Septic Shock

Summary

This ICU curriculum session focuses on defining sepsis and septic shock, outlining their clinical manifestations, and detailing treatment protocols. It emphasizes the importance of early recognition and management, including prompt administration of broad-spectrum antibiotics, fluid resuscitation with lactated ringers, and vasopressors like norepinephrine and vasopressin. The session also discusses the role of corticosteroids in refractory septic shock and the significance of source control. A case study illustrates the application of these principles in managing a patient with suspected pyelonephritis.

Takeaways

• 📚 The session focuses on defining sepsis and septic shock according to the Sepsis-3 definitions.
• 🩺 Septic shock is a subset of sepsis characterized by underlying circulatory and cellular metabolic abnormalities that significantly increase mortality.
• 🌡 Clinically, septic shock is identified by sepsis plus hypotension that does not improve despite fluid resuscitation, and a serum lactate level >2 mmol/L.
• 🚨 Sepsis is a time-sensitive medical emergency requiring prompt recognition and management to improve patient outcomes.
• 💊 Early administration of broad-spectrum antibiotics is crucial in the treatment of septic shock, with each hour's delay increasing the risk of in-hospital mortality.
• 💧 The initial fluid resuscitation for sepsis or septic shock involves a 30 mL/kg bolus of intravenous fluid, typically lactated Ringer's solution.
• 💊 Vasopressors are used to maintain a mean arterial pressure (MAP) ≥65 mmHg, with norepinephrine being the first-line agent.
• 🔍 Source control, including broad cultures and imaging, is essential in managing septic shock to identify and treat the infection site.
• 🩹 Corticosteroids, such as hydrocortisone, are considered for patients with vasopressor-refractory septic shock to improve vasopressor responsiveness.
• 📈 The session emphasizes the importance of continuous assessment and monitoring of patients in septic shock, including mental status, perfusion, urine output, and lab trends.

Q & A

What are the objectives of the fifth session in the ICU curriculum?

The objectives are to define sepsis and septic shock according to Sepsis-3 definitions, describe the pathophysiologic abnormalities and clinical manifestations of septic shock, and to describe the treatment principles for a patient in septic shock including appropriate antibiotics, fluid resuscitation, and vasopressors.

How is sepsis defined according to the Sepsis-3 task force definition from 2016?

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.

What are the clinical criteria used to identify sepsis before the Sepsis-3 definition?

Before the Sepsis-3 definition, sepsis was identified using the SIRS criteria, which include temperature greater than 38 or less than 36 degrees Celsius, heart rate greater than 90 beats per minute, respiratory rate greater than 20 breaths per minute, and white blood cell count greater than 12,000 or less than 4,000 or greater than 10 percent bands.

What is the qSOFA score and how is it used?

qSOFA stands for quick Sequential Organ Failure Assessment and is used to identify patients with suspected infection likely to have sepsis or patients with sepsis at high risk of deterioration or poor outcome. It is composed of three variables: systolic hypotension less than 100 mmHg, respiratory rate greater than 22 breaths per minute, and altered mental status.

What is the clinical definition of septic shock according to the Sepsis-3 guidelines?

Septic shock is defined as sepsis with persistent hypotension requiring vasopressors to maintain a mean arterial pressure (MAP) of at least 65 mmHg and a serum lactate greater than 2 mmol/L despite adequate fluid resuscitation.

What types of infections are most commonly associated with sepsis?

Sepsis is most commonly caused by infections of the respiratory system, followed by infections of the gastrointestinal and genitourinary systems.

What are the clinical manifestations of septic shock?

Clinical manifestations of septic shock include hypotension, tachycardia, altered mental status, and signs of poor perfusion such as mottling or oliguria.

What are the four main principles in the management of septic shock?

The four main principles in the management of septic shock are early antibiotics, fluid resuscitation, vasopressors, and source control.

What is the recommended initial fluid resuscitation for patients with sepsis or septic shock?

Patients with sepsis or septic shock should receive a bolus of 30 mL/kg of intravenous fluid for initial volume resuscitation.

Which vasopressor is typically used first in the treatment of septic shock, and why?

Norepinephrine is typically used first in the treatment of septic shock because it is a predominant alpha-1 agonist with some additional beta agonist effects, and it has been shown to be effective in maintaining blood pressure without increasing the risk of arrhythmias compared to other vasopressors like dopamine.

