SEPTIC SHOCK-DR.LANDO ELVIS O.pptx

Septic shock

1. SEPTIC SHOCK DR. LANDO ELVIS PKH-IMED

2. Overview: Normal Response to Infection Local infection Non-specific inflammatory response 3 phases Vasodilation - increased blood flow to site, infusion of antibodies and cells to fight infection Vessel permeability - antibodies and cells exit bloodstream and enter infected tissue Once infection is controlled, tissue repairs itself

3. Overview: Pathophysiology of Sepsis Uncontrolled, exaggerated immune response Endothelium damage, cell mediator activation, disruption of coagulation system homeostasis Vasodilation and capillary permeability Systemic inflammatory response End-organ damage, death

4. DEFINITIONS : SIRS Systemic Inflammatory Response Syndrome(SIRS): I s a nonspecific inflammatory response to an insult that results in activation of the immune system. This inflammatory response is the body’s way of attempting to maintain homeostasis. Requires ≥ 2 of the following: Temperature > 38°C or < 36°C Respiratory rate > 20/min, or PaCO 2 < 32 mmHg Heart rate > 90 bpm WBC count >12,000 or <4,000 cells/µL, or > 10% bands Sepsis: ≥ 2 SIRS criteria + evidence of infection ACCP/SCCM Consensus Conference . Crit Care Med 1992;20(6):864–74.

5. DEFINITIONS: Severe Sepsis Sepsis + new organ dysfunction = severe sepsis Sepsis-induced tissue hypoperfusion or organ dysfunction (any of the following): Hypotension (SBP < 90 mmHg, MAP < 70 mmHg, or SBP of 40 mmHg below baseline) Elevated lactate UOP < 0.5 mL/kg/hr x 2 hours, despite adequate IVF Creatinine > 2 mg/ dL PaO 2 /FIO 2 < 250 in absence of PNA as source PaO 2 /FIO 2 < 200 in presence of PNA as source Bilirubin > 2 mg/dL Platelets < 100,000/µL Coagulopathy (INR > 1.5) Levy MM, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250-1256.

6. Severe sepsis + refractory hypotension OR lactate ≥ 4 mmol /L = septic shock Shock in general is a state of cellular and tissue hypoxia due to: R educed O 2 delivery (e.g. anemia, hypoxemia); Outstripped O 2 consumption (e.g. thyrotoxicosis); and/or I mpaired utilization (e.g. mitochondrial dysfunction) Septic shock commonly manifests with #1 and #3 concurrently in a patient Most common clinical definition of septic shock is presence of severe sepsis + hypotension refractory to intravenous fluids alone i.e. the patient requires vasopressors generally hypotension is mean arterial pressure (MAP) < 65 mmHg Watch out for shock in a chronically hypertensive patient with “normal BP” that is significantly below baseline Some argue presence of elevated lactate (>4 mmol /L) also indicates shock regardless of MAP DEFINITIONS: Septic shock

7. Cont.. Septic shock is a distributive shock Cytokine release leads to a large-scale inflammatory response Massive vasodilation Increased capillary permeability Decreased systemic vascular resistance Blood clots form in the microvasculature Hypotension reduces tissue perfusion causing tissue hypoxia

8. DEFINITIONS: Multiple Organ Dysfunction Syndrome (MODS) MODS is altered organ function in an acutely ill patient requiring medical intervention to achieve homeostasis. Can be the end result of septic shock. Sepsis-related organ dysfunction → No organ system is immune Respiratory failure Liver failure Kidney failure Heart failure Gut permeability DIC (disseminated intravascular coagulation) Altered mental status Brain death

9. Linear model of sepsis Progression Early identification and treatment It is crucial to identify septic patients and initiate treatment as early along the continuum as possible and treat them to avoid developing organ damage or shock. SIRS + Infection Sepsis + End Organ Damage Severe Sepsis + Refractory (unresponsive) hypotension Temp. > 38 C or < 36 C, HR > 90, RR > 20 or PaCO 2 < 32, WBCs > 12,000 or < 4,000 or > 10% bands Goal: early identification here Death can result ©2019 CHA

10. Singer M, et al. Sepsis-3. JAMA. 2016;315(8):801-10. In 2016, the Society of Critical Care Medicine and European Society of Intensive Care Medicine released a consensus statement redefining the sepsis syndrome. “SIRS” and “severe sepsis” were eliminated “ Septic shock ” was redefined as hypotension despite adequate IVF requiring vasopressors to maintain MAP > 65 mmHg, and serum lactate > 2 mmol /L. New Definitions of Sepsis?

