HS2PF3 Sepsis and Shock

Sepsis mortality rate

30%

Severe sepsis mortality rate

39.4%

Canada - sepsis __ leading cause of death

12th

Sepsis associated with 1 out of __ deaths

1/18

Sepsis has high cost due to

greater hospital resources, due to aggressive treatment and 75% longer hospital stays

__% of sepsis pts require ICU stays during their hospital care

45%

4 sepsis mortality related factors:

comorbidities

gender

onset of sepsis

age

Sepsis mortality rates increase with which 3 other physiological derangements

HIV, cancers, diabetes

M or F risk of sepsis-associated death

M = 31.7/100,000

F = 23.8/100,000

Patient whose sepsis occurred after hospital admission (nosocomial infections) had __ odds of dying

56% higher

Ages most susceptible to sepsis-related deaths

neonates <1 or elderly 65+

Better treatment due to earlier diagnoses and use of sepsis bundles resulted in a __ in mortality in Canada in 2017 from 1990

40% decrease

SIRS

Systemic Inflammatory Response Syndrome (SIRS)

SIRS 4 markers

Body temperature >38° C or <36° C

Heart rate >90 beats/minute

Respiratory rate >20/minute (or a PaCO2 0f <32 mm Hg)

White blood cell count >12,000 mm3 or <4,000 mm3, or >10% immature bands

Are the 4 SIRS markers part of sepsis diagnoses?

No

Are SIRS symptoms recognized as important in detecting infections?

Yes

2 scenarios in which SIRS would give us a false answer

1. false positive - pts have SIRS symptoms but no infection

2. false negatives - pts have infection and organ failure (sepsis) but not all SIRS signs

Why is SIRS not considered accurate - 2 reasons

1 did not promote an understanding of the underlying problem or disease process which is dysregulation of the immune system

2 does not reflect the severity of the disease process

Sepsis: Life-threatening __ caused by a __

organ dysfunction; dysregulated host response to infection

2 specific clinical criteria for sepsis

1 Infection - Suspected or confirmed

2 Acute, life-threatening organ dysfunction

Organ dysfunction is described as

an increase in the SOFA of 2 points or more

SOFA

Sequential [Sepsis-related] Organ Failure Assessment (SOFA)

What is the main problem with SOFA use in practice?

requires multiple laboratory tests and may not be available in a timely manner

qSOFA

quick sepsis related organ failure assessment

qSOFA criteria

HAT

Hypotension - Systolic BP ≤ 100mm Hg

Altered mentation - GCS<13

Tachypnea - RR ≥ 22/min

qSOFA should be used

always. routinely at bedside to screen for sepsis. screen every patient; every shift; every day

qSOFA as a single screening tool

It should be a starting point!

qSOFA is no longer recommended to be used as a single screening tool

Only __ infected patients have 2+ qSOFA points, but they account for __ __

Only 1 in 4 infected patients have 2+ qSOFA points, but they account for 3 out of 4 deaths

qSOFA not met but your clinical judgement is concerned about severe infection. What do you do?

TREAT! do not withhold therapy for sepsis just because qSOFA criteria are not met

6 NEWS parameters

Respiration rate

Oxygen saturation

Systolic blood pressure

Pulse rate

Level of consciousness (or new confusion)

Temperature

NEWS score that indicates sepsis

5+

Septic shock: a subset of sepsis in which particularly profound __ are associated with a greater risk of __ than with sepsis alone

Septic shock: a subset of sepsis in which particularly profound circulatory, cellular and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone

Septic shock patients can be identified clinically by (2 things)

Elevated serum lactate levels (> than 2 mmol/L)

Fluid resistant hypotension - need for vasopressor therapy to maintain a minimum mean arterial pressure (MAP) of 65 mm Hg

Why do septic shock pts need to be identified ASAP?

poorer prognosis, increased mortality

SIRS has __ sensitivity but __ specificity

High sensitivity, but very low specificity

Compared to SIRS, qSOFA has __ sensitivity but __ specificity

low sensitivity but more specificity

PCI

Persistent Critical Illness

PCI is increasing due to medical advances because...

