What is the diagnosis and treatment for cold sepsis (septic shock with hypothermia)?

From the Guidelines

Cold sepsis requires immediate initiation of broad-spectrum antimicrobial therapy, as soon as possible after recognition and within one hour, to cover all likely pathogens, including bacterial and potentially fungal or viral coverage, as recommended by the Surviving Sepsis Campaign guidelines 1.

Key Considerations

• Cold sepsis, or sepsis without fever, is a severe infection that can present with a normal or low body temperature, and its recognition and treatment are crucial to prevent worse outcomes.
• The Surviving Sepsis Campaign guidelines recommend starting IV antimicrobials as soon as possible after recognition and within one hour for both sepsis and septic shock, with a strong recommendation and moderate quality of evidence 1.
• Empiric broad-spectrum therapy with one or more antimicrobials is recommended to cover all likely pathogens, including bacterial and potentially fungal or viral coverage, as stated in the guidelines 1.

Treatment Approach

• Appropriate initial antibiotics may include a combination of vancomycin and piperacillin-tazobactam or meropenem, although the specific choice should be guided by local antimicrobial resistance patterns and patient-specific factors.
• Simultaneously, administering IV fluids for hypotension or elevated lactate and monitoring for signs of organ dysfunction are essential components of sepsis management.
• Vasopressors, such as norepinephrine, may be necessary for patients with hypotension, and close monitoring in an ICU setting is crucial due to the potential for rapid deterioration.

Rationale

• The absence of fever in cold sepsis can occur due to impaired thermoregulatory mechanisms, particularly in elderly patients, immunocompromised individuals, and those with chronic diseases.
• Cold sepsis often indicates a more advanced stage of infection, which can lead to worse outcomes if not aggressively treated.
• The guidelines recommend optimizing dosing strategies of antimicrobials based on accepted pharmacokinetic/pharmacodynamic principles and specific drug properties in patients with sepsis or septic shock 1.

From the Research

Definition and Presentation of Sepsis

• Sepsis is a complication of severe infection characterized by a systemic inflammatory response 2
• Mortality rates from sepsis range between 25% to 30% for severe sepsis and 40% to 70% for septic shock 2
• The clinical presentation of sepsis is highly variable depending on the etiology, with fever often being the first manifestation 2
• The most common sites of infection are the respiratory, genitourinary, and gastrointestinal systems, as well as the skin and soft tissue 2, 3

Management of Sepsis

• Early goal-directed therapy completed within the first six hours of sepsis recognition significantly decreases in-hospital mortality 2
• Initial management includes respiratory stabilization followed by aggressive fluid resuscitation 2
• Vasopressor therapy is indicated when fluid resuscitation fails to restore adequate mean arterial pressure and organ perfusion 2
• Early antibiotic therapy can improve clinical outcomes, and should be given within one hour of suspected sepsis 2, 3
• Blood product therapy may be required in some cases to correct coagulopathy and anemia, and to improve the central venous oxygen saturation 2

Antibiotic Therapy in Sepsis

• Gram-negative sepsis is more common than gram-positive infection, but sepsis can also be due to fungal and viral pathogens 3
• To reduce mortality, it is necessary to give immediate, empiric, broad-spectrum therapy to those with severe sepsis and/or shock 3
• Piperacillin-tazobactam dose reduction in early phase septic shock is associated with worsened clinical outcomes 4
• Cefepime and piperacillin-tazobactam are alternative broad-spectrum antipseudomonal beta-lactam antibiotics, but the results of one study do not suggest that the use of the antipseudomonal beta-lactam antibiotic used in the initial management of septic shock is associated with differences in acute kidney injury or Clostridioides difficile infection 5
• The combination of vancomycin and piperacillin/tazobactam has been reported to be nephrotoxic, and clinicians should be aware of this potential risk 6