Strategizing against

Systemic Inflammatory Syndrome

Trey Rumph

Objectives Define SIRS and Sepsis, and understand the

difference between the two Identify those at risk for SIRS or Sepsis Understand the general pathophysiology of

SIRS Understand how organ systems may be

affected by SIRS or Sepsis Understand how the use of Nutrition can help

in the ICU patient population with SIRS or Sepsis

Prevalence Leading cause of death in critically ill patients,

claiming approximately 225,000 deaths annually in the US alone

Associated with a high mortality rate ~40-50%, even with appropriate therapy

InflammationThe Role of inflammation is to contain the site of

damage, localize the response and restore tissue function.

Initiated by microbes or tissue damage

Dilation of the small blood vessels, causes leakage in those vessels and a pathway for leukocytes to get from the blood stream into the tissue in created increased blood flow to damaged area.

Causes the heat and redness associated with inflammation

Cardinal Signs:Redness Swelling Heat Pain

Infection A pathological process involving a sterile or

colonized site that becomes over run with a pathogenic paracytic microorganism

SIRS

Systemic Inflammatory Response Syndrome 1+ symptoms

*Can be observed without the identification of an infection

Sepsis Must meet criteria for Infection + >2 SIRS

criteria

Severe Sepsis Sepsis complicated by organ dysfunction,

organ hypoperfusion or hypotension

Septic Shock Persistent arterial hypotension in a septic

patient Defined: systolic arterial pressure <90 mmHg or a

reduction in systolic pressure >40mmHg from baseline

Classification system for Sepsis

PIRO System P: predisposing conditions

I: insult, the nature and extent of the

R: response, the nature and magnitude of the host

O: organ dysfunction, the degree of concomitant

this system stratifies patients based on these criteria, but it has not gone through enough clinical trails to be applicable in practice

Pathophysiology of Septic Shock Pathogenic micro-organism Body illicit a response to fight off invader

Neuroendocrine reflexes* Inflammatory Response* Plasma Protein Cascades

Complement, Intrinsic and Extrinsic Pathways, Fibrinolytic System

Innate and Humeral Immunity Response The interaction between these different

systems is what causes the body microvascular harm organ/tissue ischemia and multiple organ dysfunction/failure

Neuroendocrine reflex The response initiated by recognition of free

LPS in the body. Fever Stimulation of the bone marrow and function of

leukocytes Catabolism Breakdown of muscle proteins Rapid increase in production of acute-phase

proteins (APP) Positive

(CRP, D-dimer, Coagulation factors, Haptoglobin, Ferritin) Negative

(Albumin, Transferrin, Retinol-binding protein)

Inflammatory Response

Inflammatory Response Hyper-inflammatory state SIRS “Systemic

inflammatory response syndrome” If severe can precipitate to Early MOF (multiple

organ failure)

As time proceeds, certain aspects of SIRS begin to down-regulate (to minimize autogenous tissue injury) CARS “counter anti-inflammatory response syndrome” If severe can cause a severe immunosuppressed

state Lead to infections, local and systemic Late MOF-

associated infections

Liver The liver actively modulates inflammatory

processes by filtering, inactivating, and clearing bacteria, bacterial products (e.g., endotoxin), vasoactive substances, and inflammatory mediators.

A stimulated liver manufactures cytokines, bioactive lipid and Acute phase proteins

Early Dysfunction (1st couple of hours) Hypoperfusion “Liver shock”

Increase in LFTs Reversed with adequate treatment

Late Dysfunction Structural and functional injury May be accounted to a bacterial, endotoxin, inflammatory

mediator spillover that trigger/sustain the MOF

Gastrointestinal Tract Instigator and victim of MOF Estimated ~70% of immune system Hypoperfusion decreased function of the intestinal

epithelium as a barrier between the enteric flora and portal circulation If toxin reaches the portal system then cycle continues, and

SIRS response intensifies Mesenteric lymph nodes are last line defense to neutralize

toxin Reperfusion initiates pro-inflammatory mediators

to be made that amplify the early SIRS contributing to MOF

Bacterial overgrowth and increased release of endotoxin contribute to late sepsis-associated MOF

Gastrointestinal Tract Disuse of the gut

Leads to ileus formation, colonization of new pathogens in the normally sterile upper gut, and increased mucosal permeability and decreased local gut immunity decreased gut immunity furthers systemic

immunosuppression Additionally, gut flora disseminate via aspiration or

translocation to become pathogenic and cause late infection.