11. Emphasis was placed on organ failure (SOFA score), especially the “quick SOFA” or qSOFA score: Presence of altered mental status Systolic blood pressure ≤ 100 mmHg Respiratory rate ≥ 22/minute A score of ≥ 2 reflects high risk for organ failure and mortality and should prompt appropriate intervention New Definitions of Sepsis ? Singer M, et al. Sepsis-3. JAMA. 2016;315(8):801-10.

12. While these definitions may prove to be clinically useful, they are not yet validated, so should be used cautiously. For example, while SIRS sacrifices specificity for sensitivity, qSOFA is likely under-sensitive, which is problematic for a screening test because it may miss septic patients. New Definitions of Sepsis ? Singer M, et al. Sepsis-3. JAMA. 2016;315(8):801-10. Additional reading on Sepsis-3 definitions: Simpson SQ. New Sepsis Criteria: A Change We Should Not Make. Chest. 2016;149(5):1117-8.

13. Risk Factors for Sepsis Extremes of age (old and young) Can’t communicate, need careful assessment Patients with developmental delay Cerebral Palsy Recent surgery, invasive procedure, illness, childbirth/pregnancy termination/miscarriage Reduced immunity

14. Increased Risk for Sepsis DIABETES, DIABETES, DIABETES Liver cirrhosis Autoimmune diseases (lupus, rheumatoid arthritis) HIV/AIDS Para/quadriplegics Sickle cell disease Splenectomy patients Compromised skin (chronic wounds, burns, ulcers)

15. Increased Risk for Sepsis Chemotherapy Post-organ transplant (bone marrow, solid organ) Chronic steroid use Recent antibiotic use Indwelling catheters of any kind (dialysis, Foley, IV, PICC, PEG tubes, etc )

16. Signs/Symptoms of Sepsis Symptoms of sepsis are often nonspecific and include the following: Fever = most common (elderly patients often do NOT mount a febrile response) Flu-like symptoms Chills/shaking (mistaken for seizure) Nausea/vomiting Mental status changes/fatigue/lethargy Patient often does NOT appear acutely ill

17. Multiple Organ System Dysfunction Cardiovascular Tachycardia Hypotension Renal Oliguria Anuria Renal failure Hematologic Consumptive coagulopathy Petechiae Purpura CNS Altered mental status Respiratory Tachypnea Hypoxia Hepatic Jaundice Liver inflammation Coagulopathy Metabolic Lactic acidosis

18. APROACH IN MANAGING SEPSIS . Lactate Blood cultures x2 before antibiotics Give antibiotics Give fluids at 30 mL/kg if: initial hypotension, lactate ≥ 4, or septic shock Reperfusion assessment ©2019 CHA

19. 1 .Lactate With sepsis, lactate is viewed as a marker of global tissue perfusion. Lactate has some predictive use: Sustained > 6 hours, an elevated lactate foreshadows increased mortality Mortality increases as lactate levels increase Lactate Level Mortality 0-2.5 mmol/L 4.9 percent mortality 2.5-4.0 mmol/L 9.0 percent mortality > 4.0 mmol/L 28.4 percent mortality (Nguyen, et al., 2004; Shapiro, et al., 2005) ©2019 CHA

20. 2 .Blood Cultures Source control: identify and stop the infection Why two sets of blood cultures? Corroboration of matching sets confirms treatment of a true pathogen versus a contaminate The goal is to prevent culture negative severe sepsis (CNSS) and septic shock Of 6.8 million severe sepsis admissions, 47 percent were culture negative CNSS was seen as a statistically significant independent predictor of death ©2019 CHA

21. 3 . The Rapid Choice of the Right Antibiotic(s) Morell MR et al. The Management of Severe Sepsis and Septic Shock Infectious Disease Clinics of North America 23 (3): 485-501, 2009 Early, broad-spectrum antibiotics are absolutely critical. Failure to treat up front with the right antibiotics increases mortality by 10-20 percentage points. Every hour antibiotic initiation is delayed increases the risk for mortality by more than eight percent. Antibiotics should be given as soon as possible after blood cultures are drawn. Preferably after the second set of cultures; however, if the second set is going to be delayed more than 30 minutes, antibiotics should be started after the first set. If more than one antibiotic is ordered, give the broadest-spectrum antibiotic first. Infuse multiple antibiotics concurrently, if appropriate.