What is the role of corticosteroids in the treatment of septic shock?

Corticosteroids are typically reserved for patients in vasopressor-refractory septic shock. They may improve vasopressor responsiveness and have been associated with faster resolution of shock, more ventilator-free days, and decreased ICU length of stay.

Outlines

00:00

🚑 Introduction to Sepsis and Septic Shock

This paragraph introduces the fifth session of the ICU curriculum, focusing on sepsis and septic shock. The session aims to define sepsis and septic shock according to the Sepsis-3 definitions, describe the physiological abnormalities and clinical manifestations, and outline the treatment principles. A case study of a 65-year-old woman with diabetes and symptoms of sepsis is presented. The patient exhibits signs of septic shock, including fever, hypotension, and tachycardia. The importance of recognizing and promptly managing sepsis and septic shock is emphasized due to their time-sensitive nature.

05:02

🔬 Understanding Sepsis and Septic Shock

The paragraph delves into the clinical definitions of sepsis and septic shock. Sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to infection. Septic shock is a subset of sepsis characterized by underlying circulatory and cellular metabolic abnormalities that significantly increase mortality. The clinical manifestations of septic shock include hypotension, elevated lactate levels, and altered mental status. The paragraph also discusses the evolution of sepsis definitions and the use of the qSOFA score to identify patients at risk of deterioration.

10:03

🩺 Pathophysiology and Treatment of Septic Shock

This section discusses the pathophysiology of septic shock, highlighting the immune response to infection and the cascade of inflammatory reactions that can lead to organ dysfunction and death. The paragraph outlines the clinical manifestations of septic shock, including effects on the brain, respiratory system, cardiovascular system, and other organs. The treatment principles for septic shock are also detailed, emphasizing the importance of early and appropriate antibiotics, fluid resuscitation, vasopressors, and source control. The use of lactated ringers and the choice of vasopressors are specifically addressed.

15:04

💊 Management Strategies for Septic Shock

The final paragraph summarizes the management strategies for septic shock, including the administration of broad-spectrum antibiotics, fluid resuscitation with lactated ringers, and the use of vasopressors. It also touches on the role of corticosteroids in treating vasopressor-refractory septic shock and the importance of source control. The paragraph concludes by reiterating the critical nature of early intervention and the need for continuous assessment and monitoring of patients with septic shock.

Keywords

💡Sepsis

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. It is a critical condition that can rapidly progress to septic shock if not treated promptly. In the script, sepsis is discussed as a time-sensitive medical emergency, emphasizing the importance of early recognition and intervention.

💡Septic Shock

Septic shock is a subset of sepsis characterized by underlying circulatory and cellular metabolic abnormalities that are profound enough to substantially increase mortality. It is clinically defined as sepsis with persistent hypotension despite adequate fluid resuscitation and a serum lactate greater than two. The script describes it as a medical emergency requiring immediate treatment to prevent high hospital mortality.

💡SIRS Criteria

Systemic Inflammatory Response Syndrome (SIRS) criteria are used to identify signs of infection in the body, including temperature greater than 38 or less than 36 degrees Celsius, heart rate greater than 90 beats per minute, respiratory rate greater than 20 breaths per minute, and white blood cell count abnormalities. The script mentions that SIRS criteria are not specific enough for recognizing sepsis, as many common medical problems can cause similar abnormalities.

💡qSOFA

The quick Sequential Organ Failure Assessment (qSOFA) is a bedside tool used to identify patients with suspected infection who are likely to have sepsis or are at high risk of deterioration. It includes variables such as systolic hypotension, respiratory rate, and altered mental status. The script uses qSOFA to illustrate how to identify the sickest patients with sepsis.

💡Lactate

Lactate levels are used as a marker for tissue hypoperfusion and are indicative of poor prognosis in sepsis and septic shock. A serum lactate greater than two, despite adequate fluid resuscitation, is part of the clinical definition of septic shock. The script emphasizes the importance of lactate levels in assessing the severity of sepsis.

💡Fluid Resuscitation

Fluid resuscitation is the administration of intravenous fluids to restore and maintain blood volume and pressure in patients with sepsis or septic shock. The script specifies that patients should receive a bolus of 30 cc's per kilogram of intravenous fluid for initial volume resuscitation, highlighting the importance of this intervention in managing sepsis.

