AND MISCONCEPTIONS IN THE MANAGEMENT OF SEPSIS

Transcription

1 MYTHS AND MISCONCEPTIONS IN THE MANAGEMENT OF SEPSIS SEPSISMADE EASY SURVIVINGSEPSIS COOKBOOK SEPSIS ISAPIE MERVYN SINGER BLOOMSBURY INSTITUTE OF INTENSIVE CARE MEDICINE UNIVERSITY COLLEGE LONDON, UK

2 DISCUSSION POINTS.. Guidelines should be slavishly followed One size fits all Every hour of antibiotic delay kills How long should a course of antibiotics last? Sepsis mortality is improving Why do people die of sepsis?

3 DISCUSSION POINTS.. Guidelines should be slavishly followed One size fits all Every hour of antibiotic delay kills How long should a course of antibiotics last? Sepsis mortality is improving Why do people die of sepsis?

4 INDIVIDUALS VERSUS POPULATION

5 INDIVIDUALS VERSUS POPULATION Patients do NOT necessarily follow the rule book MUST tailor therapy to the individual Guidelines should NOT be used as rigid protocols/rules of stone Clinical expertise is VITAL

6 INDIVIDUALS VERSUS POPULATION Patients do NOT necessarily follow the rule book MUST tailor therapy to the individual Guidelines should NOT be used as rigid protocols/rules of stone Clinical expertise is VITAL.. not my words, but David Sackett s

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9 QUALITY - OR LACK - OF EVIDENC

10 QUALITY - OR LACK - OF EVIDENC Overall evidence base for sepsis is - sadly - rather weak Only a few awarded high quality (but generally do nots rather than do s )

11 DOGMA SHOULDN T RULE Need decent evidence to confirm need to change For example, Rivers showed EGDT was beneficial in but why?

12 DOGMA SHOULDN T RULE Need decent evidence to confirm need to change For example, Rivers showed EGDT was beneficial in but why?

13 DOGMA SHOULDN T RULE Need decent evidence to confirm need to change For example, Rivers showed EGDT was beneficial in but why?

14 DOGMA SHOULDN T RULE Need decent evidence to confirm need to change For example, Rivers showed EGDT was beneficial in but why?

15 DOGMA SHOULDN T RULE Need decent evidence to confirm need to change For example, Rivers showed EGDT was beneficial in but why?

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19 TAKE-HOME MESSAGE Identify patient early Treat promptly and appropriately.. but the specific Rivers protocol doesn t seem to offer any overall added benefit

20 LOWEST COMMON DENOMINATOR? good performing hospitals not-so-good performing hospitals Standardised mortality ratio

21 LOWEST COMMON DENOMINATOR? good performing hospitals Standardised mortality ratio? rigid protocol application not-so-good performing hospitals

22 LOWEST COMMON DENOMINATOR? good performing hospitals Standardised mortality ratio? rigid protocol application? rigid protocol application not-so-good performing hospitals

23 LOWEST COMMON DENOMINATOR? good performing hospitals Standardised mortality ratio? rigid protocol application? rigid protocol application not-so-good performing hospitals

24 BUT. Guidelines are often taken too literally by: clinical zealots institutions governments

25 BUT. Guidelines are often taken too literally by: clinical zealots institutions governments.. with financial penalties or name-and-shame for non-compliance

26 TAKE-HOME MESSAGE Use guidelines/protocols as an aide memoire.. but not rules of stone Don t be afraid to deviate.. but be able to justify why

27 DISCUSSION POINTS.. Guidelines should be slavishly followed One size fits all Every hour of antibiotic delay kills How long should a course of antibiotics last? Sepsis mortality is improving Why do people die of sepsis?

28 THE INTERVENTION.. OR TARGETED ENDPOIN.. MUST BE RATIONAL FOR EVERYONE

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33 S O W H Y TA R G E T A P O P U L AT I O N, AND NOT AN INDIVIDUAL!!!!!

