Sepsis Update Allina Critical Care Conference February 28, 2018

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Sepsis Update Allina Critical Care Conference February 28, 2018 Sandy Fritzlar, MD Medical Director of the Allina Sepsis Program Emergency Care Consultants OBJECTIVES A brief HISTORY of Sepsis Understand the PATHOPHYSIOLOGY of Sepsis Improve Recognition and Outcomes for Severe Sepsis and Septic Shock patients: 1. Learn the DIAGNOSTIC CRITERIA for the clinical stages of sepsis 2. Discuss the management of the sepsis spectrum (SEPSIS BUNDLE) 3. Define Time Zero which is the start of Rapid Resuscitation Present Sepsis teaching CASES 2

OBJECTIVES A brief HISTORY of Sepsis Understand the PATHOPHYSIOLOGY of Sepsis Improve Recognition and Outcomes for Severe Sepsis and Septic Shock patients: 1. Learn the DIAGNOSTIC CRITERIA for the clinical stages of sepsis 2. Discuss the management of the sepsis spectrum (SEPSIS BUNDLE) 3. Define Time Zero which is the start of Rapid Resuscitation Present Sepsis teaching CASES 3 OBJECTIVES A brief HISTORY of Sepsis Understand the PATHOPHYSIOLOGY of Sepsis Improve Recognition and Outcomes for Severe Sepsis and Septic Shock patients: 1. Learn the DIAGNOSTIC CRITERIA for the clinical stages of sepsis 2. Discuss the management of the sepsis spectrum (SEPSIS BUNDLE) 3. Define Time Zero which is the start of Rapid Resuscitation Present Sepsis teaching CASES 4

OBJECTIVES A brief HISTORY of Sepsis Understand the PATHOPHYSIOLOGY of Sepsis Improve Recognition and Outcomes for Severe Sepsis and Septic Shock patients: 1. Learn the DIAGNOSTIC CRITERIA for the clinical stages of sepsis 2. Discuss the management of the sepsis spectrum (SEPSIS BUNDLE) 3. Define Time Zero which is the start of Rapid Resuscitation Present Sepsis teaching CASES 5 OBJECTIVES A brief HISTORY of Sepsis Understand the PATHOPHYSIOLOGY of Sepsis Improve Recognition and Outcomes for Severe Sepsis and Septic Shock patients: 1. Learn the DIAGNOSTIC CRITERIA for the clinical stages of sepsis 2. Discuss the management of the sepsis spectrum (SEPSIS BUNDLE) 3. Define Time Zero which is the start of Rapid Resuscitation Present Sepsis teaching CASES 6

OBJECTIVES A brief HISTORY of Sepsis Understand the PATHOPHYSIOLOGY of Sepsis Improve Recognition and Outcomes for Severe Sepsis and Septic Shock patients: 1. Learn the DIAGNOSTIC CRITERIA for the clinical stages of sepsis 2. Discuss the management of the sepsis spectrum (SEPSIS BUNDLE) 3. Define Time Zero which is the start of Rapid Resuscitation Present Sepsis teaching CASES 7 OBJECTIVES A brief HISTORY of Sepsis Understand the PATHOPHYSIOLOGY of Sepsis Improve Recognition and Outcomes for Severe Sepsis and Septic Shock patients: 1. Learn the DIAGNOSTIC CRITERIA for the clinical stages of sepsis 2. Discuss the management of the sepsis spectrum (SEPSIS BUNDLE) 3. Define Time Zero which is the start of Rapid Resuscitation Present Sepsis teaching CASES 8

HISTORY OF SEPSIS 9 SEPSIS: since ancient times SEPSIS is not a new condition - 5000 years ago: Ancient Egyptians described deaths from infections with conditions resembling what we call sepsis today 1-2400 years ago: Hippocrates, the ancient Greek physician, gave this condition the name of SEPSIS. 1 Derived from sipsi Greek work which means rotten - Today: despite evolving definitions and published treatment guidelines the impact on society is still great in terms of morbidity, mortality and cost 1 Borweo, Jh, et al. The history of sepsis from ancient Egypt to XIX century. INTECH open Acess Pubulisher, 2012. 10

