What is Sepsis?

Sepsis is a commonly used term of unclear definition and utility. A brief history:

Sepsis was formally defined in 1991 as dysregulated immune response to infection, characterized by the systemic inflammatory response syndrome and identifiable by its SIRS criteria.

Since sepsis had such a high mortality, the purpose of this definition was to support early recognition and treatment.

Over the next twenty years, clinical research focused on identifying diagnostic and treatment algorithms for sepsis, such as The Rivers Protocol and Early Goal Directed Therapy. Patients receiving this protocol lived longer, and this was quickly adopted as the standard of care. However, subsequent multicenter RCT's and meta analyses didn't show a mortality benefit (ProCESS, ARISE, ProMISE), suggesting that the success of the Rivers Protocol was related to the specifics of that one intensive care unit.

Recently, the definition of sepsis was updated by the Third International Consensus Definitions for Sepsis and Septic Shock in 2016, published in JAMA.

Here's a quick breakdown of that update:

-The SIRS criteria are abandoned- many patients meet SIRS but do not have systemic infection, and many patients have systemic infection but do not meet SIRS.

-"Severe Sepsis" is abandoned. Sepsis itself, with a 10% mortality, is already severe.

-The definition of sepsis is: "life-threatening organ dysfunction caused by a dysregulated host response to infection."

-"The task force recognized that no current clinical measures reflect the concept of a dysregulated host response."

-Sepsis is "predicated on infection as its trigger," but the task force "acknowledges the current challenges in the microbiological identification of infection."

-Organ dysfunction is best assessed by the SOFA score, which can be obtained through basic labs and PaO2. An increase by 2 or more points on SOFA incurs 10% mortality.

-qSOFA is NOT a definition of sepsis. It is a prompt to look for sepsis, a screening tool to identify patients who may progress to sepsis.

-qSOFA is intended as a quick bedside assessment, requiring only assessment of mental status (GCS <15 or not), blood pressure (systolic pressure less than 100), and respiratory rate (>22).  A positive qSOFA increases the likelihood of progressing to sepsis.

-Insurers have not caught up with new definitions and still reimburse according to whether patients meet traditional sepsis criteria.

Bottom Line:

You need to rely on your best clinical judgment in identifying patients with severe infection to which the body's immune response is dysregulated. Since overwhelming infection is a common cause of death, you need to act quickly to prevent or treat poor tissue perfusion and multi-organ dysfunction. Treatment involves IV antibiotics and aggressive volume resuscitation, with consideration for pulmonary edema. It is also important to identify and resolve the source of infection quickly.

Cirrhosis in the Hospital

This is a brief outline of big things to look for in the hospitalized patient with cirrhosis.


Hepatic Encephalopathy
  Diagnose: Asterixis? Confusion? Has HE historically?
  What’s the cause? Infection, bleeding, HRS (poor renal clearance), worsening liver failure.
  What to do? Lactulose, up to q2Hr to maximize clearance, titrate to mental status and stool frequency. Look for/treat underlying cause (pan culture including ascites tap, cxr, rectal, renal workup). Consider rifaximen.

Key Points: HE is dangerous in itself (aspiration, med non-adherence, falls, delirium), it is often a harbinger of badness (infection, bleed), but it's also fixable. It takes effort, and it's messy, but it's important for every patient.


Variceal bleeding
  Diagnose: Recent melena/BRBPR? Rectal exam? (Not occult blood) Worse anemia? Known varices? Last EGD? On nonselective beta blocker? Known bleed?
  What to do? If suspicious but not definite, do rectal exam, NPO, two large bore IV, type and screen, IV PPI BID, consent for blood, call GI to arrange EGD. If definitely bleeding, stat page GI, order blood, can use albumin while waiting, octreotide gtt and prophylactic ceftriaxone, low threshold to transfer to ICU.
What to worry about: Airway protection from blood and/or HE, hemorrhage requiring massive transfusion protocol. Decompensation can happen rapidly and without warning.

Key Points: The key to managing this condition is to be prepared with IV access, blood products/albumin, GI awareness, etc. Once a patient opens up, there is very little time.


Ascites
  What to do? Main concern is ruling out SBP. If obviously distended, do diagnostic and therapeutic para, though likely need IR guided if you can’t get supervised. If ascites uncertain, get and ultrasound to confirm. Ideally diagnostic fluid prior to antibiotics, but don’t hold antibiotics for delayed paracentesis. Ceftriaxone 2gm daily. For large vol para, need to give albumin to counteract fluid shifts/avoid HRS. Long term treatment is diuretic vs TIPS vs serial para vs transplant.

Key Points: This rarely becomes an emergency except for overwhelming gram negative sepsis. However, ascites complicates everything, including: Respiratory restriction, urine obstruction, and pain which often necessitates opiates.


Hepatorenal Syndrome
  Diagnose: Prerenal AKI in cirrhosis that doesn’t improve with albumin challenge.
  What to do: Hold diuretics. Albumin challenge, if fails needs octreotide and midodrine. Workup and correct underlying drivers. Call renal and hope doesn’t need dialysis.

Key Points: This is rarely an emergency, but very high mortality. You need to differentiate HRS from prerenal AKI quickly and get the relevant treatment running and renal consulted.


Less Urgent Considerations:
Transplant Status?
  Calculate MELD score, review chart and talk with patient. This is the ultimate and ideal fix for all of the above, but there are several barriers.

Heptaocellular Carcinoma
Status of last ruq u/s?

Night Medicine Talk

This talk was delivered to the Internal Medicine Residents at Baystate Health, Academic Half Day, July 10, 2018.

Please feel free to send questions to astupple@gmail.com.