Sepsis

Sepsis – Acute

Rahul Soman, M. Pharm

 

Definition  

Systemic Inflammatory Response Syndrome (SIRS) in Response to Infection  

 

* Adults :

o Presence of 2 or more general and inflammatory variables including temperature greater than 38°C or less than 36°C; heart rate greater than 90 beats/min; respiratory rate greater than 20 breaths/min (or PaCO2 less than 32 mmHg); WBC count greater than 12,000/mm3 or less than 4000/mm3, or normal WBC with greater than 10% immature forms

* Pediatrics (age less than 18 years) :

o Core temperature greater than 38.5°C or less than 36°C; measured by rectal, bladder, oral, or central catheter probe

o Tachycardia (otherwise unexplained increased heart rate more than 2 SD above the age norm or persistent increased rate, otherwise unexplained, over a 0.5- to 4-hour period) OR for children less than 1 year, bradycardia (otherwise unexplained decreased heart rate below the tenth percentile for age or persistent decreased rate over a 30-minute period)

o Tachypnea (respiratory rate greater than 2 SD of the age norm) OR need for mechanical ventilation not related to a neuromuscular disorder or anesthesia

o Leukocyte count elevation or depression outside the age norm, not related to chemotherapy, OR greater than 10% immature forms

 

Sepsis  

* Adults and Pediatrics :

o Documented or suspected infection plus evidence of a systemic inflammatory response (ie, SIRS)

 

Severe Sepsis  

* Adults :

o Sepsis plus presence of one or more organ dysfunctions manifested as acute lung injury, coagulation abnormalities, thrombocytopenia, altered mental status, renal, hepatic, or cardiac failure, or hypoperfusion with lactic acidosis

* Pediatrics :

o Sepsis plus one of the following: cardiovascular organ dysfunction OR acute respiratory distress syndrome OR two or more other organ dysfunctions

 

Septic Shock  

* Adults :

o Sepsis-induced hypotension that persists despite adequate fluid resuscitation

* Pediatrics :

o Sepsis and cardiovascular organ dysfunction despite adequate fluid resuscitation (eg, hypotension or need for vasoactive drugs or signs of decreased tissue perfusion)

 

Septicemia  

Includes sepsis, severe sepsis, and septic shock .

 

Sepsis Syndrome  

Systemic response to overwhelming infection

 

Sepsis-Induced Hypotension  

Systolic blood pressure (SBP) less than 90 mmHg or mean arterial pressure (MAP) less than 70 mmHg or a decrease in SBP greater than 40 mmHg or SBP less than 2 standard deviations below age-adjusted normal in the absence of other causes of hypotension

 

Vancomycin monitoring  

* Serum vancomycin measurement: To avoid drug resistance, a minimum serum vancomycin trough concentration above 10 mg/mL should be maintained. The trough level should be obtained just prior to the next dose once steady-state is achieved, which is typically before the fourth dose .

 

Medical History  

* Insertion of catheter into urinary bladder

* Intravenous cannulation

* Endotracheal intubation [Endotracheal intubation]

* Infectious disease of lung

* Infectious disease of abdomen

* Urinary tract infectious disease [Urinary tract infectious disease - Acute]

* Infection of skin AND/OR subcutaneous tissue

* Prosthetic joint infection

* Infection and inflammatory reaction due to cardiac valve prosthesis

* Patient immunocompromised

* Post-splenectomy septicemia

 

Findings  

* Fever

* Hypothermia - Acute

* Rigor

* Sinus tachycardia

* Bounding pulse

* Hypotension

* Tachypnea

* Oliguria

* Headache

* Altered mental status

* Warm skin

* Cool skin

* Mottling of skin

* Bowel sounds absent

* Cyanosis

* Diarrhea

* Nausea

* Vomiting

* Skin lesion

* Jaundice

 

Tests  

 

Suspected and known sepsis  

* Complete blood count with white cell differential, manual: The WBC count in sepsis is usually increased (>12,000/microL), but may be decreased (<4000/microL) or normal. A normal count with greater than 10% immature band forms may indicate an inflammatory response consistent with sepsis. Hematocrit and hemoglobin are typically elevated .

* Platelet count: A platelet count of less than 100,000/microL is associated with sepsis-induced organ dysfunction .

