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Shock and Sepsis William Graham, MD Chief Resident July 13 -14 th, 2015 Slideset Shock and Sepsis William Graham, MD Chief Resident July 13 -14 th, 2015 Slideset adapted from: Payam Parvinchiha, MD

Case 1, Part 1 It’s your first day on wards and you receive the Case 1, Part 1 It’s your first day on wards and you receive the following page: “Hi doc, new transfer in T 3 Bd 23, need diet order. FYI: HR 120, BP 80/40, pt asleep. ” When are you going to see the patient? What questions do you want to ask? What are some orders to consider? 2

Objectives v Develop a systematic approach to the patient with hypotension v Recognize the Objectives v Develop a systematic approach to the patient with hypotension v Recognize the difference between hypotension and shock v Identify the causes of shock v Define the stages of the SIRS scale v Use of lactate levels and mortality in sepsis v Initial management of the septic patient 3

Objectives v Develop a systematic approach to the patient with hypotension v Recognize the Objectives v Develop a systematic approach to the patient with hypotension v Recognize the difference between hypotension and shock v Identify the causes of shock v Define the stages of the SIRS scale v Use of lactate levels and mortality in sepsis v Initial management of the septic patient 4

Hemodynamics of Blood Pressure MAP = CO x SVR • MAP = 1/3 SBP Hemodynamics of Blood Pressure MAP = CO x SVR • MAP = 1/3 SBP + 2/3 DBP • MAP goal is to maintain perfusion of the vital organs • MAP goal is dependent on patient’s individual physiology 5

Systematic Approach to the Hypotensive Patient MAP = CO x SVR ↓ Cardiac Output Systematic Approach to the Hypotensive Patient MAP = CO x SVR ↓ Cardiac Output = Heart Rate x Stroke Volume 1) Is the Heart Rate the cause? - bradycardia - non-sinus tachycardia (shortened diastole-> ↓LVEDV) Morchi, R. Diagnosis Deconstructed: Solving Hypotension in 30 Seconds. Emergency Medicine News, March 2015 Vol. 37 - Issue 3: p 17 6

Systematic Approach to the Hypotensive Patient MAP = CO x SVR ↓ Cardiac Output Systematic Approach to the Hypotensive Patient MAP = CO x SVR ↓ Cardiac Output = Heart Rate x Stroke Volume 2) Is the venous volume adequate? - Collapsable IVC means low volume upstream: ↓ IVC volume -> RA -> RV -> pulmonary circuit -> LA -> ↓ LVEDV - Capillary leak/venodilation? Hemorrhage? 7

Systematic Approach to the Hypotensive Patient MAP = CO x SVR ↓ Cardiac Output Systematic Approach to the Hypotensive Patient MAP = CO x SVR ↓ Cardiac Output = Heart Rate x Stroke Volume 3) Is the thoracic circuit obstructed? -Tension pneumothorax -Cardiac tamponade -Constrictive Pericarditis -RV infarction -Massive PE -Pulmonary HTN -Positive Pressure Ventilation 8

Systematic Approach to the Hypotensive Patient MAP = CO x SVR ↓ Cardiac Output Systematic Approach to the Hypotensive Patient MAP = CO x SVR ↓ Cardiac Output = Heart Rate x Stroke Volume 4) Is contractility compromised? -Decompensated systolic heart failure -Severe/Acute valvular disease -Acute VSD 9

Systematic Approach to the Hypotensive Patient MAP = CO x SVR Causes of ↓ Systematic Approach to the Hypotensive Patient MAP = CO x SVR Causes of ↓ Systemic Vascular Resistance: 5) What is the tone of the arterioles? - Poor tone may be due to sepsis, anaphylaxis, or loss of sympathetic neural tone (SCI) Morchi, R. Diagnosis Deconstructed: Solving Hypotension in 30 Seconds. Emergency Medicine News, March 2015 Vol. 37 - Issue 3: p 17 10

Case 1: Part 1 “Hi doc, new transfer arrived in T 3 Bd 23, Case 1: Part 1 “Hi doc, new transfer arrived in T 3 Bd 23, need diet order. FYI, pt HR 120, BP is 80/40, sleepy. ” When are you going to see the patient? What questions do you want to ask? What are some orders to consider? 11

Questions to ask yourself: MAP = CO x SVR Is patient symptomatic? Delirium, dyspnea, Questions to ask yourself: MAP = CO x SVR Is patient symptomatic? Delirium, dyspnea, chest pain, oliguria, bleeding, vomiting, diarrhea? Why is patient in hospital? Complete Vitals: Temp, HR, BP, RR, pulse ox, trend? Meds: Antibiotics? correlation between BP and new meds? Recent procedures? procedures, surgery Endoscopy, cardiac catheterization, IR How much IVF has been given and did they respond? 12

