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• Septic shock- once a uniformly fatal condition with 100% mortality. • Present recovery rates are more than 50%.
Mortality from Sepsis
Incidence rate for 1993-1997.000 • Number of deaths in US each year – Acute myocardial infarction5 – Severe sepsis4 Centers for Disease Control and Prevention.Reference Diseases • Incidence in US (cases per 100. 2001. 4 Angus DC et al. 2001. Incidence rate for 1999. 2000.000 215. 5 National Center for Health Statistics. Crit Care Med 29:1303-1310.000) – – – – – AIDS1 Colon and rectal cancer2 Breast cancer2 Congestive heart failure3 Severe sepsis4 17 48 112 ~196 ~300 218. 2001. American Cancer Society. 1 2 .
Crit Care Clin 16(2):179-191 . transplantation) – Invasive procedures (ventilators.g. Crit Care Med 29:1303-1310. prostheses) – Resistant pathogens Angus DC et al.Sepsis on the Rise • Incidence projected to rise during the next decade – Aging population especially in developed nations – Increased awareness and diagnosis – Immunocompromised patients e. cancer therapy. catheters. Balk RA. 2001. 2000.
Definitions SIRS Sepsi Severe Septic Sepsis Shock s Infection .
< 4.Systemic Inflammatory Response Syndrome • Systemic Inflammatory Response Syndrome (SIRS)--the beginning of illness ≥ 2 of the following: • Temp > 38°C or < 36°C • Heart rate > 90 pm • Respiratory rate > 20 pm • WBC > 12. Chest 101:1644-1655 .000 or bands > 10% Bone. 1992. et al.000.
hypoperfusion or hypotension • Septic Shock – Sepsis with hypotension and perfusion abnormalities despite adequate volume replacement Bone. et al. Chest 101:1644-1655 . 1992.Sepsis • Sepsis – SIRS + infection • Severe sepsis – Sepsis with organ dysfunction.
1992. 1999.Definition Infection/ Trauma SIRS Sepsis Severe Sepsis Bone et al.101:1644. N Engl J Med.340:207. Chest. Sepsis with ≥1 sign of organ failure Cardiovascular (refractory hypotension) Renal Respiratory Hepatic Shock Hematologic CNS Unexplained metabolic acidosis . Wheeler and Bernard.
Multiple Organ Dysfunction Syndrome (MODS/MOF) Primary MODS = a well-defined insult. occurs early and can be directly attributable to the insult itself (eg. Secondary MODS = not in direct response to the insult itself.MODS/MOF = the presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention. renal failure due to rhabdomyolysis). Crit Care Med 1992. but as a consequence of a host response. 20:864 . MODS represents the more severe end of severity of illness characterized by SIRS/sepsis.
Altered Consciousn ess Confusion Psychosis Identifying Acute Organ Dysfunction as a Marker of Severe Sepsis Tachycardia Hypotensio n ↑ CVP ↑ PAOP Oliguria Anuria ↑ Creatinine Tachypnea PaO2 <70 mm Hg SaO2 <90% PaO2/FiO2 ≤ 300 Jaundice ↑ Enzymes ↓ Albumin ↑ PT ↓ Platelets ↑ PT/APTT ↓ Protein C ↑ D-dimer .
20:864 . – Hypotension = systolic BP of <90 mmHg or a reduction of ≧40 mmHg from baseline in the absence of other causes for the fall in blood pressure. oliguria. but are not limited to : lactic acidosis. or an acute alteration in mental status.Septic Shock Septic shock = sepsis induced hypotension despite adequate fluid resuscitation along with perfusion abnormalities that may include. Crit Care Med 1992.
the abdomen. P aeruginosa) – 30% are caused by gram-positive bacteria (Strept pneumoniae. Enterococ species). and the genitourinary tract.Septic shock :Causes --Common sites of infection in decreasing order : the chest. . Staph aureus. – 70% due to gram-negative bacteria (Enterobacteriaceae.
Primary Sites of Infection in a recent large study of Septic shock 60 50 40 30 20 10 0 Lung IntraUrinary Abdominal Tract Blood Skin Other Percent of Patients Drotrecogin Alfa (activated) N=850 Placebo N=840 Site of Infection .