💡Vasopressors

Vasopressors are medications used to raise blood pressure by constricting blood vessels. In the context of septic shock, they are used to maintain a mean arterial pressure greater than or equal to 65 mmHg. The script discusses norepinephrine and vasopressin as primary vasopressors used in the treatment of septic shock.

💡Broad-Spectrum Antibiotics

Broad-spectrum antibiotics are designed to target a wide range of bacteria, making them suitable for initial treatment of sepsis before the specific causative organism is identified. The script emphasizes the importance of early administration of broad-spectrum antibiotics to improve outcomes in septic shock.

💡Source Control

Source control refers to the identification and management of the infection site causing sepsis. This may involve obtaining broad cultures and imaging to guide targeted interventions. The script mentions that while antibiotics, fluids, and vasopressors are infusing, it's important to go looking for the source of infection.

💡Corticosteroids

Corticosteroids are sometimes used in the treatment of septic shock, particularly in patients with vasopressor-refractory shock. They may improve vasopressor responsiveness and have been associated with faster resolution of shock. The script discusses the mixed mortality outcomes from studies evaluating corticosteroids in septic shock and their role as a salvage therapy.

💡Cardiac Output

Cardiac output is the volume of blood pumped by the heart per minute, and it is a key factor in maintaining mean arterial pressure. In septic shock, there is often a decrease in systemic vascular resistance, which can affect cardiac output. The script uses the equation 'mean arterial pressure equals cardiac output times systemic vascular resistance' to explain the physiology of shock.

Highlights

Definition of septic shock according to Sepsis-3 guidelines.

Clinical manifestations and treatment principles for septic shock.

The importance of early recognition and management of sepsis and septic shock.

The evolution of sepsis definitions and the current Sepsis-3 criteria.

The clinical signs of sepsis using the SOFA score for severity assessment.

The distinction between sepsis and septic shock in terms of circulatory and cellular metabolism abnormalities.

The pathophysiology of septic shock, including the role of nitric oxide and mitochondrial dysfunction.

The types of infections that commonly cause sepsis and their clinical presentations.

The end-organ effects of septic shock, including encephalopathy, ARDS, and cardiovascular dysfunction.

The four main principles in the management of septic shock: early antibiotics, fluid resuscitation, vasopressors, and source control.

The significance of early and appropriate antibiotic therapy in septic shock.

The role of fluid resuscitation with lactated ringers in the initial management of septic shock.

The choice of vasopressors in septic shock, with a focus on norepinephrine and vasopressin.

The use of corticosteroids in vasopressor-refractory septic shock and their impact on outcomes.

The importance of source control in the management of septic shock.

The continuous assessment and monitoring of patients in septic shock, including vasopressor requirements and lab trends.

A checklist of high-yield management principles for septic shock.