SEPSIS: Today Impact of Sepsis in the US (2013) 1 1 1 2 1 Torio, CM, et al. National Inpatient Hospital Costs: the most expensive conditions in Payer; HCUP Statistical Brief #160, 2015 2 Sutton, JP, et al. Trends in septicemia hospitalizations and readmissions in selected HCUP states, 2005 2010. Taken from: http;//www.ncbi.nom.nih.gove/books/nbk169246 11 SEPSIS GOALS 12

GOALS: Early Recognition & Rapid Resuscitation of SEVERE sepsis & septic SHOCK Bedside nurses to screen for sepsis every shift. BKJ7 Rapid Response team to look for acute organ failure with every + sepsis screen: - NOTE: Acute organ failure with a positive sepsis screen is evidence of severe sepsis or shock UNLESS the physician attributes the organ dysfunction to something other than an infection Physicians to institute the sepsis bundle orders for patients with organ dysfunction and suspected infection. 13 13 PATHOPHYSIOLOGY OF SEPSIS 14

Slide 13 BKJ7 I changed this around a bit to get rid of the word "sepsis"--keep or toss the suggestion Boyer, Kelley J, 4/1/2016

SEPSIS: What is it? Sepsis occurs when the normal human immune response to bacterial, viral or fungal infection becomes dysfunctional and triggers widespread inflammation that results in tissue damage that leads to organ failure, shock and death 15 15 1 Gary, T, et al. The Evolving Definition of Sepsis, 2015. SEPSIS: The clinical stages Infection SIRS Sepsis Severe Sepsis Septic Shock 16 16

SEPSIS: The clinical stages SEPSIS =Infection + SIRS Systemic Inflammatory Response Syndrome (SIRS): The body s response to an insult, characterized by: HR RR Temp WBC count NOTE: SIRS can be caused by infection, or trauma, or stress SIRS Sepsis 18 SEPSIS: The clinical stages Sepsis SEVERE SEPSIS SEVERE SEPSIS = Infection + Organ Dysfunction (The development of potentially reversible organ dysfunction in a person with infection) 19

SEPSIS: The clinical stages Sepsis Severe Sepsis SEPTIC SHOCK SEPTIC SHOCK = Infection + circulatory failure (Circulatory failure is characterized by inadequate oxygen delivery to meet the metabolic demands leading end organ ischemia) 20 SEPSIS: The clinical stages Sepsis Severe Sepsis Septic Shock DEATH (DEATH is the end result of inadequate oxygen delivery to meet the metabolic needs leading to end organ ischemia) 21

DIAGNOSTIC CRITERIA 22 Diagnostic Criteria: Sepsis Infection or strongly suspected Infection + 2 of the following abnormalities Temp >100.9 (38.3 C) or <96.8 (36 C) HR >90 RR >20 WBC >12,000 or <4,000 23

Diagnostic Criteria: Severe Sepsis Infection or strongly suspected + NEW Organ Dysfunction (Patient may have severe sepsis with <2 SIRS criteria): 24 - Cardiovascular compromise: ONE documented hypotensive reading (SBP < 90 or MAP < 65) which resolves with 30 ml/kg fluid bolus - Metabolic compromise: w/ Lactate > 2.0 - Acute respiratory failure: use of invasive or non invasive mechanical ventilation to support breathing (CPAP is acute; chronic vent is NOT acute) - Acute Kidney Injury: Cr >2 (elevated Cr in ESRD on dialysis is NOT acute) - Acute Liver Injury: Bilirubin >2 - Acute Hematologic dysfunction: Platelets < 100,000 INR > 1.5 (elevated INR on Coumadin is NOT acute) Diagnostic Criteria: Severe Sepsis Infection or strongly suspected + NEW Organ Dysfunction (Patient may have severe sepsis with <2 SIRS criteria): 25 - Cardiovascular compromise: ONE documented hypotensive reading (SBP < 90 or MAP < 65) which resolves with 30 ml/kg fluid bolus - Metabolic compromise: > 2.0 - Acute respiratory failure: use of invasive or non invasive mechanical ventilation to support breathing (CPAP is acute; chronic vent is NOT acute) - Acute Kidney Injury: Cr >2 (elevated Cr in ESRD on dialysis is NOT acute) - Acute Liver Injury: Bilirubin >2 - Acute Hematologic dysfunction: Platelets < 100,000 INR > 1.5 (elevated INR on Coumadin is NOT acute)

