SEPSIS AND SEPTIC SHOCK INTERNAL MEDICINE

Carmen Chungunco, MD, FPCP, FPCC

May 4, 2021
6.6
OUTLINE lactate of 2 despite adequate serum resuscitation. Sa ating
I. Case patient (Case), di pa niya nafufulfill ang criteria na ito so we
II. Definition of Sepsis
would consider her as SEPSIS. We have a possible infectious
III. Sepsis
IV. Organ Dysfunction and Shock etiology which is your UTI
V. Clinical Manifestations
VI. Diagnosis
DEFINITION OF TERMS
VII. Complications
VIII. Treatment SYSTEMIC INFLAMMATORY RESPONSE (SIRS)
IX. Surviving Sepsis Guidelines  Two or more of the following conditions:
X. Summary o Fever (oral temperature >38°C) or hypothermia
XI. Appendix
(<36°C)
LEGEND o Tachypnea (>24 breaths/min)
 Book  Recording  Previous Trans Must know o Tachycardia (heart rate >90 beats/min) at rest
Important Concept o Leukocytosis (>12,000/L), leukopenia (<4,000/L),
or >10% bands
References:  May have a non-infectious etiology and infectious
1. Dr. Chungunco’s Powerpoint etiology
2. 2019, 2020 & 2021 Trans
3. 20 edition HPIM
SEPSIS
CASE  SIRS that has a proven or suspected microbial etiology
 84 y/o female admitted for decreased sensorium o SIRS with PROVEN INFECTION – for our case,
 Hypertensive on Ramipril, Amlodipine she has SIRS plus UTI
 Diabetic on Sitagliptin (DPP-4 inhibitor), Metformin  it is a life-threatening organ dysfunction caused by a
 3-day history of dry cough and fever, anorexia and body dysregulated host response to infection
malaise
 Common clinical features:
 Noted to be drowsy on day of consult
o Signs of infection
o (+) organ dysfunction
AT THE ER
o Altered mentation
 Drowsy, disoriented
o Tachypnea
 BP=80/40 mmHg, HR=125/min, RR=24/min, T=38.7C
o Hypotension
 Pink palpebral conjunctivae, anicteric sclerae, (-) cervical o Hepatic, renal, or hematologic dysfunction
lymphadenopathies (CLAD), (-) neck vein engorgement  OLD CRITERIA: suspected (or documented) infection
 No retractions, Clear breath sounds plus ≥ 2 SIRS criteria
 (-) Heaves/thrills, AB at 5th LICS MCL, good S1, (-)  NEW CRITERIA (2016): suspected (or documented)
murmurs infection and an acute increase in ≥ 2 sepsis-related
 Soft abdomen, NABS, nontender, liver and spleen not organ failure assessment (SOFA) points)
palpable
 (-) Edema, warm extremities, pulses +1 SEPTIC SHOCK
Warm extremities due to vasodilation  A subset of sepsis in which underlying circulatory and
cellular/metabolic abnormalities lead to substantially
LAB RESULTS increased mortality risk
 CBC – Hgb 11 g/dl, WBC 33,000, 85% neutrophils  Common clinical features:
 Chem: RBS 220, creatinine 1.8 mg/dl, Na 160, K 4 o Signs of infection
 CXR – no infiltrates o Altered mentation
 Urinalysis – (+) nitrites, WBC 70/hpf o Oliguria
o Cool peripheries
 Question: What is the most appropriate diagnosis for this o hyperlactemia
patient’s condition?  2003 criteria: suspected (or documented) infection plus
A. Systemic Inflammatory Response Syndrome persistent arterial hypotension (systolic arterial pressure
(SIRS) <90 mmHg; mean arterial pressure <60mmHg; or change
B. Sepsis in SBP by >40 mmHg less from baseline) This was very
C. Severe Sepsis tedious and very confusing for a lot of people.
D. Septic Shock  2016 CRITERIA (currently used): Suspected (or
(Refer to the 2003 and2016 definition of septic shock) If we use the old definition, documented) infection plus vasopressor therapy
then the patient in the case is in septic shock. However, in the needed to maintain mean arterial pressure at ≥65 mmHg
new definition, it is septic shock only when you are in and serum lactate >2.0 mmol/L despite adequate fluid
vasopressor therapy to maintain this MAP at 65 and serum resuscitation I want you to remember the latest definition

RAMIREZ & SUELO EDITOR: NICDAO Page 1 of 13

INTERNAL MEDICINE SEPSIS AND SEPTIC SHOCK LECTURE 6.6

of septic shock importance of that is seen in the clinical setting

now.
 Gram-negative negative bacteria most likely to cause
sepsis
o E. coli, Klebsiella, Pseudomonas
o Pseudomonas — nosocomial-acquired
pneumonia; cyano-green/blue green specimen
(sputum, urine, etc.)
 Pulmonary/respiratory (most common) and
intraabdominal infections – eightfold more likely to cause
sepsis or severe sepsis

