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SEPSIS Humberto M. Guiot, MD, FACP Infectious Disease UPR School of Medicine
SEPSIS
Humberto M. Guiot, MD, FACP
Infectious Disease
UPR School of Medicine
Objectives  To discuss the definition of sepsis  To differentiate between bacteremia, systemic inflammatory
Objectives
 To discuss the definition of sepsis
 To differentiate between bacteremia, systemic
inflammatory response syndrome (SIRS), severe
sepsis, septic shock, and multi-organ
dysfunction syndrome
 To establish strategies for management and
treatment of patients in sepsis
Vignette  A 69-year-old is brought to the emergency by his son because of hypoactivity
Vignette
 A 69-year-old is brought to the emergency by his son
because of hypoactivity and drowsiness.
 On physical examination, temperature is 40.1C, heart
rate is 132 bpm, respiratory rate is 32/min, and blood
pressure is 76/34 mmHg. The patient looks critically ill
and lethargic. Pulse oxymetry reveals an oxygen
saturation of 78%.
Q: What is the differential diagnosis?
Q:
What is the
differential diagnosis?
Definitions  SIRS – systemic inflammatory response syndrome to a variety of severe clinical insults,
Definitions
 SIRS – systemic inflammatory response syndrome to a
variety of severe clinical insults, most commonly
infectious, but also non infectious
 pancreatitis, ischemia, multiple trauma, and tissue injury,
hemorrhagic shock, immune-mediated organ injury, and
exogenous administration of inflammatory mediators (tumor
necrosis factor or other cytokines).
 2 or more of the following:
 T > 38 C or <36 C
 HR > 90 beats/min
 RR > 20 breaths/min or pCO 2 < 32 mmHg
 WBC >12,000 cells/mm 3 , <4,000 cells/mm 3 , or >10% bands
Definitions  Sepsis – SIRS to an infection.  Severe sepsis – Sepsis associated to
Definitions
 Sepsis – SIRS to an infection.
 Severe sepsis – Sepsis associated to an organ
dysfunction, perfusion abnormalities (lactic acidosis,
oliguria, AMS), or hypotension (systolic BP <90
mmHg).
 Septic shock – Sepsis and hypotension despite adequate
fluid resuscitation.
 MODS (multiorgan dysfunction syndrome) – Altered
organ function in an acutely ill patient.
 Bacteremia – presence of viable bacteria in the blood
Vignette  The patient is immediately intubated and placed on mechanical ventilation with 100% oxygen.
Vignette
 The patient is immediately intubated and placed on
mechanical ventilation with 100% oxygen. Lungs show
bilateral fine expiratory ronchi. The extremities are cold
and clammy with evidence of cyanosis.
 The patient has a history of type-2 diabetes mellitus and
benign prostatic hypertrophy. According to the son, he
was recently complaining of urinary hesitance, dribbling,
and suprapubic abdominal pain.
 Immediate fluid challenge with 2L of 0.9% saline
solution is started
 After 30 minutes, blood pressure is 82/50 mmHg
Vignette  CBC:  WBC 23,000 cells/mcL  Hct 17.2 g/dL  PTL 80,000 cells/mcL
Vignette
 CBC:
 WBC 23,000 cells/mcL
 Hct 17.2 g/dL
 PTL 80,000 cells/mcL
 ABG’s:
 pH 7.180
 pCO2 56.7 mmHg
 pO2 67.8 mmHg
 HCO3 13.2 mEq/L
 Electrolytes:
 BUN 98 mg/dL
 Creat 5.4 mg/dL
Q: What is the precise diagnosis now?
Q:
What is the
precise diagnosis now?
Sepsis and Septic Shock • 13th leading cause of death in U.S. • 500,000 episodes
Sepsis and Septic Shock
• 13th leading cause of death in U.S.
