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¡ Sepsis!

¡ Sepsis!. And Some CRITICAL CARE. Aaron Rothstein 2017. Contact. Aaron Rothstein arothstein@nosm.ca. Objectives. Focus : Learning about classification, identification, and treatment of Sepsis . Objectives :

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¡ Sepsis!

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  1. ¡Sepsis! And Some CRITICAL CARE Aaron Rothstein 2017

  2. Contact • Aaron Rothstein • arothstein@nosm.ca

  3. Objectives Focus: Learning about classification, identification, and treatment of Sepsis. Objectives: • Understand the new Sepsis 3 classification for Sepsis and the basics of the SOFA score • Learn to recognize sepsis • Know the basics of Sepsis treatment including fluids and early antibiotics

  4. Agenda • Brief History • A Case • Physiology • Definitions • Identifying • Treating • Key Studies • Review • Back to Case

  5. A Case • It’s a standard day in Sioux Lookout ER, and there are a few cases that got you thinking pretty heavily • One 26 year old Female comes in with Left flank pain, UTI symptoms, fever, otherwise AVSS • She has a leukocytosis of 26 and leuks and nits in her Urine • Diagnosis? • Pyelo • She seems a bit dry but vitally stable, and you admit her for fluids, pain control, and IV Ceftriaxone 2 g daily • But the nurse calls you in a few hours… she is newly hypotensive (98/52), tachy 112, neurologically muddled, and having chest pain!

  6. http://www.lifescienceglobal.com/blog/norway-researchers-cut-sepsis-deaths-in-half.htmlhttp://www.lifescienceglobal.com/blog/norway-researchers-cut-sepsis-deaths-in-half.html

  7. A Little History • Rivers trial 2001 • Suggested 30.5% vs 46.5% mortality for Severe Sepsis, NNT 6 for “Early Goal Directed Therapy” • SSC – Surviving Sepsis Campaign • Initiated in 2002 • Collaboration between SCCM [Society of Critical Care Medicine] and ESICD [European Society of Intensive Care Medicine] collaboration • 2004, 08, 12 Management of Sepsis Guidelines and Revisions • 2016 Sepsis 3 New Definitions for Sepsis • 2016 Newest Management Guidelines • Arise, Process, Promise Trials (2014-2015) • Early Intervention with usual care as good as EGDT!

  8. Epidemiology • Is it common? • Sepsis likely results in the #1 cause of world-wide mortality and critical illness8 • >5% of US Health Care dollars spent treating sepsis8(Sepsis 3 Consensus. JAMA 2016) • In one word: YES! • Be on the lookout for it.

  9. Sepsis Physiology • Inflammatory Response to Infection • Often caused by bacteria endotoxins eg: LPS on gram negative bacteria or by released toxins eg: Toxic Shock Syndrome Toxin – Staph Aureus, or simply response to Peptidoglycan on Gram (+) bacteria. • Macrophages activated by Toll-Like Receptors • TLR-2 = peptidoglycan wall (gram +); TLR-4 LPS (gram -). Different virulence of different organism. • Release Pro-inflammatory cytokines IL1, IL6, TNF alpha [macrophages]

  10. Sepsis Physiology • Cytokines cause tachy and decreased BP by increasing vasodilation and leakiness of capillaries and blood vessels [ Especially IL-1 and TNF alpha]! • Goal is to allow chemotaxis of macrophages and fighter cells [neutrophils] into the periphery and stimulate immune response, but this can be maladaptive! 4

  11. Sepsis Definitions • Have been challenging as there is no specific Diagnostic Test which is sensitive or specific for the illness • Tries to differentiate Sepsis from uncomplicated infections

  12. Bacteremia • Bacteremia: • Defined: Presence of live Bacteria in circulating blood • Identified: blood culture • Does not necessarily lead to Sepsis! • Sepsis is the Body Response (generally a dysregulated response!)

