Surviving Sepsis GuidelinesCrit Care Med 2004Crit Care Med 2008Crit Care Med 2012 Dr Samir Sahu Intensivist Kalinga Hospital, BBSR
SEPSIS: A Significant Healthcare Challenge • Incidence of SEPSIS increasing • Leading cause of death in non cardiac ICU • 11th leading cause of death • Graying of the worlds population • Emergence of antibiotic-resistant organism • Increasing prevalence of immunocompromised patients • Increased use of invasive procedures
SEPSIS MORTALITY • Severe Sepsis 56%-60% (1052) Brun1995 • Severe Sepsis/Septic Shock 38% (4356) Natanson 1998 • Septic Shock 49.7% (10,694) Friedman1998 Rangel 1995
DEFINATIONS -1991, Nov 2002 • SEPSIS – Inflammatory response to infn. (Fever, Tachycardia, Tachypnoea, Leucocytosis, Leucopenia, Alt. Sensorium) • SEVERE SEPSIS – Sepsis associated organ dysfunction • SEPTIC SHOCK - Refractory Hypotension Hypoperfusion (SBP<90mm Hg or reduction of >40mm Hg from baseline)
Epidemiology • Severe sepsis and septic shock together comprise a common and lethal disease • Occurring in 10% to 25% of all patients in intensive care units • Mortality rates of Severe Sepsis 40% and 60% • Mortality in Septic Shock 80-90% • Sepsis rates in cancer patients 10 times higher than in noncancer patients • People over the age of 65 years are 13 times more likely to develop sepsis than younger individuals • 27% of patients with sepsis dying in the ICU, rising to > 50% in patients with septic shock (SOAP)
Epidemiology • The average sepsis survivor requires 7-14 days of ICU support • Another 10-14 days of hospital stay • Average hospital length of stay – 3-5 weeks • Best practical predictor of outcome– SOFA • Baseline ICU mortality 10-15%, each new organ system failure add 15-20% • Severity of organ dysfunction correlates with outcome (escalating vasopressors worst prognosis) • SOFA not to be used for prognosticating individual patients (only for comparing with other studies)
General Principles of Therapy • Predisposing conditions • Nature of infection • Assess degree of organ dysfunction • Lab CBC, Complete chemistry profile, PT,ABG Urine analysis Blood C/S, Other C/S • CXR, U/S Abd
Grading of Recommendations • A – >2 large RCT • B - At least one RCT • C - Small RCT • D - Nonrandomised cotemporaneous trial • E - Nonrandomised historical controls, expert opinion, case series, uncontrolled studies
Diagnosis • Appropriate cultures before antibiotic therapy - At least 2 blood cultures(10 ml) 5-15 min apart at least 1 from peripheral line (1C) • If on Antibiotic Blood culture with - ARD as resin - Before next dose is due - Just before & during fever spike • Cultures of other sites as the clinical situation dictates (urine, wound, etc.) • Imaging studies (1C)
Diagnosis • We suggest the use of the 1,3-beta-D Glucan assay(2B), mannan & anti-mannan antibody assay for the early diagnosis of invasive Candidiasis(2C).
SIRS • Temperature >100.4°F or <96.8°F • Heart Rate >90/min • Resp. rate >20/min or PaCO2 <32mm Hg • TLC >12,000/cu mm or <4000/cu mm • Altered Sensorium • Ileus • Raised CRP • Raised S.Lactate • Raised Cytokines
Presentation • Nosocomial infections – longer LOS & higher mortality • Tachypnoea – 80% • Fever on admission – 60% • Tachycardia – almost 100% • Hypoxia > 90% • Tissue hypoperfusion develop before frank hypotension • Higher lactate clearance after 6 hrs of therapy decreased mortality
Organ Dysfunction CVS-SBP<90mm Hg for>1hr despite fluids Resp.-SpO2<90%, PaO2<70mm Hg, PaO2/FiO2<300 Renal -S.Cr x 2, Urine output<0.5ml/Kg/hr for 1hr despite fluids CNS - reduced GCS Hepatic - S.Bil.>2mg% for 2days, SGPTx2 Haem.-Platelets<1,00,000/cumm,INR>1.2
Improving Outcome • Timely recognition and diagnosis of severe sepsis is the first step • Applying the evidence-based guidelines created under the auspices of the Surviving Sepsis Campaign is the second step • Adherence to the guidelines is equally important to successfully implement change.
Screening for Sepsis & Performance Improvement • We recommend screening of critically ill patients without obvious noninfectious eitiologies of organ dysfunction for infection to increase the early identification of severe sepsis and allow implementation of early evidence based sepsis therapy(1C). • Performance improvement efforts in severe sepsis should be employed to improve patient outcomes(1C).
6 hr Sepsis Bundle (5) • Measure serum lactate level (<2) • Obtain blood cultures before antibiotic administration. (1C) • From the time of presentation, administer broad-spectrum antibiotics within 3 hours for emergency department admissions and within 1 hour for non–emergency department intensive care unit (ICU) admissions. (1B)
Blood Cultures • True blood cultures rates – 8.1% • 50% contamination • Many blood cultures are obtained long after severe sepsis is established & represent insignificant colonization Weinstein Clin Infect Dis 1983 • Recommend 1,3 Glucan-D assay(2B) & manan & antimanan assay for early diagnosis of invasive Candidiasis(2C). 2012.