Orders to consider: CBC Lactate, Troponin Cultures ABG/EKG/CXR Cortisol level/ACTH stim test IVF/Blood Transfusion Orders to consider: CBC Lactate, Troponin Cultures ABG/EKG/CXR Cortisol level/ACTH stim test IVF/Blood Transfusion Grab the ultrasound! 13

Case 1, Part 2 At Bedside: The patient is lethargic, minimally arousable, and mumbling Case 1, Part 2 At Bedside: The patient is lethargic, minimally arousable, and mumbling incoherently. There is no family at bedside. 14

Case 1, Part 2 Well so much for getting some subjective information… Onto obtaining Case 1, Part 2 Well so much for getting some subjective information… Onto obtaining the objective data: What findings on exam signs can help you narrow your differential diagnosis? 15

Examining the Hypotensive patient: GEN: 16 MAP = CO x SVR Examining the Hypotensive patient: GEN: 16 MAP = CO x SVR

Examining the Hypotensive patient: MAP = CO x SVR GEN: Delirium, confusion, lethargy, accessory Examining the Hypotensive patient: MAP = CO x SVR GEN: Delirium, confusion, lethargy, accessory muscle use HEENT: 17

Examining the Hypotensive patient: MAP = CO x SVR GEN: Delirium, confusion, lethargy, accessory Examining the Hypotensive patient: MAP = CO x SVR GEN: Delirium, confusion, lethargy, accessory muscle use HEENT: Dry mucous membranes CV: 18

Examining the Hypotensive patient: MAP = CO x SVR GEN: Delirium, confusion, lethargy, accessory Examining the Hypotensive patient: MAP = CO x SVR GEN: Delirium, confusion, lethargy, accessory muscle use HEENT: Dry mucous membranes CV: Jugular venous distension/flattening, murmurs, extra heart sounds, irregular tachycardia Lungs: 19

Examining the Hypotensive patient: MAP = CO x SVR GEN: Delirium, confusion, lethargy, accessory Examining the Hypotensive patient: MAP = CO x SVR GEN: Delirium, confusion, lethargy, accessory muscle use HEENT: Dry mucous membranes CV: Jugular venous distension/flattening, murmurs, extra heart sounds, irregular tachycardia Lungs: Asymmetric hemithorax, rales or other abnormalities Abdomen: 20

Examining the Hypotensive patient: MAP = CO x SVR GEN: Delirium, confusion, lethargy, accessory Examining the Hypotensive patient: MAP = CO x SVR GEN: Delirium, confusion, lethargy, accessory muscle use HEENT: Dry mucous membranes CV: Jugular venous distension/flattening, murmurs, extra heart sounds, irregular tachycardia Lungs: Asymmetric hemithorax, rales or other abnormalities Abdomen: Absent bowel sounds, distension, rebound • Palpate the back, groin, and thigh Extremities: 21

Examining the Hypotensive patient: MAP = CO x SVR GEN: Delirium, confusion, lethargy, accessory Examining the Hypotensive patient: MAP = CO x SVR GEN: Delirium, confusion, lethargy, accessory muscle use HEENT: Dry mucous membranes CV: Jugular venous distension/flattening, murmurs, extra heart sounds, irregular tachycardia Lungs: Asymmetric hemithorax, rales or other abnormalities Abdomen: Absent bowel sounds, distension, rebound • Palpate the back, groin, and thigh Extremities: edema Skin: 22

Examining the Hypotensive patient: MAP = CO x SVR GEN: Delirium, confusion, lethargy, accessory Examining the Hypotensive patient: MAP = CO x SVR GEN: Delirium, confusion, lethargy, accessory muscle use HEENT: Dry mucous membranes CV: Jugular venous distension/flattening, murmurs, extra heart sounds, irregular tachycardia Lungs: Asymmetric hemithorax, rales or other abnormalities Abdomen: Absent bowel sounds, distension, rebound • Palpate the back, groin, and thigh Extremities: edema Skin: Pallor, cyanosis, capillary refill, warm or cold 23

Case 1, Part 3 Patient transferred earlier today for confusion Vitals: 39⁰C, HR 130, Case 1, Part 3 Patient transferred earlier today for confusion Vitals: 39⁰C, HR 130, RR 22, BP 80/40, 98% RA, Confused Dry mucous membranes Symmetric, CTAB S 1/S 2 regular, tachycardic Cool extremities Abd Soft, mildly distended, nontender, few bowel sounds CVA tenderness on right ------UA: 200 WBC and few bacteria Urine output 10 cc/hr WBC 25, 000 24