Changes in the Documented Causes of Sepsis Martin NEJM 2003 .
Shock. 1998.Homeostasis Is Unbalanced in Severe Sepsis Carvalho AC.5:223-8. 1996. Vervloet MG et al.24:33-44. Freeman NJ. Semin Thromb Hemost. .9:51-75. 1994. Kidokoro A et al. J Crit Illness.
Why do people die from Sepsis? • Very few organisms produce toxins that cause death directly – Diptheria – Tetanus. botulism – Pseudomonas aeruginosa ? • Death from sepsis is mainly due to inflammation .
Pathogenesis of Sepsis • A wide variety of microorganisms cause sepsis • How--there must be some common mechanism • Interaction of specific Pathogen Associated Molecular Patterns (PAMPs)with Toll-like receptors (Tlrs) on the macrophage stimulate production of inflammatory mediators .
cytokines.Innate Immune response • Sepsis Interaction of a microbial signature with a toll-like receptor leads to activation of innate immune mechanism – Antimicrobial peptide (DEFENSINS) synthesis and release which can kill most organisms – Release of Mediators of inflammation . chemokines – PMN leucocytes come into the site of inflammation to phagocytize organisms--release enzymes – Normally protective but either overwhelmed by bacterial inocula or some type of dysregulation leads to severe SEPSIS .
Synthesis and release of Effector molecules leading to the SEPSIS syndrome and shock .
Crit Care Med 2000 28(4):N3-N12 .
Incomplete Rx Corticosteroid or relapse ??? High viral load Good side remove virus Cytokine Storm ? Bad side ARDS MODS Genetic predisposition to immune hyperstimulation .
Pathophysiology • What ‘type of shock’ is septic shock? Septic shock has features of : – Hypovolemic shock – Cardiac shock – Distributive shock. .
or tissue injury. inflammation.Pathophysiology of septic shock and SIRS • The hemodynamic derangements observed in septic shock and SIRS are due to a complicated cascade of inflammatory mediators released in response to infection. .
Pathophysiology of septic shock and SIRS
• Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1b, and IL-6 act synergistically with other cytokines and phospholipid-derived mediators to produce the complex alterations in vascular and myocardial function, which leads to maldistribution of blood flow
• Decreased tissue perfusion results primarily from : • 1-arterial hypotension due to reduction in SVR. • 2-reduction in effective circulating plasma volume due to: a-- decrease in venous tone and subsequent pooling of blood in venous capacitance vessels.
b-loss of intravascular volume into the interstitium due to increased capillary permeability also occurs. • Finally, primary myocardial dysfunction often is present as manifested by ventricular dilatation, decreased ejection fraction (despite normal stroke volume and cardiac output), and depressed ventricular function curves
Pathogenesis of Severe Sepsis Infection Microbial Products (exotoxin/endotoxin) Cellular Responses Platelet Activation Coagulation Activation Oxidases Kinins Complement Cytokines TNF. IL-1. IL-6 Coagulopathy/DIC Vascular/Organ System Injury Endothelial d amage Multi-Organ Failure age helial dam Endot Death .
Severe Sepsis: The Final Common Pathway Cytokine storm Endothelial Dysfunction and Microvascular Thrombosis Hypoperfusion/Ischemia Acute Organ Dysfunction (Severe Sepsis) Death .
• The Continuum of infection to MODS and Death (Clinical Definition) .Clinical Manifestations.
bounding pulses and increased pulse pressure .Frequently are warm .Physical examination: – Hypotension .Greater than 90 – Respiratory rate . .Greater than 20 – Extremities .With systolic blood pressure less than 90 mm Hg or a reduction of 40 mm Hg from baseline – Fever – Heart rate .
or decreased. or increased bands . Hypotension is still a sign of decompensation. leukopenia. • Early signs of sepsis/septic shock include — — — Fever or hypothermia Tachycardia and tachypnea Leukocytosis. • Hypotension and poor end-organ perfusion may be present despite “good” skin perfusion. increased.Septic Shock Is Unique • Cardiac output may be normal.
