Lecture By Dr Kamaran Yousif Meeqat General Hospital Madina, KSA

2. MANAGEMENT OF SEPSIS
2016 GUIDELINES/2018 UPDATE
DR KAMRAN YOUAF,
FCPS(Pak),MRCS(UK)
GEN SURGEON MEQAT HOSPITAL
MADINA MUNAWWARA

3. MASJID E NABAWI

4. ABOUT THE PRESENTATION
• HISTORICAL PERSPECTIVE
• IMPORTANCE OF THE SUBJECT
• DIAGNOSIS,SCORING,MANAGEMENT-2016
• SUMMARY-----MADE EASY

5. THE RORY STORY
AN INFECTION , UNNOTICED , TURN
UNSTOPPABLE
STAUNTON, A 12-YEAR-OLD BOY IN QUEENS, NEW YORK, CUT
HIS ARM PLAYING BASKETBALL IN SCHOOL.THE NEXT DAY, HIS
PARENTS,WORRIED ABOUT HIS FEVER AND LEG PAIN, TOOK
HIM TO SEE HIS PEDIATRICIAN AND THEN, THE DAY AFTER, TO
THE EMERGENCY DEPARTMENT AT LANGONE MEDICAL
CENTER. HE WAS DISCHARGED WITH A DIAGNOSIS OF AN
UPSET STOMACH AND DEHYDRATION BUT DIED 3 DAYS
LATER FROM SEPSIS

6. THE RORY TAUNTON FOUNDATION

7. HISTORICAL PERSPECTIVE
• INTERNATIONAL CONSENSUS ON SEPSIS AND
SEPTIC SHOCK,,,,,1991 TO 2001 AND 2004
• 2004 THROUGH 2008 SURVIVING SEPSIS
CAMPAIGN,SSC
• THIRD INTERNATIONAL CONSENSUS ON
SEPSIS ,,,2016
• HOUR-1 UPDATE 2018

8. THE TERMINOLOGIES
SSC,,,SURVIVING SEPSIS CAMPAIGN
2004,2008,2012,2016
INTERNATIONAL CONSENSUS,,,1,2,3
QOE,,,HIGH,MODERATE,LOW,V LOW
RECOMMENDATIO,,,STRONG,WEAK
BEST PRACTICE STATEMENT,,,
SEPSIS BUNDLE,,,
TIME ZERO,,,,,,,,,,

9. COMPARISON 2016-2012 GRADINGS
2016 Descriptor 2012 Descriptor
• STRENGTH STRONG 1
• WEAK 2
• QUALITY HIGH A
MODERATE B
LOW C
VERY LOW D
• UngradedSS BPS UNGRADED

10. CRITERIA FOR BEST PRACCE
STATEMENTS
1 IS THE STATEMENT CLEAR AND ACONABLE?
2 IS THE MESSAGE NECESSARY?
3 IS THE NET BENEFIT (OR HARM)
UNEQUIVOCAL?
4 IS THE EVIDENCE DIFFICULT TO COLLECT AND
SUMMARIZE?
5 IS THE RAONALE EXPLICIT?
6 IS THIS BEER TO BE FORMALLY GRADED?

11. MAJOR HEALTH CARE ISSUE
• AFFECTS MILLIONS AROUND THE GLOBE
• LOADS OF STUDIES ON EPIDEMIOLOGY,,,SIMPLE
EQUATION IS THAT THE DISEASE HAS RISEN FROM
THOUSANDS PER YEAR IN MAJOR CLINICAL
SETTINGS TO OVER A MILLION AND A HALF PER
YEAR IN THE LAST 40-50 YEARS.
• ECONOMIC BURDEN,,,20 BILLION USD IN US AND
KSA ???
• MAJOR CAUSE OF MORTALITY,,,30-50 % FOR SEP
SHOCK AND 20-30 % FOR SEPSIS

12. MAGNITUDE OF THE PROBLEM
• HOW BIG IS THE ISSUE ?
• WHY SO MUCH IMPORTANCE ?
• WHY TO INVEST TIME AND MONEY ? IS IT
WORTH IT ?

13. DEFINITE YES
• ITS AS IMPORTANT AS A CASE OF
POLYTRAUMA IN ER
• OR A CASE OF ACUTE MI
• OR A PATIENT WITH STROKE
ACUTE MD EMERGENCY,,,,,,PARAMOUNT IMP

14. KEY CONCEPTS OF SEPSIS
• PRIMARY CAUSE OF DEATH FROM INFECTION
ESP IF NOT RECOGNISED EARLY
• A SYNDROME SHAPED BY PATHOGEN FACTOR
AND HOST FACTOR
• SEPSIS INDUCED ORGAN DYSFUNCTION MAY
BE OCCULT,,,
• UNEXPLAINED ORGAN DYSFUNCTION----
UNDERLYING SEPSIS

15. KEY CONCEPTS
• SITE OF INFECTION,,,,,,,,RTI 44-60 %
• ,,,ABDOMEN 26%
• ,,,BLOODSTREAM 20%
• ,,,URIN SYSTEM 12-20 %
• ,,,,SKIN/SOFT TISSUE 14%
• NO DEFINITE SOURCE IN 20-30 %

16. PNEUMONIA

17. CONSOLIDATION

18. FULMINANT CDAD
ABD PAIN,DIARR,FEVER,DEHYDRATION,BP,WBC,MET ACID

20. SEPTIC GANGRENE IN DIABETIC FOOT

21. NECROTIZING FASCIITIS

23. CELLULITIS IN IMMUNO-
COMPROMIZED

24. BED SORE

25. BED SORE

27. PATHOGENS

30. THE PATHOGENS
• GRAM POITIVE REMAIN THE MOST FREQUENT
• GRAM NEGATIVE SUBSTANTIAL
• FUNGAL SEPSIS IS ON THE RISE BUT REMAINS
LOWER THAN THE BACTERIAL
• IN ALMOST HALF THE CASES NO PATHOGEN IS
IDENTIFIED (CULTURE NEGATIVE SEPSIS)