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38 TAKE-HOME MESSAGE

39 TAKE-HOME MESSAGE Titrate to the individual e.g. what BP suits them? MAP or 75-80?

40 TAKE-HOME MESSAGE Titrate to the individual e.g. what BP suits them? MAP or 75-80? Titrate to a goal if a patient needs fluid (if hypovolaemia -> hypoperfusion), give fluid if not hypovolaemic and hypoperfused, don t give fluid

41 TAKE-HOME MESSAGE Titrate to the individual e.g. what BP suits them? MAP or 75-80? Titrate to a goal if a patient needs fluid (if hypovolaemia -> hypoperfusion), give fluid if not hypovolaemic and hypoperfused, don t give fluid Avoid excess - too much fluid, too much oxygen, too much catecholamine

42 DISCUSSION POINTS.. Guidelines should be slavishly followed One size fits all Every hour of antibiotic delay kills How long should a course of antibiotics last? Sepsis mortality is improving Why do people die of sepsis?

43 INTERESTING FACTS - 1

44 INTERESTING FACTS - 1 Multiple papers - including EVERY prospective study I m aware of do NOT show a correlation between a short-term delay in administering antibiotics and mortality

45 INTERESTING FACTS - 2

46 INTERESTING FACTS - 2 Studies claiming every hour counts are all based on retrospective analyses of databases collected for other reasons (usually administrative), but lacking vital data e.g. antibiotic sensitivities

47 INTERESTING FACTS - 2 Studies claiming every hour counts are all based on retrospective analyses of databases collected for other reasons (usually administrative), but lacking vital data e.g. antibiotic sensitivities.. and use complex adjustments to find a mortality difference

48 INTERESTING FACTS - 2 Studies claiming every hour counts are all based on retrospective analyses of databases collected for other reasons (usually administrative), but lacking vital data e.g. antibiotic sensitivities.. and use complex adjustments to find a mortality difference.. and often incorporate very delayed treatment (>6h) into the analysis

49 INTERESTING FACTS - 2 Studies claiming every hour counts are all based on retrospective analyses of databases collected for other reasons (usually administrative), but lacking vital data e.g. antibiotic sensitivities.. and use complex adjustments to find a mortality difference.. and often incorporate very delayed treatment (>6h) into the analysis.. and often lack biological plausibility

50 INTERESTING FACTS - 2 Studies claiming every hour counts are all based on retrospective analyses of databases collected for other reasons (usually administrative), but lacking vital data e.g. antibiotic sensitivities.. and use complex adjustments to find a mortality difference.. and often incorporate very delayed treatment (>6h) into the analysis.. and often lack biological plausibility.. and cannot explain why there was a delay in treatment in some

51 Survival time following hypotension (hours)

52 Survival 7.6% decrease in survival per hour of delay time following hypotension (hours)

53 Survival 7.6% decrease in survival per hour of delay time following hypotension (hours)

54 Survival time following hypotension (hours)

55 Survival time following hypotension (hours)

56 Survival time following hypotension (hours)

57 Survival time following hypotension (hours)

58 Survival time following hypotension (hours)

59 Survival time following hypotension (hours)

60 Survival n=2154 time following hypotension (hours)

61 Survival n=2154 time following hypotension (hours)

62 Survival n=558 n=2154 time following hypotension (hours)

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67 ED Ward ICU Mortality (%) Time to antibiotic (hr) >6

68 ED Ward ICU Mortality (%) Time to antibiotic (hr) >6

69 ED Ward ICU Mortality (%) Time to antibiotic (hr) >6

70 ED Ward ICU Mortality (%) Time to antibiotic (hr) >6

71 ED Ward ICU Mortality (%) Time to antibiotic (hr) >6

72 ED Ward ICU Mortality (%) Time to antibiotic (hr) >6

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74 1373 ICU patients between coded as septic/septic shock

75 1373 ICU patients between coded as septic/septic shock

76 1373 ICU patients between coded as septic/septic shock

77 1373 ICU patients between coded as septic/septic shock

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90 and no data on antibiotic sensitivities, adequacy of dosing, source control, etc..