elevated lactate. • Physiologic parameters – widened pulse pressure. hyperglycemia . tachypnea. decreased systemic vascular resistance. compensated. hyperdynamic state • Clinical signs – Warm extremities with bounding pulses. confusion.Septic Shock: “Warm Shock” • Early. • Biochemical evidence: – Hypocarbia. increased cardiac output and mixed venous saturation. tachycardia.
increased SVR. rapid. . • Clinical signs – Cyanosis. hypoxia. hypoglycemia.Septic Shock: “Cold Shock” • Late. cold and clammy skin. oliguria. capillary leak • Biochemical abnormalities – Metabolic acidosis. cardiac output and CVP. uncompensated stage with drop in cardiac output. thrombocytopenia. shallow respirations. myocardial dysfunction. coagulopathy. • Physiologic parameters – Decreased mixed venous sats. thready pulses.
if untreated Multi-Organ System Failure: Coma. ARDS. Renal Failure. hemorrhage.Septic Shock (con’t) s Cold Shock rapidly progresses to MOSF or death. worse the prognosis s s . CHF. Ileus. DIC More organ systems involved.
...bounding pulses ..Clinical Manifestations. Recognition of Septic Shock: • Inflammatory triad– Fever – Tachycardia – flushed skin Warm Shock • Hypoperfusion – – – – Altered sensorium Urine output >CFT Wide pulse pressure...
Cold shock .Clinical Manifestations. • Hypotension – – – – – – – Cold and clammy skin Mottling Tachycardia Cyanosis Narrow pulse pressure Hypoxemia Acidosis.
Clinical Manifestations.Decompensated / Organ hypoperfusion III. End organ failure / Irreversible . Compensated / Preshock / Hyperdynamic II. Staging of Septic Shock: I.
Lab Studies: • All patients with evidence of shock should have the following studies performed: – – – – – – – – – – CBC with differential Arterial blood gas Serum lactate if metabolic acidosis or elevated anion gap is present Electrolytes BUN Creatinine (CR) Glucose Urinalysis Blood cultures Urine cultures .
• In suspected cases of cholecystitis or pancreatitis. • Flat and upright abdominal radiographs may be omitted if the abdomen is completely benign or if an obvious source of extraabdominal sepsis noted. • Consider abdominal CT scan with oral and/or intravenous contrast for other abdominal sources for sepsis .Imaging Studies: • All patients should have a chest x-ray. biliary dilatation. abdominal ultrasound is most useful to assess for cholelithiasis. and fluid collections around the gallbladder or the head of the pancreas.
bundle branch block) or acute changes of ischemia or pericarditis . low voltage. cor pulmonale.Other Tests: • ECG should be performed to examine for evidence of underlying cardiac pathology (left ventricular hypertrophy.
catheters. Prompt treatment of local infections Hospitalized patient: look out for nidus of infection.IV lines. E. 3. Immunisation 2.Management Prevention: 1.tubes .
Inflammatory triad Signs of hypoperfusion • Do not wait for the BP to fall ! • Lower limit for systolic BP in children = 70 +( age x 2) .Management Recognise septic shock early: • Remember.
Shock. Multi organ failure. • Two means of death: 1. Assure perfusion of critical vascular ( cerebral. 2.Management. beds. renal) 2. Rx underlying cause. coronary. • Aims of treatment: 1. .
and N-M Blockade in Sepsis – Glucose Control – Renal Replacement – Bicarbonate Therapy – DVT Prophylaxis – Stress Ulcer Prophylaxis – Selective Digestive Tract Decontamination (SDD) – Consideration for Limitation of Support • III. SUPPORTIVE THERAPY OF SEVERE SEPSIS – Mechanical Ventilation of Sepsis-induced ALI/ARDS – Sedation.Guidelines for Management of Severe Sepsis and Septic Shock • I. Analgesia. MANAGEMENT OF SEVERE SEPSIS – – – – – – – – – Initial Resuscitation Diagnosis Antibiotics Therapy Source Control Fluid therapy Vasopressors Inotropic Therapy Corticosteroid Recombinant Human Activated Protein C (rhAPC) – Blood Product Administration • II. Pediatric Consideration .