31. PATHOGENS,,,CONT-D
• PATHOGEN VARY,,,REGION,HOSPITAL
SIZE,SEASON,TYPE OF UNIT ETC
• 90 % OF IDENTIFIED PTHOGENS ARE GRAM
POSITIVE AND NEGATIVE
• SINCE MID 80’S,,,G POS SURPASED THE G NEG
SEPSIS
• G POS CN STAPH AUREUS,ENTERO,STREP
• G NEG E COLI,KLEB PNEUM,PSEUDOM
• E COLI REMIANS THE MOST PREVLANT SINGLE
PATHOGEN

32. PATHOGES---RESISTANCE
• THE RESISTANCE PATTERN IN ICU SETTING
• MRSA AND VRE AND E COLI RESISTANT TO
AMOX/CLAVULANIC ACID
• THE LEADING FUNGAL PATHOGEN ISOLATED
IN SEPSIS PATIENTS IS CANDIDA

33. WHY???
• WHY NEW GUIDELINES
• WHY NEW DEFINITIONS
• WHY NEW SCORING SYSTEMS ???

35. ENOUPH???
• INCIDENCE,,,,,EVER RISING NO OF PATIENTS
• HOSPITALIZATION,,,BED OCCUPANCY BY
SEPSIS RELATED PTIENTS HAS RISEN SHARPLY
• COST/ECONOMIC BURDEN,,,HEFY AMOUNT
OF MONEY AND HUMAN RESOURCES BEING
SPENT ON THEM
• MORTALITY,,,,ONE OF EVERY FOUR PATIENTS
WILL DIE

36. WHY ON THE RISE
• RISING GERIATRIC POPULATION
• INCREASE IN METABOLIC DISORDERS
• INCREASED NO OF IMMUNO-COMPROMISED
PATIENTS
• RISING DRUG RESISTANCE

37. WHY NEW DEFINITIONS
DEFINITIONS OF SEPSIS AND SEPTIC SHOCK WERE LAST
REVISED IN 2001. CONSIDERABLE ADVANCES HAVE
SINCE BEEN MADE INTO THE PATHOBIOLOGY
(CHANGES IN ORGAN FUNCTION, MORPHOLOGY, CELL
BIOLOGY, BIOCHEMISTRY, IMMUNOLOGY, AND
CIRCULATION), MANAGEMENT, AND EPIDEMIOLOGY OF
SEPSIS, SUGGESTING THE NEED FOR REEXAMINATION

38. NEW DEFINITIONS
• SEPSIS HAS BEEN REDEFINED AS LIFE-THREATENING
ORGAN DYSFUNCTION CAUSED BY A DYSREGULATED
HOST RESPONSE TO A NEW INFECTION.
• SEPTIC SHOCK HAS ALSO BEEN REDEFINED AS A
SUBSET OF SEPSIS IN WHICH PARTICULARLY
PROFOUND CIRCULATORY, CELLULAR, AND METABOLIC
ABNORMALITIES ARE ASSOCIATED WITH A GREATER
RISK OF MORTALITY THAN WITH SEPSIS ALONE

39. OLD(1991) VS NEW(2016)
DEFINITIONS

40. NEW DEFINITIONS,,, SEPTIC SHOCK
▫ CLINICAL CRITERIA IDENTIFYING SUCH
CONDITION INCLUDE THE NEED FOR
VASOPRESSORS TO OBTAIN A MAP≥ 65MMHG
AND AN INCREASE IN LACTATE
CONCENTRATION > 2 MMOL/L, DESPITE
ADEQUATE FLUID RESUSCITATION.
TERMS LIKE SEVERE SEPSIS/SEPTICEMIA HAVE
BEEN REMOVED

41. OLDER DEFINITIONS

42. DYSREGULATED RESPONSE LEADS TO

43. WHY???
• WHY NEW GUIDELINES
• WHY NEW DEFINITIONS
• WHY NEW SCORING SYSTEMS ???

44. WHICH SCORING SYTEM?

45. CHOOSING THE SCORING SYATEM
• "THE SOFA SCORE FOUND PATIENTS MORE LIKELY TO
BE SEPTIC BOTH IN AND OUT OF THE ICU. BUT IT
INVOLVES THE USE OF MANY LAB TESTS AND IS A BIT
COMPLEX.
• FOR PATIENTS NOT IN THE ICU, THE PERFORMANCE OF
QUICK SOFA SCORE WAS SIMILAR TO THAT OF THE
SEQUENTIAL ORGAN FAILURE ASSESSMENT SCORE.

46. SCORING SYSTM-COND
• IN THE OLD CRITERIA FOR SEPSIS, SIRS SCORE
WAS A MEASURE OF RESPIRATORY RATE,
WHITE BLOOD CELL COUNT, HEART RATE, AND
FEVER.
• THE SEQUENTIAL ORGAN FAILURE
ASSESSMENT SCORE( SOFA ) AND THE LOGISTIC
ORGAN DYSFUNCTION SYSTEM SCORE ( LODS )
ARE MORE RECENT ,PREDICT ORGAN
DYSFUNCTION AND MORTALITY BETTER

47. SEQUENTIAL (SEPSIS-RELATED)
ORGAN
FAILURE ASSESSMENT (SOFA)
• THE SCREENING TOOLS

48. THE SOFA SCORE
• SOFA USES SIMPLE MEASUREMENTS OF MAJOR
ORGAN FUNCTION TO CALCULATE A SEVERITY
SCORE. THE SCORES ARE CALCULATED 24 HOURS
AFTER ADMISSION TO THE ICU AND EVERY 48
HOURS THEREAFTER (THUS, THE TERM
"SEQUENTIAL" ORGAN FAILURE ASSESSMENT).
• THE MEAN AND THE HIGHEST SCORES ARE MOST
PREDICTIVE OF MORTALITY.