Hypotension vs. Shock Ø Hypotension is an abnormal vital sign. Ø Shock is a Hypotension vs. Shock Ø Hypotension is an abnormal vital sign. Ø Shock is a physiologic state, characterized by end organ hypoperfusion. ∴ Not everyone with hypotension is in shock By evaluating and treating hypotension early, you can prevent progression to shock 25

Types of Shock: CATEGORY MAP = CO x SVR ETIOLOGIES Hypovolemic ↓ venous return Types of Shock: CATEGORY MAP = CO x SVR ETIOLOGIES Hypovolemic ↓ venous return -> ↓ CO Blood loss (internal/external) Fluid losses Cardiogenic ↓ CO LV/RV failure (MI, cardiac arrest) Valvular dysfunction Arrhythmia Distributive ↓ SVR (Vasodilated) Anaphylaxis Adrenal insufficiency Neurogenic Septic Obstructive 26 PHYSIOLOGY Extra-cardiac obstruction to Tamponade blood flow -> ↓ CO Pulmonary Embolus Tension Pneumothorax

Learning Objectives v Develop a systematic approach to the patient with hypotension v Understand Learning Objectives v Develop a systematic approach to the patient with hypotension v Understand recognize the difference between hypotension and shock v Identify the different causes of shock v Define the stages of the SIRS scale v Use of lactate levels and mortality in sepsis v Initial management of the septic patient 27

SIRS Scale SIRS ≥ 2: • Temperature: <36⁰C or >38⁰C (<96. 8⁰F or >100. SIRS Scale SIRS ≥ 2: • Temperature: <36⁰C or >38⁰C (<96. 8⁰F or >100. 4⁰F) • Heart Rate > 90 • Respiratory Rate > 20 • WBC < 4000, > 12000, or >10% bands SEPSIS: 28

SIRS Scale SIRS ≥ 2: • Temperature: <36⁰C or >38⁰C (<96. 8⁰F or >100. SIRS Scale SIRS ≥ 2: • Temperature: <36⁰C or >38⁰C (<96. 8⁰F or >100. 4⁰F) • Heart Rate > 90 • Respiratory Rate > 20 • WBC < 4000, > 12000, or >10% bands SEPSIS: SIRS + proven or suspected microbial etiology SEVERE SEPSIS: 29

SIRS Scale SIRS ≥ 2: • Temperature: <36⁰C or >38⁰C (<96. 8⁰F or >100. SIRS Scale SIRS ≥ 2: • Temperature: <36⁰C or >38⁰C (<96. 8⁰F or >100. 4⁰F) • Heart Rate > 90 • Respiratory Rate > 20 • WBC < 4000, > 12000, or >10% bands SEPSIS: SIRS + proven or suspected microbial etiology SEVERE SEPSIS: Sepsis + evidence of sepsis-induced tissue hypoperfusion or organ dysfunction SEPTIC SHOCK: 30

SIRS Scale SIRS ≥ 2: • Temperature: <36⁰C or >38⁰C (<96. 8⁰F or >100. SIRS Scale SIRS ≥ 2: • Temperature: <36⁰C or >38⁰C (<96. 8⁰F or >100. 4⁰F) • Heart Rate > 90 • Respiratory Rate > 20 • WBC < 4000, > 12000, or >10% bands SEPSIS: SIRS + proven or suspected microbial etiology SEVERE SEPSIS: Sepsis + evidence of sepsis-induced tissue hypoperfusion or organ dysfunction SEPTIC SHOCK: Sepsis with hypotension refractory to adequate fluid resuscitation, or vasopressors needed to maintain SBP >90 or MAP >65 RC Bone, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. Chest, 1992; 101(6): 1644 -1655. 31

Q: Does SIRS always mean infection? 32 Q: Does SIRS always mean infection? 32

Q: Does SIRS always mean infection? 33 Q: Does SIRS always mean infection? 33

Q: What distinguishes severe sepsis vs sepsis? 34 Q: What distinguishes severe sepsis vs sepsis? 34

Q: What distinguishes severe sepsis vs sepsis? Answer: Tissue Hypoperfusion § Sepsis-Induced hypotension § Q: What distinguishes severe sepsis vs sepsis? Answer: Tissue Hypoperfusion § Sepsis-Induced hypotension § Urine output < 0. 5 cc/kg/hr for > 2 hrs § Cr > 2. 0 mg/d. L § Bilirubin > 2. 0 mg/d. L § Platelet count < 100, 000 § INR > 1. 5 § Altered mental status § Ischemic bowel § Gangrene § Elevated lactate Levy MM, Fink MP, Marshall JC, et al: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31: 1250– 1256. 35

