ICU Presentations Vanessa Ohleyer, PGY2 Severe Sepsis ICU Presentations Vanessa Ohleyer, PGY2

Definitions Sepsis Severe Sepsis Septic Shock

SIRS Temperature Heart Rate Tachypnea WBC Abnormalities <96F (36C) Heart Rate >90-100 Tachypnea RR >20 WBC Abnormalities >10,000 <4,000 Tachypnea and tachycardia are the most sensitive clinical indicators of impending sepsis syndrome

Sepsis Severe Sepsis Septic Shock Suspected or proven infection >/=2/4 SIRS Criteria Evidence of Systemic infection Sepsis + Evidence of Organ Dysfunction(s) Severe Sepsis + Decreased perfusion refractory to fluids AMS (GCS dec by >2pts) Hypotension PaO2:FiO2 <300 Metabolic/Lactic Acidosis Oliguria/Renal failure Hyperbilirubinemia Coagulopathy Sepsis mortality = 25-30% Septic Shock mortality = 40-70%

Infection SIRS Sepsis Severe Sepsis Severe SIRS MC organisms Nationally responsible for sepsis are MRSA and VRE Lung is the most common site of infection (25-50%) Intraabdominal (25%) UTI (10%) Severe SIRS

Pathophysiology MICROORGANISM HOST High burden of infection IMMUNE: innate/ adaptive Superantigens INFLAMMATORY Resistance: to opsonization/phagocytosis and antibiotics COAGULATION Progression fro infection to sepsis depends on microbiological factors and inadequate/ unregulated immune response.

Multiorgan Dysfunction Trigger Innate immune and inflammatory reaction Amplification of adaptive immunity Disturbance of pro-anti coagulant balance Immune suppression and apoptosis Multiorgan Dysfunction

Triggers Protein/lipid/carbohydrate from microbe Activated host compliment Clotting cascade component Dead host tissue Ex: endodoxin (lipopolysaccharide of GNB), TSSST-1 of Staph aureus, BGS Toxin Does NOT require organisms be present in bloodstream and toxins present transiently can cause sepsis (Ex: abscess/gut translocation) Therefore, Blood cultures often negative

Innate Immune Reaction Rapid response with pattern recognition Ex: TLR2peptidoglycan of GP bacteria Ex: TLR4 lipopolysaccharide of GN bacteria Triggers intracellular signaling to increase transcription of proinflammatory molecules TNFa, IL1b, IL10 Promotes upregulation of adhesion molecules in neutrophils and endothelials cells KILLS MICROORGANISMS INCREASES VASCULAR PERMEABILITY RELEASES NITRIC OXIDE

Adaptive-Inflammatory Response B -cells release Ig which bind microorganism then delivered by Ag presenting cells to NK cells and neutrophils TH1: secrete proinflammatory cytokines TNFa and IL-1B TH2: anti-inflammatory: IL4, IL10

Specific Organ Failures

Pulmonary Failure is RARELY absent Increased work of breathing AND increased minute ventilation requirement Usually a combination of hypoxic and hypercapnic respiratory failure Mechanical Ventilation Average 7-10d for survivors ½ develop ARDS (usually within the first 48H) <5% require chronic ventilation Severe injury reverses in 30d may take 1 yr for complete recovery 75% of severe sepsis requires mechanical ventilation

Sepsis Induced Hypotension Circulatory Sepsis Induced Hypotension MAP<60 SBP <90 Drop in BP >40

Circulatory Decreased Intravascular Volume Decreased intake Increased losses Increased insensible losses Increased Vascular Permeability NO

Circulatory Failure present at presentation in ½ Usually lasts 2-3 d Usual vol deficit = 4-6L at presentation Average requirement over 24H = >10L Usually lasts 2-3 d Pts requiring >15 DA or >7 NE  mortality of 60% (compared to 40% at lower doses) May cause ventricle dilation and decreased contractility  decreased CO (therefore may be confused w cardiogenic shock) SVR is increased in cardiogenic shock, decreased in Septic Shock

Renal Oliguria dn modest RF (Cr 2-3) common in shock, but frank renal failure is rare 10-15% require renal replacement Elderly pt w DM is at greatest risk Prompt restoration of volume and avoidance of nephrotoxic drugs are essential to prevention

Metabolic Acidosis Lactic Acidosis: decreased DO2 2/2 decreased PO2, anemia, decreased CO and cellular malfunction at level of O2 utilization by mitochondria Lactic Acidosis can occur in ANBSENCE of hypotension Resuscitation plays a much bigger role in reversal than high oxygen levels Survival correlates best with lactate levels and NOT with pH

Coagulation Multifactorial Expression of tissue factor on endothelial cells Leukocytes and cytokine generation Nearly 100% have some derangement in clotting factors Full DIC present in only 10-20% Carries a 50% mortality

CNS AMS is usually a later manifestation Even minor depression in mental status is a poor prognostic indicator Long term cognitive consequence is common among survivors Memory, concentration and executive functioning difficulty

GI Ileus due to diversion of perfusion to heart and brain GI bleeding No evidence to support delay in feeding GI bleeding Since EGDT, incidence has significantly decreased Hepatocellular toxicity shock liver elev transaminases and bilirubin, while Alk phos tends to remain NL