49. SEQUENTIAL (SEPSIS-RELATED)ORGN
FAILURE ASSESMENT
MEASUREMENTS OF ORGAN FUNCTION :
●RESPIRATORY SYSTEM – THE RATIO OF ARTERIAL OXYGEN
TENSION TO FRACTION OF INSPIRED OXYGEN (PAO2/FIO2)
●CARDIOVASCULAR SYSTEM – THE AMOUNT OF VASOACTIVE
MEDICATION NECESSARY TO PREVENT HYPOTENSION
●HEPATIC SYSTEM – THE BILIRUBIN LEVEL
●HAEMOPOETIC SYSTEM – THE PLATELET CONCENTRATION
●NEUROLOGIC SYSTEM – THE GLASGOW COMA SCORE
●RENAL SYSTEM – THE SERUM CREATININE,URINE OUTPUT

51. SOFA SCORE VARIABLES

52. IDENTIFICATION OF EARLY SEPSIS
QSOFA
MODIFIED VERSION OF SOFA,
BEDSIDE WITH QSOFA,
▫ RESPIRATORY RATE ≥22/MIN
▫ ALTERED MENTATION
▫ SYSTOLIC BLOOD PRESSURE ≤ 100MMHG
THE PRESENCE OF AT LEAST TWO OF THESE CRITERIA
STRONGLY PREDICTS THE LIKELIHOOD OF POOR
OUTCOME IN OUT-OF-ICU PATIENTS WITH CLINICAL
SUSPICION OF SEPSIS.

53. QSOFA SCORING OUTSIDE ICU

54. INTERNATIONAL CODING

55. DIAGNOSIS
• HOW ?
• WHEN ?
• AND WHERE???
• TIME ZERO/TIME OF PRESENTATION

56. DIAGNOSIS
• DIAGNOSIS OF SEPSIS IS A CONSTELLATION OF
CLINICAL,LAB,RADIOLOG,PHYSIOLOG AND
MICRBIOLOGIC DATA
• EMPIRICAL DIAGNOSIS CAN USUALLY BE
OBTAINED AT BED SIDE THROUGH HX AND
PHYSICAL EXAMINATION FINDINGS

57. DIAGNOSIS
• HISTORY SYMPTOMS AND SIGNS RELATED TO
SOURCE OF SEPSIS AND SYSTEMS AFFECTED BY
THE SEPSIS
• PHYICAL EXAMINATION
• PULSE RATE,RESP RATE,GCS,O2 SAT,YELLOW
SCLERAE,DEHYDRATION-SKIN TURGOR,FALLING
COGNITION,OLIGURIA
• LABORATORY
PLT,BILIRUBIN,CREAT,LACTATE,PT,INR,D-DIMER
AND BLOOD CULTURE

58. WHEN TO SUSPECT ?

60. MANAGEMENT -2016 GUIDELINES
• INITIAL RESUSCITATION
• SCREENING FOR SEPSIS AND PERFORMANCE IMPROVE
• DIAGNOSIS
• ANTIMICROBIAL THERAPY
• SOURCE CONTROL
• FLUID THERAPY
• VASOACTIVE MEDICATIONS
• CORTICOSTEROIDS
• BLOOD PRODUCTS
• IMMUNOGLOBULINS

61. MANAGEMENT-2016 GUIDELINES
• BLOOD PURIFICATION
• ANTICOAGULANTS
• MECHANICAL VENTILATION
• SEDATION ANALGESIA
• GLUCOSE CONTROL
• RRT
• BICARBONATE THERAPY
• VTE PROPHYLAXIS
• STRESS ULCER PROPHYLAXIS
• NUTRITION
• SETTING GOALS OF CARE

62. SYSTEM BASED PPROACH

63. MANAGEMENT OF SEPSIS-2016
GUIDELINES
• MULTI-DISCIPLINARY
• MANAGEMENT

64. MANAGEMENT OF SEPIS
HOUR-1 BUNDLE
• MEASURE S.LACATE,RE-MEA IN2-4H IF>2MM
• BLOOD CULTURE,2 SAMPLES
• BROAD SECTRUM ANTIBIOTICS
• RAPID FLUIDS 30ML/KG,CRYST-IN HYPO/4MM
• VASOPRESSORS-PERSIS HYPOTENSION
DURING/AFTER FLUIDS

65. HOUR – 1 BUNDLE
SURVIVING SEPSIS CAMPAIGN,
WWW.SURVIVINGSEPSIS.ORG

66. A. INITIAL RESUSCITATION
• SEPSIS AND SEPTIC SHOCK ARE MEDICAL
EMERGENCIES, TREATMENT AND
RESUSCITATION BEGIN IMMEDIATELY (BPS)
• IN THE RESUSCITATION FROM SEPSIS-INDUCED
HYPO PERFUSION, AT LEAST 30 ML/KG OF IV
CRYSTALLOID FLUID BE GIVEN WITHIN THE FIRST
3HOURS ( STRONG R, LOW QOE )

67. INITIAL RESUSCITATION-COTD
• FOLLOWING INITIAL FLUID RESUSCITATION,
ADDITIONAL FLUIDS BE GUIDED BY FREQUENT
REASSESSMENT OF HEMODYNAMIC STATUS (BPS)
REASSESSMENT SHOULD INCLUDE A THOROUGH
CLINICAL EXAMINATION AND EVALUATION OF AVAILABLE
PHYSIOLOGIC VARIABLES ( HR, BP , ARTERIAL OXYGEN
SATURATION, RR , T , URINE
OUTPUT, AND OTHERS, AS AVAILABLE) AS WELL AS OTHER
NONINVASIVE OR INVASIVE MONITORING, AS AVAILABLE
• FURTHER HEMODYNAMIC ASSESSMENT (SUCH AS
ASSESSING CARDIAC FUNCTION) (BPS)

68. INITIAL RESUSCITATION-COND
• DYNAMIC OVER STATIC VARIABLES BE USED TO
PREDICT FLUID RESPONSIVENESS, WHERE
AVAILABLE ( WEAK R, LOW QOE )
• INITIAL TARGET MAP OF 65 MM HG IN PATIENTS
WITH SEPTIC SHOCK REQUIRING VASOPRESSORS (
STRONG R, MOD QOE)
• GUIDING RESUSCITATION TO NORMALIZE LACTATE
IN PATIENTS WITH
ELEVATED LACTATE LEVELS AS A MARKER OF TISSUE
HYPO PERFUSION
( WEAK R, LOW QOE )

69. HOW MUCH FLUIDS?
THIS 80 KG MAN NEEDS 80 INTO 30=2400 ML

70. B. SCREENING FOR SEPSIS AND
PERFORMANCE IMPROVEMENT
WE RECOMMEND THAT HOSPITALS AND
HOSPITAL SYSTEMS HAVE A PERFORMANCE
IMPROVEMENT PROGRAM FOR SEPSIS,
INCLUDING SEPSIS SCREENING FOR ACUTELY ILL,
HIGH RISK PATIENTS (BPS).

