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$: The Case of Procalcitonin - NDSHPndshp.org/Resources/Documents/Sepsis - Recognition to Resolution.pdf · the general medical floor she developed hypotension refractory to 3 L of NS,$
Justin Jones, PharmD Sanford Medical Center, Fargo Staff Education 2015

Surviving Sepsis: A CRASH Course

Disclosures

● No financial conflicts of interest

ULN Upper limit of normal SVCO2 Central venous oxygen saturation SVO2 Mixed venous oxygen saturation MV Mechanical Ventilation SBO Small bowel obstruction LA Lactic acid T2DM Type 2 diabetes mellitus Px Prophylaxis SUP Stress ulcer prophylaxis TV Tidal volume FiO2 Fraction inspired oxygen SpO2 Oxygen saturation PEEP Positive end-expiratory pressure F/U Follow-up BC Blood culture RASS Richmond agitation-sedation scale

Abbreviations

Patient Case

History of Present Illness JL presents to the ED on 4/28 with low-grade fever (37.8o C), N/V x 3-4 weeks, decreased appetite and diffuse abdominal pain. She appears weak and in moderate distress. After initial examination, a decision is made to admit her to perform a workup for intra-abdominal infection. While waiting for a bed on the general medical floor she developed hypotension refractory to 3 L of NS, altered mental status, respiratory failure and anuria. She was intubated, rushed to the ICU and placed on MV.

NKDA Past Medical History Past Surgical History Asthma 6/13/1960 SBO/hernia repair 1/30/2014 T2DM 4/5/1998 Cholecystectomy Unknown HTN 10/30/1993 Depression 7/6/2004 Social History Morbid Obesity 8/20/1991 1-2 cigarettes every other day smoker (stopped in 1980’s)

Home Medications Albuterol MDI 2 puffs every 4-6 hours PRN SOB Metformin 850 mg One tablet by mouth twice daily Fluticasone 110 mcg inhaler 2 puffs twice daily Lisinopril 10 mg One tablet daily Mirtazapine 15 mg One tablet at bedtime Promethazine 25 mg Every 6 hours PRN N/V

Patient Case

VS: BP 87/43; P 120-153; RR 14-33; T 37.8oC; SpO2: 91% on MV; UOP (24h) 25 mL; Wt 145.5 kg; Ht 5’2” Labs:

Lab Value Unit

Na 133 mEq/L

K 2.9 mEq/L

Cl 98 mEq/L

CO2 12 mEq/L

BUN 13 Mg/dL

sCr 1.1 mg/dL

Glu 230 mg/dL

Ca 6.9 mg/dL

Mg 2.5 mg/dL

Lab Value Unit

Phos 2.5 mg/dL

Alb 2.1 g/dL

Alk Phos 127 IU/L

T. Bili 0.2 mg/dL

AST 11 IU/L

ALT 7 IU/L

Hgb 13.6 g/dL

Hct 42 %

Plt 261 x103 /mm3

Lab Value Unit

WBC 25.5 x103 /mm3

Bands 15 %

pH 7.14

pCO2 26 mmHg

pO2 189 mmHg

HCO3 8.9 mmol/L

Base def -9.3 mmol/L

Lactate 9.8 mmol/L

Assessment J.L. is a 74 year-old Caucasian woman admitted with septic shock secondary to suspected intra-abdominal infection.

Patient Case

Objectives

1. Quantify the impact of early antibiotic administration on patient outcomes in severe sepsis

2. Identify four clinical endpoints of early goal- directed therapy

3. Recommend therapeutic interventions to achieve these clinical endpoints

Definitions

Septic Shock

Severe sepsis + persistent hypotension despite adequate fluid bolus

Severe Sepsis

Sepsis + tissue hypoperfusion

• Lactate > ULN • UOP < 0.5 mL/kg/h x 2 hrs • SCr > 2.0 mg/dL • Bilirubin > 2 mg/dL • Coagulopathy ( INR > 1.5) • Sepsis-induced hypotension

Suspected infection + “some of the following” • Fever ( >38.3o C) or hypothermia (<36o C) • Tachycardia (> 90 BPM) • Tachypnea (RR > 20) • Leukocytosis (WBC > 12000/uL) • Leukopenia (WBC < 4000/uL) • Altered mental status • Thrombocytopenia (PLT < 100000/uL) • Hyperglycemia (in the absence of DM)

Sepsis

Early Goal-Directed Therapy

Parameter Endpoint (goal) Marker for: Correction:

Central Venous Pressure

8-12 mmHg Intravascular fluid status

Fluid bolus

Mean Arterial Pressure

>/= 65 mmHg Global organ perfusion

Fluid, pressors

Central Venous Oxygen Sat

> 70% Cardiac Output Inotropes

Urine Output > 0.5 mL/kg/h Renal perfusion Fluids, pressors

Within 6 hours

Surviving Sepsis Campaign Bundles

Within 3 hours

• Measure lactate • Obtain blood Cx • Administer Abx • Fluid Bolus

Within 6 hours

• Apply Vasopressors • Measure CVP* • Measure SCVO2* • Re-measure Lactate*

Additional Therapies

• Corticosteroids

• Inotropes


1. BROAD SPECTRUM IV antibiotics which will cover ALL SUSPECTED PATHOGENS administered within ONE HOUR of diagnosis and INFUSED as RAPIDLY as allowable (grade 1B/1C)