I.PATHOPHYSIOLOGY

Figure 1. Sequence

The term severe sepsis is not used anymore

Table 1. Sequential (or sepsis-related) organ failure assessment

(SOFA) score Figure 2. Select mechanisms implicated in the pathogenesis of sepsis-
Again, to delineate between sepsis and septic shock, it really is the use induced organ and cellular dysfunction
of fluid resuscitation tsaka vasopressor therapy to maintain the blood Basically, it is brought about by extreme inflammatory
pressure and serum lactate levels (SEPTIC SHOCK) response. There is an inflammatory response that happens
and the only difference is now we have a pathogen that’s
SEPSIS
causing the inflammatory response.
 Increasing incidence
Here’s the pathogen on the left corner, when it comes
o Due to increasing age and pre-existing
in, there are immune cells that recognize the pathogen and
comorbidities
start a chain reaction of inflammatory mediators, the cytokines,
o Use of immunosuppressive drugs, indwelling
which will now cause the inflammation to occur. That includes
catheters and other mechanical devices
in the microcirculation, a lot of thrombosis, so there is thrombus
(implants), antibiotic resistance This is why in the
production, there is leakage of the endothelial cells or the
first lecture that we had we talked about antibiotic
endothelial leak or dysfunction, and there’s a lot of adhesions
stewardship kasi if we give antibiotics left and
and transmigrations of the leukocytes. In the microcirculation,
right, we do run the risk of causing resistance.
because of all of these processes, you now cause some tissue
 Many things can bring in sepsis in that record. So what is
edema which goes into the interstitium. So the tissue edema
sepsis? It is usually triggered most often by microbial
now increases the 02 diffusion distance between the
pathogens which do NOT usually cause systemic
microcirculation going to the cell. Because there’s a lot of
disease in immunocompetent hosts. Usually happens in
edema in the interstitium, the oxygen diffusion from the
people who are immunocompromised. Either because of
microcirculation to the cell becomes harder. And because of
illness or immunocompromised because of a certain state.
that, tissue oxygenation goes down, lactate is produced, and
Sometimes it can be a “perfect storm”. Somebody who is
now we have a lot of lactate that is produced and causing a lot
usually immunocompetent but it happens that they were
of damage as well. So now with all of these, we will get
immunocompromised relatively because they were under
hypotension, hypovolemia and vasodilation.
a lot of stress, working long hours, not eating, and not
The inflammatory response is the same for SIRS and
really taking good care of themselves. And this exposure
sepsis. Give me an example of SIRS without an infection? For
to a pathogen in high concentration, remember we said
instance in burns, patient who have burns, there is
that for you to get any infection, it has to be a “perfect
inflammatory response. They are edematous but not really due
storm” between the host, the pathogen and the
to pathogen. Allergies is also an inflammatory response but
environment that you’re in. This is what also increases
again, there is no pathogen in that situation. If there is
your risk for sepsis. It is usually trigger by a pathogen,
pathogen that is triggering the inflammatory response, it is
o Not recognized by host receptors
sepsis.
o Elaborate toxins or other virulence factors Some
of these you encountered in microbiology last  The host response to sepsis involves multiple mechanisms that
year. Marami pinamemorize sa inyo anong lead to decreased oxygen delivery (DO2) at the tissue level.
toxins, anong virulence factors, what number, the