71. C-DIAGNOSIS
WE RECOMMEND THAT APPROPRIATE ROUTINE
MICROBIOLOGIC CULTURES (INCLUDING BLOOD) BE
OBTAINED BEFORE STARTING
ANMICROBIAL THERAPY IN PATIENTS WITH
SUSPECTED SEPSIS OR SEPTIC SHOCK IF DOING SO
RESULTS IN NO SUBSTANTIAL DELAY IN THE
START OF ANMICROBIALS (BPS).
REMARKS: APPROPRIATE ROUTINE MICROBIOLOGIC
CULTURES ALWAYS INCLUDE AT LEAST TWO SETS OF
BLOOD CULTURES (AEROBIC AND ANAEROBIC)

72. D-ANTIMICROBIAL THERAPY
• ADMINISTRATION OF IV ANTIMICROBIALS SHOULD BE
INITIATED AS SOON AS POSSIBLE AFTER RECOGNITION
AND WITHIN ONE HOUR FOR BOTH SEPSIS AND SEPTIC
SHOCK ( STRONG R, MOD QOE)
• EMPIRIC BROAD-SPECTRUM THERAPY WITH ONE OR
MORE ANTIMICROBIALS FOR PATIENTS PRESENTING
WITH SEPSIS OR SEPTIC SHOCK TO COVER ALL LIKELY
PATHOGENS (INCLUDING BACTERIAL AND
POTENTIALLY FUNGAL OR VIRAL COVERAGE) ( STRONG R,
MOD QOE)

73. • EMPIRIC ANTIMICROBIAL THERAPY BE
NARROWED ONCE PATHOGEN IDENTIFICATION AND
SENSITIVITIES ARE ESTABLISHED AND/OR
ADEQUATE CLINICAL IMPROVEMENT IS NOTED
(BPS)
• AGAINST SUSTAINED SYSTEMIC ANTIMICROBIAL
PROPHYLAXIS IN PATIENTS WITH SEVERE
INFLAMMATORY STATES OF NONINFECTIOUS
ORIGIN (E.G., SEVERE PANCREAS, BURN INJURY)
(BPS)

74. • DOSING STRATEGIES OF ANTIMICROBIALS BE
OPTIMIZED BASED ON ACCEPTED PHARMACO KINETIC
/ PHARMACO DYNAMIC PRINCIPLES AND SPECIFIC
DRUG PROPERTIES IN PATIENTS WITH SEPSIS OR
SEPTIC SHOCK (BPS)
• EMPIRIC COMBINATION THERAPY (USING AT LEAST
TWO ANTIBIOTICS OF DIFFERENT ANTIMICROBIAL
CLASSES) AIMED AT THE MOST LIKELY BACTERIAL
PATHOGEN(S) FOR THE INITIAL MANAGEMENT OF SEPTIC
SHOCK (WEAK R, LOW QOE )

75. • COMBINATION THERAPY NOT BE ROUTINELY USED FOR ONGOING
TREATMENT OF MOST OTHER SERIOUS INFECTIONS, INCLUDING
BACTEREMIA AND SEPSIS WITHOUT SHOCK ( WEAK R, LOW QOE )
THIS DOES NOT PRECLUDE THE USE OF MULTIDRUG THERAPY TO
BROADEN ANTIMICROBIAL
ACTIVITY
• AGAINST COMBINATION THERAPY FOR THE ROUTINE TREATMENT OF
NEUTROPENIC SEPSIS / BACTEREMIA ( STRONG R, MOD QOE )
THIS DOES NOT PRECLUDE THE USE OF MULTIDRUG THERAPY TO
BROADEN ANTIMICROBIAL
ACTIVITY

76. • IF COMBINATION THERAPY IS USED FOR SEPTIC SHOCK, DE-
ESCALATION WITH DISCONTINUATION OF COMBINATION
THERAPY WITHIN THE FIRST FEW DAYS IN RESPONSE TO
CLINICAL IMPROVEMENT AND/OR EVIDENCE OF INFECTION
RESOLUTION. THIS APPLIES TO BOTH TARGETED (FOR
CULTURE-POSITIVE INFECTIONS) AND EMPIRIC (FOR CULTURE-
NEGATIVE INFECTIONS) COMBINATION THERAPY (BPS)
• ANTIMICROBIAL TREATMENT DURATION OF 7 TO 10 DAYS IS
ADEQUATE FOR MOST SERIOUS INFECTIONS ASSOCIATED
WITH SEPSIS AND SEPTIC
SHOCK ( WEAK R, LOW QOE )

77. • LONGER COURSES ARE APPROPRIATE IN PATIENTS WHO HAVE A SLOW
CLINICAL RESPONSE, UNDRAINABLE FOCI OF INFECTION, BACTEREMIA
WITH STAPHYLOCOCCUS AUREUS, SOME FUNGAL AND VIRAL INFECTIONS,
OR IMMUNOLOGIC DEFICIENCIES, INCLUDING NEUTROPENIA
( WEAK R, LOW QOE )
• SHORTER COURSES ARE APPROPRIATE IN SOME PATIENTS, PARTICULARLY
THOSE WITH RAPID CLINICAL RESOLUTION FOLLOWING EFFECTIVE SOURCE
CONTROL OF INTRA-ABDOMINAL OR URINARY SEPSIS AND THOSE WITH
ANATOMICALLY UNCOMPLICATED PYELONEPHRITIS
( WEAK R, LOW QOE )

