Therapeutics ID Ronald

Flashcard maker : Sonia Kelly
Hypovolemic Shock: Etiology
Reduction in intravascular volume
Hypovolemic Shock: Conditions Causing Intravascular Volume Depletion

  • Hemorrhagic (GI bleed, trauma, surgery, internal bleeding)
  • Non-Hemorrhagic (dehydration, fluid shifting, cutaneous loss)

Hypovolemic Shock: Hemodynamic Parameters

  • Decreased PCWP and Decreased CVP due to decreased venous return (preload)
  • Decreased CO due to decreased venous return (decreased SV)
  • Compensatory increase in SVR to maintain BP, however often inadequate compensation –> hypotension and hypoperfusion prevail


Hypovolemic Shock: Management

  • Fluid resuscitation
  • Correct inadequate tissue perfusion and oxygenation
  • CVP > 12 mmHg, CI > 2.2 L/min
  • Rapid infusion of IV fluids (crystalloids or colloids) is necessary to restore intravascular volume

Cardiogenic Shock: Etiology
Abnormality in cardiac function
Cardiogenic Shock: Conditions That Precipitate Cardiogenic Shock

  • Non-Mechanical (acute MI, acute CHf exacerbation, cardiomyopathy)
  • Mechanical (Mitral or aortic valve insufficiency, severe aortic stenosis, septum or free wall rupture)

Cardiogenic Shock: Hemodynamic Parameters

  • Decrease CO due to pump failure
  • Compensatory increase SVR to maintain BP
  • Increase PCWP or CVP (esp. in CHF) b/c heart cannot pump blood through circulation –> volume overload
  • Overall, decrease in arterial BP and hypoperfusion — can lead to ischemia in various organs

Cardiogenic Shock: Management

  • Selection of agent(s) depends on patient presentation and etiology: Inotropes, diuretics, vasodilators, vasopressors, IV fluids, intra-aortic balloon pump, ventricular assist device
  • CI > 2.5, PCWP < 18, MAP > 65

Distributive (Vasodilatory) Shock: Etiology
Loss of vascular tone leading to hypotension and hypoperfusion
Distributive (Vasodilatory) Shock: Conditions Causing Distributive Shock

  • Septic shock
  • Anaphylaxis
  • Neurogenic causes — spinal injury, cerebral damage, etc.
  • Drug-induced — anesthesia, overdose of opiods, etc.
  • Acute adrenal insufficiency

Definition of Systemic Inflammatory Response Syndromes (SIRS)

Must meet 2 out of the 4 following criteria:

  1. Temp < 36°C or > 38°C
  2. HR > 90 beats/min
  3. RR > 20 RPM or PaCO2 < 32 mmHg
  4. WBC < 4000 or > 12000 or > 12% bands

Definition of Sepsis
SIRS + suspected or documented infection
Definition of Severe Sepsis
Sepsis + organ dysfunction, hypoperfusion, or hypotension
Definition of Septic Shock
Sepsis + persistent hypotension after adequate fluid resuscitation requiring vasopressor therapy
Risk Factors for Severe Sepsis

  • All critically ill patients
  • Severe Community-Acquired Pneumoniae (CAP)
  • Intra-Abdominal Surgery
  • Meningitis
  • Chronic diseases (DM, HF, Chronic HF, COPD)
  • Compromised Immune Status (HIV/AIDS, use of cytotoxic and immunosuppressive agents, malignant neoplasms, alcoholism)
  • Cellulitis
  • UTIs
  • Severe Injuries (bullet wounds, severe burns, etc.)

Patients at Greater Risk for Severe Sepsis

  • Age > 65
  • Underlying comorbidities
  • Pre-existing organ dysfunction
  • Higher body weight
  • Medical Treatment with a medical device

What are the 2 mechanisms (pathophysiology) of sepsis?

