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sepsis

Life-threatening organ dysfunction caused by a dysregulated host response to infection. [23] The presence of various pus-forming & other pathogenic organisms or their toxins, in the blood or tissues. The same organism is often isolated in both the blood & the primary site of infection. Sepsis has features of systemic inflammatory response syndrome (SIRS). Diagnosis: (Clinical criteria) 1) temp > 38 C or < 36 C 2) heart rate > 90/min 3) respiratory rate > 20/min or paCO2 < 32 torr 4) WBC > 12,000 cells/mm3 or < 4000 cells/mm3 or > 10% bands 5) documented infection Etiology: 1) gram negative organisms account for 2/3 of positive blood cultures 2) gram positive cocci account for 10-20% of positive blood cultures 3) fungi account for 5% of positive blood cultures 4) in nursing home population, 50% gram positive orgamisms, 45% gram negative organisms & 5% fungal infection; 47% due to multidrug-resistant organisms [60] 5) Rickettsia (Rocky Mountain spotted fever) 6) malaria 7) in infants a) Escherichia coli most common cause, especially when associated with urinary tract infection [19] b) Listeria monocytogenes 2nd most common cause [19] 8) PCV13 vaccines have reduced incidence of bacteremia in young children & shifted the most-commonly isolated pathogens from pneumococcus to E coli, S aureus, & Salmonella [31] 9) lower respiratory tract infections (pneumonia), abdominal infections, urinary tract infections & soft tissue infections most common [43] 10) risk factors [43] - extremes of age < 10 years, > 70 years - comorbidities (cirrhosis, alcoholism, diabetes, cardiopulmonary diseases, malignancy) - immunosuppression - major surgery, trauma, or burns - invasive procedures (catherization & other intravascular devices, prosthetic devices, endotracheal tubes) - previous antibiotic treatment - prolonged hospitalization - genetic susceptibility - obstetric factors (childbirth, abortion) - malnutrition Epidemiology: - most sepsis is community-acquired; however, healthcare exposure within 1 month of hospitalization with sepsis is common [55] - incidence of sepsis & sepsis-related mortality has not changed in recent years [38] Pathology: 1) microbial invasion of the blood stream is not essential for the development of sepsis 2) microbial endotoxins can lead to systemic symptoms 3) myocardial depression due to tumor necrosis factor (TNF) a) ventricular dilation b) reduced ventricular ejection fraction c) maintenance of stroke volume 4) in early stages of sepsis, cardiac output is maintained or even increased [43] Genetics: - CASP12 implicated in susceptibility to severe sepsis Clinical manifestations: 1) fever 2) tachycardia 3) tachypnea 4) hypotension 5) delirium 6) early recognition of sepsis is based of signs of developing end organ failure [4] - severe symptoms in septic shock - ileus - oliguria - metabolic acidosis 7) cough, dyspnea & sputum production suggest pulmonary source - ARDS (see complications) 8) dysuria, frequency & flank pain suggest urosepsis 9) nausea, vomiting & diarrhea suggest gastroenteritis 10) petechiae or purpura associated with Neisseria meningitidis 11) petechial lesions associated with Rocky Mountain spotted fever 12) generalized erythroderma associated with Staphylococcus aureus or Streptococcus pyogenes 13) ecthyma gangrenosum is a cutaneous ulceration associated with Pseudomonas aeruginosa Laboratory: 1) serum lactate [15,42] a) persistently elevated despite fluid resuscitation in severe sepsis/septic shock b) predicts mortality about as well as MEDS score c) measure within 1 hour (part of 1 hour bundle) [42] - > 2 mmol/L despite adequate hydration [43] - remeasure with 2-4 hours if > 2 mmol/L - normal serum lactate is one endpoint of resuscitation 2) blood cultures prior to administration of antibiotics: a) 2 cultures at different sites (aerobic & anaerobic) [42] b) 3 cultures 60 