* Creatinine measurement, serum: A creatinine increase greater than 0.5 mg/dL is among the organ dysfunction variables used in the diagnosis of sepsis . An increase of 0.3 mg/dL or above within 48 hours is predictive of increased mortality in critically ill patients .

 

Suspected and known sepsis  

* Electrolytes measurement, serum

* Hepatic function panel

* Glucose measurement, blood

* Bilirubin, total measurement

* Prothrombin time

 

Suspected and known sepsis  

* Lactic acid measurement: Hyperlactatemia (serum lactate level ?2 mmol/L) indicates global tissue hypoxia in septic patients .

 

Suspected and known sepsis  

* Arterial blood gas analysis: ABG analysis in septic or potentially septic patients identifies ventilatory, oxygenation, and acid-base disturbances which may affect organ function . A metabolic acidosis is a common finding ; an initial respiratory alkalosis from hyperventilation may be found in early sepsis .

 

Suspected and known sepsis  

* Blood culture: In patients with suspected sepsis, at least 2 sets of blood cultures should be obtained, preferably from peripheral venipuncture before antimicrobial therapy is initiated, if obtaining such cultures does not cause a significant delay in antibiotic administration .

 

Suspected and known sepsis  

* Urine culture

* Microbial culture of sputum

* Microbial culture, Pleural fluid

 

Suspected bacterial meningitis  

* Cerebrospinal fluid culture: Bacterial culture of the cerebrospinal fluid is critical in making the diagnosis of bacterial meningitis, identifying the causative organism, and selecting the appropriate antibiotic treatment regimen .

 

Suspected and known sepsis  

* Procalcitonin measurement, serum: Elevated plasma procalcitonin level may be useful in identifying patients with a systemic inflammatory response syndrome (SIRS) , but its use is not clearly defined in distinguishing patients with sepsis from patients with SIRS from a noninfectious cause , . Elevated levels also may predict increased mortality .

 

Suspected and known sepsis  

* Serum C reactive protein level: A C-reactive protein level >2 standard deviations above normal is a possible sign of systemic inflammation in response to infection ; however, the ability of CRP to differentiate an infectious from a noninfectious cause of a systemic inflammatory response syndrome is limited .

 

Evaluation for source of infection  

* Plain chest X-ray

* US scan of soft tissue mass

* Aspiration - diagnostic, Abscess cavity

 

Evaluation for source of infection  

* CT of chest

* Bronchoscopy and bronchoalveolar lavage

* Abdominal ultrasound

* CT of abdomen

 

Suspected DIC  

* Partial thromboplastin time, activated

* Fibrin-fibrinogen split products assay

 

Suspected DIC  

* D-dimer assay: D-dimer should be measured in conjunction with other coagulation studies when DIC is suspected . Although nonspecific, detection of D-dimer is a predicator of illness severity, organ failure, and death in critically ill patients, including those with severe sepsis .

 

Suspected DIC  

* Fibrinogen measurement: Fibrinogen, when used with other coagulation tests, may help to confirm DIC in the appropriate clinical setting .

 

Differential Diagnosis  

* Cardiogenic shock - Acute

* Hypovolemic shock

* Neurogenic shock - Acute

* Anaphylaxis - Acute

* Acute adrenal insufficiency

* Pulmonary embolism - Acute

* Thyroid storm - Acute

* Pancreatitis - Acute

* Cardiac tamponade - Acute

* Heat illness - Acute

* Diabetic ketoacidosis - Acute

* Myxedema coma - Acute

* Acute vascular insufficiency of intestine - Acute

* Toxicity of drug

* Tumor lysis syndrome - Acute

* Spontaneous bacterial peritonitis - Acute

 

Treatment  

 

Drug Therapy  

 

Empiric antibiotic monotherapy of sepsis  

 

CEFOTAXIME SODIUM  

Adults: 2 g IV every 8 hours; use every 4 hours if life-threatening

Pediatrics (age 1 month to 12 years and <50 kg): 50 mg to 160 mg/kg/day IV, divided into 4 to 6 equal doses; maximum 12 g/day

Pediatrics (age 1 month to 12 years and >50 kg): 2 g IV every 6 to 8 hours; for life-threatening infections, 2 g IV every 4 hours

 

CEFTIZOXIME SODIUM  

Adults (severe or refractory): 1 g IV every 8 hours or 2 g IV every 8 to 12 hours