Medical advances, such as support for failing organs, have allowed many to survive who would previously have died

Sepsis survivors may develop

PCI + organ dysfunction that continues up to months from the initial presentation of sepsis or septic shock

PCI increases sepsis survivor mortality and premature death by upto

75% within 5 years

Sepsis described as cellular dysfunction

energy deficit due to impaired cellular metabolism results in loss of homeostasis, barrier failure, and organ dysfunction

2 cellular hallmarks of sepsis

Metabolic derangements and mitochondrial dysfunction

Sepsis causes an energy deficit in cells via

mitochondrial dysfunction which = depletion of ATP which = organ dysfunction

Cytotoxic hypoxia means oxygen is...

delivered to the cell, but not used efficiently

Anaerobic metabolism (low O2) is indicated by

Lactate (increased glycolysis but pyruvate and lactate waste products cannot enter citric acid cycle in mitochondria)

Inadequate tissue perfusion leads to which 6 steps

1 anaerobic glycolysis

2 less ATP made = energy deficit

3 Na+/K+ fails = Na+ influx and K+ efflux

4 H2O moves into cells with Na+

5 ongoing anaerobic glycolysis and lactate buildup

6 decreased nutrients to cells = less protein synthesis and lipid deposition

Na+/K+ pump failure leads to what clinical manifestation

Na+ influx and K+ efflux

Electrochemical gradient affected - action potentials in neurons and muscle cells failed (CNS and myocardium affected quickly)

Na+ influx ALSO causes

H2O influx into cell = swelling, membrane disruption + Ca2+ influx

Glycogen in anaerobic glycolysis

decreased, used for metabolic demands

pH in anaerobic glycolysis

decreases as ATP hydrolysis releases protons

proteins in anaerobic glycolysis

used for fuel, less protein synthesis

4 usual homeostasis pathways

1 organs

2 muscles/cells

3 efferent pathways (SNS)

4 neuroendocrine system (cytokines and hormones)

organs send immune signals to brain via

afferent vagus nerve

muscles signal infection to brain via

dorsal root ganglia and spinal cord

SNS increases release of (2)

norepinephrine and cytokines

neuroendocrine system increases (2)

cytokines that infiltrate BBB

hormones affecting immune cells

Septic response is __ -inflammatory

both pro- and anti- inflammatory

Failing innate AND adaptive immune response in sepsis

T-cell exhaustion and immune cell deaths (increased apoptosis)

Why do non-immune cells die in sepsis?

Less energy is available for non-immune cells, as they are simply trying to survive, and hence they lose their specialized organ functions

Failure of epithelial and endothelial barriers in sepsis leads to

increases vascular permeability, which leads to decreased perfusion

2 examples of things seen due to barrier failures in sepsis

1 liver enzymes and renal creatinine will enter blood

2 Cytokines and immune cells will cross the blood brain barrier in sepsis

5 severe sepsis symptoms

Hypotension, hypoxemia, oliguria, metabolic acidosis, thrombocytopenia

Why is term severe sepsis considered redundant?

sepsis is serious enough to warrant "urgent attention"

Overall, how sepsis leads to failed homeostasis?

dysfunctional immune and neurological systems lead to failed homeostasis

Septic shock criteria (3)

1 sepsis

2 Hypotension requiring vasopressors to maintain (MAP) = 65

3. Lactate ≥ to 2 mmol/L

MAP calculation

mean arterial pressure = diastolic BP + 1/3rd pulse pressure

Pulse pressure

difference between systolic and diastolic

With the 3 septic shock criteria, hospital mortality exceeds

40%

Hour-1 Bundle (5 steps)

1. Measure lactate: remeasure if >2

2. Obtain blood culture

3. Administer broad spectrum antibiotics

4. Begin rapid administration of 30 mL/kg crystalloid for hypotension or lactate greater than or equal to 4

5. Apply vasopressors (epinephrine/norepinephrine) if hypotensive during or after fluid resuscitation to maintain MAP greater than or equal to 65.