RAMIREZ & SUELO EDITOR: NICDAO Page 2 of 13

INTERNAL MEDICINE SEPSIS AND SEPTIC SHOCK
 The duration, extent, and direction of these interactions are
modified by the organ under threat, host factors (e.g., age,
genetic characteristics, medications), and pathogen factors
(e.g., microbial load and virulence).
 The inflammatory response is typically initiated by an
interaction between pathogen-associated molecular patterns
(PAMPs) expressed by pathogens and pattern recognition
receptors expressed by innate immune cells on the cell
surface (Toll-like receptors [TLRs] and C-type lectin receptors
[CLRs]), in the endosome (TLRs), or in the cytoplasm (retinoic
acid inducible gene 1–like receptors and nucleotide-binding
oligomerization domain–like receptors [NLRs]).
 The resulting tissue damage and necrotic cell death lead to
release of damage associated molecular patterns (DAMPs)
such as uric acid, high-mobility group protein B1, S100 proteins,
and extracellular RNA, DNA, and histones.
 These molecules promote the activation of leukocytes,
leading to greater endothelial dysfunction, expression of
intercellular adhesion molecule (ICAM) and vascular cell
adhesion molecule 1 (VCAM-1) on the activated endothelium,
coagulation activation, and complement activation.
 This cascade is compounded by macrovascular changes
such as vasodilation and hypotension, which are exacerbated
by greater endothelial leak tissue edema, and relative
intravascular hypovolemia.
 Subsequent alterations in cellular bioenergetics lead to greater
glycolysis (e.g., lactate production), mitochondrial injury,
release of reactive oxygen species, and greater organ
dysfunction
Etiology
 Microbial invasion of the bloodstream is not essential
because local inflammation can also elicit distant organ
dysfunction and hypotension
 Blood cultures yield bacteria or fungi in only ~20–40% of
severe sepsis and 40–70% of septic shock.
 Microbiologic results were positive in 70% of individuals
considered infected;
o 62% were gram-negative bacteria: E. coli &
pseudomonas were most common
o 47% were gram positive bacteria: Staph aureus
was most common
o 19% were fungi (Candida species)
RAMIREZ & SUELO EDITOR: NICDAO
LECTURE 6.6
Figure 3. Pathogenesis
Here very clearly we see the difference. For gram
negative bacteria, the lipopolysaccharide is the one in the cell
wall of the bacteria and the one that really triggers the
response. Whereas in the gram positive bacteria, the teichoic
acid and the lipoteichoic acid come in and once they are
recognized by the cell surface, they go down the pathway (see
illustration) Proinflammatory cytokines are produced, platelet
activating factor, Nitric oxide, coagulation, and now cause an
inflammatory cascade. Now you have diffused endothelial
disruption and microcirculation defects causing global tissue
hypoxia and organ dysfunction. Eventually, if the organ
dysfunction and the vasodilation is severe, you now get a
septic shock.
II. ORGAN DYSFUNCTION AND SHOCK
 Widespread vascular endothelial injury due to
cytokines: major mechanism for multiorgan dysfunction
 Tumor Necrosis Factor (TNF) – induce vascular
endothelial cells to produce and release:
o Cytokines (IL-1 and 6)
 Increase blood flow to the target tissues
(rubor)
 Enhance permeability of local blood vessels
(tumor)
 Recruit neutrophils and other cells (calor)
 Elicit pain (dolor)
 Sepsis is a pro-inflammatory state.
o Procoagulant molecules
 Promote coagulation. It may also put the
patient at risk for DIC
o Platelet activating factor
o Nitric oxide and other mediators – induce
vasodilation and may contribute to shock
 Endothelial cell activation can promote increased vascular
permeability, microvascular thrombosis, DIC, hypotension
 Tissue oxygenation decreases
 Poorly functioning "septic" organs usually appear normal
at autopsy → Little necrosis → Organ dysfunction during
severe sepsis has a basis that is principally biochemical,
not structural. It’s the exchange of oxygen from the
microcirculation going to the cell that is diminished so the
organs die because there’s not enough tissue
oxygenation.
 HALLMARK OF SEPTIC SHOCK:
o Decrease in peripheral vascular resistance
despite increased levels of vasopressor
catecholamines So remember, septic shock
happens because of the inflammation, the
vasodilation has occurred, some of the fluids has
gone into the interstitium, and because it is
vasodilated, blood pressure drops. There is no
vascular resistance to hold it up. Catecholamines
will come out as a “fight-or-flight” response kaya
lang, what will catecholamine supposed to do?
Catecholamines are supposed to cause
vasoconstriction. However in overwhelming sepsis
leading to septic shock, even the catecholamines
are not enough to generate good vasoconstriction
causing blood pressure to drop.
Page 3 of 13
INTERNAL MEDICINE SEPSIS AND SEPTIC SHOCK
 In patients with severe sepsis, persistence of leukocyte
hyporesponsiveness has been associated with an
increased risk of dying; at this time, the most predictive
biomarker is a decrease in the expression of HLA-DR
(class II) molecules on the surfaces of circulating
monocytes (Trans 2019)
PHASES OF SEPTIC SHOCK
From Trans 2020:
 Hypodynamic vasodilatory phase – compromised
oxygen delivery to tissues  ↑ blood lactate, ↓ central
venous oxygen saturation
 Hyperdynamic vasodilatory phase – after fluid
administration
o Normal or high cardiac output, oxygen
consumption declines despite adequate oxygen
delivery; normal or increased blood lactate
o Normalization of central venous oxygen
saturation may reflect improved oxygen delivery,
decreased oxygen uptake by tissues, or left-to-
right shunting
III. CLINICAL MANIFESTATION
 Clinical manifestations are due to the local and systemic
host response to invading microbes not because of the
direct response of the toxins or the bacteria
 Fever (may be absent in elderly, immunocompromised,
uremia, alcoholism)
 Hyperventilation – an early sign of the septic response
Why would the patient go into tachypnea? Where else do
you see tachypnea happening? Pneumonia, metabolic
acidosis (Kussmaul’s phenomenon). What do you think
is causing the metabolic acidosis in sepsis? Lactic
acidosis.
 MUDPILES
 Encephalopathy (decreased sensorium/cognition)
because not enough perfusion going to the brain
 Hypotension and poor perfusion – most commonly on
the digits
 DIC
 Skin lesions
o Cellulitis, pustules, bullae, or hemorrhagic lesions
o N. meningitidis should be suspected if cutaneous
petechiae or purpura is seen
o Presence of Ecthyma gangrenosum suggests P.
aeruginosa infection.
 Why do you think skin lesion manifests? So remember
when you have low blood pressure, they will all go to the
central organs first, leading the skin and the other
peripheral organs last. So syempre because of that, you
will get poor perfusion and they are very prone to skin
breakage and stress ulceration
 Stress ulceration – for the GI tract
 Cholestatic jaundice, acute liver injury, ischemic
bowel necrosis – As we said, everything will be given to
the skin organs first.
RAMIREZ & SUELO EDITOR: NICDAO
LECTURE 6.6
IV. DIAGNOSIS
 NO SPECIFIC DIAGNOSTIC TEST FOR SEPSIS!
 Definitive etiologic diagnosis requires identification of the
organism from blood or local site of infection
o Blood cultures from 2 different sites (from two
different venipuncture sites) and we also get from
the site of infection. In this patient, if we’re
thinking UTI, we do need to send some urine
specimen as well.
o Negative (blood) cultures in many cases (prior
antibiotic use, slow-growing organism like TB,
absence of microbial invasion of bloodstream i.e
UTI/cystitis) Kung negative ang blood culture, this
does not mean that the patient doesn’t have
sepsis. You really have to go to the clinical
picture.
 Possible markers of sepsis:
o Procalcitonin (if value is >2)
 A new marker that is being used to
check if the patient have a bacterial
infection vs a viral infection.
 Prognosticating factor
 Tells you “likelihood” of sepsis
 May produce false positives
o Lactate
 The longer that tissues are not well
perfused, there is formation of lactic acid
 Serum lactate of >1.5x elevated =
likelihood of sepsis
CRITERIA
o SOFA (Sequential Organ Failure Assessment)
o qSOFA (quick SOFA) - shorter version of the
sofa
Figure 4. Algorithm of SOFA
Basically the patient comes in with a suspected
infection, we use our quick SOFA to see if they are at high risk
for sepsis. Quick SOFA includes these 3 parameters:
Respiratory rate, mental status and systolic blood
Page 4 of 13
INTERNAL MEDICINE SEPSIS AND SEPTIC SHOCK LECTURE 6.6