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92 .. yet 45% of patients (early and late treated) had septic shock!!

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95 82.5% of pts 2% of pts

96 23.6% 22.6% 82.5% of pts 2% of pts

97 82.5% of pts 15.5% of pts 2% of pts

98 82.5% of pts 15.5% of pts 2% of pts

99 82.5% of pts 15.5% of pts 2% of pts

100 82.5% of pts 15.5% of pts 2% of pts

101 PROSPECTIVE STUDIES SHOW NO DIFFERENC

102 PROSPECTIVE STUDIES SHOW NO DIFFERENC Often designed to specifically look at impact of antibiotics on outcomes None show an each-hour-delay-kills signal Puskarich, CCM 2011 septic shock (ED) Hranjec, Lancet Infect Dis 2012 sepsis/septic shock (ICU) Kaasch, Infection 2013 S aureus bacteraemia (Ward/ICU) Bloos, Crit Care 2014 sepsis/septic shock (ICU) De Groot, Crit Care 2015 ED sepsis/septic shock (ED) Fitzpatrick, Clin Microbiol Infect 2016 Gm -tive bacteraemia (Ward) Alan, Lancet Respir Dis 2018 sepsis (pre-hospital ED)

103 prospective observational study in 3 Dutch EDs hospitalized ED patients requiring iv antibiotics stratified by illness severity (low, intermediate, high) time to antibiotics <1 hour vs 1-3 hours v >3 hours 1168 patients enrolled - overall mortality 10% 85% received antibiotics within 3 hours, 95% within 6 hours

104 No association between time to a/b and surviving days outside hospital or mortality In low illness severity group, delayed (>3h) antibiotics associated with more surviving days outside hospital (HR 1.46 (95%CI )

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106 2672 patients randomised to receive pre-hospital antibiotics (ceftriaxone 2g) from paramedics on suspicion of sepsis OR start antibiotics in ED Mean 96 minute difference in time to administration of antibiotics

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112 TAKE-HOME MESSAGE

113 TAKE-HOME MESSAGE Every second doesn t count.. but reasonable/rational to treat sepsis and septic shock promptly Rather than simply throwing antibiotics at the patient, apply some thought, seek advice, and think source control

114 DISCUSSION POINTS.. Guidelines should be slavishly followed One size fits all Every hour of antibiotic delay kills How long should a course of antibiotics last? Sepsis mortality is improving Why do people die of sepsis?

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124 6 month audit in University hospital medical-surgical ICU

125 6 month audit in University hospital medical-surgical ICU 113 bacteraemia episodes in 87 patients

126 6 month audit in University hospital medical-surgical ICU 113 bacteraemia episodes in 87 patients Short-course monotherapy (4-5 days) used in 65.7%

127 6 month audit in University hospital medical-surgical ICU 113 bacteraemia episodes in 87 patients Short-course monotherapy (4-5 days) used in 65.7% Low rates of bacteraemia breakthrough/relapse

128 6 month audit in University hospital medical-surgical ICU 113 bacteraemia episodes in 87 patients Short-course monotherapy (4-5 days) used in 65.7% Low rates of bacteraemia breakthrough/relapse Very low incidence of antimicrobial resistance or fungaemia

129 6 month audit in University hospital medical-surgical ICU 113 bacteraemia episodes in 87 patients Short-course monotherapy (4-5 days) used in 65.7% Low rates of bacteraemia breakthrough/relapse Very low incidence of antimicrobial resistance or fungaemia Less ICU-acquired MRSA, MDR Gram -tives, VRE and fluconazole-resistant candidaemia c/f similar audit in 2000

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133 fluconazole-resistant

134 fluconazole-resistant methicillin -resistant

135 fluconazole-resistant methicillin -resistant VRE

136 fluconazole-resistant methicillin -resistant VRE MDR

137 fluconazole-resistant methicillin -resistant VRE MDR no fluconazole-resistance