Diagnostic Criteria: Severe Sepsis Infection or strongly suspected + NEW Organ Dysfunction (Patient may have severe sepsis with <2 SIRS criteria): 26 - Cardiovascular compromise: ONE documented hypotensive reading (SBP < 90 or MAP < 65) which resolves with 30 ml/kg fluid bolus - Metabolic compromise: Lactate > 2.0 - Acute respiratory failure: use of invasive or non invasive mechanical ventilation to support breathing (CPAP is acute; chronic vent is NOT acute) - Acute Kidney Injury: Cr >2 (elevated Cr in ESRD on dialysis is NOT acute) - Acute Liver Injury: Bilirubin >2 - Acute Hematologic dysfunction: Platelets < 100,000 INR > 1.5 (elevated INR on Coumadin is NOT acute) Diagnostic Criteria: Severe Sepsis Infection or strongly suspected + NEW Organ Dysfunction (Patient may have severe sepsis with <2 SIRS criteria): 27 - Cardiovascular compromise: ONE documented hypotensive reading (SBP < 90 or MAP < 65) which resolves with 30 ml/kg fluid bolus - Metabolic compromise: Lactate > 2.0 - Acute respiratory failure: use of invasive or non invasive mechanical ventilation to support breathing (chronic vent is NOT acute) - Acute Kidney Injury: Cr >2 (elevated Cr in ESRD on dialysis is NOT acute) - Acute Liver Injury: Bilirubin >2 - Acute Hematologic dysfunction: Platelets < 100,000 INR > 1.5 (elevated INR on Coumadin is NOT acute)

Diagnostic Criteria: Severe Sepsis Infection or strongly suspected + NEW Organ Dysfunction (Patient may have severe sepsis with <2 SIRS criteria): 28 - Cardiovascular compromise: ONE documented hypotensive reading (SBP < 90 or MAP < 65) which resolves with 30 ml/kg fluid bolus - Metabolic compromise: Lactate > 2.0 - Acute respiratory failure: use of invasive or non invasive mechanical ventilation to support breathing (chronic vent is NOT acute) - Acute Kidney Injury: Cr >2 (elevated Cr in ESRD on dialysis is NOT acute) - Acute Liver Injury: Bilirubin >2 - Acute Hematologic dysfunction: Platelets < 100,000 INR > 1.5 (elevated INR on Coumadin is NOT acute) Diagnostic Criteria: Severe Sepsis Infection or strongly suspected + NEW Organ Dysfunction (Patient may have severe sepsis with <2 SIRS criteria): 29 - Cardiovascular compromise: ONE documented hypotensive reading (SBP < 90 or MAP < 65) which resolves with 30 ml/kg fluid bolus - Metabolic compromise: Lactate > 2.0 - Acute respiratory failure: use of invasive or non invasive mechanical ventilation to support breathing (chronic vent is NOT acute) - Acute Kidney Injury: Cr >2 (elevated Cr in ESRD on dialysis is NOT acute) - Acute Liver Injury: Bilirubin >2 - Acute Hematologic dysfunction: Platelets < 100,000 INR > 1.5 (elevated INR on Coumadin is NOT acute)

Diagnostic Criteria: Severe Sepsis Infection or strongly suspected + NEW Organ Dysfunction (Patient may have severe sepsis with <2 SIRS criteria): 30 - Cardiovascular compromise: ONE documented hypotensive reading (SBP < 90 or MAP < 65) which resolves with 30 ml/kg fluid bolus - Metabolic compromise: Lactate > 2.0 - Acute respiratory failure: use of invasive or non invasive mechanical ventilation to support breathing (chronic vent is NOT acute) - Acute Kidney Injury: Cr >2 (elevated Cr in ESRD on dialysis is NOT acute) - Acute Liver Injury: Bilirubin >2 - Acute Hematologic dysfunction: Platelets < 100,000 INR > 1.5 (elevated INR on Coumadin is NOT acute) Diagnostic Criteria: Septic Shock Infection or strongly suspected + ONE of the following (Patient may have septic shock with <2 SIRS criteria): 1. Hypotension after 30cc/kg: 2 consecutive low BP readings (MAP < 65, SBP < 90) after 30cc/kg has been given 2. Or Lactate 4.0 31

