Multiple Organ Dysfunction Syndrome

Philip A. Efron

Darwin N. Ang

Lyle L. Moldawer

Frederick A. Moore

I. Introduction

Multiple organ dysfunction syndrome (MODS) is defined as the dysfunction of at least two organ systems from an inflammatory insult, usually traumatic or infectious shock.
Up to half of all SICU patients will meet the criteria for MODS.
Mortality due to MODS is proportional to the number of affected organs and the duration of dysfunction.
The advent of mechanical ventilation, nutritional support, renal replacement therapy (RRT), and other support improved the rescue of these patients and prospective characterization of this syndrome.
In theory, organ function is recoverable, but patients can fail to return to baseline due to ongoing insults, some of which are iatrogenic (mechanical ventilation, transfusion are examples).
MODS after trauma often follows one of the two distinct patterns:
- Rapid single phase MODS due to massive trauma and tissue injury.
- Delayed MODS, usually due to moderate trauma and shock. This is followed by a secondary insult, often sepsis or an infection.
After trauma, patients who develop MODS are typically older and have a greater injury severity score (ISS) or present to the emergency department with hypotension (SBP <90 mm Hg). Also, patients who develop MODS after trauma are more likely to have early elevated base deficits (greater than 8 mEq/L) and failure to normalize lactate despite resuscitation. Finally, these patients are also more likely to receive blood transfusions. Increasing units of transfused packed red blood cells (PRBCs) correlate with an increased incidence of MODS.

II. Further Classification/Definitions

Systemic inflammatory response syndrome (SIRS) (Table 35-1).
Sepsis
- SIRS due to an infection.
- Sepsis is the most common trigger or source of MODS in the surgical population.

III. Mechanisms

MODS is thought to be due to inflammatory and immune dysregulation after an insult. These triggers include:
- Injury (trauma or operation)
- Burns
- Infection
- Ischemia/reperfusion
- Pancreatitis
Although any of the above factors can trigger the response, MODS is commonly induced by multiple or sustained insults (i.e., the “2-hit” hypothesis).
Some of these insults can be the treatments being used to preserve life, for example vasoconstrictors, transfusions, or mechanical ventilation. Other triggers include secondary events such as fat emboli.

Table 35-1 Definition of SIRS

Patient must have ≥2 of the following:

Body temperature >38°C or <36°C
Heart rate >90 beats/min
Respiratory rate >20 breaths/min or PaCO₂ <32 mm Hg
White blood cell count >12,000 cells/mm³ or <4,000 cells/mm³ or >10% immature neutrophils

IV. Prediction/Prognosis

There is no singular standard to identify MODS and no laboratory test has yet proven diagnostic or prognostic.
Physiologic scoring systems calculate the function of specific organs, determine a severity score and predict outcome. These include the multiple organ dysfunction (MOD) score, the sequential organ failure assessment (SOFA), the logistic organ dysfunction (LOD) systems score, the Marshal MOF score and the Denver MOF score (Table 35-2).

The Acute Pathophysiology and Chronic Health Evaluation (APACHE II) is the most common scoring system that reflects organ dysfunction and is based on
12 physiologic variables. The maximum score is 71; a score of 25 carries a 50% mortality.

Table 35-2 Multiple Organ Failure Score

	Grade 0	Grade 1 Dysfunction	Grade 2 Dysfunction	Grade 3 Dysfunction
Pulmonary PaO₂/FiO₂ Ratio	>208	208 − 165	165 − 83	<83
Renal Creatinine (μmol/L)	<159	160–210	211–420	>420
Hepatic Total Bilirubin (μmol/L)	<34	34–68	69–137	>137
Cardiac Inotropes	No inotropes	Only one inotrope at a small dose*	Any inotrope at moderate dose or >1 agent, all at small doses*	Any inotrope at large dose or >2 agents at moderate doses*
*Inotrope doses (in ug/kg/min):
	Small	Moderate	Large
Milrinone	<0.3	0.4–0.7	>0.7
Vasopressin	<0.03	0.03–0.07	>0.07
Dopamine	<6	6–10	>10
Dobutamine	<6	6–10	>10
Epinephrine	<0.06	0.06–0.15	>0.15
Norepinephrine	<0.11	0.11–0.5	>05
Phenylephrine	<0.6	0.6–3	>3
Adapted from Moore, et al.

