8.3 Sepsis, Systemic Inflammatory Response Syndrome (SIRS) & DIC

Sepsis, Systemic Inflammatory Response Syndrome (SIRS) & DIC

Systemic Inflammatory Response Syndrome (SIRS), Sepsis, and Disseminated Intravascular Coagulation (DIC) form a continuous spectrum of critical illness in veterinary emergency and critical care. When localized inflammation escapes physiological homeostatic control, widespread endothelial activation, cytokine release, microvascular thrombosis, and mitochondrial dysfunction culminate in Multiple Organ Dysfunction Syndrome (MODS) and death.

1. Defining SIRS, Sepsis, and Septic Shock

• SIRS (Systemic Inflammatory Response Syndrome): The clinical manifestation of systemic, dysregulated immune activation triggered by infectious or severe non-infectious insults (e.g., severe acute pancreatitis, massive trauma, heatstroke, burn injury, or neoplasia).
• Sepsis: SIRS caused by a confirmed or highly suspected infectious etiology (e.g., septic peritonitis, pyometra, pyothorax, severe pneumonia, bacterial endocarditis, or bite wound abscesses) resulting in acute, life-threatening organ dysfunction.
• Septic Shock: A subset of sepsis in which profound circulatory, cellular, and metabolic abnormalities significantly increase mortality. Clinically defined as persistent arterial hypotension (Mean Arterial Pressure [MAP] $<65\text{ mmHg}$ or Systolic Blood Pressure [SBP] $<90\text{ mmHg}$) despite adequate intravascular fluid resuscitation, or hyperlactatemia ($>2.0\text{ mmol/L}$) requiring vasopressor therapy.

[The Sepsis Continuum]
  ┌─────────────────────────────────────────────────────────────┐
  │  SIRS: Systemic Inflammatory Response (Non-Infectious/Infectious)│
  └──────────────────────────────┬──────────────────────────────┘
                                 ▼
  ┌─────────────────────────────────────────────────────────────┐
  │  SEPSIS: SIRS + Documented Infection + Organ Dysfunction    │
  └──────────────────────────────┬──────────────────────────────┘
                                 ▼
  ┌─────────────────────────────────────────────────────────────┐
  │  SEPTIC SHOCK: Sepsis + Refractory Hypotension (MAP <65)    │
  │                Requiring Vasopressor Infusions              │
  └──────────────────────────────┬──────────────────────────────┘
                                 ▼
  ┌─────────────────────────────────────────────────────────────┐
  │  MODS / DIC: Multi-Organ Dysfunction & Consumptive Bleeding │
  └─────────────────────────────────────────────────────────────┘

2. Canine vs. Feline SIRS Diagnostic Criteria

Because feline cardiovascular and inflammatory physiology differs fundamentally from that of canines, distinct species-specific criteria must be applied:

| Parameter | Canine SIRS Criteria (Must meet $\ge 2$ of 4) | Feline SIRS Criteria (Must meet $\ge 2$ or $3$ of 4) | |---|---|---|| | Core Body Temperature | $<100.6^\circ\text{F}$ ($<38.1^\circ\text{C}$) or $>102.6^\circ\text{F}$ ($>39.2^\circ\text{C}$) | $<100.0^\circ\text{F}$ ($<37.8^\circ\text{C}$) or $>104.0^\circ\text{F}$ ($>40.0^\circ\text{C}$) | | Heart Rate | $>120\text{ beats/min}$ (Tachycardia) | $<140\text{ beats/min}$ (Bradycardia) or $>225\text{ beats/min}$ (Tachycardia) | | Respiratory Rate | $>20\text{ breaths/min}$ (or $P\text{aCO}_2 < 30\text{ mmHg}$) | $>40\text{ breaths/min}$ (or $P\text{aCO}_2 < 30\text{ mmHg}$) | | White Blood Cell Count (WBC) | $<6,000/\mu\text{L}$, $>16,000/\mu\text{L}$, or $>3%$ band neutrophils | $<5,000/\mu\text{L}$, $>19,000/\mu\text{L}$, or $>5%$ band neutrophils |

The Feline Septic Shock Triad: Hypothermic Bradycardia

In dogs, early sepsis classically manifests as hyperdynamic (warm) shock characterized by tachycardia, pyrexia, bright red (injected) mucous membranes, bounding pulses, and rapid CRT (<1 second).

Conversely, cats with sepsis classically present in hypodynamic (cold) shock, displaying the lethal feline triad: Hypothermia, Bradycardia ($<140\text{ bpm}$), and Severe Hypotension. Feline peripheral vessels fail to constrict appropriately during hypothermia, and endogenous opiate release and vagal stimulation suppress normal compensatory tachycardia. Warming a hypothermic, hypovolemic cat without prior volume resuscitation precipitates catastrophic vasodilation and cardiac arrest.

3. Resuscitation & Vasopressor Protocols in Septic Shock

The Emergency Sepsis Bundle (Hour-1 Management)

1. Early Diagnostic Sampling: Collect blood cultures (aerobic and anaerobic), blood lactate, baseline CBC/biochemistry, and point-of-care ultrasound (AFAST/TFAST) prior to or immediately alongside antimicrobial administration.
2. Immediate Broad-Spectrum Bactericidal IV Antimicrobials: Administer within the first hour of admission. Typical empiric four-quadrant combinations include:
   • Ampicillin/Sulbactam ($30\text{–}50\text{ mg/kg IV q8h}$) or Cefazolin ($30\text{–}40\text{ mg/kg IV q8h}$) PLUS Enrofloxacin ($10\text{–}15\text{ mg/kg IV q24h}$ in dogs; $5\text{ mg/kg IV q24h}$ in cats) or an aminoglycoside (Amikacin) if renal perfusion is preserved.
   • Add Metronidazole ($10\text{–}15\text{ mg/kg IV q12h}$) if anaerobic coverage is not fully addressed.
3. Early Goal-Directed Crystalloid Resuscitation: Administer balanced isotonic crystalloids (Plasmalyte-A, Normosol-R, LRS) in rapid titrated aliquots ($10\text{–}20\text{ mL/kg}$ in dogs; $5\text{–}10\text{ mL/kg}$ in cats) over 15 minutes, evaluating dynamic responsiveness (lactate clearance, blood pressure, CRT, pulse quality).
4. Emergent Source Control: Drain infected effusions, debride necrotizing soft tissues, or perform emergency exploratory laparotomy (e.g., for septic peritonitis or pyometra) once cardiovascular parameters are stabilized.

