DISCUSS THE MANAGEMENT OF SEPTIC SHOCK

DR SK OBIANO JNR

OUTLINE
Definition of shock Epidemiology Classes of Shock Definition of Septic shock Pathophysiology of septic shock Management of septic shock Current trends Controversies

shock
Clinical manifestations of cellular dysfunction due to inadequate tissue perfusion resulting in cellular hypoxia as a result of decreased circulatory blood volume. Tissue requirement- 3mls/kg/min 70kg Delivery- 1000mls/min

Epidemiology

Types of shock
Hypovolemic shock Cardiogenic shock Distributive shock Obstructive shock

Septic shock
State of acute circulatory failure characterised by persistent arterial hypotension despite adequate fluid rescusitation Or Tissue hypoperfusion unexplained by other causes.

Definitions
Infection A microbial phenomenon characterized by an inflammatory response to the presence of microorganisms or the invasion of normally sterile host tissue by those organisms. Bacteremia The presence of viable bacteria in the blood. SIRS systemic level of acute inflammation, that may or may not be due to infection, and is generally manifested as a combination of vital sign abnormalities including fever or hypothermia, tachycardia, and tachypnea. Severe SIRS SIRS in which at least 1 major organ system has failed

Sepsis SIRS which is secondary to infection. Severe sepsis Severe SIRS which is secondary to infection. Shock It is a serious, life threatening medical condition characterized by a decrease in tissue perfusion to a point that is inadequate to meet cellular metabolic needs. Septic shock sepsis induced hypotension despite adequate fluid resuscitation along with perfusion abnormalities manifested by a lactate greater than 4 mg/dL .

Multiple Organ Dysfunction Syndrome (MODS) The presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention.

Criteria for SIRS

Requires 2 of the following 4 features to be present:
o Temp >38 or <36.0 C o Tachypnea RR>20 o Tachycardia (HR>90, in the absence of intrinsic heart disease) o WBC > 12,000/mm3 or <4,000/mm3 or >10% band forms on differential

Criteria for Severe SIRS

Must meet criteria for SIRS, plus 1 of the following:
Altered mental status SBP<90mmHg or fall of >40mmHg from baseline Impaired gas exchange (PaO2/FiO2 ratio<200-250) Metabolic acidosis (pH<7.30 & lactate > 1.5 x upper limit of normal) o Oliguria (<0.5mL/kg/hr) or renal failure o Hyperbilirubinemia o Coagulopathy o o o o
o platelets < 80,000-100,000/mm3, o INR >2.0, PTT >1.5 x control, o elevated fibrin degredation products

Pathophysiology(septic shock)
Imbalance in oxygen supply and demand Conversion from aerobic to anaerobic metabolism Appropriate and inappropriate metabolic and physiologic responses

Pathophysiology cont
Complex interaction between pathogen and host immune systems Localised sepsis- normal response Response is systemic in septic shock

 Proinflammatory response to infection

Mediators
TNF Alpha, IL-1, IL-6 Complement system (C5 alpha) Bacterial factors
Endotoxin, bacterial cell wall products, bacterial toxins

Immunosuppressive

Infection

Vasodilation

Inflammatory Mediators

Endothelial Dysfunction

Hypotension

Microvascular Plugging

Vasoconstriction

Edema

Maldistribution of Microvascular Blood Flow

Ischemia

Cell Death

Organ Dysfunction

Risk Factors for SIRS/Sepsis

1. Extremes of age 2. Indwelling lines/catheters 3. Immunocompromised states 4. Malnutrition 5. Alcoholism 6. Malignancy 7. Diabetes 8. Cirrhosis 9. Male sex 10.Genetic predisposition?

Management

The initial treatment of sepsis and septic shock involves the administration of supplemental oxygen and volume infusion with isotonic crystalloids

Management of Sepsis-PRINCIPLES
Resuscitate: ABCs Restore tissue perfusion Identify and eradicate source of infection Assure adequate tissue oxygenation Activated Protein C Steroids Glucose Control Nutrition

Clinical Manifestations
Recognition of Septic Shock:
Inflammatory triad Fever Tachycardia

flushed skin

Hypoperfusion
Altered sensorium Urine output Wide pulse pressure.......bounding pulses

Warm shock

Clinical Manifestations
Hypotension
Cold and clammy skin Mottling Tachycardia Cyanosis Narrow pulse pressure Hypoxemia Acidosis.

