Sepsis and Septic Shock Sepsis is a potentially life-threatening complication of an infection. It occurs when chemicals released into the bloodstream to fight the infection trigger inflammation throughout the body. This inflammation can trigger changes that can damage multiple organ systems, causing them to fail. If sepsis progresses to septic shock, blood pressure drops dramatically, which may lead to death. Important components of managing patients with severe sepsis are: RECOGNIZE the severity of the infection, RESUSCITATE all patients with shock or high lactate, REASSESS treatment effectiveness, and PREVENT complications.

Algorithm 1: Recognize and Resuscitate Time Zero – On Presentation: RECOGNIZE SEVERITY OF INFECTION Patient presents with suspected infection or acute organ dysfunction or mental status changes or Modified Early Warning Score (MEWS) > 4 Does patient have at least 2 SIRS criteria and suspected infection?* Temp < 96.8 F (36 C) or > 100.4 F (38 C) HR > 90 bpm RR > 20 breaths/min or PaCO2 < 32 or need for mechanical ventilation WBC > 12,000 or < 4,000 or > 10% bands

· · · ·

YES

Consider mobilizing additional resources: Sepsis Alert Policy and Procedure, ERT

NO Does not meet criteria for sepsis, but consider presumptive treatment if no alternate diagnosis apparent.

· · ·

First 0-6 Hours Lactate > 4 mmol/L? or SBP < 90 mmHg after fluid challenge of 1-2 liters or Need for vasopressors? NO

·

Additional volume resuscitation based upon response of clinical factors to fluid challenge: ○ MAP ○ Urine output ○ Oxygenation ○ Peripheral perfusion

YES

SEPSIS

RESUSCITATE First 0-2 Hours: Initial Resuscitation and Antibiotics Obtain appropriate IV access (2 peripheral 18-gauge IVs or central line as indicated) · Blood and urine cultures (If blood cultures cannot be obtained – DO NOT delay antibiotic administration) · Administer broad-spectrum antibiotics) STAT - GOAL: < 1 hour · Antibiotic selection should be made in accordance with ASP best antibiotic practice (see grid) · IV fluid challenge of 1000-2000 ml (over 30-60 min) if no clinical contraindications · Norepinephrine to keep MAP > 65 mmHg · Draw labs: lactate, chem 7, CBC with diff., platelets, PT/PTT, INR, albumin, ALT · Other cultures or antigens as appropriate · Consider alternative etiologies of hemodynamic instability / shock · Source control (e.g., remove or address infection source) ·

SEPTIC SHOCK

Goal-Directed Resuscitation (See Appendix 1a and b) Goals of resuscitation to include: · MAP > 65 mmHg · Urine output > 0.5 ml/kg/h · Volume repletion as determined by clinical exam, ultrasound assessment, or CVP monitoring Additional resuscitation goals per core measures include: · Within 6 hours of presentation, repeat lactate level measurement if initial lactate level is elevated · Within 3 hours of presentation, resuscitate with 30 ml/kg crystalloid fluids · IF hypotension persists after fluid administration, received within six hours of presentation of septic shock administer vasopressors See Algorithm 2 for Management, Secondary Survey, and Maintenance / Recovery Phase Key: CVP = central venous pressure, MAP = mean arterial pressure, SIRS = sepsis inflammatory response syndrome

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Algorithm 2: Reassess and Prevent Complications

First 0-24 Hours: Initial Management Phase and Secondary Survey REASSESS · ·

Complete H&P Additional diagnostic testing ○ Causes of organ failure ○ Site of infection ○ Source control (remove or address infection source)

Search for additional organ failures · · · · · ·

Respiratory – ABG Hematologic – Platelets Coagulopathy – INR, PT Hepatic – Bilirubin, AST Neurologic – GCS, RASS and/or delirium Renal – Creatinine, urine output

Vasopressor refractory shock? · Need for > 50% maximum dose of single vasopressor or · Need for multiple vasopressors

ARDS? (See Appendices 2 and 3)

NO

YES

Consider corticosteroids (See Appendix 4)

Lower tidal volume ventilation (e.g., < 6 ml/kg PBW) (See Appendix 2)

Remainder of Hospitalization: Maintenance / Recovery Phase PREVENT COMPLICATIONS ·

Review cultures / source of infection and tailor antibiotics

·

Remove central line within 2 hours of positive cultures for Staphylococcus aureus, gram negative bacteria or yeast blood stream infection