minutes apart c) 6 cultures over 2 days if endocarditis suspected 3) sputum cultures 4) urinalysis & urine cultures (all patients) [43] 5) complete blood count (CBC) a) leukocytosis with predominance of neutrophils & band forms with bacteremia b) leukopenia may be present especially in elderly & immunocompromised c) thrombocytopenia with severe sepsis d) a normal WBC count does not rule out bacteremia [11] 6) serum chemistries a) basic metabolic panel - serum Na+ (hyponatremia), serum K+ (hyperkalemia) - serum Cl- (calculation of anion gap) - serum HCO3- may be low consistent with metabolic acidosis - BUN, serum creatinine to assess oliguria - serum glucose b) procalcitonin in serum only if probability of infection is low [4] 7) remove & culture all indwelling catheters 8) aspiration of joint if joint infection suspected 9) gram stain & culture of wounds 10) paracentesis of ascites fluid 11) as indicated a) lumbar puncture if intracranial infection is suspected b) serum bilirubin > 4 mg/dL with severe sepsis c) serum ALT, serum AST d) serum amylase e) DIC panel (PT/PTT, plasma fibrinogen, D-dimer) f) arterial blood gas (ABG): PaO2/FiO2 < 300 - target central venous oxygen saturation > 70% in patients with central venous catheters [15] g) serum cortisol (adrenal insufficiency) h) cosyntropin stimulation test (see Management) 12) repeat blood cultures for gram-negative sepsis most likely positive if patient is febrile [40] 13) see ARUP consult [13] Special laboratory: 1) electrocardiogram: a) 12 lead EKG b) cardiac monitor 2) echocardiogram for all septic patients a) obtain transthoracic echocardiogram (TTE) b) if TTE is negative, obtain transesophageal echocardiogram (TEE) [4] Radiology: 1) chest X-ray (all patients) [43] 2) ultrasound or CT of kidneys if complicated urosepsis suspected 3) imaging of abdominal contents if indicated Differential diagnosis: 1) anaphylaxis 2) drug overdose 3) pancreatitis 3) burns 4) adrenal insufficiency 5) pulmonary embolism 6) ruptured aortic aneurysm 7) myocardial infarction 8) hemorrhage 9) cardiac tamponade 10) drug withdrawal 11) neuroleptic malignant syndrome 12) systemic vasculitides 13) exensive crush injury 14) heatstroke 15) dehydration 16) systemic inflammatory response syndrome (SIRS) Complications: - septic shock - adrenocortical insufficiency [65] - acute respiratory distress syndrome (ARDS) (18-38%) [43] - usually within 12-48 hours of inciting event - stroke (HR=6.0) [9] - new-onset atrial fibrillation - associated with increased mortality (HR-1.5) [9] - persistent cognitive impairment & functional disability in the elderly [20] - increased risk of post-operative venous thrombosis & arterial thrombosis [21] - delays in treatment of early sepsis are associated with higher mortality [4] - increased mortality in elderly persists for at least 2 years [24] - 74% of in-hospital mortality with sepsis on admission [47] - sepsis is the immediate cause of death in 35% of patients & contributes to the deaths of another 8% [47] - nearly all deaths attributed to sepsis considered to be unpreventable [47] - 30-day hospital readmission for sepsis more common than readmission for any of the 4 CMS index conditions*, associated with longer length of stay after readmission, & is associated with higher cost [31] - increased risk for seizures up to 8 years after hospital discharge (RR=5.0) [32] - 47% of hospitalizations with sepsis from nursing homes are due to multidrug-resistant organisms [60] * readmission used by CMS as quality markers for index conditions (heart failure, MI, pneumonia, COPD) [31] Management: 1) monitor: a) temperature b) blood pressure: - mean arterial BP > 65 - target systolic BP 120-140 mm Hg c) heart rate d) respiratory rate e) pulse oximetry f) urine output g) mental status 2) NPO (nothing by mouth) until respiratory & mental status are stable 3) oxygen to maintain SaO2 > 90% 4) mechanical ventilation as