Treatment of Severe Sepsis

Hemodynamic Variables Arterial Hypotension: SBP < 90, MAP <70, SBP Decrease by >40, SBP >2 SD less than mean for age Tissue Hypoperfusion Hyperlactatemia (>1) Decreased capillary refill/mottling

General Variables Fever (>38.3C) Hypothermia (core T <36C) HR >90 or >2SD above normal value for age Tachypnea AMS Significant edema or positive fluid balance (>20mL/kg over 24H) Hyperglycemia (>140) in the absence of diabetes Inflammatory Variables Leukocytosis (>12) Leukopenia (<4) Normal WBC w >10% immature forms Plasma CRP >2SD above normal Plasma procalcitonin more than 2SD >mean

Hemodynamic Variables Arterial Hypotension: SBP < 90, MAP <70, SBP Decrease by >40, SBP >2 SD less than mean for age General Variables Fever (>38.3C) Hypothermia (core T <36C) HR >90 or >2SD above normal value for age Tachypnea AMS Significant edema or positive fluid balance (>20mL/kg over 24H) Hyperglycemia (>140) in the absence of diabetes Tissue Hypoperfusion Hyperlactatemia (>1) Decreased capillary refill/mottling Organ dysfunction variables Arterial hypoxemia (Pa/FiO2<300) Acute oliguria (UO<0.5ml/kg/hr for 2 hrs dispite fuids) Cr increase >0.5gm/dl Coagulation abnormalities (INR >1.5 or PTT >60) Ileus (absent bowel signs) Thrombocytopenia (PLT<100) Hyperbilirubinemia (tBili >4) Inflammatory Variables Leukocytosis (>12) Leukopenia (<4) Normal WBC w >10% immature forms Plasma CRP >2SD above normal Plasma procalcitonin more than 2SD >mean

Hemodynamic Variables Arterial Hypotension: SBP < 90, MAP <70, SBP Decrease by >40, SBP >2 SD less than mean for age General Variables Fever (>38.3C) Hypothermia (core T <36C) HR >90 or >2SD above normal value for age Tachypnea AMS Significant edema or positive fluid balance (>20mL/kg over 24H) Hyperglycemia (>140) in the absence of diabetes Tissue Hypoperfusion Hyperlactatemia (>1) Decreased capillary refill/mottling Organ dysfunction variables Arterial hypoxemia (Pa/FiO2<300) Acute oliguria (UO<0.5ml/kg/hr for 2 hrs dispite fuids) Cr increase >0.5gm/dl Coagulation abnormalities (INR >1.5 or PTT >60) Ileus (absent bowel signs) Thrombocytopenia (PLT<100) Hyperbilirubinemia (tBili >4) Inflammatory Variables Leukocytosis (>12) Leukopenia (<4) Normal WBC w >10% immature forms Plasma CRP >2SD above normal Plasma procalcitonin more than 2SD >mean Yellow = new criteria for “systemic inflammatory signs Red = not just sepsis, but severe sepsis

DVT Stress Ulcer Initial Resuscitation Early Goal Directed Therapy Emergent Initial Resuscitation Early Goal Directed Therapy Primary Treatment Infection Control Cardiovascular support Control of Inflammation Supportive Respiratory Sedation Blood products Renal Nutrition Prophylaxis DVT Stress Ulcer

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Initial Resuscitation Within first 6 Hours CVP 8-12 MAP >/=65 UO >/= 0.5 mL/kg/hr SCVO2 >70% SVO2 >65% Normal Lactate

Initial Resuscitation Despite “adequate” fluid resuscitation SCVO2 <70% SVO2 < 65% Transfuse if Hct <30% Begin Dobutamine

Early Goal Directed Therapy

Initial Resuscitation Early Goal Directed Therapy Emergent Initial Resuscitation Early Goal Directed Therapy Primary Treatment Infection Control Cardiovascular support Control of Inflammation

Antimicrobial Therapy Administration of effective intravenous antimicrobials within the first hour of recognition Severe infections with RF and Shock: combination therapy w ext spectrum Beta-lactam and either aminoglycoside or fluoroquinolone Streptococcus pneumonia: beta-lactam and macrolide Emperic Coverage 3-5 days until sourced, total typically 7-10 Cover neutropenic pts for MDR pathogens such as Acinetobacter and Pseuromonas Cultures as clinically appropriate before antimicrobials if does not delay administration by more than 45min Assess for de-escalation daily Do not use low procalcitonin as a marker for discontinuation

Source Control Goal for ID and control of source is 12Hours If peripancreatic necrosis is id’d as source: definitive intervention is best delayed until adequate demarcation of viable and nonviable tissues has occurred Percutaneous rather than surgical drainage of abscesses if possible If vascular access device suspected, should be promptly removed after alternate access est.

