Sepsis/Septic Shock


Sepsis Evaluation & Resuscitation
 
1. T < 97 F or > 100.4
2. HR > 90
3. ACTUAL RR > 20 or, PaCO2 < 32 mm Hg
4. WBCs >12
K or <4K or band >10%
5.
Elevated CRP
2 of 5 = SIRS
Age 18yo, pt meets 2/5 of SIRS Criteria.
SEPSIS = SIRS + INFECTION
The cause of SIRS is most likely infection (best clinical judgment).
Many pts with sepsis can be treated effectively on the ward.
SEVERE SEPSIS = SEPSIS + ORGAN DYSFUNCTION
Any organ dysfunction secondary to sepsis (e.g. SpO2 < 92%, MS Δ , Lactic acid, Mottled/cool ext., renal dysfunction, coagulopathy, etc.).
Severe sepsis commonly progresses to septic shock & requires specifit "Early Goar-Directed Therapy".
All pts with severe sepsis & septic shock should be transfered to ICU
SEPTIC SHOCK
Sepsis with refractory hypotension or signs of hypoperfusion despite adequate fluid resuscitation. (require pressors)
  • End organ dysfunctionn
  • Serum lactate > 4 mmol/dL
  • Oliguria
  • Altered mental status
Patients are defined as having septic shock if they have sepsis plus hypotension after aggressive fluid resuscitation (typically upwards of 6 liters or 30 ml/kg of crystalloid).

Overview

Organ Dysfunction Guideline

Sepsis + Sepsis Induced Organ Dysfunction = Severe Sepsis
Cardiovascular
  • Hypotension (sBP <90, MAP <65, or a sBP drop >40 from baseline)
    OR
  • Vasopressors required to maintain sBP >90 or MAP >65 (if dopamine, dose should be >5 mcg/kg/min)
Respiratory - Criteriaapply to Acute Lung Injury *, not CHF or Cardiogenic pulmonary edema
  • Bilateral pulmonary infiltrates with a new (or increased) O2 requirement to maintain SpO2 >90%.
  • Bilateral pulmonary infiltrates with PaO2/FiO2 300

Acute lung injury (ALI) is acute onset of respiratory failure with bilateral chest infiltrates on frontal CXR Not due to left-sided heart failure.
[COPD pt may quality for ALI. the definition of ALI excludes pts with chronic elevated cardiac filling pressures (e.g; L heart failure) or chronic infiltrative lung disease as the cause or physiologic changes]

Renal - does not apply to pts on chronic dialysis
  • Acute oliguria (UO < 30cc/hr or <0.5 mL/kg/hr for >2hr)
  • Acute renal failure ( Cr >2.0)
Hematologic
  • Coagulation abnormalities (INR >1.5 or a PTT >60s)
  • Thrombocytopenia (platelets <100K)
Hepatic
Hyperlactemia
  • Serum Lactate > 2.5 mmol/L
Neurologic
  • Depressed level of consciousness
  • Altered mental status.

 

Causes of Sepsis

Causes of Sepsis by Organ System

Common Causes of Sepsis by Organ System
Respiratory
Pneumonia (community acquired or HAP)
Mechanical ventilation (VAP)
Empyema
Lung abscess
Cardiovascular
Indwelling catheters (especially central lines)
Infected prosthetic device
Endocarditis
IV drug use
Intra-abdominal
Pancreatitis
Surgery
Trauma
Bowel rupture
Peritonitis
Ruptured appendix
Gall bladder
Urinary
Foley catheter
Pyelonephritis
Renal abscess
Cystitis
Prostatic abscess or prostatitis
UTIs associated with benign prostatic hypertrophy
Kidney stones
Congenital urinary tract malformation
Gynecologic
STDs
PID
Toxic shock syndrome associated with tampon use
Obstetric
Peri/post-partum complications
PROM
Endometritis
Placental retention
Cesarian or vaginal wound infections
CNS
Meningococcal sepsis
Skin and musculoskeletal
Ulcers, wounds
Osteomyelitis
 

Microbes Associated w/ Severe Sepsis

Microbes commonly associated with severe sepsis
Sepsis causes in the US: Gram+ > Gram- >fungi
Organisms associated with septic shock, high mortality, and presence of multi-drug-resistant (MDR) strains:
  • Pseudomonas aeruginosa
  • Klebsiella, Enterobacter, and Serratiaspecies
  • Acinetobacter species
  • Methicillin resistant Staphylococcus aureus (MRSA)
  • Vancomycin resistant Enterecoccus(VRE)
  • Candida species
 

