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GOOD AFTERNOON

SEPSIS - MULTIPLE ORGAN DYSFUNCTION SYNDROME :

- DR . NAVEEN

Objectives

Define SIRS / sepsis / severe sepsis - MODS septic shock

Delineate difference between sepsis SIRS and MODS

Early recognition of Sepsis Prophylaxis Early Goal Directed Therapy

Lay out of immune responses

A continuum of severity describing the host systemic inflammatory response……………

To external trauma Internal physiological uncompensated

traumaExternal or internal source of infection.

SIRS-Sepsis-MODS Spectrum

Epidemiology suggests there is a general progression of pathologic states…

SIRS Sepsis Severe Sepsis Septic Shock MODS

SIRS RESPONSE OF BODY TO STRESS

Defined as ≥2 of the following:Temperature abnormality

>38°C or <36°CHemodynamic distress

tachycardiaRespiratory distress

tachypnea, hypercarbia >32mmol, or hypoxia <70%

Inflammatory markerWBC >12k, <4k, .

Sepsis SIRS plus…

confirmed infectious processor strongly suspected infection or established by

culture or clinical examination

Severe Sepsis Sepsis plus…

organ dysfunction various organ-failures due to hypoperfusion

Septic shock Definition: sepsis plus ≥1 of the following:

decreased peripheral pulses (compared to central pulses)

capillary refill:>2 seconds mottled or cool extremities (cold shock)flash capillary refill (vasodilated / warm shock)

decreased urine output (< 1 mL/kg/hr MAP <60 mm Hg (<80 mm Hg if previous

hypertension) after adequate fluid resuscitation Need for pressors to maintain BP after fluid

resuscitation Adequate fluid resuscitation = 40 to 60 mL/kg

saline solution (NS 5L-10L) Lactate > 4mmol /L

MODS

Definitionprogressive reversible dysfunction of ≥2

organs from acute disruption of normal homeostasis requiring intervention

Primary MODSimmediate systemic response to injury or

insult Needs mostly<1 week in ICU, better

prognosis, Secondary MODS

progressive decompensation from host response & 2nd hits

Needs >1week in ICU, worse prognosis

A Typical Sequence of Organ System Dysfunction…

Circulatory insufficiencyTachycardia hypotension, myocardial depression, CHF, arrhythmia

CNS depression agitation, lethargy, coma

Respiratory failure tachypnea, hypoventilation., hypoxia, hypercarbia, pulmonary edema, ALI/ARDS

Renal insufficiency / failure fluid overload, uremia, electrolyte derangements

Hematologic derangements anemia, hemolysis, thrombocytopenia coagulopathy, DIC, consumptive-hemorrhagic complications

Gut/Hepatic dysfunction ileus, cholestasis, bacterial translocation,- internal infection gastritis, malnutrition, poor synthesis

Endocrine dysfunction insulin resistance, hyperglycemia, adrenal insufficiency

Immune system cellular and humoral immune suppression

What actually is happening

MODS is comprised of the activation and dysregulation of multiple complex overlapping physiologic systems

Overall: hormonal, cytokine, and immunologic changes leading to systemic inflammation, a procoagulant state, & organ dysfunction

Increases Stress Hormonescaetocholamines cortisolgrowth hormoneglaucagonsinsulin

Immune System Activationcompliment activationneutrophil & macrophage activationfree radical liberationtoxic oxygen metabolitesimmune-mediated proinflammatory…

peptides cytokines bioactive lipids

Inflammatory Cytokines many involved, major causes listed…tumor necrosis factors (TNF)interleukins (IL-1β, IL-6, IL-8, IL-4, IL-10)interferonscytokine receptors & receptor antagonists

Procoagulant Stateshift in tendency of coagulation system endothelial injury and dysfunctionfibrinolysis inhibitedprotein C depletion

Increased Metabolic Demandsincreased oxygen consumptionincreased gluconeogenesisincreased protein catabolism