Transcripts

welcome to the fifth session in the ICU

curriculum in this session will cover

septic shock our objectives for the

session include to define sepsis and

septic shock

according to sepsis three definitions

describe the path of physiologic

abnormalities and clinical

manifestations of septic shock and to

describe the treatment principles for a

patient in septic shock including

appropriate antibiotics fluid

resuscitation and vasopressors as a

reminder in our prior session on shock

we introduced the shock and awe physical

exam based approach for going through

the shock differential at the bedside

for an undifferentiated patient in

today's session we will be talking about

the first part of this approach let's

start with a case

the patient is a 65 year old woman with

diabetes presenting with a three day

history of dysuria and right flank pain

this morning she became lightheaded

dizzy and developed shaking chills in

the ER she has febrile to 39.5

hypotensive to 70 over 40 and

tachycardic to 140 on exam she is pale

lethargic and has super pubic and

right-sided CVA tenderness after

approximately two liters of IV fluid her

blood pressure remains 75 over 40 labs

return and she is a white blood cell

count of 17 creatinine of 2.5 and

lactate of 6 she is admitted to the ICU

for further management

it appears the patient is septic likely

from pyelonephritis and perhaps

gram-negative bacteria given her ragas

but is she in septic shock and if so how

are we going to treat her when she

arrives to the ICU sepsis is a

time-sensitive medical emergency in the

same way that stem ease and CBA's are

emergencies therefore it is important

that every doctor be able to recognize

sepsis and septic shock and initiate

evaluation and management promptly in

order to recognize sepsis and septic

shock we first need to be able to define

both terms clinically

to define septic shock you first need to

be able to recognize and define sepsis

the definition for sepsis has evolved

over the years we are currently using

the sepsis 3 task force definition from

2016 which defines sepsis as

life-threatening organ dysfunction

caused by a dysregulated host response

to infection what a sepsis look like

clinically from 1991 to 2016 sepsis was

defined as two out of four service

criteria plus a suspected site of

infection as a review the service

criteria include temperature greater

than 38 or less than 36 degrees Celsius

heart rate greater than 90 beats per

minute

respiratory rate greater than 20 breaths

per minute and white blood cell count

greater than 12,000 or less than 4000 or

greater than 10 percent bands the

problem with serves is that it is not

specific enough for recognizing sepsis

as a number of common inpatient medical

problems can cause at least two of the

after mentioned abnormalities what else

can we use then to identify the sickest

patients with sepsis the answer q sofa Q

sofa stands for quick sequential organ

failure assessment it was created to

identify patients with suspected

infection likely to have sepsis or

patients with sepsis at high risk of

deterioration or poor outcome outside of

the ICU for example patients on the

floor or in the emergency room Q sofa is

composed of three variables systolic

hypotension less than 100 millimeters of

mercury respiratory rate greater than 22

breaths per minute an altered mental

status as discussed in previous sessions

to Kipp Nia and respiratory alkalosis

are often the body's compensatory

response to the worsening metabolic

acidosis in sepsis or septic shock one

point is given for each variable present

scores greater than or equal to two or

predictive of worsened outcomes and

increased in hospital mortality so in a

patient with either unknown or suspected

infection two out of three Q sofa

variables should prompt consideration of

sepsis and/or escalation of care to the

ICU note the term severe sepsis has

largely fallen out of favor

moving on to septic shock sepsis three

define septic shock as a subset of

sepsis and which underlying circulatory

and cellular metabolism abnormalities

are profound enough to substantially

increase mortality

clinically septic shock is defined as

sepsis plus phase oppressors needed to

maintain a map greater than or equal to

65 and a serum lactate greater than two

despite adequate fluid resuscitation

here defined as 30 CC's per kilogram of

body weight basically septic shock is

sepsis plus hypotension after

appropriate fluid resuscitation know

from the sepsis three guidelines meeting

all of these criteria is associated with

greater than 40 percent hospital

mortality so we have defined sepsis and

septic shock next let's describe the

pathophysiologic abnormalities and

clinical manifestations of septic shock

at its most basic sepsis represents the

body's immune response to infection an

infection triggers a cascade of

inflammatory and immune responses that

can potentially lead to multi organ

dysfunction and death what types of

infections cause sepsis prior to the

1980s gram-negative infections

predominated in a gram-negative

infection lipopolysaccharide or LPS of

the bacterial cell wall triggers the

inflammatory response since the 1980s

gram-positive infections have been the

most common cause of sepsis

gram-positive infections namely staph

aureus and strep pyogenes trigger

inflammation via exotoxin sepsis is most

commonly caused by infections of the

respiratory system and then by

infections of the GI and GU systems next