indicated a) low tidal volume 6 mL/kg b) plateau pressures < 30 cm H2O 5) one hour sepsis bundle 6) hydration/volume a) lactated Ringer's preferred vs normal saline - lactated Ringer's associated with lower 30-day mortality than saline [53] - do not use synthetic colloid (hydroxyethyl starch) [14] - initial bolus of 30 mL/kg [16] within 3 hours [61] b) fluid resuscitation with normal saline vs lactated Ringer's result in similar outcomes [62] c) keep central venous pressure 8-12 mm Hg [16] - central venous pressure monitoring & targeting do not improve outcomes [54] d) central venous oxygen saturation > 70% e) urine output >= 0.5 mL/kg/hour [16] f) 30 mg/kg crystalloid for hypotension or serum lactate >= 4 mmol/L [44] g) time to completion of fluid bolus not associated within-hospital mortality [33] h) assessment of volume responsiveness after initial fluid bolus before initiating vasopressors [66] i) caution in patients with heart failure or renal failure j) aggressive fluid management associated with excess mortality in HIV-positive patients in Zambia [37] k) no benefit to fluid restriction in patients with septic shock [64] 7) antimicrobial therapy a) intravenous empiric antimicrobial therapy within 1 hour after specimens for blood culture & other appropriate cultures have been obtained [28,51] (severe sepsis or septic shock) [4,16,17] - begin within 1 hour even if obtaining cultures is incomplete [4] - continuous infusion of beta-lactam (especially Zosyn) improves outcomes [27] - early antibiotics for severe sepsis associated with lesser progression to septic shock & lower mortality [30] - rapid administration of antibiotics associated with lower in-hospital mortality - prehospital antibiotics in the ambulance does not improve outcomes [41] (unclear whether blood cultures were obtained in ambulance prior to antibiotics) - a 1 hour mandate lacks evidence of benefit & is achieved in only 29% of patients in the emergency department [52] - no mortality benefit to antibiotics within 1 hour vs 1-3 hours after emergency department arrival in patients with sepsis or septic shock [56] b) adjust antibiotics according to culture & sensitivities - discontinue antibiotics if cultures negative [4] c) duration of therapy: 7-10 days (3-6 weeks for S. aureus) - intravenous vancomycin or daptomycin for 4-6 weeks if MRSA sepsis with prosthetic joint [66] - 7 days of therapy adequate for gram-negative sepsis & neutropenia due to hematologic malignancy or hematopoietic stem cell transplantation [67] d) monotherapy with third generation cephalosporin or carbapenam for community-acquired septic shock - cefepime associated with lower mortality than Zosyn when used as initial monotherapy [72] e) coverage for MRSA & an anti-pseudomonas beta-lactam & either a fluoroquinolone or an aminoglycoside for nosocomial infections, immunosuppression or recent antibiotic use - cefepime, levofloxacin & vancomycin - Zosyn & cefepime similarly likely to cause acute kidney injury [69] - aztreonam, levofloxacin & vancomycin if penicillin allergy f) addition of clindamycin to decrease toxin production for suspected toxic shock syndrome g) no benefit from the addition of moxifloxacin to meropenem for the management of the severe sepsis [12] h) 3 days of IV antibiotics prior to step-down oral therapy with fluoroquinolone or beta-lactam antibiotic for Streptococcal sepsis [57] i) for patients with gram-negative sepsis responding to IV antibiotics, switch to oral therapy after 3-5 days [70] 8) catheter management - central venous access as needed - pulmonary artery catheterization not routinely indicated - removal of indwelling catheter when not needed - see catheter-related infection 9) prevention of septic shock (see septic & distributive shock) a) assessment of volume responsiveness after initial fluid bolus before initiating vasopressors [66] b) vasopressor added if hypotension persists despite