A 60-year-old diabetic male patient presented with a history of dysuria and fever. His vital signs on admission were as follows: pulse 120/min, BP 80/50 mmHg, and respiratory rate 28/min. He was disoriented and agitated.

Sepsis, which is a host response to an infection, can have a varied presentation and carries a poor prognosis. Early identification and appropriate risk stratification will help in early resuscitation with a decrease in morbidity and mortality.

Step 1: Take care of airway and breathing

•Proper airway care and, if needed, assisted ventilation should be promptly initiated in all patients with severe sepsis and shock (see Chap. 78).

Step 2: Assess severity of sepsis

•After initial resuscitation, it is important to identify and assess severity of sepsis.

•Categorizing patients into sepsis, severe sepsis, and septic shock helps in triaging, prognostication, and choosing appropriate therapy (Table 50.1).

Step 3: Maintain circulation

•Fluid resuscitation is of utmost importance in initial management of severe sepsis and septic shock patients.

M. Kharbanda, M.D., F.N.B. (*)

Department of Critical Care, AMRI Hospitals, Kolkata, India e-mail: mohitkharbanda@hotmail.com

S. Ramasubban, A.B. (C.C.M.), F.C.C.P.

Critical Care, Apollo Gleneagles Hospital, Kolkata, India

Table 50.1 Definitions

SIRS—two or more of the following:

Temperature >38°C or <36°C

Heart rate >90/min

Respiratory rate >20/min or PaCO2 < 32 mmHg

WBC > 12,000 or < 4,000 (>10% bands)

Sepsis—SIRS plus infection

Severe sepsis

Sepsis with sepsis-induced organ dysfunction or evidence of tissue hypoperfusion like elevated lactate

Sepsis-induced hypotension

Systolic blood pressure (SBP) < 90 mmHg or MAP < 70 mmHg or SBP decrease >40 mmHg or <2 SD below normal for age in the absence of other causes of hypotension

Septic shock

Sepsis with hypotension (systolic <90 mmHg) despite fluid resuscitation

•Insert a wide-bore peripheral line and give initial fluid challenge of 1,000 mL of crystalloids (normal saline or Ringer lactate) to achieve a minimum of 30 ml/kg of crystalloids over 30–60 min with careful monitoring of vital signs.

•Albumin may be added to the initial resuscitation fluid in patients having or anticipated to have a low albumin value.

•Hydroxyethyl starches with a molecular weight >200 and degree of substitution >0.4 should be avoided as these may cause nephrotoxicity.

•Fluid resuscitation should be continued as long as the hemodynamics, based on either dynamic (delta pulse pressure or stroke volume variation) or static variable (CVP, urine output), continues to improve and serum lactate continues to decrease.

•Recent trial conducted in Africa on a pediatric population with severe sepsis have shown fluid loading may be detrimental in this population.

Step 4: Send initial investigations

•As the patient is being resuscitated, send blood for complete hemogram, blood cultures (two sets), and other appropriate cultures depending on the clinical situation, urea, creatinine, electrolytes, liver function test, ECG, and chest X-ray.

•Blood lactate—send arterial blood for arterial blood gas and lactate analysis. Increased lactate is a feature of global hypoperfusion and needs urgent attention.

•Serial lactate measurement is useful in monitoring response to resuscitation.

•If lactate is not available, base deficit (metabolic acidosis) can be taken as a surrogate marker of lactic acidosis.

•Appropriate viral cultures and real-time PCR (more sensitive and specific) should be obtained but should not delay prompt administration of antiviral therapy.

Step 5: Start antimicrobial agent

•Appropriate broad-spectrum antibiotics as per hospital protocol should be started immediately, preferably within 1 h of presentation.

•Appropriate cultures should be sent before starting antibiotics, but if these are delayed for logistic reasons beyond 45 min, antibiotics should be started.

•One or more agents active against likely bacterial/fungal or viral pathogens and with good penetration into presumed source should be selected (see Chap. 49).

•Combination therapy with an extended-spectrum beta-lactam and an aminoglycoside or a fluoroquinolone is recommended for Pseudomonas aeruginosa bacteremia. Combination therapy may also be used for patients at high risk for multidrug-resistant bacteria like Acinetobacter and in neutropenic and immunocompromised patients.