45 • Lots of intravenous Fluids • Antibiotics • Effective antibiotics • Timely administration of Effective antibiotics .tachypnea leading to respiratory alkalosis – Low Pco2. pH >7.Most Effective therapies • Early recognition of preshock.
.Treatment • Nearly all patients with shock should be admitted to an ICU. • Adequate intravenous access should be obtained. • Vital signs and fluid intake and output should be measured and charted on an hourly basis.
and pressure ulcers of the skin. gastric stress ulceration. . • Most patients should have an indwelling urinary catheter placed. • All patients should be treated prophylactically against thromboembolic disease.Treatment • A central venous access device should be considered if vasoactive drug support is required.
treat infection) • 2. • The initial resuscitation should be accomplished within the first hour of treatment.reverse the initiating cause of shock (e.g.Goals of treatment • The 2 primary goals are to : • 1.stabilize the patient hemodynamical. .
or severe hypotension.Treatment • Oxygen by mask. elective endotracheal intubation and mechanical ventilation should be considered strongly.respiratory distress. • In patients with altered mental status. .
Empiric antibiotic therapy should be initiated immediately • Antimicrobial coverage should be Broad .Treatment • In all patients with sepsis.
Crit Care Med 2003. Cardiovascular management of septic shock. page 948. reproduced with permission from Dellinger RP.Initial Resuscitation Figure B. .31:946-955.
5% vs.hr-1 In hospital mortality was 30. 46.5 ml. N Engl J Med.5% in control group River et al.Early Goal-Directed Therapy • 1000 ml of crystalloid or 300-500 ml bolus of colloid q 30 min to keep CVP 8-12 mmHg • Vasoactive agents (MAP: ≧ 65 mmHg) – Vasopressors if MAP < 65 mmHg – Vasodilator if MAP > 90 mmHg • Transfusion ( Hct > 30%) and Dobutamine if ScvO2 < 70% or mixed venous < 65% • Keep urine output: ≧ 0.kg-1. 200 .
increase by 2.EGDT first 6 hours in ER 500ml bolus of colloid every 30min Dobutamin started at 2.5ug/kg/min every 30 min. or until maximal dose 20ug/kg/min given Decrease dobutamin dose if MAP >65mmHg or HR> 120bpm .5 ug/kg/min.
do not delay pending ICU admission (1C) Resuscitation goals (1C) CVP 8–12 mm Hg a Mean arterial pressure 65 mm Hg Urine output 0. maximum 20 μg/kg/min .Initial Resuscitation (2008) Initial resuscitation (first 6 hrs) Begin resuscitation immediately in patients with hypotension or elevated serum lactate 4 mmol/L.5 mL/kg/hr Central venous (superior vena cava) oxygen saturation 70% or mixed venous 65% If venous oxygen saturation target is not achieved (2C) Consider further fluid Transfuse packed red blood cells if required to hematocrit of 30% and/or Start dobutamine infusion.
Sonography suitable. (ex. transport outside unit may be dangerous) .Diagnosis • Obtain appropriate cultures before starting antibiotics provided this does not significantly delay antimicrobial administration (1C) – – – – Obtain two or more BCs One or more BCs should be percutaneous One BC from each vascular access device in place 48 hrs Culture other sites as clinically indicated • Perform imaging studies promptly to confirm and sample any source of infection. if safe to do so (1C).
Role of Infection Control • Right Drugs for Right patients at Right time • De-Escalation Therapy (For severe infection in ICU) – Why – How – Outcomes • Resistance .
each hour delay in achieving administration of effective antibiotics is associated with a measurable increase in mortality • Broad-spectrum: one or more agents active against likely bacterial/fungal pathogens and with good penetration into presumed source (1B) – Watch out MRSA in some communities and healthcare settings .Antibiotic Therapy (2008) • Begin intravenous antibiotics as early as possible and always within the first hour of recognizing severe sepsis (1D) and septic shock (1B) – In the presence of septic shock.