pressure. If more than 2 of these is affected, then we assess
for evidence of organ dysfunction and organ dysfunction is
seen more with the SOFA variables (Refer to the diagram). If
patient has more than 2 of these variables, then the patient is
in sepsis. And if you include vasodepressor and serum lactate
that we mentioned earlier, then it is septic shock. The SOFA
scores allow us to know whether the patient is at high risk for
mortality while in the hospital.
Quick (q) SOFA Points
1 point for each criteria (Remember: “HAT”)
1. Hypotension: Systolic BP ≤ 100 mmHg
2. Altered mental status: GCS < 15
3. Tachypnea: RR≥ 22/min
qSOFA ≥2 suggests high in-hospital mortality
 ICU admission
6. Renal: Creatinine and Urine Output
V. LABORATORY FINDINGS
 Leukocytosis with a left shift or leukopenia
 Thrombocytopenia (sign of hematologic organ dysfunction)
 Hyperbilirubinemia
 Proteinuria
 Prolongation of the thrombin time, decreased fibrinogen,
and the presence of D-dimers
o suggests the presence of DIC
 Azotemia
 Elevated aminotransferases – SGOT and SGPT are very
high lalo na if it’s ischemic it will go up to the thousands.
 Respiratory alkalosis (early) progressing to metabolic
acidosis
 Hypoxemia
 Hyperglycemia because of the adrenaline response
 OTHER LABORATORY FINDINGS:
o CXR: Could be normal or could show underlying
pneumonia, vol. overload, ARDS
o ECG: tachycardia or nonspecific ST-T wave
abnormalities
o Most diabetic pxs w/ sepsis develop hyperglycemia
(severe infection can precipitate DKA which could
exacerbate hypotension)
o Hypoglycemia occurs rarely and may indicate
adrenal insufficiency
o Serum albumin level declines as sepsis continues

VI. COMPLICATIONS
 CARDIOPULMONARY COMPLICATIONS
o ALI/ARDS
 Progressive diffuse pulmonary infiltrates and
Figure 5. Factore of qSOFA & SOFA arterial hypoxemia occurring within 1 week of
a known insult
Sequential Organ Failure Assessment (SOFA) Points
 Acute Lung Injury (ALI) develops in 50% of
patients with septic shock / severe sepsis
o Normal or increased cardiac output
o Decreased systemic vascular resistance
o Normal or increased cardiac output and decreased
systemic vascular resistance distinguish septic shock
from cardiogenic, extracardiac obstructive, and
hypovolemic shock
 ADRENAL INSUFFICIENCY – critical illness–related
corticosteroid insufficiency (CIRCI) from secondary cause
Table 2: Sequential Organ Failure Assessment (SOFA) Points
o Common for those who stay longer in the ICU
o Normal cortisol levels but there is increased body
**check for larger picture, demand, making it insufficient
 Scoring system if the patient is in sepsis and what are the o Maybe due to abnormalities in glucocorticoid
chances of in-hospital mortality. receptors or increased conversion of cortisol to
 Parameters: cortisone due to HIGH DEMAND caused by stress
1. Respiration: PaO2/FiO2 – ARDS parameter – you need o Major clinical manifestation of CIRCI: hypotension
to get an ABG for the arterial oxygenation and that is refractory to fluid replacement and requires
PaO2/FiO2 ratio pressor therapy
2. Coagulation: Platelet ct  RENAL COMPLICATIONS – most renal failure is due to
3. Liver: Bilirubin Acute Tubular Necrosis
4. CV: MAP = SBP+DBP/DBP – in response to o induced by hypotension or capillary injury
vasopressors o Oliguria, azotemia, proteinuria, and nonspecific
5. CNS: GCS urinary casts are frequently found

RAMIREZ & SUELO EDITOR: NICDAO Page 5 of 13

INTERNAL MEDICINE SEPSIS AND SEPTIC SHOCK
 COAGULOPATHY – thrombocytopenia/DIC
 NEUROLOGIC COMPLICATIONS
o Hypotension causing decrease perfusion in the brain
causing septic encephalopathy
o "Critical illness" polyneuropathy – may prevent
weaning from ventilator support and produce distal
motor weakness
o Delirium (Acute encephalopathy) – often an early
manifestation of sepsis (10-70%)
 IMMUNOSUPPRESSION
o Loss of delayed type hypersensitivity reactions to
common antigens, failure to control the primary
infection, and increased risk for secondary infection
VII. TREATMENT
GOALS
1. URGENT MEASURES TO TREAT INFECTIONS
 Empiric antibiotics started within 1 hour of diagnosis (refer
to Table 325-3 in the appendix)
o Should be given IV, with adjustment for those with
impaired renal function
o Empiric ANTIFUNGAL therapy strongly considered if
patient receiving broad spectrum antibiotics or
parenteral nutrition has been neutropenic for ≥5 days
or has been in ICU for a prolonged period.
2. PROVIDE HEMODYNAMIC AND RESPIRATORY SUPPORT
 Measured by BP, mentation, urine output, skin perfusion
3. REMOVE SOURCE OF INFECTION
 Seek the site of infection carefully lalo na sa lungs,
abdomen, and urinary tract.
 Catheters should be removed, and the tip cultured.
 For those with NGT, consider paranasal sinusitis din as a
source of infection
 In a neutropenic patient, check for cutaneous sites of
tenderness and erythema particularly sa perianal region
(consider AIDS)