  13. Old Sepsis Definitions Historically until 2016 (and still today for lots of people) • Defined by Sepsis 2 [2001, SCCM] –has been changed by 2016 guidelines • SIRS [Systemic Inflammatory Response Syndrome] • 2 of the following: • Temp < 36 C or > 38 C • RR > 20 • HR>90 • WBC high or low [> 12 or < 4] • Sepsis = SIRS + presumed Infection • Severe Sepsis = Sepsis + signs end organ damage • Septic Shock – Sepsis with refractory hypotension

  14. http://ionhealthcarepulse.com/2016/10/24/understanding-sepsis-severe-sepsis-septic-shock/http://ionhealthcarepulse.com/2016/10/24/understanding-sepsis-severe-sepsis-septic-shock/

  15. Severe Sepsis • Removed from Newest 2016 Sepsis 3 Criteria • Deemed redundant • Sepsis PLUS Organ dysfunction1: • SBP <90 mmHg or MAP < 65 mmHg or lactate > 2.0 mmol/L (after initial fluid challenge) • INR >1.5 or a PTT >60 s [Liver or Clotting Dysfunction] • Bilirubin >34 µmol/L [Liver or Hemolysis] • Urine output <0.5 mL/kg/h for 2 h [Renal] • Creatinine >177 µmol/L [Renal] • Platelets <100 ×109/L [heme] • SpO2 <90% on room air [Lungs] • I usually also consider: altered mental status [brain] • mortality1: 17-20% (https://lifeinthefastlane.com/ccc/sepsis-definitions/

  16. Septic Shock • Prior to 2016: defined as sepsis with refractory hypotension • hypotension is defined as SBP <90 mmHg or MAP <70 mmHg • refractory =hypotension persists after 30 mL/kg crystalloid; i.e. vasopressor dependence after adequate volume resuscitation • New Definition: requirement of Vasopressors to maintain pressure and elevated lactate (more to come) • mortality1:43-54% https://lifeinthefastlane.com/ccc/sepsis-definitions/

  17. Sepsis 3 • New Definitions in 2016 • ESICM-SCCM Sepsis Redefinitions Task Force • ESICM = European Society of Intensive Care Medicine • SCCM = Society of Critical Care Medicine (International) • Sepsis Definition: • Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection

  18. Sepsis 3 • Sepsis involves Organ Dysfunction as defined by 2+ Points on the SOFA Score (Sequential Organ Failure Assessment)

  19. SOFA Score • Sequential Organ Failure Assessment • Has been in practice since 90s in many ICUs, recently taking from seat in Sepsis • Degree of Organ Dysfunction in 6 systems • Predictive of mortality • Score of 2+ can be compatible with Sepsis • Calculate worst score in 24 hour

  20. SOFA Score

  21. qSOFA • At least it is simplified… • 2 or more of HAT: • Hypotension: SBP less than or equal to 100 mmHg • Altered mental status (any GCS less than 15) • Tachypnea: RR greater than or equal to 22 • What does it mean ?3 • qSOFAof 0-1 = Mortality 3% • qSOFA of 2+ = Mortality 24% • [UpToDate: Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis (July 2017)]

  22. Septic Shock • Septic Shock (new definition) • A Subset of Sepsis in which underlying circulatory and metabolic abnormalities are profound enough to increase mortality • Includes BOTH of: • Persistent hypotension requiring vasopressors to maintain MAP of 65 mm Hg • Lactate of 2 mM or greater • Mortality? • >40%8 • Sepsis 3 Consensus. JAMA 2016

  23. Comparison to SIRS • In Retrospectively validated the Sepsis 3 criteria1: • In ICU patients with suspected infection, SOFA (95% CI, 0.73-0.76) was superior to SIRS (95% CI, 0.62-0.66) for predicting hospital mortality • In patients outside of the ICU, SOFA (95% CI, 0.78-0.80 was similar to that with SIRS (95% CI, 0.75-0.77) for predicting hospital mortality • Who here is working in an ICU?!

  24. SIRS/SEPSIS 2 concerns • SIRS parameters are arbitrarily simplified • (e.g. heart rate of 90 and WBC count of 10 have no true physiological significance) • SIRS is a one time measurement which may change from moment to moment • SIRS is not sensitive: • 1 in 8 ICU patients with infection and organ dysfunction do not have 2 or more SIRS criteria • ·SIRS is not specific: • 4 in 5 ICU patients without infection have ‘SIRS’ criteria • ‘Septic shock’ requires refractory hypotension to be present, however hypotensive patients do not necessarily have shock (globally impaired tissue perfusion) and patients in shock may not be hypotensive*** [note this is not fixed in new definition!]

