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Initial management of
septic shock
Speaker: Mok Chi Kun
IC of Emergency medicine
Tutor: Dr. Choi Nim
Date: 2021/06/26
Initial management of septic shock 2
Outline
1 Clinical scenario
2 Hour-1 bundle for sepsis
3 New parameter for sepsis
Scenario
3
80y/M
Hx of colon cancer post OP. Follow-up CT accidentally found GB stone.
CC: recurrent epigastric pain for 4 months.
PE: fever, mild sclera icterus, no yellowish skin (the rest of the exam
was unremarkable)
Direct bilirubin elevated from 32 to 142 in one day.
ERCP was done and a small gallstone around 0.4cm came out and
plastic stent was placed.
Admitted to ward for further management and operation.
One day morning, he complaint dizziness, check Bp 70/40mmHg
ABG: serum lactate was 4mmol/L and serum bilirubin 180.
Blood test : WBC 12 CRP 20 PCT 2.3 Cr 157(baseline 83)
1. What is the impression?
2. What shouldbe the initial management for this case?
Initial management of septic shock 4
CQ
Initial management of septic shock 5
Hx of biliary tract infection
Sign and symptom suggested shock: low Bp, dizzy, vomit
Elevated lactate level, PCT and bilirubin
Impression : septic shock (biliary)
Sepsis:life-threatening organ dysfunction caused by
dysregulated host response to infection.
Septic shock:sepsis + circulatory, cellular and metabolic
abnormalities.
Septic
No hematemesis, no melena and major bleeding
Already on IV fluid for ERCP
Hypovolemic?
No SOB, Lungs are clear, no peripheral edema
Cardiogenic?
No trauma, no SOB, not likely
Obstructive?
6
Initial management of septic shock
Initial management of septic shock 7
Draw blood -- send for culture and lactate
If initial lactate > 2mmol/L, it should be re-measured within 2−4 h to
guide resuscitation to normalize lactate.
Step 1 and 2
Step 3
Give antibiotic after cultures.
Initial management of septic shock 8
Piperacillin-Tazobactam(Tazocin) 4.5 g q8h
Or Meropenem 1 g q8h
If unknown source of infection:
Vancomycin 15-20 mg/kg q8-12h
Or Linezolid 600 mg q12h
Or Daptomycin 6 mg/kg daily
Plus
Anidulafungin 200 mg IV once on day 1,
then 100 mg IV daily
Or Micafungin 100 mg IV q24h
Plus
Initial management of septic shock 9
Recommended empirical regimens for various infections
The recommended empirical regimens for various
infections
CAP-(3rd cephalosporin + Macrolide)/ (augmentin+
macrolide)/ quinolones
UTI- ceftriaxone/ quinolones
Intra-abdomen – (ceftriaxone/ quinolones) +
metronidazole
If known source of infection:
Initial management of septic shock 10
Rapid administration of crystalloid if hypotension or
lactate > 4
30ml/kg for (40kg to 100kg) => 1200ml to 3000ml
Step 4
Normal Saline?
Initial management of septic shock 11
Normal Saline is not normal
Fluid responsive -> IV fluid
Fluid unresponsive -> vasopressor
If fluid unresponsive -> IV fluid -> hyperchloremia
Initial management of septic shock 12
Chloride Sepsis + Cl -> AKI
Lactated ringer, limit by early vasopressor
Initial management of septic shock 13
Severe hyperchloremia (>110mmol/L) was associated with
increased risk of in-hospital AKI
Severe hyperchloremia is an independent predictor for in-
hospital AKI and mortality
Initial management of septic shock 14
Initial management of septic shock 15
Vasopressors if hypotension to maintain a MAP > 65
Step 5
↓ Blood pressure
Hypovolemia ↓ Vessel tone ↓ Heart function
Fluid
Cl -
Vasopressors Inotrope
Initial management of septic shock 16
Early
Early
Initial management of septic shock 17
3. Early administration of vasopressor required early
establishment of central venous access?