138 fluconazole-resistant methicillin -resistant VRE MDR 1 VRE no fluconazole-resistance

139 fluconazole-resistant methicillin -resistant VRE MDR no MRSA 1 VRE no fluconazole-resistance

140 fluconazole-resistant methicillin -resistant VRE no MRSA 1 VRE no MDR MDR no fluconazole-resistance

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143 4 vs 8 days

144 DISCUSSION POINTS.. Guidelines should be slavishly followed One size fits all Every hour of antibiotic delay kills How long should a course of antibiotics last? Sepsis mortality is improving Why do people die of sepsis?

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152 781,725??? under-reported 118,676??? over-reported 300, ,124

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158 DISCUSSION POINTS.. Guidelines should be slavishly followed One size fits all Every hour of antibiotic delay kills How long should a course of antibiotics last? Sepsis mortality is improving Why do people die of sepsis?

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162 MAINTAINING A SENSE OF PROPORTION

163 MAINTAINING A SENSE OF PROPORTION 34 million antibiotic prescriptions by English GPs in

164 MAINTAINING A SENSE OF PROPORTION 34 million antibiotic prescriptions by English GPs in million hospital patient episodes with a sepsis/infection code in England p.a.

165 MAINTAINING A SENSE OF PROPORTION 34 million antibiotic prescriptions by English GPs in million hospital patient episodes with a sepsis/infection code in England p.a... with 32,300 in-hospital deaths = 2.5% mortality rate

166 MAINTAINING A SENSE OF PROPORTION 34 million antibiotic prescriptions by English GPs in million hospital patient episodes with a sepsis/infection code in England p.a... with 32,300 in-hospital deaths = 2.5% mortality rate BUT only 11,000 cases of sepsis had an ICU admission

167 DO ALL SEPTIC PATIENTS WARRANT LIFE-PROLONGING TREATMENT???

168 DO ALL SEPTIC PATIENTS WARRANT LIFE-PROLONGING TREATMENT??? Pneumonia is the old man s friend - Sir William Osler Patients may be allowed to die from sepsis due to the severity of their underlying comorbidity - terminal cancer, severe stroke, end-stage chronic organ failure, severe dementia

169 N SUSPICIONOF SEPSIS HOSPITALADMISSIONS IN ENGLAND Age

170 SUSPICIONOF SEPSIS HOSPITALADMISSIONS IN ENGLAND N Age SUSPICIONOF SEPSIS MORTALITY Mortality (%) Age 90+

171 SUSPICIONOF SEPSIS HOSPITALADMISSIONS IN ENGLAND N Age SUSPICIONOF SEPSIS MORTALITY Mortality (%) 77.5% OF DEATHS Age 90+

172 SUSPICIONOF SEPSIS HOSPITALADMISSIONS IN ENGLAND N Age 20 8% OF DEATHS SUSPICIONOF SEPSIS MORTALITY Mortality (%) 77.5% OF DEATHS Age 90+

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175 Dementia? Stroke? Other severe disability?

176 Dementia? Stroke? Other severe disability?

177 CONCLUSION

178 CONCLUSION Apply physiology to patient management

179 CONCLUSION Apply physiology to patient management Personalization not rigid protocolization

180 CONCLUSION Apply physiology to patient management Personalization not rigid protocolization Challenge dogma based on weak/contrived evidence

181 CONCLUSION Apply physiology to patient management Personalization not rigid protocolization Challenge dogma based on weak/contrived evidence Sepsis only constitutes a small proportion of infection but should be identified and acted upon promptly.. but with some thought applied

182 CONCLUSION Apply physiology to patient management Personalization not rigid protocolization Challenge dogma based on weak/contrived evidence Sepsis only constitutes a small proportion of infection but should be identified and acted upon promptly.. but with some thought applied