THE SEPSIS BUNDLE 32 The Sepsis Bundle: 7 Elements 1. Lactate done at time of positive sepsis screen 2. Two blood cultures before antibiotics 3. Appropriate broad spectrum antibiotics 4. IV fluids 30 ml/kg (NS or LR) for: - Hypotension (MAP < 65 or SBP < 90) - Lactate 4.0 5. Repeat lactate, if initial lactate was elevated - (> 2.1 venous) 6. Vasopressors for hypotension after 30 cc/kg 7. Fluid Status Reassessment (for all shock patients) 3 Hour RAPID Resuscitation Bundle 6 Hour Resuscitation Bundle 33 33

#1 Bundle Element: Initial Lactate INITIAL LACTATE: Lactate is elevated in SEVERE sepsis (2.1 3.9) and septic SHOCK ( 4.0) higher lactate levels portending higher mortality. 1 Intermediate lactate levels (2.5 3.9) are associated with an increased risk of death, independent of the presence of hypotension 2,3 1 Jones, AE. Lactate clearance for assessing response to resuscitation in severe sepsis. Acad Emerg Med, 2013;20(8):844 847. 2 Puskarich, MA, etal. Prognosis of ED patients with suspected infection and intermediate lactate levels: a systematic review. J Crit Care, 2014;29:334 339. 3 Howell, MD, etal. Occult hypoperfusion and mortality in patients with suspected infection. Inten Care Med, 2007;33:1892 1899. 34 #1 Bundle Element: Initial Lactate INITIAL LACTATE: 35 Howell, MD, etal. Occult hypoperfusion and mortality in patients with suspected infection. Inten Care Med, 2007;33:1892 1899.

#1 Bundle Element: Initial Lactate 36 INITIAL LACTATE: A lactate of <2.0 is normal. Any lactate >2.1 is ABNORMAL NON sepsis causes of elevated lactate: Hypovolemic shock Cardiogenic shock Liver dysfunction Medications (metformin, etc) Prolonged tourniquet time Lactate Sepsis #2 Bundle Element: Antibiotics ANTIBIOTICS: Antibiotics are an emergency medication in patients with severe sepsis and septic shock Every hour antibiotics are delayed MORTALITY RISES by 7% in sepsis patients with hypotension. 1,2 37 1 Kumar et al. Crit Care Med 2006; 34:1589 1596 2 Ferrer et al. Crit Care Med 2014. 42:1749 1755.

#2 Bundle Element: Antibiotics ANTIBIOTICS: Appropriate antibiotics must be started 180 min of Time Zero. Do not delay abx > 45 mins for BC collection GOAL: start antibiotics within 60 minutes of the order SEPSIS ORDER SET: should be used to ensure appropriate broad spectrum antibiotics are given 38 #3 Bundle Element: Blood Cultures BLOOD CULTURES: 2 blood cultures are recommended Never delay ABX >45 minutes to draw BC What if blood cultures are difficult to draw? Start the ABX at 45 minutes after the order even if blood cultures could not be obtained 39

#3 Bundle Element: Blood Cultures BLOOD CULTURES: Can you give ABX before BC & still PASS CMS element #3? YES: If the provider documents the reason Smart Phrase:.sepsisbloodculture 40 #3 Bundle Element: Blood Cultures BLOOD CULTURES: Can you give ABX before BC & still PASS CMS element #3? YES: If the provider documents the reason Smart Phrase:.sepsisbloodculture 41

#4 Bundle Element: Fluids (if ) IV FLUIDS: 3 recent fluid trials published 1 3 POPULATION STUDIED: ED patients with sepsis & hypotension or sepsis w/ lactate 4.0 FINDINGS: No survival benefit to protocolized resuscitation with CVP, ScvO 2 ; Hgb; Dobutamine compared with patients that were fluid resuscitated Virtually all patients (study and control groups) received 30 ml/kg in first 6 hours, and at least that much more between hours 6 48 TAKE HOME POINT: 30 ml/kg is a start for most patients with severe sepsis & septic shock 42 1 ProCESS Trial. NEJM, 2014;370(18):1683 93. 2 Arise Trial. NEJM, 2014;371(16):1496 506. 3 ProMISe Trial. NEJM, 2015;372(14):1301 11. #4 Bundle Element: Fluids (if ) IV FLUIDS: 30 ml/kg should be given if: One single hypotensive reading (SBP <90 or MAP <65) or Lactate 4 Most patients can tolerate and need 30cc/kg. If concern for fluid overload, assess fluid responsiveness to guide fluid resuscitation. There are 3 different ways to assess fluid responsiveness: 1. PLR via NICOM 2. bedside Cardiovascular US 3. insert a CL and measure the CVP & SCvO2 (not recommended) 43