2. Cultures as clinically appropriate before antimicrobial therapy if no significant delay

(> 45 mins) in the start of antimicrobial(s) (grade 1C)

1. Empiric combination therapy should not be

administered for more than 3–5 days. De-escalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known (grade 2B)

Guideline Recommendations:

Within 3 hours


Within 3 hours



0

1

0-0.

49

0.5-

0.99

1-1.

99

2-2.

99

3-3.

99

4-4.

99

5-5.

99

6-8.

99

9-11

.99

12-2

3.99

24-3

5.99 36+

Fra

ctio

n o

f P

atie

nts

Time from hypotension onset (hrs)

Survival Fraction Cumulative effective antimicrobial initiation

~7% mortality/hr


GPC + GNR MRSA Pseudomonas Anaerobes Atypicals

Ceftriaxone + Azithromycin

Ceftriaxone + Azithromycin

Ceftriaxone + metronidazole

Ceftriaxone + metronidazole

Vancomycin + Cefepime

Vancomycin + Cefepine

Vancomycin + Cefepime

Vancomycin + pip-tazo




Vancomycin + pip-tazo + Levofloxacin





Vancomycin + Meropenem + Levofloxacin





Common Empiric Regimens for Severe Sepsis

* Addition of ESBL activity


Carbapenems

Piperacillin/ Tazobactam

Cefepime

Levofloxacin

Ceftriaxone

Ceftazidime

Vancomycin

Metronidazole

Broadest Narrowest

Sequence Matters

Within 3 hours



Crystalloids Colloids

Lactated Ringers

Normal Saline

Albumin* 25%

Albumin* 5%

Place in therapy FIRST Line

FIRST Line

Unknown Unknown

Recommended Challenge (dose)

30 mL/kg 30 mL/kg N/A N/A

“(Theoretical) Intravascular equivalent”

25 mL 25 mL 500 mL 100 mL

*May administer as rapidly as necessary to improve clinical condition.

After volume replacement: 5%: DNE 5-10 mL/minute in patients with hypoproteinemia 25%: DNE 2-3 mL/minute in patients with hypoproteinemia


Within 3 hours


Within 6 hours



• Inotropes • Corticosteroids


Within 6 hours


Vasopressor α1 β1 β2 Place in therapy

Norepinephrine ++++ ++ - First line for septic shock

Epi 0.01-0.05 mcg/kg/min

Epi > 0.05 mcg/kg/min

+ ++++ ++ Second line/adjunct for septic shock

+++ +++ +

Phenylephrine ++++ - - Salvage therapy for shock, sedation-induced HOTN

Dopamine 3-10 uc/kg/min

Dopamine > 10 ug/kg/min

- ++++ ++ Convenience, adjunct for septic shock in low CO states +++ ++++ +

Tips and Tricks: • Multiple pressors may be used concomitantly to achieve

adequate perfusion • All pressor orders should have a titration target (MAP, SBP, etc)

Within 6 hours



Illustrative Comparative Risk

Outcome Assumed Risk

Corresponding Risk

Effect N

Dopamine Norepinephrine

Mortality 530/1000 482/1000 RR 0.91 (0.83-0.99)

2043

Supra-ventricular arrhythmias

229/1000

82/1000

RR 0.47 (0.38-0.58)

1931

Ventricular arrhythmia

39/1000 15/1000 RR 0.35 (0.19-0.66)

1931

Takeaway - Pooled evidence demonstrates greater risk for arrhythmia and mortality with dopamine use vs NE as the initial vasopressor in septic shock.


Within 3 hours


Within 6 hours



• Corticosteroids • Inotropes




Hydrocortisone 50 mg q6h IV push

50 mg q6h x 7 days then stop

50 mg Q6H x 5 days, then 50 mg BID x 3 days, then 50 mg QD x 3 days

Wean/discontinue when vasopressors off


Are inotropes indicated???