22. 1. The Rapid Choice of the Right Antibiotics Review of risk factors for certain infections E.g., recent bowel surgery should make you think about gram-negatives, anaerobes, and Candida . Identification of source(s) or suspected source(s ) E.g., comprehensive work-up based on risk factors, history, physical , laboratory, and imaging studies Correct stratification of patients as hospital-acquired, health-care associated, or community-acquired E.g., recent hospitalization, SNF patient, etc. Review of prior infection history and prior microbiological cultures and sensitivities E.g., urine culture from 2 months ago grew Zosyn -resistant E. coli Early (within 60 minutes of diagnosis) delivery of antibiotics What does this look like in action? 3 . The Rapid Choice of the Right Antibiotic(s)

23. 1. The Rapid Choice of the Right Antibiotics This means EARLY involvement of procedural and surgical colleagues for adequate source control: E.g. inserting chest tubes for empyemas , biliary tubes for biliary obstructions, nephrostomy tubes for obstructing kidney stones, joint wash-out for septic arthritis, ex-laps for bowel perfs , etc. One caveat – patients much be stabilized for these procedures, which means they need to be fluid resuscitated first (see next slide). It is also common for patients to transiently worsen following source control procedure (classically drainage of liver abscess) due to “stirring up infection”. Anticipate this and stay on top of it with fluids and vasopressors! Consider inadequate source control in a patient who fails to improve with fluids and antibiotics alone Antibiotics will not effectively penetrate undrained abscesses 4 . Achieve Adequate Source Control

24. Hypotension (SBP < 90, MAP < 65) or lactate > 4 mmol /L : initial fluid bolus 20-40 ml of crystalloid (or colloid equivalent) per kg of body weight. The Society of Critical Care Medicine suggests isotonic saline (normal saline) or balanced salt solutions (lactated Ringers) for initial fluid resuscitation. Sepsis and severe sepsis without hypotension: For most patients, the provider will likely order a fluid bolus based on their assessment, but there is no specific requirement Severe sepsis with hypotension or lactate ≥ 4 mmol /L: 30 mL/kg of actual body weight for patients with a BMI < 30 30 mL/kg of ideal body weight for patients with a BMI > 30 Provider must document that they are using ideal body weight if BMI over 30 “Goal Directed Therapy” for sepsis, which targeted physiologic endpoints once patients arrived in the ICU but not before. 5 . Septic shock – Fluid therapy

25. 5 . Fluid resuscitation: Central tenet of therapy 2012 Surviving Sepsis Campaign recommends specific physiologic goals for fluid resuscitation: MAP > 65 mmHg CVP 8-12 mmHg (or 12-15 during mechanical vent) Central venous O 2 sat > 65% or Mixed venous > 70% Urine output > 0.5 ml/kg/h Normalization of lactate It is important to note that these goals are for the first 6 hours of sepsis therapy

26. First-line: Norepinephrine (dose: 0.01 - 1 µg/kg/min) Increases MAP mainly by vasoconstriction, but also is a mild inotrope which is important for sepsis-mediated cardiac stunning Low doses improve cardiac output, and cerebral, renal, and splanchnic blood flow Compared to dopamine: Less tachycardia, fewer arrhythmias, lower RR of death (0.91; 0.83–0.99 ) Second-line: Vasopressin (dose: 0.01 – 0.04 units/min) Goal is to decrease dose of NE Reasonable to start when NE dose gets to 0.2 µg/kg/min Some say dose is “fixed” at 0.04, but in reality you can adjust. 6 . Maintain Blood Pressure Support

27. Third-line: Epinephrine (dose: 0.01 - 1 µg/kg/min) Same dosing regimen as norepinephrine FYI on Epinephrine: If patient is dead , the dose is 1 mg IV q3min. If patient is alive but hypotensive, the dose is 10 mcg IV (or 1 ml of 1:100,000 concentration) q1min prn. Don’t give 1 mg! Can use Phenylephrine infusion in certain situations, e.g. avoidance of beta-adrenergic activation if patient has rapid Afib . 6 . Maintain Blood Pressure Support

28. Summary The 3 most important components of sepsis care are: Rapid administration of the right antibiotic(s) Source control within first hospital day Aggressive resuscitation with IVF, pressors , etc. during first 6 hours of care How do you judge fluid responsiveness? By all of these: Physical exam, straight leg raise, IVC ultrasound, CVP, MAP, urine output (UOP), lactate , Central venous oxyhemoglobin saturation (ScvO 2 ), trial and error, etc. etc. No single test will tell you what to do!

29. Summary Fluids should be administered as long as the patient is fluid responsive, to a point . Avoid fluid overload (edema worsens O 2 delivery due to increasing distance needed for O 2 diffusion) Conversely, using high dose vasopresors in a hypovolemic patient will cause digital necrosis So the take home message is give enough fluids up front to fill the tank (~4-5 L may be sufficient) but not too much to cause significant fluid overload…

30. END .