SURVIVING SEPSIS CAMPAIGN: INTERNATIONAL
GUIDELINES FOR SEPSIS AND SEPTIC SHOCK
 ibibigay niyo as fast drip. Ang gagawin niyo is you divide
“Sepsis and septic shock are medical emergencies and we
recommend that treatment and resuscitation begin
immediately.”
– Best Practice Statement, SSC 2016
SOURCE CONTROL
 We recommend that a specific anatomic diagnosis of
infection requiring emergent source control be
identified or excluded as rapidly as possible in
patients with sepsis or septic shock, and that any required
source control intervention be implemented as soon as
medically and logistically practical after the diagnosis is
made.
o Cultures
 Blood
 Urine
 Lungs (Sputum, Endotracheal Aspirate)
 Gastrointestinal
RAMIREZ & SUELO EDITOR: NICDAO
LECTURE 6.6
 Fecalysis
 UTZ (solid organs), CT scan (intestines)
o For intraabdominal infections
 Peritoneal aspiration if there is ascites
ANTIBIOTICS
 We recommend that administration of IV antimicrobials be
initiated as soon as possible after recognition and within
1h for both sepsis and septic shock. (Strong
recommendation, moderate quality of evidence)
 We recommend empiric broad-spectrum therapy or
combination therapy with one or more antimicrobials to
cover all likely pathogens. (Strong recommendation,
moderate quality of evidence)
 We suggest empiric combination therapy (using at least
two antibiotics of different antimicrobial classes) for
instance somebody who has pneumonia, you will give
piperacillin-tazobactam and maybe a macrolide. For UTI,
you can also give piperacillin-tazobactam while waiting for
the cultures aimed at the most likely bacterial pathogen(s)
for the initial management of septic shock. (Weak
recommendation; low quality of evidence)
o Must cover gram-negative bacteria.
o If with abscess, must also cover anaerobes.
INITIAL RESUSCITATION
 We recommend that in the resuscitation from sepsis-
induced hypoperfusion, at least 30ml/kg of intravenous
crystalloid fluid be given within the first 3 hours.
(Strong recommendation; low quality of evidence) Kahit na
sabihin na “why do we need to resuscitate wala naman
siya fluid losses hindi naman siya nagbleed hindi naman
siya nag diarrhea, why do we have to give fluid
resuscitation? Precisely because of the main problem of
sepsis which is vasodilation. All of the inflammatory
mediators have caused vasodilation so we need to give a
lot of fluids so that the microcirculation is well perfused.
Example: Patient is 60 kg, how much fluid are we going to
give in the first 3hrs? 1.8L in 3 hrs. Pero hindi lahat yan
that into the 3 hours which is about 600mL per hour. This
maybe a problem for example in patients with cardiac
dysfunction let’s say may heart failure si patient, then
maybe we can adjust. But for the most part if there is no
problem with the cardiac status of the patient, you have to
push that 600cc per hour for the first 3 hours. You have to
do this with close monitoring to the patient.
o Crystalloids (NSS, LR) are recommended!
(usually NSS)
 Albumin may be added to crystalloid if the
patient requires substantial amounts of
crystalloid
 Hydroxyethyl starches (HES) are NOT
recommended
 We recommend that following initial fluid resuscitation,
additional fluids be guided by frequent reassessment of
hemodynamic status. (Best Practice Statement)
 Goals of Initial Resuscitation:
Page 6 of 13
INTERNAL MEDICINE SEPSIS AND SEPTIC SHOCK LECTURE 6.6

o CVP maintained at 8-12 cmH2O to prevent However, do not delay the antibiotic therapy. Start therapy
pulmonary edema within an hour.
o Maintain Mean Arterial Pressure at >65 mmHg
(systolic pressure >90 mmHg)
o Urine output should be kept at >0.5 mL/kg per hour
 We suggest guiding resuscitation to normalize lactate in
patients with elevated lactate levels as a marker of
tissue hypoperfusion (weak recommendation, low quality
of evidence)

VASOACTIVE AGENTS
What if after the first hour of giving 600cc of fluid hydration
sometimes you even go beyond that, the BP is still very low.
You know that if the BP is low for a very long time will already
cause hypoperfusion for the organ. After you give fluid boluses,
you can already start vasopressors if your blood pressure does
not go up. Normally, if it’s 80/40 and you give around 600cc in
the first hour or kahit 300 in the first half hour, the blood
pressure will start to pick up a little bit. If it doesn’t, you really
have to start vasopressors.
 We recommend Norepinephrine as the first-choice
vasopressor for all patients with sepsis. It is the first
choice because it will cause vasoconstriction and hopefully
bring up the BP. (strong recommendation, moderate
quality of evidence).
 If the patient is at maximum NE, We suggest adding either
vasopressin (up to 0.03 U/min) or epinephrine to
norepinephrine with the intent of raising MAP to target, or
adding vasopressin (up to 0.03 U/min) to decrease
norepinephrine dosage. (weak recommendation; low
quality of evidence)
TARGET MAP = 65mmHg or higher
o MAP Formula:
 MAP = (SP + 2 DP) / 3
 So for our patient, BP is 80/40.
 MAP = [80 + 2 (40) ] / 3
 MAP = 53.33 (low because
target is 65)
 Dopamine is suggested as an alternative vasopressor
to norepinephrine ONLY in HIGHLY SELECTED
PATIENTS:
o Low risk of tachyarrhythmia and absolute or
relative bradycardia
Table 3. Clinical guidelines for the management of patients with sepsis
and septic shock – RESUSCITATION bigger picture in the appendix
DIAGNOSIS
 We recommend that appropriate routine microbiologic
cultures (including blood) be obtained BEFORE starting
antimicrobial therapy in patients with suspected sepsis
and septic shock if doing so results in no substantial delay
in the start of antimicrobials. (Best Practice Statement)
Table 4. Initial Antimicrobial Therapy for Severe Sepsis with No
Obvious Source in Adults with Normal Renal Function. For empirical
antibiotic therapy the appropriate choice depends on the suspected
site of infection, the location of infection onset (i.e., the community, a
nursing home, or a hospital), the patient’s medical history, and local
microbial susceptibility patterns
1. SEPTIC SHOCK for immunocompetent adult – piperacillin-
tazobactam, cefepime or meropenem.
 If they have a device in their body (e.g. catheter) –
give vancomycin loading dose
2. NEUTROPENIA –cefepime, meropenem or piperacillin
tazobactam
3. SPLENECTOMY - Ceftriaxone
o Remarks: Appropriate routine microbiologic
cultures always include at least TWO sets of
blood cultures (aerobic and anaerobic)
ANTIMICROBIAL THERAPY AND ANTIBIOTIC
STEWARDSHIP
 We recommend that empiric antimicrobial therapy be
narrowed once pathogen identification and sensitivities
are established and/or adequate clinical improvement is
noted
 We suggest that an antimicrobial treatment duration of 7-
10 days is adequate for most serious infections
associated with sepsis and septic shock sometimes up to
14 days depending on the patient’s situation.
 We recommend daily assessment for de-escalation of
antimicrobial therapy in patients with sepsis and
septic shock
o Criteria for de-escalation
 Afebrile for 24 hours
 Improved mental status (conscious)
 Able to tolerate oral meds
 Clinically better (good BP, urine output, etc)
 We suggest that measurement of procalcitonin levels
be used to support shortening the duration of antimicrobial

