Septic shock develops through an infection that triggers a systemic inflammatory reaction. Through this process, the body releases inflammatory mediators, such as histamine and cytokines, resulting in vasodilation, increased vascular permeability, and leukocyte activation in the tissue.

These changes lay the groundwork for how sepsis progresses throughout the body. The inflammatory mediators circulating the body combined with increased vascular permeability leads to increased tissue and organ damage. Also consider that a consequence for vasodilation is decreased blood pressure which can eventually lead to decreased systemic perfusion. The foundation of sepsis is centered around life threatening organ dysfunction caused by a dysregulated host response to an infection. Through complications that build upon each other, sepsis can be defined through specific stages.

Infection:  

• A microbial phenomenon characterized by an inflammatory response to the presence of microorganisms or the invasion of normally sterile host tissue by those organisms.

• Temp > 38C.

  
  

SIRS:  

• HR> 90

• RR> 20 or PaCO2 <32

• Temp > 38C or < 36C

• WBCs> 12,000 or <4,000 or >10% bands. 

• If the reaction is triggered in tissue remote from the site of infection and a large inflammatory response is started, this is defined as SIRS.  

  
  

Sepsis: SIRS + Infection  (Sepsis I)

• Suspected or known source of infection AND two or more indicators of systemic inflammation:

• HR> 90 beats/min 

• RR>20breaths/min 

• Temp >38.3C or <36C

• WBC>12 min or <4mm or 10% bands 

  
  

Severe Sepsis: Sepsis + End Organ Damage (Sepsis II)

• Sequential Organ Failure Assessment (SOFA)

  
  

Septic Shock: Severe Sepsis + Hypotension (Sepsis III)

• Sepsis AND end-organ dysfunction as evidence by two or more of the following: 

• SBP<90mm Hg or MAP < 65 mm Hg 

• Urine output < 0.05 mL/kg/h x 2h or creatine > 2.0mg/dL 

• Creatinine >0.5 mg/dL above baseline if history of chronic kidney disease 

• Platelets <100,000 mm 

• INR > 1.5 or aPTT > 60 seconds 

• Serum Lactate > 4mmol/L or serum lactate > 2mmol/L after fluid resuscitation 

• New need for noninvasive or invasive ventilation 

• fever

• hypotension

• tachycardia

• tachypnea

• warm, flushed skin

• confusion

• weakness

• decreased urine output

Late s/sx

• severe hypotension

• pale, cold, or clammy skin

• lactic acidosis

• anuria

• multi-organ failure

Risk Factors

Diabetes: Hyperglycemia can promote the growth of bacteria and impair the body's ability to heal wounds. This promotes the risk of infection and can exacerbate the compromised state of the patient.

Neutropenia: With fewer neutrophils the body is less capable of controlling and eliminating infections. Therefore, increasing the likelihood of sepsis and septic shock.

Mucositis: This compromises the natural protective barrier of the digestive tract. Then allowing bacteria and pathogens to enter the bloodstream.

Invasive Devices: These devices are important for treatment but can increase the risk for infection by having a direct pathogen entry.

Malnutrition: Malnourishment compromises the immune system by delaying wound healing and weakening epitheleal barriers and reducing an effective inflammatory response.

Complications of Cancer Induced Sepsis

• Kidney Failure: The kidneys normally filter and regulate inflammatory cytokines. Kidney failure can be induced by toxic chemotherapy agents and lead to the accumulation of inflammatory cytokines intensifying systemic inflammation during sepsis. The unchecked cytokine release contributes to organ damage, vascular leakage, and septic shock. Kidney failure also impairs fluid excretion, causing fluid accumulation and tissue edema. 

• Acute Respiratory Distress Syndrome: Inflammatory cytokines and mediators damage the capillary endothelium, causing gaps between endothelial cells. This allows fluid, proteins, and immune cells to leak from the bloodstream into the alveolar spaces, leading to pulmonary edema and impaired gas exchange. 

• Liver Failure: Sepsis often leads to hypotension and hypoperfusion of vital organs, including the liver. The liver’s dual blood supply becomes compromised during septic shock. Ischemia damages hepatocytes and impairs liver function causing jaundice, increased ammonia levels, difficulty metabolizing medications and filtering toxins. 

• GI Bleeds: Due to blood being shunted to vital organs, the acidic contents of the stomach are immobilized and cause ulcerations of the inner lining leading to bleeds. 