and minimize costs (1C) • Consider combination therapy in Pseudomonas infections (2D) • Consider combination empiric therapy in neutropenic patients (2D) . prevent resistance. avoid toxicity.Antibiotic Therapy (2008) • Reassess antimicrobial regimen daily to optimize efficacy.
longer if response is slow or there are undrainable foci of infection or immunologic deficiencies (1D) • Stop antimicrobial therapy if cause is found to be noninfectious (1D) .Antibiotic Therapy (2008) • Combination therapy 3–5 days and deescalation following susceptibilities (To single therapy) (2D) • Duration of therapy typically limited to 7–10 days.
aeruginosa continues to be associated with highest mortality – Resistance issues need to be kept in mind – A large number of patients with the sepsis syndrome will not have an organism cultured but should be treated with antibiotics • Prevent the development of septic shock .Optimum therapy of Sepsis and Shock • Antibiotics remain the most critical choice to be made – TIMELY-reduces mortality – EFFECTIVE. BROAD SPECTRUM-reduces mortality – DIFFERENT antibiotics for different patients – P.fluids and Right antibiotics .
Teicoplanin • . add an anti Staphylococcal agent --Vanco.Antibiotic Choices • Given the world wide resistance issues the most effective antibiotic choices to cover gram negatives would be – Fourth generation cephalosporins ± aminoglycoside (Geographic location) – Carbapenems ± aminoglycoside (Pseudomonas resistance during therapy of Lung infections) – Pip-Tazobactam + an aminoglycoside (Esbl resistance) If the incidence of MRSA is high and gram positive coverage is needed.
aureus. aeruginosa. – Skin infections require gram positive coverage • Lung most common site of documented infection-P. or necrotizing soft tissue infection needs anaerobic coverage. S. S. pneumoniae.coli • Give the antibiotic as soon as possible .S. aureus. if known it helps to limit choices – intraabdominal. • Know resistance picture in hospital – ESBLs. E. P. choose best drugs against these • Know resistance in community if sepsis is community acquired .Choosing the RIGHT antibiotic in Sepsis • Site of Infection. aeruginosa.
Non antibiotic therapy of septic shock 2002 opinion .
tissue debridement. removal of a potentially infected device. intestinal infarction) • Formally evaluate patient for a focus of infection amenable to source control measures (e. cholangitis. or the definitive control of a source of ongoing microbial contamination) (1C) . diffuse peritonitis.g.Source identification and control (2008) • A specific anatomic site of infection should be established as rapidly as possible (1C) and within first 6 hrs of presentation (1D) – E. necrotizing fascitis.g.. abscess drainage.
• Implement source control measures as soon as possible following successful initial resuscitation (1C) (exception: infected pancreatic necrosis. where surgical intervention is best delayed) (2B) • Choose source control measure with maximum efficacy and minimal physiologic upset (1D) – e. percutaneous rather than surgical drainage of an abscess Source identification and control (2008) • Remove intravascular access devices if potentially infected (1C) – Prompt remove after other vascular access had been established ..g.
Fluid Therapy (2008) : • Fluid resuscitation may consist of natural or artificial colloids or crystalloids (1B) .
Fluid Therapy (2008) • Resuscitation initially target a central venous pressure of 8 mm Hg (12 mm Hg in mechanically ventilated patients) (1C) • A fluid challenge technique be applied wherein fluid administration is continued as long as the hemodynamic improvement (e. arterial pressure. heart rate. urine output) continues (1D) ..g.
Fluid Therapy (2008) • The rate of fluid administration be reduced when ： cardiac filling pressures (central venous pressure or pulmonary artery balloon-occluded pressure) increase without concurrent hemodynamic improvement • (1D) .
Vasopressors (2008) • Mean arterial pressure (MAP) be maintained 65 mm Hg (≧ 65) (1C) – Sustain life and maintain perfusion in the face of life-threatening hypotension • Either NOREPI or DOPA administered through a central catheter is the initial vasopressor of choice (1C) • Epinephrine.03 units/min may be subsequently added to norepinephrine with anticipation of an effect equivalent to norepinephrine alone . phenylephrine. Vasopressin 0. or vasopressin should not be administered as the initial vasopressor in septic shock (2C).
