10. • Life threatening organ dysfunction.
• Caused by a dysregulated host response to infection.
• Body’s response to an infection injures its own tissues and organs.
• Septic shock: subset of sepsis
• Underlying circulatory and cellular/metabolic abnormalities are
profound enough to substantially increase mortality
Sepsis-3. Singer. JAMA 2016.
16. Case Presentation
• 20 yo m s/p hardware removal
• PMHx: Cerebral palsy, Seizures
• 5 days post-op presented from home to hospital
• T 39.5-40 C, BP 100/51, HR 130, RR 22, Pox 91% on room air
• Slightly confused
• UO: not voided since last night (>15 hours)
• Access: none
• Meds: oral pain meds and chronic antiepileptics
39. Appropriate Antibiotics
Initiation of Inappropriate Antimicrobial therapy results in a fivefold reduction of survival in Human Septic Shock.
Kumar. Chest 2009
69. Initial resuscitation
• Resuscitate IMMEDIATELY –Medical EMERGENCY
• 30 ml/kg IV crystalloid fluid in 3 hours
• Additional fluids guided by reassessment of hemodynamic status
• Dynamic (PPV, lactate clearance) over physical exam (capillary refill)
and static variables used to predict fluid responsiveness
• Target MAP> 65 mm Hg
• Guide resuscitation to normalize lactate (marker of tissue
hypoperfusion)
• ICU admission in 6 hours
Surviving Sepsis Campaign. CCM 2021
70. Fluid Therapy
• Fluid challenge technique – continued as long as hemodynamic factors
continue to improve
• Balanced Crystalloids – 1st choice
• Add Albumin - when substantial amounts of crystalloids are required
• HES starches & gelatins- NOT recommended
Surviving Sepsis Campaign. CCM 2021
71. Diagnosis
• Obtain microbiological cultures (inc blood cultures)
• 2 sets of blood cultures –aerobic and anaerobic
• Obtained BEFORE Abx given –IF NO DELAY in the start of Abx
Surviving Sepsis Campaign. CCM 2021
72. Antibiotics
• Intravenous antibiotics
• Within 1 hour
• Source control (d/c IV access devices)
• Empiric Abx depending on likely pathogens
• MRSA
• Low risk MDR: 1x Gram -ve agents
• High risk MDR: 2x Gram -ve agents
• Fungi: antifungal
Balci. Critical Care 2003
Surviving Sepsis Campaign. CCM 2021
73. • PK/PD dosing
• Continuous b-lactam dosing
• Daily reassessment of de-escalation
• d/c Abx if Procalcitonin <0.15 ng/mL
• very high NPV to r/o sepsis
Grupper. Clin Microbio. 2016
Surviving Sepsis Campaign. CCM 2021
74. Vasoactive medications
• Norepinephrine- 1st choice
• Then add vasopressin
• Then add epinephrine
• Dopamine (instead of NE) -only if bradycardia and low
risk of tachyarrythmias
• AGAINST low dose dopamine
• Dobutamine - in patients with cardiac dysfunction and
persistent hypoperfusion despite fluids & vasopressors
• Dosing titrated to an end point reflecting perfusion
Parillo. N Engl J Med. 2008
Surviving Sepsis Campaign. CCM 2021
75. Corticosteroids
• AGAINST iv hydrocortisone - if fluid resuscitation & vasopressors able
to restore hemodynamic stability
• If not achievable, then iv hydrocortisone 200mg per day
Surviving Sepsis Campaign. CCM 2021
76. Blood products
• RESTRICTIVE TRANSFUSION THERAPY
• RBC transfusion if Hb<7g/dL (in the absence of MI, severe hypoxemia, acute
hemorrhage)
• AGAINST erythropoietin for Rx of anemia ass with sepsis
• AGAINST FFP to correct clotting abnormalities (in the absence of bleeding,
invasive procedures)
• Prophylactic PLT transfusion
• <10,000/mm3 in the absence of bleeding
• <20,000/mm3 if significant risk of bleeding
• >50,000/mm3 for active bleeding, surgery, invasive procedures
Surviving Sepsis Campaign. CCM 2021
77. Mechanical Ventilation (Sepsis induced ARDS)
• High Flow Nasal Oxygen
• Target tidal volume 6 mL/kg predicted body weight
• Plateau pressures <30 cm H2O
• High PEEP
• Recruitment maneuvers with incremental PEEP titration