ANTIBIOTIC THERAPY • Delay in starting Antibiotic Therapy increases mortality • Immediate Administration - start IV antibiotics within 1st hour of recognition of severe sepsis after appropriate cultures. (1C) • Delays as short as 6 hours can lead to an increase in mortality Grade E
Duration of Hypotension before initiation of effective antimicrobial therapy is critical determinant of survival in human septic shock Kumar A, Crit Care Med 2006 • 14 ICUs, 2,731 patients • Recurrent or persistent Septic Shock • Effective Antimicrobial administration within the first hour of documented hypotension was associated with increased survival (79.9%) • Each hour of delay in antimicrobial administrat. over the next 6 hours was associated with an average decrease in survival of 7.6% • Only 50% received effective antimicrobial in 6 h
Association Between Timing of Antibiotic Administration and Mortality From Septic Shock in Patients Treated With a Quantitative Resuscitation Protocol Puskarich, Crit Care Med. 2011;39(9):2066-2071. • In this large prospective study of ED patients with septic shock who received standardized early recognition and aggressive resuscitation at three experienced institutions, • failed to demonstrate an association between timing of antibiotic administration from ED triage and hospital mortality.
Association Between Timing of Antibiotic Administration and Mortality From Septic Shock in Patients Treated With a Quantitative Resuscitation Protocol Puskarich, Crit Care Med. 2011;39(9):2066-2071. • A delay in antibiotics until after shock recognition, as compared with before, was associated with increased mortality; • however, if antibiotics are administered after shock recognition, there is no increase in mortality with hourly delays.
Delay in starting Antibiotic • 0 hrs – 22 • 1 hr - 25 • 2 hrs - 19 • 3 hrs - 16 • 4 hrs - 17 • 5 hrs - 7 • 6 hrs - 5 • > 6 hrs -17
Initial Empirical Therapy • Inappropriate Initial Antibiotic Therapy increases mortality four times. • Subsequent change of Antibiotics after culture results does not decrease mortality. • Broad spectrum to cover all likely pathogens. (1B) • Penetrates into the presumed source. • Choice of drug guided by local susceptibility pattern in the community & hospital. • Combination for Pseudo, septic shock, Neutrop Grade D
Piptazo – 46 Piptazo/Teico – 6 Imipenem – 8 Imipenem + Teico – 3 Imipenem + Vanco – 1 Meropenem – 15 Meropenem + Teico – 7 Meropenem + Vanco - 1 Cefipime – 3 Cefopera/sulb – 6 Amoxyclav - 2 Initial Antibiotics
Antibiotic Therapy • De-escalate (narrow the spectrum) once organism & susceptibility is known. (1C) *minimizes development of resistant path. *contains cost *prevents superinfection (candida) *only done 1/3rd of times • Antibiotic regimen should be re-assessed after 48-72hours.
Antimicrobial Therapy • The antimicrobial regimen should be reassessed daily to optimize activity, to prevent development of resistance, to reduce toxicity, and to reduce costs.(1C) • We suggest the use of low prolactin levels to assist the clinician in the discontinuation of empiric antibiotics when no infection is found.(2C) 2012.
Antimicrobial Therapy 2012 • We suggest that antiviral therapy be initiated as early as possible in patients with severe sepsis and septic shock of viral origin, when available, such as for severe influenza infection (2C). • Appropriate viral cultures and real-time PCR (more sensitive & specific) should be obtained but should not delay prompt administration of antiviral therapy.(2C)
Duration of Therapy • The decision to continue, narrow or stop antimicrobial therapy must be made on the basis of clinical judgment & other culture reports • Blood cultures are negative in majority (75%) (KHL 92.5%) • Guided by Clinical Response (7-10days) (1D) • Neutropenia - continue till duration of Neutropenia.