• 500,000 episodes each year
• 35% mortality
• 30-50% culture-positive blood
Factors Associated with Highest Mortality • Respiratory > abdominal > urinary • Nosocomial infection •
Factors Associated with
Highest Mortality
• Respiratory > abdominal > urinary
• Nosocomial infection
• Hypotension, anuria
• Isolation of enterococci or fungi
• Gram-negative bacteremia
• Body temperature lower than 38°C
• Age greater than 40
• Underlying illness: cirrhosis or malignancy
Predisposing Underlying Diseases • Heart disease-rheumatic or congenital • Splenectomy • Intraabdominal sepsis
Predisposing Underlying
Diseases
• Heart disease-rheumatic or congenital
• Splenectomy
• Intraabdominal sepsis
• Septic abortion or pelvic infection
• Intravenous drug abuse
• Immunocompromised
Most Common Etiologies • Gram-negative bacilli – E. coli – Klebsiella pneumonia – Proteus –
Most Common Etiologies
• Gram-negative bacilli
– E. coli
– Klebsiella pneumonia
– Proteus
– Pseudomonas
• Gram-positive cocci
• Gram-negative anaerobes
Organisms Responsible for Septic Shock in Relation to Host Factors Asplenia Cirrhosis Alcoholism Encapsulated
Organisms Responsible for Septic
Shock in Relation to Host Factors
Asplenia
Cirrhosis
Alcoholism
Encapsulated organisms
Pneumococcus spp.,
Haemophilus influenzae,
Neisseria meningtidis,
Capnocytophagia
canimorsus Babesiosis
Vibrio, Yersinia, and
Salmonella spp., other
Gram-negative rods (GNRs),
encapsulated organisms
Klebsiella spp.,
pnemococcus
Diabetes Steroids Mucormycosis and Pseudomonas ssp. (malignant external otitis), Escherichia coli Tuberculosis,
Diabetes
Steroids
Mucormycosis and Pseudomonas ssp.
(malignant external otitis), Escherichia
coli
Tuberculosis, fungi, herpes virus
Neutropenia
Enteric GNR, Pseudomonas,
Aspergillus, Candida, and Mucor spp.,
Staphylococcus aureus
T-cell
abnortmalities
Listeria, Salmonella, and Mycobacteria
spp., herpes virus group (herpes simplex
virus, cytomegalovirus, varicella zoster
virus)
Vignette • The patient persists on mechanical ventilation with 100% FiO2. • No urine output
Vignette
• The patient persists on mechanical ventilation
with 100% FiO2.
• No urine output has been reported.
• V/S: BP: 88/56 mmHg; HR: 122/min; RR:
28/min; T: 34 degrees
• A thermal blanket is placed and the nephrologist
is consulted
Q: What is the most appropriate next step?
Q:
What is the most
appropriate next step?
Surviving Sepsis Campaign  International initiative:  To reduce mortality rate  To improve standards
Surviving Sepsis Campaign
 International initiative:
 To reduce mortality rate
 To improve standards of care
 To secure adequate funding
Initial Resuscitation  Begin as soon as the sepsis syndrome is recognized.  CVP 8-12
Initial Resuscitation
 Begin as soon as the sepsis syndrome is recognized.
 CVP 8-12 mmHg
 Mean Arterial Pressure > 65 mmHg
 Urine output >0.5mL/kg / hr
 Central venous pressure venous oxygen saturation
>70%
 If not achieved with fluid resuscitation (CVP 8-12 mm HG)
during first 6 hours, then transfuse PRBC (to achieve HCT >
30%) or admister vasopressors
Fluid Resuscitation  Natural or artificial colloids (Dextran, gelatin) or crystalloids (NSS, D5W, Lactate) 
Fluid Resuscitation
 Natural or artificial colloids (Dextran, gelatin) or
crystalloids (NSS, D5W, Lactate)
 No evidence to support one over the other
 Resuscitation with crystalloids requires more fluid
(because Vd is much larger)
 Fluid challenge (500 – 1000 cc over 30 min) in
patients with suspected hypovolemia
Vassopressors  When fluid resuscitation fails to restore BP and organ perfusion  To sustain
Vassopressors
 When fluid resuscitation fails to restore BP and organ perfusion
 To sustain life and maintain perfusion in life-threatening
hypotension even during fluid challenge
 First choice vasopressor: norepinephrine and dopamine
(through central catheter)
 Both are preferred over epinephrine
 Norepinephrine is more potent than dopamine and may be more
effective
 Vasopressin for refractory shock despite adequate resuscitation
and high dose conventional vasopressors
Inotropic Therapy  Dobutamine may be used to increase cardiac output.  If used during
Inotropic Therapy
 Dobutamine may be used to increase cardiac
output.