Feed-Forward Cyclemetabolic/inflammatory/immunologic responses

become generalized & persistent (even in absence of original stimulus)

increased demand on organ function promotes failure (CO, ventilation, oxygenation, nutrition, fluids, excretion of waste)

Organ Failure causes metabolic/inflammatory/immunologic

responses hypoxia ischemia cell death inflammation

Imbalance between Proinflammatory Cytokines

e.g., IL-6, IL-8 & interferon-γpromote immune cell-mediated killing

Anti-inflammatory Cytokinese.g., soluble TNF receptor, IL-1 receptor

antagonist protein, IL-4, and IL-10turn off the immune response when

infection/stimulus has been cleared

Cytokines out of control…Peroxynitrite (ONOO−) can cause DNA damage

Cell program and function derangedActivation of poly ADP-ribose synthetase

depletes cells of NAD+ & ATP leads to secondary energy failure

overactivated immune cells release Fas & Fas ligand

prevents activated immune cell apoptosispromotes ongoing inflammation

ineffective and unresolving inflammation

leads to systemic organ failure

MODS- VARIETIES

THROMBOCYTOPENIA ASSOCTIATED MODS- DIC

PROLONGED MONOCYTE DEACTIVATION

PROLONGED LYMPHOPENIA WITH SUPER INFECTION

VIRAL INFECTION WITH SEQUENTIAL ORGAN FAILURE FIBROPROLIFERATIVE LUNG DISEASE WITHOUT INFECTION.

STEPS TO COMBAT SEPSIS

STEP 1: Identify SEPSIS STEP 2: Categorize SEPSIS STEP 3: Initiate TREATMENT

Cultures / Antibiotics / Labs Cultures PRIOR to Antibiotics ( 2 Sets, one peripheral and

one from any line older than 48hrs) IV Abx within 3 hrs in the ED, within 1 hr in the ICU

Broad Spectrum, combination therapy for neutropenic and patients with pseudomonas risk factors

Consider need for Source Control ! Drainage of abscess or cholangitis, removal of infected

catheters, debridement or amputation of osteomyelitis

Central Line Access (Fluid hydration +/- pressor)

1st line therapy – fluids Crystalloid equivalent to colloid Initial 1-2 Liters (20mg /kg) crystalloid or 500

ml colloid Careful in CHF patients !!

Use in Septic Shock, if NO response to vasopressors and fluidsHYDROCORTISONE 200mg -300mg / day

Divided doses (Q6hrs)Initial Dose 100mg IV x1Wean Steroids QUICKLY once off pressors

Recognize Sepsis EARLY and determine SEVERITY

EARLY Antibiotics are critical to resolution of shock

RESUSCITATE severe sepsis and septic shock

MODS PREVENTIONGeneral:

rapidly identify and eliminate inciting stimulus before host response becomes own feed-forward stimulus

Primary MODS: Measures to decrease multisystem injury/trauma/illness

through avoidance of 1st hit in a vulnerable demographic e.g., protective gear, immunizations, etc.

Secondary MODS: Measure to forestall progression of SIRS or Sepsis to MODS

through avoidance of 2nd hits in a primed system e.g., rapid medical access (EMT), special teams

MODS TREATMENT Severe infection in MODS

Appropriate antimicrobials early empiric antimicrobials timely conversion to infection-specific therapy antibiotics with best MIC

Early goal-directed hemodynamic & O2-delivery therapy

normal BP w/ IVF and SVC O2 sat >70% achieve with oxygen + PRBC + inotropes

Activated protein C Adjunctive immune therapy

GCSF / GM-CSF for neutropenic patients (esp. newborns) steroids/IVIG/etc in selected cases

Septic Shock in MODS Use of hydrocortisone plus fludrocortisone

for patients with a minimal cortisol response to corticotropin stimulation

Careful vasopressor selection in patient population

ECMO in selected cases benefit greatest in neonates > children > adults

ARDS in MODS

Lung-protective ventilation low stretch ventilation (prevent volume trauma)

Steroids in Proliferative phase criteria:

unresolving ARDS (>1 week) culture-negative (by BAL)

decreases fibrin deposition

ARF in MODS

Renal replacement therapy CVVHD > daily dialysis > intermittent dialysis CVVHD appears to alter cytokines favorably