  25. SEPSIS 3 - Concerns • Some Concerns with this new model1 • Not endorsed by ACEP** – not involved in creation of model • SOFA is COMPLICATED • Especially so if underlying organ dysfunction • May not outperform SIRS in outpatient setting • qSOFA • Retrospectively validated, unclear versatility in all settings

  26. Identifying SEPSIS • No Perfect Model • Have suspicion as it is Common • Sepsis is a common and diverse illness with different presentations • It involves organ dysfunction from body response to infection • Commonality is that it is BAD

  27. Clinical Presentation • Common Presentation: • Tachycardia, hypotension, tachypnea, fever, leukocytosis • Initially warm flushed skin (warm sepsis)  cold, shut down (cold sepsis) • Signs of dehydration • Eg: oliguria (<0.5cc/kg/hour) • Look for Infectious Source • Non-specific (Many other conditions are similar) • Eg: Pancreatitis, Hypovolemia, Cardiogenic Shock, Anaphylaxis

  28. http://epmonthly.com/article/sepsis-mimics/

  29. Laboratory Investigations • WBC > 12, < 4 • > 10 % immature cells or bands • Lactate – elevates with anaerobic metabolism • Acidemia – decreasing pH – lactate, rising creat • Hyperglycemia • High CRP • End Organ Dysfunction • Rising creatinine • Low Plts • Rising INR/PTT (beware of DIC) • HyperBili • Blood Culture? • DO THEM x 2!

  30. Key Sepsis Trials • Rivers (2001) – EGDT • Jones (2010) – Following Lactate Clearance vs EGDT the same • Process (2014) – EGDT and usual care no difference • Arise (2014) – EGDT and usual care no difference • Promise (2015) – EGDT and usual care no difference

  31. Rivers (2001) • Key trial 263 patients at tertiary hospital • Vastly reduced in hospital mortality with EGDT! • 30.5 % vs 46.5% (sick patients!) • Goals in EGDT: • CVP ≥ 8-12 mm Hg [Central line – pressure in right atrium, SVC ~ preload] • MAP ≥ 65 mm Hg [vasopressors] • Urine Output ≥ 0.5 cc/ kg/ hour • ScvO2 ≥ 70% [Central Line - saturation of O2 in right atrium] • If low: Body High needs, extracting O2 • RBC transfusion Hct > 30% • CVP, MAP optimized dobutamine • Ok… so why important? Much more aggressive with early fluid, MAP, urine output measures since!

  32. Jones (2010) • Lactateclearance by 10% Q1-2 hours to guide resuscitation • Following Lactate Clearance of 10% Equal outcomes to EGDT • Jones et al. Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A Randomized Clinical Trial. JAMA. 2010 Feb 24; 303(8): 739–746.

  33. Process 2014 • Reassess EGDT • Big trial tertiary centers : 1341 • 1) EGDT – as per Rivers 01’ • 2) Standard Therapy • No req for central lines • pRBCsif < 75 g/L • Physician directed fluids and vasopressor • 3) Usual Therapy • As per physician – no guideline • No changes in mortality • Very similar amount of fluids ~ 4 +L in 6 hours each group; high percentage on vasopressors and with central lines in all groups – generally aggressive! • Process Trial: A Randomized Trial of Protocol-Based Care for Early Septic Shock. The ProCESS Investigators, N Engl J Med 2014; 370:1683-1693, 2014.

  34. Other Trials Want a few more? • Arise 2014: EGDT = Usual Care • Promise 2015: EGDT = Usual Care

  35. SEPSIS Treatment • Surviving Sepsis Campaign Guidelines (2016) • Simple Way to Put It: • Early Antibiotics • Isotonic Fluids. Fluids. Fluids… Did I say... Fluids?

  36. Sepsis Treatment Detailedas per SSC 2016/UpToDate 20177: • Correct Hypoxia • Intubate if Necessary (Will discuss at end) • Good Venous Access • Early Antibiotics within 1st Hour • Get blood/urine cultures first ideally expediently • Do not need to wait for LP if taking time • Broad spectrum • Complex depending on suspected source and patient • Go Big and Broad, especially if source is unclear • Eg: PipTazo +/- Vanco (MRSA) +/- Clinda (Toxin producer) • PipTazo affords reasonable anaerobic, gram (+) and gram (-) including pseudomonas • Carbpenems are very reasonable substitutes with very sick patients with similar scope and also great for ESBL

  37. Give Antibiotics Fast? • Draw blood cultures first if possible, but don’t delay! • Mortality climbs _ %/hour in severe sepsis? • 8%5 Jumar et al, Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006 Vol. 34, No. 6

  38. Sepsis Treatment • Isotonic Fluid (30 cc/kg) over first 3 hour • Ie for 70 kg person > 2 Litres • Unless Cannot Tolerate (eg: Pulmonary Edema) • 500 cc boluses  reassess Status and Resp • Monitor Progress • Vital Signs • MAP (Mean Arterial Pressure) • ≥ 65 • Tachycardia • End Organ Perfusion • Urine Output (0.5cc/kg/hour) • Lactate Clearance (eg Q6H) • Mental Status

