Sepsis: Clinical sciences

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Introduction0:00–0:38

Sepsis is an exaggerated immune response to infection associated with organ dysfunction, shock, and death. The infection can be bacterial, viral, or fungal, and may originate from any tissue, initiating a complex interplay between infectious virulence factors and host defense mechanisms.
The main goals of management are to identify and treat the infection while maintaining hemodynamic stability to prevent or minimize organ damage.
Once you identify sepsis or septic shock, you should provide immediate supportive care and begin searching for the underlying source of infection.
When you encounter a patient presenting with signs and symptoms of sepsis, first perform an assessment with a validated metric, such as the systemic inflammatory response syndrome, or SIRS criteria.

Acute management0:38–6:13

There are numerous causes of SIRS like sepsis, dehydration, and adrenal insufficiency; so sepsis will cause SIRS, but SIRS is not always due to sepsis.
To diagnose SIRS, at least two criteria must be met. These include WBCs either below 4,000, so leukopenia, or above 12,000, so leukocytosis; as well as a body temperature either below 36 degrees celsius, so hypothermia, or over 38 degrees celsius, so fever; heart rate above 90 beats per minute, so tachycardia; and respiratory rate over 20 breaths per minute, so tachypnea.
Now, if the SIRS criteria are not met, you should consider an alternative diagnosis. On the other hand, the presence of known or suspected infection together with SIRS should raise suspicion for sepsis.
In addition, if systolic blood pressure, or SBP, is below 90 mmHg or falls 40 mmHg below baseline, your patient has septic shock.
While the SIRS criteria help you identify patients with sepsis, other metrics, such as the Sequential Organ Failure Assessment or SOFA score, may help identify those at greatest risk of poor outcomes.
SOFA evaluates parameters including mental status, mean arterial pressure, or MAP, respiratory function, creatinine, bilirubin levels, and platelet count.
The higher the score, the worse your patient’s prognosis.Now that sepsis or septic shock has been identified, there are several tasks, known as the 1-hour sepsis bundle, that you’ll need to complete.
These measures are to ensure that the underlying infection and hemodynamic status are addressed quickly, as failure to do so can result in disastrous outcomes for your patient.
First, measure blood lactate level STAT, which will be used soon to help guide hemodynamic management. Second, collect blood cultures, after which you will begin broad spectrum IV antibiotics.
Finally, focus on the SBP and the lactate level results. If the SBP is above 90 mmHg and the lactate level is normal, your patient has sepsis without shock.
On the other hand, if your patient's presenting or subsequent SBP is below 90 mmHg or has fallen 40 mmHg below baseline, or if the lactate level is above reference range, your patient has septic shock.
The presence of an elevated lactate level is an indirect indicator of organ dysfunction, as lactate is produced in the setting of hypoperfusion.
Alright, let’s take a look at sepsis without shock. These patients can be continued on maintenance IV fluids.
The rate of IV fluid infusion should be adequate to maintain a urine output of 0.5 mL/kg/h or more and a capillary refill time (CRT) of less than 3 seconds, as these are reliable indicators of tissue perfusion that can be observed at the bedside in a stable patient.
On the flip side, there’s patients with septic shock. These patients are inherently unstable and will require hemodynamic resuscitation.
Once septic shock is recognized, immediately begin an IV infusion of IV crystalloids dosed at 30 mL/kg. Consider admission to the ICU and placement of catheters for invasive hemodynamic monitoring, including an arterial line and a central venous catheter, or CVC.
During the infusion, MAP should be monitored, with a target of 65 mmHg or above. MAP can be calculated from manual blood pressure readings, but these are much less accurate in the setting of hypotension than those measured by an arterial line.
If the MAP falls below 65 mmHg, IV vasopressors, such as norepinephrine or dopamine, should be added. Vasopressors are best administered through a CVC, but if one has not been placed, they can also be given through a peripheral IV.
However, there is a small risk of peripheral tissue necrosis associated with peripheral infusion of vasopressors, especially if given for long periods of time.
If the MAP remains below target, additional vasopressors, corticosteroids, and even RBC transfusion may be added to reach a MAP of 65 or more.
Once a MAP of 65 mmHg is achieved, the rate of crystalloid infusion and doses of vasopressors should be continued and subsequently titrated to maintain this goal.
Now, whether your patient has sepsis with or without shock, establishing hemodynamic maintenance completes the 1-hour bundle, but you’re far from done!
You’ll need to closely monitor indicators of perfusion and hemodynamic parameters, as even stable patients with sepsis or septic shock can decompensate quickly.
Failure to maintain adequate perfusion will inevitably lead to hypoperfusion of vital organs and organ system failure. Okay, now that the 1-hour sepsis bundle is complete, you’ll need to turn your attention to a thorough history and physical examination, as well as order labs and imaging.