Initial management of septic shock 18
CQ
The Power of PowerPoint | thepopp.com 19
Initial management of septic shock
Initial management of septic shock 20
700 cases
Dopamine, epinephrine, phenylnephrine
>30hours
19 cases extravsation
Local used of NTG or phentolamine
Large bore IV access
21
Launch the Hour-1 bundle
Step 0
Initial management of septic shock
4.How torecognizesepsis?
Any limitation?
Initial management of septic shock 22
CQ
26
Initial management of septic shock
Criteria
27
Initial management of septic shock
Compare sepsis-2 and sepsis-3
28
qSOFA poorly sensitive (60.8%) and moderately (72%) specific for prediction of
mortality.
SIRS were more sensitive but much less specific.
Initial management of septic shock
4.How toimprove sepsis recognition?
Initial management of septic shock 29
CQ
Early sepsis indicatior (ESID)
More than 10 items
Limitation: Price and technique, time consuming
CRP and PCT are practical but not sensitive or specific
enoughfor sepsis.
Initial management of septic shock 30
Initial management of septic shock 31
Initial management of septic shock 32
Complement and Neutrophil
Initial management of septic shock 33
Monocyte or macrophage
Phagocytosis
Initial management of septic shock 34
Monocyte distribution width (MDW)
Cut-off value of MDW for sepsis is < 20
CBC (MDW + WBC): 30mins (from draw blood until report)
CRP and PCT : 45-60 mins
UniCel® DxH 800 hematology analyzer
Hour-1 bundle
35
Initial management of septic shock
Compare the MDW: local infection and sepsis
Initial management of septic shock 36
Posttest: positive test results Probability
WBC abnormal 44.7 %
WBC and MDW abnormal 66.53 %
WBC +T + RR + HR abnormal(sepsis 2) 72.7 %
WBC + T +RR+HR+ MDW abnormal 88.90 %
Pretest and Posttest Probabilities for Sepsis-2 Based Upon SIRS
Criteria, Alone and in Combination With MDW
Posttest: negative test results Probability
WBC normal 7.90 %
WBC and MDW normal 2.90 %
WBC +T + RR + HR normal (sepsis 2) 1.40 %
WBC + T +RR+HR+ MDW normal 0.30 %
Initial management of septic shock 37
Clinical application
MDW> 20.0 +abnormal WBC improvedsepsis detection
MDW≤ 20.0 + normal WBC, sepsis probability<3%
Posttest Probability
WBC + T +RR+HR+ MDW abnormal 88.90 %
WBC and MDW normal 2.90 %
38
The price to normalize Bp : 3000cc crystalloid
Time : 3 hours
Noradrenaline
Meropenem
Duration: 4 days to wean off vasopressor
Initial management of septic shock 39
Summary
Hour-1 bundle for sepsis
Blood cultures
Serum lactate
Antibiotic
Balanced solution
Vasopressor
Safety of peripheral IV
Novel early sepsis indicator: NDW
Initial management of septic shock 40
Reference
Haydar S, Spanier M, Weems P, et al. Comparison of QSOFA score
and SIRS criteria as screening mechanisms for emergency department
sepsis. Am J Emerg Med 2017; 35:1730–1733
Crouser ED, Parrillo JE, Seymour C, et al. Improved early detection of
sepsis in the ED with a novel monocyte distribution width
biomarker. Chest 2017; 152:518–526
Crouser ED, Parrillo JE, Seymour C, et al. Monocyte Distribution Width:
A Novel Indicator of Sepsis-2 and Sepsis-3 in High-Risk Emergency
Department Patients
Iris Castro, The Diagnostic Ability of Monocyte Distribution Width
(MDW) is not affected in Patients with Hematological Malignancy or
Immune Suppression
Elena A. Sukhacheva, Ph.D. The Role of Monocytes in the Progression
of Sepsis
Christophe Clec’h, MD, Diagnostic and prognostic value of
procalcitonin in patients with septic shock
THANK YOU FOR YOUR ATTENTION!
ANY QUESTIONS?
