Sepsis and Septic Shock

Objectives

1. Collect and assess relevant information used to diagnose and manage sepsis and septic shock

2. Design a patient specific pharmacotherapy plan for a patient with sepsis or septic shock, including drug, route, frequency and/or duration of therapy. (Must provide dosing for fluids and steroids.)

3. State rationale for drug therapy and monitoring regimens, including anticipated physiologic response to vasopressors.

4. Monitor and evaluate patient-specific medication therapy regimens for appropriateness, safety, and effectiveness, and make evidence-based recommendations for optimal medication therapy.

5. Monitor and evaluate progress toward or achievement of patient-specific goals of therapy and recommend appropriate actions for modification, where appropriate.

Sepsis Definition

• Life-threatening acute organ dysfunction due to infection

• Need to use a tool to identify the organ dysfunction

Screening Tool questions

1. What is recommended to identify organ dysfunction?

2. What is no longer used?

3. What are other potential screening tools?

1. SIRS - Systemic Inflammatory Response Syndrome

2. QSOFA

3. MEWS, MEWS2, NEWS

SIRS Criteria

Suspected or proven infection + 2 or more SIRS criteria

• Temperature > 38ºC or < 36ºC

• HR > 90 beats/minute

• RR > 20 breaths/minute

• WBC >12,000/mm3 OR < 4,000/mm3 OR >10% bands (elevated bands in bacteria infection)

**Recall there’s nothing about BP

Septic shock Definition

• Sepsis plus

• Persistent hypotension requiring vasopressor use plus

• Serum lactate > 2 mmol/L

• Despite adequate fluid resuscitation

  • 30 ml/kg IV crystalloids

In patients with sepsis and either hypotension and/or elevated lactate

• Monitoring

• Fluids

• Vasoactive agents

Monitoring

• Immediate, ongoing, at least hourly: monitor blood pressure, heart rate, respiratory rate, and level of consciousness.

• Within 1 hour: measure initial serum lactate and capillary refill time.

Fluids

• Within 3 hours: Give initial fluid resuscitation of at least 30 ml/kg intravenous crystalloids.*

• MEANING → have to get fluids into patients within 3 hours

• Use balanced solutions (e.g., Ringer's lactate).

Vasoactive agents (needs central line), if hypotensive

• Time-sensitive: consider initiating norepinephrine concurrent to fluid resuscitation in patients with life-threatening end-organ hypо-perfusion.

• Use norepinephrine as the first-line vasopressor. Start vasopressors peripherally rather than delaying administration until central access is secured.

• Target a MAP of ≥65 mm Hg, or 60-65 mm Hg in patients aged ≥65 years.

Initiate IV isotonic crystalloid fluid immediately in patients with

Elevated lactate OR Hypotension

Initial Fluid Resuscitation for Sepsis

• Dosing?

• Ideal administration?

• At least 30 ml/kg (ideal body weight) IV of crystalloid within first 3 hours of resuscitation

• Ideally administered within 1-2 hours

• Faster administration associated with faster resolution of shock

Fluid selection

• Plasmalyte or Lactated Ringers recommended over 0.9% NaCl

• Dextrose is not included unless the patient is also hypoglycemic

• No benefit to using albumin early in early resuscitation

Dosing for initial fluid resuscitation for sepsis

• Actual body weight

• If BMI > 30 kg/m2 use ideal or adjusted body weight

• IBW Women: 45.5 + (2.3 x inches over 60)

• IBW Men: 50 + (2.3 x inches over 60)

Route, frequency, duration

• IV at 1000 ml/hr

• Until shock resolves, patient develops fluid overload, or vasopressors need to be initiated

Monitoring IV fluids for efficacy in Sepsis for Efficacy

Primary measure:

• Mean arterial pressure (MAP) > 65 mmHg

• OLDER ADULTS (60-65 mm hg)

• Equation →

Secondary measure:

• Lactate

• Decreasing towards normal (<2.5 mmol/L)

