HTHSCI 2PF3B - Inflammation Part II: Sepsis & Shock

How is inflammation related to sepsis and shock?

the process of sepsis, septic shock and other types of non-bacterial shock are due to dysregulation of immune processes; can be caused by an under or overreaction of the immune system

sepsis statistics

• overall mortality of sepsis is 30%, compared to 9.1% for MI and 18% for stroke

• sepsis was the 12th leading cause of death in 2011 in Canada

sepsis costs

• Patients with sepsis usually require greater hospital resources, due to necessarily aggressive treatment and longer hospital stays (3 days vs 12-23 days for sepsis)

• Also, about 45% of sepsis patients require a stay in the ICU during their hospital care

• costs related to sepsis hospitalizations are much higher than other illnesses

factors affecting sepsis mortality

• extremes of age (less than 1 years old, 60 and older)

• co-morbidities

• gender - males have a higher risk

• onset of sepsis - patients whose sepsis occurred after hospital admission had 56% higher odds of dying

• early recognition of sepsis is important

systemic inflammatory response syndrome (SIRS)

• body temperature > 38 C or < 36 C

• heart rate > 90 bpm

• respiratory rate > 20/minute (or PaCO2 of < 32 mmHg)

• white blood cell count > 12000 mm3 or < 4000 mm3 or > 10% bands

Sepsis-3 definition

• While SIRS symptoms are still recognized as important in detecting infections, they are no longer part of the definition of sepsis

• The new definition describes sepsis as a “life- threatening organ dysfunction caused by a dysregulated host response to infection”

• In the new guidelines, organ dysfunction is described as an increase in the Sequential [Sepsis- related] Organ Failure Assessment (SOFA) of 2 points or more

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 criteria

elevated serum lactate levels (> 2 mmol/L), a need for vasopressor therapy to maintain a minimum mean arterial pressure of 65 mmHg (fluid resistant hypotension)

Quick SOFA (qSOFA) tool

can help identify clients with sepsis, if they are experiencing 2 or more of: systolic BP < 100 mmHg, altered mentation, RR > 22/min

sepsis and persistant critical illness (PCI)

those who survive may develop PCI with organ dysfunction that continues up to months after initial presentation of sepsis or septic shock (20-40% mortality rate), results in disability due to cognitive, immune system and muscle dysfunctions and increases risk of sepsis survivor mortality (up to 75% within 5 years)

original central issue of sepsis or septic shock

was thought to be lack of perfusion leading to tissue hypoxia and eventually cell death, however the situation is now thought to be more complicated

mitochondrial dysfunction

metabolic derangements and mitochondrial dysfunction are hallmarks of sepsis and can lead to ATP depletion, mitchondrial dysfunction can then lead to organ dysfunction and greater risk for mortality

hypoxia-induced metabolic changes

• the body is unable to effectively use oxygen

• without oxygen, glycolysis can proceed in the cytoplasm of the cell but its products pyruvate and lactate cannot enter the TCA cycle within the mitochondria → increased lactate levels

• very little ATP molecules are produced creating an energy deficit

• Na+ pump failure

• increased anaerobic glycolysis

• decreased glycogen, pH (protons generated through glycolysis), and protein synthesis

homeostasis and sepsis

sepsis is linked to a failure of homeostasis, altered signaling between organs, muscles & cells, the brain & efferent pathways, and the neuroendocrine system results in failure to restore homeostasis leading to sepsis, septic shock, and PCI

immune cells and sepsis

sepsis is both pro & anti-inflammatory, can increase or decrease apoptosis of immune cells and decrease cytotoxic functions and cytokine secretions; cell death & tissue necrosis is not observed in sepsis however loss of immune cells is

process of sepsis & septic shock

• microorganisms and the products of tissue damage leads to a dysregulated host immune response and the impairment of homeostasis associated with sepsis

• failure of the epithelial and endothelial barriers leads to increased vascular permeability and lack of perfusion, allows cellular substrates such as liver enzymes and renal creatinine to enter the blood. Also allows cytokines, immune mediators, and immune cells to cross blood-brain barrier and create systemic inflammatory response

• this systemic response leads to severe sepsis with organ dysfunction causing hypotension, hypoxemia, oliguria, metabolic acidosis, thrombocytopenia which can lead to septic shock

treatments for sepsis

important to recognize sepsis ASAP, qSOFA tool is used to predict risk for mortality, “Hour-1 Bundle” is the most recent protocol employed