#5 Bundle Element: Repeat Lactate (if) REPEAT LACTATE: Draw a 2 nd lactate after fluids given, if the initial lactate was >2.1. Clinical Significance: The change in lactate is used to determine if patient is improving or decompensating. Goal = Lactate Lactate clearance of 10% in 2 3 hours demonstrates an effective response to resuscitation 1 44 1 Jones, AE. Lactate clearance for assessing response to resuscitation in severe sepsis. Acad Emerg Med, 2013;20(8):844 847. #6 Bundle Element: Vasopressors (if) VASOPRESSORS: For patients that remain hypotensive after 30ml/kg start vasopressors as soon as possible! LEVOPHED (NE) is the drug of choice. If central access will delay starting vasopressors, consider starting vasopressors at low doses via the peripheral IV while preparing for central access. 45 For patients that remain hypotensive after 30ml/kg more IV fluids may still be needed Vasopressors should NOT be delayed even if more fluids are being given.

#7 Bundle Element: Shock Reassessment (if) SHOCK REASSESSMENT EXAM: The Goal of Resuscitation: Administration of fluids and pressers to achieve adequate tissue perfusion to the organs and therefore reduce morbidity and mortality Clinical Significance: The reassessment is a cardiovascular exam focused on determining if the patient has achieved adequate tissue perfusion AFTER 30cc/kg. 46 #7 Bundle Element: Shock Reassessment (if) SHOCK REASSESSMENT EXAM: FOR CMS: The physician must document a shock reassessment exam AFTER 30cc/kg (within 6hrs of Time Zero) or the case fails the 7 th and final bundle element 47

TIME ZERO 48 Time Zero Time Zero is when the clock starts for rapid resuscitation of patients with Severe Sepsis or Septic Shock Time Zero is the time at which the patient meets the diagnostic criteria for Severe Sepsis or Shock. Time Zero = the time when the physician suspects an infection & organ dysfunction is present 49

Time Zero: CMS definition Time Zero is when the clock starts for rapid resuscitation of patients with Severe Sepsis or Septic Shock Time Zero is the time at which the patient meets the diagnostic criteria for Severe Sepsis or Shock. Time Zero = the time when the physician suspects an infection & organ dysfunction is present 50 Time Zero: CMS definition Time of organ dysfunction is easy to identify: Either Time of abnormal lab result Or. Time of hypotension Once NEW organ dysfunction is found: It is imperative for the physician to decide if infection is suspected and if so, start the sepsis resuscitation bundle 51

SEPSIS CASES Breanne.Loesch@allina.com Steps to Diagnosing and Treating Sepsis 1. Is there new or worsening suspected infection? 2. Are there signs of systemic inflammatory response? 3. Is there evidence of organ dysfunction? 4. Is there signs of distributive shock? o Lactate 4.0 o Persistent hypotension = hypotension (SBP < 90, MAP < 65) AFTER 30 ml/kg fluid bolus of isotonic fluids (NS or LR) Infection Sepsis Severe Sepsis Septic Shock 53

Case Study #1 Inpatient Screening and Sepsis Severity 60 yo F admitted to Med/Surg unit with failure to thrive, falls, headaches, nausea. Patient has been tolerating a regular diet, is saline locked and working with therapy with a plan to dc to a community TCU this afternoon. AM vitals on morning of discharge is: - 0700: Temp 102.9, RR 22, HR 103, BP 110/70 (83), 94% RA Objective signs/symptoms upon nurses initial assessment: - Patient is feeling weaker this morning, has a harsh, loose, productive cough and didn t sleep well last night because of it. She just wants you to finish up quickly and let her go back to sleep. What would you do next? - Patient has 2 SIRS and a possible new infection due to weakness, fatigue, productive cough, a rapid response should be called to work up the patient for sepsis and the charge nurse on the unit and provider should be notified. 54 Rapid Response Rapid Response: assesses patient and orders labs to look for organ dysfunction. Provider contacted: asked if any other orders are suggested. CXR ordered. Sepsis Laboratory Findings: - WBC 13.3 - Lactate 3.2 - Cr 1.1 - Platelets 230 - INR 1.0 - Total bilirubin 1.3 Is there organ dysfunction? Yes 55