Infection Prevention Chlorexidine gluconate for oropharyngeal decontamination to reduce risk of VAP

Hemodynamic Support Fluids Vasopressors Inotropic therapy Crystalloids as initial choice in resuscitation Minimum challenge of 30mL/kg Do not use hydroxyethyl starches Albumin may be used in pts who required large volumes of crystalloid Vasopressors Inotropic therapy Corticosteroids

Hemodynamic Support Fluids Vasopressors Inotropic therapy #1 Norepinephrine #2Epinephrine (MAP 65) 0.03 units/min Vasopressin with NE to reach MAP or to down titrate NE (do not use alone, and increase dose ONLY as salvage therapy) DA as alternate to NE if bradycardic or LOW risk of tachyarrhythmia Do not use Phenylepherine unless: NE causes serious arrhythmia, high CO with low BP, or as salvage A line as soon as reasonable. Inotropic therapy Corticosteroids

Hemodynamic Support Fluids Fluid Challenge Vasopressors Inotropic therapy Trial of Dobutamine up to 20mcg/kg/min in presence of myocardial dysfunction or ongoing signs of hypoperfusion despite adequate volume and MAP Corticosteroids

Hemodynamic Support Fluids Fluid Challenge Vasopressors Inotropic therapy Corticosteroids Only use if goals cannot be met with fluids and vasopressors Hydrocortisone IV 200mg/day as a continuous gtt; taper when vasopressors are no longer required Do not to ACTH stim test

1H 3H 6H 12H Administer 30mL/kg crystalloid Draw lactate Draw Blood Cultures Empiric Antibiotics 3H Administer 30mL/kg crystalloid 6H Apply vasopressors CVP and SCVO2 Remeasure Lactate 12H Source Control

Initial Resuscitation Early Goal Directed Therapy Emergent Initial Resuscitation Early Goal Directed Therapy Primary Treatment Infection Control Cardiovascular support Control of Inflammation Supportive Respiratory Sedation Blood products Renal Nutrition

Respiratory Support Target TV of 6mL/kg PBW for sepsis induced ARDS Upper limit goal for plateau pressure in a passively inflated lung <30 PEEP to avoid alveolar collapse Moderate or severe ARDS higher PEEP strategies Recruitment maneuvers for refractory hypoxemia Prone positioning for P:F <100, where avail Head of bed at 30-45deg NIV for ARDS if benefits>risks Weaning protocol with daily SBT Do not use PA catheter in ARDS Conservative fluid strategy for ARDS Do not use Beta 2 agonist unless bronchospasm present

Sedation Minimal continuous/intermittent sedation with specific titration endpoints NMBA avoided in pts w/o ARDS, when used continuous infusion with train of four monitoring Sort course NMBA (<48H) in pts w early sepsis induced ARDS and P:F <150

Blood Products Anemia common PRBCs when Hbg <7 to target 7-9 TNFa and IL1 b decrease expression of erythropoietin gene and protein PRBCs when Hbg <7 to target 7-9 In absence of MI, severe hypoxemia, acute hemorrhage, ir ischemic heart disease AFTER tissue hypoperfusion has resolved Do not use erythropoietin for anemia Do not use FFP to correct coagulopathy Do not use antithrombin PLT <10 in absence of bleeding <20 if significant bleeding risk <50 if active bleeding, surgery, or invasive procedures

Glucose Hyperglycemia and insulin resistance are virtually universal Acts as a procoagulant, induces apoptosis ,impairs wound healing and is associated with increased risk of death Protocolized approach to BG when 2 consecutive levels are >180 (target <180, not <110) Monitor glucose Q 1-2 h until stable then Q4H POC may not be accurate

Renal Function CRRT and intermittent hemodialysis are equivalent in pts w severe sepsis and acute renal failure Use CRRT if pt is hemodynamically unstable Do not use bicarb for the purpose of improving hemodynamics or reducing vasopressor requirement in pt w hypoperfusion-induced lactic academia with pH>7.15

Nutrition Oral / enteral feedings within the first 48H rather than fasting/dextrose Avoid mandatory full caloric feeding (500/day) and advance as tolerated Use IV glucose and enteral nutrition over TPN Use nutrition with no specific immunomodulating supplementation

Goals of Care Discuss goals and prognosis with family Incorporate goals into treatment utilizing palliative care where appropriate Address goals as early as possible, but no later than 72H.

Control of Inflammation Do NOT use recombinant Activated Protein C Do NOT use Immunoglobulins Do NOT use Selenium Do NOT use antithrombin

DVT Stress Ulcer Initial Resuscitation Early Goal Directed Therapy Emergent Initial Resuscitation Early Goal Directed Therapy Primary Treatment Infection Control Cardiovascular support Control of Inflammation Supportive Respiratory Sedation Blood products Renal Nutrition Prophylaxis DVT Stress Ulcer

Protocols “Hospital-based performance improvement efforts in severe sepsis” “That a weaning protocol be in place and that MV patients with severe sepsis undergo SBT regularly to evaluate the ability to discontinue…” “A protocolized approach to blood glucose managementin ICU patients with severe sepsis”

1H 3H 6H 12H Administer 30mL/kg crystalloid Draw lactate Draw Blood Cultures Empiric Antibiotics 3H Administer 30mL/kg crystalloid 6H Apply vasopressors CVP and SCVO2 Remeasure Lactate 12H Source Control