·

Avoid ventilator-induced lung injury and encourage ventilator liberation: ○ Avoid injurious tidal volumes (e.g., use < 8 mL/kg PBW in non-ARDS or < 6 mL/kg PBW in all ARDS) ○ Daily assessment for spontaneous breathing trials ○ Minimization of continuous sedation according to unit protocol ○ Consider goal-directed diuresis when shock has resolved

·

Rehabilitation / psychological counseling

·

Consider glucose control (target: 140-180 mg/dl)

·

Avoid nosocomial infections: ○ Hand washing ○ Semi-recumbent positioning ○ Oral hygiene ○ Restrictive transfusion practices

·

Appropriate stress ulcer prophylaxis

·

Appropriate thromboembolism prophylaxis

·

Goals-of-care discussions

·

Appropriate immunizations

Key: ARDS = acute respiratory distress syndrome, PBW = predicted body weight.

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Reference 







Surviving Sepsis Campaign. (2013). International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Intensive Care Medicine. 39(2):165-228. The ProCESS Investigators. (2014). A Randomized Trial of Protocol-Based Care for Early Septic Shock. The New England Journal of Medicine. 370:1683-1693. The ARISE Investigators and the ANZICS Clinical Trials Group. (2014). Goal-Directed Resuscitation for Patients with Early Septic Shock. The New England Journal of Medicine. 371:1496-506. The ProMISe Investigators. (2015). Trial of Early, Goal-Directed Resuscitation for Septic Shock. The New England Journal of Medicine. 372:1301-1311.

Order Sets       

ED: Sepsis Alert [2137] ED: Sepsis Alert Triage Protocol [1279] MIC: Initial Sepsis Management [2203] MIC: Ongoing Sepsis Management [2205] INF: Immunocompromised - Severe Sepsis Antibiotic Management [2596] INF: Normal Host - Severe Sepsis Antibiotic Management [2598] MIC: Admission MICU [2216]

Quality Measures Compliance with Early Management Bundle-Severe Sepsis/Septic Shock. Percent of patients who received ALL of the following: 

Received within three hours of presentation of severe sepsis: o Initial lactate level measurement o Broad spectrum or other antibiotics administered o Blood cultures drawn prior to antibiotics



AND received within six hours of presentation of severe sepsis: o Repeat lactate level measurement if initial lactate level is elevated



AND ONLY IF septic shock present: o Received within three hours of presentation of septic shock:  Resuscitation with 30 ml/kg crystalloid fluids



AND ONLY IF hypotension persists after fluid administration, received within six hours of presentation of septic shock: o Vasopressors o Repeat volume status and tissue perfusion assessment consisting of either:



A focused exam including all of the following:  Vital signs  Cardiopulmonary exam  Capillary refill evaluation  Peripheral pulse evaluation  Skin examination



Any two of the following four:  Central venous pressure measurement  Central venous oxygen measurement  Bedside cardiovascular ultrasound  Passive leg raise or fluid challenge

Guideline Authors     

Matthew Exline, MD Naeem Ali, MD Jeffrey Caterino, MD Kurt Stevenson, MD, MPH Sam Penza, MD

Guideline Approved August 19, 2015. Third Edition. Disclaimer: Clinical practice guidelines and algorithms at The Ohio State University Wexner Medical Center (OSUWMC) are standards that are intended to provide general guidance to clinicians. Patient choice and clinician judgment must remain central to the selection of diagnostic tests and therapy. OSUWMC’s guidelines and algorithms are reviewed periodically for consistency with new evidence; however, new developments may not be represented. Copyright © 2015. The Ohio State University Wexner Medical Center. All rights reserved. No part of this document may be reproduced, displayed, modified, or distributed in any form without the express written permission of The Ohio State University Wexner Medical Center.

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Appendix 1a: Goal-Directed Resuscitation In 2014, three large randomized controlled trials failed to demonstrate a benefit to protocoled resuscitation versus usual care for septic shock1-3. All trials featured patients that received early recognition and treatment for their septic shock. While, based on these trials, this guideline cannot offer a definitive evidence-based protocol for best practice for resuscitation, attention to volume resuscitation either by clinical assessment, central-venous pressure monitoring, or ultrasound assessment for volume responsiveness is essential to ensure adequate resuscitation of septic shock patients. Two potential algorithms are included from the PROCESS Trial2.