Empiric Antibiotic • Late onset VAP - 2 Anti-pseud. + Glycopeptide/Linozolid • MRSA - prior antibiotics - chronic illness (ESRD,DM,Ca) - Steroids • Pseudo - prior antibiotics - structural lung disease - prolonged hospitalization • Acineto - prior antibiotics, device use
Gm +ve infections Lungs 9/38 Urine 9/28 Blood 7/16 Skin 5/12 Abdomen 2/8 Central line 0/2 Total 32/104 (30%) Staph aureas 23 MSSA 14 MRSA 9 Enterococci 9 Non hemolytic Strepto 1 KHL – Severe Sepsis 195 cases
Antibiotic Therapy • Staphylococcus aureus Pen - R, Ox - S - R to Amp/Amoxy/Piperacillin R to 3rd gen. Ceph & Ceftazidime - > 90% produce B-lactamases
Antibiotic Therapy • Streptococcus pneumonae • Ox - R : Clavunate does not enhance susceptibility to B-lactamases • Clinda - R : Azithro/Clarithro failure • Cipro inappropriate because of resistance
Local Susceptibility DataMRSA - KHL • Prevalence: 40.66%->34% • S - Vanco - 96% - Teico - 86% - Linco - 84% - Linezolid - 84%
Local Susceptibility DataESBL - KHL ceftazidime cefipime 2003 2004 2005 2003 2004 • E.coli: 60-65 25-38 63 10-30 10-40 • Kleb.: 50-55 28-40 56 10-20 5-15 • Pseudo:25-75 32-45 15-25 10-35 • Enterob: 40 15-74 5-15 5-25
ESBL - KHL ceftaz 4thcep Am Ci/LG PT Im • E.coli: 60-65 10-30 45 80/10 6 2 • Kleb.: 50-55 10-20 40 50/10 3 3 • Pseudo: 25-75 15-25 45 50/10 1 10 • Enterob: 40 5-15 35 • Imipenem>Piptaz>Gatifloxacin/Levoflox >Amikacin
Local Susceptibility DataResistance Gm-ve - KHL Amik L/G PipT Imi/Mer 03/ 04/ 05 03/04/05 03/04/5 03/04/05 • E.coli: 45/0-10/10 10/10/40 6/5 /.7 2/5 /.2 • Kleb.: 40/8-35/17 10/10/30 3/5/0 3/5/ 0 • Pseudo 45/5-28 10/10 1/5 10/5 • Enterob: 35/5-10 /10 /5 /5 Severe Sepsis : Meropenem/Imipenem>Piptaz> >Amikacin
Source Control • Drainage - Intra-abdominal abscess - Thoracic empyema - Septic arthritis - Pyelonephritis, Cholangitis • Debridement - Necrotizing fascitis - Infected pancreatic necrosis - Intestinal infarction - Mediastinitis (1C)
Source Control • Device Removal – Infected vascular cathet - Urinary catheter - Colonized endotracheal tube - Infected IUCD • Definitive Opern. - Diverticulitis - Gangrenous cholecystitis - Clostridialmyonecrosis amputation (1C)
Infection Prevention • We suggest SOD & SDD to reduce the incidence of Ventilator associated pneumonia in health care settings in regions where this methodology has been found to be effective(2B).2012
Fluid Resuscitation • Organ hypoperfusion - Rapid initiation of ISOTONIC crystalloid (RL or NS 20ml/kg) Grade C • Only 250ml remain intravascularly after 1L • 4-6L may be required in first 6 hrs • 500-1000ml crystalloid/300-500ml colloid in 30min • Monitor goals of fluid therapy frequently (Fluid responsive-250 ml crystalloid should raise CVP by 2 cm) • FFP if coagulopathy • Packed cells if Hct <30% • Hydroxylethyl Starch if BP still low Metanalysis CHOI:CCM:1999, SAFE (1C)
Fluid Therapy • We suggest adding Albumin in the initial resuscitation regimen of severe sepsis and septic shock if the serum albumin is known or anticipated to be low (2B). • We recommend against the use of hydroxylethyl ethyl substances with molecular weight >200 daltons & or a degree of substitution >0.4(1B).2012
Fluid Therapy • Initial fluid challenge in patients with sepsis-induced hypoperfusion with suspicion of hypovolemia be started with 1000ml of crystalloids (to achieve a minimum of 30ml/Kg of crystalloids in the first 4-6 hours)(1B).2012
Fluid Responsiveness • Fluid challenge – 250 ml crystalloid in 15 min raises CVP by 2 cm • MV not spontaneously breathing • Systolic Pressure variation • Pulse Pressure variation • Stroke volume variation • Respiratory variation in plethysmography • Passive leg raising
Fluid Responsiveness Static – Pressure : CVP, PAOP, – Volume : Echo, Picco Dynamic : • Stroke volume variation – Picco, Flotrac • Systolic Pulse variation – MV, paralysed, TV 8 ml/Kg • Fluid challenge – 10-15% of stroke volume; Echo before & after • Passive Leg raising in end expiratory pause
Fluid Therapy • Fluid challenge technique of using incremental boluses be applied wherein fluid administration is continued as long as the hemodynamic improvement either based on dynamic(delta pulse pressure, stroke volume variation) or static (arterial pressure, heart rate) variables continues(1C).2012
Sepsis in European Intensive Care Units: Results of the SOAP Study • Fluid balance may be just a marker of the severity of sepsis, but here a multivariate analysis suggested that it is more than just an indicator of severity and is an independent predictor of outcome • Negative fluid balance (≤-500 ml) achieved by the third day of treatment was a good predictor of survival in patients with septic shock.
6 hr Sepsis Bundle (5) • In the event of hypotension and/or lactate level greater than 4 mmol/L (36 mg/dL), deliver an initial minimum dose of 20 mL/kg of crystalloid (or colloid equivalent)(1C); use vasopressors for hypotension not responding to initial fluid resuscitation to maintain mean arterial pressure of 65 mm Hg or greater. (1C) • In the event of persistent hypotension despite fluid resuscitation (septic shock) and/or lactate level greater than 4 mmol/L (36 mg/dL), achieve central venous pressure of 8 mm Hg or greater & achieve central venous oxygen saturation of 70% or greater or a mixed venous oxygen saturation of 65% or greater. (1C)