Severe Sepsis And Septic Shock - Standard Treatment Guidelines

Sepsis (from Greek sepein = to rot, putrefy)is a significant problem worldwide in the intensive care unit both in terms of the burden on the healthcare and the morbidity and the mortality it causes. Despite the advances in the treatment and the understanding of the pathophysiology of sepsis, the mortality has remained unforgivably high. The site of infection is difficult to estimate and even among those patients where the site is strongly suspected, cultures might be negative or of questionable significance. Though a positive blood culture would be diagnostic, the rate of positivity is only 30 to 50 % percent. It is easy to confuse the diagnosis of sepsis with conditions that simulate it such as pancreatitis or anaphylactic reactions or drug fever. Early identification and prompt treatment is the key to reduce mortality.

Ministry of Health and Family Welfare has come out with the Standard Treatment Guidelines for Severe Sepsis And Septic Shock. Following are its major recommendations.

Case definition:

Till 2001 there was no clear definition of sepsis. As a result there was no uniformity in the treatment guidelines. International sepsis forum defined sepsis in the following way

Incidence of The Condition In Our Country

The incidence of sepsis and the number of sepsis-related deaths are increasing, although the overall mortality rate among patients with sepsis is declining. The mortality rates associated with severe sepsis and septic shock are 25% to 30% and 40% to 70% respectively Though we do not have exact statistics from India, one Indian study showed incidence of SIRS without organ dysfunction as 51.60%, SIRS with organ dysfunction as 17.10% patients, of which 76.50% were due to sepsis and 23.50% were not due to sepsis. ICU mortality of all admissions was 13.90% and that of severe sepsis was 54.10%. Hospital mortality and 28-day mortality of severe sepsis were 59.30% and 57.60%, respectively.

Differential Diagnosis

Severe Sepsis and Septic shock should be differentiated from other common cause of fever and shock in ICU or hospital like -

1) Acute pancreatitis.

2) Drug fever.

3) Anaphylaxis and anaphylactoid reactions.

4) Adrenal crisis.

5) Cardiogenic shock, hemorrhagic shock or neurogenic shock.

6) Pulmonary embolism or pulmonary infarct.

7) Myxedema coma.

8) Thyrotoxicosis.

9) Poisoning or insect bite.

10) Burn, major surgery

11) SLE crisis.

12) Macrophage activation syndrome.

Although making the distinction of the above conditions from true sepsis becomes difficult, using different biomarkers and imaging studies might be helpful in making the diagnosis. Close monitoring and optimising the patient physiological variables will give us time to identify the exact insult.

Prevention And Counseling

Sepsis is a medical emergency. Awareness and recognition are the key of survival.The following action plan should be used to reduce global mortality from severe sepsis.

• Build awareness of sepsis.


• Follow standards guidelines of care.


• Improve early and accurate diagnosis.


• Increase the use of appropriate treatments and interventions.


• Educate staff about sepsis diagnosis, treatment and management.


• Data collection for the purposes of audit and feedback

Optimal Diagnostic Criteria, Investigation, Treatment & Referral Criteria

*Situation 1: At Secondary Hospital/ Non-Metro situation: Optimal Standards of Treatment in Situations where technology and resources are limited

Clinical Diagnosis:

The presentation of sepsis varies. The most important step towards improving survival is to identify the signs of sepsis very early.

General variables:

• Altered mental status.


• Fever.


• Hypothermia.


• Tachycardia.


• Tachpnea.


• Hyperglycaemia (plasma glucose >120 mg/dL or 7.7mmol/L) in the absence of diabetes.


• Positive fluid balance.

Inflammatory variables:

• Leukocytosis.


• Leukopenia.


• Normal WBC count with >10 % band forms.

Organ dysfunction variables:

• Respiratory –Decreased oxygen saturation


• Renal – Acute oliguria urine output <0.5ml/kg/hr for atleast 2 hrs or rise in Creatinine > 0.5 mg/ dL.