•A combination of beta-lactam and a macrolide should be used in patients with pneumococcal bacteremia with septic shock.

•The duration of therapy is typically 7–10 days; longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, some fungal or viral infection, or immunologic deficiencies including neutropenia.

•Antiviral therapy should be initiated as early as possible in patients with severe sepsis or septic shock of viral origin, when available, such as for severe influenza infection.

•In patients at high risk like those with neutropenia and severe immunosuppression, empirical antifungal therapy should be started (refer to Chap. 53).

Step 6: Initiate hemodynamic monitoring

•For patients who do not maintain mean arterial pressure (MAP) of more than 65 mmHg in spite of initial fluid administration, central and arterial lines should be inserted under aseptic technique.

•Further fluid resuscitation should be done according to the principles of early goal-directed therapy.

•This has been proved to be useful for patients presenting within 6 h of septic shock.

•Keep central venous pressure (CVP) 8–10 cm H2O and 12–15 cm H2O in patients on the ventilator.

•Maintain urine output of more than 0.5 mL/Kg of body weight by fluid resuscitation.

•Keep MAP of more than 65 mmHg by fluids and vasopressors.

•Maintain ScvO2 more than 70% by fluids, by keeping hemoglobin more than 10 g% (blood transfusion), and if necessary by adding dobutamine (Table 50.2).

Step 7: Optimize vasopressor use

•If the patient remains hypotensive in spite of fluid resuscitation of more than 20 mL/Kg of crystalloid or its equivalent, the vasopressor (preferably norepinephrine) needs to be started to keep MAP more than 65 mmHg (see Chap. 16).

•Intra-arterial line should be placed in all these patients.

•Epinephrine should be the first chosen alternative agent in septic shock that is poorly responsive to norepinephrine.

Table 50.2 Severe sepsis resuscitation bundle (6-h bundle): complete tasks within 6 h of identifying severe sepsis

Measure serum lactate

Obtain blood cultures prior to antibiotic administration

Administer broad-spectrum antibiotics within 3 h of emergency department (ED) admission and within 1 h of non-ED admission

In the event of hypotension and/or serum lactate >4 mmol/L: Deliver an initial minimum of 20 mL/Kg of crystalloid

Begin vasopressors for hypotension not responding to initial fluid resuscitation to maintain MAP >65 mmHg

In the event of persistent hypotension despite fluid resuscitation (septic shock) and/or lactate >4 mmol/L:

Achieve a central venous pressure (CVP) of >8 mmHg

Achieve a central venous oxygen saturation (ScvO2) ³70% or mixed venous oxygen saturation (SvO2) ³ 65%

•Add low-dose vasopressin (0.03 unit/min) if the patient remains hypotensive on catecholamine.

•Vasopressin should not be used as a first-line agent for hypotension.

•Dopamine may be used as an alternative vasopressor agent to norepinephrine in highly selected patients at very low risk of arrythmias and with low cardiac output and/or low heart rate.

•High-dose vasopressors should always be given through the central line.

•All attempts should be made to taper off vasopressors once blood pressure stabilizes.

•Low-dose renal dopamine should not be used in managing these patients.

•Dobutamine infusion should be administered or added to vasopressor (if in use) in the presence of myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output.

Step 8: Optimize hemodynamics

•If the patient becomes hemodynamically unstable during monitoring, give further fluid challenge: 1,000 mL of crystalloids or 300–500 mL of colloids over 30 min.

•This fluid is given in addition to the maintenance fluid.

•Rate of fluid administration should be reduced if cardiac filling pressures increase without concurrent hemodynamic improvement or the patient develops signs of fluid overload and decreasing oxygen saturation.

Step 9: Identify source and assess severity of organ dysfunction

•Further investigation should be performed depending on the specific disease state.

•A specific anatomic site of infection (Table 50.3) should be established as rapidly as possible with the help of early imaging such as ultrasonography and CT scan.

•The patient should be transported for diagnostic imaging only when stable and with appropriate monitoring.