Address abdominal compartment syndrome PD catheter for decompression

Other Problems in MODS Hyperglycemia

insulin therapy normoglycemia improves outcomes in ICU patients

Hypogammaglobulinemia IVIG broader empiric antimicrobial coverage

Immunosupression in MODS cessation of immunosupressants broader empiric antimicrobial selection

SCORING

PaO2/FiO2 ratio----------------300-1000 Platelet count in 10^3/cc-- >120 Serum bilirubin in mg/dl-----1.2 Pressure adjusted Hr rate--- 0-10 HR >< CVP / MAP Glasgow coma scale------- 5-15 Serum creatinine------------- <1.1 mg/dl

Minimum-o maximum-24

0 points: ICU Mort 0%, Hosp Mort 0%, ICU Stay 2 Days

1-4 points: ICU Mort 1-2%, Hosp Mort 7%, ICU Stay 3 Days

5-8 points: ICU Mort 3-5%, Hosp Mort 16%, ICU Stay 6 Days

9-12 points: ICU Mort 25%, Hosp Mort 50%, ICU Stay 10 Days

13-16 points: ICU Mort 50%, Hosp Mort 70%, ICU Stay 17 Days

17-20 points: ICU Mort 75%, Hosp Mort 82%, ICU Stay 21 Days

21-24 points: ICU Mort 100%, Hospital Mortality 100%

Antibiotic prophylaxis for surgery

 Risk of infection The risk of SSI depends on a number of factors; these can be related to the patient or the operation and some of them are modifiable • Age • Nutritional status • Diabetes • Smoking • Obesity • Coexistent infections at a remote body site • Colonization with microorganisms (e.g. Staph. aureus) • Immunosuppression (inc. taking glucocorticoid steroids) • Length of preoperative stay • Coexistent severe disease Patient

Risk of infection Operation • Duration of surgical scrub • Preoperative shaving/ preoperative skin prep. • Length of operation • Appropriate antimicrobial prophylaxis • Operating room ventilation • Inadequate sterilization of instruments • Foreign material in the surgical site • Surgical drains • Surgical technique inc. haemostasis, • poor closure, tissue trauma • Post-operative hypothermia

The risk is also related to the amount of contamination with microorganisms which is called “class” of the operation Clean Operations in which no inflammation is encountered and the respiratory, alimentary or genitourinary tracts are not entered. There is no break in aseptic operating theatre technique. Clean-contaminated Operations in which the respiratory, alimentary or genitourinary tracts are entered but without significant spillage. Contaminated Operations where acute inflammation (without pus) is encountered, or where there is visible contamination of the wound. Examples include gross spillage from a hollow viscus during the operation or compound/open injuries operated on within four hours Dirty Operations in the presence of pus, where there is a previously perforated hollow viscus, or compound/open injuries more than four hours old.  Prophylactic antibiotics • Prophylaxis with antibiotics has decreased the high

incidence of wound infection after head and neck operations that involve incisions through oral or pharyngeal mucosa. • Prophylactic administration of antibiotics can decrease postoperative morbidity, shorten hospitalization, and reduce overall costs attributable to infections. • Additional doses during the procedure are advisable if surgery is prolonged (i. e, >4 h), major blood loss occurs, or an antimicrobial with a short half-life is used

 The aim of prophylaxis The aim of prophylaxis is to augment host defense mechanisms at the

time of bacterial invasion. Prophylaxis is an attempt to attack organisms before they have a

chance to induce infection.  Antibiotic Prophylaxis Timing for Administration Additional Intra-operative doses Post-operative antibiotic prophylaxis Timing for Administration Antibiotic prophylaxis administered too early

or too late increases the risk of SSI. Studies suggest that antibiotics are most effective when given 30 minutes before skin is incised.