Hour-1 Bundle

measure lactate (remeasure if > 2 mmol/L), obtain blood cultures, then administer broad spectrum antibiotics, then administer fluids (30 mg/kg crystalloids) in the case of hypotension or lactate > 4 mmol/L, if hypotension persists, apply vasopressors to maintain MAP of 65 mmHg

qSOFA variables

respiratory rate, mental status, systolic blood pressure

SOFA variables

PaO2/FiO2 ratio, Glasgow Coma Scale score, mean arterial pressure, administration of vasopressors with type and dose rate of infusion, serum creatinine or urine output, bilirubin, platelet count

consequences of early treatment

Creating a team consisting of a critical care nurse and physician as well as a respiratory therapist to respond quickly to deteriorating patients in regular hospital beds, has resulted in fewer patients going to the ICU with sepsis and fewer Code Blues. This was done at St. Joes which led to a 16% reduction in risk of mortality

mechanisms in sepsis

• Our understanding of sepsis is incomplete and new discoveries are constantly challenging previously- held theories

• It is now known that immunosuppression can occur, along with, or instead of the previously expected overwhelming pro-inflammatory response

• Research is underway to examine individual patterns of gene expression, as this may provide information about prognosis and guide treatment in future

types of shock

cardiogenic, obstructive, hypovolemic, distributive

cardiogenic shock

from reduced stroke volume or HR due to MI, arrhythmias, cardiomyopathy, severe valve problems, problems in ventricular flow/filling

obstructive shock

from impaired blood flow due to pulmonary embolism, pericardial effusion (tamponade), tension pneumothorax (collapsed lung)

hypovolemic shock

from reduced preload due to bleeding out (trauma or ulcer), dehydration (heat shock, diuretics, diarrhea, emesis), burns

distributive shock

from low systemic vascular resistance due to sepsis, anaphylaxis, acute brain or spinal cord injury (nerogenic), venoms, overactive thyroid

recognition of shock

• skin - pale, cool, clammy or warm, flush, dry

• respiratory - rapid breathing, shallow respirations

• metabolism - low temp, thirst, acidosis, low urine output

• neurological - restlessness, anxiety, lethargy, confusion

• cardiovascular - tachycardia, thready pulse, low CO, low BP

treatments for shock

blood volume is increased through administration of colloids and crystalloids, if needed vasoconstrictors are used to increase blood pressure and positive inotropes to increase cardiac contractility

Why is wound infection, viral meningitis, urosepsis, and ankle sprain not an example of SIRS?

they are examples of pathologies induced by infective agents and ankle sprains involve inflammation with no infection but produce a local rather than systemic response

What can cause SIRS?

pancreatitis

pathophysiology of pancreatitis

• acinar cell injury and duct obstruction can lead to edema, impaired blood flow, and ischemia and intra and extracellular activation of enzymes like trypsin and lipase

• increased CRP levels also an indication

• lipase leads to fat necrosis

• trypsin causes cell injury, proteolysis, edema, thrombosis, hemorrhage and necrosis

• this can lead to inflammation, translocation of intestinal bacteria, sepsis, pancreatic abscess, cyst or pseudocyst, shock, SIRS, ARDS, ATN, myocardial depression, coagulation disorders

common causes of pancreatitis

• 75% of pancreatitis cases: gallstones or alcoholism

• Other causes: hypertriglyceridemia, drug induced, ERCP, and abdominal trauma account for another 10%

• About 15% of cases remain idiopathic or of unknown cause

treatments for pancreatitis

• Treatment directed at pain reduction and pancreas rest (no oral food or fluids), also restoration of plasma volume with IV fluids to maintain blood pressure

• Ultrasound or endoscopic retrograde cholangiopancreatogram (ERCP) to detect gallstones; CT scans for fluid accumulation and areas of necrosis

• Cholecystectomy indicated for gallstones, surgery to remove necrosis

• Critically ill patients on TPN, removal of lipids if pancreas aggravated

summary of sepsis & shock

• No good blood markers (tests) for sepsis

• Signs & Symptoms are easy to miss; changes in BP may come later

• Early recognition and intervention with the sepsis bundle protocol helps reduce ICU admissions and Code Blue(s)

• For sepsis / shock it’s important to treat the underlying cause

• Pancreatitis causes SIRS & can quickly progress to shock

• Sepsis & Shock can quickly lead to multiple organ dysfunction syndrome (MODS)