• Haematological- Thrombocytopenia (platelet count <100,000/ µL) or coagulation abnormalities: International Normalised Ratio INR >1.5 or activated partial thromboplastin time aPTT > 60 sec.


• Liver - Hyperbilirubinemia (plasma total bilirubin>4.0 mg/ dL or 70 mmol/ L).

Tissue perfusion variables:

• Decreased capillary refill or mottling

Haemodynamic variables:

Arterial hypotension, Systolic Blood Pressure SBP <90 mm Hg, Mean Arterial Blood Pressure MAP <70 mm Hg, or SBP decrease >40 mm Hg.

Investigations:

Investigations should be directed at diagnosis, assessing the focus of sepsis, and the severity of the sepsis.

1) Hb

2) TLC

3) DLC

4) Blood Glucose.

5) Renal function tests (SE,BUN,Cr)

6) Liver function test (Bi,AST,ALT,ALKP,GGT,PT,INR,PTT)

7) Cultures with gram stain

8) Urine R/M

9) X-Ray

10) ECG

Treatment:

Standard Operating procedure

a. In Patient

Sepsis should be treated in the ICU, if recognized out side the ICU. Immediately start fluid resuscitation, collect blood culture and give broad spectrum antibiotics within 1 hr, culture collection should not delay antibiotic administration, and simultaneously organize ICUtransfer.

b. Out Patient

Resuscitation with fluid in the emergency department collect blood culture and give broad spectrum antibiotics within 3hrs , culture collection should not delay antibiotic administration, and shift the patient in the ICU.

c. Day Care

Do not admit septic patient in Day care setting.

Referral criteria:

Generally, patients can be considered for transfer for diagnosis, source control or further monitoring when they are hemodynamically stable with or without vasoactive drugs and when oxygenation and ventilation is maintained.

a) Need Invasive monitoring devices such as arterial lines, centralline, flow trac.

b) Mechanical ventilation, dialysis or CRRT required.

c) Modern surgical facilities.

d) Ultrasound and CT scan or MRI

Always communicate with receiving hospital physician, document the reason for transport and arrange appropriate staff, medication and instrument for transportation.

*Situation 2: At Super Specialty Facility in Metro location where higher-end technology is available

Clinical Diagnosis:

The presentation of sepsis varies. The most important step towards improving survival is to identify the signs of sepsis very early.

General variables:

• Altered mental status.


• Fever.


• Hypothermia.


• Tachycardia.


• Tachpnea.


• Hyperglycaemia (plasma glucose >120 mg/dL or 7.7mmol/L) in the absence of diabetes.


• Positive fluid balance.

Inflammatory variables:

• Leukocytosis.


• Leukopenia.


• Normal WBC count with >10 % band forms.

Organ dysfunction variables:

• Respiratory –Decreased oxygen saturation


• Renal – Acute oliguria urine output <0.5ml/kg/hr for atleast 2 hrs or rise in Creatinine > 0.5 mg/ dL.


• Haematological- Thrombocytopenia (platelet count <100,000/ µL) or coagulation abnormalities: International Normalised Ratio INR >1.5 or activated partial thromboplastin time aPTT > 60 sec.


• Liver - Hyperbilirubinemia (plasma total bilirubin>4.0 mg/ dL or 70 mmol/ L).

Tissue perfusion variables:

• Decreased capillary refill or mottling

Haemodynamic variables:

Arterial hypotension, Systolic Blood Pressure SBP <90 mm Hg, Mean Arterial Blood Pressure MAP <70 mm Hg, or SBP decrease >40 mm Hg.

Investigations:

ABG

SCVO2.

Serum lactate

Procalcitonin (PCT)

These biomarkers may be useful to distinguish between infectious and non-infectious causes of SIRS.PCT can be used to assess the severity of infection and prognostication. It also acts as a tool to guide Antimicrobial Therapy.

• Ultrasonography (source identification)


• CT scan if it is safe to do(source identification)


• USG or CT guided sample from the source – minimally invasive approach is advisable to prevent change in physiology and keep in mind the risk of transportation to imaging department.