Cold shock

 Localizing symptoms that are most useful clues to the etiology sepsis:
Head and neck infections - Severe headache, neck stiffness, altered mental status, earache, sore throat, sinus pain or tenderness, cervical or submandibular lymphadenopathy Chest and pulmonary infections - Cough (especially if productive), pleuritic chest pain, dyspnea Abdominal and GI infections - Abdominal pain, nausea, vomiting, diarrhea Pelvic and genitourinary infections - Pelvic or flank pain, vaginal or urethral discharge, dysuria, frequency, urgency Bone and soft-tissue infections - Focal pain or tenderness, focal erythema, edema, fluctuance

Work-up
Laboratory studies
o o o o CBC Comprehensive chemistry panel Coagulation studies Blood & urine cultures

Imaging studies
o Chest radiography o Abdominal radiography o Others according to the suspected cause.

Laboratory studies
CBC:
o The WBC count and differential. o Hemoglobin concentration dictates oxygen-carrying capacity in blood.
o The goal is to maintain hematocrit >30% and hemoglobin >10 g/dL.

o Platelets are an acute-phase reactant and are typically elevated in the setting of inflammation. However, platelet counts may decrease in the setting of DIC.

Comprehensive chemistry panel

Sodium and chloride levels are abnormal in severe dehydration. Decreased bicarbonate can point to acute acidosis. Increased BUN and creatinine levels can point to severe dehydration or renal failure. Glucose control is important in the management of sepsis, with hyperglycemia associated with higher mortality.

LFTs and bilirubin, alkaline phosphatase, and lipase levels are important in evaluating multiorgan dysfunction or a potential source (eg, biliary disease, pancreatitis, hepatitis).

Serum lactate
It is the best serum marker for tissue perfusion. There is also evidence that lactate can be elevated in sepsis in the absence of tissue hypoxia due to mitochondrial dysfunction and down-regulation of pyruvate dehydrogenase, which is the first step in oxidative phosphorylation. Lactate levels >2.5 mmol/L are associated with an increase in mortality. It has been hypothesized that lactate clearance is a measure of tissue reperfusion and an indication of adequate therapy.

Coagulation studies (PT/aPTT)

o o PT and activated aPTT are elevated in DIC. Fibrinogen levels are decreased and FDP are increased in the setting of DIC.

Blood cultures
o Blood cultures should be obtained in patients who have suspected sepsis in order to isolate a specific organism and tailor antibiotic therapy. Positive in < 50% of cases of sepsis. A set of cultures from an indwelling intravenous catheter is especially important, as these catheters are a frequent source of bacteremia.

o o

Urinalysis and urine culture

o o Urinary tract infection is a common source of sepsis, especially in elderly patients. Febrile adults without localizing symptoms or signs have a rate of occult urinary tract infection of 10-15%.

Gram stain and culture, when applicable

o o o Sputum specimen should be obtained if pneumonia is suspected. Any abscess should be drained promptly, and purulent material sent to the microbiology laboratory for analysis. CSF specimen should be obtained if meningitis is suspected.

Imaging studies
CXR routine in the workup of fever with an unclear etiology. o Infiltrates are detected with a chest radiograph in about 5% of febrile adults without localizing signs of infection.

Abdominal plain films should be obtained if clinical evidence of bowel obstruction or perforation exists. Abdominal ultrasonography is indicated when evidence of acute cholecystitis or ascending cholangitis exists

Rescusitation
Patients with septic shock should be treated in an ICU Airway: AMS, unable to protect airway Breathing: Respiratory failure Circulation: Restoration of blood pressure to levels which perfuse core organs

Restoration of tissue perfusion

Causes of poor tissue perfusion
Leaky vessels Decreased vascular tone Myocardial depression

Interventions
Volume infusion
Intravenous fluids PRBCs

Vasopressors Inotropes

Intravenous Fluids
Practice parameters for hemodynamic support of sepsis in adult patient in sepsis . Task Force of the ACCCM/SCCM. Critical Care Medicine 1999

Administered in well-defined, rapidly infused boluses Continued until blood pressure, tissue perfusion, and oxygen delivery acceptable or presence of pulmonary edema Colloid vs. Crystalloid: No evidence to recommend one over the other.