RAMIREZ & SUELO EDITOR: NICDAO Page 7 of 13

INTERNAL MEDICINE SEPSIS AND SEPTIC SHOCK
therapy in sepsis patients. Procalcitonin levels is the signal
to go to the oral antibiotics therapy.
CORTICOSTEROIDS
What role do corticosteroids play in sepsis? Generally, sepsis
causes adrenal insufficiency because of the overwhelming
inflammatory response. The body is in a fight-or-flight mode
and one of them is to bring up cortisol. If that happens, we
have a patient who is hypotensive and kahit magbigay tayo ng
vasopressors and fluids, hindi tumataas ang kanilang BP. In
those cases, that’s the only time that we can assume that there
might be some adrenal insufficiency and give some IV
hydrocortisone.
 We suggest AGAINST using intravenous
hydrocortisone to treat septic shock patients IF adequate
fluid resuscitation and vasopressor therapy are able to
restore hemodynamic stability. If this is not achievable, we
suggest intravenous hydrocortisone at a dose of 200
mg per day. (Weak recommendation; low quality of
evidence)
 For CIRCI: Hydrocortisone (50 mg IV every 6 hours)
should be given
VENTILATOR THERAPY (HARRISON’S)
 Indicated for progressive hypoxemia, hypercapnia,
neurologic deterioration, or respiratory muscle failure
 Sustained tachypnea (RR of >30 breaths/min) is a
harbinger of impending respiratory collapse; therefore,
mechanical ventilation is necessary
 Stress ulcer prophylaxis
o Histamine H2 receptor antagonist may decrease
the risk of GI hemorrhage in ventilated patient
OTHER RECOMMENDATIONS
 Glucose control:  180mg/dL
 Nutrition: Enteral feeding as soon as possible
 oral or NGT
 Use of prokinetics –allow the gut to move forward to
avoid ileus from happening
SETTING GOALS OF CARE
 We recommend that goals of care and prognosis be
discussed with patients and families. (Best Practice
Statement)
o Guarded prognosis for the first 72 hours
 We recommend that the goals of care be incorporated into
treatment and end-of-life care planning, utilizing palliative
care principles where appropriate. (Strong
recommendation; moderate quality of evidence)
 We suggest that goals of care be addressed as early as
feasible, but no later than within 72 hours of ICU
admission. (Weak recommendation; low quality of
evidence)
RAMIREZ & SUELO EDITOR: NICDAO
LECTURE 6.6
Table 5. Clinical guidelines for the management of patients
with sepsis and septic shock bigger picture in the appendix
1. INFECTION CONTROL
2. RESPIRATORY SUPPORT –
 Target tidal volume of 6mL/kg body weight.
 Prone Positioning – we do this a lot in our
covid patients trying to see if we can avoid
them being intubated or if they’re intubated,
we do prone positioning so they can be
extubated as quickly as possible.
 Conservative fluid strategy
 Read the table above
3. GENERAL SUPPORTIVE CARE
 Vasopressor
 Hydrocortisone
 Sedation – sometimes being in the ICU for
patients who have sepsis is very difficult.
Sometimes they fight the ventilators and try
to take out all of the tubes so they do need a
little bit of sedation
 Prophylaxis for DVT – because they are
quite sedentary and they can be
hypercoagulable as you have seen in the
inflammatory cascade, procoagulants are
produced. So those who have sepsis have a
really high risk for DVT
 Stress ulcer prophylaxis (PPIs) – to prevent
gastritis and GI bleeding.
 PROGNOSIS (HARRISON’S)
 20-35% of patients with severe sepsis and 40-60% with
septic shock die within 30 days
 Age and prior health status are the most important risk
factors
 Septic shock is also a strong predictor of both short and
long-term mortality
 PREVENTION (HARRISON’S)
 Reduce number of invasive procedures undertaken
 Limit use of indwelling vascular and bladder catheters
 Reduce incidence and duration of profound neutropenia
 Aggressively treat nosocomial and community acquired
infections
Indiscriminate use of antimicrobial agents and glucocorticoids
should be avoided, and optimal infection-control measures
should be used.
Page 8 of 13
INTERNAL MEDICINE SEPSIS AND SEPTIC SHOCK
VIII. BACK TO THE PATIENT
What is the most appropriate diagnosis for this patient’s
condition?
A. Urinary Tract Infection
B. Systemic Inflammatory Response Syndrome (SIRS)
C. Sepsis
D. Septic Shock
SEPSIS – considering that the patient was not given any
intervention yet like vasopressors, fluids, etc.
SEPTIC SHOCK – consider this if after an hour in the ER with
intervention if the patient is still hypotensive
Sepsis and SIRS – warm extremities due to vasodilation
Cardiogenic shock and hypovolemia - cold and clammy
extremities
What other diagnostic tests will we do?
o Urine and blood culture
 Why do you need blood cultures? If your
urine CS is positive for bacteria and
sensitivities are there, is that enough to
diagnose sepsis? Not really because Urine
CS will tell us a localized source of infection
but not really a systemic one. Sepsis tends
to be a systemic response. Usually it should
be in the blood as well like bacteremia and
septicemia can confirm the diagnosis (if
we’re just talking about labs. But in our
patient we have a clinical picture, urine CS
is enough to diagnose sepsis.
What is the best management for this patient?
o Hydration: 30mL/kg for the first 3 hrs
 If no improvement, give inotrope –
Norepinephrine
o Empiric Antibiotics: within an hour (i.e. 3rd-gen
cephalosporins) and broad spectrum (PipTazo)
o Consider giving CORTICOSTEROIDS if necessary
(indications are discussed above)
o Admit to ICU until stable
o check for fluid status: Urine Output - insert a
catheter; JVP
 Sunken eyeballs are only used as a parameter
for PEDIA px
o If hypoxemic: Intubate
o Feeding: NGT since pt. is drowsy; preferred over
TPN total parenteral nutrition (may cause further
infection and more expensive)
IX. QUIZZES FROM PREVIOUS BATCH
 Patient with infection, drowsy, BP = 80/60, tachycardic, did not
respond to administration of IV fluid. What category?
o Severe sepsis
o Sepsis
o Septic Shock
o Refractory Septic Shock
o Multiorgan dysfunction
 Initial management for septic shock?
o Start antibiotic therapy
RAMIREZ & SUELO EDITOR: NICDAO
LECTURE 6.6
o Get blood culture
o HCO3 infusion
o Start epinephrine drip
o Start norepinephrine drip
Not sure if A or E, kasi septic shock na and by
definition, nabigyan na po sya ng fluids over 3 hours
and still not responsive. Also, empiric antibiotics should
be given within 1 hour of diagnosis.
I-aassume na ba na nabigyan sya ng antibiotics? Wala
po sila sagot 
A 48 year old diabetic patient is brought to the ER for decreased
sensorium. Upon examination, she is drowsy, with BP=80/60,
HR=120/min, RR=24/min and temp=39C, lung and cardiac exams are
unremarkable, a gangrenous non-healing wound with foul-smelling
purulent discharge is noted on her left leg. Her relatives claim that the
patient had been self-medicating the wound for the past month with no
improvement.
 Which is the most appropriate diagnosis for this patient’s
condition?
o Systemic inflammatory response syndrome (SIRS)
o Sepsis
o Septic shock
o Refractory septic shock
o Multiple-organ dysfunction syndrome (MODS)
 Which is NOT included in the criteria for systemic inflammatory
response syndrome (SIRS)?
o Temperature < 36C
o WBC >12,000 u/L
o Heart rate >100/min
o Bacteremia
o May be due to non-infectious etiology
 Which of the following statements about sepsis is TRUE?
o Tissue factor activates both the intrinsic and
extrinsic clotting pathways.
o Intravascular coagulation enables the spread of
microorganisms through the bloodstream.
o Protein C levels are markedly elevated in patients with
sepsis.
o Serum cortisol acts as a pro-inflammatory stimulus.
o All of the above
RATIONALE:
B: Intravascular thrombosis， a hallmark of the local
inflammatory response， may help wall off invading
microbes and prevent infection and inflammation from
spreading to other tissues.
C: Clotting is also favored by impaired function of the protein
C-protein S inhibitory pathway and depletion of antithrombin
and proteins C and S
D: Glucocorticoids inhibit cytokine synthesis by monocytes in
vitro; the increase in blood cortisol levels that occurs early in
the systemic response presumably plays a similarly inhibitory
role
 Which is the first-line treatment for this patient’s hypotension?
o Crystalloids and colloids
o Ventilatory support with positive end-expiratory
pressure
o Nitric oxide analogues
o Oxygen supplementation
o Intravenous inotropic support such as dopamine
END OF TRANS
Page 9 of 13
INTERNAL MEDICINE SEPSIS AND SEPTIC SHOCK LECTURE 6.6