Causes of noninfectious SIRS

Causes of noninfectious SIRS
Causes of noninfectious SIRS include:
  • Pancreatitis
  • Extensive trauma
  • Extensive burns
  • Anaphylaxis
  • Thrombosis (pulmonary embolism)
  • Autoimmune diseases (eg, systemic lupus erythomatosus)
  • Systemic vasculitis
  • Surgery
  • Jarisch-Herxheimer reaction (eg, post-Lyme disease treatment "the herxes")
 

Common mimickers of SIRS and Sepsis

Common mimickers of SIRS and sepsis
The following conditions may mimic the symptoms of SIRS and sepsis:
  • Pulmonary embolism
  • Myocardial infarction
  • Adrenal insufficiency
  • Diabetic ketoacidosis
  • Massive aspiration/atelactesis
  • Drug overdose
  • Shock Hemorrhagic
  • Cardiogenic
  • Neurogenic
  • Anaphylactic
 
 

Diagnosis/Labs

(Perform first 4 in the first 6 hours)
1. LABS:
  • Serum Lactic Acid level (repeat if elevate to monitor decreasing levels).
  • Procalcitonin (associated with bacterial sepsis)
  • CBC, CMP, UA w/ c&s, ABG, Amylase, Lipase, Serial cardiac enzymes, PT/INR.
  • Blood culture prior to antibiotic, Sputum culture (BAL), Line/port culture, Wound culture, Surgical Site culture, Legionella Ag, Strep Pneumonia Ag, MRSA swab, Flu swab, H1N1
  • Fungal: Cryptococcal Ag (blood and urine)
  • ? Paracentesis, Thoracentesis
2. IMAGING:
  • CXR, Spiral CT, Abdominal US (Cholecystitis, Cholangitis). CT/MRI abd (intra-abdominal abscess or other internal infection).
 

Management

Early goal-directed therapy:
  • Administer fluids to CVP of 8-12. [30 cc/kg over 30 min or less (up to ~2-3 L)]
  • Begin norepinephrine if MAP < 65 mmHg.
  • Transfuse PRBCs to Hgb >10 g/dL if ScvO2 <70%.
  • Begin dobutamine if ScvO2 remains <70%.
 
 

NOTE:

  • If you need to intubate, Get a central line first and have pressors ready.
    • WHY? because Vent will increase cardiac pressure = venous return to heart (which is already decreased in septic pt) = CO & BP


(Perform first 4 in the first 6 hours)
1. LABS:

  • Serum Lactic Acid level (repeat if elevate to monitor decreasing levels).
  • Procalcitonin (associated with bacterial sepsis)
  • CBC, CMP, UA w/ c&s, ABG, Amylase, Lipase, Serial cardiac enzymes, PT/INR.
  • Blood culture prior to antibiotic, Sputum culture (BAL), Line/port culture, Wound culture, Surgical Site culture, Legionella Ag, Strep Pneumonia Ag, MRSA swab, Flu swab, H1N1
  • Fungal: Cryptococcal Ag (blood and urine)
  • ? Paracentesis, Thoracentesis
2. IMAGING:
  • CXR, Spiral CT, Abdominal US (Cholecystitis, Cholangitis). CT/MRI abd (intra-abdominal abscess or other internal infection).
3. Broad spectrum ABx within first 3 hours of ED admission.
Mercy Sparks
Zosyn 3.375g IV q6h
+
Levaquin 750mg IV qd
+
Vancomycin
 
Cefepim 2g IV q8h
+
Cipro 400mg IV q8h
+
Vancomycin
 

Other ABx

Early broad spectrum antibiotics

Empiric (source unknown) coverage for nonneutropenic patient:
Find & Tx infxn w/in 1st hr of presentation