1.  Inflammation


  • In response to an infection, ischemia, or injury — inflammatory cytokines are produced by the body
  • Release of cytokines and other mediators lead to:

↑ capillary permeability (↓ intravascular volume) –> vasodilation of blood vessels (hypoperfusion) and ultimately cellular death and multiple organ failure

  • TNF-α is one of the primary mediators of sepsis


2.  Coagulation

  • Activation of coagulation cascade –> pro-coagulation –> microvascular thrombosis
  • Increased Pro-Coagulants:


Plasminogen activator inhibitor

Thrombin activatable fibrinolysis inhibitor

  • Decreased Anticoagulants

Protein C


Antithrombin III

Signs and Symptoms of Early Sepsis

  • Fever/Chills/Myalgias
  • Increased/Decreased WBCs: left shift
  • Hypoxia (PaO2 < 70%)
  • HR > 90
  • Hyperventilation (RR > 20, PaCO2 > 30)
  • Changes in mental status

Signs and Symptoms of Severe Sepsis/Septic Shock

  • Oliguria/Anuria (UO < 0.5 ml/kg/hr)
  • Increased SCr
  • Lactic Acidosis (lactic acid > 1.5 ULN)
  • Hypotension/Myocardial Depression
  • Elevated LFTs
  • Disseminated Intravascular Coagulopathy (decreased platelets/decrease fibrinogen)
  • ARDS (lung injury)

Diagnosis of Sepsis/Septic Shock

1.  Presumed or known site of infection

  • Purulent sputum or respiratory sample
  • Chest radiograph with new infiltrates not explained by a noninfectious process
  • Spillage of bowel contents noted during operation
  • Radiographic or physical examination evidence of an infected collection
  • WBCs in normally sterile fluid
  • Positive blood culture
  • Evidence of infected mechanical hardware by physical or radiographic examination

2.  Evidence of SIRS (2 out of 4 criteria)

3.  Sepsis-Induced Organ failure

  • Cardiovascular dysfunction (MAP < 60 mmHg) – need vasopressors to maintain BP in the face of adequate intravascular volume (CVP > 8-10) or after an adequate fluid challenge has been given
  • Respiratory organ failure – respiratory distress requiring mechanical ventilation
  • Renal dysfunction – UO < 0.5 ml/kg/hr for 1 hr in the face of adequate intravascular volume or after an  adequate fluid challenge
  • Hematologic dysfunction – thrombocytopenia or a 50% drop in platelets in the previous 3 days, INR > 1.2 that cannot be explained by liver dz or warfarin usage
  • Anion-Gap Metabolic Acidosis – pH < 7.30, plasma lactate > 1.5 x the upper limit of normal

Goals of Therapy for Early-Goal Directed Therapy

Should be started in the ER, within the initial 6 hrs, and not delayed until patient reaches ICU

  • CVP 8-12 mmHg (12-15 if pt on ventilator)
  • MAP > 65
  • UO > 0.5 ml/kg/hr
  • Central Venous O2 saturation (SVO2) > 70% or Mixed Venous O2 Saturation (MVO2) > 65%

Choice of Fluids for Early Goal Directed Therapy

1.  Crystalloids

  • Rate of 500-1000 ml q 15-30 min
  • Isotonic sol’n — 0.9% NaCl or LR
  • Recommended initially to expand intravascular volume — cheaper than colloids and more readily available

2.  Colloids

  • Expand intravascular space for longer duration than crystalloids
  • More expensive and more side effects — higher incidence of renal failure when pts put on hetastarch compared to LR
  • May be beneficial in pts w/ low albumin or pts not responding to crystalloids

Vasopressors for Early Goal Directed Therapy

  • First Line Agents: Dopamine or Norepinephrine
  • Vasopressors increase MAP
  • Initiate if hemodynamic instability (MAP < 65 mmHg) persists despite adequate fluid resuscitation (CVP 8-10 mmHg)
  • Refractory hypotension despite high doses of NE — consider adding vasopressin 0.04 units/min


Blood Product Administration for Early Goal Directed Therapy

  • Indicated if SVO2 < 70% and Hct < 30%
  • Transfuse to achieve a Hct of 30%

Inotropic Therapy for Early Goal Directed Therapy

  • First Line Agent: Dobutamine
  • Increases CO
  • Indicated if SVO2 < 70% and Hct > 30%

Antibiotic Therapy: Adminstration time, spectrum coverage

  • Obtain cultures prior to antibiotc therapy
  • Antibiotics should be administered within 1 hr of recognizing the clinical syndrome of sepsis
  • Choice of antibiotics should cover MRSA and P. aeruginosa and other G-, G+, and Anaerobic organisms
  • Empiric double coverage of Pseudomonas from 2 different classes as well as MRSA coverage
  • Choice of antibiotics similar to Late Onset/MDR Pathogen Nosocomial Pneumonia treatment

Recommended Antibiotics for Sepsis/Septic Shock

Antipseudomonal Cephalosporin


Antipseudomonal Carbapenem


β-Lactam/β-Lactamase Inhibitor


Aztreonam (if β-Lactam allergy)