41
42

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Sepsis caster

  • 1. Initial management of septic shock Speaker: Mok Chi Kun IC of Emergency medicine Tutor: Dr. Choi Nim Date: 2021/06/26
  • 2. Initial management of septic shock 2 Outline 1 Clinical scenario 2 Hour-1 bundle for sepsis 3 New parameter for sepsis
  • 3. Scenario 3 80y/M Hx of colon cancer post OP. Follow-up CT accidentally found GB stone. CC: recurrent epigastric pain for 4 months. PE: fever, mild sclera icterus, no yellowish skin (the rest of the exam was unremarkable) Direct bilirubin elevated from 32 to 142 in one day. ERCP was done and a small gallstone around 0.4cm came out and plastic stent was placed. Admitted to ward for further management and operation. One day morning, he complaint dizziness, check Bp 70/40mmHg ABG: serum lactate was 4mmol/L and serum bilirubin 180. Blood test : WBC 12 CRP 20 PCT 2.3 Cr 157(baseline 83)
  • 4. 1. What is the impression? 2. What shouldbe the initial management for this case? Initial management of septic shock 4 CQ
  • 5. Initial management of septic shock 5 Hx of biliary tract infection Sign and symptom suggested shock: low Bp, dizzy, vomit Elevated lactate level, PCT and bilirubin Impression : septic shock (biliary) Sepsis:life-threatening organ dysfunction caused by dysregulated host response to infection. Septic shock:sepsis + circulatory, cellular and metabolic abnormalities. Septic No hematemesis, no melena and major bleeding Already on IV fluid for ERCP Hypovolemic? No SOB, Lungs are clear, no peripheral edema Cardiogenic? No trauma, no SOB, not likely Obstructive?
  • 6. 6 Initial management of septic shock
  • 7. Initial management of septic shock 7 Draw blood -- send for culture and lactate If initial lactate > 2mmol/L, it should be re-measured within 2−4 h to guide resuscitation to normalize lactate. Step 1 and 2 Step 3 Give antibiotic after cultures.
  • 8. Initial management of septic shock 8 Piperacillin-Tazobactam(Tazocin) 4.5 g q8h Or Meropenem 1 g q8h If unknown source of infection: Vancomycin 15-20 mg/kg q8-12h Or Linezolid 600 mg q12h Or Daptomycin 6 mg/kg daily Plus Anidulafungin 200 mg IV once on day 1, then 100 mg IV daily Or Micafungin 100 mg IV q24h Plus
  • 9. Initial management of septic shock 9 Recommended empirical regimens for various infections The recommended empirical regimens for various infections CAP-(3rd cephalosporin + Macrolide)/ (augmentin+ macrolide)/ quinolones UTI- ceftriaxone/ quinolones Intra-abdomen – (ceftriaxone/ quinolones) + metronidazole If known source of infection:
  • 10. Initial management of septic shock 10 Rapid administration of crystalloid if hypotension or lactate > 4 30ml/kg for (40kg to 100kg) => 1200ml to 3000ml Step 4 Normal Saline?