78. THE COMBINATION THERAPY
IF PSEUDOMONAS IS AN UNLIKELY PATHOGEN: COMBINING VANCOMYCIN;
●CEPHALOSPORIN, 3RD GENERATION OR 4TH GENERATION
OR
●BETA-LACTAM/BETA-LACTAMASE INHIBITOR
OR
●CARBAPENEM
IF PSEUDOMONAS IS A POSSIBLE PATHOGEN :COMBINING VANCOMYCIN WITH TWO
;
●ANTIPSEUDOMONAL CEPHALOSPORIN (EG, CEFTAZIDIME, CEFEPIME), OR
●ANTIPSEUDOMONAL CARBAPENEM (EG, IMIPENEM, MEROPENEM), OR
●ANTIPSEUDOMONAL BETA-LACTAM/BETA-LACTAMASE INHIBITOR (TAZOCIN) OR
●FLUOROQUINOLONE WITH GOOD ANTI-PSEUDOMONAL (CIPROFLOXACIN), OR
●AMINOGLYCOSIDE ( GENTAMICIN, AMIKACIN), OR
●MONOBACTAM (AZTREONAM)

79. ANTIMICROBIALS???
THE CHOICE OF ANTIBIOTICS CAN BE COMPLEX
AND SHOULD CONSIDER THE PATIENT'S
HISTORY , RECENT ANTIBIOTICS RECEIVED ,
COMORBIDITIES, CLINICAL CONTEXT
(COMMUNITY- OR HOSPITAL-ACQUIRED),
GRAM STAIN DATA, AND LOCAL RESISTANCE
PATTERNS

80. • DAILY ASSESSMENT FOR DE-ESCALATION OF
ANTIMICROBIAL THERAPY IN PATIENTS WITH SEPSIS AND
SEPTIC SHOCK (BPS)
• MEASUREMENT OF PROCALCITONIN LEVELS CAN BE
USED TO SUPPORT SHORTENING THE DURATION OF
ANTIMICROBIAL THERAPY IN SEPSIS PATIENTS (WEAK R,
LOW QOE )
• PROCALCITONIN LEVELS CAN BE USED TO SUPPORT THE
DISCONTINUATION OF EMPIRIC ANTIBIOTICS IN PATIENTS
WHO INITIALLY APPEARED TO HAVE SEPSIS, BUT
SUBSEQUENTLY HAVE LIMITED CLINICAL EVIDENCE OF
INFECTION (WEAK R, LOW QOE )

81. E-SOURCE CONTROL
• SPECIFIC ANATOMIC DIAGNOSIS OF INFECTION REQUIRING
EMERGENT SOURCE CONTROL SHOULD BE IDENTIFIED OR
EXCLUDED AS RAPIDLY AS POSSIBLE IN PATIENTS WITH SEPSIS
OR SEPTIC SHOCK, AND THAT ANY REQUIRED SOURCE
CONTROL INTERVENTION SHOULD BE IMPLEMENTED AS
SOON AS MEDICALLY AND LOGISTICALLY PRACTICAL AFTER
THE DIAGNOSIS IS MADE (BPS)
• PROMPT REMOVAL OF INTRAVASCULAR ACCESS DEVICES
THAT ARE A POSSIBLE SOURCE OF SEPSIS OR SEPTIC SHOCK
AFTER OTHER VASCULAR ACCESS HAS BEEN ESTABLISHED
(BPS)

82. WIDE DEBRDMNT,FASCIOTOMY

83. COLECTOMY

84. F-FLUID THERAPY-MAINTAINANCE
• FLUID CHALLENGE TECHNIQUE BE APPLIED WHERE FLUID
ADMINISTRATION IS CONTINUED AS LONG AS HEMODYNAMIC
FACTORS CONTINUE TO IMPROVE (BPS)
• CRYSTALLOIDS AS THE FLUID OF CHOICE FOR INITIAL
RESUSCITATION AND SUBSEQUENT INTRAVASCULAR VOLUME
REPLACEMENT IN PATIENTS WITH SEPSIS AND SEPTIC SHOCK (
STRONG R, MOD QOE)
• USING EITHER BALANCED CRYSTALLOIDS OR SALINE FOR
FLUID RESUSCITATION OF PATIENTS WITH SEPSIS OR SEPTIC
SHOCK
(WEAK R, LOW QOE )

85. • USING ALBUMIN IN ADDITION TO CRYSTALLOIDS
FOR INITIAL RESUSCITATION AND SUBSEQUENT
INTRAVASCULAR VOLUME REPLACEMENT IN
PATIENTS WITH SEPSIS AND SEPTIC SHOCK, WHEN
PATIENTS REQUIRE SUBSTANTIAL AMOUNTS OF
CRYSTALLOIDS
( WEAK R, LOW QOE )
• AGAINST USING HYDROXYETHYL STARCHES FOR
INTRAVASCULAR VOLUME REPLACEMENT IN
PATIENTS WITH SEPSIS OR SEPTIC SHOCK
( STRONG R, HIGH QOE )

86. • USING CRYSTALLOIDS OVER GELATINS WHEN
RESUSCITATING PATIENTS WITH SEPSIS OR
SEPTIC SHOCK (WEAK R, LOW QOE )

87. G-VASOACTIVE MEDICATIONS
• NOREPINEPHRINE AS THE FIRST-CHOICE
VASOPRESSOR
( STRONG R , MOD QOE )
• ADDING EITHER VASOPRESSIN (UP TO 0.03
U/MIN) ( WEAK R , MODQOE ) OR EPINEPHRINE (
WEAK R , LOW QOE )TO NOREPINEPHRINE WITH
THE INTENT OF RAISING MAP TO TARGET, OR
ADDING VASOPRESSIN (UP TO 0.03 U/MIN) ( WEAK
R , MOD QOA )TO DECREASE NOREPINEPHRINE
DOSAGE

88. USING DOPAMINE AS AN ALTERNATIVE
VASOPRESSOR AGENT TO NOREPINEPHRINE ONLY
IN HIGHLY SELECTED PATIENTS (E.G., PATIENTS
WITH LOW RISK OF TACHYARRHYTHMIAS AND
ABSOLUTE OR RELATIVE BRADYCARDIA) (WEAK R,
LOW QOE )
• AGAINST USING LOW-DOSE DOPAMINE FOR
RENAL PROTECTION
( STRONG R , HIGH QOE )