X. TISSUE A. Start prophylactic proton-pump inhibitors

CASE QUESTIONS B. Do tracheostomy instead
CASE 1: 65-year old female is seen at the ER for 3-day C. Suction secretions frequently
history of fever, chills, cough, and dyspnea. D. Start prophylactic antibiotic
E. Maintain the head of bed at an angle >30
PE: Looks weak , BP 100/60 , HR 125, RR 26, TEMP 39C,
degrees
Warm ext, (+) Dullness on percussion, right lower lung field QUIZ
LABS: CBC: Hgb 10g/dL, WBC 18,000, Neutrophils 80%,
Creatinine 1.8mg/dL 1. Which of the following is TRUE regarding the
CXR: consolidation, Shows right lower lobe pathophysiology of sepsis and septic shock?
A. Organ dysfunction in severe sepsis mainly occurs due to
1. DIAGNOSIS? SEPSIS widespread vascular endothelial injury caused by release of
2. Which of the following is the most appropriate pro-inflammatory cytokines
additional initial treatment for this patient? B. The hallmark of septic shock is increased peripheral
A. Normal saline vascular resistance with low levels of vasopressor
B. Hydrocortisone catecholamines
C. Blood transfusion with PRBC C. Bacterial pathogens directly attack the different organs in
D. Norepinephrine severe sepsis causing widespread dysfunction.
D. Gram positive pathogens are more likely to cause sepsis.
CASE 2: ST, an 80-yeard old diabetic male, is admitted for
an acute infarct in the right cerebral hemisphere. He is
intubated upon admission due to respiratory distress. On his SUMMARY
4th hospital day, he develops ventilator-associated SIRS  Two or more of the following
pneumonia and is started on IV antibiotics. However, he is
conditions:
then noted to have BP 70/50, HR 110/min, RR 30/min, and
T 38.6C. He is given IL of intravenous normal saline as fast o Fever (oral temperature
drip but the blood pressure does not improve. A urine >38°C) or hypothermia
catheter is placed to monitor his output. (<36°C)
o Tachypnea (>24
1. Which of the following is most effective in breaths/min)
preventing catheter-associated UTI? o Tachycardia (heart rate
A. Administration of a prophylactic antibiotic
>90 beats/min) at rest
B. Changing the catheter every 72 hours
C.Checking for and treating asymptomatic o Leukocytosis
bacteriuria (>12,000/L), leukopenia
D.Removing the urinary catheter as soon as (<4,000/L), or >10%
possible bands
E. Using silver-impregnated urinary catheters  Infectious or non-infectious
2. What is the single most important strategy in
preventing this patient from getting a hospital-
SEPSIS  SIRS that has a proven or
acquired infection? suspected microbial etiology
A. Foregoing the weaning process and immediately  life-threatening organ dysfunction
extubating the patient caused by a dysregulated host
B. Administration of a prophylactic antibiotic response to infection
C. Advising this patient to wear a mask at all time
 NEW CRITERIA (2016):
D. Placing this patient in reverse isolation
E. Following strict staff hand hygiene practices suspected (or documented)
3. Which is the most appropriate diagnosis of this infection and an acute
patient’s present condition? increase in ≥ 2 sepsis-related
A. Severe sepsis organ failure assessment
B. Septic shock (SOFA) points)
C. SIRS SEPTIC  A subset of sepsis in which
D. Sepsis SHOCK
E. Refractory septic shock underlying circulatory and
4. Goals of initial resuscitation cellular/metabolic
A. CVP maintained at 10-12 cmH2O abnormalities lead to
B. MAP at <65mmHg substantially increased
C. Urine Output of 0.5ml/kg per hour mortality risk
D. LDH < 40
 2016 CRITERIA (currently
5. What should be your next step in management?
A. Start norepinephrine drip used): Suspected (or
B. Change IV antibiotics for broader spectrum documented) infection plus
coverage vasopressor therapy needed to
C. Start dopamine drip maintain mean arterial pressure
D. Administer sodium bicarbonate at ≥65 mmHg and serum lactate
E. Administer hydrocortisone IV >2.0 mmol/L despite adequate
6. Which of the following is the most appropriate
fluid resuscitation
measure to prevent another ventilator-associated
pneumonia in this patient?  PHASES