• Altered Mental Status: Sepsis increases the permeability of the blood brain barrier due to endothelial damage and oxidative stress. This allows toxins, inflammatory mediators, and immune cells to enter the brain, further promoting inflammation and neuronal injury. This combined with the “Brain Fog” from chemotherapy can make it difficult to arouse the patient and determine whether perfusion is adequate.

How Co-Morbidities Confound the Disease Process

 * Delayed Recognition and Diagnosis of Sepsis

- Symptoms of infection (fever, tachycardia) may be masked or attributed to chemotherapy side effects, delaying treatment.

* Increased Treatment Resistance

- Patients with prior infections may harbour multidrug-resistant organisms, making sepsis harder to treat.

* Higher Mortality Risk

- Co-morbidities reduce physiological reserves, making it harder for patients to recover from septic shock.

• Fever, Chills, Elevated heat rate, and changes in blood pressure

• Daily assessment of redness, swelling, or drainage on the skin, mucous membranes, or IV sites

Rationale:

• Monitoring for signs of infection in a patient with septic shock caused by chemotherapy is critical because chemotherapy weakens the immune system, making the patient more susceptible to infections. Chemotherapy-induced neutropenia significantly impairs the patient to be able to launch an effective immune response. This increases the risk of opportunistic infections that can rapidly escalate to septic shock.

  
  

  2. Sepsis 1-hour bundle:

  • Obtain serum lactate, blood cultures

  • Administer broad spectrum antibiotics

  • Hypotensive? --> Rapid crystalloid bolus (NS/D5)

  • MAP < 65? --> Norepinephrine or Vasopressin

  • MAP < 65 and HF? --> Dobutamine

    
    

    Rationale:

  • The 1-hour bundle is crucial in a patient with septic shock caused by chemotherapy. Chemotherapy-induced immunosuppression leaves the patient highly vulnerable to infections, which can escalate rapidly. The 1-hour bundle helps ensure that treatment is started as soon as possible, increasing the likelihood of survival and reducing the long-term complications of septic shock in this vulnerable population.

    
    

3. Monitor Organ Function:

• Brain, Heart, Lungs, Kidney function, Liver function, and GI function

  Rational:

• In a patient with septic shock caused by chemotherapy, monitoring organ function is crucial because chemotherapy can already compromise organ systems, making them more vulnerable to the effects of sepsis. Chemotherapy-induced immunosuppression weakens the body’s ability to fight infection, increasing the risk of sepsis and multi-organ dysfunction. Sepsis exacerbates this risk by causing hypoperfusion, inflammation, and tissue damage, which can quickly lead to organ failure, especially in the kidneys, liver, and lungs.

• Thrombosis 

• Bleeding 

• Anemia 

• Hair loss 

• Stomatitis 

• Nausea/Vomiting 

• Constipation/Diarrhea 

• Chemo brain 

• Peripheral neuropathy 

• Infection 

• Fatigue 

• Fertility problems

• Fluids

  • Fluid overload

  • Electrolyte imbalance

• Antibiotics

  • Adverse drug reactions

  • Risk for drug resistance

• Vasopressors

  • Tissue ischemia

  • Tachyarrhythmias

• Ventilator

  • Oxygen toxicity

• Dialysis

  • Hemodynamic instability

Benefits

• Fluids

  • Corrects hypovolemia

  • Improves organ function

• Antibiotics

  • Target a wide-range of potential bacteria

• Vasopressors

  • Corrects vascular tone

  • Improves organ perfusion pressure

• Ventilator

  • Improves gas exchange

  • Reduces work of breathing

• Dialysis

  • Removes waste from blood

• Impaired cardiac function 

• Worsening renal function 

Antibiotics: 

• Increased inflammatory response

• C.difficile infections 

• Further organ dysfunction

Vasopressors:

• Increased tachycardia 

• Increased blood lactate levels 

Ventilator:

• Further decrease in cardiac output 

• Ventilator-associated pneumonia  

Dialysis:

• Worsening systemic infection through vascular access site 

• Unstable blood pressure fluctuation 

• Heart rate 

• Blood pressure 

• Lactate 

• MOD- AST, ALT, BUN, and creatinine 

• WBC 

• ABG 

• Immunosuppression

• Organ dysfunction

Benefits

• Reduces tumor size

• Prevents cancer progression