 If used during low blood pressure, it should be
combined with vasopressor therapy
Vignette  V/S are now: BP: 92/61 mmHg; HR: 102/min; RR: 22/min; T: 36 degrees
Vignette
 V/S are now: BP: 92/61 mmHg; HR: 102/min; RR:
22/min; T: 36 degrees
 B/C: positive for GNB in 2 hours
 U/A: turbid urine with sediments. WBC are TNTC,
many bacteria, positive nitrites, positive leukoesterase
 Abdominopelvic CT scan shows an enlarged prostate.
There is bilateral obstructive ureterolithiasis with
hydronephrosis and prominent perinephric fat stranding
suggestive of bilateral pyelonephritis.
Q: How should the infection be treated?
Q: How should the
infection be treated?
PRIOR TO ANTIBIOTICS: Diagnosis!!!  Cultures are to be obtained before antimicrobials are started 
PRIOR TO ANTIBIOTICS:
Diagnosis!!!
 Cultures are to be obtained before antimicrobials are
started
 At least 2 B/C (one peripherally and one through
central catheter)
 Culture of other sites (CSF, urine, wounds, respiratory
secretions)
 Imaging studies and sampling of likely sources of
infection should be performed, but some patients may
be too unstable.
Antibiotic Therapy  Started within 1 hour of recognition  One or more drugs with
Antibiotic Therapy
 Started within 1 hour of recognition
 One or more drugs with activity against the
most likely pathogens and that penetrate the
presumed source of sepsis
 Guided by susceptibility pattern
 Use of procalcitonin (or similar markers) to
assist clinicians in the discontinuation of
antibiotics
 Re-assess after 48-72 hours with the aim of
narrowing spectrum
Antibiotic Therapy  Duration: 7-10 days and guided by clinical response (longer courses in MRSA,
Antibiotic Therapy
 Duration: 7-10 days and guided by clinical
response (longer courses in MRSA, some fungal
and viral infections in immunodeficiencies,
patients with slow clinical response, etc)
 Combination therapy against Pseudomonas and
Acinetobacter and in neutropenic patients
 Stop antibiotics if clinical syndrome is
determined not to be infectious
Antibiotic Therapy  Urosepsis  (Piperacilllin/tazobactam, higher general cephalosporin or carbapenem) ±
Antibiotic Therapy
 Urosepsis
 (Piperacilllin/tazobactam, higher general
cephalosporin or carbapenem) ± aminoglycoside
 Intra-abdominal infection
 (Piperacilllin/tazobactam, higher general
cephalosporin or carbapenem) ± aminoglycoside ±
metronidazole
 Pneumonia
 (Cefepime, meropenem or impinem) PLUS
(aminoglycoside or quinolones) ± (vancomycin or
linezolid)
Antibiotic Therapy  CNS infection  Vancomycin PLUS (ceftriaxone or cefotaxime or cefepime or meropenem)
Antibiotic Therapy
 CNS infection
 Vancomycin PLUS (ceftriaxone or cefotaxime or
cefepime or meropenem) ± ampicillin ± acyclovir
 Skin infection
 (linezolid or vancomycin) ±
(piperacillin/tazobactam or cephalosporins or
carbapenem)
 Endocarditis
 depending on organism
Source control  Evaluate the presence of a focus of infection amenable for source control
Source control
 Evaluate the presence of a focus of infection amenable for
source control measures within 12 hours, if feasible
 Drainage of abscess
 Debridement of infected necrotic tissue
 Removal of infected device
 Source control with the least physiological effect
 Percutaneous rather than surgical drainage, for example
 Source control as soon as possible following initial resuscitation
 GI perforation
 Intestinal ischemia
 Promptly remove infected central lines/intravascular devices
Vignette  The patient was administered meropenem and gentamicin  On the following day, the
Vignette
 The patient was administered meropenem and
gentamicin
 On the following day, the patient undergoes
hemodialysis.
 Urologic Surgeon performs a bilateral double-J catheter
placement
Q: What other strategies are recommended in the treatment of sepsis?
Q:
What other
strategies are
recommended in the
treatment of sepsis?