Apoxia

Elevated lactate

Monitoring IV fluids for toxicity in sepsis

• 0.9% NaCl toxicity

• Lactated Ringers toxicity

• Plasmalyte toxicity

0.9% NaCl toxicity

• Hyperchloremic metabolic acidosis

• AKI

• Peripheral or pulmonary edema

Lactated Ringers toxicity

• Peripheral or pulmonary edema

• Hyperkalemia

• Hypercalcemia

Plasmalyte toxicity

• Peripheral or pulmonary edema

• Hyperkalemia

First line vasopressor therapy

Norepinephrine continuous IV infusion

(can titrate)

Consider initiating concurrent to IV fluids in patients with

Life-threatening hypoperfusion or hypotension

IV Access for Vasopressors

• Long term vs. Short term

Long-term: Central IV line

Short-term: Peripheral acceptable until central access obtained

Vasopressor Efficacy Monitoring

• MAP > 65 mmHg

• Lactate normalization

Vasopressor Toxicity Monitoring

• Norepinephrine

• Epinephrine

• Vasopressin

Norepinephrine

• Tachycardia

• Arrhythmia

• Decreased GI and digital perfusion

Epinephrine

• Tachycardia

• Arrhythmias

• Impaired splanchnic circulation

• Lactate production

• Hyperglycemia

Vasopressin

• Splanchnic, digital, cardiac ischemia

If hypotension and/or lactate elevation persist after initial fluid resuscitation

1. Initiate norepinephrine, if not already initiated and hypotension persists after initial fluid resuscitation.

2. Use hydrocortisone, ± fludrocortisone, if norepinephrine requirement persists.

3. Add vasopressin, if norepinephrine dose is increasing.

4. Add epinephrine as third-line agent, if norepinephrine dose is still increasing.

5. Add dobutamine or use epinephrine, if cardiac dysfunction is present.

Antimicrobials in Sepsis and Septic Shock - Specimen collection

• Two sets of blood cultures before antimicrobial initiation

• Other cultures depending on suspected site of infection

Risk factors use empirical antimicrobial therapy with coverage for this MDR pathogen

• Colonization with a specific MDR pathogen

• Previous infection with specific MDR pathogen

• Prolonged use of broad-spectrum antibiotics

• Prolonged hospitalization in a unit with a high prevalence of specific MDR pathogens

Add anaerobic coverage only in those at risk, including

• Intra-abdominal infection

• Deep seated gynecological or obstetric source of infection

• Necrotizing soft tissue infection

• Head and neck infection

• CNS abscesses or empyema

Empiric antifungal therapy not recommended • Consider in patients with risk factors

• Immunosuppression

• Prolonged use of antibiotics

• Prolonged hospitalization

• Intra-abdominal sources of infection

Empiric Antimicrobial Selection – Unknown Source

Antimicrobial Dosing

Beta-lactams

• Initial bolus followed by prolonged infusion

Therapeutic drug monitoring & weight based dosing as appropriate for other drugs

Antimicrobial Duration of Therapy

• 5-8 days depending on site of infection

• Refer to disease-specific guidelines

• Shorter duration preferred

Antimicrobial Efficacy

• Fever resolves

• Oxygenation improves

• WBC normalizes

• Hemodynamics stabilize

Antimicrobial Toxicity

Beta-lactams

• Seizures

• Rash

• Anaphylaxis

• Diarrhea

• Acute interstitial nephritis

Vancomycin

• Vancomycin flushing syndrome

• Thrombocytopenia (HIT)

• Rash • Ototoxicity

• Renal failure

• AUC:MIC ratio

De-escalation of Therapy when

• Confirmed microbiological diagnosis and susceptibility profile available

• No pathogens are identified on final micro report

• Remove agents and/or narrow spectrum

• Procalcitonin + clinical evaluation can be used to aid antimicrobial discontinuation decisions

  • PCT levels will drop when bacterial infection improves

ABG

Abg

Supportive care

• Stress ulcer prophylaxis

• VTE prophylaxis

• Blood glucose control

Stress ulcer prophylaxis

• Indicated if high risk of bleeding

• Coagulopathy

• Chronic liver disease

• Shock

VTE prophylaxis

• Use unless contraindicated due to bleeding

• LMWH preferred over UFH

• No need to add mechanical prophylaxis

Blood glucose control

• Target 140-180 mg/dL

• Insulin gtt for glucose >180 mg/dl