  • 11. Initial management of septic shock 11 Normal Saline is not normal Fluid responsive -> IV fluid Fluid unresponsive -> vasopressor If fluid unresponsive -> IV fluid -> hyperchloremia
  • 12. Initial management of septic shock 12 Chloride Sepsis + Cl -> AKI Lactated ringer, limit by early vasopressor
  • 13. Initial management of septic shock 13 Severe hyperchloremia (>110mmol/L) was associated with increased risk of in-hospital AKI Severe hyperchloremia is an independent predictor for in- hospital AKI and mortality
  • 14. Initial management of septic shock 14
  • 15. Initial management of septic shock 15 Vasopressors if hypotension to maintain a MAP > 65 Step 5 ↓ Blood pressure Hypovolemia ↓ Vessel tone ↓ Heart function Fluid Cl - Vasopressors Inotrope
  • 16. Initial management of septic shock 16 Early Early
  • 17. Initial management of septic shock 17
  • 18. 3. Early administration of vasopressor required early establishment of central venous access? Initial management of septic shock 18 CQ
  • 19. The Power of PowerPoint | thepopp.com 19 Initial management of septic shock
  • 20. Initial management of septic shock 20 700 cases Dopamine, epinephrine, phenylnephrine >30hours 19 cases extravsation Local used of NTG or phentolamine Large bore IV access
  • 21. 21 Launch the Hour-1 bundle Step 0 Initial management of septic shock
  • 22. 4.How torecognizesepsis? Any limitation? Initial management of septic shock 22 CQ
  • 23. 26 Initial management of septic shock Criteria
  • 24. 27 Initial management of septic shock Compare sepsis-2 and sepsis-3
  • 25. 28 qSOFA poorly sensitive (60.8%) and moderately (72%) specific for prediction of mortality. SIRS were more sensitive but much less specific. Initial management of septic shock
  • 26. 4.How toimprove sepsis recognition? Initial management of septic shock 29 CQ
  • 27. Early sepsis indicatior (ESID) More than 10 items Limitation: Price and technique, time consuming CRP and PCT are practical but not sensitive or specific enoughfor sepsis. Initial management of septic shock 30
  • 28. Initial management of septic shock 31
  • 29. Initial management of septic shock 32 Complement and Neutrophil
  • 30. Initial management of septic shock 33 Monocyte or macrophage Phagocytosis
  • 31. Initial management of septic shock 34 Monocyte distribution width (MDW) Cut-off value of MDW for sepsis is < 20 CBC (MDW + WBC): 30mins (from draw blood until report) CRP and PCT : 45-60 mins UniCel® DxH 800 hematology analyzer Hour-1 bundle
  • 32. 35 Initial management of septic shock Compare the MDW: local infection and sepsis
  • 33. Initial management of septic shock 36 Posttest: positive test results Probability WBC abnormal 44.7 % WBC and MDW abnormal 66.53 % WBC +T + RR + HR abnormal(sepsis 2) 72.7 % WBC + T +RR+HR+ MDW abnormal 88.90 % Pretest and Posttest Probabilities for Sepsis-2 Based Upon SIRS Criteria, Alone and in Combination With MDW Posttest: negative test results Probability WBC normal 7.90 % WBC and MDW normal 2.90 % WBC +T + RR + HR normal (sepsis 2) 1.40 % WBC + T +RR+HR+ MDW normal 0.30 %
  • 34. Initial management of septic shock 37 Clinical application MDW> 20.0 +abnormal WBC improvedsepsis detection MDW≤ 20.0 + normal WBC, sepsis probability<3% Posttest Probability WBC + T +RR+HR+ MDW abnormal 88.90 % WBC and MDW normal 2.90 %
  • 35. 38 The price to normalize Bp : 3000cc crystalloid Time : 3 hours Noradrenaline Meropenem Duration: 4 days to wean off vasopressor
  • 36. Initial management of septic shock 39 Summary Hour-1 bundle for sepsis Blood cultures Serum lactate Antibiotic Balanced solution Vasopressor Safety of peripheral IV Novel early sepsis indicator: NDW
  • 37. Initial management of septic shock 40 Reference Haydar S, Spanier M, Weems P, et al. Comparison of QSOFA score and SIRS criteria as screening mechanisms for emergency department sepsis. Am J Emerg Med 2017; 35:1730–1733 Crouser ED, Parrillo JE, Seymour C, et al. Improved early detection of sepsis in the ED with a novel monocyte distribution width biomarker. Chest 2017; 152:518–526 Crouser ED, Parrillo JE, Seymour C, et al. Monocyte Distribution Width: A Novel Indicator of Sepsis-2 and Sepsis-3 in High-Risk Emergency Department Patients Iris Castro, The Diagnostic Ability of Monocyte Distribution Width (MDW) is not affected in Patients with Hematological Malignancy or Immune Suppression Elena A. Sukhacheva, Ph.D. The Role of Monocytes in the Progression of Sepsis Christophe Clec’h, MD, Diagnostic and prognostic value of procalcitonin in patients with septic shock
  • 38. THANK YOU FOR YOUR ATTENTION! ANY QUESTIONS? 41
  • 39. 42

Notas del editor

  1. Hello everyone, here is Mok Chi Kun, IC of emergency medicine. My tutor is Dr. Choi Nim. My topic of presentation is initial management of septic shock, and something new about that.
