Authors:
Ray Smith. NREMT‐P, CCEMT‐P, PNCCT
North Shore ‐ Long Island Jewish Health System Center for EMS, Syosset, NY
R. Shawn Bowe, NREMT‐P, CCEMT‐P, PNCCT, FP‐C
Operations Officer, Training and Development
North Shore ‐ Long Island Jewish Health System Center for EMS, Syosset, NY
Reviewers:
Becca Saul, RN, MSN, EMT‐P, ACNP, PNP‐AC
Adult Acute Care Nurse Practitioner and Pediatric Acute Care Nurse Practitioner: Department of
Emergency Medicine, Wellspan Health Hospital, York, PA
Flight Nurse/Paramedic (ret): Regional One Air Medical, Spartanburg, SC
Charlotte Newman Charfen, MD, FACEP
Medical Director: Air Med Augusta, Doctor’s Hospital Burn Center, Augusta, GA
Founder and Medical Director: International Program for Emergency Medicine Development,
Guanajuato, Mexico
Emergency Medicine Physician: Medical College of Georgia, Augusta, GA
Mike Clumpner, PhD(c), MBA, CHS, NREMT‐P, CCEMT‐P, PNCCT, EMT‐T, FP‐C
1
Faculty, Professional and Continuing Education: UMBC, Baltimore, MD
Crista Lenk Stathers, MA, NREMT‐P, CCEMT‐P, PNCCT
Director, Professional and Continuing Education: UMBC, Baltimore, MD
1
Temporal and spatial regulation of resolution. (A) Current paradigm: Breaches in host
defense such as pathogen invasion, host trauma, or loss of barrier function initiate
the inflammatory response with AA rapidly converted to PGs and LTs (e.g., LTB4) via
COX enzymes. LTB4 is a potent chemoattractant of neutrophils to the site of
inflammation (red arrow). As the inflammatory response progresses, a temporal
switch from initiation to resolution occurs with the transcellular generation of lipoxins
(LXA4) that inhibit the further recruitment of polymorphonuclear neutrophils (PMNs)
(blue line). As the inflammatory response continues, monocytes are recruited via the
release of the monocyte chemotactic protein‐1. Macrophages release
proinflammatory cytokines IL‐6 and TNFα, but engulfment of apoptotic PMNs causes
macrophages to change to a nonphlogistic phenotype releasing TGF‐β, IL‐10, and
lipoxin. At the end of an acute inflammatory response, macrophages and
lymphocytes leave the site of inflammation via the draining lymphatics, stimulated by
lipoxins (blue arrow). (B) New addition to the paradigm: At the onset of the
inflammatory response, PGD2 is generated from AA via COX to PGH2 and then
converted to PGD2 by hPGD2S. PGD2 is metabolized nonenzymatically to 15‐dPGJ2.
PGD2 acts on the DP1 receptor expressed on macrophages and lymphocytes, whereas
15‐dPGJ2 is likely to interact with peroxisome proliferator‐activated receptor‐γ.
Working in tandem, they decrease proinflammatory cytokines such as TNFα and
increase antiinflammatory cytokines such as IL‐10, but like the lipoxin family, they
also promote egress of macrophages and lymphocytes to the draining lymphatics
(blue arrows).
Chemotactic factors released from damaged cells
Chemotaxis of WBC’s to site of inflammation
Margination
Diapedesis
11
Brief definition describing the difference between the three before in‐depth
discussion begins on each.
1992, American College of Chest Physicians introduced definitions for:
Systemic inflammatory response syndrome (SIRS)
Sepsis
Severe sepsis
Septic shock
Multiple organ dysfunction syndrome (MODS)
13
The SIRS criteria, originally established by the American College of Chest Physicians
specify that an elevated respiratory rate or a PaCO2<30 something fulfills the criteria
for diagnosis. This criteria attempts to capture people who are "early" in the
progression of sepsis, where a respiratory alkalosis is a compensatory measure for
elevated temperature and an hypermetabolic state. As patients get "sicker,"
respiratory failure can develop. Thus, an elevated CO2 indicates end organ
dysfunction. The SIRS criteria were develop to assist in early recognition of the sepsis
syndrome. Its true, then, that respiratory failure by itself wouldn't qualify as one of
the SIRS criteria. Half of our chronic COPD patients walk around with an elevated
PaCO2. Fortunately, SIRS criteria are universal. Patients either meet them or not.
Respiratory alkalosis is seen early in the course of illness. The elevated respiratory
rate helps clinicians clue into patients that are compensating.
The diagnosis of sepsis relies LESS on objective criteria. Its simply SIRS + a source.
Septic shock is, of course, diagnosed, when there is injury a particular organ system.
That's when the criteria of an elevated PaC02 may contribute to the clinical picture.
16
Graph demonstrating the overlapping effect of infection, sepsis, and SIRS.