For operations lasting more than 4 hours re-dosing may be necessary. Antibiotic Recommended re-dosing interval/dose to give Cefuroxime 4 hours, 750mg IV Clindamycin 4 hours , 300mg IV Co-amoxiclav 4 hours, 1.2g IV Metronidazole 8 hours, 500mg IV

FOUR GUIDLINES

Safety An appropriate NARROW specrum of coverage of relevant

pathogens Little or no reliance on the agent for therapy of infection-to

prevent resistence Administration of drug at appropriate time before incision and for

defined period thereof mostly single dose no longer than 24hrs

Risks of prophylaxis

Drug allergy- anaphylaxis Steven Johnson syndrome TENS Antibiotic induced dirrhoea Coolonisation by opportunistic flora Antibiotic resistance Multiresistance carriage and spread. Catheter related infections

Is prophylaxis mandatory?

Facial surgeries without implant Gall bladder surgery with no risk of bile leak Uncomplicated inguinal, femoral, incisional, either laparoscopic

or open with mesh or without Diagnostic endoscopy except ercp Tonsillectomy,adenoidectomy, Splenectomy in immunocompetent patient CAN BE MANAGED WITH OUT PROPHYLAXIS AND PROPHYLAXIS IS

NOT RECOMMENDED AS A ROUTINE

ALL OTHER surgical procedures including Therapeutic endoscopy, shockwave lithotripsy routinely

prophylaxis is recommended Soft tissue surgery of hand can be considered for prophylaxis on

need basis depending on type of wound

Antimicrobials May be: Bacteriostatic – inhibits growth of Bacteria, so acts by

preventing bacteria from multiplying and then hosts defences deal with the small number of bacteria left

Bactericidial – kills Bacteria, so eliminates bacteria

Concentration dependent bactericidal activity-Aminoglycosides-Quinolones-Carbapenems Time dependent bactericidal activity-B-lactams-Glycopeptides Bacteriostatic Activity-Erythromycin-Tetracycline

If vancomycin is selected it must be used in institutions with established MRSA infection risk

First generation cephalosporin can be used for CTVS-median sternotomy(clindamycin) pacemaker insertion

defibrillators vascular procedures.(except carotid endarterectomy)

Pulmonary resection Lower limb amputation(gentamycin and metronidazole) Cholecystectomy high risk (gentamycin) Gastrectomy, hepatobilliary(G M) Malor debridement(G) Genito urinary(ciproflox) Hysterectomy(doxycycline) LSCS- STAT DOSES (M OR Doxy)

Surgery in oral or pharyngeal cavity with mucosal breach(G C or M)

CRANIOTOMY(C,V) ORTHROPLASTY(V) Appendicectomy- colonsurgery-prenetating trauma abdomen

SECOND generation cephalosporins(Metronidaz plus gentamycin)

THANK YOU

Superficial Incisional SSI: Occurs within 30 days postoperatively and involves skin or subcutaneous tissue of the incision and at least one of the following: (1) purulent drainage from the superficial incision, (2) organisms isolated from an aseptically obtained culture of fluid or tissue from the superficial incision, (3) at least one of the following signs or symptoms of infection: pain or tenderness, localized swelling, redness, or heat, and superficial incision is deliberately opened by surgeon and is culture-positive or not cultured (a culture-negative finding does not meet this criterion), and (4) diagnosis of superficial incisional SSI by the surgeon or attending physician

Deep Incisional SSI: Occurs within 30 days after the operative procedure if no implant is left in place or within one year if implant is in place and the infection appears to be related to the operative procedure, involves deep soft tissues (e.g., fascial and muscle layers) of the incision, and the patient has at least one of the following: (1) purulent drainage from the deep incision but not from the organ/space component of the surgical site, (2) a deep incision spontaneously dehisces or is deliberately opened by a surgeon and is culture-positive or not cultured and the patient has at least one of the following signs or symptoms: fever (>38 °C) or localized pain or tenderness (a culture-negative finding does not meet this criterion), (3) an abscess or other evidence of infection involving the deep incision is found on direct examination, during reoperation, or by histopathologic or radiologic examination, and (4) diagnosis of a deep incisional SSI by a surgeon or attending physician