Mortality exceeds 50% for patients with ≥3 organ dysfunction. MODS patients are more likely than non-MODS patients to develop complications. Correspondingly, it takes longer to liberate these patients from the ventilator.
The requirement for hemodialysis is also associated with increased mortality in these patients, with some surgical populations having up to a 50% mortality.
Most MODS patients who survive their hospital course will require prolonged rehabilitation, sometimes requiring transfer to a long-term acute care hospital. Up to 1/3 to 1/2 of older patients with significant organ failure die within months of discharge from the ICU.
Trauma patients who survive MODS have a higher overall mortality after discharge than the general population.

V. Pathophysiology

Neurologic
- Brain dysfunction during MODS is characterized by encephalopathy and a reduced level of consciousness.
- Alterations in brain function are best considered MODS until disproven; start immediate efforts to isolate and treat any possible cause.
- Lack of improvement after supportive measures and source control may require imaging (CT scan or MRI), functional (EEG) or invasive testing (lumbar puncture), or drug levels to exclude other etiologies of brain dysfunction.
- Critical illness polyneuropathy is commonly found with sepsis and prolonged use of steroids or paralytic agents. Patients develop diffuse axonal motor and sensory neuropathy which may manifest as weakness and failure to wean from the ventilator.
- B. Pulmonary (see Chapter 38) Patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) (Table 35-3) demonstrate lung injury associated with hypoxemia, non-cardiogenic pulmonary edema, decreased lung compliance, and increased capillary leakage.
- The cause of ALI/ARDS can be direct (e.g., aspiration, pneumonia, chest trauma) or indirect (e.g., pancreatitis, ischemia/reperfusion of the intestines).
- ALI/ARDS is divided into two phases:
  - An initial acute exudative phase, characterized by acute onset hypoxemia and decreased compliance. This phase is refractory to supplemental O₂ but responsive to PEEP.
  - A subsequent fibroproliferative phase, characterized by persistent hypoxemia, worsening compliance, pulmonary hypertension, and CO₂ retention. This phase is less responsive to PEEP. Pneumonia is the most common infection in MODS patients and is a major cause of subsequent morbidity and mortality.
- COPD and other underlying pulmonary diseases are exacerbated by sepsis.

Cardiac

MODS can lead to overall myocardial dysfunction, regardless of the cause.

Underlying causes include repeated ischemic events, inflammatory mediators and altered splanchnic perfusion.

Table 35-3 Definition of Acute Lung Injury and Acute Respiratory Distress Syndrome

Bilateral pulmonary infiltrates on chest x-ray
Pulmonary capillary wedge pressure <18 mm Hg Or no clinical suspension
PaO₂/FiO₂ <300 mm Hg = ALI
PaO₂/FiO₂ <200 mm Hg = ARDS

Table 35-4 RIFLE Criteria

	GFR criteria	Urine output criteria
Risk	↑ serum Cr × 1.5 or ↓ GFR >25%	Urine output <0.5 mL/kg/h for 6 h
Injury	↑ serum Cr × 2.0 or ↓ GFR >50%	Urine output <0.5 mL/kg/h for 12 h
Failure	↑ serum Cr × 3.0; or ↓ GFR >75% or serum Cr ≥4 mg/dL with >0.5 mg/dL ↑ serum Cr	Urine output <0.3 mL/kg/h for 24 h or anuria for 24 h
Loss	Persistent AKI or complete loss of renal function for >4 wks
End-stage kidney disease	End-stage renal disease for >3 mos
GFR, glomerular filtration rate; Cr, Creatinine. The classification system includes separate criteria based on creatinine and urine output and assessment is based on the worst possible value, if both are present.