what are the clinical manifestations of

septic shock as discussed in the shock

session the equation mean arterial

pressure equals cardiac output times

systemic vascular resistance defines

much of the physiology encountered

within the ICU in shock the mean

arterial pressure decreases therefore

there are two ways to achieve a low mean

arterial pressure either a decrease in

the cardiac output or systemic vascular

resistance septic shock Falls him to the

broad category of distributive shock and

is characterized by a decrease in the

systemic vascular resistance and often a

compensatory increase in the cardiac

output why does the decrease in SVR

occur the answer excessive an

uncontrolled release of nitric oxide via

an inducible nitric oxide synthase

excess nitric oxide caused a systemic

baser dilation and decreases vascular

tone for this reason patients with

septic shock rough and warm and flushed

there is also a mitochondrial damage

which impairs cellular oxygen

utilization the peripheral tissues and

vital organs what are the end organ

effects of pathologic vasodilation and

cellular hypoxia on the screen is a

figure used in the shock session we will

again use this figure to discuss

clinical effects and end organ

dysfunction and septic shock in a

head-to-toe fashion in the brain septic

shock causes encephalopathy and delirium

in part due to decreased cerebral

perfusion referring back to earlier in

the session

remember that altered Mental Status is

also one of the cue sofa criteria from a

respiratory standpoint septic shock can

cause the acute respiratory distress

syndrome or a RDS a RTS is one of the

most important and organ effects of

septic shock and is associated with the

significant amount of

immortality of present pictured in this

x-ray are the characteristic bilateral

alveolar infiltrates of a RDS within the

cardiovascular system septic shock can

cause ventricular dysfunction there are

multiple GI FX of septic shock

including bowel ischemia due to

hypoperfusion ileus shock liver and

cholestasis in a calculous cholecystitis

approximately 50% of patients with

septic shock will develop acute kidney

injury secondary to acute tubular

necrosis or a TN patients may also

develop relative adrenal insufficiency

disseminated intravascular coagulation

and thrombocytopenia at this point we've

discussed definitions of sepsis and

septic shock

clinical manifestations and end organ

damage the CEM result next how do we

treat septic shock in order to minimize

the chance of all these horrible things

happening we stated at the beginning of

the session that septic shock is a

medical emergency requiring immediate

treatment there are four main principles

in the management of septic shock early

antibiotics fluid resuscitation

vasopressors and source control let's go

through each of these principles one by

one first antibiotics the life-saving

intervention in sepsis and septic shock

from a study in 2014 for every one hour

delay in antibiotics and septic shock

there is a three to seven percent

increase in the odds of in hospital

death what is an appropriate initial

antibiotic regimen the initial regimen

should include broad gram-negative

coverage plus Pseudomonas as well as

methicillin-resistant Staph aureus or

Mrs a coverage for gram-negative

coverage possible options include

piperacillin Tazo back dam cefepime plus

metronidazole and meropenem

metronidazole is included with cefepime

for improved anaerobic coverage for mrs

a coverage possible options include

vancomycin and lynnae's illud

antibiotics need time to work therefore

we need to support the patient's blood

pressure and profuse the vital organs

while the antibiotics kick in we

accomplish this with fluid resuscitation

and vasopressors first fluid

resuscitation

patients with sepsis or septic shock

should receive a bolus of 30 CC's per

kilogram of intravenous fluid for

initial volume resuscitation nope fluid

resuscitation and sepsis and septic

shock is currently under further

investigation with numerous ongoing RCTs

at this time guidelines continue to

recommend an initial 30 CC per kilogram

bolus within the first three hours and

management this guideline is from the

surviving sepsis campaign report of 2016

and is a strong recommendation with low

quality evidence so we've decided to

give our patient 30 CC's per kilogram of

IV fluid should the patient receive

crystalloid meaning lactated ringers and

normal saline or colloid meaning albumin

or starches

the answer crystal a Cochrane review

from 2018 found no difference in

outcomes including mortality and need

for renal replacement therapy between

crystalloid and colloid with

crystalloids being cheaper and more

readily available so we decided to give

our patient of 30 cc per kilogram bolus

of crystalloid for our crystalloid

should we choose lactated ringers or

normal saline the answer lactated

ringers the smart med trial from

Vanderbilt in 2018 enrolled more than

15,000 patients and compared LR to NS

for initial volume resuscitation and

critically ill adults admitted to the

ICU the study found the LR reduced death

from any cause need for new renal

replacement therapy or persistent renal

dysfunction

therefore LR should be the choice in

almost all situations for initial volume

resuscitation in critically ill adults

finally it is important to keep in mind

that each patient is different and some

patients may require additional fluid

after the initial 30 CC per kilogram

bolus fluid administration at that time

