Sepsis&

Septic Shock

Presented by:

Mohamed Adam Mohamed

Master of Clinical Pharmacy

University of Khartoum

Learning objectives:

Introduction

Definition of sepsis& septic shock

Classification of shock

Pathophysiology of Sepsis

Major Signs & Symptoms associated with Sepsis

Intervention & Management

Introduction

• Sepsis is the best known yet most poorly understood medical disorders. Sepsis leads to shock, multiple organ failure and death if not recognized early and treated promptly.

• The most common sites of infection are the lungs (40%), abdomen (30%) and urinary tract (10%) .

• Gram-positive and poly microbial infection accounted for 30%-50% and 25% of cases respectively.

Definition of Sepsis:

According to National Institute of Health define as an illness in which the body has a severe response to microbial infection.

Sepsis is a life-threatening organ

dysfunction that results from the

body’s response to infection

Organ dysfunction:

is defined as an acute change in total Sequential Organ Failure Assessment (SOFA) score of 2 points or greater secondary to the infection cause.

qSOFA : allowing for quick bedside analysis of organ dysfunction in patients with suspected or documented infection.

The qSOFA score includes:

a respiratory rate of 22 breaths/minute or more

systolic blood pressure of 100 mm Hg or less

altered level of consciousness. (Glasgow Coma Scale score < 15)

Septicemia:

Is a state of microbial invasion from a portal of entry into the blood stream which causes sign of illness.

Note:

Not all patients with bacteremia have signs of sepsis.

Therefore, that sepsis and septicemia are not in fact identical.

Definition Septic shock:

Septic shock is defined by persisting hypotension requiring vasopressors to maintain a mean arterial pressure of 65 mm Hg or higher and a serum lactate level greater than 2 mmol/L (18 mg/dL) despite adequate volume resuscitation.

Classification of shock

• Shock can be subdivided into 3 distinct classes on the basis of underlying mechanism and characteristic hemodynamics, as follows:

Hypovolemic shock

Distributive shock

Cardiogenic shock

Hypovolemic Shock

Hemorrhagic

- Gastrointestinal bleeding

- Trauma

- Internal bleeding:ruptured aortic aneurysm, retroperitoneal bleeding

Non- hemorrhagic

- Dehydration: vomiting, diarrhea, diabetes mellitus, diabetes insipidus, overuse of diuretics

- Sequestration: ascites, third-space accumulation

- Cutaneous: burns, nonreplaced perspiration and insensible water

Cardiogenic Shock: Nonmechanical causes:

Acute myocardial infarction

Low cardiac output syndrome

Right ventricular infarction End-stage cardiomyopathy

Mechanical causes

Rupture of septum or free wall

Mitral or aortic insufficiency

Papillary muscle rupture or dysfunction Critical aortic stenosis

Pericardial tamponade

Distributive Shock: - Septic shock

- Anaphylaxis

Neurogenic

- Spinal injury, cerebral damage, severe dysautonomia

Drug-induced

- Anesthesia, ganglionic and adrenergic blockers, overdoses of barbiturates and narcotics Acute adrenal insufficiency

Pathogenesis of septic shock:

The majority of bacteremia do not develop to sepsis.

Bacteria usually are cleared from the bloodstream.

Humoral immunity and oxygen released from erythrocytes are the main bactericidal factors in the bloodstream.

Sepsis begins when bacteria are resistant to oxidation and start to proliferate in erythrocytes.

Hormonal dysregulation cause multiple organs’ failure.

Pathogenesis of septic shock conti.

Abundant release of oxygen from erythrocyte to the plasma triggers a cascade of events that cause:

1. oxygen delivery failure to cells and hypoxia

2. oxidation of plasma components and impairment of hormonal regulatory mechanisms.

3. Hypoxia and hormonal dysregulation cause multiple organs’ failure.

Sepsis develops when the chemicals of the immune system releases into the bloodstream to fight an infection cause inflammation throughout the entire body instead. Severe cases of sepsis can lead to septic shock, which is a medical emergency.

Shock is take place when volume replacement fails to increase blood pressure to acceptable levels (Hypotension) lead to inadequate perfusion of major organ systems, with progressive failure of organ system functions.

Signs and symptoms:

The clinical syndrome of sepsis is the result of excessive activation of host defense mechanisms rather than the direct effect of microorganisms.