• Prone positioning- if PaO2/FiO2 ratio <150
• AGAINST HFOV
Surviving Sepsis Campaign. CCM 2021
78. • Use neuromuscular blocking drugs <48 hours
• Conservative fluid management if no evidence of tissue hypoperfusion
• Head of bed elevated 30-450 degrees
• limit aspiration risk and prevent VAP
• Minimize sedation
• Use weaning protocols
• Spontaneous breathing trials (SBT) in patients ready to wean
Surviving Sepsis Campaign. CCM 2021
79. Glucose control
• Protocolized approach
• Goal Gluc <180 mg/dL
• If Gluc >180mg/dL at 2 consecutive measurements- start IV insulin
• Use arterial, instead of capillary point of care testing
Surviving Sepsis Campaign. CCM 2021
81. Stress ulcer prophylaxis
• PPI or H2 blockers used
• ONLY to patients with risk factors for GI bleeding
• MV >48 hrs AND coagulopathy
• risk of pneumonia & C.Diff
Surviving Sepsis Campaign. CCM 2021
82. • Antithrombin
• IV immunoglobulins
• Vitamin C
• Na Bicarbonate (unless pH < 7.2 & AKIN score 2-3)
• routine PAC
• b-2 agonists (if no bronchospasm)
• arrhythmia
• tachycardia
• ventilator free days
• survival to hospital discharge
LOVIT. Lamontagne.NEJM. 2022
Surviving Sepsis Campaign. CCM 2021
83. Nutrition
• Early (within 72 hrs) enteral nutrition
• If not feasible: initiate iv glucose +/- early trophic/hypocaloric feeding
& advance as tolerated
• Avoid early TPN or in combination with enteral feeds if patient can be
fed enterally
• Post-pyloric feeding in patients at risk of aspiration
Surviving Sepsis Campaign. CCM 2021
84. Renal Replacement Therapy (RRT)
• RRT - used with definite indications for dialysis
• not for oliguria, or increase Cr
• Continuous or intermittent RRT
• Continuous - facilitate fluid balance in HD unstable patients
Surviving Sepsis Campaign. CCM 2021
85. Televoting 2
• Our previous septic patient comes to the OR for wound debridement
and washout. What would be among our first priorities during the
case?
• 1. Place a central line
• 2. Transfuse for a Hb <8 g/dL
• 3. Hydrocortisone 500 mg iv bolus
• 4. HES 500 cc bolus
• 5. Broad spectrum antibiotics ASAP even before wound cultures obtained
86. Answer 2
• Our previous septic patient comes to the OR for wound debridement
and washout. What would be among our first priorities during the
case?
• 1. Place a central line
• 2. Transfuse for a Hb <8 g/dL
• 3. Hydrocortisone 500 mg iv bolus
• 4. HES 500 cc bolus
• 5. Broad spectrum antibiotics ASAP even before wound cultures obtained
89. REFERENCES
• Surviving Sepsis Campaign. International Guidelines for Management of Severe
Sepsis and Septic Shock. 2012. Dellinger R, et al. Crit Care Med. 2013; 41:580-
637.
• Epidemiology of Severe Sepsis in the United states: Analysis of incidence,
outcome, and associated costs of care. Angus DC, et al. Crit Care Med. 2001:
Jul;29(7):1303-10.
• The epidemiology of Sepsis in the United States from 1979 through 2000. Martin
G et al. N Eng J Med. 2003; 348:1546-1554.
• Septic Shock: A review article. Khadija Q, et al. BJMP 2008:1(2) 7-12.
• Definitions for Sepsis and organ failure and guidelines for the use of innovative
therapies in Sepsis. The ACCP/SCCM Consensus Conference Committee.
American College of Chest Physicians/ Society of Critical Care Medicine. Chest.
101.6 (1992): 1644-655. Web. 17 Feb. 2012.
90. • The third international consensus definitions for Sepsis and Septic Shock
(Sepsis-3). Singer M, Deutschman CS, Seymour CS, et al. JAMA. 2016:
315(8):801-10.
• Early Goal Directed Therapy in the treatment of Sepsis and Septic Shock. EGDT
collaborative group. Rivers E et al. N Engl J Med. 2001; 345:1368-1377.
• ARISE Investigators. Goal-directed resuscitation for patients with early Septic
Shock. N Engl J Med. 2014;371(16):1496-506.