  2. In the following, I would like to talk about a clinical scenario for sepsis, hour-1 bundle of surviving sepsis campaign and new parameter for sepsis.
  3. Here is a scenario I met in our ward. An 80y male patient, Hx of colon cancer post OP many years ago. Follow-up CT scan accidentally found GB stone. He visited ER due to epigastric pain. Physical exam found fever and sclera icterus. Bilirubin level was elevated so ERCP was requested, a small stone in 0.4cm came out and plastic stent was placed. Post ERCP day 2, he was found dizziness, check Bp low, 70/40, blood gas found elevated lactate. Blood test found elevated inflammatory markers and AKI
  4. So, What is the most probably cause of hypotension and initial management for this case?
  5. The clinical picture suggested septic shock as the first impression since he had hx of prolonged biliary tract infection. There was no other clues suggesting the hypotension was caused by another reason.
  6. According to surviving sepsis campaign, the previous version of hour-3 and hour-6 bundle was replaced by Hour-1 bundle for initial resuscitation for sepsis and septic shock. As we know, Sepsis is a medical emergency, we need to initiate hour-1 bundle upon recognition of sepsis or septic shock. Including, measure the lactate level, obtain blood cultures, administer broad-spectrum of antibiotics. Rapid administration of crystalloid, and apply vasopressors if hypotension to maintain MAP more than 65 Here is a question, which step do you thick is the most important step in this page? And, I will give you my answer at the end.
  7. First, obtain blood samples, and send for cultures and serum lactate. If lactate is more than 2, repeat it later after initial resuscitation. Then give antibiotic early.
  8. For unknown source of infection, pip/tazo or meropenem. If concerning MRSA or fungal infection, we add vancomycin or anidulafungin as well.
  9. If known source of infection: For lungs and urinary tract, we have beta-lactam, cephalosporin, macrolide and fluroquinolone For intra-abdominal infection, we add metronidazole for anaerobic coverage.
  10. Step 4 Rapid IV fluid boluses 30cc/kg, around 1 to 3 liters, usually we can give 2 In the past, many years ago, we used to choose NS. But there is something new nowadays.
  11. Normal saline is not normal, it not only rich in sodium, but also chloride. Some patients with hypotension are fluid responsive, most cases are not and required vasopressor. For those cases of fluid unresponsive, if we give fluid in order to increased Bp without vasopressor, we could not avoid to give too much fluid and chloride which leading to hyperchloremia.
  12. If we give too much chloride, the macula densa detected high concentration of chloride which can lead to afferent arteriole constriction, hence decrease renal blood flow. In sepsis, the patients might already had acute kidney injury, and chloride can make this situation worse. To prevent this, we choose balanced solution such as lactated ringer. Besides, we can limited fluids consumption by giving vasopressor earlier.
  13. Severe hyperchloremia (>110mmol/L) was associated with increased risk of in-hospital AKI and increased mortality.
  14. So. Instead of NS, we choose balanced fluid which chloride concentration is similar to serum level.
  15. Step 5 is vasopressor. Give until MAP reach 65 To treat the low blood pressure, We usually start off with fluids But fluid should only be given to those fluid responsive patient Most forms of shock are not only due to hypovolemia as this slide showed, bedsides, vasodilation and cardio-inhibition can also contribute to low blood pressure. Many patients with low Bp are fluid unresponsive Then, we need to add vasopressor, the first line is epinephrine, the second is vasopressin. We can limit fluids by giving vasopressor earlier to avoid giving to much chloride.
  16. Here is early versus delayed administration of vasopressor From the picture below, we can see early used of vasopressor can reach target MAP earlier, besides improved serum lactate clearance.