89. • USING DOBUTAMINE IN PATIENTS WHO SHOW
EVIDENCE OF PERSISTENT HYPOPERFUSION DESPITE
ADEQUATE FLUID LOADING AND THE USE OF
VASOPRESSOR AGENTS (WEAK R , LOW QOE )
IF INITIATED, DOSING SHOULD BE TITRATED TO AN END
POINT REFLECTING PERFUSION, AND THE
AGENT REDUCED OR DISCONTINUED IN THE FACE OF
WORSENING HYPOTENSION OR
ARRHYTHMIAS
• ALL PATIENTS REQUIRING VASOPRESSORS HAVE AN
ARTERIAL CATHETER PLACED AS SOON AS PRACTICAL IF
RESOURCES ARE AVAILABLE (WEAK R , LOW QOE )

90. H-CORTICOSTEROIDS
• AGAINST USING IV HYDROCORTISONE TO TREAT
SEPTIC SHOCK PATIENTS IF ADEQUATE FLUID
RESUSCITATION AND VASOPRESSOR THERAPY ARE
ABLE TO RESTORE HEMODYNAMIC STABILITY. IF
THIS IS NOT ACHIEVABLE, WE SUGGEST IV
HYDROCORTISONE AT A DOSE OF 200 MG PER DAY
( WEAK R , LOW QOE )

91. I-BLOOD PRODUCTS
• RBC TRANSFUSION OCCUR ONLY WHEN
HEMOGLOBIN CONCENTRATION
DECREASES TO < 7.0 G/DL IN ADULTS IN THE
ABSENCE OF EXTENUATING CIRCUMSTANCES,
SUCH AS MYOCARDIAL ISCHEMIA, SEVERE
HYPOXEMIA, ACUTE HEMORRHAGE ( STRONG R
, HIGH QOE )

92. • AGAINST THE USE OF ERYTHROPOIETIN FOR
TREATMENT OF ANEMIA ASSOCIATED WITH
SEPSIS ( STRONG R , MOD QOE )
• AGAINST THE USE OF FFP TO CORRECT
CLOTING ABNORMALITIES IN THE ABSENCE OF
BLEEDING OR PLANNED INVASIVE PROCEDURES
( WEAK R , VERY LOW QOE )

93. • PROPHYLACTIC PLATELET TRANSFUSION
WHEN COUNTS ARE <10,000/MM3 IN
ABSENCE OF APPARENT BLEEDING AND WHEN
COUNTS ARE < 20,000/MM3 IF THE PATIENT
HAS SIGNIFICANT RISK OF BLEEDING. HIGHER
PLATELET COUNTS ( ≥ 50,000/MM3) ARE
ADVISED FOR ACTIVE BLEEDING, SURGERY, OR
INVASIVE PROCEDURES ( WEAK R , VERY LOW
QOE )

94. J-IMMUNOGLOBULINS
• AGAINST THE USE OF IV IMMUNOGLOBULINS
IN PATIENTS WITH SEPSIS OR SEPTIC SHOCK
(WEAK R , LOW QOE )

95. K-BLOOD PURIFICATION
• NO RECOMMENDATION REGARDING THE USE
OF BLOOD PURIFICATION

96. L-ANTICOAGULANTS
• AGAINST THE USE OF ANTITHROMBIN FOR
THE TREATMENT OF SEPSIS AND SEPTIC SHOCK (
STRONG R , MOD QOE )
• NO RECOMMENDATION REGARDING THE USE
OF THROMBOMODULIN OR HEPARIN FOR THE
TREATMENT OF SEPSIS OR SEPTIC SHOCK

97. M-MECHANICAL VENTILATION
• USING A TARGET TV OF 6 ML/KG PBW COMPARED WITH
12 ML/KG IN ADULT PATIENTS WITH SEPSIS-INDUCED
ARDS
( STRONG R , HIGH QOE )
• USING AN UPPER LIMIT GOAL FOR PLATEAU PRESSURES
OF 30 CM H2O OVER HIGHER PLATEAU PRESSURES IN
ADULT PATIENTS WITH SEPSIS INDUCED SEVERE ARDS (
STRONG R , MOD QOE )
• USING HIGHER PEEP OVER LOWER PEEP IN ADULT
PATIENTS WITH SEPSIS-INDUCED MOD TO SEVERE ARDS (
WEAK R ,MOD QOE)

98. USING RECRUITMENT MANEUVERS IN ADULT
PATIENTS WITH SEPSISINDUCED,SEVERE ARDS (
WEAK R , MOD QOE )
• USING PRONE OVER SUPINE POSITION IN ADULT
PATIENTS WITH SEPSISINDUCED ARDS AND A
PAO2/FIO2 RATIO < 150
( STRONG R , MOD QOE )
• AGAINST USING HFOV IN ADULT PATIENTS WITH
SEPSIS-INDUCED ARDS ( STRONG R , MOD QOE )

99. NO RECOMMENDATION REGARDING THE USE OF NIV FOR
PATIENTS
WITH SEPSIS-INDUCED ARDS
• USING NMB AGENTS FOR 48 HOURS IN ADULT PATIENTS
WITH SEPSISINDUCED
ARDS AND A PAO2/FIO2 RATIO < 150 MM HG
( WEAK R , MOD QOE )
• CONSERVATIVE FLUID STRATEGY FOR PATIENTS WITH
ESTABLISHED
SEPSIS-INDUCED ARDS WHO DON’T HAVE EVIDENCE OF
TISSUE
HYPOPERFUSION ( STRONG R , MOD QOE )

100. N-SEDATION AND ANALGESIA
• CONTINUOUS OR INTERMITTENT SEDATION BE
MINIMIZED IN MECHANICALLY VENTILATED
SEPSIS PATIENTS, TARGETING SPECIFIC
TITRATION END POINTS (BPS)