Surviving Sepsis Campaign 2002 -2012 Within 3 Hours of Identifying Within 6 Hours of Surviving Sepsis Campaign 2002 -2012 Within 3 Hours of Identifying Within 6 Hours of Identifying Sepsis: 1. Measure lactic acid 5. Vasopressors for hypotension refractory to initial resuscitation for goal MAP ≥ 65 2. Obtain blood cultures before antibiotics 6. For persistent hypotension despite resuscitation (septic shock!) 3. Start broad-spectrum or lactate > 4, check: antibiotics - CVP (goal ≥ 8)* - Scv. O 2 (goal ≥ 70%)* 4. Administer 30 cc/kg crystalloid for low BP or lactate > 4 7. Repeat lactate if initially elevated Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013; 41(2): 580 -637. Intensive Care Med. 2013; 39(2): 165 -228. 36

Lactate and Mortality in Sepsis What is it? Lactic acid is generated by anaerobic Lactate and Mortality in Sepsis What is it? Lactic acid is generated by anaerobic metabolism. Elevated lactic acid is evidence of suboptimal tissue O 2 delivery to the endorgans. 37

Serum lactate is associated with mortality in severe sepsis independent of organ failure and Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock Figure 3. Association between serum lactate level and 28 -day mortality, stratified by the presence of shock. Serum lactate categorized as follows: low = 0 -1. 9 mmol/L intermediate = 2 -3. 9 high = 4 Critical Care Medicine. 2009. 37(5): 1670 -1677 38

Hemodynamic Resuscitation It’s all about optimizing oxygen delivery to the tissue. The delivery of Hemodynamic Resuscitation It’s all about optimizing oxygen delivery to the tissue. The delivery of oxygen to the tissues per minute (DO 2) is calculated by: DO 2 = [1. 39 x Hb x Sa. O 2 + (0. 003 x Pa. O 2)] x CO Remember!!! MAP = CO x SVR 39

Early Goal Directed Therapy Early hemodynamic resuscitation in the first 6 hours based on Early Goal Directed Therapy Early hemodynamic resuscitation in the first 6 hours based on specific goals for CVP, MAP, Scv. O 2, Hct Randomized, controlled, single-center study Urban center ED 130 assigned to early goal directed therapy 133 assigned to standard therapy Achieving these targets resulted in a 15. 9% absolute reduction in 28 day mortality Rivers E, et al. Early Goal Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. The New England Journal of Medicine. 2001. 345(19): 1368 -1377. 40

Goals of EGDT: The first 6 hours: Minimum resuscitation = 30 cc/kg CVP 8 Goals of EGDT: The first 6 hours: Minimum resuscitation = 30 cc/kg CVP 8 -12, achieved with IVF boluses MAP > 65, achieved with vasopressors Mixed venous oxygen saturation >70%, achieved with PRBC transfusions or dobutamine • Urine output > 0. 5 cc/kg/hr • • 41

Case 1, Part 4 Patient receives 6 L of IVF, CVP 12, and BP Case 1, Part 4 Patient receives 6 L of IVF, CVP 12, and BP now 80/60, urine output 15 cc/hr, lactate 5 How would you classify this patient? 42

Case 1, Part 4 Patient receives 6 L of IVF, CVP 12, and BP Case 1, Part 4 Patient receives 6 L of IVF, CVP 12, and BP now 80/60, urine output 15 cc/hr, lactate 5 How would you classify this patient? SEPTIC SHOCK 43

EGDT Algorithm: The First 6 Hours: 44 DO 2 = [1. 39 x Hb EGDT Algorithm: The First 6 Hours: 44 DO 2 = [1. 39 x Hb x Sa. O 2 + (0. 003 x Pa. O 2)] x CO

Vasopressors Vasopressors

Vasopressors First line: Norepinephrine (Levophed) Second line: Epinephrine Third line: Vasopressin (0. 04 units/min Vasopressors First line: Norepinephrine (Levophed) Second line: Epinephrine Third line: Vasopressin (0. 04 units/min fixed dose) 46

Protocol for Early Goal-Directed Therapy 47 DO 2 = [1. 39 x Hb x Protocol for Early Goal-Directed Therapy 47 DO 2 = [1. 39 x Hb x Sa. O 2 + (0. 003 x Pa. O 2)] x CO