  17. Adversely, delayed used of vasopressor in patients with septic shock will have adverse effect on mortality.
  18. We want to give vasopressor early but the problem here is we did not have central venous access.
  19. In general, when we first encounter a patient with septic shock, we didnt have any central venous access. We want to give vasopressor early, we need a central line to prevent extravasation, but waiting for a central line can delay the use of vasopressor.
  20. Some studies demonstrate the safety of peripheral administration of vasopressor. It included 700 cases, received dopamine, epinephrine and phenylephrine for at least 30 hours. 19 cases was found extravasation without tissue injury after local used of phentolamine or NTG. For sure, we should choose a large bore, secure IV access for vasopressor.
  21. Here is the problem, the hour-1 bundle required early recognition of sepsis or septic shock. If fail to early recognized, the hour-1 bundle cannot be initiated, and also delayed the treatment.
  22. Current guidelines emphasize on the benefit of early detection of sepsis. Each hour delay of antibiotic treatment is associated with 5-10% mortality increase. So, How to recognize sepsis? Is there any limitation for those method?
  23. Early recognition of sepsis is challenging. In the past, we had sepsis-2 and now upgrade to sepsis-3 to detect sepsis. The criteria were shown above. Sepsis-2 is suspect or known source of infection, plus SIRS positive Sepsis-3 is suspect or known source of infection, plus qSOFA positive The elements in the blue box are subjective and those in red are objective, so that sepsis criteria remained subjective to detect sepsis.
  24. We can compare the performance of sepsis-2 and sepsis-3 criteria by comparing SIRS and qSOFA. SIRS and qSOFA have similar areas under the ROC curve, indicating that they have a similar overall test performance. qSOFA has a higher specificity than SIRS, but this comes at the cost of a lower sensitivity.  Thus, qSOFA is not better than SIRS, it has merely traded sensitivity for specificity.
  25. Further, the overall sensitivity of sepsis-3 might be lower than 50%. Neither sensitive nor specific enough to detect sepsis.
  26. Question 4 again, How to improve sepsis recognition?
  27. There are more than 10 items of early sepsis indicator Since there is some limitation, price, technique and time, CRP and PCT become the most popular and practical. But they are not sensitive or specific enough for sepsis detection.
  28. Recently, there was a prospective cohort study found that monocyte distribution width is a novel indicator for early sepsis detection.
  29. When people get infected, the immune system start to defense. Including complement and neutrophils. Neutrophil cannot detect the cell wall of the bacteria and start cytotoxic effect.
  30. The same for the monocyte, they start phagocytosing. When the bacteria of the local infection gets into the blood, they met monocyte. The monocytes start to engulf and destroyed the microbes. Since the ingestion and phagocytosis, the monocytes increased in their size
  31. Therefore, we can detect the elevation of monocyte distribution width in the peripheral blood. The cut-off value of MDW for sepsis is < 20 More importantly, this item and analyzer were available in our lab and it will be released for clinical practice in the future. It takes 45 minutes of time for processing, make it fits into the hour-1 bundle.
  32. Compare the MDW for those patients with local infection and sepsis. The sepsis group had higher MDW and usually > 20
  33. Compare to WBC or sepsis-2 alone, combination with MDW will improve the detection of sepsis. Normal WBC or sepsis-2 criteria, combination with normal MDW will further decrease the probability of sepsis.
  34. If a patient with sepsis-2 criteria and MDW are all abnormal, the probability of sepsis is 90& If WBC and MDW are normal, the probability of sepsis is less than 3%.
  35. The price for my case to normalize Bp by 3L of fluid. It takes 3 hours of monitor and finally need vasopressor to go for CT. Meropenem And need 4 days to recover.
  36. For the initial management of sepsis, the hour-1 bundle included blood cultures, lactate, antibiotic, balanced solution for IV fluid and early administration of vasopressor. Peripheral IV access remain safe and should not delay giving vasopressor Novel early sepsis indicator: NDW can improve early sepsis recognition
  37. Here is my reference