation, hemorrhage, or pulmonary embolism [PE]).

Progression of lung disease occurs to meet the ARDS criteria. Pulmonary dysfunction may be accompanied by encephalopathy or mild coagulopathy and persists for 2-3 weeks. At this time, the patient either begins to recover or progresses to develop fulminant dysfunction in other organ systems. Patients who develop another major organ dysfunction often do not survive.

In the second, less common, form of MODS, the presentation is quite different. Patients affected by this form often have an inciting source of sepsis in organs other than the lung; the most common sources are intra-abdominal sepsis, extensive blood loss, pancreatitis, and vascular catastrophes.

Not only does ALI or ARDS develop early, but dysfunction also develops in other organ systems, including the hepatic, hematologic, cardiovascular, and renal systems and central nervous system (CNS). Patients remain in a pattern of compensated dysfunction for several weeks, then either recover or deteriorate further.

Criteria for mild and severe organ dysfunction have been established by the 2012 Surviving Sepsis Guidelines (see Table 2, below). Of note, even though this is the last update of the Surviving Sepsis Campaign, they still separate sepsis and severe sepsis, which was more recently modified by the Sepsis-3 consensus in 2016. [1]

Table 2. Surviving Sepsis Guidelines Criteria for Organ Dysfunction (Open Table in a new window)

Organ System

Sepsis Criteria

Severe Sepsis Criteria


Arterial hypoxemia: PaO2/FIO2<300

Arterial hypoxemia: PaO2/FIO2<250 in absence of pneumonia and <200 in presence of pneumonia


Hyperbilirubinemia: Plasma total bilirubin >4 mg/dL or 70 µmol/L

Hyperbilirubinemia: Plasma total bilirubin >2 mg/dL or 34.2 µmol/L


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


Ileus: Absent bowel sounds



INR >1.5, aPTT >60 s, or platelets <100,000/µL

INR >1.5 or platelets <100,000/µL


Hyperlactatemia >1 mmol/L; decreased capillary refill or mottling

Hemodynamic status: SBP 40 mm Hg

Hyperlactatemia: Above upper limits of laboratory normal

Hemodynamic status: SBP 40 mm Hg

Central nervous system

Confusion, lethargy, coma





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]

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!