GI motility is generally decreased following: Neurologic injury Severe trauma

Gastrointestinal Tract Figure 20.1 “conceptual framework for the

role of the gut in late MOF.”

Nutritional Clinical Effects Protein, Carbohydrates and Lipids

Risks associated with overfeeding

Clinical Pearls

TPN Formulation Protein Aminosyn 15%

GOAL: attenuate the loss of lean body mass (high protein)

Normal 1.2 – 2.0 g/kg (ABW) BMI <30

Obese > 2.0 g/kg (IBW) BMI 30-40 > 2.5 g/kg (IBW) BMI > 40

During Stress the body is in an increased metabolic state and more

proteolysis is occurring, use nutrition to attenuate damage incurred by supplying enough protein to maintain the nitrogen balance.

TPN Formulation Carbohydrates Dextrose 70%

GOAL: reduce excess glucose Patients are in a catabolic state and experience glucose

intolerance

During Stress hepatic glucose production is double the normal rates

during stressed state, and the provision of glucose at a rate of 4mg/kg/min is only able to suppress 50% of the endogenous glucose production.

TPN Formulation Lipids Liposyn 20%/30%

GOAL: limit serum FFA

During Stress Insulin secretion is inhibited Lipolysis is activated Hepatic clearance of FFA increases Increased production of hepatic TG Increased hepatic TG leads to accumulation in the liver

“fatty liver”

Summary

Consequences Overfeeding Protein

Impair kidney function due to the following: Uremia Hypertonic dehydration Metabolic acidosis

Carbs Fatty Liver, mechanical ventilation

Hyperglycemia Hypercapnia

Fats Fatty Liver

Hypertriglyceridemia Fat overload syndrome

During a stress response the patient will have increase glucose circulation along with FFA mobilization increased metabolic activity (ICU patients)

Important to realize is that this therapy does Important to realize is that this therapy does not prevent catabolism it merely minimizes not prevent catabolism it merely minimizes the amount of damage that could possibly the amount of damage that could possibly incur in the patient without proper nutritionincur in the patient without proper nutrition

Clinical Pearls Tight Glycemic control (BG < 150)

No more than 3.0mg/kg/min Patients become insulin intolerant

Limit Lipids Due to increased FFA during sepsis limit lipids to <

20% of NP Ample Protein on board

To help prevent proteolysis we add between 1.2-2.5g/kg, depending on the BMI of the patient

Questions???

“The microorganisms…turn out…to be rather more like bystanders. It is our response to their presence that makes the disease. Our

arsenals for fighting off bacteria are so powerful…that we are more in danger from

them than the invaders.”-Lewis Thomas

Germs NEJM 1972;287:553-5

Table 6-1 Criteria for Systemic Inflammatory Response Syndrome

General variables Hemodynamic variables

  Fever [core temp >38.3°C (100.9°F)]   Arterial hypotension (SBP <90 mmHg, MAP <70, or SBP decrease >40 mmHg)

  Hypothermia [core temp <36°C (96.8°F)]   SVO2 >70% 

  Heart rate >90 bpm    Cardiac index >3.5 L/min per square meter

  Tachypnea Organ dysfunction variables

  Altered mental status   Arterial hypoxemia

  Significant edema or positive fluid balance (>20 mL/kg over 24 h)

  Acute oliguria

   Hyperglycemia in the absence of diabetes   Creatinine increase

Inflammatory variables   Coagulation abnormalities

  Leukocytosis (WBC >12,000)   Ileus

  Leukopenia (WBC <4000)   Thrombocytopenia

  Bandemia (>10% band forms)   Hyperbilirubinemia

  Plasma C-reactive protein > 2 s.d. above normal value

Tissue perfusion variables

  Plasma procalcitonin >2 s.d. above normal value

  Hyperlactatemia

  Decreased capillary fillingbpm = beats per minute; MAP = mean arterial pressure; SBP = systolic blood pressure; s.d. = standard deviations; SVO2 = venous oxygen saturation; WBC = white blood cell count.