Antipseudomonal Fluoroquinolone













Source/Site of Infection Control

  • All pts presenting with signs and symptoms of sepsis should be evaluated for source/site of infection
  • Unable to identify via physical assessment –> X-Ray/Ultrasound/CT Scan/MRS, etc.
  • Once focal source identified:

Abcess – drainage/debridement

Wound – debridement of necrotic/infected tissue

Medical Device – removal of device if possible

  • Evaluate risk vs benefit of intervention for source removal
  • Inability/failure to remove source of infection prolongs sepsis and leads to poor outcomes


Duration of Antimicrobial Therapy

  • 7-10 days recommended
  • Should be dictated by patient response and site of infection
  • Should treat for recommended duration for specific infection that caused sepsis (ie, endocarditis 4-6 weeks, osteomyelitis 4-6 weeks, etc.)

Reasoning behind corticosteroid use in sepsis/septic shock patients

  • Relative Adrenal Insufficiency commonly occurs in sepsis:

-inflammatory cytokines released in response to infection suppress the cortisol response to Adrenocorticotropic Hormone (ACTH)

-this leads to relative adrenal insufficiency

-ultimately leads to deregulation of inflammatory process and loss of vascular tone –> hypotension

  • Guidelines recommend use in septic shock when hypotension remains poorly responsive to adequate fluid resuscitation AND vasopressors
  • Steroids may be DC’d or weaned once vasopressors are no longer required



What is the recommended corticosteroid therapy in sepsis/septic shock pts?

Hydrocortisone 200-300 mg IV divided 3-4 x daily




Fludrocortisone 50 mcg PO daily


What are the Benefits/Risks of Corticosteroid therapy in pts with sepsis/septic shock?


  • improvement in shock reversal in pts unresponsive to fluid resuscitation and vasopressors


  • immunosuppressive properties — increasing risk of infection
  • increased risk of critical care myopathy (especially when used while pt. on neuromuscular blockers)
  • increased risk of GI bleed
  • hyperglycemia


Drotrecogin Alpha: MOA

  • Recombinant activated protein C (rhAPC)
  • Activated protein C decreased in sepsis leading to inflammation and coagulopathy
  • rhAPC inhibits clotting factors Va and VIIIa –> ↓ thrombin production
  • Also promotes anti-inflammatory (suppresses TNF-α, IL-1, and IL-6) and pro-fibrinolytic response

What pts should receive Drotrecogin Alpha?

  • Adults with Sepsis-Induced Organ Dysfunction or Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS)
  • Clinical assessment of high-risk of death
  • No contraindications
  • Optimal results if started within 24 hrs of sepsis onset

Drotrecogin Alpha: Adverse Effects and Contraindications

Adverse Effect:





  • Platelets < 30,000
  • Hemorrhagic stroke within 3 months
  • Severe head trauma
  • Intracranial or intraspinal surgery within 2 months
  • Need for epidural catheter
  • Any factor that would increase likelihood of life-threatening bleeding


Supportive Therapy: Glucose Control

  • Hyperglycemia associated w/ insulin resistance common in sepsis
  • Prolonged hyperglycemia can lead to:

infectious complications

critical-illness polyneuropathy

multiple organ failure

  • Target blood glucose 140-180 mg/dL
  • ICU insulin protocols should be implemented
  • Sliding-scale insulin protocols and/or continuous IV insulin

Supportive Therapy: Stress Ulcer Prophylaxis

  • All patients with sepsis should receive stress ulcer prophylaxis
  • H2 blocker (famotidine, ranitidine, etc.)
  • Proton Pump Inhibitor (Omeprazole, Esomeprazole, etc.)

Risk Factors for Stress Ulcers:

  1. Mechanical ventilation
  2. Coagulopathy
  3. Acute renal failure
  4. Acute hepatic failure
  5. Major surgery
  6. Severe head trauma
  7. Major burns


Supportive Therapy: DVT Prophylaxis

  • Incidence of DVT ranges from 10-80% in ICU patients
  • All patients without CI should receive DVT prophylaxis with either:

Heparin 5000 units SubQ TID

Enoxaparin 40 mg  SubQ daily

Fondaparinux 2.5 mg SubQ daily

  • Patients with CI UFH/LMWH should receive mechanical prophylaxis (graduated compression stockings or intermittent compression devices)
  • Very high risk pts should receive a combination of pharmacological therapy and mechanical therapy

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