Empiric therapy (unknown source) ALL IV 

  • Aminoglycoside + beta-lactam +/- vancomycin
    • Aminoglycoside (choose 1)
      • Gentamycin: 5 mg/kg/d OR
      • Tobramycin: 5 mg/kg/d OR
      • Amikacin: 15 mg/kg/day
    • Beta-lactam (choose 1)
      • Cefotaxime: 3 g q6h OR
      • Ceftriaxone: 1 g q12h OR
      • Cefepime: 2 g q12h OR
      • Ceftazidime: 3 g q8-12h OR
      • Imipenem: 0.5-1 g q8h OR
      • Meropenem: 1 g q8h OR
      • Piperacillin-tazobactam: 3.375 g q6h
      • Ampicillin/sulbactam 3 g q6h
    • Vancomycin 1 g q12h
  • Neutropenia:
    • Ceftazidime 3 g q6h, imipenem 0.5-1 g q8h OR cefepime 2 g q12h
    • +/- aminoglycoside
  • Intra-abdominal sepsis suspected
    • Ticarcillin-clavulanate 3.1 g q4-6h, Piperacillin-tazobactam 3.375 g q6h, OR Imipenem 0.5-1 g q8h
    • +/- aminoglycoside
    • Fluoroquinolones
      • Levofloxacin 500 mg IV q12hrs
      • Moxifloxacin 400 mg IV qD
      • Ciprofloxacin 400 mg IV q8hrs
    • Consider anaerobic coverage
      • Metronidazole 1g IV q12hrs
      • Clindamycin 600 mg IV q8hrs

 



4.
IF hypotensive OR Lactate > 4 mmol/L
  • Bolus Crystalloid 30 cc/kg (up to ~2-3 L)
  • IF MAP < 65:  
    • Levophed (start: 1 mcg/min, max: 30) if not responsive to initial fluid bolus, maintain MAP >65
    • May add Vasopressin (0.04 units/min) with intent of either raising MAP or decreasing Levophed dosage
       
  • IF persistent hypOtension despite fluids and pressors:
    • Give (Solu-cortef) Hydrocortisone 50 mg IV Q6h, taper over 11 days.
    • 200-300 mg bolus or infusion qd appears safe & effective
    • Improves shock reversal at 7 days.
       
  • IF persistent hypotension despite fluids, and/or lactate >4 mmol/L,
    • Albumin: Buminate 25% inj IV q2h x 2 doses (250 ml)

    Get Central line:

    • CVP goal:
      • ON vent = 12-15
      • OFF vent: 8-12
CVP
 ↓
 @ Goal

NOT
@ Goal
 ↓
Check   SvO2
IV Fluids

OR

Albumin
>65% <65%
Septic Shock Check
Hgb
>10 <10
Cardiogenic Shock ?

add
dobutamine
2.5 - 20 mcg/kg/min

 



PRBC
[SvO2 = Mixed Venous Oxygen Saturation > 65%]
[ScvO2 = Central Venous Oxygen Saturation > 70%]

 
5. CBG Goal :  <180
 
6. Prophylaxis:
  • DVT: Heparin 5000 Units SQ q8h
  • Stress ulcer: Protonix 40mg IV qd OR Pepcid 20 mg IV bid, Carafate
7. Nutrition:
  • PO or Enteral feeding as tolerated within first 48 hours
  • Low caloric feeding in first week (eg, 500 cal/day)
  • IV glucose or enteral nutrition rather than TPN alone in first 5 days.
  • Enteral Nutrition at DAY 5
    • Start Jevity (1cal/cc) 30 cc/hour, advance 20 cc/hour q 8-24 hours if stable to goal.
    • Goal 25-30 kcal/kg/day (sick ICU patient) check residual q 4 hours (70 kg goal is 2100 kcal/day, approx 88 cc/hour)
    • Diabetic pt.: Use Glucerna instead of Jevity.
8. Mechanical Ventilation
  • Lung-protective ventilation with tidal volume (Vt) 6 mL/kg (predicted body weight)
  • Analgesia and sedation to maintain a calm, comfortable state
  • Keep plateau pressure ≤30 cmH2O
  • Allow permissive hypercapnia if pH ≥ 7.2 and no increased intracranial pressure
  • Keep head of the bed elevated to 45°
  • Chlorhexidine 15 mL oral rinses bid prn
  • Daily interruption of continuous sedation and minimize use of benzodiazepines
  • Avoid neuromuscular blockers if possible; less risk of critical illness polyneuropathy
  • Use a weaning protocol with spontaneous breathing trials to assess extubation readiness
  • Use a conservative fluid strategy for patients with ALI or ARDS and who are no longer in shock
9. BicarbTherapy
  • Consider for severe lactic acidosis with pH < 7.15 ( no clear outcome benefit)
10. Xigris no longer indicated. DO NOT USE
 
11. Communication with family
  • Understand what the pt's wishes would be in terms of extent of care
  • Address spiritual needs and psychosocial concerns
  • Consider limitation of support or withdrawal of pt's failing to improve or for severe deterioration despite maximal medical therapy.
 