RAMIREZ & SUELO EDITOR: NICDAO Page 10 of 13

INTERNAL MEDICINE SEPSIS AND SEPTIC SHOCK LECTURE 6.6

o Hypodynamic hospital mortality

vasodilatory phase –  ICU admission
compromised oxygen COMPLICATIONS
delivery to tissues  ↑  Cardiopulmonary
blood lactate, ↓ central  Adrenal insufficiency
venous oxygen  Renal complications
saturation
 Coagulopathy
o Hyperdynamic
 Neurological complications
vasodilatory phase –
 Immunosuppression
after fluid administration
TREATMENT
CLINICAL MANIFESTATIONS
GOAL
 Clinical manifestations are due to the local and 1. Urgent measures to treat infections
systemic host response to invading microbes not 2. Provide Hemodynamic and respiratory support
because of the direct response of the toxins or the 3. Remove source of infection
bacteria Source control specific anatomic diagnosis of
o Fever (may be absent in elderly, infection requiring emergent source
immunocompromised, uremia, alcoholism) control be identified or excluded as
o Hyperventilation – an early sign of the rapidly as possible in patients
septic response
Antibiotics  Administration of IV
o Encephalopathy (decreased
antimicrobials be initiated as
sensorium/cognition)
soon as possible after
o Hypotension and poor perfusion – most
recognition and within 1h for
commonly on the digits
both sepsis and septic
o DIC
shock.
o Skin lesions- Cellulitis, pustules, bullae, or
 Empiric broad-spectrum
hemorrhagic lesions
therapy or combination
o Stress ulceration – for the GI tract
therapy with one or more
o Cholestatic jaundice, acute liver injury,
antimicrobials to cover all
ischemic bowel necrosis – As we said,
likely pathogens.
everything will be given to the skin organs
 Empiric combination
first.
therapy (using at least two
DIAGNOSIS
NO SPECIFIC DIAGNOSTIC TEST FOR SEPSIS! antibiotics of different
antimicrobial classes)
Definitive Identification of the organism from
etiologic blood or local site of infection Initial Resuscitation from sepsis-induced
diagnosis o Blood cultures from 2 resuscitation hypoperfusion, at least 30ml/kg of
different sites (from two intravenous crystalloid fluid be
different venipuncture sites) given within the first 3 hours.
o Negative (blood) cultures in Vasoactive  Norepinephrine as the first-
many cases (prior antibiotic agent choice vasopressor for all
use, slow-growing organism patients with sepsis.
like TB, absence of microbial  Dopamine is suggested as
invasion of bloodstream i.e an alternative vasopressor
UTI/cystitis) to norepinephrine ONLY in
Possible  Procalcitonin (if value is >2) HIGHLY SELECTED
markers  Lactate PATIENTS
SOFA (Sequential Organ Failure Corticosteroid AGAINST using intravenous
Assessment) hydrocortisone to treat septic shock
qSOFA (quick SOFA) - shorter version of the patients IF adequate fluid
sofa resuscitation and vasopressor
therapy are able to restore
1 point for each criteria (Remember: hemodynamic stability. If this is not
“HAT”) achievable, we suggest intravenous
4. Hypotension: Systolic BP ≤ 100 hydrocortisone at a dose of 200 mg
mmHg per day. (Weak recommendation; low
5. Altered mental status: GCS < quality of evidence)
15 Ventilator Indicated for progressive hypoxemia,
6. Tachypnea: RR ≥ 22/min Therapy hypercapnia, neurologic deterioration,
or respiratory muscle failure
qSOFA ≥2 suggests high in-

RAMIREZ & SUELO EDITOR: NICDAO Page 11 of 13

INTERNAL MEDICINE SEPSIS AND SEPTIC SHOCK LECTURE 6.6

APPENDIX

Table 2: Sequential Organ Failure Assessment (SOFA) Points

Table 3&5. Clinical guidelines for the management of patients with sepsis and septic shock (Lifted from HPIM).

RAMIREZ & SUELO EDITOR: NICDAO Page 12 of 13

INTERNAL MEDICINE SEPSIS AND SEPTIC SHOCK LECTURE 6.6

Table 4. Initial Antimicrobial Therapy for Severe Sepsis with No Obvious Source in Adults with Normal Renal Function. For empirical
antibiotic therapy the appropriate choice depends on the suspected site of infection, the location of infection onset (i.e., the community,
a nursing home, or a hospital), the patient’s medical history, and local microbial susceptibility patterns

RAMIREZ & SUELO EDITOR: NICDAO Page 13 of 13