• Low central/mixed venous oxygen saturation • Signs of hypoperfusion despite adequate MAP • Elevated cardiac filling pressures • Low cardiac output

Inotrope α1 β1 β2 Range Parameters

Dobutamine - ++++ - 0-20 mcg/kg/min Heart rate or MAP



Parameter Endpoint (goal) Marker for: Correction:

Central Venous Pressure

8-12 mmHg Intravascular fluid status

Fluid bolus

Mean Arterial Pressure

>/= 65 mmHg Global organ perfusion

Fluid, pressors

Central Venous Oxygen Sat

> 70% Cardiac Output Inotropes

Urine Output > 0.5 mL/kg/h Renal perfusion Fluids, pressors

Within 6 hours

Early Goal-Directed Therapy


Within 3 hours


Within 6 hours



• Corticosteroids

• Inotropes

Patient Case

History of Present Illness JL, 74 yo female, presents to the ED on 4/28 with low-grade fever (37.8o C), N/V x 3-4 weeks, decreased appetite and diffuse abdominal pain. She appears weak and in moderate distress. After initial examination, a decision is made to admit her to perform a workup for intra-abdominal infection. While waiting for a bed on the general medical floor she developed hypotension refractory to 3 L of NS, altered mental status, respiratory failure and anuria. She was intubated, rushed to the ICU and placed on MV.

NKDA Past Medical History Past Surgical History Asthma 6/13/1960 SBO/hernia repair 1/30/2014 T2DM 4/5/1998 Cholecystectomy Unknown HTN 10/30/1993 Depression 7/6/2004 Social History Morbid Obesity 8/20/1991 1-2 cigarettes every other day smoker (stopped in 1980’s)

Home Medications Albuterol MDI 2 puffs every 4-6 hours PRN SOB Metformin 850 mg One tablet by mouth twice daily Fluticasone 110 mcg inhaler 2 puffs twice daily Lisinopril 10 mg One tablet daily Mirtazapine 15 mg One tablet at bedtime Promethazine 25 mg Every 6 hours PRN N/V

Patient Case

VS: BP 87/43; P 120-153; RR 14-33; T 37.8oC; SpO2: 91% on MV; UOP (24h) 25 mL; Wt 145.5 kg; Ht 5’2” Labs:

Lab Value Unit

Na 133 mEq/L

K 2.9 mEq/L

Cl 98 mEq/L

CO2 12 mEq/L

BUN 13 Mg/dL

sCr 1.1 mg/dL

Glu 230 mg/dL

Ca 6.9 mg/dL

Mg 2.5 mg/dL

Lab Value Unit

Phos 2.5 mg/dL

Alb 2.1 g/dL

Alk Phos 127 IU/L

T. Bili 0.2 mg/dL

AST 11 IU/L

ALT 7 IU/L

Hgb 13.6 g/dL

Hct 42 %

Plt 261 x103 /mm3

Lab Value Unit

WBC 25.5 x103 /mm3

Bands 15 %

pH 7.14

pCO2 26 mmHg

pO2 189 mmHg

HCO3 8.9 mmol/L

Base def -9.3 mmol/L

Lactate 9.8 mmol/L

Assessment J.L. is a 74 year-old Caucasian woman admitted with septic shock secondary to suspected intra-abdominal infection.

Patient Case

Patient Case

Question #1: What interventions and/or therapies should be accomplished within the first 6 hours of all septic shock or severe sepsis patients?

Parameter Goal Management Strategy

Central Venous Pressure (CVP)

8-12 mmHg Crystalloids

Mean Arterial Pressure (MAP)

>65 mmHg Crystalloids, Pressors

UOP >0.5 mL/kg/hr Crystalloids, Pressors

SVCO2/SVO2 >70%/65% As above, inotropes, PRBs

Measure Lactate Obtain BCs Fluid Bolus Antibiotics

Within 3 Hours

Vasopressors Measure CVP Measure SVCO2

Within 6 Hours

Fluids to target CVP

Pressors to target MAP

Deescalate Antibiotics as appropriate

To resolution

Treatment Bundles

Dellinger 2012

Patient Case

Patient Case

Question #2: What type of fluid should be recommended to appropriately resuscitate patients with septic shock/severe sepsis

Agent Volume Rate Goal

Crystalloid (NS,LR)

20-30 mL/kg 1000 mL bolus CVP 8-12 mmHg

Colloid (Albumin)

250-500 mL bolus CVP 8-12 mmHg

DO NOT USE: Hetastarch (Renal dysfunction) D5W (Does not stay intravascular)

Patient Case

Question #3: When should vasopressor agents be considered in the treatment of hypotension related to sepsis, and which agents are appropriate?

Receptor Norepinephrine* Epinephrine (0.01-0.05

mcg/kg/min)

Dopamine Phenylephrine

Alpha1 +++ ++ Variable ++++

Beta1 +++ ++++ Variable +

Beta2 + +++ Variable

Dopamine1 ++++

Add on option: Vasopressin 0.03 units/min

Justin Jones, PharmD Sanford Medical Center, Fargo Staff Education 2015

Surviving Sepsis: A CRASH Course

References and further reading Delinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock. Crit Care Med 2013;41:580-637. Kumar A, Roberts D, Wood KE, 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;34(6):1589-96. The SAFE Study Investigators. A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit N Engl J Med 2004; 350:2247-2256 Annane D, Véronique Sébille, Claire Charpentier et al. Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock. JAMA. 2002;288(7):862-871 Sprung CL, et al. "Hydrocortisone therapy for patients with septic shock". New England Journal of Medicine. 2008. 358(2):111-24.