Patients with suspected septic shock require an initial crystalloid fluid challenge of 20-30 mL/kg (1-2 L) over a period of 30-60 minutes with additional fluid challenges at rates of up to 1 L over 30 minutes.

Crystalloid administration is titrated to a CVP goal between 8 and 12 mm Hg or signs of volume overload (dyspnea, pulmonary rales, or pulmonary edema on the chest radiograph).
A fluid challenge refers to the rapid administration of volume over a particular time period followed by an assessment of the response. Patients with septic shock often require a total 4-6 L or more of crystalloid resuscitation.

It is also important to monitor urine output (UOP) as a measure of dehydration. UOP <30-50 mL/h should prompt further fluid resuscitation

Vasopressor agents
Vasopressor administration is required for persistent hypotension once adequate intravascular volume expansion has been achieved. Persistent hypotension is typically defined as systolic blood pressure (SPB) <90 mm Hg or mean arterial pressure (MAP) <65 mm Hg with altered tissue perfusion. The goal of vasopressor therapy is to reverse pathologic vasodilation and altered blood flow distribution. The recommended first-line agent for septic shock is either norepinephrine or dopamine

 Norepinephrine:
Has predominant alpha-receptor agonist effects results in potent peripheral arterial vasoconstriction without significantly increasing heart rate or cardiac output. So it is preferred in warm septic shock where peripheral vasodilatation exists in association with normal or increased cardiac output. Dose: 5-20 mcg/min

Dopamine:
has a much greater effect on beta-receptors increasing mean arterial pressure primarily through increasing myocardial contractility, stroke volume, and heart rate. At high doses it has some alpha-receptor effect and so causing peripheral vasoconstriction. It is more useful in the setting of cold shock, where peripheral vasoconstriction exists and cardiac output is too low to maintain tissue perfusion. Doses range from 2-20 mcg/kg/min.

 Antibiotics should be administered within the first hour of recognition of septic shock, and delays in antibiotic administration have been associated with increased mortality. Antibiotic choice must be broad spectrum, covering gram-positive, gram-negative, and anaerobic bacteria when the source is unknown.

One regimen for septic shock of unknown cause is o gentamicin or tobramycin 5.1 mg/kg IV once/day o 3rd generation cephalosporin cefotaxime 2 g q 6 to 8 h or ceftriaxone 2 g once/day o or if pseudomonas is suspected ceftazidime 2 g IV q 8 h
Vancomycin must be added if resistant staphylococci or enterococci are suspected. If there is an abdominal source, a drug effective against anaerobes should be included metronidazole Antibiotics are continued for at least 5 days after shock resolves and evidence of infection subsides Abscesses must be drained and necrotic tissues (eg, infarcted bowel, gangrenous gallbladder, abscessed uterus) surgically excised. The patient's condition will continue to deteriorate despite antibiotic therapy unless septic foci are eliminated.

 The patient's condition will continue to deteriorate despite antibiotic therapy unless septic foci are eliminated. 4 Ds

Steroid therapy
It has theoretical benefits in the setting of severe sepsis by inhibiting the massive inflammatory cascade.

Recent guidline is that steroids should be administered only in patients with septic shock whose hypotension is poorly responsive to fluid resuscitation and vasopressor therapy.

Activated protein C
Recombinant drug with fibrinolytic and anti-inflammatory activity, seems beneficial for severe sepsis and septic shock if begun early; benefit has been shown only in patients with significant risk of death. Dose: 24 mcg/kg/h by continuous IV infusion for 96 h. Bleeding is the most common complication; Contraindications include: hemorrhagic stroke within 3 mo, spinal or intracranial surgery within 2 mo, acute trauma with a risk of bleeding intracranial neoplasm.

Blood sugar
Normalization of blood glucose improves outcome in critically ill patients, even those not known to be diabetic. A continuous IV insulin infusion (crystalline zinc 1 to 4 U/h) is titrated to maintain glucose between 80 to 110 mg/dL . This approach necessitates frequent (eg, q 1 to 4 h) glucose measurement.