 

Pressors

Agent Receptor Activity Effects Indication
a1 b1 b2 DA
(Levophed)
Norepinephrine
1-30 mcg/min
+++

 

++ 0 0 SVR ↑↑
CO ↔↓↑
Sepsis
Phenylephrine
(Neo-synephrine)
40-180 mcg/min
+++

 

0

 

0

 

0

 

SVR ↑↑
CO ↔/↑
Sepsis,
Neurogenic shock
Epinephrine +++

 

+++ ++ 0

 

CO ↑↑
SVR ↓ (L)
SVR ↔/↑ (H)
Anaphylaxis,
ACLS,
Sepsis
Dopamine (mcg/kg/min)
Low-dose (0.5-2) 0 + 0 ++ CO ↑
SVR ↑↓
Sepsis,
Cardiogenic shock
Mid-dose(5-10) + ++ 0 ++ CO ↑
High-dose(10-20) ++ ++ 0 ++ SVR ↑↑
Doubutamine
2.5-20 mcg/kg/min
0/+ +++ ++ 0 CO ↑
SVR ↓
Cardiogenic shock
Isoproterenol
2-10 mcg/min
0

 

+++ +++ 0 CO ↑
SVR ↓
Cardiogenic shock w/
bradycardia
Vasopressin
(Adjunct)
0.01-0.04 U/min
        V2 receptors Vasoconstriction
Augments catecholamine
 

Pressor Mechanism

Receptor Functions
Receptor Function
α1  vascular smooth muscle contraction
pupillary dilator muscle contraction (mydriasis), 
intestinal and bladder sphincter muscle contraction
α2 sympathetic outflow, 
Insulin release
 lipolysis, 
platelet aggregation
β1 Heart rate
Contractility
Renin release
Lipolysis
β2 Vasodilation
Bronchodilation 
Heart rate
 Contractility
lipolysis
 Insulin release
 Uterine tone (tocolysis)
Ciliary muscle relaxation
 Aqueous humor production
M1 CNS, enteric nervous system
M2  Heart rate and contractility of atria
M3  exocrine gland secretions (e.g., lacrimal, salivary, gastric acid), 
gut peristalsis, 
bladder contraction,
Bronchoconstriction, 
pupillary sphincter muscle contraction (miosis),
Ciliary muscle contraction (accommodation)
D1 Relaxes renal vascular smooth muscle
D2 Modulates transmitter release, especially in brain
H1 nasal and bronchial mucus production, 
vascular permeability
Contraction of bronchioles
Pruritus
Pain
H2 gastric acid secretion
V1 vascular smooth muscle contraction
V2 H2O permeability and reabsorption in the collecting tubules of the kidney (V2 is found in the 2 kidneys)

Admit Orders: Sepsis

1. Admit to: ICU

2. Diagnosis: Sepsis

3. Condition:

4. Vital Signs: q1h; Call physician if BP >160/90, <90/60; P >120, <50; R>25, <10; T >38.5°C; urine output < 25 cc/hr for 4h, O2 saturation <90%.

5. Activity: Bed rest.

6. Nursing: Inputs and outputs, pulse oximeter. Foley catheter to closed drainage.

7. Diet: NPO

8. IV Fluids: 1 liter of normal saline wide open, then D5 ½ NS at 125 cc/h

9. Special Medications:

-Oxygen at 2-5 L/min by NC or mask.

Antibiotic Therapy

A. Initial treatment of life-threatening sepsis should include
 - a third-generation cephalosporin (cefepime, ceftazidime, cefotaxime, ceftizoxime or ceftriaxone),
   or
- Piperacillin/tazobactam,
   or
- Ticarcillin/clavulanic acid
   or
- Imipenem
  PLUS
 Fluoroquinolone
   PLUS
- Vancomycin
If Enterobacter aerogenes or cloacae is suspected, treatment should begin with meropenem or imipenem with an aminoglycoside.
 

