Sepsis and Septic Shock
Anyone working in a critical care setting has likely been exposed to numerous patients with varying degrees of sepsis, such that understanding the diagnostic criteria and potential therapeutic measures have become of utmost importance; this is especially true when trying to source control and nip an infection in the bud before it progresses into fulminant multi-organ system dysfunction, or worse, before the patient succumbs to their illness.
As with many life-threatening conditions, sepsis is a time-sensitive diagnosis. As depicted in the table below, criteria for identifying sepsis has changed over time with new medicinal developments and continued clinical research.
EARLY Identification of sepsis is critical in order to prevent progression into septic shock. SIRS (systemic inflammatory response syndrome) with suspected infectious source was an earlier description of sepsis. Meeting SIRS criteria meant a patient presented two out of four of the following: Temp >38 or <36C, HR>90, RR>20 or PaCO2<32, WBCs <4 or >12, or 10% bands.
Now, with new diagnostic criteria, identification can be made via alterations in hepatic function, renal function, mental status, respiratory effort, circulatory collapse, rising/elevated lactic acid (>/=2), as well as elevated procalcitonin. Blood cultures are of course an important and preliminary diagnostic tool, and should ideally be obtained prior to IV antibiotic treatment.
Upon initial assessment of a patient, one should of course return to the basics, A.B.C - Airway, Breathing, Circulation. An important sign of sepsis is, as listed above, exhibiting increased respiratory effort. When a patient necessitates oxygen administration to maintain SaO2>92% or breathing appears labored, this is an important clue. Moreover, if signs of altered mental status or encephalopathy manifest, intubation and mechanical ventilation may be warranted to protect their airway. After addressing A and B, circulation must be assessed. If a patient is hypotensive, with SBP<90, IV Fluid should be administered (ideally 30 cc/kg within 3-4 hrs) to maintain MAP>65. If patients are unresponsive to fluid administration, vasopressors/ionotropes must be considered to assure adequate tissue perfusion, especially to vital organs such as the heart, kidneys, and brain.
Aside from volume resuscitation, an equally important, and even more time-sensitive modality of treatment, is early administration of empiric broad spectrum IV antibiotics, preferably within one hour of sepsis identification. Depending on clinical picture (abdominal pain, upper respiratory symptoms, dysuria, etc.), patients may be covered with Gram positive, Gram negative, or potentially both in the event of septic shock. The most commonly identified organisms isolated in patients with sepsis include: E. coli, Staph aureus, Klebsiella pneumoniae, and Strep pneumoniae. Length of antibiotic course varies from patient to patient, but typically 7-10 days is recommended.
To evaluate a patient’s responsiveness to treatment, one may utilize procalcitonin levels, lactic acid levels (goal <2), ScvO2 (requiring central line insertion, goal>70), MAP goals >/=65, and urine output >0.5cc/kg/hr.
If the above are not met given lack of response to fluid and antibiotic administration, initiation of a/an vasopressor/ionotrope may be indicated. Levophed (Norepinephrine) infusion is first line, followed by Epinephrine vs. Vasopressin infusions for refractory hypotension. Dopamine is last line, unless a patient is bradycardic and would benefit from its beta adrenergic effects. Meanwhile, vasopressin becomes a preferred agent in a patient with tachycardia given its absense of beta effects. Dobutamine is another ionotrope that may be beneficial in patients with lower heart rates, who require additional ionotropic support.
Other therapies currently being studied include: glucocorticoid (IV hydrocortisone), vitamin C, and thiamine (i,e, Marik protocol).
Vitamin C was found to play an important role in the synthesis of norepinephrine as well as provide anti-oxidant effects. Stores of vitamin C become depleted during the physiologic stress of sepsis, which leads to vascular permeability and coagulopathy. Administration of this vitamin has been shown to aid in refractory hypotension and reduce exogenous catecholamine administration.
Thiamine, on the other hand, plays an important role in aerobic metabolism. Its administration can help expedite lactate clearance. Thiamine also alters vitamin C metabolism.
Hydrocortisone is thought to work alongside vitamin C by altering inflammatory mediators, augmenting catecholamine production, and enhancing the sensitivity of vasopressors.
As studies continue, more therapeutic options are becoming unveiled in the treatment of sepsis.
References:
Ho, Vanessa P., et al. “Sepsis 2019: What Surgeons Need to Know.” Surgical Infections, 2019, doi:10.1089/sur.2019.126.
Schmidt, Gregory A., et al. “Evaluation and Management of Suspected Sepsis and Septic Shock in Adults.” UpToDate, 2019, www.uptodate.com/contents/evaluation-and-management-of-suspected-sepsis-and-septic-shock-in-adults/print?search=sepsis&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2.
Hager, D.N., Hooper, M.H., Bernard, G.R. et al. The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) Protocol: a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial. Trials 20, 197 (2019) doi:10.1186/s13063-019-3254-2