Sepsis Laboratory Findings: - WBC 13.3 - Lactate 3.2 - Cr 1.1 - Platelets 230 - INR 1.0 - Total bilirubin 1.3 56 What is the severity of sepsis? - Sepsis, severe sepsis or septic shock Severe Sepsis Treatment Now what? - Nurse should notify provider of abnormal result (lactate >2). - Provider should recognize there is acute organ dysfunction PLUS new infection (infiltrate on CXR) and use a sepsis orderset to order antibiotics and complete sepsis bundle. - Nurse should complete the sepsis bundle orders and continue to monitor the patient closely for hypotension 2 IV access s should be confirmed to ensure emergent and immediate completion of the sepsis bundle. Phlebotomy paged for blood cultures if not already done Pharmacy to send Antibiotics ASAP 57

Treatment What is the expected treatment? - DRAW Blood cultures x 2 prior to starting antibiotics Recommended to 2 blood culture sets collected simultaneously, sequentially, from 2 different peripheral sites. If it is a difficult draw a central line, PICC or port may be used. If antibiotics are unable to be drawn due to a difficult draw it is appropriate to start antibiotics after 45 minutes of attempting cultures. Continue to attempt to draw blood cultures and notify the provider to document reason antibiotics given prior to blood cultures. It is also appropriate for the nurse to document this reason for not being able to complete the order. 58 START Broad spectrum antibiotics (started within 45 minutes of order) Gold standard is to start antibiotics at the same time If there is limited IV access : Broad spectrum antibiotic should be started first. Remember FAST is FIRST Broad Spectrum antibiotics include: Piperacillin/Tazobactam (Zosyn) Ampicillin/Sulbactam Carbapenem: Imipenem/Cilastatin, Meropenem Cephalosporins: Cefazolin, Ceftriaxone, Cefepime Fluoroquinolones: Ciprofloxacin, Levofloxacin 59 59

GIVE IV fluids per provider order expect some amount of fluids will be ordered due to elevated lactate. 15 ml/kg of NS is typical. Typical fluid orders are to be completed within 30 60 minutes of order to assist in rapid resuscitation - DRAW a repeat lactate AFTER fluids are completed. - Ask for assistance in completing bundle elements quickly Outcomes - Blood pressure remains normotensive, HR and fever improve, patient remains on Med/Surg floor due to early screening and rapid interventions 60 Case Review #2 91 yo female presents to the ED with behavior change, lethargic, and shaking. Groin cellulitis suspected ED Triage Vitals 2115: Temp 101.8, HR 105, RR 28, BP 85/48 (60) What would you do next? 2 SIRS + possible infection; use ED Triage order set to order lactate and other sepsis labs screening for organ dysfunction Notify Provider 61

Lab Results @ 2200 WBC 16.7 Lactate 4.3 Cr 0.65 Total bilirubin 2.1 INR 1.3 Plt 86 Is there organ dysfunction? 62 What is the severity of sepsis? Sepsis, severe sepsis or septic shock Septic Shock Now what? Nurse should notify provider of abnormal result (lactate >2). Provider should recognize there is acute organ dysfunction PLUS new infection (cellulitis) and use a sepsis order set to order antibiotics and complete sepsis bundle. Nurse should complete the sepsis bundle orders and continue to monitor the patient closely for hypotension What is the expected treatment? Blood cultures x 2 drawn at 2215 and 2220 Antibiotics started within 45 minutes of order started at 2130 30 ml/kg IVF bolus given in 60 minutes started at 2205 Repeat lactate ordered for 0000 2 hours after lactate was resulted 63

64 30 ml/kg fluids was completed at 2245. IV bolus documented as complete and monitoring for persistent hypotension BP @ 2250 85/46 (59) BP @ 2255 84/51 (62) Persistent Hypotension recognized vasopressors are ordered and started as soon as the medication is verified by pharmacy at 2310. Titrate vasopressor to SBP > 90 and MAP > 65 to ensure perfusion of vital organs Patient is in SEPTIC SHOCK Anticipate admission to ICU Case Review #3 Elderly patient with a history significant for traumatic brain injury and quadriplegia who presents to the ED for evaluation of fever arrives via EMS EMS REPORT: found down with decreased LOS, diaphoretic and warm at living facility. BS was normal and HR 140. VS on arrival @ 2000 Temp 102.1, HR 142, RR 18, BP 99/67 (78), 88% RA Assessment by provider rhonchi in both lungs 65