volume resuscitation - norepinephrine vasopressor of choice - epinephrine added if adequate blood pressure cannot be maintained [16] - circumstances may exist where epinephrine may be substituted for norepinephrine [16] c) initiate vaspressor via peripheral access, vs waiting for placement of central venous access [61] d) target mean arterial pressure > 65 mm Hg [16,42] e) phenylephrine not recommended except if - norepinephrine is associated with serious arrhythmias - cardiac output is high & blood pressure persistently low f) add dobutamine up to 20 ug/kg/minute if cardiac output low despite norepinephrine [16] g) intravenous glucocorticoid if ongoing vasopressor therapy [61] 10) corticosteroid replacement a) of no benefit [6] - hydrocortisone 50 mg bolus followed by 200 mg IV infusion daily does not prevent septic shock [25] - no role in sepsis without septic shock [4] - adrenocortical insufficiency [65] b) AVOID in the absence of refractory shock [16] c) other, older - if serum cortisol is < 9 ug/dL after 250 ug cosyntropin stimulaton test - hydrocortisone 15-240 mg IV every 12 hours - low dose corticosteroid (< 300 mg cortisol QD equivalent) for 5-11 days may improve outcomes [5] - grade 2C recommendation [7] - thiamine, vitamin C (6 g IV QD), hydrocortisone (50 mg Q6h) - may reduce mortality (9% vs 41% in a single-center study) [34] - does not increase ventilator- & vasopressor-free days [58] - vitamin C not recommended [61] - intravenous vitamin C associated with increased 28 day mortality [63] - IV hydrocortisone (200 mg/day) suggested for patients who are hemodynamically unstable despite fluids & vasopressors [16] - mortality is lower with 200 mg hydrocortisone QD at 28 days, but not at 90 days [46] 11) blood transfusion - after tissue hypoperfusion is corrected, RBC transfusion only when blood hemoglobin < 7.0 g/dL - target blood hemoglobin of 7.0-9.0 g/dL in adults [16] 12) platelet transfusion indicated for patients with severe sepsis (possible DIC) when platelet count is < 10,000/mm3 [43] 12) sodium bicarbonate should not be used if arterial pH >= 7.15 [16] 13) stress ulcer prophylaxis - ranitidine 50 mg IV every 8 hours 14) DVT prophylaxis - TEDs/SCD or subcutaneous heparin 15) IV insulin for hyperglycemia after initial stabilization - maintain plasma glucose < 180 mg/dL [4] - see glycemic control 16) recombinant human activated protein C (drotrecogin alfa) for severe sepsis & high risk of death if risk of bleeding is low [4,8] 17) early broad-spectrum antibiotics & drotrecogin alfa independently associated with lower hospital mortality in ICU patients 18) continued statin use associated may improve outcomes in ICU patients with sepsis [18] - benefit of statins only apparent in prior statin users 19) - no mortality benefit to early renal replacement therapy [45] 20) early enteral nutrition if possible [4] Notes: - New York has a mandate that all hospitals use evidence-based protocols for identification & management of sepsis & that they report data on protocol adherence & clinical outcomes to the state [33] - more rapid completion of a 3-hour bundle of sepsis care associated with lower in hospital mortality [33] - Severe Sepsis/Septic Shock Early Management Bundle (SEP-1) adherence 54% [36] - sepsis-related mortality decreases with mandated bundled care & reporting [50] - CMS Sepsis Performance Measure (SEP-1) has not improved outcomes [59]

Related

distributive shock; vasodilatory shock (multiple organ dysfunction syndrome) mortality in emergency department sepsis (MEDS) score Severe Sepsis/Septic Shock Early Management Bundle (SEP-1)

Specific

gram-negative sepsis; gram-negative bacteremia Lemierre syndrome (septic thrombosis of the jugular vein) neonatal sepsis pyemia septic shock urosepsis

General

bacterial infection bacteremia systemic inflammatory response syndrome (SIRS)

References

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