Vasopressors (2008) • Epinephrine be the first chosen alternative agent in septic shock that is poorly responsive to norepinephrine or dopamine (2B) • Do not use low-dose dopamine for renal perfusion (1A) – Bellomo et al. place an arterial catheter as soon as possible.(1D) . Lancet 2000 • In patients requiring vasopressors.
and epinephrine on the splanchnic circulation in septic shock: Which is best? Crit Care Med 2003. Effects of dopamine. 31:1659-1667 . norepinephrine. reproduced with permission from De Backer D. and Epinephrine on the Splanchnic Circulation in Septic Shock Figure 2.Effects of Dopamine. Creteur J. Silva E. Vincent JL. Norepinephrine. page 1665.
Corticosteroid (2008) • Consider intravenous hydrocortisone for adult septic shock when hypotension responds poorly to adequate fluid resuscitation and vasopressors (2C) • ACTH stimulation test is not recommended to identify the subset of adults with septic shock who should receive hydrocortisone (2B) • Hydrocortisone is preferred to dexamethasone (2B) .
NEJM 1987. NEJM 1987. et al. 317-658 VA Systemic Sepsis Cooperative Study Group. 317:659-665 .Corticosteroid in Septic Shock • High doses of corticosteroids do not improve survival and may worsen outcomes by increasing the frequency of secondary infections • Low-dose (?physiologic?) steroids may be beneficial because of relative adrenal insufficiency – Treat patients who still require vasopressors despite fluid replacement with hydrocortisone 200-300 mg/day. for 7 days in three or four divided doses or by continuous infusion Bone.
there were more episodes of superinfection. 86/251 (34. including new sepsis and septic shock.5%) in the placebo group (P=0. 2008 . NEJM 358(2): 111. double-blind. shock was reversed more quickly than in the placebo group • However. the dose was then tapered during a 6-day period – 248 patients iv placebo • 28-day mortality.Hydrocortisone Therapy for Patients with Septic Shock • In the multicenter. Sprung et al. randomized.3%) in the hydrocortisone group vs 78/248 (31.51) • In the hydrocortisone group. placebocontrolled trial – 251 patients: 50 mg hydrocortisone iv q6h for 5 days.
Fludrocortisone if optional if hydrocortisone is used (2C) • Steroid therapy may be weaned once vasopressors are no longer required (2D) • Hydrocortisone dose should be 300 mg/day (1A) • Do not use corticosteroids to treat sepsis in the absence of shock unless the patient’s endocrine or corticosteroid history warrants it (1D) .Corticosteroid (2008) • Fludrocortisone (50 g orally once a day) may be included if an alternative to hydrocortisone is being used that lacks significant mineralocorticoid activity.
JAMA 2002.Steroid Therapy Figure 2A. et al. page 867. 288:862-871 . reproduced with permission from Annane D. Charpentier C. Sébille V. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.
Human Activated Protein C Endogenous Regulator of Coagulation Protein C (Inactive) Blood Vessel Protein C Activity Protein S Blood Flow ⇒ Protein C Receptor Thrombomodulin Thrombin .
anti-inflammatory and pro-fibrinolytic properties – Drotrecogin Alfa is the first anti-inflammatory agent that proved effective in the treatment of sepsis From Recombinant human activated protein c worldwide evaluation in severe sepsis (PROWESS) study group Bernard et al. 2001 . NEJM.Human Activated Protein C in Septic Shock • Activated protein C had anti-thrombotic.
Results: 28-Day All-Cause Mortality results 2-sided p-value Adjusted relative risk reduction 35 Increase in odds of survival 30. with permission from Bernard GR.1% Mortality (%) 25 20 15 10 5 0 24. 344:699-709 .7% 6.005 19.1% absolute reduction in mortality Placebo (n-840) Drotrecog in alfa (activated ) (n=850) Adapted from Table 4. page 704. Laterre PF.4% 38. et al.8% 30 Primary analysis 0. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001. Vincent JL.