101. O-GLUCOSE CONTROL
• PROTOCOLIZED APPROACH TO BLOOD GLUCOSE MANAGEMENT IN ICU
PATIENTS WITH SEPSIS, COMMENCING INSULIN DOSING WHEN TWO
CONSECUTIVE BLOOD GLUCOSE LEVELS ARE > 180 MG/DL. THIS
APPROACH SHOULD TARGET AN UPPER BLOOD GLUCOSE LEVEL ≤ 180
MG/DL RATHER THAN AN UPPER TARGET BLOOD GLUCOSE LEVEL ≤ 110
MG/DL ( STRONG R , HIGH QOE )
• BLOOD GLUCOSE VALUES BE MONITORED EVERY 1 TO 2 HOURS UNTIL
GLUCOSE VALUES AND INSULIN INFUSION RATES ARE STABLE, THEN EVERY
4 HOURS THEREAFTER IN PATIENTS RECEIVING INSULIN INFUSIONS (BPS)

102. GLUCOSE LEVELS OBTAINED WITH POINT-OF-CARE
TESTING OF CAPILLARY BLOOD BE INTERPRETED
WITH CAUTION BECAUSE SUCH MEASUREMENTS
MAY NOT ACCURATELY ESTIMATE ARTERIAL BLOOD
OR PLASMA GLUCOSE VALUES (BPS)
• USE OF ARTERIAL BLOOD RATHER THAN
CAPILLARY BLOOD FOR POINT-OF CARE
TESTING USING GLUCOSE METERS IF PATIENTS HAVE
ARTERIAL CATHETERS ( WEAK R , LOW QOE )

103. P-RRT
• EITHER CONTINUOUS OR INTERMITTENT RRT BE USED
IN PATIENTS WITH SEPSIS AND AKI (WEAK R , MOD QOE )
• USING CONTINUOUS THERAPIES TO FACILITATE
MANAGEMENT OF FLUID BALANCE IN
HEMODYNAMICALLY UNSTABLE SEPTIC PATIENTS ( WEAK
R , VERY LOW QOE )
• AGAINST THE USE OF RRT IN PATIENTS WITH SEPSIS
AND AKI FOR INCREASE IN CREATININE OR OLIGURIA
WITHOUT OTHER DEFINITIVE INDICATIONS FOR DIALYSIS (
WEAK R , LOW QOE )

104. Q-BICARBONATE THERAPY
• AGAINST THE USE OF SODIUM BICARBONATE
THERAPY TO IMPROVE HEMODYNAMICS OR TO
REDUCE VASOPRESSOR REQUIREMENTS IN
PATIENTS WITH HYPO PERFUSION-INDUCED
LACTIC ACIDEMIA WITH PH ≥7.15 ( WEAK R ,
MOD QOE )

105. R-VTE PROPHYLAXIS
• PHARMACOLOGIC PROPHYLAXIS ( UFH OR LMWH )
AGAINST VTE IN THE ABSENCE OF CONTRAINDICATIONS
TO THE USE OF THESE AGENTS
( STRONG R , MOD QOE )
• LMWH RATHER THAN UFH FOR VTE PROPHYLAXIS IN
THE ABSENCE OF CONTRAINDICATIONS TO THE USE OF
LMWH ( STRONG R , MOD QOE )
• COMBINATION PHARMACOLOGIC VTE PROPHYLAXIS
AND MECHANICAL PROPHYLAXIS, WHENEVER POSSIBLE (
WEAK R , LOW QOE )

106. • MECHANICAL VTE PROPHYLAXIS WHEN
PHARMACOLOGIC VTE IS CONTRAINDICATED (
WEAK R , LOW QOE )

107. S-STRESS ULCER PROPHYLAXIS
• STRESS ULCER PROPHYLAXIS BE GIVEN TO
PATIENTS WITH SEPSIS OR SEPTIC SHOCK WHO
HAVE RISK FACTORS FOR GI BLEEDING ( STRONG R ,
LOW QOE )
• USING EITHER PPIS OR H-2 RECEPTOR
ANTAGONISTS WHEN STRESS ULCER PROPHYLAXIS
IS INDICATED (WEAK R , LOW QOE )
• AGAINST STRESS ULCER PROPHYLAXIS IN
PATIENTS WITHOUT RISK FACTORS FOR GI
BLEEDING (BPS)

108. T-NUTRITION
• AGAINST THE ADMINISTRATION OF EARLY PARENTERAL NUTRITION ALONE
OR PARENTERAL NUTRITION IN COMBINATION WITH ENTERAL FEEDINGS
(BUT RATHER INITIATE EARLY ENTERAL NUTRITION) IN CRITICALLY ILL
PATIENTS WITH SEPSIS OR SEPTIC SHOCK WHO CAN BE FED ENTERALLY
( STRONG R , MOD QOE )
• AGAINST THE ADMINISTRATION OF PARENTERAL NUTRITION ALONE OR IN
COMBINATION WITH ENTERAL FEEDS (BUT RATHER TO INTIATE IV
GLUCOSE AND ADVANCE ENTERAL FEEDS AS TOLERATED) OVER FIRST 7
DAYS IN CRITICALLY ILL PATIENTS WITH SEPSIS/SEPTIC SHOCK FOR WHOM
EARLY ENTERAL FEEDING IS NT FEASIBLE ( STRONG R , MOD QOE )

109. • EARLY INITIATION OF ENTERAL FEEDING RATHER THAN
A COMPLETE FAST OR ONLY IV GLUCOSE IN CRITICALLY
ILL PATIENTS WITH SEPSIS OR SEPTIC SHOCK WHO CAN
BE FED ENTERALLY (WEAK R , LOW QOE )
• EITHER EARLY TROPHIC / HYPOCALORIC OR EARLY FULL
ENTERAL FEEDING IN CRITICALLY ILL PATIENTS WITH
SEPSIS OR SEPTIC SHOCK; IF TROPHIC / HYPOCALORIC
FEEDING IS THE INITIAL STRATEGY, THEN FEEDS SHOULD
BE ADVANCED ACCORDING TO PATIENT TOLERANCE
( WEAK R , MOD QOE )

