Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated inflammatory response to infection and/or trauma. Normally, an infection or tissue injury triggers a local immune response. In some patients, however, a systemic spill-over of inflammatory mediators triggers a more generalised reaction.
The inflammatory response may initially start locally (eg an abscess on a limb) but, if severe, can progress to cause systemic signs when inflammatory mediators enter the circulatory system and instigate global activation of the inflammatory system. The body’s normal response to pathological inflammation balances the activation of proinflammatory mediators with the activation of anti-inflammatory mediators. This suspicion of infection, in conjunction with evidence of organ dysfunction through the use of the sequential organ failure assessment (SOFA), is a new addition to the definitions of sepsis in the Surviving Sepsis Campaign Guidelines 2021.
Septic shock, as defined in 2016, is the presence of profound circulatory, cellular and metabolic abnormalities. This subset of sepsis greatly increases the patient’s risk of mortality and requires immediate intervention to support the circulatory system with the use of vasopressors.
[Septic shock] greatly increases the patient’s risk of mortality and requires immediate intervention to support the circulatory system with the use of vasopressors
The consensus in human medicine is against the use of systemic inflammatory response syndrome (SIRS) criteria as a marker for sepsis; however, no strong consensus has been reached in the veterinary community. Criteria for SIRS are derived from a small surgical and necropsy study, therefore bearing little relevance to septic patients. However, the presence of SIRS may still raise suspicion of sepsis as a differential, though the criteria do not need to be met for a patient to be officially “septic”.
Pathophysiology of sepsis
As sepsis is a dysregulated form of the host’s immune response, which is designed to localise and destroy pathogens, it can manifest as endothelial cell damage, coagulopathies, microcirculatory and haemodynamic alterations, and metabolic and immunological abnormalities.
During Gram-negative sepsis, there is an activation of macrophages, transcription of cytokines and generation of anti-inflammatory cytokines. Dysregulated by cytokine release, tissue factor levels are upregulated to initiate the coagulation cascade, leading to the haemostatic balance favouring a procoagulant state.
Recognition of pathogens occurs through pattern recognition molecules (PRRs) that are found in cellular membranes and excreted in the bloodstream and interstitial fluids. These PRRs engage pathogen-associated molecular patterns (PAMPS) to identify damage-associated molecular patterns (DAMPS). These PRRs are activated by DNA and RNA from pathogens, as well as the circulating white blood cells, platelets and fibroblasts, initiating pro- and anti-inflammatory responses.
Other cellular processes that occur in response to the immune triggers result in vasodilation, apoptosis, cytokine storm, inflammation and tissue damage. Endothelial injury occurs from microcirculatory derangements that increase vascular permeability.
Along with changes to the endothelial glycocalyx, this alteration to vascular permeability, compounded by hypoalbuminaemia and myocardial dysfunction, creates the perfect storm for the patient, and is an important pathophysiological consequence of sepsis.
Biomarkers and clinical manifestations
Currently, there is no ideal and clinical gold standard for the diagnosis of sepsis, as microbiology may not be sensitive enough and laboratory tests are unspecific for use as a reference standard. However, monitoring septic patients has traditionally been achieved by measuring physiological parameters. Notable sepsis markers that can be used to track trends easily in the general veterinary hospital setting include activated partial thromboplastin time (aPTT), troponin and lactate.
Notable sepsis markers that can be used to track trends easily in the general veterinary hospital setting include activated partial thromboplastin time, troponin and lactate
Patients presenting with sepsis often have a non-specific medical history. Clinical signs include:
- Lethargy
- Weakness
- Hyporexia or anorexia
- Abdominal discomfort or abnormal posturing
- Vomiting
- Diarrhoea
- Increased respiratory rate and/or effort
- Fever
- Erythema
- Swelling of extremities and/or joints (with possible limping)
- Abnormal wounds
- Changes in heart rate and/or respiration rate
- Injected mucous membrane colour
- Rapid capillary refill time
- Altered level of consciousness
The clinical presentation of sepsis will vary depending on the severity and stage of the disease process. Physical parameters in early sepsis will reveal fever, tachycardia, tachypnoea, brick-red or muddy mucous membranes, rapid capillary refill time (under 1 second), bounding pulses and mental depression.