Drotrecogin alfa (activated) (recombinant human activated protein C) fordeaths the treatment of severe sepsis.Mortality and APACHE II Quartile 50 45 40 35 30 25 20 15 10 5 0 Mortality (percent) Placebo Drotrecogin 118:80 58:48 57:49 26:33 1st (3-19) 2nd (20-24) 3rd (25-29) 4th (30-53) APACHE II Quartile *Numbers above bars indicate total Adapted from Figure 2.]:S85-S90 . with permission from Bernard GR. Crit Care Med 2003. page S90. 31[Suppl.
page S91.Mortality and Numbers of Organs Failing 60 50 Percent Mortality 40 30 20 Placebo Drotrecogin 10 0 1 2 3 4 5 Number of Organs Failing at Entry Adapted from Figure 4. Crit Care Med 2003. 31[Suppl. with permission from Bernard GR.]:S85-S90 . Drotrecogin alfa (activated) (recombinant human activated protein C) for the treatment of severe sepsis.
Contraindications to Use of Recombinant Human Activated Protein C (rhAPC) • Active internal bleeding • Recent (within 3 months) hemorrhagic stroke • Recent (within 2 months) intracranial or intraspinal surgery. or severe head trauma • Trauma with an increased risk of life threatening bleeding • Presence of an epidural catheter • Intracranial neoplasm or mass lesion or evidence of cerebral herniation • Known hypersensitivity to rhAPC or any component of the product .
g.0 g/dL (70 g/L) to target a hemoglobin of 7.0–9. or lactic acidosis) • . myocardial ischaemia.Blood Product Administration (2008) Red Blood Cells • Give red blood cells when hemoglobin decreases to 7. severe hypoxemia. cyanotic heart disease. acute hemorrhage..0 g/dL in adults (1B). A higher hemoglobin level may be required in special circumstances (e.
Blood Product Administration (2008) • Do not use erythropoietin to treat sepsis-related anemia. (1B) • Do not use fresh frozen plasma to correct laboratory clotting abnormalities unless there is bleeding or planned invasive procedures (2D) • Do not use antithrombin therapy (1B) . Erythropoietin may be used for other accepted reasons (chronic renal failure).
000/mm3 [50x 109/L]) are required for surgery or invasive procedures .000/mm3 (5–30x109/L) and there is significant bleeding risk • Higher platelet counts (50.Blood Product Administration (2008) • Administer platelets when (2D) – Counts are 5000/mm3 (5x 109/L) regardless of bleeding – Counts are 5000–30.
Mechanical Ventilation of SepsisInduced ALI/ARDS (2008) .
Consider chest wall compliance when assessing plateau pressure (1C) – If plateau pressure remain > 30 after reduction of tidal volume to 6 ml/kg PBW. tidal volume should be reduced further to as low as 4 ml/kg .Mechanical Ventilation of Sepsis-Induced ALI/ARDS • Target a tidal volume of 6 mL/kg (predicted) body weight in patients with ALI/ARDS (1B) • Target an initial upper limit plateau pressure 30 cm H2O.
to minimize plateau pressures and tidal volumes (1C) – – Permissive hypercapnia Be limited in patients with preexisting metabolic acidosis and contraindicated in patients with increased initracranial pressure. if needed. Guided by the FiO2 required to maintain adequate oxygenation – PEEP > 5 cm H20 to avoid lung collapse . • Set PEEP to avoid extensive lung collapse at end-expiration (1C) – Titrate PEEP based on 1.Mechanical vent • Allow PaCO2 to increase above normal. Bedside measurement of thoracopulmonary compliance 2.
page 1306.ARDSnet Mechanical Ventilation Protocol Results: Mortality 40 35 30 % Mortality 25 20 15 10 5 0 6 ml/kg 12 ml/kg Adapted from Figure 1.342:1301-1378 . with permission from The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000.
N Engl J Med 2001.345:610-2. et al.65 group 6 90 12 15 18 0 Days 0 0 0 Kaplan-Meier estimates of survival at 6 Gattinoni L. Slutsky AS.The Role of Prone Positioning in ARDS Survival (%) 70% of prone patients improved oxygenation 70% of response within 1 hour 10-day mortality rate in quartile with lowest PaO2:FIO2 ratio (≤ 88) Prone — 23. months . N Engl J Med 2001.345:568-73.2% 10 0 7 5 5 0 2 5 0 0 3 0 Supine group Prone P=0.1% Supine – 47.