Protocol for Early Goal-Directed Therapy (EGDT)

Supplemental oxygen + endotracheal intubation and mechanical ventilation

Insert central line with oximetric port

Sedation, analgesia, and/or paralysis (if intubated)

500 cc fluid bolus if CVP < 8 mmHg

CVP

< 8 mmHg

8-12 mmHg

MAP

< 65 mmHg > 90mmHg

Vasoactive agents

NO ≥ 65 mmHg ≤ 90 mmHg

ScvO2

If HCT < 30%, transfuse PRBCs

Inotropic agents

≥ 70% ≥ 70% Goals achieved? YES Reassess Q15-30 min 1. Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. The New England Journal of Medicine. 2015;372:1301-11. 2. Pro CI, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. The New England Journal of Medicine. 2014;370:1683-93. 3. Investigators A, Group ACT, Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. The New England Journal of Medicine. 2014;371:1496-506.

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Appendix 1b: Goal-Directed Resuscitation Protocol for Standard Therapy

Supplemental oxygen + endotracheal intubation and mechanical ventilation

2 large bore (≥18g) IV’s (central line if unable to achieve)1

Sedation, analgesia, and/or paralysis (if intubated)

500-1000 ml fluid bolus* (min. initial total fluid2=2L* unless fluid replete/overload3)

SBP* Shock Index (SI) · SBP < 100 mmHg or · SI ≥ 0.8 or · On vasopressors

SBP ≥ 100 mmHg1

Isotonic IVF 250-500 ml/hr3

NO YES Fluid replete/ overload?

YES

Vasopressors 4

Hypoperfusion 5,6?

NO · · ·

Reassess Q30 min Monitor fluid overload 3 Consider recheck lactate, HCT

1. Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. The New England Journal of Medicine. 2015;372:1301-11. 2. Pro CI, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. The New England Journal of Medicine. 2014;370:1683-93. 3. Investigators A, Group ACT, Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. The New England Journal of Medicine. 2014;371:1496-506.

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Appendix 2 Acute Respiratory Distress Syndrome (ARDS)

Definition    

Acute onset of respiratory failure requiring intubation and assisted breathing. Bilateral infiltrates on chest radiograph. Hydrostatic edema not the primary cause of respiratory failure (not pulmonary edema) ARDS Severity: PaO2/FiO2 300-200(mild), 200-100(moderate), 30 cm H2O, decrease by 1 ml/kg < 2 hours until Pplat < 30 and/or at 4 ml/kg PBW. If Pplat < 25 and breath stacking, may increase tidal volume by 1 ml/kg steps to maximum 8 ml/kg if Pplat remains < 30 cm H2). If pH 7.15-7.30, may increase RR until pH > 7.30 or PaCO2 < 25 or RR = 35. If pH < 7.15, increase RR to 35. If pH remains < 7.15, tidal volume may be increased by 1 ml/kg steps until pH > 7.15 (regardless of Pplat). Consider bicarbonate infusion and/or renal replacement therapy. Set PEEP based on clinical response and to maintain Pplat < 30 cm H2O. If non-volume control modes used, exhaled tidal volume should be 6 ml/kg, except in instances listed above.

Relative contraindications to lower tidal volume ventilation in ARDS   

Pregnancy Increased intracranial pressure Sickle cell disease

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Height-Based Tidal Volumes – MALE

Height in centimeters

Height in inches

122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161

48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63

ARDS Initial Tidal Volume (6cc/kg PBW)

Non-ARDS Initial Tidal Volume (8cc/kg PBW)

Height in centimeters

Height in inches

134 139 145 150 156 161 167 172 178 183 189 194 200 205 210 216 221 227 232 238 243 249 254 260 265 271 276 281 287 292 298 303 309 314 320 325 331 336 341 347

179 186 193 201 208 215 222 230 237 244 251 259 266 273 281 288 295 302 310 317 324 332 339 346 353 361 368 375 383 390 397 404 412 419 426 433 441 448 455 463

162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201

64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79

ARDS Initial Tidal Volume (6cc/kg PBW)

352 358 363 369 374 380 385 391 396 402 407 412 418 423 429 434 440 445 451 456 462 467 473 478 483 489 494 500 505 511 516 522 527 533 538 544 549 554 560 565

Non-ARDS Initial Tidal Volume (8cc/kg PBW)

470 477 484 492 499 506 514 521 528 535 543 550 557 565 572 579 586 594 601 608 615 623 630 637 645 652 659 666 674 681 688 696 703 710 717 725 732 739 747 754

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Height-Based Tidal Volumes - FEMALE

Height in centimeters

122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161

Height in inches

48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63

ARDS Initial Tidal Volume (6cc/kg PBW)

107 112 118 123 129 134 140 145 151 156 162 167 173 178 183 189 194 200 205 211 216 222 227 233 238 244 249 254 260 265 271 276 282 287 293 298 304 309 314 320

Non-ARDS Initial Tidal Volume (8cc/kg PBW)