Inotropes First line: Dobutamine (max dose 20 mcg/kg/min) - myocardial dysfunction - ongoing hypoperfusion Inotropes First line: Dobutamine (max dose 20 mcg/kg/min) - myocardial dysfunction - ongoing hypoperfusion despite adequate intravascular volume and MAP 48

Is EGDT all it’s cracked up to be? Controversy: - TRICC trial (1999) showed Is EGDT all it’s cracked up to be? Controversy: - TRICC trial (1999) showed mortality reduction using a restrictive transfusion strategy for septic shock patients - accuracy of CVP as surrogate for intravascular volume determination has been controversial Landmark follow-up studies since River’s EGDT: -Pro. CESS trial- NEJM 2014 - US -ARISE trial- NEJM 2014 - Australia -Pro. MISe trial- NEJM 2015 - UK 49

Is EGDT all it’s cracked up to be? Controversy: - TRICC trial (1999) showed Is EGDT all it’s cracked up to be? Controversy: - TRICC trial (1999) showed mortality reduction using a restrictive transfusion strategy for septic shock patients - accuracy of CVP as surrogate for intravascular volume determination has been controversial Landmark follow-up studies since River’s EGDT: -Pro. CESS trial- NEJM 2014 - US -ARISE trial- NEJM 2014 - Australia -Pro. MISe trial- NEJM 2015 - UK No difference in 60/90 day mortality between patients randomized to receive EGDT from standard care * Achieving specific goals did not improve mortality * Fewer transfusions in non-EGDT groups * Shorter LOS in ICU in non-EGDT groups 50

Surviving Sepsis Campaign 2015 Update “With publication of 3 trials that do not demonstrate Surviving Sepsis Campaign 2015 Update “With publication of 3 trials that do not demonstrate superiority of required use of a CVC to monitor CVP and SCVO 2 in all patients with septic shock who have received timely antibiotics and fluid resuscitation compared with controls or in all patients with lactate > 4, the SSC Executive committee has revised the improvement bundles. ” - SSC Executive Committee Statement, April 2015 51

Surviving Sepsis Campaign 2015 Update Within 3 Hours of Identifying Within 6 Hours of Surviving Sepsis Campaign 2015 Update Within 3 Hours of Identifying Within 6 Hours of Identifying Sepsis: 1. Measure lactic acid 5. Vasopressors for hypotension refractory to initial resuscitation for goal MAP ≥ 65 2. Obtain blood cultures before antibiotics 6. For persistent hypotension despite resuscitation (septic shock!) 3. Start broad-spectrum or lactate > 4, check: antibiotics - CVP (goal ≥ 8)* - Scv. O 2 (goal ≥ 70%)* 4. Administer 30 cc/kg crystalloid Reassess volume status and tissue perfusion for low BP or lactate > 4 clinically (vitals, capillary refill, pulse, skin), OR by CVP, Scv. O 2 or CV ultrasound 7. Repeat lactate if initially elevated 52

UCI Severe Sepsis Order Set 53 UCI Severe Sepsis Order Set 53

54 54

In Summary v Use a systematic approach to the hypotensive patient, based on: MAP In Summary v Use a systematic approach to the hypotensive patient, based on: MAP = CO x SVR v Hypotension is a vital sign, shock is a physiologic state v Shock can be Hypovolemic, Cardiogenic, Distributive, and/or Obstructive v Lactate levels correlate with mortality in septic shock v Key to managing patients with septic shock is to treat early with fluids, antibiotics, and pressors if needed v Specific hemodynamic goals are less important than ensuring starting treatment ASAP. 55

Case Scenario A 77 -year-old woman was evaluated in the ED for a UTI Case Scenario A 77 -year-old woman was evaluated in the ED for a UTI and hypotension. Antibiotics were administered in the ED, and she was admitted to the floor. Eight hours after admission, she is confused and lethargic. Temp 37. 8 C (100. 0 F), BP 88/50 mm Hg, HR 112/min, and RR 28/min. Other than tachycardia, the cardiopulmonary examination is normal. Her extremities are cool and mottled appearing. She has had no urine output since admission to the hospital. Hb 10. 5 Cr: Normal 56 WBC 16, 700 Plts 110, 000 Electrolytes: normal ECG: sinus tachycardia

What is the next best step? A) Hydrocortisone 50 mg IV q 6 H What is the next best step? A) Hydrocortisone 50 mg IV q 6 H B) IV fluid bolus C) Norepinephrine D) Two units RBCs 57

What is the next best step? A) Hydrocortisone 50 mg IV q 6 H What is the next best step? A) Hydrocortisone 50 mg IV q 6 H B) IV fluid bolus C) Norepinephrine D) Two units RBCs 58