B. Intra-abdominal or pelvic infections, likely to involve anaerobes, should be treated with ampicillin, gentamicin and metronidazole; or either ticarcillin/clavulanic acid, ampicillin/sulbactam, piperacillin/tazobactam, imipenem, cefoxitin or cefotetan, each with an aminoglycoside.

C. Febrile neutropenic patients with neutrophil counts <500/mm3 should be treated with vancomycin and ceftazidime, or piperacillin/tazobactam and tobramycin or imipenem and tobramycin.

D. Dosages for Antibiotics Used in Sepsis

-Cefepime (Maxipime) 2 gm IV q12h.

-Cefotaxime (Claforan) 2 gm q4-6h.

-Ceftizoxime (Cefizox) 1-2 gm IV q8h.

-Ceftriaxone (Rocephin) 1-2 gm IV q12h (max 4 gm/d).

-Cefoxitin (Mefoxin) 1-2 gm q6h.

-Cefotetan (Cefotan) 1-2 gm IV q12h.

-Ceftazidime (Fortaz) 1-2 g IV q8h.

-Ticarcillin/clavulanate (Timentin) 3.1 gm IV q4-6h (200-300 mg/kg/d).

-Ampicillin/sulbactam (Unasyn) 1.5-3.0 gm IV q6h.

-Piperacillin/tazobactam (Zosyn) 3.375-4.5 gm IV q6h.

-Piperacillin or ticarcillin 3 gm IV q4-6h.

-Imipenem/cilastatin (Primaxin) 1.0 gm IV q6h.

-Meropenem (Merrem) 0.5-1.0 gm IV q8h.

-Gentamicin, tobramycin 100-120 mg (1.5 mg/kg) IV, then 80 mg IV q8h (1 mg/kg) or 7 mg/kg in 50 mL of D5W over 60 min IV q24h.

-Amikacin (Amikin) 7.5 mg/kg IV loading dose; then 5 mg/kg IV q8h.

-Vancomycin 1 gm IV q12h.

-Metronidazole (Flagyl) 500 mg (7.5 mg/kg) IV q6-8h.

-Aztreonam (Azactam) 1-2 gm IV q6-8h; max 8 g/day.

Nosocomial sepsis with IV catheter or IV drug abuse

-Nafcillin or oxacillin 2 gm IV q4h 
OR
-Vancomycin 1 gm q12h (1 gm in 250 cc D5W over 60 min) 
AND

Gentamicin or tobramycin as above 
AND EITHER

Ceftazidime (Fortaz)
OR
 
Ceftizoxime (Cefizox)1-2 gm IV q8h 
OR

Piperacillin, ticarcillin or mezlocillin 3 gm IV q4-6h.
 

Blood Pressure Support

-Dopamine 4-20 mcg/kg/min (400 mg in 250 cc D5W, 1600 mcg/mL).

-Norepinephrine 2-8 mcg/min IV infusion (8 mg in 250 mL D5W).

-Dobutamine 5 mcg/kg/min, and titrate blood pressure to keep systolic BP >90 mm Hg; max 10 mcg/kg/min.
 

10. Symptomatic Medications:

-Acetaminophen (Tylenol) 650 mg PR q4-6h prn temp >39°C.

-Famotidine (Pepcid) 20 mg IV/PO q12h.

-Heparin 5000 U SQ q12h or pneumatic compression stockings.

-Docusate sodium 100-200 mg PO qhs.
 

11. Extras: CXR, KUB, ECG. Ultrasound, lumbar puncture.

12. Labs: CBC with differential, CMP, ABG, INR/PTT, UA. Cultures of urine, sputum, wound, IV catheters, decubitus ulcers, pleural fluid. Serum Lactic Acid level (repeat if elevate to monitor decreasing levels). Procalcitonin (associated with bacterial sepsis), Amylase, Lipase, Serial cardiac enzymes. Blood culture x2 prior to antibiotic, Sputum culture (BAL), Line/port culture, Wound culture, Surgical Site culture, Legionella Ag, Strep Pneumonia Ag, MRSA swab, Flu swab, H1N1, Fungal: Cryptococcal Ag (blood and urine), ? Paracentesis, Thoracentesis

 


Source:

Dr Stephan Taylor, Mercy ICU, Fort Smith AR