Sepsis and its sequelae represent a continuum of clinical and pathophysiologic severity.

Signs and symptoms:• Signs and symptoms of sepsis are often nonspecific and

include the following:

Fever (usually >101°F [38°C]), chills, or rigors

Confusion

Anxiety

Difficulty breathing

Fatigue, malaise

Nausea and vomiting

decreased urine output

cyanosis (bluish discoloration of the lips

It is important to identify the potential source of infection:

Head and neck infections

– Severe headache

– neck stiffness

– altered mental status

– earache

– sore throat

– sinus pain/tenderness

– cervical/submandibular lymphadenopathy

Chest and pulmonary infections:

– Cough (especially if productive)

– pleuritic chest pain

– dyspnea

– dullness on percussion

– bronchial breath sounds

– any evidence of consolidation

Cardiac infections

– Any new murmur, especially in patients with a history of injection or IV drug use

Abdominal and gastrointestinal (GI) infections:

– Diarrhea

– abdominal pain

– abdominal distention

– guarding or rebound tenderness

– rectal tenderness or swelling

Pelvic and genitourinary (GU) infections:

– Pelvic or flank pain

– adnexal tenderness or masses

– vaginal or urethral discharge

– dysuria

Bone and soft-tissue infections:

– Localized limb pain or tenderness

– focal erythema

–edema

– swollen joint

– crepitus in necrotizing infections

– joint effusions

Skin infections:

– Petechiae – purpura – erythema – ulceration – bullous formation, – fluctuance

Laboratory tests:

The following are investigative studies to detect a clinically suspected infection, the presence of a clinically and complications of sepsis and septic shock:

Complete blood count

Coagulation studies

prothrombin time [PT]

activated partial thromboplastin time [aPTT], fibrinogen levels

Blood chemistry

Sodium, Chloride, Magnesium, Calcium, Phosphate, Glucose, Lactate)

Renal and hepatic function tests:

Creatinine, blood urea nitrogen, bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, albumin, lipase

Blood cultures (To identify the likely pathogen)

Urinalysis and urine cultures

Gram stain and culture of secretions and tissue

Imaging studies

Chest, abdominal, or extremity radiography

Abdominal ultrasonography

Computed tomography of the abdomen or head

Lumbar puncture

A lumbar puncture/spinal fluid test is indicated in the following circumstances:

Clinical evidence or suspicion of meningitis

Clinical evidence or suspicion of encephalitis

Management:

Patients with sepsis and septic shock require admission to the hospital.

Initial treatment includes support of respiratory and circulatory function

Supplemental oxygen

Mechanical ventilation

Volume infusion. (resuscitation)

Start adequate antibiotics (proper spectrum and dose) as early as possible (Empiric Treatment)

Goals of treatment:

1. Resuscitate the patient to correct hypoxia, hypotension, and impaired tissue oxygenation (hypo- perfusion)

2. Identify and eradicate source of infection

3. Maintain adequate organ system function, guided by cardiovascular monitoring

Management principles for septic shock include the following:

Early recognition

Early and adequate antibiotic therapy

Source control

Early hemodynamic resuscitation and continued support

Pharmacotherapy:

Alpha-/beta-adrenergic agonists:

(epinephrine,norepinephrine,dopamine,dobutamine,

vasopressin, phenylephrine)

Isotonic crystalloids:

– Normal saline

– Ringer lactate

Pharmacotherapy:Volume expanders

– albumin

Antibiotics: ( cefotaxime, ticarcillin clavulanate, piperacillin-tazobactam, imipenem-cilastatin, meropenem, clindamycin, metronidazole, ceftriaxone, ciprofloxacin, cefepime, levofloxacin, vancomycin)

Corticosteroids:

– Hydrocortisone

– dexamethasone

•http://pathways.nice.org.uk/pathways/sepsis

:Surgery

Patients with focal infections should be sent for definitive surgical treatment after initial resuscitation and administration of antibiotics.

These patient refer to surgeon because may be not respond to standard treatment for septic shock until the source of infection is surgically removed

eg, intra-abdominal sepsis [perforation, abscesses], empyema, mediastinitis, cholangitis, pancreatic abscesses, pyelonephritis or renal abscess from ureteric obstruction