Treatment:

Follow the Surviving Sepsis Campaign (SSC) International guidelines for management of severe sepsis.Rapid diagnosis, expeditious treatment multidisciplinary approaches are critical and necessary in the treatment of sepsis. The management of patients with sepsis starts on arrival at the emergency room prior to ICU admission. Special focus on fluid and hemodynamic resuscitation and early antibiotics.

(1) Within the first 6 hours (Early goal-directed therapy)

Fluid therapy

1. Start resuscitation with fluid boluses if hypotension or serum lactate >4mmol/L to maintain

• Central venous pressure (CVP) more than or equal to 8-12 mm Hg and 12-15mmHg in mechanically ventilated patient or intra abdominal hypertension.


• Mean arterial pressure (MAP) more than >65 mm Hg


• Urine output more than 0.5 ml/kg/hr


• Mixed venous oxygen saturation Svo2 >65% and central venous oxygen saturation (Scv02).


• Rate of fluid administration should be reduced if cardiac filling pressures increase without concurrent hemodynamic improvement.


• If mixed venous oxygen saturation Svo2 <65% transfuse packed red blood cells to achieve a hematocrit of >30% and/or dobutamine infusion (up to a maximum of 20 µg/kg/min).

Diagnosis

1) Cultures with gram stain- Obtain appropriate cultures before starting antibiotics provided this does not significantly delay antimicrobial administration.

• Two or more blood cultures.


• One or more BCs should be percutaneous.


• One BC from each vascular access device in place for >48 hours.


• Other site cultures as clinically indicated Eg. Tracheal culture, sputum culture, ascetic fluid culture, Urine cultures. (should be sent in lab within one hour)

Antibiotic therapy

1. Begin intravenous antibiotics early within the first hour of recognizing Severe sepsis or septic shock.

• Broad-spectrum agents


• Active against likely bacterial/fungal pathogens


• Good penetration into the source

2. Reassess antimicrobial regimen daily

3. Combination therapy in Pseudomonas infections and in neutropenic patient.

4. De-escalation after culture sensitivity report.

Early and appropriate antibiotic therapy and control of the source of infection arethe major therapies shown to improve survival in sepsis.

Source identification and control

1. Source of infection should be established as rapidly as possible and start measures to control the source within the first 6 hours of presentation as soon as the initial resuscitation is done e.g. abscess drainage, tissue debridement and removal of central line. In pancreatitis avoid early surgical intervention.

2. Source control measures must be directed at achieving maximal efficacy with minimal physiological upset.

Vasopressor

1. Use norepinephrine or dopamine through central line to keep MAP ≥ 65mmHg administered as the initial vasopressors of choice.

2.Epinephrine, phenylephrine, or vasopressin should not be used as the initial vasopressor in septic shock

3.Vasopressin 0.01 to 0.04 units/min may be subsequently added.

4.Epinephrine as the first alternative agent in septic shock when norepinephrine is not effective.

5.Do not use low-dose dopamine for renal protection.

6.In patients requiring vasopressors arterial catheter should be put as soon as practical.

Inotropic support

1.In case of myocardial dysfunction as evidenced by increased cardiac filling pressures and decreased cardiac output dobutamine can be used.

2.Dobutamine infusion (up to a maximum of 20 µg/kg/min) if mixed venous oxygen saturation Svo2 <65%.

3.Do not target predetermined supranormal levels of cardiac index.

(2) After initial resuscitation (24 hours goal)

Steroid

1. Consider use of low dose intravenous Hydrocortisone (≤300mg/day)

a. Septic shock poorly responsive to fluid and vasopressors

b. Endocrine or corticosteroid history warrants it

2.Do not use steroids to treat sepsis in the absence of shock and wean it once vasopressors are no longer required

3. Hydrocortisone is preferred to dexamethasone

4. There is no role of ACTH stimulation test while determining whether the patient should receive hydrocortisone to treat septic shock.