4 types of shock

cardiogenic, obstructive, hypovolemic, distributive

Cardiogenic shock

REDUCED SV/HR

Cardiogenic shock is __ failure

pump failure; inability of the heart to contract in a coordinated manner

5 causes of cardiogenic shock

MI (heart attack)

Arrhythmias (connections)

Cardiomyopathy (ischemia, late CAD)

Severe valve problems

Problems in ventricular flow / filling

Obstructive shock

IMPAIRED BLOOD FLOW

What is impeded in obstructive shock?

impeded filling and emptying of heart

3 causes of obstructive shock

1 Pulmonary embolism

2 Pericardial effusion (tamponade - filling)

3 Tension pneumothorax (lung collapse, vena cava and right atrium collapse too)

Hypovolemic shock

REDUCED PRELOAD

Hypovolemic shock is mainly a decrease in

total blood volume

3 main causes of hypovolemic shock

bleeding

dehydration

burns

In hypovolemic shock, if blood loss is __ then CO and perfusion are affected. If blood loss is __ then no CO and no MAP at all.

Blood loss >10% = CO and perfusion affected

>35-45% = no CO, no MAP

4 compensatory mechanisms in hypovolemic shock

1 increased HR and cardiac contractility

2 vasoconstriction of nonvital organs (preserve blood)

3 RAAS and ADH act on kidneys to decrease urine output

4 thirst stimulated by hypothalamus

Distributive shock

LOW SYSTEMIC VASCULAR RESISTANCE

Distributive shock is mainly caused by vaso__

Vasodilation, can't maintain BP with normal blood volume

Distributive shock is often due to

increased capillary permeability

In distributive shock there is no loss of fluid, but

redistribution of it that impairs tissue perfusion - rare and generally transitory

3 MAIN types of distributive shock

sepsis

anaphylaxis

neurogenic

Anaphylaxis

Allergic response, varies based on antigen amount and patient sensitivity to said antige

How does an epi-pen help in anaphylactic shock?

Epi-pen (IM or IV) =

1 vascular constriction,

2 reversed airway constriction,

3 decreased mast cell and basophil degranulation,

4 decreased histamine (so less vasodilation)

Neurogenic shock is caused by (3)

1 Acute brain or spinal cord injury

2 depressant drugs, anesthetics

3 insufficient glucose to brain from excess insulin

In neurogenic shock, there is an imbalance between

sympathetic and parasympathetic stimulation = massive vasodilation (SNS suppressed)

3 BIG metabolic consequences of shock

1 anaerobic metabolism

2 energy deficit (low ATP)

3 decreased glucose delivery to cells

Lack of glucose in cells causes (3 things)

1 Lipolysis

Increased free fatty acids in blood (cytotoxic)

2 Glycogenolysis

Limited supply, reduced energy stores

3 Gluconeogenesis

Leads to organ failure, bc uses proteins for it

4 consequences of gluconeogenesis in glucose deficit

1 low serum albumin (Depleted plasma protein levels = movement of more fluid out of the vasculature in response to lower oncotic pressure)

2 Protein used from muscles = wasting of skeletal/cardiac fibers

3 Increases urea, toxic ammonia

4 Alanine converted to pyruvate - which just increases lactate levels more

Shock symptoms may initially masked by

compensatory mechanisms

ALL types of shock feature (3 things)

low BP, low urine production, poor perfusion = acidosis

Step 1 in treating any type of shock

find and eliminate cause of shock

Pancreatitis

inflammation of the pancreas

Pancreatitis time course

acute or chronic

Pancreas as which type of gland

exocrine and endocrine

pancreas as exocrine gland

delivers digestive enzymes produced in the acinar cells into the duodenum