As the sepsis progressively worsens, cardiac output is decreased. Vascular leakage and vasodilation result in decreased venous return and decreased cardiac output, leading to decompensated sepsis or “hypodynamic” septic shock.
SOFA scoring
SOFA scoring (Figure 1) is one of the most common organ dysfunction scoring systems in human medicine.
By using markers commonly used to assess critically ill patients, such as coagulation (thrombocytopenia), hypoxaemia (measuring lung dysfunction), brain dysfunction (Glasgow coma score), liver dysfunction (increased total bilirubin concentration) and heart and kidney dysfunction (hypotension and increased creatinine concentrations, respectively), SOFA scoring can predict potential outcomes. A patient’s SOFA score should be noted at admission and then repeated throughout the hospital stay to observe any progression or initiation of organ injury.
By using markers commonly used to assess critically ill patients […] SOFA scoring can predict potential outcome
Treatment bundles
Patients with sepsis require immediate stabilisation and treatment. It is recommended that treatment be centred on fluid resuscitation, antimicrobial therapy, infectious source control and overall supportive care (eg pain control, nutrition). A “bundle of care” refers to a group of therapies that, when initiated together, produce better results than when initiated alone. These bundles have been shown to decrease morbidity and mortality in human studies by prioritising and standardising sepsis protocols.
Early goal-directed therapy was first proposed in human medicine in 2001, with the aim to ensure adequate tissue oxygenation and survival. Parameters that should be monitored intensively and managed aggressively to specified targets are:
- Central venous pressure (CVP)
- Mean arterial blood pressure (MAP)
- Urine output
- Mixed venous oxygen saturation (SvO2)
- Haematocrit
Monitoring the septic patient
It is important to recognise that the septic patient can rapidly decompensate. Vital signs, including heart rate and rhythm, respiratory rate, body temperature, mucous membrane colour, capillary refill time and pulse quality, should be checked regularly and will provide information on cardiovascular status. Patient monitoring includes assessment of vital signs every two to ten minutes during initial stabilisation and every one to four hours during hospitalisation. Further, Kirby’s Rule of Twenty (developed several years ago by Rebecca Kirby, DVM, DACVIM, DACVECC) provides a guideline to make sure that all monitoring parameters are met to prevent any additional morbidities, or even death, in our hospitalised patients.
It is important to recognise that the septic patient can rapidly decompensate. Vital signs […] should be checked regularly and will provide information on cardiovascular status
Commonly, septic patients require continuous electrocardiography monitoring and frequent blood pressure measurement. For those patients with respiratory system compromise (which will be flagged on any sequential SOFA scoring), oxygen therapy and monitoring of additional respiratory parameters (eg respiratory effort, SpO2, arterial blood gas) may be indicated. Urinary catheters require care every six to eight hours to prevent a secondary infection. Feeding tubes require daily maintenance to ensure patency. In patients with disseminated intravascular coagulation (DIC), blood component therapy with fresh frozen plasma may be indicated and require a transfusion with frequent monitoring. Post-operative patients may have wound drains that need to be quantified and maintained.
Nutrition
Nutritional support is often overlooked as a part of care for septic patients; however, it is necessary for recovery from all disease processes and should be instituted for every patient. Enteral nutrition is preferred as it is the most physiologically appropriate method of feeding. Early initiation helps to maintain the gastrointestinal mucosa, prevent bacterial translocation from the gut, maintain glycaemic control and increase wound healing and the immune response.
Sepsis produces a hypermetabolic state that requires support with adequate nutrition. The gut has been identified as a key organ in sepsis, and gastrointestinal dysfunction is common. Early nutritional support is primarily used to maintain the integrity of the intestinal mucosal barrier and decrease the chances of bacterial translocation.
If abdominal surgery is required for the underlying problem, then consideration should be given to the placement of an oesophageal or gastrostomy tube. If enteral feeding is not tolerated, partial parenteral nutrition can provide nutritional support for a few days until enteral nutritional support is reinstituted. Gastric protectants may be required to prevent ulceration and treat gastrointestinal bleeding, and glucose monitoring is suggested for these patients.
If enteral feeding is not an option, parenteral nutrition is typically administered through a centrally placed intravenous catheter due to its high osmolality, which may cause thrombophlebitis if given peripherally. However, isotonic parenteral nutrition solutions can be delivered through a peripheral catheter if central venous access is not possible.