110. • AGAINST THE USE OF OMEGA-3 FATTY ACIDS AS AN IMMUNE
SUPPLEMENT IN CRITICALLY ILL PATIENTS WITH SEPSIS OR SEPTIC
SHOCK( STRONG R , LOW QOE )
• AGAINST ROUTINELY MONITORING GASTRIC RESIDUAL VOLUMES IN
CRITICALLY ILL PATIENTS WITH SEPSIS OR SEPTIC SHOCK( WEAK R ,
LOW QOE )HOWEVER, MEASUREMENT OF GASTRIC RESIDUALS IN
PATIENTS WITH FEEDING INTOLERANCE OR WHO ARE CONSIDERED TO
BE AT HIGH RISK OF ASPIRATION (WEAK R , VERY LOW QOE )
THIS RECOMMENDATION REFERS TO NONSURGICAL CRITICALLY ILL
PATIENTS WITH SEPSIS OR
SEPTIC SHOCK

111. • USE OF PROKINETIC AGENTS IN CRITICALLY ILL
PATIENTS WITH SEPSIS OR SEPTIC SHOCK AND
FEEDING INTOLERANCE ( WEAK R , LOW QOE )
• PLACEMENT OF POST-PYLORIC FEEDING TUBES IN
CRITICALLY ILL PATIENTS WITH SEPSIS OR SEPTIC
SHOCK WITH FEEDING INTOLERANCE OR WHO ARE
CONSIDERED TO BE AT HIGH RISK OF ASPIRATION
( WEAK R , LOW QOE )
• AGAINST THE USE OF IV SELENIUM TO TREAT
SEPSIS AND SEPTIC SHOCK( STRONG R , MOD QOE )

112. • AGAINST THE USE OF ARGININE TO TREAT
SEPSIS AND SEPTIC SHOCK( WEAK R , LOW
QOE )
• AGAINST THE USE OF GLUTAMINE TO TREAT
SEPSIS AND SEPTIC SHOCK( WEAK R , LOW QOE )
• NO RECOMMENDATION ABOUT THE USE OF
CARNITINE FOR SEPSIS AND SEPTIC SHOCK

115. 2018 UPDTE
Hour-1 Surviving SSC Bundle of Care
• MEASURE LACTATE LEVEL : REMEASURE IF INITIAL LACTATE IS >
2MMOL/L (WEAK R, LOW QOE )
• OBTAIN BLOOD CULTURE PRIOR TO ADMINISTRATION OF
ANTIBIOTICS
( BPS )
• ADMINISTER BROAD SPECTRUM ANTIBIOTICS ( STRONG R, MOD
QOE )
• BEGIN RAPID ADMINISTRATION OF 30ML/KG CRYSTALLOID FOR
HYPOTENSION OR LACTATE ≥4MMOL/L ( STRONG R, LOW QOE )
• APPLY VASOPRESSORS IF PATIENT IS HYPOTENSIVE DURING OR
AFTER FLUID RESUSCITATION TO MAINTAIN MAP ≥ 65 MMHG

116. • THE MOST IMPORTANT CHANGE IN THE
REVISION OF THE SSC BUNDLES IS THAT THE 3-
H AND 6-H BUNDLES HAVE BEEN COMBINED
INTO A SINGLE “HOUR-1 BUNDLE” WITH THE
EXPLICIT INTENTION OF BEGINNING
RESUSCITATION AND MANAGEMENT
IMMEDIATELY.

117. SETTING GOALS OF CARE
• GOALS OF CARE AND PROGNOSIS BE DISCUSSED
WITH PATIENTS AND FAMILIES (BPS)
• GOALS OF CARE BE INCORPORATED INTO
TREATMENT AND END-OF-LIFE CARE PLANNING,
UTILIZING PALLIATIVE CARE PRINCIPLES WHERE
APPROPRIATE ( STRONG R , MOD QOE )
• GOALS OF CARE BE ADDRESSED AS EARLY AS
FEASIBLE, BUT NO LATER THAN WITHIN 72 HOURS
OF ICU ADMISSION
( WEAK R , LOW QOE )

118. FINALY
“IT TOOK US MORE THAN 10 YEARS TO UNDERSTAND
SEPSIS , NOW WE WILL HAVE TO CHANGE IT ALL ……”
“…… IS IT THE FINAL WORD IN SEPSIS .. ? … OR THE
STARTING POINT OF DISCUSSION AND ADDITIONAL
RESEARCH INTO THIS DEADLY CONDITION ”
JULIE A. JACOB, MA JAMA. 2016;315(8):739-740.
DOI:10.1001/JAMA.2016.0736.SEPSIS-3 GUIDELINES ITH
H-1 2018 UPDATE HAS BEEN ESTABLISHED WITH THE AIM
OF FOSTERING FUTUTE UPDATES,,,

119. SUMMARY
• 2016 GUIDELINES HOUR-1 BUNDLE-OUTCOME
• APPLIED IN ER,FLOOR,ICU
• TIME ZERO-IDENTIFY EARLY AND ACT EARLY
• HX/EXAM-BLOOD FOR LACTATE/CULTURES
• RAPID FLUIDS 30 ML/KG>3 H,MONITOR
• BROAD SPEC ANTIBIOTICS>HOUR-1
• VASOACTIVE MED IF NEEDED
• QSOFA SCORING---ICU ?

120. SUMMARY
• SORCE CONTROL-EARLY INTRVNTN
• GLUCOSE CONTROL
• BLOOD PRODUCTS-RBC,FFP,PLT
• VTE PROPHYLAXIS-PHARM/MECH OR BOTH
• STRESS ULCER PROPHYLAXIS-PPI/H2 ANTAG
• NEED FOR ORGAN SUPPORT-VENT/RRT
• FAMILY COUNSELLING/SOCIAL WORKER

121. TO SUMMARIZE

122. TAKE HOME MESSAGE
APPLY HOUR-1
• IDENTIFY SEPSIS EARLY,MEASURE S LACTATE
• MORE AND FASTER FLUID
• SEND CULTURES EARLY
• ANTIBIOTIC FAST <1 HR,
• EARLY SOURCE CONTROL,ORGAN SUPPORT
• EARLIER VASOACTIVE, USE NOREPINEPHRINE
• WET FIRST, DRY LATER-FAMILY COUNSELLING

124. KHYBER PASS-----ROAD TO
AFGHANISTAN

125. KHYBER MEDICAL
UNIVERSITY,PESHAWAR, PKISTAN