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

When are you going to see the patient? Case 1, Part 1 It’s your first day on wards and you receive the following page: “Hi doc, new transfer in T3Bd23, 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?

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

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

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 If you only take one thing away from this lecture, its that I want you to develop a pavlovian response with equation. Every time you are paged about a patient with hypotension, I want you to immediately think of this equation. Sear it into your minds. The mean arterial pressurse is the product of the cardiac output and the systemic vascular resistance It is also the sum of 1/3 the SBP plus 2/3 the DBP

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) We can break down the components of this equation to guide our approach to the hypotensive patient. There are 5 basic questions to ask yourself: Tx: electrical Morchi, R. Diagnosis Deconstructed: Solving Hypotension in 30 Seconds. Emergency Medicine News, March 2015 Vol. 37 - Issue 3: p 17

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? SV = EDV - ESV

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 i.e. is IVC volume actually becoming LVEDV?

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

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

Case 1: Part 1 “Hi doc, new transfer arrived in T3Bd23, 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? Do not spend 20 minutes chart reviewing, unless you want the nurse to call a rapid response. The computer will not have the answer for why the patient is hypotensive. Go assess the patient at bedside. “I am on my way.”

Questions to ask yourself: MAP = CO x SVR Questions to ask yourself: 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? Endoscopy, cardiac catheterization, IR procedures, surgery How much IVF has been given and did they respond?

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

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

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?

Examining the Hypotensive patient: MAP = CO x SVR Examining the Hypotensive patient: GEN: think about the components of the equation to guide your exam! Get audience participation

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

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

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

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

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

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

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

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 S1/S2 regular, tachycardic Cool extremities Abd Soft, mildly distended, nontender, few bowel sounds CVA tenderness on right ------------- UA: 200 WBC and few bacteria Urine output 10cc/hr WBC 25,000 Seniors: Is this hypotension or shock? Seniors: What kind of shock is this? Seniors: What level of care is best for this patient?

∴ Not everyone with hypotension is in shock Hypotension vs. Shock Hypotension is an abnormal vital sign. 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 What is a “normal” BP? It’s relative. Hypotension is simply a vital sign. It is something the nurse measures and pages you about. Shock, on the other hand, is a physiological state. It is an assessment of the consequences of sustained hypotension due to some underlying pathology. Some patients have low BP but have adequate vital organ perfusion (ex. 80/50 in a cirrhotic or high cervical cord disease). This is not shock.

Types of Shock: MAP = CO x SVR CATEGORY PHYSIOLOGY 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 Extra-cardiac obstruction to blood flow -> ↓ CO Tamponade Pulmonary Embolus Tension Pneumothorax

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

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 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:

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:

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.

Q: Does SIRS always mean infection?

Q: Does SIRS always mean infection?

Q: What distinguishes severe sepsis vs sepsis?

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/dL Bilirubin > 2.0 mg/dL 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.

Surviving Sepsis Campaign 2002-2012 Within 3 Hours of Identifying Sepsis: Measure lactic acid Obtain blood cultures before antibiotics Start broad-spectrum antibiotics Administer 30cc/kg crystalloid for low BP or lactate > 4 Within 6 Hours of Identifying Sepsis: Vasopressors for hypotension refractory to initial resuscitation for goal MAP ≥ 65 For persistent hypotension despite resuscitation (septic shock!) or lactate > 4, check: - CVP (goal ≥ 8)* - ScvO2 (goal ≥ 70%)* 7. Repeat lactate if initially elevated How do we manage sepsis? SSC international guidelines, first in 2002, updated twice since, most recently 2012 Lets look at the different components of this bundle, starting with the lactate. 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.

Lactate and Mortality in Sepsis What is it? Lactic acid is generated by anaerobic metabolism. Elevated lactic acid is evidence of suboptimal tissue O2 delivery to the end- organs. Why do we measure it?

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 So: if poor O2 delivery causes elevated lactate… and elevated lactate is associated with worsening mortality… lets improve O2 delivery! Critical Care Medicine. 2009. 37(5):1670-1677

Hemodynamic Resuscitation It’s all about optimizing oxygen delivery to the tissue. The delivery of oxygen to the tissues per minute (DO2) is calculated by: DO2 = [1.39 x Hb x SaO2 + (0.003 x PaO2)] x CO Remember!!! MAP = CO x SVR In sepsis low vascular tone, vasodilated. Therefore to optimize MAP and perfusion of vital organs, you have to optimize CO and Increase vascular tone with vasopressors

Early Goal Directed Therapy Early hemodynamic resuscitation in the first 6 hours based on specific goals for CVP, MAP, ScvO2, 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 EGDT is how we resuscitate patients with severe sepsis and septic shock. 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.

Goals of EGDT: The first 6 hours: Minimum resuscitation = 30cc/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 > 0.5cc/kg/hr

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

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

EGDT Algorithm: The First 6 Hours: DO2 = [1.39 x Hb x SaO2 + (0.003 x PaO2)] x CO

Vasopressors Alpha 1 Norepinephrine Epinephrine vasopressin

Vasopressors First line: Norepinephrine (Levophed) Second line: Epinephrine Third line: Vasopressin (0.04 units/min fixed dose)

Protocol for Early Goal-Directed Therapy DO2 = [1.39 x Hb x SaO2 + (0.003 x PaO2)] x CO

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

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: ProCESS trial- NEJM 2014- US ARISE trial- NEJM 2014- Australia ProMISe trial- NEJM 2015- UK

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: ProCESS trial- NEJM 2014- US ARISE trial- NEJM 2014- Australia ProMISe trial- NEJM 2015- UK * Achieving specific goals did not improve mortality * Fewer transfusions in non-EGDT groups * Shorter LOS in ICU in non-EGDT groups No difference in 60/90 day mortality between patients randomized to receive EGDT from standard care

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 SCVO2 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

Surviving Sepsis Campaign 2015 Update Within 3 Hours of Identifying Sepsis: Measure lactic acid Obtain blood cultures before antibiotics Start broad-spectrum antibiotics Administer 30cc/kg crystalloid for low BP or lactate > 4 Within 6 Hours of Identifying Sepsis: Vasopressors for hypotension refractory to initial resuscitation for goal MAP ≥ 65 For persistent hypotension despite resuscitation (septic shock!) or lactate > 4, check: - CVP (goal ≥ 8)* - ScvO2 (goal ≥ 70%)* Reassess volume status and tissue perfusion clinically (vitals, capillary refill, pulse, skin), OR by CVP, ScvO2 or CV ultrasound 7. Repeat lactate if initially elevated

UCI Severe Sepsis Order Set

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

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 37.8C (100.0F), 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 WBC 16,700 Plts 110,000 Cr: Normal Electrolytes: normal ECG: sinus tachycardia

What is the next best step? Hydrocortisone 50mg IV q6H IV fluid bolus Norepinephrine Two units RBCs

What is the next best step? Hydrocortisone 50mg IV q6H IV fluid bolus Norepinephrine Two units RBCs