Vasopressor & Inotropic Therapy in Refractory Septic Shock

When fluid resuscitation restores intravascular volume but arterial hypotension persists (MAP $<65\text{ mmHg}$ or SBP $<90\text{ mmHg}$), vasopressor constant rate infusions (CRIs) must be initiated immediately via a central or secure peripheral line:

• Norepinephrine (First-Line Vasopressor of Choice):
  • Dose: $0.1\text{ to }1.0\text{ mcg/kg/min IV CRI}$ (titrated to maintain MAP $\ge 65\text{ mmHg}$).
  • Pharmacology: Potent $\alpha_1$-adrenergic receptor agonist causing systemic vasoconstriction, with modest $\beta_1$-inotropic support. Significantly superior to dopamine in reversing sepsis-induced vasodilation without inducing severe tachyarrhythmias.
• Vasopressin (Second-Line / Adjunct Vasopressor):
  • Dose: $0.5\text{ to }2.0\text{ mU/kg/min}$ ($0.0005\text{–}0.002\text{ U/kg/min IV CRI}$). Non-adrenergic $V_1$ vascular smooth muscle agonist; restores vascular tone in acidic, catecholamine-resistant vascular beds.
• Dobutamine (Inotropic Agent):
  • Dose: $2.5\text{ to }10\text{ mcg/kg/min IV CRI}$ (Dogs); $1.0\text{ to }5.0\text{ mcg/kg/min}$ (Cats). $\beta_1$-adrenergic agonist indicated when myocardial contractility is blunted despite restored MAP.

4. Disseminated Intravascular Coagulation (DIC)

Disseminated Intravascular Coagulation is not a primary disease but a catastrophic, acquired secondary syndrome characterized by systemic, unchecked activation of coagulation. Driven by massive tissue factor release and cytokine storm, DIC progresses through two distinct clinical phases:

[Biphasic Evolution of DIC]
  PHASE 1: HYPERCOAGULABLE (NON-OVERT DIC)     PHASE 2: HYPOCOAGULABLE (OVERT / CONSUMPTIVE DIC)
  • Systemic microvascular fibrin deposition    • Exhaustion of clotting factors & platelets
  • Organ ischemia & micro-thrombi              • Widespread hyperfibrinolysis
  • ATIII consumed (<60-70%)                    • Spontaneous mucosal & cavitary bleeding
  • Normal or minimally altered PT/aPTT         • Markedly prolonged PT/aPTT (>25%)
  • Subclinical, silent multi-organ damage      • Schistocytes, severe thrombocytopenia

The DIC Diagnostic Biomarker Panel

Because no single laboratory test confirms DIC, diagnosis requires satisfying at least 3 to 4 of the following diagnostic criteria in an at-risk patient:

1. Prolongation of Coagulation Times (PT and aPTT): Both Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) are prolonged by $>25%$ above upper reference intervals, reflecting severe consumption of extrinsic, intrinsic, and common pathway coagulation factors.
2. Severe Thrombocytopenia: Progressive, severe decline in circulating platelet count (often $<50,000\text{–}100,000/\mu\text{L}$) due to entrapment in widespread microvascular thrombi.
3. Schistocytes (RBC Fragmentation): Helmet cells and sheared erythrocyte fragments identified on peripheral blood smears, caused by mechanical bisection of red cells as they squeeze through fibrin-clogged capillaries.
4. Elevated D-Dimers and Fibrin Degradation Products (FDPs): High levels confirm both extensive thrombin-mediated fibrin clot formation and secondary plasmin-mediated fibrinolysis ($D\text{-dimers } >500\text{ ng/mL}$ or $>0.5\text{ mcg/mL}$).
5. Depleted Antithrombin III (ATIII): ATIII activity drops below $60\text{–}70%$ (normal 80–120%) due to rapid consumption while binding active thrombin and loss through microvascular capillary permeability.
6. Hypofibrinogenemia: Fibrinogen concentration plunges in end-stage consumptive DIC as clotting substrate is exhausted.

Therapeutic Management of DIC

• Treat the Underlying Primary Trigger: Eradicate sepsis (surgery, drainage, antibiotics), resect necrotic tissue, or stabilize severe pancreatitis.
• Plasma Component Therapy: Administer Fresh Frozen Plasma (FFP: $10\text{–}20\text{ mL/kg IV}$) or Cryoprecipitate to replenish critical Antithrombin III, fibrinogen, and coagulation factors.
• Anticoagulant Therapy (Heparin):
  • In the early hypercoagulable phase, Low-Molecular-Weight Heparin (Enoxaparin $0.8\text{–}1.0\text{ mg/kg SC q8h}$) or Unfractionated Heparin ($100\text{–}200\text{ U/kg SC q8h}$) can halt microvascular thrombosis, provided adequate ATIII is present (heparin requires ATIII to exert its anticoagulant effect; co-administer with FFP if ATIII is depleted).
  • Heparin is strictly contraindicated in the end-stage, severely hemorrhaging hypocoagulable phase.