should be based upon objective measures

of fluid responsiveness including

passive straight leg raise bedside

ultrasound etc so we've administered

broad-spectrum antibiotics and the

patient has received their initial 30 cc

per kilogram bolus of lactated ringers

however as in our example from the

beginning of the session the patient

remains hypotensive with an elevated

lactate what do we do next the answer ad

vasopressors our goal with Basel

pressors is to maintain a mean arterial

pressure greater than or equal 65

millimeters of mercury in order to

maintain perfusion of the vital organs

the main bays opressors available in the

ICU are norepinephrine epinephrine

phenol Efren and vasopressin of these

which phase opressor do we reach for

first typically our first phase

oppressor is norepinephrine

norepinephrine is a predominant alpha-1

agonist with some additional beta

agonist why norepinephrine soap 2 was a

large RCT in 2010 that compared

norepinephrine to dopamine for treatment

of septic shock the study found no

difference in 28-day mortality but an

increased risk of arrhythmias with

dopamine compared to norepinephrine

therefore norepinephrine became the

first pressure of choice so we add

norepinephrine

but unfortunately the patient's mean

arterial pressure remains less than 65

on increasing doses of norepinephrine

what pressor do we typically add next

the answer

vasopressin vasopressin unsurprisingly

acts on the vasopressin receptors

vasopressin has given it a fixed dose of

point zero 3 or point zero four units

per minute because dose is greater than

point zero 4 it increased the risk of

coronary and mesenteric ischemia

why add vasopressin to norepinephrine

the vast trial in 2008 compared adding

additional norepinephrine to vasopressin

for patients with septic shock who were

already receiving norepinephrine well

the study found no mortality benefit

from vasopressin vasopressin use did

allow for decreased dosages of

norepinephrine therefore for patients

with norepinephrine refractory shock

vasopressin is an appropriate second

agent to add

unfortunately after adding vasopressin

the patient remains hypotensive with the

map less than 65 while trying to figure

out why the patient is deteriorating we

can add fennel Efren and or epinephrine

for blood pressure support fennel Efrain

is a pure alpha one agonist it is

typically the third vasopressor added

after norepinephrine and vasopressin

but can also be used as a primary base

oppressor for patients that develop

tachyarrhythmias like a fib with rbr or

SVT from the beta agonizing HEPA nephron

works via the alpha 1 and beta receptors

no it has more beta agonizing than

norepinephrine it is typically the third

or fourth phase of pressure added if

needed take a second again to review the

receptors on which the various phase

oppressors act

as antibiotics fluids and BAE's

oppressors are infusing it's important

to go looking for the source of

infection with broad cultures and

imaging if possible

what about corticosteroids for example

hydrocortisone in the treatment of

septic shock corticosteroids are

typically reserved for patients in

vasopressor refractory shock vasopressor

refractory shock is typically defined as

shock requiring both norepinephrine and

vasopressin to maintain a map greater

than 65 if a patient is requiring both

norepinephrine and vasopressin we can

add on hydrocortisone

at a dose of either 50 milligrams every

six hours or 100 milligrams every eight

hours as discussed earlier patients in

septic shock may have relative adrenal

insufficiency and corticosteroids may

improve vasopressor responsiveness there

have been numerous landmark studies over

the last two decades evaluating the role

of corticosteroids in septic shock to

name a few there has been the French

trial otherwise known as the anon trial

in 2002 cortico sand 2008 and adrenal

and approaches in 2018 these studies

have demonstrated mixed mortality

outcomes the French trial and approaches

both demonstrated mortality benefit from

corticosteroids while QWERTY kisum

adrenal do not demonstrate a mortality

benefit however all of these landmark

studies demonstrate that corticosteroids

are associated with faster resolution of

shock more ventilator free days and

decreased ICU length of stay all of

which are objectively good things but

what about corticosteroids for patients

with sepsis without shock the high press

trial in 2016 found no role for

hydrocortisone and patients with sepsis

without shock

in summary corticosteroids represent an

evidence-based Salvage therapy for

patients with vasopressor refractory

septic shock we discussed the importance

of early antibiotics IV fluid

resuscitation phase opressors

corticosteroids and source control you

know these interventions are working by

continuously assessing the patient's

exam including mentation perfusion

status urine output etc their

vasopressin requirements and by trending

labs every four to six hours

on this page is a checklist highlighting

the high yield management principles

just discussed

in summary in this session we define

sepsis and septic shock

according to sepsis three definitions we

describe the pathophysiologic

abnormalities and clinical

manifestations of septic shock and

finally describe the treatment

principles for a patient in septic shock

including early broad-spectrum

antibiotics fluid resuscitation with

lactated ringers and bayes oppressors

thank you for your participation