18
One study noted the following progression of patient with SIRS:
26% developed sepsis
18% developed severe sepsis
4% developed septic shock
22
Risk factors
DM
End‐stage renal disease
COPD
Cirrhosis
Immunosuppression
Invasive devices / procedures
Advanced age
Burns
27
It is difficult to exactly determine the mortality of SIRS since it falls into the SIRS /
severe sepsis / septic shock continuum. The mortality rate is believed to be about 7%
for SIRS, 10‐40% for severe sepsis, and 30 – 60% for septic shock. (Comstedt,
Storgaard, Lassen. “The systemic inflammatory response syndrome in acutely
hospitalized medical patients: A cohort study.” Scand J Trauma Resus Med.
2009;17(67):1‐6)
28
DIC is discussed extensively in the hematology module
41
Aberrancies in mediator production
Sepsis occurs when there is a massive release of proinflammatory molecules
The inflammatory agents cause an increase in specific mediators such as
tumor necrosis factor (TNF)
Patients with increased levels of TNF have been shown to have
increased levels of mortality
42
•Gram negative
–Release endotoxins
–Mortality rate of 20 – 50%
•Gram positive
–Release exotoxins
48
Risk factors include:
Diabetes mellitus
Cirrhosis
Burns
Invasive procedures and devices
Immunosuppression
Extremes of age
49
Interesting analysis that shows the rate of mortality with sepsis compared to other
acute conditions.
51
The mortality rate in patients with sepsis varies from 20 – 51%.
52
Make sure to keep all patients NPO
54
Biliary tract infections (e.g. cholecystitis and cholangitis). Note that approximately
10% of all sepsis patients fail to receive prompt antibiotic therapy
56
Eighteen‐year‐old male patient with severe Gustilo type IIIC injury of the ankle after a
motorcycle accident. An initial attempt for limb salvage with anastomosis of the
posterior tibial artery was followed by delayed amputation five days postoperatively
due to severe sepsis
59
Other causes:
–GI tract infections (account for 15% of sepsis)
–Soft tissue infections (account for 15% of sepsis)
–Intravascular devices (account for 10% of sepsis)
–Foreign bodies (account for 5% of sepsis)
–Miscellaneous infections (account for 5% of sepsis)
60
This baby died of an overwhelming bacterial infection shortly after birth. The opened
chest shows the heart, in the center, covered here with the yellowish pericardial and
mediastinal tissues. On each side are the red lungs. Below, in the abdominal cavity,
you can see the liver. The white nodules in the liver are abscesses, pockets of pus. At
the lower portion of the picture are the intestines.
61
A study by VHA, Inc. in 2004 found the following regarding severe sepsis:
–Average hospital length of stay was 20 days
–Average cost for hospitalization was $22,100
–Annual cost for treatment of severe sepsis is $16.7 billion dollars
–52% of patients were older than 65
–31% of patients were older than 75
63
Note the controversy surrounding "Colloids preferred to correct hypoalbuminemia“
(from Dr. Ameen Ramzy, one of the CCEMTP program medical directors):
Albumin is sometimes given to correct hypoalbumeinemia, while other physicians
choose colloids or crystalloids first. Severe sepsis implies hypotension and
hypoperfusion and in that state, there is likely a capillary leak, and giving albumin
may worsen pulmonary failure. There are survival studies comparing crystalloid and
colloid, which are not favorable to colloid, although this is controversial. Another
reality is that giving albumin is not going to really replete the albumin ‐‐ much of it is
washed out. The patient has to be returned to positive nitrogen balance, which is
more complex than just giving albumin.
67
Endotoxins released from phagocytized bacteria
Lipopolysaccharide (LPS)
LPS triggers release of cytokines from monocytes & macrophages
Cytokines
TNF‐
Interleukin‐1
69
Increased serum glucose causes glycogenolysis and gluconeogenesis
72
There is an increasing number of gram‐positive cases of septic shock due to the
increase in pneumonia and the use of intravascular devices
73
Respiratory alkalosis = There is time to fix the problem with the right treatment (fluid)
Metabolic acidosis = Time to call the funeral home
82
Anti‐inflammatory antibodies
•Endotoxin
•Tissue necrosis factor
•Interleukin‐1
84
Al‐Khafaji, AH. (2012) “Multiple organ dysfunction syndrome in sepsis.” Available at
www.emedicine.com
97
Al‐Khafaji, AH. (2012) “Multiple organ dysfunction syndrome in sepsis.” Available at
www.emedicine.com
98
Al‐Khafaji, AH. (2012) “Multiple organ dysfunction syndrome in sepsis.” Available at
www.emedicine.com
99
Al‐Khafaji, AH. (2012) “Multiple organ dysfunction syndrome in sepsis.” Available at
www.emedicine.com
100