History and Physical6:13–7:16

Your goal is to identify the source of infection and any organ dysfunction as soon as possible so that proper investigations and interventions can be undertaken.
When gathering your patient’s history, ask questions or explore the chart for clues to the source of infection. If the patient is already hospitalized, let's say for pneumonia, then that’s your most likely source… underlying pneumonia.
It won’t always be that obvious though, so taking a thorough history that covers all organ systems and common infectious manifestations is important.
Similarly, your physical examination should be comprehensive, looking for abnormalities that might point toward underlying infection or organ system dysfunction.
The presence of suprapubic tenderness, for example, might suggest a genitourinary infection, while findings of bruising and petechiae may indicate disseminated intravascular coagulation, or DIC, as a manifestation of circulatory failure.

Labs and Imaging7:16–8:45

Now, let’s look at labs. Get a CBC with differential and look for elevated WBC count with a left shift.
Order electrolytes, liver function test, BUN and creatinine, and an ABG to help you identify organ dysfunction. Coagulation studies and a D-dimer help evaluate for DIC.
In the event the infection is difficult to localize, an elevated procalcitonin supports your suspicion of a bacterial infection and helps direct antibiotic management decisions.
Lactate levels can be used to guide the intensity of hemodynamic resuscitation measures. Next, let’s look at microbiology.
You have already sent blood samples for culture. So, now you should send other suspected infectious source samples for culture, such as a sputum sample if pneumonia is suspected or a CSF sample if there are signs of meningitis.
Finally, you'll want to order imaging studies to evaluate potential sources of infection based on findings from the history and physical, like a chest x-ray to evaluate for pneumonia, or to identify complications that guide clinical decisions, like a head CT to rule out increased intracranial pressure in suspected meningitis prior to performing lumbar puncture to obtain CSF.
Clues from your history and physical or imaging results have helped you narrow down suspected sources of infection, while cultures have hopefully identified the causative organism.

Reassess antibiotics8:45–9:53

Now let’s reassess your patient’s antibiotic coverage. A confirmed infectious source will help you choose the most appropriate antibiotics and how long you will give them, as well as which ones can be discontinued.
Tailored antibiotics are continued for a duration specific to the underlying infection, like after 3 days for uncomplicated UTI or 7 days for hospital acquired pneumonia.
On the other hand, if the source and cause of infection remain a mystery, you will continue the broad spectrum antibiotics started early on.
In this event, decisions about the intensity and and timing of antibiotics can be made by following procalcitonin levels.
A procalcitonin level that falls from baseline indicates a resolving infection. Even after being started on appropriate antibiotics, a patient with sepsis can still decompensate quickly.
Be sure and check hemodynamic parameters frequently and intervene rapidly if developing shock is recognized. If your patient remains hemodynamically stable, their current fluid or vasopressor regimen should be continued.

Assessment and management of end-organ dysfunction9:53–11:27

Don’t forget that sepsis is associated with organ dysfunction. This is closely related to hemodynamic maintenance, as failure is inevitable when an organ is underperfused, as well as to direct tissue damage caused by circulating proinflammatory cytokines and bacterial endotoxins.
New exam findings may emerge, such as a drop in oxygen saturation or development of edema, that might indicate that one or more organ systems is failing.
In addition, as your patient’s lab results return, you may find abnormalities that suggest organ dysfunction. Significantly elevated AST and ALT, sometimes into the range of 10,000 U/L, as well as elevated bilirubin levels, may indicate acute liver failure.
Similarly, a significant acute elevation in the serum creatinine or decrease in urine output should raise your suspicion for acute kidney injury.
Prolonged PT and PTT, especially if there is an acute drop in platelet count, may suggest the presence of disseminated intravascular coagulation, or DIC for short.
Finally, some manifestations of organ dysfunction manifest on imaging, like the development of pulmonary edema on chest x-ray.
If there are lab and imaging abnormalities suggestive of organ dysfunction, you should consider consulting with a specialist.
It’s not uncommon for multiple specialities, such as pulmonology, nephrology, and infectious disease, to be involved in the management of a patient with sepsis or septic shock.Alright, as a quick recap… Sepsis is a life-threatening condition that occurs when an overwhelming systemic response to infection results in organ dysfunction, shock, or even death.

Review11:27–12:08

The diagnosis of sepsis is clinical, but aided by validated screening tools like the SIRS criteria, which takes into account the patient’s WBC count, body temperature, heart rate, and respiratory rate.
Early stabilization of hemodynamic status, identification of infection, and initiation of antibiotics are the keys to successful management.
Even when these measures are undertaken, your patient must be monitored very closely to avoid decompensation and increase the likelihood of good outcomes.