Blood product administration

1. Packed red blood cells should be given to patients with hemoglobin less than 7.0 g/dL (<7.0 g/L). Achieve target hemoglobin of 7.0 -9.0 g/dL in adults.In certain special circumstances, A higher hemoglobin level may be required. (e.g.: myocardial ischemia, severe hypoxemia, acute hemorrhage, cyanotic heart disease, or lactic acidosis)

2. Erythropoietin must not be used to treat sepsis-related anemia

3. In case of active bleeding, fresh frozen plasma may be used. But its use for correcting laboratory clotting abnormalities is contraindicated unless an invasive procedure is planned.

4.platelets should be transfused in case of -

- Counts< 5000/ µL regardless of bleeding.

- Counts between 5000 to 30,000/ µL and there is significant bleeding risk.

- Higher platelet counts ≥ 50,000/ µL in case of surgery or invasive procedures.

Mechanical ventilation of sepsis-induced acute lung injury (ALI)/ARDS

1.Target a tidal volume of 6mL/kg (predicted) body weight and plateau pressure ≤30cmH2O in patients with ALI/ARDS.

2. Positive end expiratory pressure (PEEP) should be set according ARDS NET protocol to avoid extensive lung collapse at end expiration and prevent over distention of normal lung.

3. Allow permissive hypercapnia if needed, to minimize plateau pressures and tidal volumes

4. Weaning protocol and a spontaneous breathing trial (SBT) regularly to evaluate the potential for discontinuing mechanical ventilation.(1A)

• Daily SBT (spontaneous breathing trial)

• Before the SBT, patients should:

– be arousable

– be hemodynamically stable without vasopressors

– have no new potentially serious conditions

– have low ventilatory and end-expiratory pressure requirement

– require FiO2 levels that can be safely delivered with a face mask or nasal cannula

5. Do not use a pulmonary artery catheter for the routine monitoring.

6. Consider early prone position or rescue therapy for refractory hypoxia

7. Use a conservative fluid strategy for patients with established ALI/ARDS after initial resuscitation.

Lung protective ventilation strategy using low tidal volume ventilation reduces ventilatorinduced lung injury like volutrauma, barotrauma, atelectrauma and biotrauma. This is the only ventilator manipulation that has been shown definitively to reduce injury and absolute mortality reduction of 9%.

Sedation, analgesia, and neuromuscular blockade in sepsis

1. Use sedation protocols with a sedation goal for critically ill mechanically ventilated patients.

2. Avoid neuromuscular blockers where possible. Monitor depth of block with trainof-four when using continuous infusions.

Glucose control

1.Aim to keep blood glucose 150 - 180mg/dL using a validated protocol for insulin dose adjustment.

Renal replacement

1.Consider early renal replacement therapy

2.Intermittent hemodialysis and continuous veno-venous hemofiltration (CVVH) are considered equivalent.

3.CVVH offers easier management in hemodynamically unstable patients.

Bicarbonate therapy

1.Do not use bicarbonate therapy to improve hemodynamics or reducing vasopressor requirements with lactic acidemia and pH < 7.15.

Deep vein thrombosis (DVT) prophylaxis

1.Use either low-dose unfractionated heparin (UFH) or low-molecular weight heparin (LMWH), unless contraindicated.

2.Use a mechanical prophylactic device, such as compression stockings or an intermittent compression device, when heparin is contraindicated.

3.Combination of pharmacologic and mechanical therapy high risk for DVT.

Stress ulcer prophylaxis

1.Provide stress ulcer prophylaxis using H2 blocker or proton pump inhibitor.

Consideration for limitation of support

1.Discuss advance care planning with patients and families. Describe likely outcomes and set realistic expectations.

Guidelines by The Ministry of Health and Family Welfare :

FN Kapadia, Consultant Physician & Intensivist, PD Hinduja National Hospital, Mumbai

Rishi Kumar Badgurjar, Associate Intensive Care Unit Consultant, PD Hinduja National Hospital, Mumbai