143 150 157 165 172 179 186 194 201 208 215 223 230 237 245 252 259 266 274 281 288 296 303 310 317 325 332 339 347 354 361 368 376 383 390 397 405 412 419 427

Height in centimeters

Height in inches

162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201

64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79

ARDS Initial Tidal Volume (6cc/kg PBW)

325 331 336 342 347 353 358 364 369 375 380 385 391 396 402 407 413 418 424 429 435 440 446 451 458 462 467 473 478 484 489 495 500 506 511 517 522 527 533 538

Non-ARDS Initial Tidal Volume (8cc/kg PBW)

434 441 448 456 463 470 478 485 492 499 507 514 521 529 536 543 550 558 565 572 579 587 594 601 609 616 623 630 638 645 652 660 667 674 681 689 696 703 711 718

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Appendix 3 Fluid Management Algorithm Acute respiratory distress syndrome (ARDS)

Patient with ARDS

MAP > 60 and no vasopressors?

YES

CVP < 4 mmHg?

YES

Fluid bolus and reassess in 1 hour

Urine output > 0.5 ml/kg/h

YES

Observe and reassess in 4 hours

Urine output < 0.5 ml/kg/h

YES

Fluid bolus and reassess in 1 hour

YES

Furosemide and reassess in 4 hours

NO

NO

Fluid resuscitation and/ or inotropes per clinician discretion

YES

Urine output < 0.5 ml/kg/h

NO

CVP 4-8 mmHg?

YES

No

Urine output > 0.5 ml/kg/h

NO

CVP > 8 mmHg?

YES

Furosemide and reassess in 1 hour

Relative contraindications/exclusions to fluid management algorithm for ARDS · Absence of CVP measurement · Burns > 40% body surface area · Acute myocardial infarction within last 30 days · Pregnancy · Renal failure requiring renal replacement therapy · Furosemide allergy Notes: 1. Fluid bolus = 15 ml/kg NS or LR (rounded to nearest 250 ml) or 1 unit PRBC or 25 grams albumin. 2. Furosemide dosing = begin with 20 mg bolus or last known effective dose. Double each subsequent dose until goal achieved (oliguria reversed or target CVP 3 mg/dl, ATN is present or CRRT being used. ○ Maximum furosemide dose = 160 mg X 3 and DO NOT exceed 620 mg/d. 3. Consider addition of an inotrope for patients with evidence of cardiac failure, poor urine output and CVP > 8. 4. Daily fluid input and output should be recorded. Source: NEJM 2006;354:2564-75. Key: ATN= acute renal failure, CRRT=continuous renal replacement therapies, CVP=central venous pressure, MAP=mean arterial pressure. PRBC=packed red blood cells

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Appendix 4 Corticosteroids in Septic Shock Guidelines Background Corticosteroids have been shown to promote the reversal of septic shock in adults, but no clear mortality benefit has been 1-2 established . Current guidelines support the use only in a select group of patients who have been deemed poorly 3 responsive to fluid resuscitation and vasopressor therapy . The ACTH stimulation test does not appear to be helpful in 2-3 identifying those patients who may benefit from intravenous corticosteroids .

Septic Shock++

Presence of vasopressor refractory shock* despite adequate volume resuscitation† YES

Consider treatment with:  

Hydrocortisone 50 mg IVP QH +/Fludocortisone 50 mcg NG Q24H

x7 days or until vasopressors discontinued

NO

Continue ongoing resuscitation measures with goals:   

MAP >= 65 Urine output ≥ 0.5ml/kg/h Adequate volume resuscitation as determined by clinical assessment

++Excludes patients with known adrenal dysfunction and those on chronic steroid therapy. *Vasopressor refractory shock is defined here as hypotension requiring high doses of a single vasopressor (>phenylephrine 7.5 mcg/kg/min, >norepinephrine 1.5 mcg/kg/min, >epinephrine 0.5 mcg/kg/min, or >dopamine 10 mcg/kg/min) or the concurrent use of more than one vasopressor (norepinephrine, epinephrine, dopamine, phenylephrine, or vasopressin) after at least 6 hours of adequate volume resuscitation.† †Adequate volume resuscitation is considered an initial administration of 20 ml/kg (or 2000 ml) of crystalloid over 60 minutes with repeat boluses based on clinical assessment, response and tolerance until other ongoing resuscitation goals have been met.

References 1. Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288:862-71. 2. Sprung C, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. NEJM 2008; 358(2):111-24. 3. Dellinger R, Levy M, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Intensive Care Med; 39(2):165-228.