• ProCESS Investigators. A randomized trial of protocol-based care for early
Septic Shock. N Engl J Med. 2014; 370(18):1683-93.
• ProMISE Trial Investigators. Trial of early goal directed resuscitation for Septic
Shock. N Engl J Med. 2015; 372(14):1301-11.
91. • Early, Goal-Directed Therapy for Septic Shock- a Patient-Level Meta-analysis. The
PRISM Investigators. N Engl J Med. 2017 376;23:2223-2234.
• Duration of hypotension before initiation of effective antimicrobial therapy is the
critical determinant of survival in human Septic Shock. Kumar A, et al. Crit Care Med.
2006; 34: 1589-1596.
• Initiation of Inappropriate Antimicrobial therapy results in a fivefold reduction of
survival in human Septic Shock. Kumar A, et al. Chest. 2009; 136:1237-1248.
• Vasopressin versus Norepinephrine Infusion in patients with Septic Shock. For the
VASST Investigators. Russell J, et al. N Engl J Med. 2008; 358: 877-887.
• Comparison of Dopamine and Norepinephrine in the treatment of Shock. For the
SOAP II Investigators. De Backer D, et al. N Engl J Med. 2010; 362:7779-789.
• A comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit.
The SAFE study Investigators. N Engl J Med. 2004;350:2247-2256.
92. • Hydroxyethyl Starch or saline for Fluid resuscitation in Intensive Care. CHEST
investigators. Myburgh J.A., et al. N Engl J Med. 2012;367:1901-11.
• Effect of treatment with low dose hydrocortisone and fludrocortisone on
mortality in patients with Septic Shock. Annane D, et al. JAMA. 2002; 288: 862-
871.
• Hydrocortisone Therapy for patients with Septic Shock. CORTICUS Study
Group. Sprung C.L., et al. N Engl J Med. 2008; 358: 877-887.
• Efficacy and safety of recombinant human activated protein C for Severe
Sepsis. PROWESS Study. Bernard G.R., et al. N Engl J Med. 2001; 344: 699-709.
• Drotrecogin Alfa (Activated) in Adults with Septic shock. PROWESS SHOCK
Study. RanieriV. M., et al. N Engl J Med. 2012; 366:2055-2064.
93. • Intensive Insulin Therapy in Critically ill patients. Van Den Berghe G., et al. N Engl J
Med 2001; 345: 1359-1367.
• Intensive versus conventional glucose control in critical ill patients. The NICE-
SUGAR Study Investigators. N Engl J Med. 2009; 360: 1283-1297.
• Surviving sepsis campaign: International guidelines for management of Severe
Sepsis and Septic Shock 2016. Rhodes A, et al. Crit Care Med. 2017;4593):486-552.
• Usefulness of procalcitonin for diagnosis of sepsis in the intensive care unit. Balci
C., et al. Critical Care. 2003; 7: 85-90.
• Septic Shock – Vasopressin, Norepinephrine and urgency. Parillo J.E. N Engl J Med.
2008; 358: 954-956.
• The Surviving Sepsis Campaign Bundle: 2018 update. Levy M, et al. Intensive Care
Medicine. 2018;44:925-928.
94. • Surviving Sepsis Campaign Bundle: 2021 update. Evans L, et al. Critical Care
Medicine. 2021;49(11):1063-1143.
• Global, regional, and national sepsis incidence and mortality , 1990-2017:
analysis for the Global Burden of Diseases Study. Rudd K, et al. Lancet
2020;395(10219):200-211.
Editor's Notes
Distinguishes sepsis from uncomplicated infection
EGDT may not be as critical to sepsis care as previously thought
Guidelines, although useful to clinicians, to manage complex problems, restrict their ability to respond uniquely to special circumstances
Vasopressin + norepi vs norepi
Severe sepsis with shock (on vasopressors)
Less sick patients
Sepsis but no true shock
Glucose 80-110
Procalcitonin is a peptide. Low levels indicate that the persons symptoms are due to a cause other than bacterial infection
PCT <0.15 ng/mL. NPV as a marker of bacterial infection , useful to r/o sepsis
AGAINST low dose dopamine for renal protection
HOB 30-45: to limit aspiration risk and prevent VAP
Clinical predictors of GI bleeding : mechanical ventilation >48 hrs and coagulopathy
Concern about increased pneumonia/c.diff
RRT - used with definite indications for dialysis (not for oliguria, or increase Cr)