Adults (life-threatening): 3 g to 4 g IV every 8 hours; maximum 2 g IV every 4 hours

Pediatrics (6 months and older): 50 mg/kg IV every 6 to 8 hours; maximum 12 g/day

 

CEFTAZIDIME  

Adults: 1 g IV or IM every 8 hours; maximum 2 g IV every 8 hours

Pediatrics (1 month to 12 years): 30 mg/kg to 50 mg/kg IV every 8 hours; maximum 6 g/day

 

CEFEPIME HYDROCHLORIDE  

Adults: 2 g IV every 12 hours; every 8 hours if neutropenic

 

IMIPENEM/CILASTATIN  

Adults: 500 mg to 1 g IV every 6 to 8 hours; maximum 50 mg/kg/day, not to exceed 4 g/day

Pediatrics (4 weeks to 3 months, non-CNS infection): 25 mg/kg IV every 6 hours

Pediatrics (older than 3 months, non-CNS infection): 15 mg/kg to 25 mg/kg IV every 6 hours

 

MEROPENEM

Adults: 1 g IV every 8 hours

 

DORIPENEM

Adults: 500 mg IV as a 1 hour infusion every 8 hours

 

ERTAPENEM SODIUM  

Adults: 1 g IV every 24 hours

 

TICARCILLIN DISODIUM/CLAVULANATE POTASSIUM  

Adults (60 kg or more): 3.1 g IV every 4 hours

Adults (less than 60 kg): 200 mg/kg/day to 300 mg/kg/day IV, based on ticarcillin component, in divided doses every 4 hours

Pediatrics (more than 3 months, less than 60 kg): 50 mg/kg/dose IV, based on ticarcillin component, every 6 hours (mild to moderate infection) or every 4 hours (severe infection)

 

PIPERACILLIN SODIUM/TAZOBACTAM SODIUM  

Adults: 3.375 g IV every 4 hours or a 4 hour infusion of 3.375 g every 8 hours

 

Empiric combination antibiotic therapy of sepsis of unknown source  

 

VANCOMYCIN HYDROCHLORIDE - LEVOFLOXACIN - CEFTRIAXONE SODIUM  

Adults: Vancomycin 1 g IV every 12 hours AND levofloxacin 750 mg IV every 24 hours AND ceftriaxone 2 g IV every 24 hours

 

Empiric combination antibiotic therapy of sepsis associated with community-acquired pneumonia  

 

VANCOMYCIN HYDROCHLORIDE - LEVOFLOXACIN - CEFTRIAXONE SODIUM  

Adults: Vancomycin 1 g IV every 12 hours AND levofloxacin 750 mg IV every 24 hours AND ceftriaxone 2 g IV every 24 hours

 

Additional antibiotic to improve empiric coverage of staphylococcal infection  

 

NAFCILLIN SODIUM  

Adults: 2 g IV every 4 hours

 

OXACILLIN SODIUM  

Adults: 2 g IV every 4 hours

 

Empiric combination antibiotic therapy of sepsis associated with meningitis  

 

VANCOMYCIN HYDROCHLORIDE - CEFTRIAXONE SODIUM - AMPICILLIN  

Adults: Vancomycin 1 g IV every 12 hours AND ceftriaxone 2 g IV every 12 hours; add ampicillin 2 g IV every 4 hours if over 50 years or immunocompromised

 

Empiric antibiotic therapy of sepsis associated with urinary tract infection, intraabdominal infection, or pelvic infection  

 

PIPERACILLIN SODIUM/TAZOBACTAM SODIUM - GENTAMICIN SULFATE  

Adults: Piperacillin/tazobactam 3.375 g IV every 6 hours AND gentamicin 7 mg/kg IV every 24 hours

 

Empiric antibiotic therapy of sepsis associated with skin and soft tissue infection or necrotizing infection  

 

VANCOMYCIN HYDROCHLORIDE - PIPERACILLIN SODIUM/TAZOBACTAM SODIUM - CLINDAMYCIN PHOSPHATE  

Adults: Vancomycin 1 g IV every 12 hours AND piperacillin/tazobactam 4.5 g IV every 8 hours AND clindamycin 900 mg IV every 8 hours

 

Empiric Gram-positive antibiotic therapy for sepsis in beta-lactam hypersensitivity or suspected resistance to Gram-positive bacteria in the community or hospital  

 

VANCOMYCIN HYDROCHLORIDE  

Adults: 1 gm IV every 12 hours

 

LINEZOLID  

Adults: 600 mg IV every 12 hours

 

QUINUPRISTIN/DALFOPRISTIN  

Adults: 7.5 mg/kg IV every 8 hours through central line

 

Septic patients with candidemia or at high risk for invasive candidiasis  

 

FLUCONAZOLE  

Adults: 400 to 800 mg IV or orally daily, continuing for 14 days after last positive blood culture .