Mechanical Ventilation of Severe Sepsis • Maintain mechanically ventilated patients in a semirecumbent position (head of the bed raised to 45°) unless contraindicated (to limit aspiration risk and to prevent the development of VAP) (1B). 354:1851-1858 • . Lancet 1999. between 30° and 45° (2C) Drakulovic et al.
Sedation and Analgesia in Sepsis (2008) Use sedation protocols with a sedation goal for critically ill mechanically ventilated patients – Ramsay score: daytime: 2-3. Re-titrate if necessary (1B) Kollef. 27:2609-2615 Kress. et al. night time: 4-5 • Use either intermittent bolus sedation or continuous infusion sedation to predetermined end points (sedation scales). 342:1471-1477 . with daily interruption/ lightening to produce awakening. Chest 1998. et al. et al. NEJM 2000. 114:541-548 Brook. CCM 1999.
Neuromuscular Blockers • Avoid neuromuscular blockers where possible – Risk of prolonged neuromuscular blockade following discontinuation • Monitor depth of block with train-of-four when using continuous infusions (1B) .
JAMA. Mayo Clin Proc. 2004 .Glucose Control • After initial stabilization – Glcose be maintained <150 mg/dl – Continuous infusion insulin and glucose or feeding (enteral preferred) – Monitoring • Initially: q30-60 mins • After stabilizaiton: q4h Van den Berghe et al. NEJM. 2001 Finney et al. 2003 Krinsley.
to facilitate management of fluid balance in septic patients. no improved in regional perfusion and survival benefit Grade 2D .2008 update Renal Replacement • Absence of hemodynamic instability – Intermittent hemodialysis and continuous venovenous filtration equal (CVVH) Grade 2B • Hemodynamic instability – CVVH preferred --.
CCM 1991. Ann Intern Med 1990.15 • Will increase Na. fluid overload. 112:492-498 Mathieu. et al.Bicarbonate Therapy Bicarbonate therapy not recommended to improve hemodynamics in patients with hypoperfusion-induced lactic acidemia pH >7. 19:1352-1356 . et al. increase lactate and PCO2 Grade 1B Cooper.
use mechanical prophylactic device (1A) – Mechanical device (unless contraindicated) such as graduated compression stockings or intermittent compression devices .Deep Vein Thrombosis Prophylaxis • Heparin (either UFH 2-3times perday or LMWH once daily) was recommended in patients with severe sepsis unless contraindications (1A) • If contraindication for heparin.
Stress Ulcer prophylaxis
• H2 blocker Grade 1A Grade 1B • Proton pump inhibitor • The benefit of prevention of upper GI bleed must be weighed against the potential effect of an increased stomach pH on development of ventilator-associated pneumonia
Intensive Care Med 2006;32:1151-1158
Monitoring a Child With Septic Shock.
• Frequent monitoring is MOST IMPORTANT to recognise and Rx complications. 1. Pulse 5. Urine output. 2. BP6. ABG 3. Level of consciousness 7. PT/PTT/PC 4. 02 saturation 8. CVP
Management- summary. Five important points
1. ABC, supplement 02 always. 2. IV or IO access and fluid resuscitation upto 60 mL/Kg. 3. Early dopamine infusion @10µg/Kg/min 4. Empirical antibiotic. 5. Frequent monitoring.
Summary: gain in mortality in sepsis • Activated protein C 31% vs 25% (-6%) – Bernard et al. JAMA 2002. 123: 1615-1624 . NEJM 2001. 344: 699-709 • Early goal 47% vs 30% (-17%) – River et al. NEJM 2001. Chest 2003. 345: 1368-73 • Hydrocortisone 63% vs 53% (-10%) – Annane et al. 288: 862-871 • Adequate antibiotics therapy 63% vs 31% (32%) – Valles J et al.
hypoperfusion and organ dysfunction. armed with the sepsis bundles. Crit Care Med 2004.A clinician. 320(Suppl):S595S597 . attacks the three heads of severe sepsis: hypotension.
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