  39. Assessing Fluid Responsiveness • Key Question! • Most septic patients are very dry but can be overloaded • How to? • Exam: • hypotension, tachycardia (although can also reflect cardiac cause, etc) • Dry mouth • JVP down • Edema (often not good intravascular assessment!) • Pulmonary Edema • Labs • BUN>> creat • CVP (Central Venous Pressure) • Ultrasound • B lines for pulmonary edema • JVP assessment • IVC collapsibility • Advanced: Ventricular Size, Stroke Volume, Arterial velocity • Xray • Pulmonary edema • Response to treatment • Give 500 cc bolus and R/A • Consider autotransfusion – raising legs is like giving around 500 cc of effective circulating volume

  40. How Much Fluid? • 0-6H, how much do you think?9

  41. Hypotension – When Pressors? • This is a key question in Sepsis • Often fluid resuscitation alone can bring MAP ≥ 65 Patients who Benefit: • Patients with prohibitory Pulmonary Edema • Adequate Fluid Resuscitation with Hypotension • Challenging to know ? • Consider Total Volume/Rate given without improvement, poor response to fluid challenges, early pulmonary edema

  42. Vasopressors • Vasoactive Agents: 2 effects • Vasopressor • Alpha-1 Catecholamine receptor • Squeeze vessels tight • Norepinephrine, Vasopressin, Phenylephrine, Dopamine (some inotropy as well) • Inotrope • Beta-1 Catecholamine Receptor • Heart Sqeezes harder (Pump can improve) • Dobutamine, Milrenone, Epinephrine (does both well) • In Sepsis: • First Line? • Vasopressor • Norepinephrine = Levofed

  43. Norepinephrine • How to actually give it?! • Start GOOD Peripheral IV (18G Antecubital) or Central line • Try 8 mcg/ minute and titrate • Here is how you Mix that up: • Follow your protocol OR • 1 amp (4000 mcg) in 500 cc bag NS and run at 60 cc/hour • 1 amp (4000 mcg) in 250 cc bag NS and run at 30 cc/hour • This is 8 mcg /min! ie a good starting dose • Now you can just double that flow to get 16 mcg/min • Titrate to effect • Limb Checks Q30 min if giving peripherally • Make sure IV doesn’t come out, can cause extravasation injury

  44. Phenylephrine • A great Alpha1 Vasoconstrictor to bring up MAP in a pinch • Fast acting (IV bolus T1/2 = 5 min) • How to draw that up? • 1 vial 10 mg = 10,000 mcg • Place in 100 cc bag (1/100 dilution) • Have 100 mcg/ cc • Give in boluses of 100-200 mcg = 1-2 cc • Pocket Presser! • I also always draw this up before I intubate.

  45. Pressor Basics • Delivery: Can give via good peripheral IV, central line, or IO

  46. CRITICAL CARE! • ABCs + IV O2 Monitors Glucose • Constantly reassess • Stay calm. Getting frenzied helps no one. • Work as a team • Have a designated leader who takes a step back • Have the leader assign tasks • Temporize and ask for help • Practice practicepractice

  47. ABCs Airway • When to intubate for Sepsis? • Unable to Oxygen • Unable to Ventilate • Unable to Protect airway • Altered LOC (GCS ≤8, Intubate!) • Secretions • Take away work of breathing • Transport

  48. ABCs • Breathing • Pneumonia or Pulmonary edema may be impeding • Acidosis causes significant Tachypnea and people may tire! • We have discussed Oxygenation! Should Maintain normal sats for patient if possible • If truly unable to oxygenate eg: sats dropping < 90-92% with flush NRB for patient with normal baseline, I would highly consider intubating • Rising pCO2 on ABG/VBG can represent a patient tiring and will contribute to acidosis! • If patient cannot ventilate, highly consider intubation

  49. Intubation in Sepsis • Always a harrowing experience with a sick patient! • Get help if possible! • Acidosis or Baseline hypoxia means you will have less time • ER docs often prefer RSI = Rapid Sequence Intubation • This involves giving Induction Anesthetic AND muscle relaxant • Other Options • Awake Intubation (some sedation but not apnea, no muscle relaxant, lidocaine for cords) • Delayed Sequence Intubation (Preoxygenateeg: with BiPAP with sedation  RSI)

  50. RSI Induction Agent UpToDate: Rapid sequence intubation (RSI) for adults outside of the OR

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