 

CASPOFUNGIN ACETATE  

Adults: 70 mg IV on day 1, followed by 50 mg IV daily until 14 days after last positive blood culture

 

AMPHOTERICIN B LIPID COMPLEX  

Adults: 5 mg/kg IV daily until 14 days after last positive blood culture

 

AMPHOTERICIN B

Adults: 0.6 mg/kg to 1.0 mg/kg IV daily until 14 days after last positive blood culture

 

AMPHOTERICIN B

Adults: Amphotericin B 0.7 mg/kg IV daily AND fluconazole 800 mg IV or orally daily for 4 to 7 days, then fluconazole 800 mg orally daily until 14 days after last positive blood culture

 

Staph aureus sepsis  

 

VANCOMYCIN HYDROCHLORIDE  

Adults (seriously ill patients): Loading dose of 25 to 30 mg/kg (actual body weight) IV may be used to achieve rapid target trough serum vancomycin concentration

Adults: 15 to 20 mg/kg (actual body weight) IV every 8 to 12 hr to achieve target trough serum vancomycin concentrations of 15 to 20 mg/L (when the MIC is 1 mg/L or less)

 

Sepsis-induced hypotension unresponsive to fluid challenge  

 

NOREPINEPHRINE BITARTRATE  

Adults: 2 mcg/min to 20 mcg/minute IV, titrate as needed

 

DOPAMINE HYDROCHLORIDE  

Adults: 5 mcg/kg/minute to 20 mcg/kg/minute IV, titrate as needed

 

VASOPRESSIN  

Adults: 0.03 units/min added to catecholamine vasopressor if needed to maintain mean arterial pressure at 65 mmHg or above

 

EPINEPHRINE  

Adults: 1 mcg/minute to 10 mcg/minute IV, titrate as needed; use when response to norepinephrine or dopamine is poor

 

PHENYLEPHRINE HYDROCHLORIDE  

Adults: 40 mcg/minute to 200 mcg/minute IV; use as alternative vasopressor

 

Low cardiac output despite adequate fluid resuscitation in septic shock and for the early treatment of sepsis-induced hypoperfusion  

 

DOBUTAMINE HYDROCHLORIDE  

Adults: 2.5 to 20 mcg/kg/minute IV, titrated to effect

 

Procedural Therapy  

 

Respiratory distress  

* Airway management: Airway management must assume the first priority in the management of any seriously ill or injured patient .

 

Severe sepsis or septic shock  

* Intravenous fluid replacement: Rapid fluid infusion assists in achieving early goals of mean blood pressure of 65 mmHg, urinary output above 1 mL/kg/hour, central venous pressure 8 to 12 mmHg, and central venous oxygen saturation above 70% within the first 6 hours.

 

Severe sepsis or septic shock  

* Central venous pressure monitoring: During initial fluid resuscitation of sepsis-induced hypoperfusion, the goal is to achieve a central venous pressure of 8 to 12 mmHg .

 

Severe sepsis or septic shock  

* Systemic arterial pressure monitoring: Septic patients requiring vasopressors to maintain adequate blood pressure should have an arterial catheter placed for continuous blood pressure monitoring; the goal is to achieve a mean arterial blood pressure between 65 mmHg and 90 mmHg .

 

Severe sepsis or septic shock  

* Venous oxygen saturation measurement: During the initial resuscitation of sepsis-induced hypoperfusion, a goal is to achieve a central venous O2 saturation of at least 70% or a mixed-venous O2 saturation of at least 65% .

 

Anemia  

* Transfusion of packed red blood cells: Patients with a HCT >30% rarely require RBC transfusion; patients with acute anemia and a HCT <21% typically require transfusion .