Corticosteroids  IV Hydrocortisone (200-300 mg/day) is recommended for 7 days in patients with septic
Corticosteroids
 IV Hydrocortisone (200-300 mg/day) is recommended for 7 days in patients
with septic shock requiring vasopressors
 Three or four divided doses or continuous infusion
 Rationale: a trial showed shock reversal and reduction in mortality in patients
with relative adrenal insufficiency (post-adrenocorticotropic hormone cortisol
increase <9 mcg/dL)
 ACTH test to identify responders (>9mcg/dL increase in cortisol). No
steroids for responders, as these patients do not have relative adrenal
insufficiency.
 Taper steroids after resolution of shock
 Other authorities taper doses of corticosteroids at the end of therapy
 No high dose hydrocortisone (>300 mg/day)
 No shock = no steroids
 Dexamethasone does not interfere with ACTH test
Activated Protein C  Recombinant human activated protein C (rhAPC or drotrecogin alfa, Xigris®) was
Activated Protein C
 Recombinant human activated protein C
(rhAPC or drotrecogin alfa, Xigris®) was
recommended in patients at high risk of death
(APACHE II>25, sepsis-induced MOF, septic
shock, or sepsis-induced ARDS) with no
absolute contraindication (mostly related to
bleeding or risk of bleeding).
 Withdrawn from the US Market on October
2011 due to failure to show survival benefit
Blood Product Administration  After initial resuscitation  PRBC transfusion for Hb < 7 g/dL
Blood Product Administration
 After initial resuscitation
 PRBC transfusion for Hb < 7 g/dL to a target of 7-9 g/dL
 Erythropoetin is not recommended as specific treatment of
anemia associated to severe sepsis
 No FFP in the absence of bleeding or planned procedure
 Antithrombin administration is not recommended for the
treatment of severe sepsis and shock
 Platelet transfusion
 <5,000
 5,000-30,000 + risk of bleeding
 >50,000 for surgery of invasive procedure
Glucose Control  BS < 150 mg/dL  Studies have used continuous infusion of insulin
Glucose Control
 BS < 150 mg/dL
 Studies have used continuous infusion of insulin and
glucose
 Best results with BS between 80-110 mg/dL
 Glucose should be monitored frequently after
initiation of the protocol (every 30-60 mins) and on
a regular basis (every 4 hours) once BS has been
stabililized.
 Nutrition protocol with preferential use of
enteric route
DVT Prophylaxis  Severe sepsis patients should receive prophylaxis with low-dose unfractionated heparin or LMWH.
DVT Prophylaxis
 Severe sepsis patients should receive prophylaxis
with low-dose unfractionated heparin or
LMWH.
 In patients who have contraindications for heparin
use, mechanical prophylactic device (compression
stockings, intermittent compression device) is
recommended
Stress Ulcer Prophylaxis  Should be given to all patients with severe sepsis  H2
Stress Ulcer Prophylaxis
 Should be given to all patients with severe sepsis
 H2 receptor blockers are more efficacious than
sucralfate
 PPIs have not been assessed in a direct comparison
with H2 receptor antagonists
Vignette  72 hours after admission:  Vasopressors could be discontinued  Creat is now
Vignette
 72 hours after admission:
 Vasopressors could be discontinued
 Creat is now 1.5 mg/dL and dialysis is put on hold
 FiO2 has been decreased to 40%
 Final B/C and U/C report: MDS E. coli
 WBC are 11,000 cells/mcL while PTL count is 140,000
cells/mcL
Q: What is the most appropriate next step?
Q:
What is the most
appropriate next step?
Q: What would be done if the course had been different?
Q:
What would be
done if the course had
been different?
Consideration for Limitation of Support  Advance care planning (communication of likely outcomes and realistic
Consideration for Limitation of Support
 Advance care planning (communication of likely
outcomes and realistic goals) should be
discussed with patients and relatives.
 Decisions for less aggressive support or
withdrawal of support may be in the patient’s
best interest.
References  “Surviving Sepsis Campaign: International Guidelines for the Management of Severe Sepsis and Septic
References
 “Surviving Sepsis Campaign: International
Guidelines for the Management of Severe Sepsis
and Septic Shock”. Crit Care Med. 2013; 41:
580-637.
 “Surviving Sepsis Campaign: Guidelines for the
Management of Severe Sepsis and Septic
Shock”. Crit Care Med. 2004; 32: 858-873.
 Gorbach SL. Infectious Diseases, 3 rd edition.