Clinical Course Provider uses ED Sepsis order set @2015: Labs including Lactate, CBC, CMP, INR, LFT, Blood Cultures, and UA Chest Xray 30 ml/kg NS Fluid Bolus over 30 60 minutes Vanco and Primaxin Labs result at 2100 istat lactate 2.6 WBC 18 Plt 200 INR 1.0 Cre 0.7 Bili 0.4 66 66 CT scan at 2115 reveals bilateral infiltrates in the lower lobes AND a 5 x 10 mm stone in the right renal pelvis with minimal hydronephrosis, Urinalysis ordered based on CT findings suggests urinary tract infection Fluids (1836 ml) given 2030 2130 Provider notified fluids are finished and vital signs are monitored for persistent hypotension Time 2130 2135 Blood Pressure 78/54 (62) 89/54 (67) Persistent Hypotension = SEPTIC SHOCK START VASOPRESSORS!! 67

Job Well Done! Norepinephrine started at 2200 at 5 mcg/min via peripheral IV and provider preps for a central line to continue pressors in the ICU NICOM shows patient is fluid responsive with a 500 ml fluid bolus. Patient given 1 L and NICOM was repeat after. Non responsive. Patient was weaned off levophed at 0730 the next morning. Discharged 2 days later back to her living facility 68 Case Study #4 50 y.o. female with history of epilepsy on Keppra arrives to ED via EMS due to seizures Per EMS patient was hypotensive on arrival post ictal VS @1900 on ED ARRIVAL: Temp 99.6, HR 82, RR 12, BP 79/51 (60), 90% RA Assessment by provider finds decreased LOC however patient received Ativan and versed en route prn for seizures 69

70 On arrival at 2100 provider orders diagnostic labs, seizure precautions and 2 L fluid bolus 2130 labs result: WBC 8.1 Plt 203 INR 1.1 Cre 1.11 Blood pressure continues to trend down 1900 1930 2000 2030 2100 2130 BP 78/53 81/51 75/52 74/50 72/47 75/50 MAP 61 60 60 56 55 59 At 2200 provider orders lactate, 1 L fluid bolus, chest xray, blood cultures, UA, troponin and 1 L of fluids It was a full and busy ED, labs drawn at 2300 2345 Lactate results at 3.5 30 ml/kg fluid bolus complete at 2230 71 Chest xray reveals pneumonia at 2130 At 2145 Vanco and Zosyn were ordered by the provider If there was infection on arrival AND hypotension on arrival Time Zero is? 1900 due to hypotension Vanco started at 2155 (2 h 55 min after time zero) Zosyn started at 2230 (3 h 30 min after time zero) Levo started at 2230 2215 2230 2245 2300 2315 2330 BP 80/51 78/40 97/52 92/48 89/52 94/55 MAP 61 57 71 66 66 71 Patient transfers to the ICU at 0100 after a central line is placed Lactate was ordered at 0030 while still in the ED, ICU nurse finds the order at 0200, waits to drawn lab with morning labs at 0400. WBC was 14.8 on morning labs. Blood cultures grew out positive

What are our learnings from this case? Time Zero = the time when the physician suspects an infection & organ dysfunction is present 1900 with hypotension as the organ dysfunction Lactate = ordered at 2000, results 3.5 at 2145 (2h 45 min) Pass but untimely BROAD Spectrum antibiotics should always be hung first = Fail Every hour antibiotics are delayed MORTALITY RISES by 7% in sepsis patients with hypotension ALWAYS think infection in the presence of organ dysfunction ALWAYS look for organ dysfunction when there is an infection 72 Steps to Diagnosing and Treating Sepsis 1. Is there new or worsening suspected infection? 2. Are there signs of systemic inflammatory response? 3. Is there evidence of organ dysfunction? 4. Is there signs of distributive shock? o Lactate 4.0 o Persistent hypotension = hypotension (SBP < 90, MAP < 65) AFTER 30 ml/kg fluid bolus of isotonic fluids (NS or LR) Infection Sepsis Severe Sepsis Septic Shock 73

MHA s road maps provide hospitals and health systems with evidence-based recommendations and standards for the development of topicspecific prevention and quality improvement programs, and are intended to align process improvements with outcome data 74

thank you! Sandy.Fritzlar@allina.com Breanne.Loesch@allina.com